Allogeneic Stem Cell Transplantation From HLA-Mismatched Donors for Pediatric Patients with Acute Lymphoblastic Leukemia Treated According to the 2003 BFM and 2007 International-BFM Studies: Impact of Disease Risk on Outcomes.

Summary Rational Allogeneic HSCT is beneficial for pediatric patients with relapsed or (very) high-risk ALL in remission. A total of 1115 consecutive patients were included in the ALL SCT 2003 BFM study and the ALL SCT 2007-International study and were stratified according to relapse risk (Standard vs. High vs. Very High Risk of Relapse) and donor type (Matched Sibling vs. Matched Donor vs. Mismatched Donor). Patients and methods A total of 148 patients (60% male, median age 8.7 years; B-cell precursor ALL: 75%) were transplanted from MMD, which was defined as either less than 9/10 HLA-compatible donors or less than 5/6 unrelated cord blood after myelo-ablative conditioning regimen (TBI-based: 67%) for HRR (n=42) or VHRR disease (n=106). The stem cell source was either BM (n=31), unmanipulated PBSCs (n=28), T-cell ex vivo depleted PBSCs (n=59) or cord blood (n=25). The median follow-up was 5.1 years. Results The 4-year OS and EFS was 56±4% and 52±4%, respectively, for the entire cohort. Patients transplanted from MMD for HRR disease obtained remarkable 4-y OS and EFS values of 82±6% and 80±6%, respectively, while VHRR patients obtained values of 45±5% and 42±5% (p Conclusion HSCT with a mismatched donor is feasible in pediatric ALL patients but leads to inferior results compared to HSCT with better matched donors, at least for patients transplanted for VHRR. The results are strongly affected by disease status. The main cause of treatment failure is still relapse, highlighting the urgent need for interventional strategies after HSCT for patients with residual leukemia before and/or after transplantatio

Long-Term Outcomes of Cord Blood Transplantation from an HLA-Identical Sibling for Patients with Bone Marrow Failure Syndromes : A Report From Eurocord, Cord Blood Committee and Severe Aplastic Anemia Working Party of the European Society for Blood and Marrow Transplantation

Cord blood transplantation (CBT) from HLA-identical siblings is an attractive option for patients with bone marrow failure (BMF) syndrome because of the low risk of graft-versus-host disease (GVHD) and the absence of risk to the donor. We analyzed outcomes of 117 patients with inherited or acquired BMF syndrome who received CBT from a related HLA-identical donor in European Society for Blood and Marrow Transplantation centers between 1988 and 2014. Ninety-seven patients had inherited and 20 patients acquired BMF syndrome. Eighty-two patients received a single cord blood (CB) unit, whereas 35 patients received a combination of CB and bone marrow cells from the same donor. Median age at CBT was 6.7 years, and median follow-up was 86.7 months. The cumulative incidence function (CIF) of neutrophil recovery was 88.8% (95% CI, 83.1% to 94.9%), 100-day CIF of grades II to IV acute GVHD was 15.2%, and 7-year CIF of chronic GVHD was 14.5%. Overall survival at 7 years was 87.9% (95% CI, 80.8% to 92.6%), 89% for inherited and 81% for acquired BMF syndromes (P=.66). Results of this study are consistent with outcomes of bone marrow transplantation shown by previous series in the same setting and indicate that in pediatric patients with BMF syndrome, CBT from an HLA-identical sibling donor is associated with excellent long-term outcomes and that collection of CB unit at birth of a new sibling is strongly recommended. (C) 2017 American Society for Blood and Marrow Transplantation.Peer reviewe

Outcome of relapse after allogeneic HSCT in children with ALL enrolled in the ALL-SCT 2003/2007 trial

Relapse remains the major cause of treatment failure in children with high-risk acute lymphoblastic leukaemia (ALL) undergoing allogeneic haematopoietic stem-cell transplantation (allo-SCT). Prognosis is considered dismal but data on risk factors and outcome are lacking from prospective studies. We analysed 242 children with recurrence of ALL after first allo-SCT enrolled in the Berlin-Frankfurt-Munster (BFM) ALL-SCT-BFM 2003 and ALL-SCT-BFM international 2007 studies. Median time from allo-SCT to relapse was 7·7 months; median follow-up from relapse after allo-SCT until last follow-up was 3·4 years. The 3-year event-free survival (EFS) was 15% and overall survival (OS) was 20%. The main cause of death was disease progression or relapse (86·5%). The majority of children (48%) received salvage therapy without second allo-SCT, 26% of the children underwent a second allo-SCT and 25% received palliative treatment only. In multivariate analyses, age, site of relapse, time to relapse and type of salvage therapy were identified as significant prognostic factors for OS and EFS, whereas factors associated with first SCT were not statistically significant. Combined approaches incorporating novel immunotherapeutic treatment options and second allo-SCT hold promise to improve outcome in children with post allo-SCT relapse

Front-line imatinib treatment in children and adolescents with chronic myeloid leukemia: results from a phase III trial

A total of 156 patients (age range 1.3-18.0 years, median 13.2 years; 91 (58.3%) male) with newly diagnosed CML (N = 146 chronic phase (CML-CP), N = 3 accelerated phase (CML-AP), N = 7 blastic phase (CML-BP)) received imatinib upfront (300, 400, 500 mg/m(2), respectively) within a prospective phase III trial. Therapy response, progression-free survival, causes of treatment failure, and side effects were analyzed in 148 children and adolescents with complete data. Event-free survival rate by 18 months for patients in CML-CP (median follow-up time 25 months, range: 1-120) was 97% (95% CI, 94.2-99.9%). According to the 2006 ELN-criteria complete hematologic response by month 3, complete cytogenetic response (CCyR) by month 12, and major molecular response (MMR) by month 18 were achieved in 98, 63, and 59% of the patients, respectively. By month 36, 86% of the patients achieved CCyR and 74% achieved MMR. Thirty-eight patients (27%) experienced imatinib failure because of unsatisfactory response or intolerance (N = 9). In all, 28/148 patients (19%) underwent stem cell transplantation (SCT). In the SCT sub-cohort 2/23 patients diagnosed in CML-CP, 0/1 in CML-AP, and 2/4 in CML-BP, respectively, died of relapse (N = 3) or SCT-related complications (N = 2). This large pediatric trial extends and confirms data from smaller series that first-line imatinib in children is highly effective

Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?-A multicenter EBMT-PDWP study.

Although most children with acute lymphoblastic leukemia (ALL) receive fractionated total body irradiation (FTBI) as myeloablative conditioning (MAC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT), it is an important matter of debate if chemotherapy can effectively replace FTBI. To compare outcomes after FTBI versus chemotherapy-based conditioning (CC), we performed a retrospective EBMT registry study. Children aged 2-18 years after MAC for first allo-HSCT of bone marrow (BM) or peripheral blood stem cells (PBSC) from matched-related (MRD) or unrelated donors (UD) in first (CR1) or second remission (CR2) between 2000 and 2012 were included. Propensity score weighting was used to control pretreatment imbalances of the observed variables. 3.054 patients were analyzed. CR1 (1.498): median follow-up (FU) after FTBI (1.285) and CC (213) was 6.8 and 6.1 years. Survivals were not significantly different. CR2 (1.556): median FU after FTBI (1.345) and CC (211) was 6.2 years. Outcomes after FTBI were superior as compared with CC with regard to overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), and nonrelapse mortality (NRM). However, we must emphasize the preliminary character of the results of this retrospective "real-world-practice" study. These findings will be prospectively assessed in the ALL SCTped 2012 FORUM trial