Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide in Children with High-Risk Leukemia Using a Reduced-Intensity Conditioning Regimen and Peripheral Blood as the Stem Cell Source

Trujillo, Ángela Maria; Karduss, Amado; Suárez, Guillaume; Pérez, Rosendo; Ruiz, Giovanni; Cardona, Angelica; Ramı́rez, Mónica; Betancur, José

doi:10.1016/j.jtct.2021.02.010

Cited by 13 publications

(8 citation statements)

References 34 publications

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“…Reviewing the literature, however, some trends can be observed (see Table 2 for a summary) (9,12,14,35,41,60,74,75,78,79,95,(99)(100)(101)(102)(103). Generally, the cumulative incidence rates of severe (grade III-IV) aGvHD and overall as well as extensive cGvHD are higher in patients treated with the PTCy platform compared with those treated with ex vivo TCD (Table 1) (35,95).…”

Section: Graft-vs-host Diseasementioning

confidence: 99%

T-Cell-Replete Versus ex vivo T-Cell-Depleted Haploidentical Haematopoietic Stem Cell Transplantation in Children With Acute Lymphoblastic Leukaemia and Other Haematological Malignancies

Kleinschmidt

Yanir

et al. 2021

Front. Pediatr.

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Allogeneic haematopoietic stem cell transplantation (HSCT) represents a potentially curative option for children with high-risk or refractory/relapsed leukaemias. Traditional donor hierarchy favours a human leukocyte antigen (HLA)-matched sibling donor (MSD) over an HLA-matched unrelated donor (MUD), followed by alternative donors such as haploidentical donors or unrelated cord blood. However, haploidentical HSCT (hHSCT) may be entailed with significant advantages: besides a potentially increased graft-vs.-leukaemia effect, the immediate availability of a relative as well as the possibility of a second donation for additional cellular therapies may impact on outcome. The key question in hHSCT is how, and how deeply, to deplete donor T-cells. More T cells in the graft confer faster immune reconstitution with consecutively lower infection rates, however, greater numbers of T-cells might be associated with higher rates of graft-vs.-host disease (GvHD). Two different methods for reduction of alloreactivity have been established: in vivo T-cell suppression and ex vivo T-cell depletion (TCD). Ex vivo TCD of the graft uses either positive selection or negative depletion of graft cells before infusion. In contrast, T-cell-repleted grafts consisting of non-manipulated bone marrow or peripheral blood grafts require intense in vivo GvHD prophylaxis. There are two major T-cell replete protocols: one is based on post-transplantation cyclophosphamide (PTCy), while the other is based on anti-thymocyte globulin (ATG; Beijing protocol). Published data do not show an unequivocal benefit for one of these three platforms in terms of overall survival, non-relapse mortality or disease recurrence. In this review, we discuss the pros and cons of these three different approaches to hHSCT with an emphasis on the significance of the existing data for children with acute lymphoblastic leukaemia.

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Section: Graft-vs-host Diseasementioning

confidence: 99%

T-Cell-Replete Versus ex vivo T-Cell-Depleted Haploidentical Haematopoietic Stem Cell Transplantation in Children With Acute Lymphoblastic Leukaemia and Other Haematological Malignancies

Kleinschmidt

Yanir

et al. 2021

Front. Pediatr.

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“…Trujillo et al reported on 26 children with ALL who received RIC followed by hHSCT-PTCy. The incidence of acute grade III-IV GvHD was 17%, OS was 56%, and EFS was 46%, with no association between these outcomes and donor-recipient kinship (38).…”

Section: Optimal Donor Choice In Hhsctmentioning

confidence: 94%

“…Majority of patients received bone marrow graft and two patients received peripheral blood graft. Another recent study by Trujillo et al reported on 42 children with highrisk malignancies (22 with ALL) who underwent hHSCT-PTCy with RIC (fludarabine plus busulfan or melphalan, and low-dose TBI) and peripheral blood as the stem cell source (38). The group demonstrated outcomes comparable to studies utilising myeloablative regimens, with 1-year TRM of 14%, a relapse rate of 26%, 3-year OS of 56%, and 3-year EFS of 46%.…”

Section: T-cell Replete Hhsct With Ptcymentioning

confidence: 99%

HLA-Haploidentical Family Donors: The New Promise for Childhood Acute Lymphoblastic Leukaemia?

Rahman

Matić

Yordanova³

et al. 2022

Front. Pediatr.

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Allogeneic haematopoietic stem cell transplantation (HSCT) is indicated in children with high-risk, relapsed or refractory acute lymphoblastic leukaemia (ALL). HLA-matched grafts from cord blood and stem cell repositories have allowed patients without suitable sibling donors to undergo HSCT. However, challenges in procuring matched unrelated donor (MUD) grafts due to high cost, ethnic disparity and time constraints have led to the exponential rise in the use of stem cells from human leukocyte antigen (HLA)-haploidentical family donors. Whilst HLA-haploidentical HSCT (hHSCT) performed in adult patients with acute leukaemia has produced outcomes similar to MUD transplants, experience in children is limited. Over the last 5 years, more data have emerged on hHSCT in the childhood ALL setting, allowing comparisons with matched donor transplants. The feasibility of hHSCT using adult family donors in childhood ALL may also address the ethical issues related to selection of minor siblings in matched sibling donor transplants. Here, we review hHSCT in paediatric recipients with ALL and highlight the emergence of hHSCT as a promising therapeutic option for patients lacking a suitable matched donor. Recent issues related to conditioning regimens, donor selection and graft-vs.-host disease prophylaxis are discussed. We also identify areas for future research to address transplant-related complications and improve post-transplant disease-free survival.

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“…The reports on haplo-HSCT with PTCY in children are summarised in Table 1 [28][29][30][31][32][33][34][35][36]. Notably, most paediatric reports are single-centre studies, analyse a small number of patients, include mixed underlying diseases, and are retrospective studies.…”

Section: Haplo-hsct With Ptcy and Its Current Progress In Paediatric ...mentioning

confidence: 99%

Human Leukocyte Antigen–Haploidentical Haematopoietic Stem Cell Transplantation Using Post-Transplant Cyclophosphamide for Paediatric Haematological Malignancies

Nishikawa

2024

Cancers

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The use of human leukocyte antigen (HLA)–haploidentical haematopoietic stem cell transplantation (HSCT) with post-transplant cyclophosphamide (PTCY), which markedly reduces the risk of graft-versus-host disease, has rapidly increased worldwide, even in children. It was initially developed for post-transplant relapse or non-remission at transplant for patients with high-risk haematologic malignancies. However, this strategy is currently used more frequently for standard-risk, transplant-eligible paediatric haematological malignancies. It has recently been recognised in adults that the transplant outcomes after PTCY-based HLA–haploidentical HSCT are comparable with those achieved after HLA-matched HSCT. Therefore, even in children, parental donors who are HLA–haploidentical donors and cord blood are currently considered the next donor candidates when an HLA-matched related or unrelated donor is unavailable. This review addresses the current status of the use of haplo-HSCT with PTCY for paediatric haematologic malignancies and future directions for donor selection (sex, age, ABO blood type, and HLA disparity), donor source, the dose of infused CD34+ cells, optimal conditioning, the concomitant graft-versus-host disease prophylaxis other than PTCY, and the pharmacokinetic study of CY and CY metabolites. These aspects present key solutions for further improvements in the outcomes of haplo-HSCT with PTCY for paediatric haematological malignancies.

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Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide in Children with High-Risk Leukemia Using a Reduced-Intensity Conditioning Regimen and Peripheral Blood as the Stem Cell Source

Cited by 13 publications

References 34 publications

T-Cell-Replete Versus ex vivo T-Cell-Depleted Haploidentical Haematopoietic Stem Cell Transplantation in Children With Acute Lymphoblastic Leukaemia and Other Haematological Malignancies

T-Cell-Replete Versus ex vivo T-Cell-Depleted Haploidentical Haematopoietic Stem Cell Transplantation in Children With Acute Lymphoblastic Leukaemia and Other Haematological Malignancies

HLA-Haploidentical Family Donors: The New Promise for Childhood Acute Lymphoblastic Leukaemia?

Human Leukocyte Antigen–Haploidentical Haematopoietic Stem Cell Transplantation Using Post-Transplant Cyclophosphamide for Paediatric Haematological Malignancies

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