Article from St Jude followed by Medline abstracts
http://www.stjude.org/disease-summaries/0,2557,449_2165_2991,00.html
Myelodysplasia (MDS) refers to a group of disorders in which the bone marrow does not function normally and produces insufficient number of normal blood cells.
MDS affects the production of any, and occasionally all, types of blood cells including red blood cells, platelets, and white blood cells (cytopenias).
About 50 percent of pediatric myelodysplasia can be classified in five types of MDS: refractory anemia, refractory anemia with ring sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia.
The remaining 50 percent typically present with isolated or combined cytopenias such as anemia, leucopenia and/or thrombocytopenia (low platelet count). Although chronic, MDS progresses to become acute myeloid leukemia (AML) in about 30 percent of patients.
Incidence
- Fewer than 100 new cases of myelodysplasia are reported in the United States each year in children.
- MDS is found most often in adults over the age of 50 (median age 65 years old), but is also seen in children of all ages.
Influencing Factors - There is a slightly higher incidence of myelodysplasia in males than in females.
- Genetic and environmental factors have been implicated in the etiology of MDS. Exposure to excessive radiation, some toxic chemicals, certain medicines, and viral infections may cause MDS in some people.
Survival Rates
Up to 60 percent of patients that receive bone marrow transfusions achieve long-term survival.
Treatment Strategies - Allogeneic hematopoietic stem cell transplantation (transfusions using marrow, peripheral blood or cord blood from a compatible donor) is the most effective form of treatment for most types of myelodysplasia.
- Chemotherapy is a form of treatment for some patients with a high risk of MDS progressing into AML.
- Supportive treatments include blood and platelet transfusions and antibiotics.
Medline Abstracts - Alternative supportive therapy
Ann Hematol. 2006 Jan 12;:1-7 [Epub ahead of print]
Erythropoietin plus granulocyte colony-stimulating factor is better than erythropoietin alone to treat anemia in low-risk myelodysplastic syndromes: results from a randomized single-centre study.
Balleari E,
Rossi E,
Clavio M,
Congiu A,
Gobbi M,
Grosso M,
Secondo V,
Spriano M,
Timitilli S,
Ghio R.
Department of Hematology and Oncology, University of Genoa, Azienda Ospedaliera Universitaria San Martino di Genova, Genoa, Italy.
Haemopoietic growth factors (HGF), i.e. erythropoietin [recombinant human erythropoietin (rHEPO)] or granulocyte colony stimulating factor (G-CSF), alone or in combination, have largely been used to treat anemia in myelodysplastic syndromes (MDS), but whether combined rHEPO and G-CSF is really superior to rHEPO alone is still under debate. In particular, randomized studies comparing front-line rHEPO vs rHEPO+G-CSF are still lacking. The aim of this study was to compare the effects of "standard" doses of rHEPO with the combination of rHEPO and G-CSF in the treatment of anemic patients with low-risk MDS in a prospective randomized trial.Anemic patients with low-risk MDS were randomly assigned to receive either rHEPO (10,000 IU s.c. three times a week) or the same dosage of rHEPO+G-CSF (300 mug s.c. twice a week) for a minimum of 8 weeks. Patients who were unresponsive to rHEPO were offered the combination therapy for another 8 weeks, whereas non-responders to rHEPO+G-CSF were considered "off study". Responders continued the treatment indefinitely. Both haematological response and changes in quality-of-life (QoL) scores (Functional Assessment of Cancer Therapy-Anemia) were recorded and evaluated.Thirty consecutive patients [10 refractory anemia (RA), 5 RA with ringed sideroblasts, 7 refractory cytopenia with multilineage dysplasia, 5 RA with less than 10% blasts and 3 5q-syndrome] were enrolled in the study. All of them (15 in the rHEPO arm and 15 in the rHEPO+G-CSF arm) were valuable after the first 8 weeks of treatment. Erythroid response was observed in 6/15 (40%) patients in the rHEPO arm and in 11/15 (73.3%) patients in the rHEPO+G-CSF arm. In 4/9 (44.4%) patients who were unresponsive to rHEPO, the addition of G-CSF induced erythroid response at 16 weeks. No relevant adverse effects were recorded for either treatment in any of the study patients. Erythroid response to HGF was associated with a relevant improvement in QoL.Twenty responders continued the treatment. Afterwards, 8/20 (40%) discontinued therapy because of the following: losing response (2), progression to high-risk MDS (3) and death due to other causes (3). The remaining 12 are still responding and continuing treatment, with a median follow-up of 28 months.Progression to acute leukemia was cumulatively observed in 4/30 (13.3%) patients (2 in each arm).Although our data were obtained from a relatively small cohort of patients, they indicate that the rHEPO+G-CSF treatment is more effective than rHEPO alone for correcting anemia in low-risk MDS patients and for making a relevant improvement in their QoL.
J Natl Compr Canc Netw. 2006 Jan;4(1):78-82.
Related Articles, Links
Developmental therapeutics for myelodysplastic syndromes.
Naing A,
Sokol L,
List AF.
H. Lee Moffitt Cancer Center & Research Institute, University of South Florida College of Medicine, Tampa, FL, USA.
The management strategy for patients with myelodysplastic syndromes (MDS) has evolved from sole reliance on supportive measures to active treatment guided by disease risks. Recent progress in understanding the molecular pathogenesis of MDS has accelerated the discovery of new therapeutic targets, and consequently launched the development of several novel therapeutics that are currently in varied stages of clinical testing. One such agent is lenalidomide, which has shown remarkable effectiveness in the cytogenetically defined subset of MDS with the chromosome 5q31 deletion. The advent of new and effective targeted therapeutics may beneficially affect outcomes of an ever-increasing number of patients with MDS. This discussion summarizes the preliminary results of selected novel therapeutics.
Leuk Lymphoma. 2006 Mar;47(3):433-40.
Related Articles, Links
Phase II study of topotecan and thalidomide in patients with high-risk myelodysplastic syndromes.
Raza A,
Lisak L,
Billmeier J,
Pervaiz H,
Mumtaz M,
Gohar S,
Wahid K,
Galili N.
The Radhey Khanna Center for MDS Research, University of Massachusetts Medical Center, Worcester, MA, USA.
This phase II trial investigated the safety and preliminary efficacy of a topotecan/thalidomide combination therapy in patients with myelodysplastic syndrome who had refractory anemia with excess blasts (RAEB), RAEB with transformation, or chronic myelomonocytic anemia. Patients received three 21-day cycles of topotecan 1.25 mg/m(2) on days 1-5, which was repeated for two additional cycles in patients whose bone marrow blast percentages did not decrease. Oral thalidomide was then started at 100 mg/day (with the dose escalated up to 300 mg/day if well tolerated) for up to 1 year. Patients were monitored throughout the trial for hematologic and clinical adverse events, and efficacy was assessed using International Working Group (IWG) criteria. Forty-five patients, mostly elderly (median age 68 years; range 52-79 years), were enrolled. Therapy was generally well tolerated compared to high-dose chemotherapy. Three patients died from disease progression/infections during topotecan therapy, and four patients discontinued topotecan because of high-grade neutropenia (two patients), syncope (one patient), or hip surgery (one patient). Of 24 patients who received thalidomide, three discontinued because of treatment-related toxicity. Thirty-eight patients were evaluable for response: nine (24%) had hematologic improvement and 13 (34%) had stable disease. Responses occurred in patients with all disease subtypes. Six patients achieved transfusion independence, and one patient had a trilineage response. Approximately one-third of the patients had decreases in bone marrow blasts of 50%. Therefore, a topotecan and thalidomide combination therapy is promising, although further studies are needed to determine the optimum doses and schedule.