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

Abstract

There is currently a major concern regarding the optimal immunosuppression therapy to be administered after hematopoietic stem cell transplantation (HSCT) to reduce both the toxicity of GvHD and the rate of relapse. We report the outcome of high-risk leukemia children transplanted with a new way of managing cyclosporine (CsA)-based GvHD prophylaxis. A total of 110 HSCT in 109 ALL or AML children who received CsA without mycophenolate or methotrexate in matched related as well as in matched or mismatched unrelated stem cell transplantation were included. CsA dosage regimens were individualized to obtain specific trough blood concentrations values. The incidences of grade I-II and III-IV acute GvHD were 69.1% and 1.8%, respectively, and 8.4% for chronic GvHD. GvHD was neither more frequent nor severe in unrelated than in related HSCT. GvHD occurred in 87% of patients with a mean CsA trough concentration ⩽ 120 ng/mL versus 43% with concentration 4120 ng/mL (Po 0.0001). Five-year disease-free survival (DFS) and overall survival were 78% and 83.6%, respectively. DFS was 76.9% for ALL and 80.4% for AML patients. There was no difference in DFS between matched siblings and matched unrelated or mismatched unrelated HSCT. DFS in patients with minimal residual disease (MRD) ⩾ 10 − 3 and in those with MRD o 10 − 3 before SCT was comparable. Our results indicate that a GvHD prophylaxis regimen based on CsA without mycophenolate or methotrexate is safe and effective whatever the donor compatibility is. These results suggest that GvL effect may be enhanced by this strategy of GvHD prophylaxis.

Minimal residual disease prior to allogeneic hematopoietic cell transplantation in acute myeloid leukemia: a meta-analysis

“…On subgroup analysis of age 0–20, 18,25,26,30,36 21–40, 28,31,34 and >40, 17,19,21,22,24,27,29,32,33,35 we found no difference in the effect of MRD between groups. The same was true after exclusion of studies with a high risk of bias.…”

“…17–19,21,22,24–37 Details of transplant and conditioning regimens are shown in the Online Supplementary Table S3 . The sole method of MRD detection was MFC in 9 studies 22,24,26–29,33,36,37 and WT1 PCR in 5, 17,18,30–32 while one study reported results separately for MFC- and WT1 PCR-based detection. 19 Four studies used combination methods; 21,25,34,35 all of these included MFC, and 3 also included PCR-based detection.…”

“…19 Four studies used combination methods; 21,25,34,35 all of these included MFC, and 3 also included PCR-based detection. Among studies using MFC-based detection, the cut-point between MRD positivity and negativity was fairly uniform: 11 of 14 used the limit of detection for the assay (around 0.1%), while 3 specified a cutoff of 0.1%, 26,33,36 which corresponded roughly to the limit of detection in these cases. In other words, heterogeneity in cut-points was primarily determined by differences in performance characteristics and interpretation of the assay rather than the cut-points selected.…”

“…For 11 studies, we were able to obtain HRs for all reported outcomes from the manuscript or personal communication; for the other 8 studies, HRs were extrapolated from Kaplan-Meier curves or survival point estimates (n=4). 18,26,34,36 MRD was measured within 60 days of HCT in all studies in which this information was reported, and within 30 days in all but one study. 35 …”

Late effects in children who underwent hematopoietic stem cell transplantation (review)

“…Наиболее подвержены тяжелым последствиям именно пациен-ты после ТГСК, что связано с токсическими осложне-ниями предшествующего лечения, самой процедуры ТГСК, замедленным восстановлением числа и функ-ции иммунокомпетентных клеток, развитием острой и хронической реакций «трансплантат против хозяи-на» (РТПХ), которая может преследовать пациентов в течение всей жизни [4,5]. У больных, получивших ТГСК, каждый орган может рассматриваться как «ми-шень» [6].…”