Transplantation for myelodysplastic syndromes 2013

Abstract

Purpose of review: The only current treatment capable of curing patients with myelodysplastic syndromes (MDS) is allogeneic haematopoietic stem cell transplantation (HCT). However, many MDS patients are older, often with substantial comorbid conditions, and the disease is heterogeneous. As a consequence, results of HCT vary considerably, and the practices of HCT for MDS are evolving.

Recent findings: The newly published modified International Prognostic Scoring System (IPSS-R), developed for nontransplanted patients, also correlates with post-HCT outcome, with the patient's karyotype having the strongest impact. The presence of monosomal karyotype and various genetic and molecular markers have also been shown to have a prognostic value. The use of hypomethylating agents, before or after HCT, may reduce the post-HCT relapse risk or delay relapse. Low and reduced-intensity conditioning regimens have allowed to transplant growing numbers of older patients with MDS, and the development of novel regimens may lead to improved relapse-free survival even in patients with high-risk cytogenetics. The optimal stem cell source may differ for different patient populations and different disease risk categories.

Summary: Transplant results for MDS have improved in recent years. Some patients even in the eighth decade of life have been transplanted successfully. Ongoing studies are aimed at further reducing transplant-related toxicity, graft-versus-host disease and post-HCT relapse.

FIGURE 1. Impact of monosomal karyotype (MK) on posttransplant relapse and overall survival (OS)

Incidence among patients with poor-risk karyotype (by 5-group classification), without or with concurrent MK. (This figure was originally published in Blood. H.J. Deeg, B.L. Scott, M. Fang, H.M. Shulman, B. Gyurkocza, D. Myerson, J.M. Pagel, U. Platzbecker, A. Ramakrishnan, J.P. Radich, B.M. Sandmaier, M. Sorror, D.L. Stirewalt, W.A. Wilson, R. Storb, F.R. Appelbaum, T. Gooley. Five-group cytogenetic risk classification, monosomal karyotype, and outcome after hematopoietic cell transplantation for MDS or acute leukemia evolving from MDS. Blood. 2012;120(7):1398–1408. © the American Society of Hematology.)

FIGURE 2. RFS by disease risk (A) and cytogenetic risk (B)

(A) Disease risk was classified using CIBMTR criteria. Low risk: ALL or AML in first remission or MDS-RA; standard risk: AML or ALL in second or greater remission; high risk: relapsed or primary refractory ALL or AML, RAEB and RAEBT. (B) Cytogenetic abnormalities were classified as favorable if t(8;21), t(15;17) or inversion 16 for AML or hyperdiploidy for ALL were present; high risk included 11q23 abnormalities, monosomy 7, monosomy 5, deletion 5q or abnormalities of 3q, t(9;22), extreme hypodiploid for ALL or complex abnormalities (≥3 chromosomes); intermediate risk included all other abnormalities. (This figure was originally published in Biology of Blood and Marrow Transplantation. E.R. Nemecek, K.A. Guthrie, M.L. Sorror, B.L. Wood, K.C. Doney, R.A. Hilger, B.L. Scott, T.J. Kovacsovics, R.T. Maziarz, A.E. Woolfrey, A. Bedalov, J.E. Sanders, J.M. Pagel, E.J. Sickle, R.Witherspoon, M.E. Flowers, F.R. Appelbaum, H.J. Deeg. Conditioning with Treosulfan and Fludarabine followed by Allogeneic Hematopoietic Cell Transplantation for High-Risk Hematologic Malignancies. Biology of Blood and Marrow Transplantation. 2011;17(3):341–350. © Elsevier.)

FIGURE 3. Survival curves comparing overall survival in patients treated with azacitidine at the first sign of relapse (including MRD) after allogeneic transplantation for MDS/AML as compared to historical controls [47] from our Center

Survival for the patients treated with azacitidine is calculated from the start of treatment. Survival for historical controls is calculated from the date of relapse. (A) Improved OS prolonged survival for patients treated with azacitidine compared to the controls population if relapse occurred prior to day 100 (n=17). (B) In patients relapsing after day 200, no improvement in overall survival was seen compared to the historical population, but numbers were small (n=6).