Allograft with unrelated donor accentuates the gastrointestinal toxicity associated with high‐dose melphalan and total body irradiation preparative for bone marrow transplantation in children

Abstract

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/m2) 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 +2 to +4) 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.

Pediatric marrow transplantation for acute leukemia using unrelated donors and T-replete or -depleted grafts: a case-matched analysis

“…The use of melphalan with TBI in particular appears to be associated with an increased risk of toxic complications. 11 Furthermore, the use of only serology in HLA typing for class I antigens runs the risk of one of the two groups being less polymorphic than the other. The possible effect of this cannot be evaluated in our analysis.…”

Total body irradiation and melphalan as a conditioning regimen for children with hematological malignancies undergoing transplantation with stem cells from HLA‐identical related donors

“…This reason is that all patients in our study received transplantation from HLAidentical related donors. As Vettenranta et al (16) reported, allograft from an unrelated donor might accentuate the gastrointestinal toxicity associated with MEL and TBI. Various studies have found that the DFS after HLA-identical related donor transplantation in children with acute leukemia in CR1 or CR2 ranges from 30% to 70% (17)(18)(19)(20)(21).…”

“…As Vettenranta et al. (16) reported, allograft from an unrelated donor might accentuate the gastrointestinal toxicity associated with MEL and TBI.…”