title: High-dose BEAM chemotherapy with autologous haemopoietic stem cell transplantation for Hodgkin's disease is unlikely to be associated with a major increased risk of secondary MDS/AML.
abstract: Hodgkin's disease is curable in the majority of patients, although a proportion of patients are resistant to or relapse after initial therapy. High-dose therapy with autologous stem cell support has become the standard salvage therapy for patients failing chemotherapy, but there have been reports of a high incidence of myelodysplasia/acute myeloid leukaemia (MDS/AML) following such treatment. Patients who receive such therapy form a selected group, however, who have already been subjected to other leukaemogenic factors, such as treatment with alkylating agents. In order to ascertain the true risk of MDS/AML, comparison must be made with other patients subjected to the same risks but not undergoing transplantation. We report a retrospective comparative study of 4576 patients with Hodgkin's disease from the BNLI and UCLH Hodgkin's databases, which includes 595 patients who have received a transplant. Statistical analysis including Cox's proportional hazards multivariate regression model with time-dependent covariates was employed. This analysis reveals that the risk of developing MDS/AML was dominated by three factors, namely quantity of prior therapy (relative risk [RR] 2.01, 95% confidence intervals [CI] 1.49-2.71, for each treatment block, P < 0.0001) and whether the patient had been exposed to MOPP (RR 3.61, 95% CI 1.64-7.95, P = 0.0009) or lomustine chemotherapy (RR 4.53, 95% CI 1.96-10.44, P = 0.001). Following adjustment for these factors in the multivariate model the relative risk associated with transplantation was 1.83 (95% CI 0.66-5.11, P = 0.25). This study provides no evidence of a significantly increased risk of MDS/AML associated with BEAM therapy and autologous transplantation in Hodgkin's disease. Concern over MDS/AML should not mitigate against the timely use of this treatment modality.
authors.affiliation: University College Medical School, London, UK.
authors.forename: C N
authors.initials: CN
authors.lastname: Harrison
authors.forename: W
authors.initials: W
authors.lastname: Gregory
authors.forename: G V
authors.initials: GV
authors.lastname: Hudson
authors.forename: S
authors.initials: S
authors.lastname: Devereux
authors.forename: A H
authors.initials: AH
authors.lastname: Goldstone
authors.forename: B
authors.initials: B
authors.lastname: Hancock
authors.forename: D
authors.initials: D
authors.lastname: Winfield
authors.forename: A K
authors.initials: AK
authors.lastname: MacMillan
authors.forename: P
authors.initials: P
authors.lastname: Hoskin
authors.forename: A C
authors.initials: AC
authors.lastname: Newland
authors.forename: D
authors.initials: D
authors.lastname: Milligan
authors.forename: D C
authors.initials: DC
authors.lastname: Linch
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002330:Carmustine / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D002699:Chlorambucil / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000628:therapy; D006801:Humans; D015994:Incidence; D007223:Infant; D007951:Leukemia, Myeloid / Q000139:chemically induced / Q000453:epidemiology*; D015993:Life Tables; D008130:Lomustine / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008466:Mechlorethamine / Q000008:administration & dosage / Q000009:adverse effects; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000139:chemically induced / Q000453:epidemiology*; D016609:Neoplasms, Second Primary / Q000139:chemically induced / Q000453:epidemiology*; D011034:Podophyllotoxin / Q000008:administration & dosage / Q000009:adverse effects; D011239:Prednisolone / Q000008:administration & dosage / Q000009:adverse effects; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011344:Procarbazine / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies; D012306:Risk; D016879:Salvage Therapy / Q000009:adverse effects; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D003561:Cytarabine; D002699:Chlorambucil; D011344:Procarbazine; D008466:Mechlorethamine; D014750:Vincristine; D014747:Vinblastine; D005047:Etoposide; D008130:Lomustine; D004317:Doxorubicin; D011239:Prednisolone; D011034:Podophyllotoxin; D008558:Melphalan; D002330:Carmustine; D011241:Prednisone