Transplantation strategies for the management of patients with myelodysplastic syndromes

Abstract

Allogeneic stem cell transplantation (SCT) is the only therapeutic modality at present that may be delivered with curative intent in patients with myelodysplastic syndromes (MDS). Allogeneic CST replaces recipient dysplastic hemopoiesis with healthy donor haemopoiesis and immune system with an attendant graft-versus-leukemia (GvL) effect. Its applicability, however, is limited by the age of MDS patients, high rates of transplant-related mortality (TRM) and availability of a suitable HLA-matched donor. Results from several large centres indicated 3-year overall survival (OS) rates of 20-45%, which are almost equal with the results obtained by intensive chemotherapy alone. Failure was due primarily to TRM in patients with low-risk MDS and to disease recurrence in patients with high-risk MDS. Allogeneic SCT from matched unrelated donors produce poorer results than matched related siblings' transplantations. In an attempt to reduce TRM and deliver allogeneic SCT in a greater subgroup of MDS patients, many researchers used reduced-intensity allografts (RIC or "mini"-allograft) for MDS. Although differences in patient populations, preparative regimens, and graft-versus-host disease (GvHD) prophylaxis, as well as donor source (related vs. unrelated) have to be considered, OS of up to 40% at 3 years and disease-free survival (DFS) rates of almost 35% at 3 years have been reported in selected centres. However, randomized prospective studies are needed to further address the optimal choice of transplant conditioning intensity in MDS. Autologous SCT has been extremely investigated in MDS. It is limited to patients who have achieved a complete remission (CR), can be harvested, and are candidates for the procedure. Autologous SCT after successful induction chemotherapy may increase the proportion of long-term survivors, thus improving CR duration in some patients with MDS, particularly in younger patients in remission. Results for older patients are unsatisfactory. The relapse rate is up to 75%, with a 2-year probability of DFS of only 25% for patients 40-60 years of age. Therefore, there is very limited enthusiasm for the future of autologous SCT in the management of MDS patients.