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W Gassmann, L Uharek, HU Wottge, N Schmitz, H Loffler and W Mueller-Ruchholtz
Department of Internal Medicine II, University of Kiel, FRG.
Etoposide and cytarabine have been shown to exert high antileukemic
activity and are currently under study as preparatory agents before
allogeneic bone marrow transplantation. However, data concerning their
engraftment-promoting potency are scarce. Therefore, we tested these agents
in LEW rats receiving a myeloablative dose of busulfan followed by transfer
of F1 (CAP X LEW) marrow, which is unable to induce a graft- v-host
reaction (GVHR). Since busulfan by itself has only minor immunosuppressive
potency, graft rejection ensues unless etoposide, cytarabine, or
cyclophosphamide provide additional immunosuppression to facilitate durable
engraftment. Before allogeneic bone marrow transplantation in humans, 120
mg/kg of cyclophosphamide, 60 mg/kg of etoposide, or 900 mg/kg of
cytarabine are the standard doses given in conjunction with total body
irradiation. Seventy-five percent of these doses administered in addition
to busulfan resulted in rejection rates of 75% for cytarabine and 58% for
etoposide, respectively, whereas no rejections were observed with
cyclophosphamide. These data indicate that etoposide and cytarabine are
inferior to cyclophosphamide in their rejection-preventing potential. Using
either of these agents as substitutes for cyclophosphamide before
allogeneic bone marrow transplantation may increase the risk of graft
rejection in HLA- mismatched bone marrow transplantation and, in case of
HLA identity, if T-depleted marrow is administered.
This article has been cited by other articles:
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| Copyright © 1988 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
