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Reduced toxicity matched sibling bone marrow transplant results in excellent outcomes for severe congenital neutropenia.
Oved, Joseph H; Gibson, Nora M; Venella, Kimberly; Elgarten, Caitlin W; Wray, Lisa; Warren, Julia T; Olson, Timothy S.
Afiliación
  • Oved JH; Division of Pediatric Transplantation & Cellular Therapies, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
  • Gibson NM; Division of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
  • Venella K; Division of Hematology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
  • Elgarten CW; Division of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
  • Wray L; Division of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
  • Warren JT; Division of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
  • Olson TS; Division of Hematology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Front Immunol ; 15: 1369243, 2024.
Article en En | MEDLINE | ID: mdl-38469307
ABSTRACT
Severe congenital neutropenia (SCN) is caused by germline mutations, most commonly in ELANE, impacting neutrophil maturation and leading to high risk of life-threatening infections. Most patients with ELANE-mutant SCN can achieve safe neutrophil counts with chronic Granulocyte-Colony Stimulating Factor (G-CSF). However, up to 10% of patients have neutropenia refractory to G-CSF and require allogeneic stem cell transplant. Traditional conditioning for these patients includes busulfan and cyclophosphamide which is associated with significant toxicities. We present five patients with SCN without myeloid malignancy transplanted using a reduced toxicity regimen of busulfan, fludarabine and thymoglobulin. 5 pediatric patients with SCN underwent matched sibling donor bone marrow transplant (MSD-BMT) between 2014-2022 on or per CHP14BT057 (NCT02928991), a prospective, single center trial testing elimination of cyclophosphamide from conditioning in pediatric patients with single lineage inherited BMF syndromes. All patients had MSDs and no evidence of MDS. Conditioning consisted of PK-adjusted busulfan, fludarabine, and thymoglobulin, with calcineurin inhibitor and mycophenolate mofetil GVHD prophylaxis. With median follow-up of 48.4 months, overall and event-free survival were 100%. There was no acute GVHD and one instance of chronic limited GVHD. Patients exhibited >95% donor myeloid chimerism at 5 years post-BMT. Two patients experienced CMV reactivation without end-organ disease, and no other viral reactivation or significant infections occurred. MSD-BMT with reduced toxicity myeloablation for SCN provides excellent outcomes while minimizing toxicity. These data suggest that busulfan, fludarabine, and ATG can be considered an efficacious, low-toxicity standard of care regimen for patients with SCN undergoing MSD-BMT.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trasplante de Células Madre Hematopoyéticas / Enfermedad Injerto contra Huésped / Neutropenia Límite: Child / Humans Idioma: En Revista: Front Immunol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trasplante de Células Madre Hematopoyéticas / Enfermedad Injerto contra Huésped / Neutropenia Límite: Child / Humans Idioma: En Revista: Front Immunol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza