title: Leukemia following low-dose total body irradiation and chemotherapy for non-Hodgkin's lymphoma.
abstract: OBJECTIVE
  Low-dose total body irradiation (TBI) is used to treat non-Hodgkin's lymphoma (NHL) and several other malignancies. Large volumes of bone marrow and other tissue receive considerable exposure, but few studies have quantified late carcinogenic sequelae.
  
  
  METHODS
  A cohort of 61 2-year survivors of NHL treated initially with low-dose TBI was monitored for second cancer occurrence. Data on primary and subsequent therapy were collected, and cumulative dose of radiation to active bone marrow (ABM) (median, 5.2 Gy) was reconstructed.
  
  
  RESULTS
  Thirteen second primary cancers occurred. Four patients developed acute nonlymphocytic leukemia (ANLL), which represents a relative risk (RR) of 117 (95% confidence interval [CI], 31.5 to 300) compared with population rates. A fifth patient was diagnosed with myelodysplastic syndrome (MDS). All five patients with secondary hematologic malignancies subsequently received salvage treatment, with either alkylating agents alone (n = 1) or combined modality therapy (CMT) (n = 4). Overall, eight solid tumors were observed (RR = 2.0; 95% CI, 0.9 to 4.0). The 15-year cumulative risks of all second cancers and secondary ANLL were 37% and 17%, respectively.
  
  
  CONCLUSIONS
  Despite the small number of subjects, a considerable risk of leukemia was observed among patients treated with low-dose TBI in combination with CMT including alkylating agents. Based on these results, approximately eight to nine excess ANLLs might be expected to occur among 100 NHL patients treated with low-dose TBI and salvage treatment and followed-up for 15 years.
authors.affiliation: National Cancer Institute, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD 20892, USA.
authors.forename: L B
authors.initials: LB
authors.lastname: Travis
authors.forename: J
authors.initials: J
authors.lastname: Weeks
authors.forename: R E
authors.initials: RE
authors.lastname: Curtis
authors.forename: J T
authors.initials: JT
authors.lastname: Chaffey
authors.forename: M
authors.initials: M
authors.lastname: Stovall
authors.forename: P M
authors.initials: PM
authors.lastname: Banks
authors.forename: J D
authors.initials: JD
authors.lastname: Boice
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001853:Bone Marrow / Q000528:radiation effects; D003131:Combined Modality Therapy; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000209:etiology; D007953:Leukemia, Radiation-Induced / Q000209:etiology*; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000209:etiology; D016609:Neoplasms, Second Primary / Q000209:etiology*; D011879:Radiotherapy Dosage; D016879:Salvage Therapy; D014916:Whole-Body Irradiation / Q000009:adverse effects*