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Table of Contents Purpose of This PDQ Summary
General Information About Myelodysplastic Syndromes
Classification of Myelodysplastic Syndromes
Treatment Option Overview
De Novo and Secondary Myelodysplastic Syndrome
Previously Treated Myelodysplastic Syndrome
Get More Information From NCI
Changes to This Summary (11/06/2008)
More Information
Purpose of This PDQ Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of myelodysplastic syndromes. This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board.
Information about the following is included in this summary:
- Prognostic factors.
- Cellular classification.
- Treatment options by cancer stage.
This summary is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Some of the reference citations in the summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations.
This summary is available in a patient version, written in less technical language, and in Spanish.
Back to Top General Information About Myelodysplastic Syndromes
The myelodysplastic syndromes (MDS) are a group of disorders characterized by one
or more peripheral blood cytopenias secondary to bone marrow dysfunction. The MDS are diagnosed in slightly more than 10,000 people in the United States yearly for an annual age-adjusted incidence of 3.4/100,000 people.[1] The MDS are more common in men and whites. The
syndromes may arise de novo, or secondarily after treatment with chemotherapy
and/or radiation therapy for other diseases. Secondary myelodysplasia usually
has a poorer prognosis than does de novo myelodysplasia. Prognosis is directly
related to the number of bone marrow blast cells and to the amount of
peripheral blood cytopenias. The MDS transform to acute myeloid leukemia (AML)
in about 30% of patients after various intervals from diagnosis and at
variable rates. (Refer to the Cellular Classification section for more
information.)
The acute leukemic transformation is much less responsive to
chemotherapy than is de novo AML. Prognosis is also related to the type of
myelodysplastic syndrome. Supportive care has been the mainstay of treatment.
Judicious use of platelet and blood transfusions and iron chelation may prevent or delay
alloimmunization and iron overload and favorably affect prognosis.
The MDS are characterized by abnormal bone marrow and blood cell morphology.
Megaloblastic erythroid hyperplasia with macrocytic anemia, which is associated with
normal vitamin B12 and folate levels, is frequently observed. Circulating granulocytes
are frequently severely reduced, often hypogranular or hypergranular, and may display the
acquired pseudo-Pelger-Huët abnormality. Early, abnormal myeloid progenitors
are identified in the marrow in varying percentages, depending on the type of
myelodysplastic syndrome. Abnormally small megakaryocytes
(micromegakaryocytes) may be seen in the marrow and hypogranular or giant
platelets may appear in the blood.
The MDS occur predominantly in older patients (usually >60 years),
though patients as young as 2 years have been reported.[2] Anemia, bleeding,
easy bruising, and fatigue are common initial findings. (Refer to the PDQ summary on Fatigue for more information.) Splenomegaly or
hepatosplenomegaly may occasionally be present in association with an overlapping myeloproliferative disorder. Approximately 50% of the
patients have a detectable cytogenetic abnormality, most commonly a deletion of all
or part of chromosome 5 or 7, or trisomy 8.[3] Although the bone marrow is
usually hypercellular at diagnosis, 15% to 20% of patients present with a
hypoplastic bone marrow.[4] Hypoplastic myelodysplastic patients tend to have
profound cytopenias and may respond more frequently to immunosuppressive therapy.
A variety of risk classification systems have been developed to predict the
overall survival of patients with MDS and the evolution from MDS to AML. These
classification systems include the French-American-British classification,[5]
the Bournemouth score,[6] the Sanz score,[7] the Lille score,[8] and the World Health Organization classification.[9] Clinical
variables in these systems have included bone marrow and blood myeloblast
percentage, specific cytopenias, age, lactate dehydrogenase level, and bone
marrow cytogenetic pattern.
An International MDS Risk Analysis Workshop was
convened, and the clinical data from 816 patients with primary MDS from seven
previously reported studies, which used independent risk-based prognostic
systems, were combined and collated.[10] The combined data were analyzed
centrally, and a global analysis was performed, which formed the basis of a new
prognostic system called the International Prognostic Scoring System for
MDS.[10] In multivariate analyses, significant predictors for both survival and
AML evolution included bone marrow blast percentage, number of peripheral blood
cytopenias, and cytogenetic subgroup. The data are used to assign MDS
patients a score, which stratifies patients into one of four risk groups: low risk,
intermediate-1, intermediate-2, and high risk. The time for the development of
AML in the risk groups was 9.4 years, 3.3 years, 1.1 years, and 0.2 years,
respectively. Median survival for the groups was 5.7 years, 3.5 years, 1.2
years, and 0.4 years, respectively. The system has been incorporated
into clinical trial design for MDS.
References
-
Ma X, Does M, Raza A, et al.: Myelodysplastic syndromes: incidence and survival in the United States. Cancer 109 (8): 1536-42, 2007.
[PUBMED Abstract]
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Tuncer MA, Pagliuca A, Hicsonmez G, et al.: Primary myelodysplastic syndrome in children: the clinical experience in 33 cases. Br J Haematol 82 (2): 347-53, 1992.
[PUBMED Abstract]
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Gyger M, Infante-Rivard C, D'Angelo G, et al.: Prognostic value of clonal chromosomal abnormalities in patients with primary myelodysplastic syndromes. Am J Hematol 28 (1): 13-20, 1988.
[PUBMED Abstract]
-
Nand S, Godwin JE: Hypoplastic myelodysplastic syndrome. Cancer 62 (5): 958-64, 1988.
[PUBMED Abstract]
-
Bennett JM, Catovsky D, Daniel MT, et al.: Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 51 (2): 189-99, 1982.
[PUBMED Abstract]
-
Mufti GJ, Stevens JR, Oscier DG, et al.: Myelodysplastic syndromes: a scoring system with prognostic significance. Br J Haematol 59 (3): 425-33, 1985.
[PUBMED Abstract]
-
Sanz GF, Sanz MA, Vallespí T, et al.: Two regression models and a scoring system for predicting survival and planning treatment in myelodysplastic syndromes: a multivariate analysis of prognostic factors in 370 patients. Blood 74 (1): 395-408, 1989.
[PUBMED Abstract]
-
Aul C, Gattermann N, Heyll A, et al.: Primary myelodysplastic syndromes: analysis of prognostic factors in 235 patients and proposals for an improved scoring system. Leukemia 6 (1): 52-9, 1992.
[PUBMED Abstract]
-
Brunning RD, Bennett JM, Flandrin G, et al.: Myelodysplastic syndromes. In: Jaffe ES, Harris NL, Stein H, et al., eds.: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press, 2001. World Health Organization Classification of Tumours, 3, pp 61-73.
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Greenberg P, Cox C, LeBeau MM, et al.: International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 89 (6): 2079-88, 1997.
[PUBMED Abstract]
Back to Top Classification of Myelodysplastic Syndromes
The myelodysplastic syndromes (MDS) are classified according to features of cellular morphology, etiology, and clinical presentation. The morphological classification of the MDS is largely based on the percent of myeloblasts in the bone marrow and blood, the type and degree of myeloid dysplasia, and the presence of ringed sideroblasts.[1] The clinical classification of the MDS depends upon whether there is an identifiable etiology and whether the MDS has been treated previously.
Cellular Classification
Work on the French-American-British (FAB) classification scheme for the MDS began in the late 1970s under the direction of the French-American-British Cooperative Group (see table below). The version published in 1982 was the first diagnostic classification scheme to clearly and reproducibly distinguish MDS from acute myelogenous leukemia (AML).[1] According to the FAB scheme, the percentage of bone marrow blasts required for the diagnosis of MDS ranges from less than 5% to as much as 29%. The FAB scheme is still frequently used by clinicians to categorize the MDS.
Several weaknesses were identified in the FAB classification of MDS. The inclusion of chronic myelomonocytic leukemia (CMML) was problematic; CMML is a disease that combines features of both MDS and chronic myeloproliferative disorders.[2] In addition, the FAB classification did not take cytogenetic findings into account. For example, the cytogenetically defined MDS subtype del(5q) represents a distinct clinical entity.[3]
In 1997, under the auspices of the World Health Organization (WHO), a working group of pathologists and clinicians from around the world agreed to a new cellular classification scheme for hematopoietic and lymphoid malignancies.[4] Significant changes to the FAB classification of these malignancies were made. For the classification of MDS, the new WHO classification lowered the threshold to 20% for the number of myeloblasts required to make the diagnosis of AML.[5] This arbitrary threshold value for blast percentage eliminated the cellular type, refractory anemia with excess blasts in transformation (RAEB-t), found in the FAB classification scheme. In the WHO cellular classification scheme, RAEB-t is no longer considered a distinct clinicopathologic entity; instead, RAEB-t is included within the broader category, AML with multilineage dysplasia, and identified as AML with multilineage dysplasia following a myelodysplastic syndrome.[6] (Refer to the PDQ summary on Adult Acute Myeloid Leukemia Treatment for more information.)
The elimination of RAEB-t from the WHO cellular classification scheme met some resistance. Some have argued that the biology of RAEB-t is distinct from AML and should be retained as a diagnostic category of MDS.[7,8] Others have emphasized the similar prognoses and responses to treatment for RAEB-t and AML with trilineage dysplasia.[9,10] The diagnosis of AML, which is based upon a threshold of 20% bone marrow or peripheral blood myeloblasts, does not represent a therapeutic mandate. The decision to treat must include other factors, such as patient age, prior history of MDS, clinical findings, disease progression, and most importantly, patient preference, in addition to the blast count. The same factors influence treatment options for patients with 30% or more myeloblasts in the blood or marrow. (Refer to the PDQ summary on Adult Acute Myeloid Leukemia Treatment for more information.)
The addition of refractory cytopenia with multilineage dysplasia (RCMD), myelodysplastic syndrome, unclassifiable (MDS-U), and the myelodysplastic syndrome associated with an isolated del(5q) chromosome abnormality completes the WHO cellular classification scheme for MDS. Finally, the WHO classification of MDS removed CMML from MDS and placed it in a new category, myelodysplastic syndromes and myeloproliferative diseases (MDS and MPD).[11] (Refer to the PDQ summary on Myelodysplastic and Myeloproliferative Diseases Treatment for more information.)
Myelodysplastic Syndromes: Comparison of the FAB and WHO Classifications
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FAB (1982)
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WHO (1997)
|
|
Myelodysplastic Syndromes
|
Myelodysplastic Syndromes
|
| Refractory anemia |
Refractory anemia |
|
Refractory cytopenia with multilineage dysplasia |
| Refractory anemia with ringed sideroblasts |
Refractory anemia with ringed sideroblasts |
| Refractory anemia with excess blasts |
Refractory anemia with excess blasts |
|
Myelodysplastic syndrome, unclassifiable |
|
Myelodysplastic syndrome associated with del(5q) |
|
Reclassified from MDS to:
|
| Refractory anemia with excess blasts in transformation |
Acute Myeloid Leukemia identified as, AML with multilineage dysplasia following a myelodysplastic syndrome |
| Chronic myelomonocytic leukemia |
Myelodysplastic and Myeloproliferative Diseases
|
MDS cellular types and subtypes in either cellular classification scheme have different degrees of disordered hematopoiesis, frequencies of transformation to acute leukemia, and prognoses. All WHO cellular types and subtypes and the FAB cellular type, RAEB-t, are described in detail below.
Refractory anemia (RA)
In patients with RA, the myeloid and megakaryocytic series in the bone marrow appear normal, but
megaloblastoid erythroid hyperplasia is present. Dysplasia is usually
minimal. Marrow blasts are less than 5%, and no peripheral blasts are present. Macrocytic anemia with reticulocytopenia is present in the blood. Transformation to acute leukemia is rare, and median survival varies from 2 years to 5 years in most series. RA accounts for 20% to 30% of all patients with MDS.
Refractory anemia with ringed sideroblasts (RARS)
In patients with RARS, the blood and marrow are identical to those in patients with RA, except that
at least 15% of marrow red cell precursors are ringed sideroblasts. Approximately 10% to 12% of patients present with this type, and prognosis is identical to that of RA. Approximately 1% to 2% of RARS evolve to AML.
Refractory anemia with excess blasts (RAEB)
In patients with RAEB, there is significant evidence of disordered myelopoiesis and megakaryocytopoiesis in addition to abnormal erythropoiesis. Because of differences in prognosis related to progression to a frank AML, this cellular classification is comprised of two categories, refractory anemia with excess blasts-1 (RAEB-1) and refractory anemia with excess blasts-2 (RAEB-2). Combined, the two categories account for approximately 40% of all patients with MDS. RAEB-1 is characterized by 5% to 9% blasts in the bone marrow and less than 5% blasts in the blood. Approximately 25% of cases of RAEB-1 progress to AML. Median survival is approximately 18 months. RAEB-2 is characterized by 10% to 19% blasts in the bone marrow. Approximately 33% of cases of RAEB-2 progress to AML. Median survival for RAEB-2 is approximately 10 months.
Refractory anemia with excess blasts in transformation (RAEB-t)
In the FAB classification, RAEB-t represents a panmyelosis in which 20% to 30% of marrow cells are blasts, and more than 5% blasts are seen in the blood. Auer rods may be seen. Sixty percent to 75% of patients develop overt acute leukemia, and median survival is 6 months or less. Approximately 25% of patients present with RAEB-t. In the WHO classification, RAEB-t is not a distinct clinical entity; rather, it is included within the broader category, AML with multilineage dysplasia, and identified as AML with multilineage dysplasia following a myelodysplastic syndrome.[6] (Refer to the PDQ summary on Adult Acute Myeloid Leukemia Treatment for more information.)
Refractory cytopenia with multilineage dysplasia (RCMD)
In patients with RCMD, bicytopenia or pancytopenia is present. In addition, dysplastic changes are present in 10% or more of the cells in two or more myeloid cell lines. There are less than 1% blasts in the blood and less than 5% blasts in the bone marrow. Auer rods are not present. Monocytes in the blood are less than 1 × 109. RCMD accounts for approximately 24% of cases of MDS. The frequency of evolution to acute leukemia is 11%. The overall median survival is 33 months. Refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS) represents another category of RMDS. In RCMD-RS, features of RCMD are present, and more than 15% of erythroid precursors in the bone marrow are ringed sideroblasts. RCMD-RS accounts for approximately 15% of cases of MDS. Survival in RCMD-RS is similar to that in primary RCMD.
Unclassifiable myelodysplastic syndrome (MDS-U)
The cellular subtype, MDS-U, lacks findings appropriate for classification as RA, RARS, RCMD or RAEB. Blasts in the blood and bone marrow are not increased.
Myelodysplastic syndrome associated with an isolated del(5q) chromosome abnormality
This MDS cellular subtype, the 5q- syndrome, is associated with an isolated del(5q) cytogenetic abnormality. Blasts in both blood and bone marrow are less than 5%. This subtype is associated with a long survival. Karyotypic evolution is uncommon. Additional cytogenetic abnormalities may be associated with a more aggressive MDS cellular subtype or may evolve to acute myeloid leukemia.
Clinical Classification
The clinical classification of MDS is used to determine disease prognosis and treatment strategy, and to define entry requirements for many MDS clinical trials.
De novo myelodysplastic syndrome
Most MDS cases occur de novo with no known cause.
Secondary myelodysplastic syndrome
The risk of developing MDS may be increased by exposure to a variety of agents including:[12-14]
- Tobacco smoke.
- Ionizing radiation.
- Organic chemicals (e.g., benzene, toluene, xylene, and chloramphenicol).
- Heavy metals.
- Herbicides.
- Pesticides.
- Fertilizers.
- Stone and cereal dusts.
- Exhaust gases.
- Nitro-organic explosives.
- Petroleum and diesel derivatives.
- Alkylating agents.
- Marrow-damaging agents used in cancer chemotherapy.
Patients with documented exposure to such agents are referred to as having secondary MDS or treatment-related MDS and constitute as many as 30% of all patients with MDS. Secondary MDS typically has a poorer prognosis than does de novo MDS.
Previously treated myelodysplastic syndrome
Previously treated MDS are de novo or secondary cases of MDS that have progressed despite previous treatment and, in many cases, are receiving additional treatment.
References
-
Bennett JM, Catovsky D, Daniel MT, et al.: Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 51 (2): 189-99, 1982.
[PUBMED Abstract]
-
Vardiman JW, Pierre R, Bain B, et al.: Chronic myelomonocytic leukaemia. In: Jaffe ES, Harris NL, Stein H, et al., eds.: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press, 2001. World Health Organization Classification of Tumours, 3, pp 49-52.
-
Mathew P, Tefferi A, Dewald GW, et al.: The 5q- syndrome: a single-institution study of 43 consecutive patients. Blood 81 (4): 1040-5, 1993.
[PUBMED Abstract]
-
Harris NL, Jaffe ES, Diebold J, et al.: World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J Clin Oncol 17 (12): 3835-49, 1999.
[PUBMED Abstract]
-
Brunning RD, Matute E, Harris NL, et al.: Acute myeloid leukemia with multilineage dysplasia. In: Jaffe ES, Harris NL, Stein H, et al., eds.: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press, 2001. World Health Organization Classification of Tumours, 3, pp 88-9.
-
Brunning RD, Matutes E, Harrris NL, et al.: Acute myeloid leukemia: introduction. In: Jaffe ES, Harris NL, Stein H, et al., eds.: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press, 2001. World Health Organization Classification of Tumours, 3, pp 77-80.
-
Huh YO, Jilani I, Estey E, et al.: More cell death in refractory anemia with excess blasts in transformation than in acute myeloid leukemia. Leukemia 16 (11): 2249-52, 2002.
[PUBMED Abstract]
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Greenberg P, Anderson J, de Witte T, et al.: Problematic WHO reclassification of myelodysplastic syndromes. Members of the International MDS Study Group. J Clin Oncol 18 (19): 3447-52, 2000.
[PUBMED Abstract]
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Estey E, Thall P, Beran M, et al.: Effect of diagnosis (refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, or acute myeloid leukemia [AML]) on outcome of AML-type chemotherapy. Blood 90 (8): 2969-77, 1997.
[PUBMED Abstract]
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Bernstein SH, Brunetto VL, Davey FR, et al.: Acute myeloid leukemia-type chemotherapy for newly diagnosed patients without antecedent cytopenias having myelodysplastic syndrome as defined by French-American-British criteria: a Cancer and Leukemia Group B Study. J Clin Oncol 14 (9): 2486-94, 1996.
[PUBMED Abstract]
-
Vardiman JW: Myelodysplastic/myeloproliferative diseases: introduction. In: Jaffe ES, Harris NL, Stein H, et al., eds.: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press, 2001. World Health Organization Classification of Tumours, 3, pp 47-8.
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West RR, Stafford DA, Farrow A, et al.: Occupational and environmental exposures and myelodysplasia: a case-control study. Leuk Res 19 (2): 127-39, 1995.
[PUBMED Abstract]
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Nisse C, Lorthois C, Dorp V, et al.: Exposure to occupational and environmental factors in myelodysplastic syndromes. Preliminary results of a case-control study. Leukemia 9 (4): 693-9, 1995.
[PUBMED Abstract]
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Rigolin GM, Cuneo A, Roberti MG, et al.: Exposure to myelotoxic agents and myelodysplasia: case-control study and correlation with clinicobiological findings. Br J Haematol 103 (1): 189-97, 1998.
[PUBMED Abstract]
Back to Top Treatment Option Overview
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
The mainstay of treatment of the myelodysplastic syndromes (MDS) has traditionally been supportive
care.[1,2] Prophylactic platelet transfusion should be avoided to forestall
alloimmunization, which will make platelet transfusion for bleeding difficult.
Anemia should be treated with red cell transfusions regularly, and patients receiving chronic red cell transfusions should be considered for iron chelation therapy with subcutaneously
administered desferrioxamine and vitamin C or oral deferasirox.[1,3] (For information on anemia, refer to the Fatigue summary.) Desferrioxamine may improve
granulocyte and platelet counts in some patients, and it may reduce red cell
transfusion requirements.[4] The use of erythropoietin may
improve anemia. The likelihood of response to exogenous erythropoietin
administration is clearly dependent on the pretreatment serum erythropoietin
level and on baseline transfusion needs. In a meta-analysis summarizing the data on erythropoietin in 205
patients with MDS from 17 studies, responses were most likely in those patients
who were anemic but who did not yet require a transfusion, patients who did not
have ringed sideroblasts, and patients who had a serum erythropoietin level of
less than 200 u/L.[5] Effective treatment requires substantially
higher doses of erythropoietin than are used for other indications (150–300
µg/kg/day).
One decision model found that the likelihood of responding to growth factors was higher in patients with a low serum erythropoietin level (defined as a level <500/µL) and low transfusion needs (defined as <2 units of packed red blood cells every month), but ineffective in patients with a high erythropoietin level and high transfusion needs.[6] Some patients with poor response to
erythropoietin alone may have improved response with the addition of low doses
of granulocyte colony-stimulating factor (GCSF) (0.5–1.0 µg/kg/day).[7-9] Rates of response to the combination treatment vary with the French-American-British (FAB) classification, with responses more likely in those with refractory anemia and ringed
sideroblasts RARS, and less likely for those with excess blasts.[10] Patients with RARS are unlikely to respond to erythropoietin
alone.[5]
A pooled analysis of published MDS trials from 1985 to 2005 examined 1,587 patients from 83 studies of growth factors. The growth factors included recombinant human erythropoietin and GCSF. With the exclusion from analysis of patients with more advanced MDS subtypes and with standardized response criteria, an approximate 40% overall response rate to growth factors was found.[11] The use of high-dose darbepoietin (300 µg/dose weekly) has been reported to produce a major erythroid response rate of almost 50% in patients whose endogenous erythropoietin level was less than 500 u/mL.[12]
Hormones, such as glucocorticoids and androgens, are generally of little benefit to patients with MDS.
Recombinant myeloid growth factors such as granulocyte-macrophage colony-stimulating
factor (GM-CSF) have been studied in myelodysplasia.[13] Circulating
granulocytes usually increase in a dose-dependent manner during therapy with
GM-CSF but usually return to pretreatment levels when the agent is
discontinued. Platelet and reticulocyte counts usually do not respond. The
effect of GM-CSF treatment on infection rate, morbidity, mortality, and disease
progression is not yet known.[14-17] Some patients respond to GM-CSF with
increased circulating blasts.[15] A randomized trial in which granulocytopenic MDS patients were assigned to GM-CSF or observation showed no advantage to the prophylactic use of that cytokine.[18]
The nucleoside 5-azacitidine is an inhibitor of DNA methyltransferase. Following a series of phase II studies suggesting significant activity of 5-azacitidine in patients with MDS, a randomized trial was conducted by the Cancer and Leukemia Group B. In the trial, 191 patients were randomized to receive 5-azacitidine (75 mg/m2/day subcutaneously daily for 7 days every 28 days) or observation. The antineoplastic nucleoside 5-azacitidine was continued for a minimum of four cycles. Patients who did not improve on the observation arm crossed over to receive 5-azacitidine. Hematologic responses occurred in 60% of patients on the 5-azacitidine arm (7% complete response, 16% partial response, and 37% improved response) compared with 5% in the observation arm (responses in the latter group consisted of hematologic improvement associated with an increased white cell count caused by the progression to acute leukemia). The response data of the original Cancer and Leukemia Group B trial have been reanalyzed in the CALGB-8421, CALGB-8921, and CALGB-9221 studies, respectively, using the International Working Group MDS Response Criteria; total hematologic response rate was 47% and included 10% complete responses.[19] Median time to leukemic transformation or death was 21 months for azacitidine versus 13 months for supportive care (P = .007). Median duration of response was 15 months, and fewer than 1% of treated patients died on study. Quality-of-life assessment found significant major advantages in physical function, symptoms, and psychological state for patients initially randomized to azacitidine.[20-22][Level of evidence: 1iiDii]
Preliminary results were reported from a phase III randomized control trial of 5-azacitidine versus other regimens.[23] The other regimens included low-dose cytarabine, acute myeloid leukemia-type remission induction chemotherapy, or best supportive care, and the trial was limited to patients with higher-risk MDS subtypes. The median and 2-year overall survival (OS) favored the 5-azacitidine arm, at 24 months versus 16 months (P = .0001) and 51% versus 26% (P < .0001), respectively.[23][Level of evidence: 1iiA]
The azacitidine congener decitabine demonstrated similar activity in phase II trials with an overall response rate of 49% and a median response duration of 39 weeks.[24] A randomized trial of decitabine versus supportive care in patients with International Prognostic Scoring System
(IPSS) Int-1 or greater led to an overall response rate of 30% in the decitabine arm versus 7% in the observation arm (P < .001).[25] Median time to AML or death was 12.1 months in the treated arm versus 7.8 months in the supportive care arm (P = not significant). Fourteen percent of patients treated with decitabine died on the study. Quality-of-life assessment found advantages to decitabine similar to those of 5-azacitidine. Although considerably fewer than originally planned, the median number of cycles administered was three, the decrease possibly attributable to the toxicity of the dose schedule studied[25][Level of evidence: 1iiDii]
Median number of cycles required to see first hematologic response to 5-azacitidine was 3; 90% of responders showed response by 6 cycles;[19] the median number of cycles of decitabine required to see first response was 2.2.[25]
Phase I and II studies have suggested that decitabine can be given as daily intravenous or subcutaneous infusions at doses that differ from the labeled schedule, which requires a minimum 3-day hospitalization; hematologic response rates are at least as good as in the phase III study.[26,27]
Administration of both nucleosides has been associated with reversal of methylation of cytosines in the promoter regions of silenced genes; however, it is not clear whether the clinical activity of these drugs requires methylation reversal.[28-30] While the mechanism of the clinical activity of 5-azacitidine and decitabine are not fully known, these two nucleosides demonstrated the highest single-agent response rates in this group of disorders. Both of these drugs have been approved for refractory anemia, RARS (if accompanied by neutropenia, or thrombocytopenia, or requiring transfusions), RAEB, and refractory anemia with excess blasts in transformation.[31] Trials studying the combinations of both azacytosine nucleosides with histone deacetylase inhibitors have been completed, including the Eastern Cooperative Oncology Group's ECOG-E1905 trial, and are ongoing, including the NCT00336170 study.[30,32,33]
Lenalidomide (CC-5013), a congener of thalidomide, induced erythroid responses in approximately 50% of MDS patients in a phase I and II study, including transfusion independence in 20 out of 32 patients.[34] Patients with MDS that was characterized by interstitial deletions of chromosome 5q31.1 (5q-) appeared particularly sensitive, with responses in 10 out of 12 patients compared with 13 out of 23 patients with a normal karyotype. In a phase II study of 148 low-risk and intermediate-risk I patients with 5q- chromosomal abnormalities (alone, or associated with other abnormalities), lenalidomide-induced transfusion independence in 67%, with a median time to response of 4 to 5 weeks. The median duration of transfusion independence had not been reached after a median of 104 weeks of follow-up. Of 62 evaluable patients, 38 patients developed complete cytogenetic remission.[35] Lenalidomide administration is limited by dose-limiting neutropenia and thrombocytopenia.[34][Level of evidence: 3iiiDiv]
Antithymocyte globulin (ATG) has shown activity in MDS patients in several small series. The National Heart Lung and Blood Institute conducted a phase II trial including 25 MDS patients with less than 20% blasts. Of all the patients studied, 11 or 44% responded and became transfusion-independent after ATG (three complete responses, six partial responses, and two minimal responses).[36] Multivariate analysis identified HLA-DR-15 (phenotype) expression, briefer period of red cell transfusion dependence, and younger age as predictors of response to ATG.[37]
Although therapy with cytotoxic agents has occasionally been beneficial,
results are usually disappointing, and responses are often brief when
achieved.[1,2,38] Low-dose cytarabine has benefitted some patients; however,
this treatment was associated with a higher infection rate when compared to
observation in a randomized trial. No difference in time to
progression or OS was observed for patients treated with low-dose cytarabine
or supportive care. In those patients who responded to low-dose cytarabine,
response appeared to be caused by a cytotoxic effect of the drug.[39] Low doses
of oral melphalan have a similar response rate to
low-dose cytarabine in small trials; however, the long-term consequences of
ongoing alkylator therapy in this patient population are unknown and
potentially harmful.[40] Topotecan, at doses that induce bone marrow aplasia
(2.0 mg/m2/day continuous infusion for 5 days),
induced complete hematologic remissions in 28% of patients. Toxic effects were
significant, and the median duration of remission was 8 months. The extent to
which the hematologic improvement induced by this therapy may be offset by
adverse changes in quality of life is not clear.[41][Level of evidence: 3iiiDiv] The combination of topotecan and cytarabine has induced complete
remission in 56% of patients with MDS; however, median duration of complete
response was only 50 weeks, and patients required monthly maintenance
therapy.[42][Level of evidence: 3iiDiv] The combination of fludarabine,
cytarabine, and granulocyte-colony stimulating factor also appears to have a
high response rate (74% complete response); however, this benefit was
restricted to patients with good-risk or intermediate-risk cytogenetic
abnormalities according to the IPSS.[43][Level of evidence: 3iiDiv]
Autologous bone marrow or peripheral blood progenitor cell transplantation is
under clinical evaluation for subsets of patients who achieve remission
following cytotoxic remission induction therapy. A retrospective review of 114
patients from the European Group for Blood and Marrow Transplantation reported
25% disease-free survival (dfs) following high-dose therapy and autologous rescue for
patients treated in first complete remission. Cytogenetics and the IPSS score were not provided for this patient cohort. Given that the
overall remission rate for this group of diseases is not better than
approximately 50%, participation in clinical trials is encouraged.[44][Level of
evidence: 3iiiA]
Patients with advanced MDS or acute myeloid leukemia (AML), which has progressed from MDS,
may be treated with remission induction chemotherapy similar to patients with
de novo AML. A retrospective review has suggested that the complete remission
rate for patients with RAEB who are treated with dose-intensive cytarabine-based
regimens is comparable to the complete response rate for patients with de novo
AML; however, event-free survival (EFS) was inferior for RAEB patients. Only 50% of
RAEB patients in this series had cytopenias documented for at least 1 month
prior to treatment; thus, some of these patients may have had evolving AML with
less than 30% bone marrow blasts rather than the more typical MDS.[45][Level of evidence: 3iiDiii] In multivariate analysis, diagnosis of RAEB (as opposed to
AML) was not a predictor of EFS. Rather, cytogenetic subset,
duration of hematologic abnormalities, and increasing age were all strong
predictors of failure to achieve complete remission, and decreased EFS. This suggests that risk assessment for chemotherapy outcome in MDS
and AML should not be based solely on FAB classification. Previous studies
using conventional seven plus three AML induction regimens have reported inferior
remission rates in patients with MDS or AML following MDS.[46]
Allogeneic bone marrow transplantation (BMT) for young patients with MDS offers
the potential for long-term dfs.[38] In two large studies, 45%
to 60% of patients with de novo MDS were projected to be long-term disease-free
survivors.[47,48] Outcome tends to be better in younger patients with fewer
bone marrow blasts, but long-term benefit has been noted in all
FAB classification types, and in patients with marrow
fibrosis, a variety of karyotypic findings, and different preparative
regimens.[47-49] A retrospective review of outcomes of allogeneic BMT
according to pretransplant IPSS score showed that the IPSS score predicted
relapse rate and dfs. The 5-year dfs rates
were 60% for the low-risk and intermediate-1 risk group, 36% for the intermediate-2 risk group, and 28% for the high-risk group.[50][Level of evidence: 3iiDii] A
review of 118 young MDS patients (median age 24, age range 0.3–53 years) who
received allogeneic BMT from matched unrelated donors reported an actuarial
survival of 28% at 2 years. Transplant-related mortality was influenced by the
age of the patient (18 years or younger, 40%; age 18 to 35 years, 61%; 35 years or older, 81%). Relapse rate was influenced by FAB classification. This study
included patients who received transplants as early as 1986, which may have
influenced the patient survival data.[51][Level of evidence: 3iiiA] Outcomes
may not be as good for patients with treatment-related MDS (5-year dfs of 8% to 30%).[52]
Allogeneic stem cell transplantation with nonmyeloablative conditioning is under clinical evaluation for treatment of MDS. A retrospective analysis of 836 allogeneic transplants for MDS using HLA-matched sibling donors was performed and included 215 patients who received nonmyeloablative conditioning regimens. The 3-year probabilities of progression-free survival and OS were similar in both groups (39% after myeloablative condition vs. 33% in reduced intensity conditioning RIC and 45% vs. 41%, respectively; these differences were not significant). Relapses were more common in the reduced intensity group, but nonrelapse mortality was decreased.[53][Level of evidence: 3iiiA]
The farnesyl transferase inhibitor tipifarnib, which is under clinical evaluation, has been examined in 82 patients; 32% of patients responded, and 15% had complete responses. Median response duration was 11 months.[54][Level of evidence: 3iiiDiv]. Arsenic trioxide induced major hematologic improvement in approximately 20% of 185 MDS patients treated in two multicenter phase II trials.[55,56]
References
-
Tricot GJ, Lauer RC, Appelbaum FR, et al.: Management of the myelodysplastic syndromes. Semin Oncol 14 (4): 444-53, 1987.
[PUBMED Abstract]
-
Boogaerts MA: Progress in the therapy of myelodysplastic syndromes. Blut 58 (6): 265-70, 1989.
[PUBMED Abstract]
-
Greenberg PL: Myelodysplastic syndromes: iron overload consequences and current chelating therapies. J Natl Compr Canc Netw 4 (1): 91-6, 2006.
[PUBMED Abstract]
-
Jensen PD, Jensen IM, Ellegaard J: Desferrioxamine treatment reduces blood transfusion requirements in patients with myelodysplastic syndrome. Br J Haematol 80 (1): 121-4, 1992.
[PUBMED Abstract]
-
Hellström-Lindberg E: Efficacy of erythropoietin in the myelodysplastic syndromes: a meta-analysis of 205 patients from 17 studies. Br J Haematol 89 (1): 67-71, 1995.
[PUBMED Abstract]
-
Hellström-Lindberg E, Gulbrandsen N, Lindberg G, et al.: A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin + granulocyte colony-stimulating factor: significant effects on quality of life. Br J Haematol 120 (6): 1037-46, 2003.
[PUBMED Abstract]
-
Hellström-Lindberg E, Ahlgren T, Beguin Y, et al.: Treatment of anemia in myelodysplastic syndromes with granulocyte colony-stimulating factor plus erythropoietin: results from a randomized phase II study and long-term follow-up of 71 patients. Blood 92 (1): 68-75, 1998.
[PUBMED Abstract]
-
Hellström-Lindberg E, Kanter-Lewensohn L, Ost A: Morphological changes and apoptosis in bone marrow from patients with myelodysplastic syndromes treated with granulocyte-CSF and erythropoietin. Leuk Res 21 (5): 415-25, 1997.
[PUBMED Abstract]
-
Negrin RS, Stein R, Doherty K, et al.: Maintenance treatment of the anemia of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor and erythropoietin: evidence for in vivo synergy. Blood 87 (10): 4076-81, 1996.
[PUBMED Abstract]
-
Jädersten M, Montgomery SM, Dybedal I, et al.: Long-term outcome of treatment of anemia in MDS with erythropoietin and G-CSF. Blood 106 (3): 803-11, 2005.
[PUBMED Abstract]
-
Golshayan AR, Jin T, Maciejewski J, et al.: Efficacy of growth factors compared to other therapies for low-risk myelodysplastic syndromes. Br J Haematol 137 (2): 125-32, 2007.
[PUBMED Abstract]
-
Mannone L, Gardin C, Quarre MC, et al.: High-dose darbepoetin alpha in the treatment of anaemia of lower risk myelodysplastic syndrome results of a phase II study. Br J Haematol 133 (5): 513-9, 2006.
[PUBMED Abstract]
-
Greenberg PL: Treatment of myelodysplastic syndromes with hemopoietic growth factors. Semin Oncol 19 (1): 106-14, 1992.
[PUBMED Abstract]
-
Thompson JA, Lee DJ, Kidd P, et al.: Subcutaneous granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndrome: toxicity, pharmacokinetics, and hematological effects. J Clin Oncol 7 (5): 629-37, 1989.
[PUBMED Abstract]
-
Hoelzer D, Ganser A, Völkers B, et al.: In vitro and in vivo action of recombinant human GM-CSF (rhGM-CSF) in patients with myelodysplastic syndromes. Blood Cells 14 (2-3): 551-9, 1988.
[PUBMED Abstract]
-
Estey EH, Kurzrock R, Talpaz M, et al.: Effects of low doses of recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) in patients with myelodysplastic syndromes. Br J Haematol 77 (3): 291-5, 1991.
[PUBMED Abstract]
-
Yoshida Y, Hirashima K, Asano S, et al.: A phase II trial of recombinant human granulocyte colony-stimulating factor in the myelodysplastic syndromes. Br J Haematol 78 (3): 378-84, 1991.
[PUBMED Abstract]
-
Greenberg PL: The role of hemopoietic growth factors in the treatment of myelodysplastic syndromes. International Journal of Pediatric Hematology/Oncology 4 (3): 231-8, 1997.
-
Silverman LR, McKenzie DR, Peterson BL, et al.: Further analysis of trials with azacitidine in patients with myelodysplastic syndrome: studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B. J Clin Oncol 24 (24): 3895-903, 2006.
[PUBMED Abstract]
-
Silverman LR, Demakos EP, Peterson BL, et al.: Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol 20 (10): 2429-40, 2002.
[PUBMED Abstract]
-
Kantarjian HM: Treatment of myelodysplastic syndrome: questions raised by the azacitidine experience. J Clin Oncol 20 (10): 2415-6, 2002.
[PUBMED Abstract]
-
Kornblith AB, Herndon JE 2nd, Silverman LR, et al.: Impact of azacytidine on the quality of life of patients with myelodysplastic syndrome treated in a randomized phase III trial: a Cancer and Leukemia Group B study. J Clin Oncol 20 (10): 2441-52, 2002.
[PUBMED Abstract]
-
Fenaux P, Mufti GJ, Santini V, et al.: Azacitidine (AZA) treatment prolongs overall survival (OS) in higher-risk MDS patients compared with conventional care regimens (CCR): results of the AZA-001 phase III study. [Abstract] Blood 110 (11): A-817, 2007.
-
Wijermans P, Lübbert M, Verhoef G, et al.: Low-dose 5-aza-2'-deoxycytidine, a DNA hypomethylating agent, for the treatment of high-risk myelodysplastic syndrome: a multicenter phase II study in elderly patients. J Clin Oncol 18 (5): 956-62, 2000.
[PUBMED Abstract]
-
Kantarjian H, Issa JP, Rosenfeld CS, et al.: Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer 106 (8): 1794-803, 2006.
[PUBMED Abstract]
-
Issa JP, Garcia-Manero G, Giles FJ, et al.: Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2'-deoxycytidine (decitabine) in hematopoietic malignancies. Blood 103 (5): 1635-40, 2004.
[PUBMED Abstract]
-
Kantarjian H, Oki Y, Garcia-Manero G, et al.: Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood 109 (1): 52-7, 2007.
[PUBMED Abstract]
-
Daskalakis M, Nguyen TT, Nguyen C, et al.: Demethylation of a hypermethylated P15/INK4B gene in patients with myelodysplastic syndrome by 5-Aza-2'-deoxycytidine (decitabine) treatment. Blood 100 (8): 2957-64, 2002.
[PUBMED Abstract]
-
Yang AS, Doshi KD, Choi SW, et al.: DNA methylation changes after 5-aza-2'-deoxycytidine therapy in patients with leukemia. Cancer Res 66 (10): 5495-503, 2006.
[PUBMED Abstract]
-
Gore SD, Baylin S, Sugar E, et al.: Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasms. Cancer Res 66 (12): 6361-9, 2006.
[PUBMED Abstract]
-
Kaminskas E, Farrell A, Abraham S, et al.: Approval summary: azacitidine for treatment of myelodysplastic syndrome subtypes. Clin Cancer Res 11 (10): 3604-8, 2005.
[PUBMED Abstract]
-
Garcia-Manero G, Kantarjian HM, Sanchez-Gonzalez B, et al.: Phase 1/2 study of the combination of 5-aza-2'-deoxycytidine with valproic acid in patients with leukemia. Blood 108 (10): 3271-9, 2006.
[PUBMED Abstract]
-
Soriano AO, Yang H, Faderl S, et al.: Safety and clinical activity of the combination of 5-azacytidine, valproic acid, and all-trans retinoic acid in acute myeloid leukemia and myelodysplastic syndrome. Blood 110 (7): 2302-8, 2007.
[PUBMED Abstract]
-
List A, Kurtin S, Roe DJ, et al.: Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med 352 (6): 549-57, 2005.
[PUBMED Abstract]
-
List A, Dewald G, Bennett J, et al.: Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med 355 (14): 1456-65, 2006.
[PUBMED Abstract]
-
Molldrem JJ, Caples M, Mavroudis D, et al.: Antithymocyte globulin for patients with myelodysplastic syndrome. Br J Haematol 99 (3): 699-705, 1997.
[PUBMED Abstract]
-
Saunthararajah Y, Nakamura R, Nam JM, et al.: HLA-DR15 (DR2) is overrepresented in myelodysplastic syndrome and aplastic anemia and predicts a response to immunosuppression in myelodysplastic syndrome. Blood 100 (5): 1570-4, 2002.
[PUBMED Abstract]
-
Cheson BD: Chemotherapy and bone marrow transplantation for myelodysplastic syndromes. Semin Oncol 19 (1): 85-94, 1992.
[PUBMED Abstract]
-
Miller KB, Kim K, Morrison FS, et al.: The evaluation of low-dose cytarabine in the treatment of myelodysplastic syndromes: a phase-III intergroup study. Ann Hematol 65 (4): 162-8, 1992.
[PUBMED Abstract]
-
Omoto E, Deguchi S, Takaba S, et al.: Low-dose melphalan for treatment of high-risk myelodysplastic syndromes. Leukemia 10 (4): 609-14, 1996.
[PUBMED Abstract]
-
Beran M, Kantarjian H, O'Brien S, et al.: Topotecan, a topoisomerase I inhibitor, is active in the treatment of myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood 88 (7): 2473-9, 1996.
[PUBMED Abstract]
-
Beran M, Estey E, O'Brien S, et al.: Topotecan and cytarabine is an active combination regimen in myelodysplastic syndromes and chronic myelomonocytic leukemia. J Clin Oncol 17 (9): 2819-30, 1999.
[PUBMED Abstract]
-
Ferrara F, Leoni F, Pinto A, et al.: Fludarabine, cytarabine, and granulocyte-colony stimulating factor for the treatment of high risk myelodysplastic syndromes. Cancer 86 (10): 2006-13, 1999.
[PUBMED Abstract]
-
De Witte T, Van Biezen A, Hermans J, et al.: Autologous bone marrow transplantation for patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia following MDS. Chronic and Acute Leukemia Working Parties of the European Group for Blood and Marrow Transplantation. Blood 90 (10): 3853-7, 1997.
[PUBMED Abstract]
-
Estey E, Thall P, Beran M, et al.: Effect of diagnosis (refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, or acute myeloid leukemia [AML]) on outcome of AML-type chemotherapy. Blood 90 (8): 2969-77, 1997.
[PUBMED Abstract]
-
Hamblin TJ: Intensive chemotherapy in myelodysplastic syndromes. Blood Rev 6 (4): 215-9, 1992.
[PUBMED Abstract]
-
Appelbaum FR, Barrall J, Storb R, et al.: Bone marrow transplantation for patients with myelodysplasia. Pretreatment variables and outcome. Ann Intern Med 112 (8): 590-7, 1990.
[PUBMED Abstract]
-
De Witte T, Zwaan F, Hermans J, et al.: Allogeneic bone marrow transplantation for secondary leukaemia and myelodysplastic syndrome: a survey by the Leukaemia Working Party of the European Bone Marrow Transplantation Group (EBMTG) Br J Haematol 74 (2): 151-5, 1990.
[PUBMED Abstract]
-
O'Donnell MR, Nademanee AP, Snyder DS, et al.: Bone marrow transplantation for myelodysplastic and myeloproliferative syndromes. J Clin Oncol 5 (11): 1822-6, 1987.
[PUBMED Abstract]
-
Appelbaum FR, Anderson J: Allogeneic bone marrow transplantation for myelodysplastic syndrome: outcomes analysis according to IPSS score. Leukemia 12 (Suppl 1): S25-9, 1998.
[PUBMED Abstract]
-
Arnold R, de Witte T, van Biezen A, et al.: Unrelated bone marrow transplantation in patients with myelodysplastic syndromes and secondary acute myeloid leukemia: an EBMT survey. European Blood and Marrow Transplantation Group. Bone Marrow Transplant 21 (12): 1213-6, 1998.
[PUBMED Abstract]
-
Witherspoon RP, Deeg HJ, Storer B, et al.: Hematopoietic stem-cell transplantation for treatment-related leukemia or myelodysplasia. J Clin Oncol 19 (8): 2134-41, 2001.
[PUBMED Abstract]
-
Martino R, Iacobelli S, Brand R, et al.: Retrospective comparison of reduced-intensity conditioning and conventional high-dose conditioning for allogeneic hematopoietic stem cell transplantation using HLA-identical sibling donors in myelodysplastic syndromes. Blood 108 (3): 836-46, 2006.
[PUBMED Abstract]
-
Fenaux P, Raza A, Mufti GJ, et al.: A multicenter phase 2 study of the farnesyltransferase inhibitor tipifarnib in intermediate- to high-risk myelodysplastic syndrome. Blood 109 (10): 4158-63, 2007.
[PUBMED Abstract]
-
Schiller GJ, Slack J, Hainsworth JD, et al.: Phase II multicenter study of arsenic trioxide in patients with myelodysplastic syndromes. J Clin Oncol 24 (16): 2456-64, 2006.
[PUBMED Abstract]
-
Vey N, Bosly A, Guerci A, et al.: Arsenic trioxide in patients with myelodysplastic syndromes: a phase II multicenter study. J Clin Oncol 24 (16): 2465-71, 2006.
[PUBMED Abstract]
Back to Top De Novo and Secondary Myelodysplastic Syndrome
Standard treatment options:
- Myeloablative allogeneic stem cell transplantation.
- Erythropoeitic growth factors, in patients with endogenous erythropoietin levels less than 500 u/mL.
- 5-azacitidine or decitabine.
- Lenalidomide for patients with deletions of chromosome 5q31.
- Antithymocyte globulin.
Treatment options under clinical evaluation:
- Nonmyeloablative stem cell transplantation.
- Farnesyl transferase inhibitors (tipifarnib and lonafarnib).
- Combination regimens.
- Thrombopoietic agents.
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with de novo myelodysplastic syndromes and secondary myelodysplastic syndromes. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
Back to Top Previously Treated Myelodysplastic Syndrome
With the exception of the use of lenalidomide for low risk patients with abnormalities of chromosome 5, there are no clinical trials informing the appropriate selection of current therapies for patients with specific subtypes of myelodysplastic syndrome. Patients who have ceased to respond or did not respond to one therapy are frequently offered another from the therapies described in the previous sections. There are currently no data evaluating the success of switching from one azacytosine analogue to the other in the case of nonresponse. Patients who have responded, as in the CALGB-8421, CALGB-8921, and CALGB-9221 trials, to an azacytosine nucleoside and relapse off-therapy may respond to the reinstitution of the nucleoside.[1] Relapsed patients should be considered for enrollment in clinical trials. In patients previously treated with growth factors, there are studies that have shown responses to non–growth factor approaches.
Standard treatment options:
- Myeloablative allogeneic stem cell transplantation.
- Erythropoeitic growth factors, in patients with endogenous erythropoietin levels less than 500 u/mL.
- 5-azacitidine or decitabine.
- Lenalidomide for patients with deletions of chromosome 5q31.[2,3]
- Antithymocyte globulin.
- Supportive care.
Treatment options under clinical evaluation:
- Nonmyeloablative stem cell transplantation.
- Farnesyl transferase inhibitors (tipifarnib and lonafarnib).
- Combination therapies.
- Thrombopoietic agents.
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with previously treated myelodysplastic syndromes. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References
-
Silverman LR, McKenzie DR, Peterson BL, et al.: Further analysis of trials with azacitidine in patients with myelodysplastic syndrome: studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B. J Clin Oncol 24 (24): 3895-903, 2006.
[PUBMED Abstract]
-
List A, Kurtin S, Roe DJ, et al.: Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med 352 (6): 549-57, 2005.
[PUBMED Abstract]
-
List A, Dewald G, Bennett J, et al.: Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med 355 (14): 1456-65, 2006.
[PUBMED Abstract]
Back to Top Get More Information From NCI
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For more information, U.S. residents may call the National Cancer Institute's (NCI's) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 9:00 a.m. to 4:30 p.m. Deaf and hard-of-hearing callers with TTY equipment may call 1-800-332-8615. The call is free and a trained Cancer Information Specialist is available to answer your questions.
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Back to Top Changes to This Summary (11/06/2008)
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Editorial changes were made to this summary.
Back to Top More Information
About PDQ
Additional PDQ Summaries
Important:
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