Allogeneic Hematopoietic Stem-Cell Transplantation for Myelodysplastic Syndrome

Abstract

Transplantation is the only known cure for myelodysplastic syndrome (MDS). While some comparative analyses have demonstrated early transplantation to be the preferred strategy for all MDS patients, many of these analyses are biased. Using newly identified prognostic factors and models, a rational approach to transplantation can be undertaken. Factors such as transfusion dependency, cytogenetics, medical comorbidity, and World Health Organization (WHO) histologic subtype should all be considered when deciding on the role of transplantation for the MDS patient. Unresolved issues in transplantation include the impact of pre-transplant tumor debulking with traditional chemotherapeutic agents or the new DNA hypomethylating agents, and the optimal timing of reduced-intensity conditioning transplantation for older patients or for those with medical comorbidities.Despite the approval of three novel agents for myelodysplastic syndrome (MDS) therapy, allogeneic hematopoietic stem-cell transplantation (HSCT) is the only known curative procedure for MDS. Transplantation for MDS occurs frequently, as MDS is currently the third most common indication for allogeneic HSCT as reported to the Center for International Blood and Marrow Transplantation Research. 1 MDS is a disease predominantly of older individuals, and with the increased use and acceptance of reduced intensity conditioning (RIC) into the eighth decade of life, it is anticipated that the number of transplantations for MDS will continue to increase in the coming years. As novel therapies emerge for MDS, it is imperative to determine the optimal role for and timing of HSCT in the MDS patient.Comparative registry analyses have documented the benefit of transplantation over conventional supportive and disease-modifying therapeutics in the treatment of MDS, 2 but this should not be interpreted as an indication for transplantation in all MDS patients. Despite the curative potential of HSCT, transplantation is not undertaken lightly, and careful consideration must be made regarding the appropriateness of each potential transplant recipient and the timing at which transplantation is offered. Despite this, all patients who are potential candidates for transplantation should be referred to a transplantation center early in their disease course so that a discussion regarding the appropriateness of transplantation can occur and a donor search can be initiated when appropriate. This review focuses on appropriate patient selection for HSCT for MDS. Timing of TransplantationThe timing of transplantation has always been the most controversial topic of discussion for both patients and physicians. Faced with the uncertainty of transplantation outcomes but the certainty of eventual MDS disease progression, decisions are often made based on patient preference. Supporting these decisions are a number of single-and multi-institution experiences that have demonstrated improved outcomes with early transplantation. It is clear that there is inherent bias in these types of analyses, because ...

Current therapy of myelodysplastic syndromes

“…As recent advances in the field of alloSCT and the introduction of reduced intensity conditioning (RIC) regimens have led to important reductions in TRM, relapse has become the leading impediment to achieving long-term survival of transplanted MDS patients [180,181]. Therefore, although alloSCT should be considered in all MDS patients, careful selection of patients based on a thoughtful evaluation of risk/benefit ratio is of paramount importance [182–184]. …”

Wilms Tumor Gene 1 Expression as a Predictive Marker for Relapse and Survival after Hematopoietic Stem Cell Transplantation for Myelodysplastic Syndromes

“…Therefore, relapse is now considered to be a major cause of treatment failure after allo-HSCT. Previous studies reported a relapse rate of 5% to 20% in early MDS and up to 60% in advanced MDS, and they suggested MDS stage, bone marrow (BM) blast counts, advanced age, and cytogenetics are risk factors for relapse [1,[5][6][7]. For patients at high risk, various transplantation strategies can be applied, including modification of conditioning intensity, early withdrawal of immunosuppressive agents, preemptive cellular therapy of donor lymphocyte infusion (DLI) or natural killer cells, and post-HSCT maintenance of hypomethylating agents (HMA) [8].…”

Absence of aberrant myeloid progenitors by flow cytometry is associated with favorable response to azacitidine in higher risk myelodysplastic syndromes

“…The majority of patients (11/18, 61%) that showed HI, had combined HI-E, HI-N and/or HI-P. Nine patients with initial HI lost response or progressed after median time of 6.9 months (range [4][5][6][7][8][9][10][11][12][13][14] and median number of 9 cycles (range 5-15).…”