Nilotinib treatment‐associated cerebrovascular disease and stroke

also resulted from relapse and undergoing allogeneic hematopoietic cell transplantation (alloHCT). More importantly, it is obvious that patient number will decrease from beginning to the end of any therapy. Therefore, the primary question remains whether the decline rate is higher with HiDAC compared to other consolidations and the rate of decline worsens with each cycle of HiDAC. Two major prospective studies comparing HiDAC with other consolidations [4,7] showed that completion rate of the planned consolidation therapy course was similar in the HiDAC cohort compared to the other cohort. Thomas et al. noted that “despite the repetition of consolidation courses in the arm with HiDAC, toxicity was more acceptable in this arm than the arm with only one course of time-sequential chemotherapy (TSC)” (the other consolidation cohort comprised of daunorubicin, mitoxantrone, and cytarabine) [7]. Withdrawal from the study was observed in 3/ 151 (2%) in the HIDAC cohort compared to 7/155 (4.5%) in the multiagent chemotherapy (MAC) cohort [4]. One study indicated that perhaps toxicity was more common with HiDAC compared to that with MAC [6]. However, mortality rates were similar in both cohorts in the study. In addition, alloHCT was the most common reason for both cohorts not to pursue the following planned cycle. There was no evidence of accumulating toxicity of HiDAC with increased number of HiDAC cycles; the nadir of leukocyte count rates and the duration of leukopenia were the same throughout the HiDAC cycles even this study [6]. This article does not intend to discuss of HiDAC efficacy or safety compared with other consolidations. However, it shows that the published studies do not support the perception that there is accumulating hematologic or nonhematologic toxicity with increased cycle number of HiDAC. This is an interesting phenomenon and should be investigated. For at least hematologic toxicity, it might be speculated that deepening response with each HiDAC cycle may ablate suppressive effect of AML cells on normal granulocytemacrophage colony formation [10]. In addition, the number and functions of surviving neutrophils remain similar between each HiDAC cycle number, which can in part explain similar rate of infections. In conclusion, the evidence does not support the accumulative toxicity of HiDAC, and decline in patient number with each cycle is not worse than that observed with other intensive consolidation regimens. ANDRES WIERNIK WOLFGANG R. SPERR DANIEL WEISDORF PETER VALENT CELALETTIN USTUN Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, Minnesota; Division of Hematology & Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Waehringer Guertel 18–20, A-1090 Vienna, Austria Conflict of interest: Nothing to report. *Correspondence to: Celalettin Ustun, MD, Professor of Medicine, Division of Hematology Oncology and Transplantation, Department of Medicine, University of Minnesota, 14-142 PWB, 516 Delaware Street SE, Minneapolis, MN 55455. E-mail: custun@umn.edu Received for publication 13 March 2013; Accepted 15 March 2013 Published online 22 March 2013 in Wiley Online Library (wileyonlinelibrary.com) DOI 10.1002/ajh.23440