E-Mail karger@karger.com Editorial Comment Acta Haematol 2015;134:38–39 DOI: 10.1159/000369243 Azacitidine and Allogeneic Stem Cell Transplantation: When and Why? Basem M. William Department of Medicine, Stem Cell Transplantation Program, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, Ohio, USA In this issue of Acta Haematologica, Ahn et al. [3] at- tempt to answer whether azacitidine therapy before pro- ceeding to alloSCT can improve the outcome of patients with high-grade MDS [3]. Although 57% of the patients responded to azacitidine, the response did not seem to favorably influence the risk of relapse after alloSCT; this remains comparable to prior reports. MDS and AML are considered to be diseases with ‘intermediate sensitivity’ to the immunologic graft-versus-leukemia effect of alloSCT and, hence, the reduced-intensity conditioning regimen used in the study was shown to decrease the risk of relapse after alloSCT. It was a fludarabine and busulfan reduced-intensity conditioning regimen, which translat- ed into a favorably low treatment-related mortality, but, as expected, had a higher risk of relapse. They did indeed observe a higher risk of relapse in the multivariate analy- sis, i.e. with the use of sibling donors (where the graft- versus-leukemia effect is less brisk than in more immu- nogenic unrelated donors). The use of ‘intermediate intensity’ conditioning regi- mens like fludarabine and melphalan and/or unrelated or partially mismatched donors have been associated with less-than-expected rates of relapse of MDS/AML at the expense of higher rates of graft-versus-host disease and treatment-related mortality. These nullify any improve- ment in survival due to fewer relapses [4]. Ahn et al. [3] suggest that no harm occurred with the use of azacitidine prior to alloSCT, as most patients were able to proceed to alloSCT as planned. It is not known if Allogeneic stem cell transplantation (alloSCT) is cur- rently the only known curative treatment for myelodys- plastic syndrome (MDS). However, the most appropriate timing for this treatment remains unknown. Patients with high-risk MDS have a dismal prognosis with an av- erage survival that can be measured in months. Azaciti- dine represents an important therapeutic advance in the treatment of patients with high-risk MDS. The sobering reality remains, however, that 40–50% do not respond to therapy and most responders experience disease progres- sion within 2 years [1]. Moreover, patients with more ad- vanced disease (refractory anemia with excess blasts in transformation) have a median overall survival of only 5.6 months and the probability of 2-year survival is only 15% [2]. Azacitidine is frequently used as a measure to tempo- rize the disease, especially in patients with bone marrow blasts >10%, until a donor is identified and the pre- alloSCT standard work-up is complete. Unfortunately, data that support this approach are lacking. It is also not clear if patients with intermediate-2 or high-risk MDS would benefit from azacitidine if they have no excess blasts in their bone marrow. Given the dismal prognosis of proceeding to alloSCT after a patient has developed frank acute myeloid leukemia (AML) and in an attempt to avoid the toxicities of aggressive induction chemother- apy, many transplant physicians would proceed directly to alloSCT for patients with high-risk MDS if a suitable donor is identified and the patient is healthy enough to tolerate the procedure. Received: October 14, 2014 Accepted: October 21, 2014 Published online: June 6, 2015 Basem M. William, MD, MRCP (UK) Department of Medicine, Stem Cell Transplantation Program University Hospitals Seidman Cancer Center, Case Western Reserve University 11100 Euclid Ave, LKS 5079 Cleveland, OH 44106 (USA) E-Mail basem.william  @  uhhospitals.org © 2015 S. Karger AG, Basel 0001–5792/15/1341–0038$39.50/0 www.karger.com/aha Downloaded by: Freie Universität Berlin 149.126.78.65 - 6/30/2015 10:24:45 AM