Chromosome abnormalities in patients treated with 4-hydroperoxycyclophosphamide-purged autologous bone marrow transplantation

Abstract

Autologous bone marrow transplantation (ABMT) offers potentially curative therapy for patients with acute leukemia and lymphoma, yet little information exists about the chromosome abnormalities observed in ABMT recipients. Clonal abnormalities of chromosome 1 were reported by van den Akker [1]. We report the cytogenetic results of 55 patients who underwent ABMT between November 1987 and July 1990: acute nonlymphocytic leukemia (ANLL, 22), acute lymphocytic leukemia (ALL, eight), Hodgkin's disease (seven), lymphoma (16), other (two). ANLL patients received busulfan and cytoxan, and the others received cytoxan and total body irradiation as their preparative regimen before transplant. BM was purged ex vivo with 4-hydroperoxycyclophosphamide (4-HC) at 30–100 μg/ml before reinfusion to kill tumor cells. Cytogenetic analysis was performed before and after transplant. Between one and four posttransplant specimens of BM were analyzed per patient (range 36–921 days). Chromosome abnormalities were observed in 14 of 55 patients after transplant. Seven had clonal abnormalities; all were in leukemic relapse, and one karyotype had complex rearrangements. Clonal abnormalities of chromosome 1 were not observed. Seven patients had nonclonal changes, and three of these have had overt clinical relapse. Our data suggest that clonal abnormalities observed posttransplant are best explained by clinical relapse of tumor and that ex vivo marrow purging with 4-HC is not likely to induce clonal chromosome abnormalities in normal cells. Long-term observation of these patients will be required to answer that question definitively, however.