Donor age matters in T-cell depleted haploidentical hematopoietic stem cell transplantation in pediatric patients: Faster immune reconstitution using younger donors

González‐Vicent, Marta; Molina, Blanca; Deltoro, Natalia; Sevilla, Julián; Vicário, José L.; Castillo, Ana Pérez; Ramírez, Manuel; Díaz, Miguel Ángel

doi:10.1016/j.leukres.2017.03.001

Cited by 37 publications

(34 citation statements)

References 15 publications

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“…The main problem with the use of ruxolitinib is the increase in opportunistic infections, some of them life‐threatening. Viral reactivations of adenovirus and CMV are similar to our previous experience with an incidence of around 25%, and a slight increase in zoster infections up to 23%. CMV infections, which were one of the main concerns of the use of ruxolitinib, were adequately controlled with treatment without stopping ruxolitinib.…”

Section: Discussionsupporting

confidence: 88%

Ruxolitinib treatment for steroid refractory acute and chronic graft vs host disease in children: Clinical and immunological results

et al. 2018

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Ruxolitinib is a promising treatment for steroid refractory graft-vs-host disease (GvHD). However, data concerning effects on T cells are probably involved in increased risk of opportunistic infections. We analyzed clinical and immunological changes in children with GvHD taking ruxolitinib. Twenty-two children that underwent transplantation and received ruxolitinib were included. Ruxolitinib indication was acute and chronic GvHD in 13 and 9 patients, respectively.Overall response rate (ORR) in acute GvHD and chronic GvHD was high, of 77% and 89%, respectively. Ruxolitinib was associated with an increase in CD4 effector memory (EM), and decrease of CD4 central memory percentage. CD4 regulatory T cells percentage decreased significantly. Patients who achieved complete response to ruxolitinib had higher natural killer (NK) cells before ruxolitinib that patients who did not respond. Also there was an increase of CD4 lymphocytes percentage, with decrease of CD8 and NK cells percentage in responders against non-responders. There were 54%, 18% and 13% of infections caused by virus, bacteria and fungi, respectively. Cumulative incidence of relapse and non-relapse mortality was 19 AE 9% and 28 AE 10%, respectively. Overall survival and disease-free survival rate at 2 years were 62 AE 11% and 58 AE 11%, respectively. Ruxolitinib is a promising treatment for acute and chronic GvHD with a high ORR of 77% and 89%, respectively. It produces important changes in immune system, such as increase of CD4 EM cells and decrease in NK and regulatory T cells. Now, we need pharmacokinetic studies to determine ruxolitinib dose in children and close surveillance and antimicrobial prophylaxis.

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Section: Discussionsupporting

confidence: 88%

Ruxolitinib treatment for steroid refractory acute and chronic graft vs host disease in children: Clinical and immunological results

et al. 2018

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“…However, when controlling for the recipient age, only donor relationship was independently associated with survival in multivariate analysis, not donor age. Of note, younger donor age has been associated with better survival in both UD [53][54][55][56] and haplo [13,57] HSCT, although neither of the latter studies evaluated a PTCy-based strategy. There are much less data regarding the impact of donor relationship on outcome of haplo HSCT.…”

Section: Discussionmentioning

confidence: 99%

Selecting the Best Donor for Haploidentical Transplant: Impact of HLA, Killer Cell Immunoglobulin-Like Receptor Genotyping, and Other Clinical Variables

Solomon

Aubrey²,

Zhang

et al. 2018

Biology of Blood and Marrow Transplantation

101

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The use of post-transplant cyclophosphamide (PTCy)-based haploidentical (haplo) transplant is increasing worldwide. However, because multiple potential haplo donors are usually available, data-driven guidance is clearly needed to help transplant centers prioritize donors. To that end, we retrospectively analyzed 208 consecutive donor-recipient pairs receiving PTCy-based haplo transplant at a single institution. Median recipient and donor age were 52 years (range, 19 to 75) and 38 years (range, 15 to 73), peripheral blood stem cell was the stem cell source in 66%, and myeloablative conditioning was used in 41%. Median follow-up for surviving patients was 33 months (range, 7 to 130). Donor variables analyzed included age, sex, relationship, cytomegalovirus (CMV) status, ABO compatibility, HLA disparity, and several natural killer (NK) alloreactivity models. Multivariate Cox analysis was used to adjust for known patient, disease, and transplant covariates. Donor characteristics independently associated with improved survival included presence of HLA-DR mismatch, HLA-DP nonpermissive mismatch, killer cell immunoglobulin-like receptor (KIR) receptor-ligand mismatch, and KIR B/x haplotype with KIR2DS2. Donor characteristics associated with inferior survival included parental donor relationship and the use of a CMV-seronegative donor for a CMV-seropositive patient. Increased HLA disparity (≥4/10 HLA allelic mismatches [graft-versus-host direction]) resulted in relapse protection at the expense of increased nonrelapse mortality with no associated survival effect. We further propose a donor risk factor scoring system to permit a more evidence-based selection algorithm for potential haplo donors. This large, single-institution analysis demonstrates the importance of HLA-DR/HLA-DP disparity, NK alloreactivity, and other clinical variables in the haplo donor selection process and suggests that KIR and HLA-DP genotyping should be performed routinely for haplo donor selection.

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“…The donor's KIR B haplotype appears to be a favorable prognostic factor only in the ex vivo TCD platform. Choosing the right donor for each platform when more than one is available could be a determinant factor in the outcome of HSCT . Future efforts should concentrate on improving relapse probability on both platforms.…”

Section: Discussionmentioning

confidence: 99%

Haploidentical transplantation in high‐risk pediatric leukemia: A retrospective comparative analysis on behalf of the Spanish working Group for bone marrow transplantation in children (GETMON) and the Spanish Grupo for hematopoietic transplantation (GETH)

et al. 2019

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A total of 192 pediatric patients, median age 8.6 years, with high-risk hematological malignancies, underwent haploidentical stem cell transplantation (haplo-HSCT) using post-transplantation cyclophosphamide (PT-Cy), or ex vivo T cell-depleted (TCD) graft platforms, from January 1999 to December 2016 in 10 centers in Spain. Some 41 patients received an unmanipulated graft followed by PT-Cy for graft-vs-host disease (GvHD) prophylaxis. A total of 151 patients were transplanted with CD3-depleted peripheral blood stem cells (PBSCs) by either CD34 + selection, CD3 + CD19 + depletion, TCRαβ + CD19 + depletion or CD45RA + depletion, added to CD34 + selection for GvHD prophylaxis. The PBSCs were the only source in patients

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Donor age matters in T-cell depleted haploidentical hematopoietic stem cell transplantation in pediatric patients: Faster immune reconstitution using younger donors

Cited by 37 publications

References 15 publications

Ruxolitinib treatment for steroid refractory acute and chronic graft vs host disease in children: Clinical and immunological results

Ruxolitinib treatment for steroid refractory acute and chronic graft vs host disease in children: Clinical and immunological results

Selecting the Best Donor for Haploidentical Transplant: Impact of HLA, Killer Cell Immunoglobulin-Like Receptor Genotyping, and Other Clinical Variables

Haploidentical transplantation in high‐risk pediatric leukemia: A retrospective comparative analysis on behalf of the Spanish working Group for bone marrow transplantation in children (GETMON) and the Spanish Grupo for hematopoietic transplantation (GETH)

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