Myelodysplastic Syndromes
Pathophysiology
Granulopoiesis in acute myeloid leukemia and preleukemia.
Greenberg PL, Nichols W, Schrier SL.
N Engl J Med. 1971;284:1225-1231.
Description: Bridging basic research and clinical disease, this paper described differential in vitro hematopoietic growth regulation between preleukemia and AML.
PubMed citation number: 5280338
Distinct haematological disorder with deletion of the long arm of no. 5 chromosome.
van den Berghe H, Cassiman J-J, Fryns J-P, Michaux J-L, Sokal G.
Nature. 1974;251:437-438.
Description: In the setting of previously described association of CML with the Philadelphia chromosome, this case series of 3 patients with refractory anemia and a novel karyotypic abnormality (5q-) reinforced the theory that acquired clonal cytogenetic abnormalities are associated with distinct clinical and pathological phenotypes and spurred the discovery of hematopoietic growth regulators on the long arm of chromosome 5.
PubMed citation number: 4421285
Therapy-related leukemia and myelodysplastic syndrome: clinical, cytogenetic, and prognostic features.
Kantarjian HM, Keating MJ, Walters RS, et al.
J Clin Oncol. 1986;4:1748-1757.
Description: This study helped to define the distinct clinical and biological features of secondary MDS/AML, facilitating changes in oncology practices to reduce the risk of secondary MDS/AML while highlighting the need for earlier consideration of experimental therapy given the particularly poor prognosis of secondary MDS/AML.
PubMed citation number: 3783201
Clonal analysis of myelodysplastic syndromes: evidence of multipotent stem cell origin.
Janssen JWG, Buschle M, Layton M, et al.
Blood. 1989;73;248-254.
Description: Using RFLP and X-inactivation analysis, this report demonstrated that MDS is a clonal disorder arising from a multipotent myeloid-lymphoid stem cell. Techniques assessing clonality in MDS have applications in prognostication research into the genetic lesions responsible for leukemogenesis.
PubMed citation number: 2562924
Diagnosis
Preleukemic acute human leukemia.
Block M, Jacobson LO, Bethard WF.
JAMA. 1953;152:1018-1028.
Description: This case series of 12 patients provided evidence of a preleukemic period characterized by indolent bone marrow failure with progressive cytopenias and morphological marrow changes.
PubMed citation number: 13052490
Proposals for the Classification of the Myelodysplastic Syndromes.
Bennett JM, Catovsky D, Daniel MT, et al: the French- American-British (FAB) Cooperative Group.
Br J Haematol. 1982;51:189-199.
Description: This systematic and straightforward morphologic classification of MDS created diagnostic criteria and established the prognostic significance of MDS subtypes: this framework facilitated further clinical and basic research based on the distinctions among the subtypes.
PubMed citation number: 6952920
Treatment
Maintenance treatment of patients with myelodysplatic syndromes using recombinant human granulocyte colony-stimulating factor.
Negrin RS, Haeuber DH, Nagler A, et al.
Blood. 1990;76:36-43.
Description: This study was the first to establish the tolerability, efficacy, and mechanism (differentiation of the abnormal clone) of long-term subcutaneous G-CSF administration for improving neutropenia in MDS patients and prompted further investigations into the long-term use of G-CSF.
PubMed citation number: 1694702
Allogeneic bone marrow transplantation for 93 patients with myelodysplastic syndrome.
Anderson JE, Appelbaum FR, Fisher LD, et al..
Blood. 1993;82:677-681.
Description: This relatively large study (93 patients) confirmed that allogeneic BMT is associated with a long-term remission in approximately 40% of eligible MDS patients. Additional follow-up currently available has been useful for establishing prognostic factors for MDS patients receiving allogeneic BMT.
PubMed citation number: 8329721
Unrelated donor marrow transplantation for myelodysplastic syndromes: outcome analysis in 510 transplants facilitated by the National Marrow Donor Program.
Castro-Malaspina H, Harris RE, Gajewski J, et al.
Blood. 2002;99:1943-1951.
Description: This was a large series showing the results of patients with MDS undergoing a unrelated AlloBMT. Two-year disease free survival was 29%, with a treatment-related mortality rate at 2 years of 54%.
PubMed citation number: 11877264
A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome.
Cutler CS, Lee SJ, Greenberg P, et al.
Blood. 2004;104:579-585.
Description: Statistical model attempting to determine the timing for an AlloBMT in MDS patients. This is a significant issue, since premature transplantation risks excessive short-term toxicities, but delay risks the development of more advanced disease, at which time additional chemotherapy may be necessary to reduce blast count.
PubMed citation number: 15039286
Apoptosis in bone marrow biopsy samples involving stromal and hematopoietic cells in 50 patients with myelodysplastic syndromes.
Raza A, Gezer S, Mundle S, et al.
Blood. 1995;86:268-276.
Description: This paper describes the high incidence of intramedullary apoptosis in MDS, providing an explanation for the observed “ineffective hematopoiesis” of MDS, where peripheral cytopenias may paradoxically coexist with normal or hypercellular marrows.
PubMed citation number: 7795232
International Scoring System for Evaluating Prognosis in Myelodysplastic Syndromes.
Greenberg P, Cox C, LeBeau MM, et al.
Blood. 1997;89:2079-2088.
Description: The IPSS improved on the prognostic ability of the FAB classification of MDS, allowing for more accurate design and interpretation of clinical trials as well as risk-based treatment strategies.
PubMed citation number: 9058730
Antithymocyte globulin for patients with myelodysplastic syndrome.
Molldrem JJ, Caples M, Mavroudis D, Plante M, Young NS, Barrett AJ.
Br J Haematol. 1997;9:699-705.
Description: Antithymocyte globulin (ATG) is a treatment option for patients with MDS (not necessarily just MDS patients with hypocellular marrows).
PubMed citation number: 12394172
HLA-DR15 (DR2) is overrepresented in myelodysplastic syndrome and aplastic anemia and predicts a response to immunosuppression in myelodysplastic syndrome.
Saunthararajah Y, Nakamura R, Nam JM, et al.
Blood. 2002;100:1570-1574.
Description: HLA type may help predict response to antithymocyte globulin (ATG).
PubMed citation number: 12176872
A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin + granulocyte colony-stimulating factor: significant effects on quality of life.
Hellstrom-Lindberg E, Gulbrandsen N, Lindberg G, et al: Scandinavian MDS Group.
Br J Haematol. 2003;120:1037-1046.
Description: This paper validates a previously developed decision model for treatment of anemia in MDS based on both quality of life and laboratory measurements of improvement.
PubMed citation number: 12648074
Health, economic, and quality-of-life effects of erythropoietin and granulocyte colony-stimulating factor for the treatment of myelodysplastic syndromes: a randomized, controlled trial.
Casadevall N, Durieux P, Dubois S, et al.
Blood. 2004;104:321-327.
Description: Phase 3 trial of EPO plus G-CSF versus supportive care for treatment of anemic MDS patients. Erythroid responses were seen, as expected, but in addition, patients with an erythroid response had improved survival compared with nonresponders (there is no explanation why this should be so). There was no increased risk of AML transformation in the growth-factor treatment arm. Effect on quality of life was not examined (Miller K, et al. Blood, 2004;104: abstract no. 70).
PubMed citation number: 15054036
Efficacy of lenalidomide in myelodysplastic syndromes.
List A, Kurtin S, Roe DJ, et al.
N Engl J Med. 2005;352:549-557.
Description: CC-5013 shown to be effective for treating anemia of MDS, particularly in patients with del(5q). PubMed citation number: 15703420
Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group.
Silverman LR, Demakos EP, Peterson BL, et al.
J Clin Oncol. 2002;20:2429-2440.
Description: Phase 3 trial showing 5-azacytidine plus supportive care improved time to progression to AML, a trend toward improved survival, and response in patients with MDS compared with supportive care alone. PubMed citation number: 12011120
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.
Kornblith AB, Herndon JE 2nd, Silverman LR, et al.
J Clin Oncol. 2002;20:2441-2452.
Description: Phase 3 trial showed improved quality of life in patients receiving 5-azacytidine compared with patients receiving supportive care.
PubMed citation number: 12011121
Review
The myelodysplastic syndrome(s): a perspective and review highlighting current controversies.
Steensma DP, Tefferi A.
Leuk Res. 2003;27:95-120.
Description: Discusses recent developments and controversies in MDS, including the WHO reclassification proposal.
PubMed citation number: 12526916