Successful Hematopoietic Stem Cell Transplantation Following a Cyclophosphamide-Containing Preparative Regimen with Concomitant Phenobarbital Administration

Catherine Weber,Heather Kasberg,Edward Copelan

doi:10.1155/2012/721857

Abstract

Cyclophosphamide is an immunosuppressive agent and an anticancer prodrug which requires bioactivation catalyzed primarily by cytochrome P450 enzymes in order to be transformed into its active alkylating compounds. Concomitant administration of drugs known to inhibit or induce this enzyme system is a clinical concern. Herein, we present the case of a chronically ill 21-year-old patient who received high-dose cyclophosphamide, equine antithymocyte globulin (eATG), and total body irradiation (TBI) followed by an allogeneic hematopoietic stem cell transplant (HSCT) for severe aplastic anemia. Throughout her hospitalization, she continued to receive quadruple anticonvulsant therapy including phenobarbital for her long-standing seizure history. The preparative regimen was tolerated well aside from a hypersensitivity reaction to eATG, and minimal cyclophosphamide-related toxicities. Safe and effective administration of high-dose cyclophosphamide was possible with multidisciplinary care consisting of physician, nursing, pharmacy, neurology consultation, as well as social work and case management.

Highlights

Allogeneic hematopoietic stem cell transplantation is curative in most patients with aplastic anemia
This procedure is associated with toxicities from the preparative regimen and subsequent immunosuppressive therapy, as well as graft versus-host disease (GVHD) and graft failure
Cyclophosphamide is a standard component of preparative regimens for allotransplantation; the parent drug requires metabolism primarily by cytochrome P450 enzymes in order to produce its active alkylating compounds, and concomitant administration of interacting medications is of particular concern in the setting of hematopoietic stem cell transplant (HSCT) due to the intensity of the preparative regimen administered

Summary

Case Report

Concomitant administration of drugs known to inhibit or induce this enzyme system is a clinical concern. We present the case of a chronically ill 21-yearold patient who received high-dose cyclophosphamide, equine antithymocyte globulin (eATG), and total body irradiation (TBI) followed by an allogeneic hematopoietic stem cell transplant (HSCT) for severe aplastic anemia. Throughout her hospitalization, she continued to receive quadruple anticonvulsant therapy including phenobarbital for her long-standing seizure history. Safe and effective administration of high-dose cyclophosphamide was possible with multidisciplinary care consisting of physician, nursing, pharmacy, neurology consultation, as well as social work and case management

Introduction

Marrow infusion

Discussion

Tacrolimus dose