title: High risk of therapy-related leukemia after BEAM chemotherapy and autologous stem cell transplantation for previously treated lymphomas is mainly related to primary chemotherapy and not to the BEAM-transplantation procedure.
abstract: A cohort of 76 patients with previous chemotherapy for Hodgkin's disease and non-Hodgkin lymphomas received high-dose carmustine, etoposide, cytosine-arabinoside and melphalan (BEAM) followed by autologous stem cell transplantation (ASCT) and was followed for relapse and development of leukemic complications. Six patients, four with Hodgkin's disease and two with non-Hodgkin lymphomas, developed leukemic complications, myelodysplasia (MDS) in four cases and overt acute myeloid leukemia (AML) in two. All six showed an abnormal karyotype, in four of them highly characteristic of therapy-related MDS (t-MDS) and therapy-related AML (t-AML). The cumulative risk of t-MDS and t-AML increased from 16 months after start of the primary chemotherapy for lymphoma and reached 17.3% (s.e. 8.5%) after 74 months. If calculated from start of BEAM and ASCT, the cumulative risk increased as early as 4 months and reached 24.3% (s.e. 12.9%) after 43 months. For the whole course of the disease, the relative risk (RR) of AML was 357 (95% CI: 43-1290), as two overt leukemias were observed vs 0.0056 expected cases of de novo AML. In the present cohort the risk of t-MDS and t-AML although high, did not differ from our previous experience in patients treated conventionally for Hodgkin's disease and non-Hodgkin lymphomas, and did not differ for patients receiving stem cells isolated from the bone marrow as compared to patients receiving stem cells isolated from peripheral blood. Antecedent chemotherapy seems to be the critical factor for the development of t-MDS and t-AML rather than the BEAM and ASCT regimen, which however may accelerate the evolution of the disease.
authors.affiliation: Department of Hematology, Laboratory for Cancer Genetics and Cytogenetics, Finsen Center, Rigshospitalet, Copenhagen, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Pedersen-Bjergaard
authors.forename: M
authors.initials: M
authors.lastname: Pedersen
authors.forename: J
authors.initials: J
authors.lastname: Myhre
authors.forename: C
authors.initials: C
authors.lastname: Geisler
mesh_terms: D000208:Acute Disease; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D002330:Carmustine / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006689:Hodgkin Disease / Q000188:drug therapy / Q000628:therapy*; D006801:Humans; D007951:Leukemia, Myeloid / Q000139:chemically induced* / Q000209:etiology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000628:therapy*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000139:chemically induced* / Q000209:etiology; D016609:Neoplasms, Second Primary / Q000139:chemically induced* / Q000209:etiology; D011034:Podophyllotoxin / Q000008:administration & dosage / Q000009:adverse effects; D012307:Risk Factors
chemical_list: D003561:Cytarabine; D011034:Podophyllotoxin; D008558:Melphalan; D002330:Carmustine