Allogeneic hematopoietic cell transplantation for MDS: for whom, when and how?

Abstract

Hematopoietic cell transplantation (HCT) is currently the only treatment with curative potential for patients with myelodysplastic syndrome (MDS). However, treatment-related mortality and relapse have remained major barriers to uniform success. Therefore, important questions remain to be answered, such as whom to transplant, when and how. With reduced intensity conditioning (RIC) regimens, patients in their 70s and patients with comorbid conditions have been transplanted successfully, although the relapse incidence with this approach tends to be increased in comparison to high intensity regimens. Success rates are higher in patients transplanted at an early stage of their disease. Encouraging is the fact, that results with unrelated donors who are HLA-matched by high resolution typing are comparable to those achieved with HLA genotypically identical siblings. The establishment of cord blood as a source of stem cells, and the recent success with HLA-haploidentical related donors will allow the offering of HCT to virtually all patients. Dependent upon disease stage and characteristics, some 25% to 75% of transplanted patients will be cured. While 20%-30% of patients experience chronic medical problems after HCT, 70% report a "good to excellent" quality of life. New studies must focus on further reducing GVHD for all patients and on overcoming high relapse rates in patients with high risk disease.

Figure 1. Impact of IPSS risk category on transplant outcome

A) Probability of RFS, B) Probability of relapse. All patients were conditioned with a busulfan/cyclophosphamide regimen and transplanted with marrow or PBPCs from siblings or unrelated donors. This research was originally published in Blood. Deeg HJ, Storer B, Slattery JT, Anasetti C, Doney KC, Hansen JA, Kiem H-P, Martin PJ, Petersdorf E, Radich JP, Sanders JE, Shulman HM, Warren EH, Witherspoon RP, Bryant EM, Chauncey TR, Getzendaner L, Storb R, Appelbaum FR. Conditioning with targeted busulfan and cyclophosphamide for hemopoietic stem cell transplantation from related and unrelated donors in patients with myelodysplastic syndrome. Blood 2002; 100: 1201-1207. © the American Society of Hematology

Figure 2. Relapse-free survival in patients with MDS or AML conditioned with fludarabine plus treosulfan and transplanted from HLA matched related or unrelated donors

Shown are the results based on cytogenetic risk (per IPSS criteria for MDS, and per cooperative group criteria for AML). Reprinted from Biology of Blood and Marrow Transplantation. Conditioning with Treosulfan and fludarabine followed by allogeneic hematopoietic cell transplantation for high-risk hematologic malignancies. 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. Bedelov, J.E. Sanders, J.M. Pagel, E.J. Sickle, R. Witherspoon, M.E. Flowers, F.R. Appelbaum, H. Joachim Deeg, Biology of Blood and Marrow Transplantation 2011; 17:341-350. © 2011, with permission from Elsevier.