Posttransplant cyclophosphamide for haploidentical stem cell transplantation in children with Wiskott–Aldrich syndrome

Yan, Yonggao; Shi, Xiaodong; Song, Zeliang; Qin, Jiayue; Li, Junhui; Feng, Shunqiao; Liu, Rong

doi:10.1002/pbc.27092

Cited by 13 publications

(8 citation statements)

References 20 publications

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“…HSCT is a curative treatment for WAS, with excellent results for patients with HLA-matched family or unrelated donors [27]. A recent report by Yue et al showed promising results in a case series of five patients who underwent haploidentical HSCT with PT-Cy for WAS [28].…”

Section: Discussionmentioning

confidence: 99%

Haploidentical stem cell transplantation with post-transplant cyclophosphamide for osteopetrosis and other nonmalignant diseases

Even‐Or

NaserEddin

Schejter

et al. 2020

Bone Marrow Transplant

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Allogeneic hematopoietic stem cell transplantation (HSCT) is curative for a variety of nonmalignant disorders including osteopetrosis, bone marrow failures, and immune deficiencies. Haploidentical HSCT is a readily available option in the absence of a matched donor, but engraftment failure and other post-transplant complications are a concern. Post-transplant cyclophosphamide (PT-Cy) regimens are gaining popularity and recent reports show promising results. We report our experience with nine pediatric patients with nonmalignant diseases who were transplanted from a haploidentical donor with PT-Cy. From 2015 to 2019, nine children with nonmalignant diseases underwent haploidentical HSCT with PT-Cy, two as a second transplant and seven as primary grafts after upfront serotherapy and busulfan-based myeloablative conditioning. Patient's diseases included osteopetrosis (n = 5), congenital amegakaryocytic thrombocytopenia (n = 2), hemophagocytic lymphohistiocytosis (n = 1), and Wiskott Aldrich syndrome (n = 1). Two patients failed to engraft following upfront PT-Cy transplants, one was salvaged with a second PT-Cy transplant, and the other with a CD34+ selected graft. None of the patients suffered from graft-versus-host disease. Three patients died from early posttransplant infectious complications and six patients are alive and well. In conclusion, haploidentical HSCT with PT-Cy is a feasible option for pediatric patients with nonmalignant diseases lacking a matched donor.

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Section: Discussionmentioning

confidence: 99%

Haploidentical stem cell transplantation with post-transplant cyclophosphamide for osteopetrosis and other nonmalignant diseases

Even‐Or

NaserEddin

Schejter

et al. 2020

Bone Marrow Transplant

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“…Most recently, the introduction of post-transplant cyclophosphamide (PT-Cy) 55 , 56 or the use of TCRαβ/CD19-depletion 57–62 have yielded favorable results in alternative donor transplantation for WAS and other PIDs. Both methods reduce the incidence of acute and chronic GvHD and improve immune reconstitution.…”

Section: Hematopoietic Stem Cell Transplantationmentioning

confidence: 99%

“…All 5 patients engrafted, and are alive at last follow-up, with full donor chimerism and no post-HSCT autoimmune cytopenias. 55 …”

Section: Hematopoietic Stem Cell Transplantationmentioning

confidence: 99%

“…46,48,54 As has been the case with other graft sources, OS improved to 91.7% for recipients of MMRD-HSCT after 2000, compared to OS of 52.2% for those WAS patients transplanted between 1980 and 1999. 47 Most recently, the introduction of post-transplant cyclophosphamide (PT-Cy) 55,56 or the use of TCRαβ/ CD19-depletion [57][58][59][60][61][62] have yielded favorable results in alternative donor transplantation for WAS and other PIDs. Both methods reduce the incidence of acute and chronic GvHD and improve immune reconstitution.…”

mentioning

confidence: 99%

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Hematopoietic Stem Cell Therapy for Wiskott–Aldrich Syndrome: Improved Outcome and Quality of Life

Mallhi

Petrović

Ochs

2021

JBM

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The Wiskott–Aldrich syndrome (WAS) is an X-linked disorder caused by mutations in the WAS gene resulting in congenital thrombocytopenia, eczema, recurrent infections and an increased incidence of autoimmune diseases and malignancies. Without curative therapies, affected patients have diminished life expectancy and reduced quality of life. Since WAS protein (WASP) is constitutively expressed only in hematopoietic stem cell-derived lineages, hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) are well suited to correct the hematologic and immunologic defects. Advances in high-resolution HLA typing, new techniques to prevent GvHD allowing the use of haploidentical donors, and the introduction of reduced intensity conditioning regimens with myeloablative features have increased overall survival (OS) to over 90%. The development of GT for WAS has provided basic knowledge into vector selection and random integration of various viral vectors into the genome, with the possibility of inducing leukemogenesis. After trials and errors, inactivating lentiviral vectors carrying the WAS gene were successfully evaluated in clinical trials, demonstrating cure of the disease except for insufficient resolution of the platelet defect. Thus, 50 years of clinical evaluation, genetic exploration and extensive clinical trials, a lethal syndrome has turned into a curable disorder.

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“…A prospective study of 5 patients who received haploidentical stem cell transplant and post-transplantation cyclophosphamide showed an overall 100% survival and an average of 27.5 d to platelet counts over 50,000/mm 3 . All recipients showed 100% donor chimerism, with an average follow-up time of 2 years[33].…”

Section: Wiskott-aldrich Syndromementioning

confidence: 99%

Considerations for hematopoietic stem cell transplantation in primary immunodeficiency disorders

Гаврилова

2019

WJT

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Primary immunodeficiency disorders (PIDs) result from inborn errors in immunity. Susceptibility to infections and oftentimes severe autoimmunity pose life-threatening risks to patients with these disorders. Hematopoietic cell transplant (HCT) remains the only curative option for many. Severe combined immunodeficiency disorders (SCID) most commonly present at the time of birth and typically require emergent HCT in the first few weeks of life. HCT poses an unusual challenge for PIDs. Donor source and conditioning regimen often impact the outcome of immune reconstitution after HCT in PIDs. The use of matched or unmatched, as well as related versus unrelated donor has resulted in variable outcomes for different subsets of PIDs. Additionally, there is significant variability in the success of engraftment even for a single patient’s lymphocyte subpopulations. While certain cell lines do well without a conditioning regimen, others will not reconstitute unless conditioning is used. The decision to proceed with a conditioning regimen in an already immunocompromised host is further complicated by the fact that alkylating agents should be avoided in radiosensitive PIDs. This manuscript reviews some of the unique elements of HCT in PIDs and evidence-based approaches to transplant in patients with these rare and challenging disorders.

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Posttransplant cyclophosphamide for haploidentical stem cell transplantation in children with Wiskott–Aldrich syndrome

Abstract: Our pilot study suggests that HSCT with modified PTCy is a safe and effective treatment for WAS, which needs further clinical practice and research.

Cited by 13 publications

References 20 publications

Haploidentical stem cell transplantation with post-transplant cyclophosphamide for osteopetrosis and other nonmalignant diseases

Haploidentical stem cell transplantation with post-transplant cyclophosphamide for osteopetrosis and other nonmalignant diseases

Hematopoietic Stem Cell Therapy for Wiskott–Aldrich Syndrome: Improved Outcome and Quality of Life

Considerations for hematopoietic stem cell transplantation in primary immunodeficiency disorders

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