Spring 2001 • Volume 6, Issue 1 THE MDS NEWS The Newsletter of The Myelodysplastic Syndromes Foundation From the Guest
years, whereas those with lower risk can expect tosurvive for several years, even without treatment. Editor’s Desk
Once the prognostic grouping is determined, thetreatment plan is developed. Relatively low intensity
Elihu H. Estey, MD
treatments are recommended for patients with
MD Anderson Cancer Center, Houston, Texas
low risk. Higher intensity treatments, such aschemotherapy, are not usually recommended for
Treatment of Myelodysplastic Syndromes
these patients as the risks associated with the
Selection of the treatment plan for a patient with
treatments themselves may be greater than those
myelodysplastic syndromes (MDS) depends upon
associated with the disease. Furthermore, adverse
the prognosis for the disease course. Currently, the
effects of the high-intensity treatments may preclude
best approach for assessing prognosis is to utilize
the patient from benefiting from new treatments
the International Prognostic Scoring System (IPSS).
which are under development. Patients in the high
The IPSS incorporates the results from three types
risk groups, however, are candidates for both low-
of analyses — the levels of blood counts, the percent
of immature cells (“blasts”) in the bone marrow, and
While it is important to note that no therapy for
the karyotype (chromosome pattern) of the bone
MDS has been shown to prolong survival, it is equally
marrow cells — to distinguish four prognostic risk
important to comment that new approaches may be
groups; the four groups are Low, Intermediate-1,
successful in this regard. After all, effective treatments
Intermediate-2, and High. Patients having lower risk
have only recently been developed for diseases like
(Low and Intermediate-1 groups) generally do not
tuberculosis, hypertension, and HIV infection. Of
have excess blasts in the bone marrow but rather
course, determination of the effectiveness of potential
have blood counts which are mildly to moderately
treatments must be first proven through formal clinical
abnormal. Higher risk patients, meaning those in the
trials before the treatment program can be broadly
Intermediate-2 or High Risk groups, have severely
available. Participation in clinical trials of new MDS
abnormal blood counts, excess blasts in the marrow,
therapies will bring all patients closer to improved
and/or chromosomal abnormalities. The higher risk
patients are more likely to experience MDStransformation into acute myeloid leukemia (AML)
Clinical trials and experience have also shown
and to have shorter survival, often less than 1-2
that some therapies may no longer be appropriate. Included on this list are androgens (male hormonessuch as danazol) and amifostine (Ethyol®), except for
certain uses undergoing evaluation in clinical trials. In addition, “colony-stimulating factors” (such as
G-CSF, also known as filgrastim or Neupogen®, and
GM-CSF, also known as sargramostim or Leukine®)
are no longer recommended as solo treatments;
while G-CSF and GM-CSF effectively increase the
number of normal white blood cells, these treatments
do not prevent infection or prolong life expectancy.
Recommendations for other treatments vary. Some
treatments, such as transfusions of red cells and/or
platelets, remain an important part of the manage-
ment of MDS. Management also includes monitoring
for iron overload that often accompanies frequent
red cell transfusions as well as administration of
deferoxamine (Desferal®) which counteracts iron
overload, thus lessening the risk of future heart and
liver problems and diabetes. Other treatments are
less broadly used, such as the combination of G-CSF
and erythropoietin, because only certain patients are
likely to respond, as has been shown in this case
immunosuppressive drug ATG has been shown to
occasionally raise blood counts in MDS and is now
New low- and high-intensity treatments are under
being combined with other immunosuppressive
investigation and are providing encouraging results,
agents, such as cyclosporine and fludarabine,
with patience as a key part of the treatment program.
When used to treat MDS, 3-4 months may be
High-Intensity Therapies Being Evaluated for
required before response to the various low-intensity
Treatment of MDS
approaches can be observed. Response to high-
1. Chemotherapy – While chemotherapy is a standard
intensity approaches may be observed within
procedure, new drugs and combinations of new
drugs with both older drugs are being evaluated
Low-Intensity Therapies Being Evaluated for
for treatment of MDS. Some of the new combi-
Treatment of MDS
nation drugs are troxacitabine, Mylotarg®, and a
1. Inhibitors of Ras – Ras is a protein that participates
drug (“genasense”) that opposes the action of
in signaling abnormal cells to continue to divide
Bcl2, a protein that prevents the killing of cancer
which, in turns, leads to an excess of blast cells.
Drugs known as farnesyl transferase inhibitors block
2. Bone marrow transplantation – New methods of
the functioning of Ras and, therefore, slow the
transplantation are being investigated, with the
accumulation of blast cells. In a study of R115777,
goal of reducing the intensity of the chemotherapy
a farnesyl transferase inhibitor, for treatment of
treatment which is administered prior to the
acute myeloid leukemia, some patients did respond
transplant. If successful, older patients will have
to the treatment, although the exact response rate
less risk associated with the procedure. New
is unknown and at least some of the patients might
methods to specifically reduce complications of
have responded to standard therapies.
transplant are also being investigated.
2. Inhibitors of angiogenesis – Angiogenesis is the
For further information about treatments for MDS or
term applied to the formation of new blood vessels.
about MDS in general, go to www.mds-foundation.org
Because the bone marrow of MDS patients often
has an abnormally high number of blood vessels,
transcripts.htm, a website established by the National
therapies that inhibit angiogenesis are of interest.
Cancer Institute to disseminate information shared
at a “State of the Science” meeting on MDS held in
bevacizumab. The former has been reported to
Desferal® is a trademark of Novartis Pharmaceutical Corporation.
although, once again, the benefit over standard
Ethyol® is a trademark of Alza Pharmaceuticals.
therapies has not yet been established.
Leukine® is a trademark of Immunex Corporation.
3. Thalidomide – This drug, which was removed from
Myelotarg® is a trademark of Wyeth-AyerstNeupogen® is a trademark of Amgen Inc.
the marketplace in the 1950s after it produced fetalmalformations, has been shown to have remarkableactivity for treatment of myeloma (cancer of a type
Thank You to
of white blood cell). Thalidomide has also beenreported to increase blood counts in MDS patients,
although these reports as yet require confirmation.
4. Decitabine – Through inappropriate methylation,
genes that normally suppress cancer becomeinactivated in MDS. Demethylation of these genes,
We would like to thank our pharmaceutical
therefore, slows the development of cancer. An
partners for their support of the Foundation and
inducer of demethylation, 5-azacytidine, was shown
its work. They have contributed in the form of
to improve blood counts and quality of life for patients
unrestricted educational grants, which support
with MDS. Decitabine is similar to 5-azacytidine
not only this newsletter but also the development
but, being a more potent inducer of demethylation,
of the MDS home page on the World Wide Web,
decitabine may be even more effective.
the Centers of Excellence program, continuing
5. ATG + cyclosporine or fludarabine – Inappropriate
medical education programs, the Patient Registry,
activity of the immune system may result in low
and the dissemination of patient information.
blood counts, a characteristic of MDS. The
About the Foundation MDS Board of Directors John M. Bennett, MD
The Myelodysplastic Syndromes Foundation was established
by an international group of physicians and researchers to
provide an ongoing exchange of information relating to MDS.
Until the Foundation was set up, no formal working group
had been devoted to MDS. During the past decade we have
Jeanne E. Anderson, MD
conducted five international symposia — in Austria, England,
the United States, Spain, and the Czech Republic. The Sixth
International Symposium will be held in Stockholm, Sweden,
One major role of the Foundation is our internationalinformation network. This network provides patients with
Pierre Fenaux, MD, PhD Professor of Hematology
referrals to Centers of Excellence, contact names for
available programs, sharing of new research and treatment
options, and extension of educational support to both
physicians and patients. Ultimately, we hope to provide
Peter L. Greenberg, MD
funding and oversight for international studies in MDS.
In response to the needs expressed by patients, families,
and physicians, we are establishing patient advocacy
groups, research funding, and physician education.
The MDS Foundation is a publicly supported organization,
Terry Hamblin, MD, FRCP, FRC Path Treasurer
exempt from federal income tax under section 501(C)(3)
Our Web Site Kathy Heptinstall, BSN, RN Operating Director The MDS Foundation has established its own Web page for healthcare professionals, patients, and other interested people. The Professional Forum and the Professor G.J. Mufti Patient Forum are integral parts of our Web site.
Head of Haematological MedicineHealthcare NHS Trust
The Web site has recently been updated to better serve the needs of our patients, their families, and the physicians who treat them. Charlotte M. Niemeyer, MD We welcome your suggestions.
Professor of PediatricsUniversity Children’s Hospital
Please visit us at http://www.mds-foundation.org Hussain I. Saba, MD, PhD Professor of Medicine University of South Florida Tampa, Florida, USA Franz Schmalzl, MD Professor, Department of Internal Medicine University Hospital of Innsbruck Innsbruck, Austria Jody Simon, MS, RPh Tampa, Florida, USA Ortho Biotech, Inc., has supplied the MDSRobert J. Weinberg, Esq. Foundation with an unrestricted educational grant.
Pepper Hamilton LLPPhiladelphia, Pennsylvania, USA
Patient Services Patient Advocacy
The MDS Foundation is pleased to share with our
patients and their families that flight services areavailable within the continental United States to
Established by the AirLifeLine is a nationwide organization of over MDS Foundation
1,100 pilots who are caring, committed andcompassionate individuals donating their time,
The MDS Foundation has been working todevelop a strategy for setting up patient groups
aircraft and fuel to provide free transportation for
nationwide. Until recently, we did not have the
Generally, the criteria for patient travel with us are:
wished. Thanks to the generosity of families
• The patient must be ambulatory or be mobile
and friends of patients lost to this disease,
enough to board and exit the aircraft. The patient
the Foundation was able to establish a Patient
must be able to sit in a seat and wear a seatbelt.
Patient may bring along a family member or a
support person to assist them. In the case of a
forming nationwide patient advocacy groups,
developing new information for patients andplanning fund raising programs to support these
• The patient should be medically stable and able to
activities. Committee members include Jennifer
fly in an unpressurized aircraft. Our pilots are not
Rand, Jody Simon, Joe and Charlotte Pagano,
medically trained and their planes are not medically
and Foundation representatives: Kathy Heptinstall,
equipped. Oxygen is allowed with the pilot’s consent.
John Bennett, Betty Anne Nixon, Laura Ciesielski,
• The patient must demonstrate financial need and
be unable to afford other means of commercial
Any member of the Foundation, patients, friends
transportation. We do waive this requirement for
and family members are invited to join with us to
financial need if the patient has a time critical
move these projects forward. Please contact
situation such as an organ transplant.
Betty Anne Nixon at the Foundation office:
• The patient’s flight should be less than approxi-
mately 1,000 from his or her home to the medical
Your help is needed!!
destination. The average mission is between250–500 miles. However, we can coordinateflights up to 1,000 miles one way.
It is the mission of Angel Flight to ensure that no financially needy patient is denied access to distant, Marrow Donor
specialized treatment for lack of means of airtransportation.
For those patients diagnosed with a fatal blood disorder,bone marrow transplantation (BMT) is often the only
chance of survival. Related donors provide suitable
matches only 33 percent of the time. This leavesnearly 70 percent of patients without a match. Corporate Angel Network
The need is especially critical in racial and ethnic
National Patient Travel Center
Registering as a donor is simple. A blood sample isall you need to enter your tissue type into the NationalMarrow Donor Program (NMDP) computerized registry. If you are in good health and between the ages of 18and 55, you can contact NMDP at 1-800-MARROW-2. They will send additional information, including the
The MDS Foundation is supported by an unrestrictededucational grant from Amgen, Thousand Oaks, California.6th International Saturday, June 16, 2001 Symposium on Myelodysplastic
■ Mini Symposium – Sideroblastic Anemia
■ The Role of Mitochondria in Iron Transport and
June 14-17, 2001 Sunday, June 17, 2001 Stockholm, Sweden SCIENTIFIC TOPICS ORGANIZING COMMITTEE
Eva Hellström-Lindberg, PresidentÄke Öst, Vice PresidentSCIENTIFIC PROGRAM Thursday, June 14, 2001
■ Classification of Myelodysplastic Syndrome:
For further information please contact: Friday, June 15, 2001 Symposium Secretariat Scientific Secretariat Suzanne Fleishman Memorial Lecture Hosted by The Myelodysplastic SyndromesAdditional information available from the Congress
■ Complimentary and Alternative Therapies
website: http://www.congrex.com\mds2001. A Living Endowment
condolence card to the family, making them awareof the gift. The Lees have made a commitment tocontinue to donate to the Foundation, not only on
One Family’s Pledge
occasions of loss, but even as remembrances for
The family of MDS patient, Eugene Lee, is one of
birthdays and anniversaries. The Foundation sends
many thousands of families living with the reality of
a handwritten acknowledgement card to the family,
MDS. They have come up with an extraordinary way
making them aware of these gifts in the Lees name.
to contribute to the MDS Foundation and support
A fund has been initiated established in Eugene’s
our mission of working as a resource for patients,
name for this purpose, and the funds will be used
families, and healthcare professionals.
Eugene and Meta Lee recently learned of friends
The MDS Foundation is very grateful for the heartfelt
who had experienced the unfortunate loss of their
support of Eugene and Meta Lee. Our work as a non-profitorganization depends on public funding. If you would like
mother. The Lees made a decision to honor their
to contribute in this way, or if you have a unique idea of
friends and their mother by making a donation to
your own, please write to us at PO Box 353, 36 Front Street,
the MDS Foundation. The Foundation sent a personal
Crosswicks, NJ 08515, or call us at 1-800-MDS-0839.Selected
(4.5+, 6+ and 3+ respectively). Clearly, patients withlow cytokine and apoptosis levels appear to benefit
Abstracts in MDS
from the treatment with Thalidomide. This constitutes abiologically recognizable subgroup of good-riskpatients who are likely to respond to manipulations of
Adapted from abstracts presented at
cytokine pathways. The precise mechanism of
the American Society of Hematology,
Thalidomide activity in MDS remains obscure and is
December 2000, San Francisco, California
most likely a result of its anti-angiogenic, anti-cytokineand immunomodulatory effects. Biologic Determinants of Clinical Response to Thalidomide in Myelodysplasia Thalidomide as a Single Agent or in Combi- S. Mundle, F. Zorat,* V. Shetty, K. Allampallam, nation With Topotecan, Pentoxifylline and/or S. Alvi,* L. Lisak,* L. Little,* L. Dean,* R. Nascimben,* Enbrel in Myelodysplastic Syndromes (MDS) M. Ekbal,* M. duRandt,* E. Broderick,* P. Venugopal, A. Raza, L. Lisak,* L. Little,* M. Ekbal,* M. du Rant,* A. Raza E. Ali,* F. Nascimben,* M. Tareen,* P. Venugopal Rush Cancer Institute, Rush-Presbyterian-St. Luke’s Rush Cancer Institute, Rush-Presbyterian- Medical Center (RPSLMC), Chicago, IL St. Luke’s Medical Center, Chicago, IL
Based on the earlier observations of increased levels of
Recent biologic insights have led to the development
tumor necrosis factor a (TNFα) and excessive
of novel therapeutic venues for the treatment of MDS
apoptosis in the bone marrow (BM) of patients with
designed to suppress pro-inflammatory cytokines
myelodysplastic syndromes (MDS), a suppressor of
and/or angiogenesis, as well as modulation of the
TNFα; Thalidomide, was used in the therapy of MDS at
immune system. Thalidomide has activity in all three
our center on a protocol approved by the IRB of
areas. In our first trial, 83 MDS patients received
RPSLMC. Thalidomide was administered at an initial
thalidomide starting at 100 mg PO and increasing as
total daily oral dose of 100 mg PO increased to 400 mg
tolerated to 400 mg PO for 12 weeks; 32 went off study
as tolerated. Thirty-one patients [refractory anemia
due to side effects (26) or disease progression (6)
(RA)-18, RA with ringed sideroblasts (RARS)-6, RA with
while 51 are evaluable for response. The median age
excess blasts (RAEB)-6 and chronic myelomonocytic
of these 51 patients was 68 years, there were 36
leukemia (CMML)-1] completed 12 weeks of therapy.
males / 15 females, 48 had primary and 3 had
Significant hematological responses were noted in 16
secondary MDS, 44 had normo- or hypercellular and
patients (11/18 RA and 5/6 RARS). In order to
7 had a hypocellular marrow. Initial FAB showed 28
determine the biologic correlates of these responses,
RA, 9 RARS, 12 RAEB, 1 RAEB-t, and 1 CMMoL. IPSS
patients’ sera were assessed by ELISA for the levels of
scoring showed that 17 had low risk, 26 had int-1, 4
TNFα, transforming growth factor ß (TGFß), basic
had int-2 and 4 had high risk disease. Abnormal
fibroblast growth factor (bFGF) and vascular
cytogenetics were present in 35 while 16 had normal
endothelial growth factor (VEGF). Additionally, plastic
karyotypes. There were no complete responders,
embedded bone marrow biopsy sections were
partial responses were seen in 21/51 (41%) patients,
examined for the extent of apoptosis by in situ end
8 patients who were transfusion dependent became
labeling (ISEL) and for the presence of TNFα, and TGFß
completely independent of transfusions. The median
by immunohistochemistry using a subjective rating
duration of response has not been reached yet, the
scale of 1+ to 8+. In the sera of both responders [R]
longest treated patients having completed 1 year of
and non-responders [NR] the VEGF levels correlated
therapy. Responses were noted in all three lineages,
positively with TGFß and TNFα levels. Interestingly, a
but were most effective in the erythroid series. Low
significant correlation was seen with bFGF (r=0.679,
risk patients with no excess blasts and higher pre-
p=0.04) only in NR. Also, while VEGF correlated
therapy platelets were more likely to respond. In half
negatively with hemoglobin (Hgb) levels in this
the RAEB cases, the blasts remained unaffected even
group (r= –0.8, p=0.03), demonstrated a positive
though hematopoiesis improved significantly. Several
correlation with Hgb in R group (r=0.609, p=0.058).
cases responded 1-10 weeks after stopping therapy.
Surprisingly, in the R group, BM biopsies showed
Currently, low risk MDS are treated with either a
significantly lower median levels of apoptosis, TGFß
combination of thalidomide with Enbrel, or PCD
and TNFα, (1+, p=0.19; 1+, p=0.012, and 2+, p=0.04
(pentoxifylline, Cipro, dexamethasone), while topotecan
respectively), as compared to those in the NR group
is administered initially to reduce the blast count in
high-risk patients followed by thalidomide. Initial
months with 6 patients maintaining their responses for
results on these combination therapies appear to be
over 12 months. Headaches and nausea were the
superior to thalidomide alone. Mechanism of response
most common reported side effects but they were not
remains unclear, although post-therapy levels of pro-
severe enough to interrupt therapy in any patients. Liver
inflammatory cytokines, apoptosis and angiogenesis
function tests did not rise significantly above baseline.
were decreased. Delayed responses appear to
At the time of analysis, 12 patients remain alive and
indicate immune-modulation as the likely mechanism
free from progression. Ten patients transformed to
in at least a subset of patients. In conclusion,
AML. Of the remaining 7 patients, 1 died from intra-
thalidomide appears to be a promising addition to MDS
cranial hemorrhage, 1 from perforated bowel, 2 from
therapeutic armament and deserves further study.
other causes, and 3 were lost to follow-up. Inconclusion, danazol may be effective in MDS patients
Danazol for the Treatment of Thrombocytopenia in Myelodysplastic Syndrome Geoffrey W. Chan,* Gina DiVenuti,* Low Dose Interleukin-11 is Well-Tolerated and Kenneth B. Miller Induces Platelet Responses in Myelodysplasia and Other Bone Marrow Failure States Department of Hematology/Oncology, Tufts– New England Medical Center, Boston, MA, USA R. Kurzrock, J. Cortes, D. Thomas, S. Pilat,* M. Talpaz
Therapy for thrombocytopenia in myelodysplastic syn-drome remains limited. Danazol, an attenuated
University of Texas M.D. Anderson Cancer Center,
androgen with immunomodulatory properties, is
Houston, TX, USA
effective in some patients with ITP. We report on 29
Interleukin-11 (IL-11) is a thrombopoietic cytokine that
MDS patients, 9 RA, 11 RAEB, 5 RAEB-t, 4 CMML,
attenuates post-chemotherapy thrombocytopenia.
who were treated with danazol 200 mg po tid. Median
The dose used post-chemotherapy is ≅ 50 µg/kg/day
age was 68.5 years (range 44 to 93 years) with 18
s.c. Very little is known about the activity of IL-11 in
males and 11 females. Cytogenetic studies revealed 4
bone marrow failure states. Our preliminary experience
patients with 5q-, 4 with monosomy 7, 3 with three or
with IL-11 at doses of 50 µg/kg/day suggested that
more chromosomal abnormalities, 10 with other
bone marrow failure patients developed significant
abnormalities, and 8 with normal karyotypes. Median
peripheral and pulmonary edema after the prolonged
platelet count prior to therapy was 41,000 per mm3
dosing necessary for treating these conditions. We
(range 10,000 to 97,000 per mm3). Seven patients
therefore initiated a study of low-dose IL-11 (10 µg/kg/d).
required platelet transfusions prior to initiating therapy.
Response criteria included doubling of platelets and
After six weeks, 22 out of 29 patients (76%)
rise to >50 x 109/L or tripling of platelets and rise to
responded with elevations in platelet counts ranging
>20×109/L. Sixteen patients are evaluable for response.
from 1,000 to 181,000 per mm3. Nine responders had
Their median age was 58 years (range, 5 to 84 years).
started with platelet counts less than 30,000 per mm3
Six patients had diploid cytogenetics; the others had a
and another seven responders had started with
variety of chromosomal abnormalities. Six of 16 patients
platelet counts between 30,000 and 50,000 per mm3.
(38%) showed a platelet response to IL-11 and two
Ten patients (34%) increased their platelet counts by
had a multi-lineage response (to IL-11 alone [N=1];
more than 50%, 14 of 22 responders increased their
to IL-11 + G-CSF and EPO [N = 1]). Responders
platelet counts above 50,000 per mm3, and 5
included 5 of 11 patients with myelodysplasia (MDS)
responders who were platelet transfusion dependent
and 1 of 4 patients with aplastic anemia (AA).
no longer required platelets. After three months, 18 out
Response duration was 12, 13, 14+, 22+, 25 and 30
of 26 patients (72%) had an elevation in platelet
weeks. Side-effects of IL-11 were mild (peripheral
counts. Thirteen patients (50%) had increased their
edema, N=7; conjunctival injection, N=7 or myalgia
platelet counts by more than 50%. Responses were
[N=1]) (all grade 1). Seven patients had no side-
seen in all FAB subtypes at six weeks (9/9 RA, 9/11
effects. Our pilot study suggests that administration of
RAEB, 1/5 RAEBT, 4/4 CMML) and at twelve weeks
low dose IL-11 (10 µg/kg/day) can raise platelet counts,
(7/9 RA, 6/ 10 RAEB, 3/3 RAEB-t, 3/4 CMML). There
without significant toxicity, in selected thrombocytopenic
was no correlation between the pretreatment platelet
count and response to danazol. No appreciableincreases in the hematocrit or white blood cell countswere observed. Mean duration of treatment was 9.4
High Dose (HD) Chemotherapy in High Risk Comparison of Interphase Fish and (HR) Myelodysplastic Syndrome (MDS): Covariate Metaphase Cytogenetics to Study Adjusted Comparison of Five Regimens Myelodysplasia: An Eastern Cooperative Miloslav Beran,1 Yu Shen,*2 Hagop Kantarjian,1 Oncology Group (ECOG) Study Simona Despa,*2 Elihu Estey1 G. Dewald,* G. Hicks,* R. Higgins,* C. Griffin,* 1Leukemia, The University of Texas MD Anderson A. Cherry*, J. Rowe, M. Tallman, J. Bennett, Cancer Center, Houston, TX; 2Biomathematics, K. Miller The University of Texas MD Anderson Cancer Mayo Clinic, Rochester, MN, USA Center, Houston, TX
This investigation compared standard metaphase
To further define the role of high dose combination
chromosome studies with interphase studies using
chemotherapy in patients with diagnosis (Dx) of HR
chromosome specific DNA probes with fluorescence
MDS (RAEB, RAEBt) we have analyzed (a) association
in situ hybridization (FISH) to detect neoplastic clones
between covariates and CR status, (b) relationship
in bone marrow from patients with myelodysplastic
between diagnosis and CR status (c) significance of
syndromes (MDS). FISH was used with chromosome
treatment effect for time to relapse and death (d)
specific DNA probes to detect abnormalities of
covariate-adjusted activity of five consecutive
chromosomes 5, 7, 8, 11, 13 and 20. For each patient,
treatment regimens. In the cohort of 394 patients, 229
the percentage of neoplastic nuclei in 200
(58%) achieved CR. The CR rates by regimens are
consecutive cells for each probe was established.
Chromosome studies were done on ≤ 25 metaphasesfor the same specimens. FISH was done on 34 fixed
p value ————— ———— ———— ———— ———— ———— ————
cell pellets from cytogenetic studies and 8 bone
marrow aspirate smears from morphology studies.
NO CR (%) 19 (28) 30 (39) 61 (52) 30 (41) 25 (42)
Patients included 5 with high risk MDS (E3996) and 37
with low risk MDS (E1996). Excluding -Y as a marker
* I=idarubicin; F=fludarabine; A=intermediate or high dose cytosine
of clonality, an abnormal clone was identified in
arabiaosidc; T=topotecan; C=cyclophosphamide.
metaphases from 14/42 (33.3%) patients and 28
In multivariate analysis, disease duration (AHD),
(66.7%) were normal. By comparison, interphase FISH
performance status (PS), protected environment (PE)
studies on these same specimens detected an
and days to response but not IPSS were significant
abnormal clone in 11/41 (26.8%), only normal nuclei in
predictors of CR (two-sided p<0.05). With covariate
30 (73.2%) and failed in 1 (2.4%). Among patients with
an abnormal clone by cytogenetics 1 had RA, 3 RARS,
comparable CR rates. Dx was not associated with CR
8 RAEB and 2 RAEB-T. Among patients with normal
status in IA, CAT, FA and FAI; within TA group RAEB
cytogenetics 4 had RA, 13 RARS, 7 RAEB, 2 RAEB-T
was more likely to achieve CR than RAEBt (p=0.01).
and 1 CMML. Abnormalities were detected in
Overall logrank test documented significant treatment
metaphases of 3 patients that were not evident by
effect in terms of overall survival (p<0.01), and time to
FISH in interphase cells either because the FISH
relapse (p=0.01). The trend for time to relapse was
strategy was not designed to detect the abnormality or
the same as for time to death among five treatment
probe hybridization failed. Each of the 28 patients with
groups. Multivariate analysis for time to death
only normal metaphases also had only normal
revealed treatment, cytogenetics, age, prior
interphase cells. FISH detected ≥1 abnormalities of
chemotherapy, PE, PS, hemoglobin and platelets
chromosome 5,7,8, 11,13 and 20 in 2,3,4, 0,0 and 4
independent risk factors. Survival for IA patients was
patients, respectively. FISH failed for all probes in 1/34
comparable to TA, both being superior to FAI, FA and
fixed cell pellets, for chromosome 11 in 1/8 smears,
CAT. IA was more effective in sustaining remission
and for chromosome 20 in 3/8 smears. Results of this
than FA or FAI but not different from TA. In summary,
study dispel the argument that patients with MDS
no difference between anthracycline or non-
often have chromosome abnormalities that are missed
anthracycline-containing regimens were observed.
by chromosome studies due to sampling errors. The
Effective in inducing CR, particularly in e.g. – 5 / – 7
results indicate that approximately 70% of patients
karyotype, HD therapy is not associated with
with low risk MDS do not have abnormalities that are
improvement in CR duration and survival.
detectable by either chromosome studies or FISH. Theresults suggest that the sensitivity of interphase FISHstudies for MDS is nearly as good as cytogenetic
studies. FISH may be useful in clinical practice to
morphologic findings of marrow dysplasia still carries
study bone marrow specimens when chromosome
a risk of leukemia transformation or death from
studies are not successful or when only smears are
cytopenias. The cytogenetic abnormalities in this
group are generally typical of MDS, with del(20)qbeing the most frequently encountered. Del(20)q wasseen alone in 19% of our patients; in a recent series of
Clonal Cytogenetic Anomalies Suggestive of A Myelodysplastic Syndrome in Patients With
640 MDS patients, this anomaly was seen alone in only
Morphologically Normal Bone Marrow
2% of cases with the refractory anemia FAB subtype. Aspirates
Continued follow-up will more clearly define theprognosis in this heterogeneous cohort. David P. Steensma, Gordon W. Dewald,* Janice M. Hodnefield,* Ayalew Tefferi, Curtis A. Hanson Mayo Clinic, Rochester, MN, USA Addition of Thalidomide (T) to Chemotherapy Did Not Increase Remission Rate in Poor
Clonal cytogenetic abnormalities are found in the
bone marrow cells of 40 to 60% of patients with
Elihu Estey, Maher Albitar, Jorge Cortes, Francis Giles, Deborah Thomas, Charles Koller, Miloslav
occasionally observed patients with morphologically
Beran, Hagop Kantarjian
normal bone marrow aspirates, but with clonalabnormalities on conventional cytogenetic analysis
M.D. Anderson Cancer Center, Houston, TX, USA
suggestive of MDS. Between October 1994 and April
Marrow microvascular density (MVD) appears
2000, 58 such patients were seen at our institution (36
increased in AML (Blood 95:309, 2000) and high
men, 22 women; age range, 19–88 years; median
levels of cellular vascular epithelial growth factor
age, 71). The indications for marrow aspiration in this
(VEGF) seem independently associated with worse
group were cytopenias alone (32 patients), staging or
treatment outcome (Blood 95:2637,2000). Therefore
follow-up of a lymphoproliferative or plasma cell
we randomly assigned adults with newly-diagnosed
disorder (21 patients), or another miscellaneous
AML, RAEB-t, or RAEB to receive liposomal
reason (5 patients). 27 of the 58 patients had
daunorubicin (LD, 100 mg/m2 daily days 1–3) and ara-
previously been treated with an alkylating agent (14
C (A, 1 g/m daily days 1–4) with or without the “anti-
cyclophosphamide, 7 melphalan, 4 chlorambucil, 1
angiogenesis” agent T (400 mg daily × 1 week, then
BCNU, 1 nitrogen mustard) starting a median of 68
600 mg daily) for remission induction. In remission,
months earlier. 51 patients were anemic, 30 had
patients received 6 mos of LDA, +/– T as originally
erythrocyte macrocytosis, 30 were leukopenic, and 40
assigned. Eligibility required an abnormal karyotype
were thrombocytopenic; 26 were pancytopenic. The
other than t(15;17), t(8;21), or inv (16). A Bayesian
marrow was hypocellular in 21 cases, normocellular
design stipulated that accrual into either arm would
in 14, and hypercellular in 23. As of August 2000, with
stop should the probability become <0.02 that the
a median follow-up of 7 months, 18 of the 58 patients
early CR (ECR, Blood 95:72,2000) rate was not at least
were dead. Of these 18 patients, 1 died of acute
20% higher than the 46% rate seen in patients with the
myelogenous leukemia (AML), 4 of complications
described cytogenetics given other regimens
related to cytopenias, 6 of a previously diagnosed
1991–99. With this stopping rule, the probability of
lymphoproliferative disorder, and 7 of unrelated
early termination should the true ECR rate with an arm
causes. The cytogenetic findings were as follows:
be >0.66 (0.46 + 0.2) was 0.07. 74 patients were
among those with 1 or 2 clonal cytogenetic anomalies,
the most common abnormality was del(20)q [11patients], followed by: del(7)q or monosomy 7 [6
LDA (38 patients) LDA+T (36 pis)
patients], trisomy 8 [4 patients], del(5)q [3 patients],
del(13)q [3 patients], and t(1;7)(q10;p10) [2
—————————————— —————— ——————
patients]. 21 patients had other unique clonal
cytogenetic anomalies, and 11 patients had a complex
karyotype (3 or more anomalies). There were no
significant differences between the karyotypes ofpatients treated with alkylating agents and untreated
patients. We conclude that a clonal cytogenetic
anomaly suggestive of MDS in the absence of
These ECR rates led to termination of both arms. In
transfusion-independence following ATG or
particular, the probability that the ECR rate with
cyclosporine (p < 0.05). HLA DR15 frequency in
LDA + T is ≥20% higher than historical is <0.01; the
responders was 57% compared with 31% for non-
probability that it is ≥10% higher is .05. Early death
responders (p=0.03). The high frequency of HLA
(weeks 1–7) rates were 24% LDA, 19% LDA + T;
DR15 in MDS, comparable to that seen in AA,
relapse rates also appear similar. The median daily
suggests a link between HLA DR2/15 and immune-
dose of T was only 57% of that scheduled, principally
mechanisms of marrow failure in MDS and AA.
because of fatigue. Achievement of ECR was
Furthermore, DR15 typing could help predict MDS
unrelated to daily administered T dose (p=0.91) or
patients most likely to improve marrow function after
pre-Rx values of MVD (p=0.69, assessed in 18
patients, 10 ECRs) or plasma VEGF (p = 0 .33assessed in 40, 19 ECRs); the latter observations also
Validation of the WHO Proposals for a New
applied considering only the LDA + T group. Addition
Classification of Myelodysplastic Syndromes:
of T to LDA seems unlikely to improve average
Analysis of 1640 Patients
remission rate in poor prognosis AML/MDS. U. Germing,* N. Gattermatm, C. Strupp,* M. Aivado,* C. Aul* HLA DR15 (DR2) is Over-Represented in Dept. of Hematology, Heinrich-Heine-University, Myelodysplastic Syndrome (MDS) and is Düsseldorf; Dept. of Hematology, St. Johannes Associated With a Response to Hospital, Duisburg, Germany Immunosuppression
A working group of the World Health Organisation
Yogen Saunthararajah, Ryotaro Nakamura,
proposed a new classification of MDS. Jamie Robyn, Fausto Loberiza, Kevin E. Brown,
Myeloproliferative CMML and RAEB-T were removed
Neal S. Young, A. John Barrett
and RAEB was split into two groups, with medullary
Hematology Branch, National Heart, Lung, and
blast counts below and above 10%. A group of
Blood Institute, National Institute of Health,
patients with less than 5% medullary blasts but
Bethesda, MD, USA
multilineage dysplasia was defined. MDS patients with
In vitro and clinical data suggests that immune-
5q- were considered a separate group. The present
mediated marrow suppression, well defined in
study validates this classification with respect to
aplastic anemia (AA), is also a feature of some
prognosis and cytogenetic features in a large series of
patients with MDS. However autoimmune mechanisms
patients (n=1640) with a long-term follow up.
in MDS, and the characteristics of patients likely torespond to immunosuppression remain incompletely
defined. Since HLA-DR2 and its commonest defined
p < 0.00005
allele HLA DR15 are known to be overexpressed in
AA, we studied serologically-defined HLA DR
frequencies in 1752 AA and 707 MDS (RA, RAEB,
and RARS) patients undergoing stem cell transplants
reported to the International Bone Marrow Transplant
Registry (IBMTR) and molecularly-defined HLA DR
frequencies in patients with AA (n=100) or MDS
(n=82) treated with immunosuppressive regimens at
NIH. Compared with 14.2% (n=3978) in healthy North
American controls, the frequencies of HLA DR-2 in
MDS and AA patients were 26.5% (χ2=62, p ≤ 0.0001)
and 38% (χ2=400, p < 0.0001), respectively. In the NIHCaucasian patients, molecular typing revealed that
Figure 1. PSA=pure sideroblastic anemia; PRA=pure refractoryanemia; RCMD=refractory cytopenia with multilineage dysplasia;
HLA-DR 15 frequency (constituting >80% of the
RSCMD=refractory sideroblastic anemia with multilineage dysplasia.
serologically defined HLA DR2 allele) was increasedin both AA (58%, χ2= 92, p<0.0001) and MDS (41%
We confirmed a significant difference in survival and
χ2=30, p<0.0001) compared with Caucasian controls
frequency of AML evolution between RAEB I and
(14.4%, n=4980). In multivariate analysis of NIH MDS
RAEB II, and a striking difference between pure
patients, HLA DR15 was significantly associated with
refractory anemia and multilineage dysplasia (with or
without ring sideroblasts). Karyotype anomalies weremore frequent in patients with multilineage dysplasia.
The good prognosis of 5q- patients was restricted tothose with medullary blast below 5%. The WHO
classification defines morphological subgroups thatclearly differ with respect to prognosis.
The MDS Foundation relies entirely on gifts andmembership fees to further its work. We would
Myelodysplastic Syndromes, from FAB to
like to acknowledge the generosity of the
WHO: Comparison of Classifications on 431
following individuals and organizations that
Unselected Patients from a Single Institution
have recently provided gifts to the Foundation:
T. Noesslinger,* R. Reisner,* H. Gruener,* H. Tuechler,* E. Pittermann,* M. Pfeilstoecker* Mrs. Naomi J. Sapp (Intr. by Renate Heinz) Dansville, NY 3rd Med. Dept. for Haematology and Ludwig Mrs. Hertisene C. Griffin Boltzmann Institute for Hematology and Leukemia Hamlet, NC Research, both Hanusch Hospital Vienna, Vienna, Austria H. Joachim Deeg, MD Seattle, WA
In 1976 the FAB group established for the first timediagnostic criteria for myelodysplastic syndromes
Mr. Norman Greer
(MDS). In 1982 the same group introduced the FAB-
Long Beach, NY
classification (RA, RARS, RAEB, RAEB-t, CMML). In
Mr. Aaron Rabinowitz
1999 a revised classification (WHO) was published: RA,
RARS, Refractory Cytopenia with multilineagedysplasia (RC+Dys), RAEB, 5q- syndrome and MDS
Mr. George C. Allen
unclassifiable; CMML and RAEB-t should be excluded. Koloa, HI and Ellsworth, ME
Between 1976 and 1999 431 patients (median survival
The Foundation extends its sincerest thanks to
30 months) were diagnosed at our institution as
primary MDS according to FAB-classification: 142RA (med. surv. 66 mo), 47 RARS (73 mo), 92 RAEB(15 mo), 51 RAEB-t (9 mo), 99 CMML (24 mo). 281patients (median survival 43 months) were classifiableaccording to WHO: 43 RA (66 mo), 4 RARS (65 mo),91 RC+Dys (86 mo, in FAB: 65 RA, 26 RARS), 92
MDS Patient Registry
RAEB (15 mo), 1 5q-syndrome, 50 MDS unclassifiable(67 mo, in FAB: 33 RA, 17 RARS). We compared bothclassifications using morphological and clinical data,
Pharmacia & Upjohn generously provided an
as well as cytogenetics. In addition we studied the
unrestricted grant to help support the Myelodysplastic
homogeneity of the above mentioned subgroups by
Syndromes Foundation’s Patient Registry. The
evaluating prognostic scoring systems, especially the
Foundation gratefully acknowledges this support and
IPSS, taking into account cytogenetic data. The first
looks forward to building the Patient Registry with our
expected phenomenon was a significant patient shift
Centers of Excellence. The Patient Registry will help
into the lower risk groups according to the IPSS (FAB
further research into the treatment of MDS.
58% vs. WHO 76% of the patients in low- andintermediate-1 risk group).
Our data stress the necessity of incorporatingcytogenetic results in classification parameters. Consequences for future clinical trials and also forfuture prognostic systems will be discussed. MDS Centers of Excellence Would you like your treatment center to become part of the referral system for MDS patients and be designated as a Center of Excellence? To be recognized as a Center of Excellence, an institution must have the following:
■ An established university (or equivalent) program
■ Documentation of peer-reviewed publications in the field
■ Recognized morphologic expertise in MDS
■ The ability and intention to register patients in the MDS
■ Available cytogenetics and/or molecular genetics
■ Ongoing research, including Institutional Review
Please contact the Foundation for further information andan application form for your center.The following centers have qualified as MDS Centers of Excellence: UNITED STATES Seattle Cancer Care Alliance OUTSIDE THE UNITED STATES Patras University Hospital University of Washington Cedars-Sinai Medical Center A.C. Camargo Hospital – Cancer Center Peter MacCallum Cancer Institute Southwest Regional Cancer Center University of Melbourne City of Hope National Medical Center Academic Hospital Free University Amsterdam Stanford University St. Johannes Hospital Stanford University Medical Center Dana-Farber Cancer Institute Heinrich-Heine University Centre Hospitalier Service des maladies de Sang Tufts University School of Medicine Duke University Universitaire of Lille South Hampton University New England Medical Center Duke University Medical Center The Royal Bournemouth Hospital D’ Hematologie Hôpital Cochin University of Arizona Indiana University University Paris V Service Tokyo Medical College Arizona Cancer Center Indiana University Medical Center Heinrich-Heine University Düsseldorf University of Aarhus University of Chicago Johns Hopkins Oncology Center University Hospital The University Hospital University of Chicago Medical Center Johns Hopkins Institutions Hôpital Saint Louis University of Athens University of Nebraska Mayo Clinic University Paris VII Laikon Hospital University of Nebraska Medical Center MCP Hahnemann University Hospital Universitario de Salmanca University of Cape Town University – New York Presbyterian Hospital Groote Schuus Hospital Weill Medical College of Cornell Medical College of Wisconsin Hospital Universitario La Fe Physicians and Clinics University of Dundee Medical School University Of Pennsylvania Bone Marrow Transplant Program Dundee Teaching Hospital University of Pennsylvania Cancer Center Johann Wolfgang Goethe University Memorial Sloan-Kettering University of Innsbruck Cancer Center University of Rochester Community Hospital Karolinska Institute University of Rochester Medical Center Huddinge University Hospital Prim. Univ. Prof. Dr. Franz SchmalzlNew York Medical College University of Nijmegen Zalmen A. Arlin Cancer Center University of South Florida University Hospital St. Radboud King Chulalongkorn H. Lee Moffitt Cancer Center Memorial Hospital and Research Institute New York Presbyterian Hospital University of Tasmania Columbia College of Physicians Royal Hobart Hospital and Surgeons King’s Healthcare NHS Trust University of Texas King’s College Hospital Health Sciences Center University Tor Vergata New York University Ospedale S. Eugenio School of Medicine Kyoto University Hospital University of Texas North Shore University Hospital MD Anderson Cancer Center Medizinische Hochschule Hannover University of Vienna Hannover Medical School Oregon Health Science University Washington University School of Medicine Oregon Cancer Center Barnard Cancer Center Odense University Hospital Rush Presbyterian – William Beaumont Hospital, St. Luke’s Medical Center Cancer Center Rush Cancer Institute In Memorium A memorial fund has been established in the name of Mr. Jerry Dashe
Donations have been made in Mr. Dashe’s memory by:
A memorial fund has been established in the name of Mr. Frank T. Akins
Donations have been made in Mr. Akins’ memory by:
A memorial fund has been established in the name of
Barry Mizes and Ellen Bern, Saint Louis, MOMrs. Eva Diossy
Donations have been made in Mrs. Diossy’s memory by:
A memorial fund has been established in the name of Mrs. Frances N. Artuso
Donations have been made in Mrs. Artuso’s memory by:
William & Linda IversenPalatine, ILA memorial fund has been established in the name of Mrs. Jean Hackney
Donations have been made in Mrs. Hackney’s memory by:
A memorial fund has been established in the name of Mrs. Irene Kulnis
Donations have been made in Mrs. Kulnis’ memory by:
A memorial fund has been established in the name of Mr. Eduardo Perez Casalduc
Donations have been made in Mr. Casalduc’s memory by:
A memorial fund has been established in the name of A memorial fund has been established in the name of Mr. Kenneth Dale Cash Mr. Henry Lauro
Donations have been made in Mr. Cash’s memory by:
Donations have been made in Mr. Lauro’s memory by:
Robert & Jo-Ann Freund, Oakland, NJA memorial fund has been established in the name of Mrs. Marianne Lottes
Donations have been made in Mrs. Lottes’s memory by:
A memorial fund has been established in the name of Mrs. Peggy S. Cope A memorial fund has been established in the name of
Donations have been made in Mrs. Cope’s memory by:
Mr. David Miquelon
Donations have been made in Mr. Miquelon’s memory by:
Donna Peterson Byron Family, Collins, OKA memorial fund has been established in the name of Mrs. Anna M. Pagano
Donations have been made in Mrs. Pagano’s memory by:
Charles & Patricia Gallagher, Fairfield, NJA memorial fund has been established in the name of Mr. Eduardo Perez
Donations have been made in Mr. Perez’s memory by:
A memorial fund has been established in the name of Mr. Leo Pompliano
Donations have been made in Mr. Pompliano’s memory by:
risk hematologic malignancies. Contact: M. Laughlin, MD. Phone: 216-844-8609. Trials: An Update NCI-G98-1431. Case Western Reserve University/Ireland Cancer Center. Phase II study of unrelated umbilical cord blood transplantation for severe aplastic anemia,
The following trials are current as of the date of this
inborn errors in metabolism, or inherited hematologic
newsletter. We will update the list in The MDS News each
stem cell disorders. Contact: M. Laughlin, MD. Phone:
quarter. If you are a treating physician who would benefit
from any such study, you may want to contact the
NCI-G98-1444. Memorial Sloan-Kettering Cancer Center.
appropriate institution. If you are an MDS patient, you may
Phase II study of decitabine for MDS. Contact: S. Nimer,
wish to discuss a trial with your primary treating physician
to see if you qualify as a candidate. NCI-G99-1523. Phase II study of unrelated umbilical cord
Clinical trials study new interventions (drugs or
blood transplantation in patients with malignant or
procedures) to evaluate their safety and effectiveness in
nonmalignant hematological disease. Contact: E. Sievers,
humans. Trials follow a careful set of steps, allowing for
the systematic gathering of information to answer ques-
NCI-G99-1542. Phase I pilot study of RAS peptide cancer
tions and confirm hypotheses that were formed earlier, in
vaccine and sargramostim (GM-CSF) in patients with MDS.
either laboratory experiments or preliminary trials.
Contact: S.D. Nimer, MD. Phone: 212-639-7871.
A clinical trial falls into one of four phases:
NCI-G99-1543. Phase II study of allogeneic bone marrow Phase I. This is the first time a drug is used in humans.
transplantation in patients with hematologic malignancies.
The trial is designed to determine dosage, route of
Contact: P.V. O’Donnell, MD. Phone: 410-614-0205.
administration (oral, intravenous, or by injection), andschedule of administration (how many times a day or
NCI-G99-1544. Phase III study of sargramostim (GM-
week). In this phase researchers also begin to determine
CSF) following T-cell depleted allogeneic bone marrow
the drug’s safety. The phase I trial is normally conducted
transplantation in patients with MDS. Contact: P.V. O’Donnell, MD. Phone: 410-614-0205.
in healthy adults and enrolls only a small number ofpeople. NCI-G99-1573. Cancer Institute of New Jersey. Phase I Phase II. Patients with the disease receive the drug at
study of 12-O-tetradecanoylphorbol-13-acetate (TPA) in
dose levels determined in the earlier phase. The phase II
patients with relapsed or refractory hematologic malig-
trial begins to determine the effectiveness of the drug and
nancies or bone marrow disorders. Contact: R. Strair, MD. Phone: 908-235-6777.
provides more information about its safety. Phase III. The drug is tested alone or against an
NCI-G99-1603. UCLA-Jonsson Comprehensive Cancer
approved standard drug. The typical phase III trial enrolls
Center. Phase I pilot study of nonmyeloablative chemo-
a large number of patients. If it is a comparison trial,
therapy followed by unrelated peripheral blood stem cell
patients may be randomly assigned to receive either the
transplantation in patients with advanced hematologicmalignancies. Contact: C. Emmanouilides, MD. Phone:
new drug or the standard intervention. Phase IV. In phase IV the drug, already approved by theFDA and available to the public, undergoes continued
NCI-G99-1617. Duke University. Phase II study of
evaluation. The phase IV designation is rare.
allogeneic mixed chimerism peripheral blood stem celltransplantation utilizing in vivo and in vitro monoclonal
Some trials — screening studies evaluating supportive
antibody CD52 (campath-1H) in patients with high risks
care or prevention — are not conducted in phases. In
hematologic malignancies or diseases. Contact: D.A.
these trials a group following a certain disease combating
strategy, such as a detection method, is compared to acontrol group. NCI-G99-1618. University of Chicago. Phase II study of allogeneic peripheral blood stem cell transplantation following non-myeloblative chemotherapy in patients with U.S. Trials
hematologic malignancies. Contact: T. Zimmerman, MD. Phone: 773-702-4145. NATIONAL CANCER INSTITUTE TRIALS* NCI-G99-1660. Robert H. Lurie Comprehensive Cancer NCI-G97-1354. Ireland Cancer Center at Case Western
Center. Phase I study of unmanipulated bone marrow
Reserve University. Phase II study of allogeneic peripheral
augmented with CD34+ enriched peripheral blood stem
blood progenitor cell transplantation using histocompatible
cells in patients with hematologic malignancies
sibling-matched donor cells after high-dose busulfan/
undergoing allogeneic transplantation. Contact: Richard
cyclophosphamide for hematologic malignancy. Contact:
H. Lazarus, MD. Phone: 216-844-3629. NCI-G99-1661. Memorial Sloan-Kettering Cancer Center. NCI-G98-1406. Roswell Park Cancer Center. Phase II study
Phase I study of sodium salicylate in patients with
of cord blood transplantation for hematologic malignancies.
advanced MDS or refractory or relapsed acute
Contact: R. Wells, MD. Phone: 513-636-4266.
myelogenous leukemia. Contact: Stephen D. Nimer, MD. NCI-G98-1429. Ireland Cancer Center at Case Western
Reserve University. Phase II pilot study of unrelated
NCI-G99-1658. Robert H. Lurie Comprehensive Cancer
umbilical cord blood transplantation in patients with high-
Center, Northwestern University. Phase III randomized
study of captopril in patients undergoing autologous bone
antibody M195 and etoposide followed by autologous
marrow or stem cell transplantation. Contact: Leo I.
peripheral blood stem cell transplantation in patients with
advanced MDS or refractory leukemia. Contact: Peter
NCI-G00-1686. Robert H. Lurie Comprehensive Cancer
Center, Northwestern University. Phase II study of high
NCI-G00-1816. Johns Hopkins Oncology Center. Phase I
dose busulfan and cyclophosphamide followed by
study of nonmyeloablative cyclophosphamide plus
allogeneic bone marrow transplantation in patients with
haploidentical allogeneic bone marrow transplantation in
AML or MDS. Contact: Martin Stuart Tallman, MD. Phone:
patients with hematologic malignancies. Contact: Paul V.
O’Donnell, MD. Phone: 410-614-0205. NCI-G00-1688. Robert H. Lurie Comprehensive Cancer NCI-G00-1868. Ireland Cancer Center. Phase II study of
Center, Northwestern University Phase II pilot study of
nonmyeloablative conditioning using fludarabine, cyclo-
busulfan and etoposide with autologous bone marrow
phosphamide, and anti-thymocyte globulin, followed by
transplantation and filgrastim (G-CSF) in patients with
allogeneic peripheral blood stem cell transplantation in
acute myelogenous leukemia or MDS. Contact: Martin
patients with high risk hematologic malignancies or severe
Stuart Tallman, MD. Phone: 312-695-6180.
anaplastic anemia. Contact: Mary J. Laughlin, MD. Phone:
NCI-G00-1691. Robert H. Lurie Comprehensive Cancer
Center, Northwestern University. Phase I pilot study of T-
NCI-G00-1891. Herbert Irving Comprehensive Cancer
cell depleted partially matched related donor hematopoietic
Center. Phase II study of allogeneic peripheral blood stem
stem cell transplantation using intense pre- and post-
cell transplantation in patients with hematologic malignancy.
transplantation immunosuppression and megadose
Contact: David G. Savage, MD. Phone: 212-305-9783.
CD34 “Veto” cells in patients with high risk hematologic
NCI-G00-1897. Herbert Irving Comprehensive Cancer
malignancies. Contact: Richard K. Burt, MD. Phone: 312-
Center. Phase II Study of fludarabine and melphalan
followed by allogeneic or syngeneic bone marrow or
NCI-G00-1732. Ireland Cancer Center. Phase I study of
peripheral blood stem cell transplantation in patients with
fludarabine, carboplatin, and topotecan in patients with
hematologic malignancies or genetic disorders (summary
relapsed or refractory acute leukemia or advanced MDS.
last modified 01/2001). Contact: David G. Savage, MD.
Contact: Brenda Cooper, MD. Phone: 216-844-3213. NCI-G00-1742. University of Texas – MD Anderson Cancer NCI-G00-1898. Memorial Sloan-Kettering Cancer Center.
Center. Phase I study of psoralen (S-59) treated allogeneic
Phase III randomized study of caspofungin acetate versus
cellular immunotherapy plus mega T-cell depleted HLA
amphotericin B liposomal in patients with persistent fever
nonidentical blood progenitor cell transplantation in
and neutropenia following treatment for cancer. Contact:
patients with hematologic malignancies or bone marrow
Kent Sepkowitz, MD. Phone: 212-639-2441.
failure. Contact: James Gajewski, MD. Phone: 713-792-2933. NCI-G00-1899. Herbert Irving Comprehensive Cancer NCI-G00-1755. H. Lee Moffitt Cancer Center and Research
Center. Phase II study of allogeneic umbilical cord and
Institute. Phase II study of allogeneic bone marrow
placental blood transplantation in patients with chronic
transplantation using closely matched related and unrelated
myeloid leukemia, acute leukemia, lymphoma, myeloma,
donors in patients with malignant or nonmalignant
myelodysplasia, aplastic anemia, Fanconi’s Anemia,
hematologic disorders. Contact: Steven C. Goldstein, MD.
histiocytosis, hereditary immunodeficiency, or storage
disorder. Contact: David G. Savage, MD. Phone: 212-305-9783. NCI-G00-1759. H. Lee Moffitt Cancer Center and Research Institute. Phase II study of allogeneic bone NCI-G00-1900. Fred Hutchinson Cancer Research
marrow transplantation in patients with hematologic
Center. Phase II study of gemtuzumab ozogamicin,
malignancies. Contact: Steven C. Goldstein, MD. Phone:
fludarabine, and total body irradiation followed by
allogeneic peripheral blood stem cell or bone marrowtransplantation with cyclosporine and mycophenolate
NCI-G00-1762. Fred Hutchinson Cancer Research Center.
mofetil in patients with advanced acute myeloid leukemia
Phase I pilot study of fludarabine and low dose total body
or myelodysplastic syndrome. Contact: Eric Sievers, MD.
irradiation, followed by unrelated donor stem cell
transplantation, followed by unrelated donor lymphocyteinfusions in patients with hematologic malignancies. NCI-G01-1916. Jonsson Comprehensive Cancer Center,
Contact: Michael Maris, MD. Phone: 206-667-2480.
UCLA. Phase II/III randomized study of monoclonalantibody ABX-CBL versus anti-thymocyte globulin in
NCI-G00-1793. Fred Hutchinson Cancer Research Center.
patients with steroid resistant acute graft-versus-host
Phase II study of anti-thymocyte globulin and tumor
disease. Contact: Mary Carol Territo, MD. Phone: 310-
necrosis factor receptor IgG chimera in patients with MDS.
Contact: H. Joachim Deeg, MD. Phone: 206-667-5985. NCI-H98-0023. Johns Hopkins Oncology Center. Phase I NCI-G00-1801. Dana-Farber Cancer Institute. Phase I study
study of total body irradiation, tacrolimus, and
of HLA haploidentical bone marrow transplantation after ex
mycopheno-late mofetil with HLA-identical related-donor
vivo exposure to anti-B7 antibodies in patients with refractory,
bone marrow transplantation. Contact: E. Fuchs, MD.
high risk hematologic malignancies or bone marrow failure.
Contact: Eva Guinan, MD. Phone: 617-632-4932. NCI-H99-0028. Phase II study of iodine I 131 mono-clonal NCI-G00-1815. Memorial Sloan-Kettering Cancer Center.
antibody BC8 plus cyclophosphamide and total body
Phase I study of Yttrium Y 90 humanized monoclonal
irradiation followed by HLA matched related or unrelated
bone marrow transplantation in patients with advanced
NCI-T99-0080. Division of Clinical Sciences. Phase I study
acute myeloid leukemia or MDS. Contact: D.C. Matthews,
of arsenic trioxide in pediatric patients with refractory
leukemia or lymphoma. Contact: Frank Milton Balis, MD. Phone: 301-496-0085. NCI-H99-0031. Phase II study of donor lymphocyte infusion in patients with relapsed malignancies after allogeneic NCI-T99-0092. Johns Hopkins Oncology Center. Phase I
hematopoietic transplantation. Contact: M.E.D. Flowers,
study of azacitidine in combination with phenylbutyrate in
patients with recurrent, refractory, or untreated AML or
NCI-H00-0051. Memorial Sloan-Kettering Cancer Center.
MDS. Contact: Carole Miller, MD. Phone: 410-955-8603.
Phase I study of suberoylanilide hydroxamic acid (SAHA)
NCI-V96-0809. Memorial Sloan-Kettering Cancer Center.
in patients with advanced malignancies. Contact: William
Phase II study of T-cell-depleted marrow grafts with G-
CSF-stimulated, CD34-selected, E rosette-depleted PBPC
NCI-H00-0054. Fred Hutchinson Cancer Research Center.
from HLA haplotype-matched related donors for patients
Phase II study of bone marrow transplantation using
with leukemia who lack an HLA-matched related or
unrelated donors incompatible for 1 HLA locus antigen in
unrelated donor. Contact: R. O’Reilly, MD. Phone: 212-
patients with hematologic malignancies. Contact: Claudio
NCI-V96-0848. University of Washington Medical Center. NCI-H01-0067. Fred Hutchinson Cancer Research Center.
Phase I trial of subcutaneous outpatient interleukin-2 for
Phase I/II study of beclomethasone in patients with
patients with MDS. Contact: John Thompson, MD. Phone:
intestinal graft-versus-host disease with contraindication to
high-dose immunosuppressive therapy. Contact: David
NCI-V96-0941. Memorial Sloan-Kettering Cancer Center.
Hockenbery, MD. Phone: 206-667-4611.
Phase II study of high-dose cytarabine with a single high
NCI-P97-0097. Cancer and Leukemia Group B. Phase I/II
dose of idarubicin for newly diagnosed acute myelo-
study of omega-3 fatty acids in advanced cancer patients
genous leukemia: the AML-3 protocol. Contact: P. Maslak,
with cachexia. Contact: C.P. Burns, MD. Phone: 319-356-2038. NCI-P00-0168. North Central Cancer Treatment Group. NCI-V96-0950. Temple University Cancer Center. Phase II
Phase III randomized study of ondansetron in patients with
study of unrelated bone marrow transplantation with
advanced cancer and chronic nausea and emesis not due
cyclophosphamide and total-body irradiation for hemato-
to antineoplastic therapy. Contact: Steven R. Alberts, MD.
logic malignancies/disorders. Contact: K. Mangan, MD. NCI-T97-0027. Indiana University Cancer Center. Phase I NCI-V97-1361. Ireland Cancer Center at Case Western
study of recombinant human interleukin-12 (IL-12) after
Reserve University. Phase II study of busulfan, cyclo-
high-dose chemotherapy and autologous hematopoietic
phosphamide, and allogeneic bone marrow trans-
stem cell support in patients with hematologic
plantation in patients with leukemia, MDS, multiple
malignancies and solid tumors. Contact: M. Robertson,
myeloma, or lymphoma. Contact: H. Lazarus, MD. Phone:
NCI-T98-0001. MD Anderson Cancer Center. Phase I study NCI-V98-1387. Johns Hopkins Oncology Center. Phase I
of Dolastatin 10 in patients with refractory or relapsed acute
study of combined chemotherapy and donor lymphocyte
leukemia, MDS, or chronic myelogenous leukemia in blast
infusion for aggressive hematologic malignancies in
phase. Contact: J. Cortes, MD. Phone: 713-794-5783.
relapse after allogeneic bone marrow transplantation. NCI-T98-0017. University of Texas–MD Anderson Cancer
Contact: B. Mookerjee, MD. Phone: 410-614-6025.
Center. Phase I/II randomized study of PR1 leukemiapeptide vaccine and montanide ISA-51 in patients with
NCI-V98-1433. Marlene and Stewart Greenebaum Cancer
chronic myeloid leukemia, AML, or MDS. Contact: Jeffrey J.
Center at University of Maryland. Phase IV study of
allogeneic bone marrow transplantation depleted of T cellsby CD34 selection in patients undergoing transplantation
NCI-T98-0068. Johns Hopkins Oncology Center. Phase I
with a matched or mismatched antigen donor. Contact: M.
study of phenylbutyrate and tretinoin in patients with
Myelodysplastic Syndromes, chronic myelomonocyticleukemia, or acute myeloid leukemia. Contact: Steven D. NCI-V98-1447. Phase II Study of amifostine and high dose
cytarabine and mitoxantrone in patients with high risk andrelapsed acute myeloid leukemia and blast crisis chronic
NCI-T99-0013. Cancer Research Campaign, Glasgow.
myelogenous leukemia. Contact: H.D. Preisler, MD. Phone:
Phase I/II study of geldanamycin analogue (AAG) in
patients with advanced malignancies. Contact: S.B. Kaye,MD. Phone: 011-1-41-221-2824. NCI-V98-1455. Phase I/II study of high dose melphalan NCI-T99-0069. University of Michigan Comprehensive
with autologous peripheral blood stem cell support and
Cancer Center. Phase II study of azacitidine plus
amifostine cytoprotection in cancer patients. Contact: G.L.
amifostine in patients with MDS. Contact: Harry Paul Erba,
NCI-V98-1460. Johns Hopkins Oncology Center. Study of NCI-T-99-0071. Mayo Clinic Cancer Center. Phase I study
stem cell-augmented, elutriated grafts for prevention of
of PS-341 in patients with advanced malignancies or B-cell
graft-versus-host disease in patients undergoing allogeneic
lymphoproliferative disorders. Contact: Alex A. Adjei, MD.
bone marrow transplantation. Contact: P. O’Donnell, MD. NCI-V98-1485. Allegheny University Hospitals. Phase I/II study of topotecan, fludarabine, cytarabine, and filgrastim Membership Information
(T-FLAG) induction therapy followed by maintenancetherapy of either peripheral blood stem cells or isotretinoin
The MDS Foundation would like to have you as a member.
in patients with poor-prognosis acute myeloid leukemia,MDS, and recurrent or refractory acute lymphocytic
Membership is US$35 a year for physicians and other
leukemia. Contact: E. Besa, MD. Phone: 215-842-6980.
professionals. Patients, their families, and others interested
NCI-V98-1501. San Antonio Cancer Institute. Phase I study
in MDS may join at the reduced rate of $20.
of R115777 with gemcitabine in patients with advanced
Membership benefits include quarterly issues of the MDS
cancer. Contact: S.G. Eckhardt, MD. Phone: 210-616-5798. News, a special subscription rate of $105 for LeukemiaNCI-V99-1527. Phase II/III study of standard and novel Research (a substantial discount from the current
conditioning therapy and allogeneic blood or marrow
subscription rate of $1,193), and the worldwide Centers
transplantation in patients with severe aplastic anemia orhematologic malignancy. Contact: P.L. McCarty, Jr, MD.
of Excellence patient referral service.
If you would like additional information, please
NCI-V99-1533. Phase II study of amifostine, topotecan and
cytarabine in patients with poor risk MDS. Contact: H.C. Fung, MD. Phone: 626-359-8111. NCI-V99-1545. Phase II study of arsenic trioxide in patients
with recurrent or refractory acute myeloid leukemia, blastcrisis chronic myeloid leukemia, or MDS. Contact: Janice P. NCI-V00-1588. Marlene & Stewart Greenebaum Cancer
Center. Phase I pilot study of combined chemotherapy and
donor lymphocyte infusion in patients with hematologicmalignancies in relapse after allogeneic stem celltransplantation. Contact: Bijoyesh Mookerjee, MD. Phone:410-614-6025. NCI-V00-1608. Washington University Barnard Cancer NCI-951. Johns Hopkins Oncology Center. Phase I study
Center. Phase I/II study of arsenic trioxide with or without
of Bryostatin 1 and Sargramostim (GM-CSF) in patients
tretinoin in patients with refractory hematologic malignancies.
with refractory myeloid malignancies. Contact: B. Douglas
Contact: Randy A. Brown, MD. Phone: 314-454-8227. NCI-V00-1624. Marlene & Stewart Greenebaum Cancer NCI-99-C-0143. National Cancer Institute. Phase I pilot
Center, University of Maryland. Phase II study of
study of donor Th2 cells for prevention of graft-versus-host
nonmyeloablative conditioning regimen followed by HLA
disease following non-myeloablative, HLA-matched
matched sibling donor peripheral blood stem cell
allogeneic peripheral blood stem cell transplantation in
transplantation in patients with hematologic malignancies.
patients with hematologic malignancies. Contact: Michael
Contact: Bijoyesh Mookerjee, MD. Phone: 410-328-7394. NCI-2. Rush Cancer Institute. Phase II study of azacitidine in patients with relapsed or refractory acute myelogenous PHARMACEUTICAL TRIALS LISTED WITH NCI
leukemia or Myelodysplastic Syndrome. Contact: HarveyD. Preisler, MD. Phone: 312-563-2190. SUGEN-SU541. Called for institution. Phase II study of SU5416 in patients with advanced or refractory hemato- NCI-38. Stanford University Medical Center. Phase I/II
logic malignancies. Contact: Paul Scigalla, MD. Phone:
study of R115777 in patients with myeloproliferative
disorders. Contact: Peter L. Greenberg, MD. Phone: 650-725-8355. CHIMERIC-HM01. Chimeric Therapies Incorporated. Phase II/III randomized study of processed versus NCI-42. University of Chicago Cancer Research Center.
unprocessed unrelated bone marrow transplantation in
Phase I randomized study of R115777 in patients with
patients with acute or chronic leukemia or Myelodysplastic
advanced hematologic malignancies. Contact: Mark J.
Syndrome. Contact: James N. Lowder, MD. Phone: 949-
NCI-94. University of Texas–MD Anderson Cancer Center. Phase I study of PS-341 in patients with refractory or *For more information on NCI trials, contact cancernet.
relapsed AML, acute lymphoblastic leukemia, MDS, or
chronic myeloid leukemia in blast phase. Contact: JorgeCortes, MD. Phone: 713-794-5783. OTHER U.S. TRIALS NCI-450. University of Texas–MD Anderson Cancer Center. Phase I study of BMS-214662 in patients with acute CLB-69803. Cancer and Leukemia Group B. Phase I study
leukemia, Myelodysplastic Syndrome, or chronic myeloid
of 506U78 in patients with hematologic malignancies and
leukemia in blast phase. Contact: Jorge Cortes, MD.
renal or hepatic impairment. Contact: Todd S. Zimmerman,
Cedars-Sinai Medical Center. 104864-A/201. Phase III Eastern Cooperative Oncology Group. E-1996. Phase III
open-label multicenter, randomized, comparative study of
study of epoetin alfa with or without filgrastim (G-CSF) vs
topatecan, Ara-C and G-CSF (TAG) VS idarubicin, Ara-C
supportive therapy alone in patients with Myelodysplastic
and G-CSF (IDAG) in patients with RAEB (high risk), RAEB-
Syndromes. Contact: Kenneth B. Miller, MD. Phone: 617-
t or in patients with AML from a preceding phase of MDS.
Contact: M. Lill, MD. Phone: 310-423-2997. Eastern Cooperative Oncology Group. E-2998. Phase III Children’s Cancer Group. CCG-2951. Children’s Hospital
randomized study of Flt3 ligand in patients with acute
Medical Center. Phase II study of salvage chemotherapy
myeloid leukemia in second or subsequent complete
for acute myeloid leukemia or MDS in first relapse or
remission. Contact: Richard L. Schilsky, MD. Phone: 773-
refractory to initial remission-induction therapy and for
secondary acute myeloid leukemia. Contact: R. Wells, MD. Fred Hutchinson Cancer Research Center. FRCRC
#1536. Transplantation of peripheral blood stem cells from
Children’s Cancer Group. CCG-2961. Multicenter. Phase
related or unrelated volunteer donors in patients with “less
III randomized study for untreated pediatric acute myelo-
advanced” MDS. Conditioning therapy includes busulfan
genous leukemia and MDS: intensively timed induction
(targeted to a pre-determined plasma level) and cytoxan
chemotherapy followed by consolidation with the same
(targeted BUCY); patients up to 65 years of age. Contact:
chemotherapy versus fludarabine/cytarabine/idarubicin
followed by intensification either with high-dose cytarabine/
Fred Hutchinson Cancer Research Center. FHCRC #1006.
asparaginase with versus without subsequent IL-2 or with
Autologous stem cell transplantation for myelofibrosis
A1 BMT. Contact: B. Lange, MD. Phone: 215-590-2249.
following conditioning with busulfan. Patients up to 70 years
Children’s Cancer Group. CCG-A2971. Phase III study of
of age. Contact: H.J. Deeg, MD. Phone: 206-667-4324.
children with Down Syndrome and transient myelo-
Fred Hutchinson Cancer Research Center. FHCRC
proliferative disorder, AML, or MDS. Contact: Alan Scott
#1032. Transplantation for myelofibrosis from related or
unrelated donors after conditioning with busulfan plus
Children’s Cancer Group. CCG-B942. Detection of minimal
cytoxan or busulfan plus TBI. Patient age limit 65. Contact:
residual disease in children receiving therapy for AML or
MDS. Contact: E. Sievers, MD. Phone: 206-667-5757. Fred Hutchinson Cancer Research Center. FHCRC City of Hope National Medical Center. IRB #97128.
#1463. Low-dose TBI and fludarabine followed by unrelated
Molecular pathogenesis of MDS and AML in the elderly.
donor stem cell transplantation for patients with hema-
Contact: R. Bhatia, MD. Phone: 626-359-8111, x 2683.
tological malignancies. This multi-center trial targets older
City of Hope National Medical Center. IRB #99041.
(>55 years) patients, and patients who, because of
Phase II study of IV busulfan combined with 12cGy of
concurrent medical problems, cannot tolerate a traditional
fractionated TBI and etoposide (VP-16) as a preparative
transplant. Patients from the following diagnoses are eligible
regime for allogeneic bone marrow transplantation for
for therapy: CML, AML, ALL, MDS, multiple myeloma, and
patients with advanced RAEB and RAEB-t hematological
lymphoma. Contact: M. Maris, MD. Phone: 206-288-1024.
malignancies. Contact: A. Stein, MD. Phone: 626-359-
Fred Hutchinson Cancer Research Center. #1519.
Transplantation of peripheral blood stem cells from relatedor unrelated donors in patients with “advanced” MDS. City of Hope National Medical Center. IRB #99045. Autologous stem cell transplantation for MDS in first remission.
Conditioning consists of fludarabine and busulfan
Contact: H. Fung, MD. Phone: 626-359-8111, x2405.
(targeted to a predetermined plasma level). Patients up to65 years are eligible. Contact: Claudio Anasetti, MD. City of Hope National Medical Center. IRB 398056.
Treatment of poor risk MDS with the combination of
Fred Hutchinson Cancer Research Center. #1555.
amifostine, topotecan and Ara-C as a phase II study.
Transplantation of peripheral blood stem cells from related
Contact: H. Fung, MD. Phone: 626-359-8111, x 2405.
or unrelated donors for the treatment of “advanced” MDS
Cleveland Clinic. SMC-101-1020. Phase IIb study of thymo-
(CD33+). Conditioning includes Mylotarg (for two doses),
globulin in transfusion dependent patients with RA or RAEB.
fludarabine and 200 cGy of total body irradiation. Patients
Contact: Matthew Kalaycio, MD. Phone: 216-444-3705.
are being evaluated individually for eligibility. Contact: Eric
Dana Farber Cancer Institute. DFCI 99-249. Vaccine
trial–phase I–patients with MDS or relapsed acute myelo-
Fred Hutchinson Cancer Research Center. #1596.
genous leukemia. Cells will be harvested via bone marrow
Transplantation from related donors for high risk patients
biopsy and aspirate or phersis. Injection will be
with MDS. Conditioning includes a "non-myeloblative"
administered via sub-Q at specified times. Contact: D.
regimen of fludarabine and 200 cGy of total body
irradiation. Patients are evaluated individually for eligibility. Duke University Medical Center. Multicenter trial of
Contact: David Maloney, MD, PhD. Phone: 206-288-1024.
induction-type chemotherapy for patients with high-risk
Fred Hutchinson Cancer Research Center. FHCRC
MDS as defined by the International Prognostic Scoring
#1478. Non-transplant therapy for “less advanced” MDS
System. Contact: C. de Castro, MD. Phone: 919-684-8964.
with ATG plus Enbrel. No age restrictions. Contact: H.J. Duke University Medical Center. Phase II study of
amifostine in patients with MDS. Contact: C. de Castro, MD. Guthrie Clinic, Ltd. ECOG 1996. Phase III evaluation of
EPO with or without G-CSF versus supportive therapy
alone in the treatment of MDS. Contact: Michele Chaborek,
MCP Hahneman University. T-MDS-001. A randomized,
double blind, placebo-controlled trial composing best
Hahnemann University at MCP.
supportive care and thalidomide for the treatment of
combination study of topotecan, fludarbine, cytosine,
anemic patients with MDS followed by an open-label
arabinoside and G-CSF (TFLAG) induction therapy in
treatment with thalidomide. Contact: Emmanuel Besa, MD.
patients with poor prognosis AML, MDS and relapsed/
refractory ALL. Contact: E. Besa, MD. Phone: 215-842-6980. MD Anderson Cancer Center. ID99-059. ATG +/– Hoosier Oncology Group. Phase II trial of topotecan in
cyclosporin +/– fludarabine in RA, RARS, RAEB <10%
patients with MDS. Contact: Paul Walker, MD. Phone: 765-
blasts Contact: Jeff Mollaren, MD. Phone: 713-745-4820.
MD Anderson Cancer Center. DM 00-101. Mylotarg +/– Indiana University Medical Center. B3T-MC-JTAH(a). Phase
IL-II in AML, RAEB, RAEB-t, CMML, >10% blasts in
II study of LY335979 plus daunorubicin and cytarabine in
patients 65 years and older with normal cytogenetics.
subjects with de nova high risk acute myelogenous
Contact: Elihu Estey, MD. Phone: 713-794-7544.
leukemia or relapsed/refractory acute myelogenous
MD Anderson Cancer Center. Idarubicin and Ara-C CI in
leukemia. Contact: L. Cripe, MD. Phone: 317-274-3545.
AML, RAEB, RAEB-t, CMML, with >10% blasts in patients
Indiana University Medical Center. IU #9907-25. Induction
65 years and older with abnormal cytogenetics. Contact:
Chemotherapy with the addition of a new MDR inhibitor for
patients with RAEB-t or AML that has progressed from a
MD Anderson Cancer Center. DM00-186. Thalidomide in
documented phase of MDS. Contact: L. Cripe, MD. Phone:
RA, RARS, MDS with low to intermediate risk IPSS.
Contact: Deborah Thomas, MD. Phone: 713-745-4616.
Indiana University School of Medicine. Phase II trial of MD Anderson Cancer Center. IDP00-269. Reverse
subcutaneously administered recombinant human inter-
transcriptase inhibitors in refractory or relapsed MDS, AML,
leukin-11 in thrombocytopenic patients with MDS. Contact:
MPD. Contact: Hagop Kartarjian, MD. Phone: 713-792-7026.
MD Anderson Cancer Center. DM99-142. Oral Topotecan James Haley Veterans Hospital-Tampa. SMC-101-1029.
in hematologic myeloid malignancies Contact: Miloslav
Phase IIb study of thymoglobulin in transfusion dependent
patients with RA or RAEB. Contact: Hussain Saba, MD. Phone: 813-972-7582.
MD Anderson Cancer Center. ID95-124. 9-Nitrocamp- tothecin in MDS, CML, MPD. Contact: Jorge Cortes, MD. Johns Hopkins Oncology Center. J0051. Phase I trial:
GM-CSF and Bryostatin-1 in combination to treat MDS,AML, and other myeloid malignancies. Therapy is designed
MD Anderson Cancer Center. Idarubicin and Ara-C
to enhance differentiation of myeloid progenitors and blasts
double induction in AML, RAEB, RAEB-t, CMML with >10%
to improve marrow function and eliminate tumor cell clone.
blasts in patients < 50 years old. Contact: Elihu Estey, MD.
Cotnact: Douglas Smith, MD. Phone: 410-614-5068. Johns Hopkins Oncology Center. J9852. GM-CSF after MD Anderson Cancer Center. Mylotarg and BID
T-lymphocyte-depleted allogeneic BMT for MDS. Contact:
Fludarabide/Ara-C and cyclosporin in AML, RAEB,
P. O’Donnell, MD, PhD. Phone: 410-614-0205.
RAEB-t, CMML with .10% blasts in patients aged 50–64years. Contact: Elihu Estey, MD. Phone: 713-792-7544.
Johns Hopkins Oncology Center. J9845. Non-myelo- ablative allogeneic BMT for hematologic malignancies. Medical College of Wisconsin. MCW 91-126. Marrow
Contact: Ian W. Flinn, MD. Phone: 410-955-8781.
transplantation for patients with hematologic malignancies. Contact: D. Vesole, MD. Phone: 414-805-4646. Johns Hopkins Oncology Center. Opening March 2000. A phase I, dose finding trial of sodium phenylbutyrate in Medical College of Wisconsin. MCW 93-23. Allogeneic
combination with all transretinoic acid in patients with MDS
marrow transplantation for patients with hematologic
and AML. Contact: Steven Gore, MD. Phone: 410-955-8781.
malignancies and marrow failure states from genotypicallyhaplo-identical family members. Contact: D. Vesole, MD. Mayo Clinic. 0-215-98. A pilot study of antithymocyte
globulin in anemic patients with RA or RAEB. Contact:Doctors A. Tefferi, M. Elliott, L. Letendre, M. Litzow, D. Medical College of Wisconsin. MCW 95-18. T-cell
depletion in unrelated-donor marrow transplantation. Contact: D. Vesole, MD. Phone: 414-805-4646. MCP Hahneman University.
randomized study of the safety and efficiency of 2 dose
Medical College of Wisconsin. MCW 97-137. Amifostine/
schedules of Gentuzumab Ozogomicin (mylotarg) in
pentoxifylline/ciprofloxacin/dexamethasone for low-risk
patients with Intermediate-2 or High Risk MDS. Contact:
MDS. Contact: D. Vesole, MD. Phone: 414-805-4646. Medical College of Wisconsin. MCP Hahneman University. A Phase II study of a
Amifostine/topotecan versus pentoxifylline/ciprofloxacin/
combination of topetecan, fludirabine, ARA-C and G-CSF CT-
dexamethasone for high-risk MDS. Contact: D. Vesole,
Flag. Contact: Emmanuel Besa, MD. Phone: 215-842-6980.
MCP Hahneman University. E1996. Phase III evaluation of Medical College of Wisconsin. MCW 99-10. Total
EPO with or without G-CSF versus supportive therapy
lymphoid irradiation, melphalan and fludarabine for T-cell-
alone in the treatment of MDS. Contact: Emmanuel Besa,
depleted allogeneic peripheral-blood stem cell trans-
plantation. Contact: D. Vesole, MD. Phone: 414-805-4646. Memorial Sloan Kettering Cancer Center. 190. Phase II
RAEB-t; (c) high risk MDS defined by IPSS of 2.0; or (d)
study of Arsenic Trioxide in relapsed or refractory, CML.
AML which has evolved from a pre-existing MDS. Contact:
Contact: David Scheinberg, MD. Phone: 212-639-5010.
C. Hesdorffer, MD. Phone: 212-305-4907. Multicenter. SMC-101-1020. Phase IIb study of thymo- Pediatric Oncology Group. POG-9720. Phase II study of
glogulin in transfusion dependent patients with RA or RAEB.
idarubicin and cladribine in children with recurrent or
Contact: Elizabeth Squiers, MD. Phone: 510-789-4535.
refractory AML. Contact: Craig A. Hurwitz, MD. Phone: 207-
National Heart, Lung and Blood Institute. NHLBI-99-H-
0050. Phase II study of nonmyeloablative allogeneic
Pediatric Oncology Group. POG-9362. Phase II study of
peripheral blood stem cell transplantation in patients with
IFN-A for pediatric HIV-related malignancies. Contact: V.M.
hematologic disease or cancer. Contact. R.W. Childs, MD. Rush Cancer Institute. MDS-9914. A pilot study of National Heart Lung and Blood Institute. Phase II study of
thalidomide combined with pentoxifylline, ciprofloxacin,
leucovorin in patients with 5q- syndrome. MDS subtypes
and dexamethasone (PCD) in patients with MDS. Contact:
RA, RARS, and RAEB are eligible. Patients must have 5q-
as their sole cytogenetic abnormality and meet criteria for
Rush Cancer Institute. MDS 9906. A pilot study of anti-CD-
moderate to severe cytopenias. Phone: 301-496-5150.
20 monoclonal antibody (Rituxan) in the treatment of patients
National Heart Lung and Blood Institute. Clinical
with MDS. Contact: A. Raza, MD. Phone: 312-455-8474.
protocol studying the use of G-CSF-mobilized T-depleted
Rush Cancer Institute. MDS 2000-02. Combination of
donor peripheral blood progenitor/stem cells followed by
thalidomide and topetecan in the treatment of patients with
delayed donor T cells to optimize graft-verses-tumor
high risk MDS. Contact: A. Raza, MD. Phone: 312-455-8474.
effects in patients with hematologic malignancies. Phone:
Rush Cancer Institute. MDS 2000-03. Combination of
etanercept (TNFR:Fc) and thalidomide in the treatment of
National Heart Lung and Blood Institute. Phase II study
patients with MDS. Contact A. Raza, MD. Phone: 312-
of antithymocyte globulin (ATG) and cyclosporine in
patients with MDS (RA, RARS, RAEB) who have moderate
Rush Cancer Institute. MDS 2000-04. An open label,
to severe cytopenias. Contact: Laura B. Wisch, RN.
prospective, randomized, stratified, controlled, multi-
center, phase Iib study of the impact of thymoglobulin
New York Medical College. 30/38. A phase III, open-label,
therapy on transfusion needs of patients with early MDS.
multicenter, randomized, comparative study of topetecan,
Contact: A. Raza, MD. Phone: 312-455-8474.
Ara-C and G-Csf (TAG) versus idarubicin, Ara-C and G-
Rush Cancer Institute. MDS 2000-05. A three year
CSF (IDAG) in MDS patients RAEB (high risk), RAEB-t or in
evaluation of the overall and leukemic free survival of
patients with AML from a preceding phase of MDS.
patients who received thymoglobulin therapy for early
Contact: Karen Seiter, MD. Phone: 914-493-8374.
MDS. Contact: A. Raza, MD. Phone: 312-455-8474. New York Medical College. 0012-2000. An open-label, Rush Cancer Institute. 0903B1-207-US. A randomized
prospective, stratified, randomized, controlled, multicenter,
study of the safety and efficacy of two dose schedules of
phase IIB study of the impact of thymoglobulin therapy on
gemtuzumab ozogamacin in patients with intermediate-2 or
transfusion needs of patients with early MDS. Contact:
high risk MDS. Contact: A. Raza, MD. Phone: 312-455-8474. Rush Cancer Institute. MDS 2000-08. A pilot study to test New York Medical Hospital. SMC-101-1020. Phase IIb
the efficacy of glivec (ST1571) in patients with chronic
study of thymoglobulin in transfusion dependent patients
myelomoncytic leukemia. Contact: A. Raza, MD. Phone:
with RA or RAEB. Contact: Michael Schuster, MD. Phone:
Rush Presbyterian. SMC-101-1020. Phase IIb study of New York Presbyterian Hospital – Columbia Medical
thymoglobulin in transfusion dependent patients with RA or
Center. 104864-A/201 Study. Phase III open label,
RAEB. Contact: Azra Raza, MD. Phone: 312-455-8474.
randomizes comparative study of topotecan, Ara-C and G-CSF (TAG) vs. idarubicin, Ara-C and GCSF (IDAG) in MDS. Southwest Oncology Group. SWOG-S9920. Phase III
Over the age of 18 with either: (a) RAEB; (b) RAEB-t; (c)
randomized study of total body irradiation (TBI) plus
high risk MDS defined by IPSS of 2.0; or (d) AML which has
busulfan versus TBI plus cyclophosphamide followed by
evolved from a pre-existing MDS. Contact: Charles
allogeneic peripheral blood stem cell transplantation in
patients with advanced MDS or MDS related AML. Contact:Charles A. Coltman, Jr., MD. Phone: 210-616-5580. New York Presbyterian Hospital – Columbia Medical Center. Camp 026. Autologous peripheral stem cell Texas Cancer Center. SMC-101-1020. Phase IIb study of
harvesting and transplantation for high risk MDS. IPS score
thymoglobulin in transfusion dependent patients with RA or
greater than 2.0, no allo match, age 18–70. Idarubicin/Ara-
RAEB. Contact: Craig Rosenfeld, MD. Phone: 972-566-7790.
C for mobilization followed by BMT with a BU/Cy regimen. University of Connecticut Health Center.
Contact: Charles Hesdorffer, MD. Phone: 212-305-4907.
Cooperative Group Trial. EPO+/– GCSF VS. supportive care
New York Presbyterian Hospital – Columbia Medical
alone. Contact: B. Greenberg, MD. Phone: 860-679-2100. Center. 104864-A/201 Study. Phase III open label, University of Connecticut Health Center. 99-285. Partial
randomizes comparative study of topotecan, Ara-C and
matched related donor allogeneic stem cell transplant with
G-CSF (TAG) vs. Idarubicin, Ara-C and GCSF (IDAG) in
a non-myeloablative preparative regimen. Contact: R.
MDS. Over the age of 18 with either: (a) RAEB; (b)
University of Connecticut Health Center. 99-262. Non- University of Texas Health Science Center. IRB # 978-
myeloablative therapy followed by adoptive immuno-
5008-302. Sequential antithymocyte globulin (ATG) and
therapy with allogeneic HLA matched stem cell transplant.
amifostine for the treatment of MDS. ATG is given as an
Contact: R. Bona, MD. Phone: 860-679-2257.
intravenous infusion in the hospital over 4 days. Skin
University of Chicago. UC 9581. Allogeneic peripheral
testing for sensitivity to ATG performed prior to the first
blood stem cell transplantation using a non-myeloblative
dose. Amifostine is given as an IV pus. Contact: J.
preparative regimen for patients with hematologic malig-
nancies. Contact: R.A. Larson, MD. Phone: 773-702-2070. University of Washington, Seattle Cancer Care Alliance. University of Florida. SMC-101-1020. Phase IIb study of
95-04570-A 05. Determining safety, tolerance, and maximum
thymoglobulin in transfusion dependent patients with RA
tolerated dose of SC Interleukin-2 in MDS patients.
or RAEB. Contact: Katarzyna Finiewicz, MD. Phone: 352-
Contact: John A. Thompson, MD. Phone: 206-288-2041.
Wake Forest. SMC-101-1020. Phase IIb study of thalido- University of Iowa Hospitals and Clinics. Cancer and
mide in transfusion dependent patients with RA or RAEB.
Leukemia Group B. CLB-69803. Phase I study of 506U78 in
Contact: Kenneth Zamkoff, MD. Phone: 336-716-7972.
patients with hematologic malignancies and renal or
Washington University in St. Louis. 95-0384. Washington
hepatic impairment. Contact: Todd M. Zimmerman, MD.
University School of Medicine. A phase II study to evaluate
the tumor response rate and toxicity of granulocyte-colony
University of Maryland Greenebaum Cancer Center.
stimulating factor (G-CSF) primed donor leukocyte infusion
UMGCC 0050. Phase I trial of oral medication MS-275,
administered to patients with relapsed hematologic
given for 28 days to reinstate the expression of genes
malignancy occurring after allogeneic bone marrow or
which cause cells to mature. Contact: Judith E. Karp, MD.
peripheral blood stem cell transplant. Contact: D.R. University of Maryland Greenebaum Cancer Center. Washington University in St. Louis. 95-0763. Washington
UMGCC 0052. Flavopiridol’s role in cell death (apoptosis)
University School of Medicine. High dose rate/low total
and proliferation in order to increase sensitivity to Ara-C
dose-single exposure total body irradiation as conditioning
and mitoxantrone. Contact: Judith E. Karp, MD. Phone:
for related donor allogeneic peripheral blood stem celltransplantation. A phase II study to evaluate engraftment
and duration of neutropenia. Contact: D. Adkins, MD. University of Maryland Greenebaum Cancer Center.
UMGCC 0001. The use of topetecan, Ara-C, and
Washington University in St. Louis. 97-0793. Washington
mitoxantrone TST in aggressive MDS. Contact: Judith E.
University School of Medicine. High dose rate/low total
dose-single exposure total body irradiation as conditioning
University of Maryland Greenebaum Cancer Center.
for unrelated and mismatched related donor bone marrow
UMGCC 0076. Use of bevacizumab to inhibit vascular
transplantation: A phase II study to evaluate engraftment.
endothelial growth factor (VEGF) production after
Contact: D. Adkins, MD. Phone: 314-454-8490.
chemotherapy with Ara-C and Mitoxantrone. Contact:
Washington University in St. Louis. 98-0502. Washington
Judith E. Karp, MD. Phone: 410-328-7394.
University School of Medicine. Stem cell transplantation for
University of Michigan Comprehensive Cancer Center.
Aplastic Anemia and various malignancies. Contact: R.
UMCC 0068. A randomized study of the safety and efficacy
of two dose schedules of gemtuzumab ozogamicin
Washington University in St. Louis. 101-1020. An open-
(Mylotarg) in patients with intermediate-2 or high risk MDS
label, prospective, stratified, randomized, controlled,
Contact: Harry P. Erba, MD, PhD. Phone: 734-647-8921.
multicenter, phase IIB study of the impact of thymoglobulin
University of Michigan Medical Center. UMCC 9906.
therapy on transfusion needs of patients with early MDS.
Combination of azacitadine and amifostine in the treatment
Contact: John F. DiPersio, MD, PhD. Phone: 314-454-8317.
of adults with MDS. Contact: Harry P. Erba, MD. Phone:
734-647-8921. JoAnn Goodson, Data Manager.
Washington University in St. Louis. 101-1022. A three University of Michigan Medical Center. Clinical treatment
year evaluation of the overall and leukemic free survival of
via bone marrow transplant for hematological malignancies.
patients who received thymoglobulin therapy for early
Contact: Dr. Harry D. Erba, MD, PhD. Phone: 734-647-8921.
MDS. Contact: John F. DiPersio, MD, PhD. Phone: 314-
University of Rochester Cancer Center. 18400. A phase
2 study of SU5416 in patients with hematologic malignancies,
Westchester Medical Center, New York Medical College.
including refractory acute myeloid leukemia, myelodysplasia,
008/2000. Non-myeloblative chemotherapy with pentostatin,
refractory acute lymphocytic leukemia, philadelphia nega-
mitoxantrone and cytarabine for engraftment of allogeneic
tive myeloproliferative disorders or chronic myelogenous
hematopoietic progenitor cells in patients with hemato-
leukemia. Contact: Wanda Bates, Administrative Assistant.
logical malignancies. Contact: Delong Liu, MD and Karen
Myria Christophini Selected Exhibitions 2011: Bealtainne, The Glue Factory, Glasgow (30 April-14 May 2011). 2010: Half-knowledge/half., Grace and Clark Fyfe Gallery, Glasgow(12-28 2007: If it is to be, The BRIDGE Gallery, London (07-12 September 2007). 2007: Out of Nothing, Canterbury Environment Centre, Canterbury(01-10 May 2005: Transmission: Laurence Rathsack, Liz B
Lutte contre les addictions Lutte contre les addictions - Activité des sénateurs - Les questions au gouvernement - Les questions orales - Date de mise en ligne : mercredi 11 juin 2008 Sénateurs du groupe CRC-SPG Lutte contre les addictions Monsieur le président, madame la ministre, mes chers collègues, au lieu du mot : « addictions », j'aurais préféré quesoit employé le