Outcome of allogeneic bone marrow transplantation for children with advanced acute myeloid leukemia

Abstract

Summary:Allogeneic bone marrow transplantation (BMT) may offer the only chance of cure for children with acute myeloid leukemia (AML) in second complete remission (CR2) or with relapsed disease, but the outcome of these patients has not been clearly defined. We conducted a retrospective study of 58 children, median age 7.4 years (range 0.8-17.3), who received matched related or unrelated BMT at our institution for AML in CR2 (n ¼ 12), in untreated first relapse (n ¼ 11) or with refractory disease (n ¼ 35), to identify risk factors associated with disease-free survival (DFS). Life threatening to fatal regimen-related toxicity was observed in 22% of patients. Estimates of DFS at 5 years (95% confidence interval) for patients in CR2, with untreated first relapse and refractory disease were 58% (27-80%), 36% (11-63%) and 9% (2-21%), respectively. Non-relapse mortality estimates were 0%, 27% (0-54%) and 17% (5-30%), and relapse estimates were 42% (14-70%), 36% (8-65%) and 74% (60-89%), respectively. Advanced disease phase and cytogenetic abnormalities at the time of transplantation were each associated with decreased DFS and increased relapse in multivariable regression models. Survival for children transplanted in CR2 or untreated first relapse is higher than that previously reported, but relapse remains the major cause of treatment failure regardless of disease stage.

Treosulfan-based preparative regimens for allo-HSCT in childhood hematological malignancies: a retrospective study on behalf of the EBMT pediatric diseases working party

“…7,24,25 In the context of a substantially increased risk of lifethreatening transplant-related complications, the CI of NRM was unexpectedly low, and amounted to only 4% at day þ 100, 8% at 1 year and 16% after 4 years from transplantation. The observed CI of NRM was comparable with that reported recently in standard-risk children conditioned for allo-HSCT with standard-prep-reg, 41,43,46 and even lower than in children receiving a RIC regimen. 34 In contrast to the high incidence of NRM in patients conditioned for second HSCT with standard-prep-reg, 47,48 in the children studied here, the 4-year CI of NRM was almost the same after the first or a second HSCT.…”

“…These findings seem to confirm the significant anti-leukemic efficacy of TREO-prep-reg, which appears to be comparable with that of standard-prep-reg in childhood hematological malignancies. 43,46,49,50 The significant anti-leukemic effect of TREO-based conditioning regimens along with their low toxicity, makes them also an attractive alternative to RIC regimens, especially for patients with high-risk hematological malignancies, in whom relapse remains the most common obstacle to a successful outcome of RIC. 4,[35][36][37] However, as a prodrug nonenzymatically activated to alkylating mono-and diepoxides, TREO demonstrates gonadotoxicity and mutagenicity, and thus monitoring and evaluation of its long-term effects, including secondary MDS in children demonstrating mixed chimerism, will be of special importance in children conditioned for HSCT with high-dose TREO.…”

Achieving stringent CR is essential before reduced-intensity conditioning allogeneic hematopoietic cell transplantation in AML

“…9 It is clear that patients with active leukemia had more relapse and worse OS after allo-HCT regardless of donor type or patient age. [10][11][12][13][14][15] Following allo-HCT, 40-60% of AML patients in CR1 enjoy long-term OS, whereas o20% of refractory or relapsed AML patients survive. 1,11 Yet even for allo-HCT during CR, relapse remains the most frequent complication of allo-HCT.…”

Akut Myeloblastik Lösemili Çocuklarda Kök Hücre Nakli

“…Ayrıca, uzun dönem zararlı etkisi olduğundan dolayı, uzun süredir bu hastalarda önerilmemektedir. Fraksiyone TBI, seçilmiş bazı AML olgularının hazırlık rejimlerinde kullanılmaktadır 13 . Treosulfan, busulfanın bir anoloğu olup, son dönemlerdeki allojenik kök hücre naklinde, malin olan (AML içeren) ve olmayan birkaç çalışmada kullanılmıştır 14 .…”