Phase I study of graft-versus-host disease prophylaxis including bortezomib for allogeneic hematopoietic cell transplantation from unrelated donors with one or two HLA loci mismatches in Japanese patients.
Int J Hematol
; 110(6): 736-742, 2019 Dec.
Article
en En
| MEDLINE
| ID: mdl-31560116
ABSTRACT
This phase I study was designed for graft-versus-host disease (GVHD) prophylaxis including bortezomib in allogeneic hematopoietic cell transplantation (allo-HCT) from human leukocyte antigen (HLA)-mismatched unrelated donors in Japanese patients. Patients were administered bortezomib on days 1, 4, and 7, with short-term methotrexate and tacrolimus. Three bortezomib dose levels were prepared (1.0, 1.3, and 1.5 mg/m2). A dose of 1.3 mg/m2 was planned for administration to the initial six patients, and was adjusted if dose-limiting toxicity developed. Five of six patients enrolled for the initial dose had bone marrow donors. Two cases had single-antigen and single-allele mismatches; four had single-antigen mismatch at the A, B, C, and/or DRB1 loci in the GVH direction. All patients achieved neutrophil engraftment and complete donor chimerism. Three patients developed grade II acute GVHD, and none developed grade III-IV GVHD or any dose-limiting toxicity attributable to bortezomib by day 100. Two patients developed late-onset acute GVHD, and two developed chronic GVHD, but all cases were manageable. All patients were alive without relapse after a median follow-up period of 52 months. The optimal dose of bortezomib was determined to be 1.3 mg/m2. Prophylaxis against GVHD using a regimen including bortezomib thus seems feasible for HLA-mismatched unrelated allo-HCT.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trasplante de Células Madre Hematopoyéticas
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Donante no Emparentado
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Bortezomib
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Enfermedad Injerto contra Huésped
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Histocompatibilidad
Tipo de estudio:
Etiology_studies
Límite:
Adolescent
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Adult
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Female
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Humans
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Male
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Middle aged
País/Región como asunto:
Asia
Idioma:
En
Revista:
Int J Hematol
Asunto de la revista:
HEMATOLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Japón