Allo-SCT using BU, CY and melphalan for children with AML in second CR

Abstract

Based on the results from the AML-BFM 98 trial, hematopoietic SCT (HSCT) is recommended for children with AML in second CR only. Here, we retrospectively analyze interphase data of children who underwent HSCT after myeloablative conditioning with BU, CY, and melphalan (BuCyMel) for AML in second remission (CR2) between 1998 and 2009. Out of 152 children, transplant data were available on 109 individuals. Sixty out of 109 children (55%) received BuCyMel. Median age at HSCT was 12.2 years (range 3.0; 18.3). GVHD prophylaxis mostly consisted of CsA and short term MTX with or without antithymocyte globulin. Matched-sibling donors were used for 6/60 analyzed recipients, the remainder either received grafts from matched unrelated (30/60) or mismatched donors. OS after 5 years was 62% (s.e. 6%), relapse incidence 35% (18/60 children) and treatment-related mortality accounted for 12% (7/60) of fatal events. In conclusion, even taking into account possible selection bias in this retrospective analysis, HSCT in CR2 using BuCyMel resulted in a respectable OS. Based on this data the prospective, controlled and centrally monitored AML SCT-BFM 2007 trial has started to recruit patients in January 2010 aiming to generate valid outcome data for further strategy decisions.

Outcome of children with high-risk acute myeloid leukemia given autologous or allogeneic hematopoietic cell transplantation in the aieop AML-2002/01 study.

“…The choice of adopting a preparative regimen consisting of 3 alkylating agents was inspired by studies demonstrating the safety and efficacy of this therapy in both AML and juvenile myelomonocytic leukemia. 18,31 Since we transplanted patients in CR1, the risk of TRM and of leukemia recurrence in our allograft recipients (7% and 17%, respectively) are in line with those (12% and 33%, respectively) reported by Beier et al 32 in children with AML in CR2, after the same conditioning regimen. Moreover, preparative regimens before the allograft which do not include TBI are particularly attractive for children, since radiation-induced late effects may be especially deleterious for very-young children.…”

A critical review of which children with acute myeloid leukaemia need stem cell procedures

“…The limited improvements in OS after HSCT compared with chemotherapy alone and the higher burden of late effects after transplantation led the Berlin‐Frankfurt‐Münster (BFM) group to abandon HSCT in CR1 for all risk groups in 2006 and reserve HSCT for salvage therapy after relapse (Beier et al , ) but HSCT is planned to be reintroduced for high‐risk (HR) AML in the new protocol.…”

In vitro and in vivo anti-leukemic activity of the peptidase-potentiated alkylator melflufen in acute myeloid leukemia

“…In patients with hematologic malignancies, allogeneic hematopoietic stem cell transplantation (HSCT) using reduced-intensity conditioning with regimens including melphalan has been evaluated in clinical studies [28–30]. In proliferating CD34 + progenitor cells, the melflufen IC 50 was comparable to that found in the low proliferating primary AML cell cultures.…”

“…high frequency of relapse) has often been attributed to the inability of standard chemotherapeutic agents to target AML stem/progenitor cells. This activity of melflufen on the immature (stem cell like) model might contribute to the superior clinical activity over melphalan and could indicate a potential role as a replacement of melphalan in stem cell transplantation [28–30]. Interestingly, the side effect profile of intravenous melflufen, including its myelotoxicity, observed in a clinical phase I study, appeared similar to that of melphalan treatment, both qualitatively and quantitatively [27].…”