Donor choice in haploidentical stem cell transplantation: fetal microchimerism is associated with better outcome in pediatric leukemia patients

Kruchen, Anne; Stahl, Tanja; Gieseke, Friederike; Binder, Thomas; Özcan, Zakir; Meisel, Roland; Kreyenberg, Hermann; Bader, Peter; Gruhn, Bernd; Greil, Johann; Pfeiffer, Mat­thias; Döring, Michaela; Handgretinger, Rupert; Müller, Ingo

doi:10.1038/bmt.2015.136

Cited by 11 publications

(16 citation statements)

References 20 publications

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“…Haplo-HSCT has gained great interest over the last 2 decades, and in 2015, despite numerous publications, only a few included a pediatric patient population [26][27][28][29] with a different platform of haplo-HSCT. However, these studies have proven that this type of HSCT can be offered to a large proportion of pediatric patients irrespective of the underlying disease.…”

Section: Discussionmentioning

confidence: 99%

Feasibility and Outcome of Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplant High-Dose Cyclophosphamide for Children and Adolescents with Hematologic Malignancies: An AIEOP-GITMO Retrospective Multicenter Study

Berger

Lanino

Cesaro

et al. 2016

Biology of Blood and Marrow Transplantation

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Post-transplant high-dose cyclophosphamide (PTCy) is a novel approach to prevent graft-versus-host disease (GVHD) and rejection in patients given haploidentical hematopoietic stem cell transplantation (HSCT). Thirty-three patients with high-risk hematologic malignancies and lacking a match-related or -unrelated donor were treated with PTCy haploidentical HSCT in 5 Italian AIEOP centers. Nineteen patients had a nonmyeloablative preparative regimen (57%), and 14 patients received a full myeloablative conditioning regimen (43%). No patients received serotherapy; GVHD prophylaxis was based on PTCy (50 mg/kg on days +3 and +4) combined with mycophenolate plus tacrolimus or cyclosporine A. Neutrophil and platelet engraftment was achieved on days +17 (range, 14 to 37) and +27 (range, 16 to 71). One patient had autologous reconstitution for anti-HLA antibodies. Acute GVHD grades II to IV and III to IV and chronic GVHD developed in 22% (95% CI, 11 to 42), 3% (95% CI, 0 to 21), and 4% (95% CI, 0 to 27) of cases, respectively. The 1-year overall survival rate was 72% (95% CI, 56 to 88), progression-free survival rate was 61% (95% CI, 43 to 80), cumulative incidence of relapse was 24% (95% CI, 13 to 44), and transplant-related mortality was 9% (95% CI, 3 to 26). The univariate analysis for risk of relapse incidence showed how 3 significant variables, mother as donor (P = .02), donor gender as female (P = .04), and patient gender as female (P = .02), were significantly associated with a lower risk of relapse. Disease progression was the main cause of death. PTCy is a safe procedure also for children and adolescents who have already received several lines of chemotherapy. Among the different diseases, a trend for better 1-year rates of overall survival was obtained for nonacute leukemia patients.

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Section: Discussionmentioning

confidence: 99%

Feasibility and Outcome of Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplant High-Dose Cyclophosphamide for Children and Adolescents with Hematologic Malignancies: An AIEOP-GITMO Retrospective Multicenter Study

Berger

Lanino

Cesaro

et al. 2016

Biology of Blood and Marrow Transplantation

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“…Younger recipients of maternal kidney allografts experienced a lower rate of acute rejection compared to children who received a kidney allograft from the father 19 . In bone marrow transplantation, a superior overall survival and reduction in cases of severe graft‐versus‐host disease were reported after transplant from maternal donors compared to paternal graft recipients 20,21 . The potential impact of donor‐specific HLA alloantibodies (DSA) in maternal‐LLD graft recipients when compared to non‐maternal‐LLD grafts and DDLT grafts has yet to be explored.…”

Section: Introductionmentioning

confidence: 99%

Immunologic benefits of maternal living donor allografts in pediatric liver transplantation: fewer rejection episodes and no evidence of de novo allosensitization

Barbetta

Meeberg

Rocque

et al. 2021

Pediatric Transplantation

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Background Pediatric liver transplant (LT) recipients of maternal living liver donor (LLD) grafts have been reported to experience fewer rejection episodes. However, it is unclear whether this benefit translates to reduction in developing donor‐specific antibody (DSA) among maternal‐LLD recipients. The aim of this study was to compare immunologic outcomes among maternal‐LLD, non‐maternal‐LLD, and deceased donor liver transplant (DDLT) recipients. Methods Children (≤18 years) who underwent LT between 1/1998 and 12/2019 at two high‐volume LT centers in North America were evaluated. Patients were divided into three groups by type of graft received (maternal‐LLD, non‐maternal LLD, and DDLT). Clinical variables and outcomes were compared according to each graft type. Results A total of 450 pediatric primary LT were analyzed: 275 (61.1%) DDLT, 73 (16.2%) maternal‐LLD, and 102 (22.6%) non‐maternal‐LLD. Children receiving LLD grafts were less likely to develop rejection when compared to the DDLT group (DDLT 46.9% vs. maternal‐LLD 31.5% vs. non‐maternal‐LLD 28.4%, p = 0.001). There was no difference in rejection rates between maternal and non‐maternal‐LLD recipients. A higher percentage of maternal‐LLD recipients were on immunosuppression monotherapy compared to non‐maternal‐LLD and DDLT recipients (6.7% vs. 1.2 vs. 2.4%, respectively). A subgroup of 68 patients were tested for DSA post‐LT. Maternal‐LLD recipients were less likely to develop de novo DSA (maternal‐LLD 11.8% vs. non‐maternal‐LLD 19.3% vs. DDLT 43%, p = 0.018). None of the maternal‐LLD recipients developed antibody‐mediated rejection. Conclusions These data support the concept of immunologic benefit of maternal‐LLD in pediatric LT, with lower rates of rejection and allosensitization post‐LT when compared to DDLT recipients.

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“…The most probable explanation would be the combination of donor-recipient. It is well accepted that fetal micro-chimerism is helpful in increasing survival rates in pediatric HSCT cases [ 36 ]. Besides, HSCT using matched related donors showed superior NRM compared with that using haplo-identical donors.…”

Section: Discussionmentioning

confidence: 99%

Salvaged allogeneic hematopoietic stem cell transplantation for pediatric chemotherapy refractory acute leukemia

et al. 2017

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There is an ongoing debate concerning the performance of salvaged allogeneic hematopoietic stem cell transplantation (allo-HSCT) in pediatric patients with acute refractory leukemia, in whom the prognosis is quite dismal. Few studies have ever been conducted on this subject. This may be partly due to missed opportunities by majority of the patients in such situations. To investigate the feasibility, evaluate the efficiency, and identify the prognostic factors of allo-HSCT in this sub-setting, the authors performed a single institution-based retrospective analysis. A total of 44 patients, of whom 28 had acute myeloid leukemia (AML), 13 had acute lymphocytic leukemia (ALL), and 3 had mixed phenotype leukemia (MPL), were enrolled in this study. With a median follow-up of 19 months, the estimated 2-year overall survival (OS) and progression free survival (PFS) were 34.3% (95% CI, 17.9–51.4%) and 33.6% (95% CI, 18.0–50.1%), respectively. The estimated 2-year incidence rates of relapse and non-relapse mortality (NRM) were 43.8% (95% CI 26.4–60.0%) and 19.6% (95% CI 9.1–32.9%), respectively. The estimated 100-day cumulative incidence of acute graft versus host disease (aGvHD) was 43.6% (95% CI 28.7–57.5%), and the 1-year cumulative incidence of chronic GvHD (cGvHD) was 45.5% (95% CI 30.5–59.3%). Compared with the previous studies, the multivariate analysis in this study additionally identified that female donors and cGvHD were associated with lower relapse and better PFS and OS. Male recipients, age younger than 10 years, a diagnosis of ALL, and the intermediate-adverse cytogenetic risk group were associated with increased relapse. On the contrary, extramedullary disease (EMD) and aGvHD were only linked to worse PFS. These data suggested that although only one-third of the patients would obtain PFS over 2 years, salvaged allo-HSCT is still the most reliable and best therapeutic strategy for refractory pediatric acute leukemia. If probable, choosing a female donor, better management of aGvHD, and induction of cGvHD promotes patient survival.

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Donor choice in haploidentical stem cell transplantation: fetal microchimerism is associated with better outcome in pediatric leukemia patients

Cited by 11 publications

References 20 publications

Feasibility and Outcome of Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplant High-Dose Cyclophosphamide for Children and Adolescents with Hematologic Malignancies: An AIEOP-GITMO Retrospective Multicenter Study

Feasibility and Outcome of Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplant High-Dose Cyclophosphamide for Children and Adolescents with Hematologic Malignancies: An AIEOP-GITMO Retrospective Multicenter Study

Immunologic benefits of maternal living donor allografts in pediatric liver transplantation: fewer rejection episodes and no evidence of de novo allosensitization

Salvaged allogeneic hematopoietic stem cell transplantation for pediatric chemotherapy refractory acute leukemia

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