Nonhematologic malignancies after allogeneic hematopoietic stem cell transplantation: incidence and molecular monitoring

Bone Marrow Transplant. 2004 Dec;34(11):981-5. doi: 10.1038/sj.bmt.1704674.

Abstract

Survivors of allogeneic hematopoietic stem cell transplantation (HSCT) are at a life-long increased risk of secondary nonhematologic malignancies. In 615 adult Chinese allogeneic HSCT patients, nine developed nonhematologic malignancies. The 5-year cumulative incidence was 6.1%, 4.5 times the background cancer incidence. Early-onset (within first 6 months) and late-onset (>3 years) subtypes were observed. Secondary cancers included hepatocellular carcinoma, oral and esophageal squamous cell tumors and lung adenocarcinoma in a female nonsmoker. The spectrum reflected local cancer epidemiology, which was different from Western populations. The pathogenesis might be related to acceleration of pre-existing cancers (early-onset type), or prolonged immunosuppression (late-onset type). DNA chimerism studies showed that all tumors were recipient-derived. In the plasma, DNA in all cases was apparently donor-derived, although aberrantly methylated p15 was detectable in a patient with a p15-methylated secondary cancer, implying that minute quantities of tumor (and therefore recipient) derived DNA might be present.

MeSH terms

  • Adult
  • Carcinoma / etiology
  • Carcinoma / genetics*
  • Cell Cycle Proteins / genetics*
  • Cyclin-Dependent Kinase Inhibitor p15
  • DNA Methylation*
  • DNA, Neoplasm / genetics*
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Male
  • Middle Aged
  • Monitoring, Physiologic
  • Neoplasms, Second Primary / etiology
  • Neoplasms, Second Primary / genetics*
  • Retrospective Studies
  • Transplantation Chimera / genetics
  • Transplantation Conditioning* / adverse effects
  • Tumor Suppressor Proteins / genetics*

Substances

  • CDKN2B protein, human
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p15
  • DNA, Neoplasm
  • Tumor Suppressor Proteins