Bone Marrow Transplantation, (1998) 21, 395–399  1998 Stockton Press All rights reserved 0268–3369/98 $12.00 New clonal karyotypic abnormalities acquired following autologous bone marrow transplantation for acute myeloid leukemia do not appear to confer an adverse prognosis KR Imrie, I Dube ´ , HM Prince, C Girouard, M Crump and A Keating The University of Toronto Autologous Blood and Marrow Transplant Program, The Toronto Hospital and the University of Toronto Cancer Cytogenetics Program, The University of Toronto, Toronto, Canada Summary: of myelodysplasia or secondary AML 5,6 and consequently a shortened survival. 7 Indeed, the development of cytogenetic abnormalities and MDS following ABMT for lymphoma We undertook a retrospective review of all 76 patients with AML transplanted between August 1986 and appear to be related to exposure to alkylating agents during conventional-dose chemotherapy rather than the high- March 1995 at our center. All patients received mel- phalan (140–160 mg/m 2 ), etoposide (60 mg/kg) and total dose regimen. 8 As induction and consolidation chemotherapy for AML body irradiation. All patients had bone marrow cyto- genetic analysis at regular intervals following ABMT. do not generally include alkylating agents, we were inter- ested in determining the incidence and significance of new The primary study end point was the development of the new cytogenetic abnormalities. Secondary end isolated cytogenetic abnormalities after ABMT for AML. points were the development of myelodysplasia (MDS) or AML. Sixty-two of 77 patients were alive at least 6 months post transplant. Cytogenetic abnormalities Patients and methods developed in 7/62 patients (11%) following ABMT. No patients demonstrated MDS or AML. At a median of We evaluated all patients undergoing ABMT for AML at our center between 1986 and 1995 to determine the fre- 30 months after development of the cytogenetic abnor- mality, only one patient developed features suggestive quency and clinical significance of new clonal karyotypic abnormalities following transplantation. Patients 61 years but not diagnostic of MDS. All seven patients remain alive and leukemia-free up to 70 months after detection of age with ECOG performance status 2 were candidates for ABMT. Patients with persistent cytogenetic abnormali- of the abnormal clone. There was no increased incidence of cytogenetic abnormalities developing in patients ties or morphologic evidence of myelodysplasia following induction therapy were not eligible for ABMT. Intensive receiving a purged autograft. New cytogenetic abnor- malities are frequent following ABMT for AML but do therapy and autotransplantation were performed in first or subsequent remission or early relapse with a marrow auto- not appear to predict development of myelodysplasia or acute myeloid leukemia. These abnormalities may relate graft collected in morphologic and cytogenetic remission. The intensive therapy regimen consisted of intravenous to use of total body radiation as part of the high-dose therapy. melphalan (140–160 mg/m 2 ), etoposide (VP-16) (60 mg/kg) and total body irradiation (TBI). The etoposide was Keywords: bone marrow transplantation; cytogenetics; acute myeloid leukemia; myelodysplasia administered as an infusion over 5 h for patients with good cardiac function and over 32 h for patients with left ven- tricular ejection fraction 45%. Patients in first complete remission were given a single fraction of TBI at a median Clonal cytogenetic abnormalities occur in the bone marrow rate of 50 cGy/min (range 30–60) to a total dose of 500 cGy of 50–90% of patients with acute myeloid leukemia (AML) while those in other disease states received six fractions of at the time of diagnosis and are strongly implicated in its 200 cGy administered at the same rate (total dose 1200 pathogenesis. 1,2 Furthermore, recurrence of the initial cGy). Patients were assessed at 3-monthly intervals for the malignant cytogenetic clone in the marrow of patients after first 2 years following ABMT and at 6-monthly intervals conventional-dose induction chemotherapy is usually asso- thereafter. Follow-up studies included a complete physical ciated with morphologic relapse. 3,4 examination, complete blood count and bone marrow aspir- New clonal cytogenetic abnormalities appearing after ation with cytogenetic analysis. Cytogenetic studies were conventional chemotherapy for lymphoma or other malig- performed according to standard methods with the karyo- nancies are generally felt to be associated with a high risk types described according to the international system for cytogenetic nomenclature (ISCN). 9 We defined new cyto- genetic abnormalities following ABMT as persistent clonal Correspondence: Dr K Imrie, Toronto Sunnybrook Regional Cancer cytogenetic abnormalities apparently unrelated to the initial Centre, 2075 Bayview Ave, Room T2054, North York, Ontario, Canada, malignant karyotype. For those patients with such abnor- M4N 3M5 Received 10 July 1997; accepted 7 October 1997 malities the precise nature and frequency of the abnormal