Post-transplant cyclophosphamide pharmacokinetics and haploidentical hematopoietic cell transplantation outcomes: an exploratory study.
Leuk Lymphoma
; 63(11): 2679-2685, 2022 Nov.
Article
en En
| MEDLINE
| ID: mdl-35699967
ABSTRACT
Pharmacokinetics of cyclophosphamide has been explored to optimize conditioning dosing. We hypothesized that post-transplant cyclophosphamide (PTCy) metabolite carboxy-ethyl phosphoramide mustard (CEPM) pharmacokinetics might impact haploidentical transplantation (haplo-HCT) outcomes. CEPM area under the curve (AUC0-48) was determined by eleven sampling timepoints on day +3/+4 using LC-MS/MS. The median CEPM AUC0-48 in a cohort of 30 patients was 14.2 (14) mg·hr/L. The incidence of severe chronic graft-versus-host disease (GVHD) (73% vs. 11%, p = 0.02), and GVHD-/relapse-free survival (GRFS) was significantly inferior in the CEPM AUC0-48 < 14 mg·hr/L group (54 days vs. 344 days, p = 0.02). There was, however, no difference in grade III-IV acute GVHD (38% vs. 14%, p = 0.12) and overall survival (295 days vs. not reached, p = 0.2). CEPM AUC0-48, is associated with severe chronic GVHD and GRFS post-haplo-HCT in this exploratory study. There is scope for personalizing day + 4 PTCy dose based on day + 3 CEPM AUC0-8.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Trasplante de Células Madre Hematopoyéticas
/
Enfermedad Injerto contra Huésped
Tipo de estudio:
Etiology_studies
/
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Leuk Lymphoma
Asunto de la revista:
HEMATOLOGIA
/
NEOPLASIAS
Año:
2022
Tipo del documento:
Article
País de afiliación:
India