Chromosome Abnormalities in Patients Treated with 4-Hydroperoxycyclophosphamide-Purged Autologous Bone Marrow Transplantation Nandita K. Shah, John R. Wingard, Steven Piantadosi, Scott Rowley, George Santos, Constance A. Griffin ABSTRACT: Autologous bone marrow transplantation (ABMT) offers potentially curative therapy for pa- tients with acute leukemia and lymphoma, yet little information exists about the chromosome abnormali- ties observed in ABMT recipients. Clonal abnormalities of chromosome I 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), Hodg- kin'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 ~g/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 abnormali- ties were observed in 14 of 55 patients after transplant. Seven had clonal abnormalities; all were in leu- kemic 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. INTRODUCTION 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. Alkylating agents are known to damage DNA and have been associated with mutagenesis, teratogenesis, and carcinogen- esis. In addition to the intensive cytoreductive therapy given to the recipient of an autograft, 4-hydroperoxycyclo- phosphamide (4-HC, the activated form of cyclophospha- mide) is often used in ex vivo BM purging. Consequently, we sought to determine the incidence of cytogenetic abnor- malities in patients who have undergone ABMT and had re- ceived 4-HC-purged BM. We report the results of cytogenetic evaluation of 55 patients who underwent ABMT between November 1987 and July 199o. The Johns Hopkins Oncology Center, Baltimore, Maryland. Address reprint requests to: Constance Griffin, M.D., The Johns Hopkins Oncology Center, Room 1-109,600 N. Wolfe St., Baltimore, MD 212O5. Received July 29, 1992; accepted September 4, 1992. © 1993 Elsevier Science Publishing Co., Inc. 655 Avenue of the Americas, New York, NY 10010 MATERIALS AND METHODS Patients All patients receiving an autologous BM graft for treatment of malignant disease at The Johns Hopkins Oncology Cen- ter (JHOC) between January 1, 1987 and July 31, 1990 were eligible for this study, and patients were followed until De- cember 31, 1990. In all, 299 patients underwent ABMT at our institution during this period; of these, 169 patients had leukemia or lymphoma and comprised the population eligi- ble for this study. We studied only those patients for whom both pretransplant and posttransplant samples were avail- able for cytogenetic studies. Most patients were referred to JHOC from elsewhere for ABMT and returned to their refer- ring physicians after ABMT. Thus, the length of follow-up during which BM was available for this study varied between 36 and 921 days. Preparative Regimen Patients were prepared for ABMT as follows: those with acute nonlymphocytic leukemia (ANLL) received busulfan 4 mg/kg/day on each of 4 days plus cyclophosphamide 50 mg/kg/day on each of 4 days [2]; those with acute lympho- cytic leukemia (ALL), lymphoma, or other disease received 135 Cancer Genet Cytogenet 65:135-140 (1993) 0165~4608/93/$06.90