title: Continuing increased risk of oral/esophageal cancer after allogeneic hematopoietic stem cell transplantation in adults in association with chronic graft-versus-host disease.
abstract: BACKGROUND
  The number of long-term survivors after hematopoietic stem cell transplantation (HSCT) showed steady increase in the past two decades. Second malignancies after HSCT are a devastating late complication. We analyzed the incidence of, risk compared with that in the general population, and risk factors for secondary solid cancers.
  
  
  METHODS
  Patients were 17 545 adult recipients of a first allogeneic stem cell transplantation between 1990 and 2007 in Japan. Risks of developing secondary solid tumors were compared with general population by using standard incidence ratios (SIRs).
  
  
  RESULTS
  Two-hundred sixty-nine secondary solid cancers were identified. The cumulative incidence was 0.7% [95% confidence interval (CI), 0.6%-0.9%] at 5 years and 1.7% (95% CI, 1.4%-1.9%) at 10 years after transplant. The risk was significantly higher than that in the general population (SIR=1.8, 95% CI, 1.5-2.0). Risk was higher for oral cancer (SIR=15.7, 95% CI, 12.1-20.1), esophageal cancer (SIR=8.5, 95% CI, 6.1-11.5), colon cancer (SIR=1.9, 95% CI, 1.2-2.7), skin cancer (SIR=7.2, 95% CI, 3.9-12.4), and brain/nervous system cancer (SIR=4.1, 95% CI, 1.6-8.4). The risk of developing oral, esophageal, or skin cancer was higher at all times after 1-year post-transplant. Extensive-type chronic graft-versus-host disease (GVHD) was a significant risk factor for the development of all solid tumors (RR=1.8, P<0.001), as well as for oral (RR=2.9, P<0.001) and esophageal (RR=5.3, P<0.001) cancers. Limited-type chronic GVHD was an independent risk factor for skin cancers (RR=5.8, P=0.016).
  
  
  CONCLUSIONS
  Recipients of allogeneic HSCT had a significantly higher ∼2-fold risk of developing secondary solid cancers than the general population. Lifelong screening for high-risk organ sites, especially oral or esophageal cancers, is important for recipients with active, or a history of, chronic GVHD.
authors.affiliation: Department of HSCT Data Management and Biostatistics, Nagoya University Graduate School of Medicine, Nagoya.
authors.forename: Y
authors.initials: Y
authors.lastname: Atsuta
authors.forename: R
authors.initials: R
authors.lastname: Suzuki
authors.forename: T
authors.initials: T
authors.lastname: Yamashita
authors.forename: T
authors.initials: T
authors.lastname: Fukuda
authors.forename: K
authors.initials: K
authors.lastname: Miyamura
authors.forename: S
authors.initials: S
authors.lastname: Taniguchi
authors.forename: H
authors.initials: H
authors.lastname: Iida
authors.forename: T
authors.initials: T
authors.lastname: Uchida
authors.forename: K
authors.initials: K
authors.lastname: Ikegame
authors.forename: S
authors.initials: S
authors.lastname: Takahashi
authors.forename: K
authors.initials: K
authors.lastname: Kato
authors.forename: K
authors.initials: K
authors.lastname: Kawa
authors.forename: T
authors.initials: T
authors.lastname: Nagamura-Inoue
authors.forename: Y
authors.initials: Y
authors.lastname: Morishima
authors.forename: H
authors.initials: H
authors.lastname: Sakamaki
authors.forename: Y
authors.initials: Y
authors.lastname: Kodera
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D006086:Graft vs Host Disease / Q000150:complications* / Q000453:epidemiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy; D015470:Leukemia, Myeloid, Acute / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000453:epidemiology / Q000209:etiology*; D016609:Neoplasms, Second Primary / Q000453:epidemiology / Q000209:etiology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy; D012307:Risk Factors; D014184:Transplantation, Homologous; D055815:Young Adult
keywords: hematopoietic stem cell transplantation; late effect; secondary solid cancers