Hematopoietic stem cell transplantation for children with high-risk acute lymphoblastic leukemia in first complete remission: a report from the AIEOP registry

Abstract

© F e r r a t a S t o r t i F o u n d a t i o n N o c o m m e r c i a l u s eThe dynamic evolution of the results obtained with chemotherapy protocols has led to relevant modifications of the eligibility criteria for allogeneic hematopoietic stem cell transplantation (HSCT), so that, for instance, patients with B-cell precursor ALL and more than 100x10 9 /L white blood cells at diagnosis not responding to the steroid prephase should not be offered transplantation.Several retrospective studies suggested that allogeneic HSCT from an HLA-identical sibling improves the prognosis of high-risk ALL patients in first complete remission compared with further intensified chemotherapy protocols. [16][17][18][19][20] In 1995, a prospective, cooperative randomized study was carried out through the collaboration between the International Berlin-Frankfurt-Münster (I-BFM) Study Group and the Pediatric Working Party of the European Blood and Marrow Transplantation (EBMT) Group with the aim of comparing the results of allogeneic HSCT from a compatible related donor with those of children with high-risk ALL in first complete remission diagnosed between 1995 and 2000 and treated with chemotherapy alone. 21 In this study, 357 children were enrolled, 280 of whom received chemotherapy while the other 77 were given chemotherapy followed by related-donor HSCT, on the basis of genetic chance (i.e., availability of an HLA-identical donor). The 5-year disease-free survival was 40.6% in children allocated to chemotherapy and 56.7% in those given HSCT (P=0.02). Balduzzi et al. concluded that children with high-risk ALL in first complete remission benefit more from related-donor HSCT than from chemotherapy alone. The gap between the two strategies increases as the risk profile of the patient worsens. Indeed, children who were eligible for the study because of induction failure benefited more than others from related-donor availability. 21Based on the same cohort of patients they had previously analyzed, Balduzzi et al. recently discussed the impact of the time elapsed in first complete remission on prognosis, as well as the potential influence of waiting time to transplantation. The relative advantage of HSCT from compatible related donors in high-risk childhood ALL was found whatever the time elapsed from first complete remission to HSCT. 22The issue of whether patients with high-risk ALL in first complete remission should undergo HSCT from donors other than an HLA-identical sibling remains controversial. The outcome of unrelated donor HSCT has improved greatly in recent years, mostly because of high-resolution HLA-typing and improved prevention/treatment of graftversus-host disease (GvHD). 23,24 In order to further investigate the impact of allogeneic HSCT in high-risk ALL patients, we carried out a retrospective, multicenter study to analyze the outcome of 211 consecutive ALL pediatric patients who underwent HSCT from a related or unrelated donor for ALL in first complete remission and whose data were reported to the Italian Assoc...

Improved outcome of children transplanted for high-risk leukemia by using a new strategy of cyclosporine-based GVHD prophylaxis

“…Second, as this study is monocentric, patients in this study did not receive various combinations of immunosuppressive agents as usually reported. 25,28,30,35,54 MRD before HSCT had no prognostic value in our cohort. The DFS of patients with negative or positive MRD before HSCT was similar.…”

“…DFS usually reported in children transplanted for high-risk leukemia from sibling or unrelated donors vary between 50 and 70%. 25,[27][28][29][30][31][32][33]40 Weiss et al 37 report a similar DFS (84%) using CsA alone as GVHD prophylaxis but in patients transplanted only from MSDs. 37 They also used CsA while targeting a lower and narrower TBC range (80-130 ng/mL) compared with those usually recommended (100-200 ng/mL).…”

“…This confirms the major role of antithymocyte globulin as part of GvHD prophylaxis in patients transplanted from unrelated donors. 11 We also report a low rate of TRM compared with other series where average TRM reaches 20-25%, 25,29,30,34 even though a large variability (7-45%) is possible. 27,35,38,39 Our results suggest that close monitoring of CsA therapy may permit a substantial reduction of GvHD-related mortality.…”

“…The incidence of severe aGvHD reported in most studies on transplanted children for leukemia is generally much higher (8-19%), although GvHD prophylaxis regimens also include short courses of MTX or MMF. [27][28][29][30][31][32][33] However, observed values of CsA TBC are almost never reported, making difficult any comparison of CsA monitoring. The incidence of chronic GvHD reported in previous similar cohorts varies between 14 and 46%, 31,34 with a majority between 20 and 30%.…”

“…The incidence of chronic GvHD reported in previous similar cohorts varies between 14 and 46%, 31,34 with a majority between 20 and 30%. 30,32,[33][34][35][36][37] The incidence of chronic GvHD we report is lower (8.2%). The incidence of GvHD was not different between matched siblings or unrelated HSCT in our cohort, despite targeting similar CsA TBC.…”