Nonhematologic malignancies after allogeneic hematopoietic stem cell transplantation: incidence and molecular monitoring.
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.
Au
W-Y
WY
Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong.
Chan
E C
EC
Pang
A
A
Lie
A K W
AK
Liang
R
R
Yuen
A P W
AP
Shek
T W H
TW
Kwong
Y-L
YL
D000328:Adult; D002277:Carcinoma / Q000209:etiology / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D016609:Neoplasms, Second Primary / Q000209:etiology / Q000235:genetics*; D012189:Retrospective Studies; D018183:Transplantation Chimera / Q000235:genetics; D019172:Transplantation Conditioning / Q000009:adverse effects; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C493966:CDKN2B protein, human; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D004273:DNA, Neoplasm; D025521:Tumor Suppressor Proteins