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Allograft with unrelated donor accentuates the gastrointestinal toxicity associated with high‐dose melphalan and total body irradiation preparative for bone marrow transplantation in children
Author(s) -
Vettenranta K.,
Hovi L.,
Taskinen M.,
SaarinenPihkala U.
Publication year - 2000
Publication title -
pediatric transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.457
H-Index - 69
eISSN - 1399-3046
pISSN - 1397-3142
DOI - 10.1034/j.1399-3046.2000.00132.x
Subject(s) - medicine , total body irradiation , melphalan , toxicity , gastroenterology , conditioning regimen , transplantation , incidence (geometry) , bone marrow , graft versus host disease , regimen , surgery , chemotherapy , immunology , hematopoietic stem cell transplantation , cyclophosphamide , physics , optics
The use of high‐dose melphalan ( l ‐phenyalalanine mustard or l ‐PAM) has been shown to be associated with both hematological and non‐hematological toxicity. It has been employed in the conditioning for allogeneic stem cell transplants from related donors but experience on its use in the unrelated setting has not been reported. As an attempt to elucidate the role of high‐dose l ‐PAM (210 mg/m 2 ) and total body irradiation (TBI) as a preparative regimen for allogeneic marrow transplantation from matched unrelated donors, they were employed in an institutional pilot series of seven pediatric patients. When compared with recipients of unrelated marrow grafts conditioned using other regimens, those treated with high‐dose l ‐PAM experienced a markedly more severe acute graft‐vs.‐host disease (GvHD). The overall incidence of grade III–IV acute GvHD was higher (86% vs. 14%) among those treated with l ‐PAM. As judged by gastrointestinal (GI) symptoms, clinically significant (stages ++ to ++++) gut GvHD was strikingly more prevalent among those treated with l ‐PAM (86% vs. 9%, p<0.005). Toxic mortality prior to day +100 was 29% in the l ‐PAM group and 9% in the non‐ l ‐PAM group of patients. With a mean follow‐up of 21 months no increase in the incidence of chronic GvHD has been encountered among those conditioned with l ‐PAM. We conclude that the use of preparative L ‐PAM for allogeneic transplants from unrelated donors is associated with considerable procedure‐related toxicity. We strongly suggest its use in this setting to be viewed with caution.