Comparison of melphalan‐ And busulfan‐based myeloablative conditioning in children undergoing allogeneic transplantation for acute myeloid leukemia or myelodysplasia

Abstract

Background:The optimal conditioning regimen for alloHCT in children with myeloid malignancies remains undefined. Procedure:We performed a retrospective review of children undergoing alloHCT for AML and MDS over a 10-year period (2008-2018) at our institution, comparing the outcomes of recipients of either a myeloablative busulfan-or reduced toxicity mel/ thio-based conditioning regimen.Results: A total of 49 patients underwent alloHCT for AML/MDS (mel/thio, N = 21; busulfan, N = 28). Mel/thio recipients were selected due to pretransplant comorbidities. Recipients of mel/thio were more likely to have t-AML, and less likely to have MRD <0.1% at the time of alloHCT (57.1% vs 82.1%). Graft failure was more common in busulfan recipients; engraftment kinetics were similar between groups. Sinusoidal obstructive syndrome was diagnosed in 21% of busulfan and no mel/thio recipients (P = .03). One patient in each group died from TRM. Relapse incidence was comparable (mel/thio-29% vs busulfan-32%); however, relapse occurred significantly later in recipients of mel/thio conditioning (median d + 396 vs d + 137; P = .01). As a result, there was a trend toward improved OS at 1 and 3 years in mel/thio recipients (95% vs 74%, P = .06; and 75% vs 50%, P = .11; respectively). Conclusion:In our single institution, when compared to myeloablative busulfanbased conditioning, use of a mel/thio-based reduced toxicity regimen resulted in comparable outcomes, despite higher risk patient and disease characteristics. Mel/ thio recipients had both more comorbidities and higher risk disease profile, which did not translate into higher rates of either TRM or relapse. K E Y W O R D Sacute myeloid leukemia, hematopoietic cell transplantation, myelodysplastic syndrome, pediatric, reduced toxicity conditioning

The Role of Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Leukemia

“…In a prospective II phase study evaluating safety and efficacy of a conditioning regimen based on Treosulfan, Fludarabine and Thiotepa in 29 pediatric patients with AML, the 3-year PFS and OS were 79% and 84%, respectively [109]. Results on other RIC or reduced toxicity regimens have been published in smaller cohorts of pediatric patients, reporting promising safety and efficacy results [110][111][112][113]. Of note, use of RIC or reduced toxicity regimen was explored in children with relapsed/refractory (R/R) AML in association with Clofarabine.…”

Melphalan and cytarabine as a salvage therapy in children with relapsed or refractory acute leukemia

“…Therefore a low toxicity regimen is needed. Melphalan is an alkylating drug with myeloablative and antitumour effect, which has been used in conditioning regimens prior to stem cell transplantation in different hematologic and non-hematologic malignancies [6][7][8] . The dose-limiting toxicity of melphalan is its bone marrow suppression, the extramedullary toxicity is low including mucosal damage, increase of liver enzymes and the development of interstitial pneumonia 6 .…”