Long Term Outcome and Immune Function After Hematopoietic Stem Cell Transplantation for Primary Immunodeficiency

Gennery, Andrew R.; Lankester, Arjan C.; Transplantation, Marrow

doi:10.3389/fped.2019.00381

Cited by 32 publications

(26 citation statements)

References 62 publications

(75 reference statements)

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“…Recently, the Pediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation has established recommendations for the diagnosis and pre-emptive procedures that should be offered to all children and adolescents in Europe who undergo life-saving allogeneic SCT [12]. Emerging reports describe fertility and gonadal function in transplanted SCID [13][14][15], but actually, no specific studies on ADA-SCID have been performed. We recommend that these aspects deserve special attention considering the systemic manifestations of the condition (ADA-SCID) and the potential effects of its treatments on gonadal function.…”

Section: Discussionmentioning

confidence: 99%

Urogenital Abnormalities in Adenosine Deaminase Deficiency

et al. 2020

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Background Improved survival in ADA-SCID patients is revealing new aspects of the systemic disorder. Although increasing numbers of reports describe the systemic manifestations of adenosine deaminase deficiency, currently there are no studies in the literature evaluating genital development and pubertal progress in these patients.Methods We collected retrospective data on urogenital system and pubertal development of 86 ADA-SCID patients followed in the period 2000-2017 at the Great Ormond Street Hospital (UK) and 5 centers in Italy. In particular, we recorded clinical history and visits, and routine blood tests and ultrasound scans were performed as part of patients' follow-up. Results and Discussion We found a higher frequency of congenital and acquired undescended testes compared with healthy children (congenital, 22% in our sample, 0.5-4% described in healthy children; acquired, 16% in our sample, 1-3% in healthy children), mostly requiring orchidopexy. No urogenital abnormalities were noted in females. Spontaneous pubertal development occurred in the majority of female and male patients with a few cases of precocious or delayed puberty; no patient presented high FSH values. Neither ADA-SCID nor treatment performed (PEG-ADA, BMT, or GT) affected pubertal development or gonadic function. Conclusion In summary, this report describes a high prevalence of cryptorchidism in a cohort of male ADA-SCID patients which could represent an additional systemic manifestation of ADA-SCID. Considering the impact urogenital and pubertal abnormalities can have on patients' quality of life, we feel it is essential to include urogenital evaluation in ADA-SCID patients to detect any

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Section: Discussionmentioning

confidence: 99%

Urogenital Abnormalities in Adenosine Deaminase Deficiency

et al. 2020

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“…There was no difference in overall survival based on receiving conditioning (44). While IR is improved with pre-transplant conditioning, there are significant potential toxicities and optimal conditioning therapy is still not known (38,44).…”

Section: Primary Immunodeficiencymentioning

confidence: 92%

“…In the absence of donor B cell engraftment, patients often require lifelong immunoglobulin replacement. In contrast, patients with interleukin-7 receptor (IL7R)-deficient SCID have intact function of B cells, which can produce immunoglobulin with help from donor T cells (38). Notably, without donor stem cell engraftment, patients are at risk of early T cell exhaustion due to limited donor-derived thymopoiesis (38).…”

Section: Primary Immunodeficiencymentioning

confidence: 99%

“…In contrast, patients with interleukin-7 receptor (IL7R)-deficient SCID have intact function of B cells, which can produce immunoglobulin with help from donor T cells (38). Notably, without donor stem cell engraftment, patients are at risk of early T cell exhaustion due to limited donor-derived thymopoiesis (38). In ADA-deficient SCID, the majority of patients who receive non-conditioned MRD HCT graft engraft donor stem cells and have sustained cellular and humoral IR (43).…”

Section: Primary Immunodeficiencymentioning

confidence: 99%

“…In ADA-deficient SCID, the majority of patients who receive non-conditioned MRD HCT graft engraft donor stem cells and have sustained cellular and humoral IR (43). SCID patients with mutation of RAG1, RAG2 or DCLRE1C (ARTEMIS) have arrest of thymopoiesis at later developmental stages and require conditioning to achieve recovery of donor immunity (38). A recent prospective study demonstrated that patients with SCID who received conditioning (RIC or MAC) prior to HCT had significantly higher levels of T, B, and myeloid cell donor chimerism at day 100, which persisted at 1 year post HCT (44).…”

Section: Primary Immunodeficiencymentioning

confidence: 99%

See 2 more Smart Citations

Immune Reconstitution in Pediatric Patients Following Hematopoietic Cell Transplant for Non-malignant Disorders

Bhatt

Bednarski

2020

Front. Immunol.

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Allogeneic hematopoietic cell transplant (HCT) is curative for pediatric patients with non-malignant hematopoietic disorders, including hemoglobinopathies, bone marrow failure syndromes, and primary immunodeficiencies. Early establishment of donorderived innate and adaptive immunity following HCT is associated with improved overall survival, lower risk of infections and decreased incidence of graft failure. Immune reconstitution (IR) is impacted by numerous clinical variables including primary disease, donor characteristics, conditioning regimen, and graft versus host disease (GVHD). Recent advancements in HCT have been directed at reducing toxicity of conditioning therapy, expanding donor availability through use of alternative donor sources, and addressing morbidity from GVHD with novel graft manipulation. These novel transplant approaches impact the kinetics of immune recovery, which influence post-transplant outcomes. Here we review immune reconstitution in pediatric patients undergoing HCT for non-malignant disorders. We explore the transplant-associated factors that influence immunologic recovery and the disease-specific associations between IR and transplant outcomes.

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Feasibility study of busulfan, fludarabine, and thiotepa conditioning regimen for allogeneic hematopoietic stemcell transplantationfor children and young adults with nonmalignant disorders

Fraser

Castillo

Cascio

et al. 2023

Pediatric Blood & Cancer

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Background Hematopoietic stem cell transplant (HSCT) is the only curative treatment for several pediatric non‐malignant disorders. A widely used conditioning backbone is busulfan, fludarabine, and rabbit anti‐thymocyte globulin (rATG). Thiotepa has improved engraftment when added to this regimen, however the minimum effective dose (MED) of thiotepa to achieve engraftment while minimizing toxicities has not been well established. Objectives The primary objective of this prospective feasibility study was to determine the MED of thiotepa (5mg/kg) in combination with reduced‐dose busulfan, fludarabine or cyclophosphamide, and rATG required to achieve engraftment in >90% of HSCT recipients for non‐malignant disorders with acceptable toxicity. Results Six patients who received fully matched HSCT were enrolled. Patient diagnoses included Wiskott‐Aldrich syndrome (n = 1), CD40L deficiency (n = 1), sickle cell disease (n = 2), autoinflammatory syndrome (n = 1), and paroxysmal nocturnal hemoglobinuria (n = 1). All six patients achieved engraftment prior to Day +42 and five patients had stable full donor engraftment. Two of the six patients (33%) developed acute GVHD and/or chronic GHVD, both of whom had sickle cell disease. At a median follow‐up of 2.25 years post‐transplant, all patients were alive without evidence of disease recurrence. None of the patients experienced grade 4 or 5 toxicities. Three out of six patients (50%) developed grade 3 adverse events. Neurocognitive functioning of children under 10 years of age was not adversely affected by this regimen. Conclusion This approach shows acceptable toxicity and reliable engraftment in children with non‐malignant disorders receiving related or unrelated HLA‐matched transplants.

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Long Term Outcome and Immune Function After Hematopoietic Stem Cell Transplantation for Primary Immunodeficiency

Cited by 32 publications

References 62 publications

Urogenital Abnormalities in Adenosine Deaminase Deficiency

Urogenital Abnormalities in Adenosine Deaminase Deficiency

Immune Reconstitution in Pediatric Patients Following Hematopoietic Cell Transplant for Non-malignant Disorders

Feasibility study of busulfan, fludarabine, and thiotepa conditioning regimen for allogeneic hematopoietic stemcell transplantationfor children and young adults with nonmalignant disorders

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