Comparison of Intensive Chemotherapy and Hypomethylating Agents before Allogeneic Stem Cell Transplantation for Advanced Myelodysplastic Syndromes: A Study of the Myelodysplastic Syndrome Subcommittee of the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplant Research

Abstract

The European Society for Blood and Marrow Transplant Research data set was used to retrospectively analyze the outcomes of hypomethylating therapy (HMA) compared with those of conventional chemotherapy (CC) before hematopoietic stem cell transplantation (HSCT) in 209 patients with advanced myelodysplastic syn-dromes. Median follow-up was 22.1 months and the median age of the group was 57.6 years with 37% of the population older than > 60 years. The majority of patients (59%) received reduced-intensity conditioning and 34% and 27% had intermediate-2 and high international prognostic scoring system (IPSS) scores. At time of HSCT, 32% of patients did not achieve complete remission (CR) and 13% had primary refractory disease. On univariate analysis, outcomes at 3 years were not significantly different between HMA and CC for overall survival (OS), relapse-free survival (RFS), cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM): OS (42% versus 35%), RFS (29% versus 31%), CIR (45% versus 40%), and NRM (26% versus 28%). Comparing characteristics of the groups, there were more patients < 55 years old, more patients in CR (68% versus 32%), and fewer patients with primary refractory disease in the CC group than in the HMA group (10% versus 19%, P < .001). Patients with primary refractory disease had worse outcomes than those in CR with regard to OS (hazard ratio [HR], 2.42; 95% confidence interval [CI], 1.41 to 4.13; P ¼ .001), RFS (HR, 2.27; 95% CI, 1.37 to 3.76; P ¼ .001), and NRM (HR, 2.49; 95% CI, 1.18 to 5.26; P ¼ .016). In addition, an adverse effect of IPSS-R cytogenetic risk group was evident for RFS. In summary, outcomes after HSCT are similar for patients receiving HMA compared with those receiving CC, despite the higher proportion of patients with primary refractory disease in the HMA group.

Better transplant outcome with pre-transplant marrow response after hypomethylating treatment in higher-risk MDS with excess blasts

“…However, a recent study by Potter et al using a large registry data suggested that, unlike for patients with primary refractory disease, the post-transplant outcomes of patients with MDS not in CR were not significantly worse than those in CR [24]. This is in line with our results which showed that continued marrow response even without HI at HSCT was an independent predictor of a favorable prognosis, and that CR was not a prerequisite for prolonged survival.…”

The Role of Hypomethylating Agents Prior to Allogeneic Hematopoietic Stem Cells Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome

“…Частота ответов на ГМП сопоставима с данными, полученными в исследованиях других авторов [13][14][15][16][17].…”

“…Так, сообщается о преимуществах у пациентов с моносомией/делецией хромосомы 7 при лечении азацитидином [20]. В литературе глубокому анализу подвергается прогностическое значение цитогенетических аномалий [14,21]. В проведенном нами многофакторном анализе влияние цитогенети-ческих изменений не было статистически значимым.…”

“…Potter и соавт. [14], а также группы исследователей под руководством S.A. Yahng [24], ответ на ГМП и его сохранение до момента выполнения аллоТГСК ста-тистически значимо улучшали показатели ОВ и БСВ [14,24]. Однако ряд исследователей [16] не находят связи между ответом на ГМП и исходом заболевания.…”

Decitabine Containing Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Intermediate- and High-Risk Myelodysplastic Syndrome/Acute Myeloid Leukemia: Potential Decrease in the Incidence of Acute Graft Versus Host Disease

“…Dec therapy was shown to be associated with reduced incidence of GvHD, lower relapse rate, and increased overall survival with acceptable tolerance. [6][7][8][9] Thus, Dec may be an ideal candidate for use in combination with standard preparative regimen for patients scheduled to undergo allo-HSCT. In this study, we retrospectively evaluated the efficacy and safety of Dec-containing conditioning regimen in 76 patients with intermediate-or high-risk MDS/AML.…”