Article Type: Editorial
Accepted date: 11/27/2014
Clinical outcome after failure of hypomethylating therapy for myelodysplastic syndromes.
Angelo M. Carella, Director, Hematology Unit IRCCS AOU San Martino-IST, Genoa, Italy Corresponding Author Mail Id: [email protected]
The myelodysplastic syndromes (MDS), a very complex heterogeneous myeloid disorder that frequently affect older patients, are characterized by ineffective hematopoiesis in one or more lineages of the bone marrow.
In the last decade there has been a revolution in our knowledge of these disorders followed by new effective therapies. In general, the patients are stratified into lower and higher risk groups. Of course, the therapeutic strategies are different since in the first cohort of patients the goal is to improve hemoglobin levels and the quality of life while in higher risk patients the goal is to increase the overall survival. Many patients are treated with hypomethylating agents with clinical benefits; unfortunately patients who do not respond or those who progress during This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/ejh.12521 This article is protected by copyright. All rights reserved.
hypomethylating therapy (HMT) have a poor outcome. It has been demonstrated in this cohort of patients that allogeneic transplantation result in better overall survival with respect to those treated with conventional therapy.
In the article that accompanies this editorial, Lee et al. discuss the clinical outcome of patients after failure to HMT. In their article, the Authors updated the results of 91 patients who resulted Azacitidine or Decitabine failure. Fifty-four patients were treated with not-transplant therapies with very low objective response while 17 out of 23 patients, who receiving allografting, achieved a complete remission. The overall survival probability at 2 years was 60,9% : 78,6% for patients allografted during MDS and 33,3% for those receiving transplant after AML evolution. As suggested in the paper, many questions arise in this and other similar papers but the most important is: which is the best timing for allografting - at the time of remission or later in progressive disease? According to the worse results with allografting achieved when the patients experienced progression under HMT, the best approach should be to offer it to patients who did not progress after HMT. It is hoped that the identification of newer prognostic markers will help us to define the optimal selected patient for transplant, which should be performed as soon as possible. Of course, the advent of reduced-intensity conditioning for transplant (RIC), has determined considerable reduction in the early and late mortality (1-3) even if a higher relapse rate (4-6) has been reported, mainly in older and advanced stage disease patients (4). For this reason, the best approach could be to pretreat the disease with HMT prior to allografting.
This article is protected by copyright. All rights reserved.