Secondary malignancies after marrow transplantation for leukemia or aplastic anemia.
We conclude that the most common secondary cancers which develop after marrow transplantation are lympho-proliferative disorders and solid tumors. The consequences of the secondary malignancies are serious, with more than 90% of the patients with non-Hodgkin lymphomas associated with EBV infection and more than 75% of the patients with solid tumors dying despite treatment. Secondary leukemia developing in donor T-s is rare, but was fatal in all cases. EBV infection plays a major role in leading to the non-Hodgkin lymphomas in a setting of immune dysregulation from ATG or anti-T-cell monoclonal antibody treatment of acute GVHD. Other factors are also important for development of non-Hodgkin lymphoma and include T-cell depletion of donor marrow and HLA-mismatching between donor and recipient, known to lead to dysregulation of T-lymphocyte function. These factors set up an environment of proliferative stimuli which cannot be controlled by the recovering immune system, setting the stage for a secondary cancer. The role of irradiation is becoming more prominent in association with solid tumors, particularly in aplastic anemia patients conditioned with irradiation. The final event of tumor expression is most likely the result of a cascade of events, perhaps initiated with the conditioning regimen or with stimuli to proliferation, which, after later signals, leads to malignant transformation. For lymphoproliferative disorders, the time of latency is shorter than for solid tumors, suggesting a different molecular mechanism. The incidence of oncogene expression or mutation in tumor suppressor genes in these solid tumor patients has not been investigated.(ABSTRACT TRUNCATED AT 250 WORDS)
Witherspoon
R P
RP
Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Deeg
H J
HJ
Storb
R
R
D000741:Anemia, Aplastic / Q000628:therapy*; D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002471:Cell Transformation, Neoplastic; D006566:Herpesviridae Infections; D004854:Herpesvirus 4, Human; D006801:Humans; D007938:Leukemia / Q000628:therapy*; D008228:Lymphoma, Non-Hodgkin / Q000209:etiology / Q000235:genetics; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000235:genetics; D016609:Neoplasms, Second Primary / Q000209:etiology* / Q000235:genetics; D014412:Tumor Virus Infections