Abstract

Allogeneic hematopoietic cell transplantation (HCT) is the only curative option for bone marrow failure or hematopoietic malignant diseases for Fanconi anemia (FA) patients. Although results have improved over the last decades, reaching more than 90% survival when a human leukocyte antigen (HLA)-identical donor is available, alternative HCT donors are still less reported. We compared HCT outcomes using HLA-mismatched unrelated donors (MMUD; n=123) or haplo-identical donors (HDs), either using only in vivo T cell depletion (n=33) or T cells depleted in-vivo with some type of graft manipulation ex-vivo (n=59) performed for FA between 2000 and 2018. Overall survival (OS) by 24 months was 62% (53-71%) for MMUD, versus 80% (66-95%) for HDs with only in vivo T cell depletion and 60% (47-73%) for HDs with in vivo and ex vivo T cell depletion (p 0.22). Event free survival (EFS) was better for HD-transplanted FA patients with only in vivo T cell depletion 86% (73-99%) than for those transplanted from a MMUD 58% (48-68%) or those with graft manipulation 56% (42-69%) (p=?0.046). Grade II-IV acute graft-versus-host disease (GVHD) was 41% (MMUD) versus 40% (HDs with no graft manipulation) versus 17% (HDs with T cell depleted graft), (p=0.005). No differences were found for the other transplant related outcomes. These data suggest that HDs might be considered as an alternative option for FA patients with better EFS using unmanipulated grafts. This article is protected by copyright. All rights reserved.

Abstract

PURPOSE Immunosuppressive therapy following pediatric hematopoietic stem cell transplantation is essential for the patient's prognosis, as the antibioprophylaxis and the isolation measures. But medication adherence is suboptimal for children and adolescents, from 52 to 73% in literature. The aim of this study is to provide an understanding of medication adherence after pediatric allogeneic stem cell transplantation (SCT), by identifying facilitators and barriers. METHOD Semi-structured interviews were conducted by a pharmacist with caregivers and healthcare providers in a pediatric centre. Four topics were discussed: transplantation, post-transplantation therapies, caregivers' experience and the healthcare system. Interviews were audiotaped, transcribed and analysed by inductive approach. FINDINGS Semi-structured interviews with 15 caregivers and 21 healthcare providers identified factors of medication adherence and hygiene measures. The long-term nature of therapy and difficult transitions of care were identified as major barriers. Recognizing the benefits of medication and parental involvement are facilitators. Furthermore, caregivers expressed the need to take into consideration the family entity. They would like also to receive earlier information from healthcare providers before hospital discharge. Those needs were not always identified by healthcare providers. CONCLUSION This analysis revealed barriers and facilitators to the medication adherence and to the care. It demonstrated similarities and differences between caregivers and healthcare providers' perceptions and has thereby initiated an improvement process of the healthcare system. As part of this process, medical and paramedical healthcare providers at this French pediatric centre are currently working on a support program for post-alloSCT hospital-home transition.

Abstract

We previously reported in a French prospective randomized study that transplantation of 2 unrelated cord blood (UCB) units instead of 1 does not decrease the risk of transplantation failure but may enhance alloreactivity. We present here the influence of pre-transplant minimal residual disease (MRD) on leukemia relapse and survival after single versus double-UCB transplantation. Among 137 children and young adults who were transplanted in the randomized study, 115 had available MRD assessment immediately before their conditioning regimen. MRD was considered positive when ≥ 10(-4), which was the case of 43 out of 115 patients. Overall, the 3-year survival probability was 69.1+/-4.4% and it was not significantly influenced by the MRD level: 70.7+/-5.4% in MRD- (<10(-4)) patients (n=72), 71.1+/-9.4% in MRD+ with 10(-4)≤MRD<10(-3) (n=26), and 58.8+/-11.9% in MRD+ ≥ 10(-3) patients (n=17). In the MRD+ group, we found a significantly lower risk of relapse in the double- versus single-unit arm (10.5+/-7.2% vs 41.7+/-10.4%; p=0.025) leading to a higher 3-year survival rate (82.6+/-9.3% vs 53.6+/-10.3%, p=0.031). This difference was only observed in patients who had not received anti-thymocyte globulin (ATG) during their conditioning regimen. In the MRD- group, no difference was found between the single- and the double-unit arms. We conclude that, even in case of positive pre-transplant MRD, UCB transplantation in children and young adults with acute leukemia results in a high cure rate and that a double-unit strategy may enhance graft-vs-leukemia effect and survival in these patients.

Abstract

Transplantation of 2 unrelated cord blood (UCB) units instead of 1 has been proposed to increase the cell dose. We report a prospective randomized study, designed to compare single- vs double-UCB transplantation in children and young adults with acute leukemia in remission or myelodysplasia. Eligible patients had at least two 4-6 HLA-identical UCBs with >3 x 10(7) nucleated cells/kg for the first and >1.5 x 10(7) for the second. The primary end point was the 2-year cumulative incidence of transplantation strategy failure, a composite end point including transplant-related mortality (TRM), engraftment failure, and autologous recovery. Randomized patients who did not proceed to transplantation due to refractory disease were considered transplantation failures. A total of 151 patients were randomized and included in the intent-to-treat analysis; 137 were transplanted. Double-UCB transplantation did not decrease transplantation strategy failure (23.4% +/- 4.9% vs 14.9% +/- 4.2%). Two-year posttransplant survival, disease-free survival, and TRM were 68.8% +/- 6.0%, 67.6% +/- 6.0%, and 5.9% +/- 2.9% after single-unit transplantation compared with 74.8% +/- 5.5%, 68.1% +/- 6.0%, and 11.6% +/- 3.9% after double-unit transplantation. The final relapse risk did not significantly differ, but relapses were delayed after double-unit transplantation. Overall incidences of graft-versus-host disease (GVHD) were similar, but chronic GVHD was more frequently extensive after double-UCB transplantation (31.9% +/- 5.7% vs 14.7% +/- 4.3%, P = .02). In an exploratory subgroup analysis, we found a significantly lower relapse risk after double-unit transplantation in patients receiving total body irradiation without antithymocyte globulin (ATG), whereas the relapse risk was similar in the group treated with busulfan, cyclophosphamide, and ATG. Single-UCB transplantation with adequate cell dose remains the standard of care and leads to low TRM. Double-unit transplantation should be reserved for patients who lack such units. This trial was registered at www.clinicaltrials.gov as #NCT01067300.

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 120ng/mL versus 43% with concentration >120ng/mL (P<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 <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.