MALIGNANCIES AFTER MARROW TRANSPLANTATION FOR APLASTIC-ANEMIA AND FANCONI-ANEMIA - A JOINT SEATTLE AND PARIS ANALYSIS OF RESULTS IN 700 PATIENTS

Risk factors for the development of a new (secondary) malignancy after marrow transplantation are still incompletely defined. In the present study, we analyzed results in 700 patients with severe aplastic anemi a treated with allogeneic marrow transplantation at the Fred Hutchinso n Cancer Research Center in Seattle WA, or at the Hopital St Louis in Paris, France. Twenty three patients developed a malignancy 1.4 to 221 months (median, 91 months) after transplantation for a Kaplan-Meier e stimate of 14% (95% confidence interval, 4% to 24%) at 20 years. Five cases were lymphoid malignancies (two acute lymphoblastic leukemias an d three lymphoproliferative disorders) occurring 1.4 to 14.6 months (m edian, 3 months) posttransplant and 18 were solid tumors (17 squamous cell and one mucoepidermoid carcinoma) presenting 30 to 221 months (me dian, 99 months) posttransplant. Thus, the hazard for lymphoid maligna ncies declined rapidly posttransplant, while the hazard for solid tumo rs increased progressively with time posttransplant. Risk factors for solid tumors identified in univariable analysis included the underlyin g diagnosis of Fanconi anemia (P=.0002), azathioprine therapy for chro nic graft-versus-host disease (GVHD) (P <.0001), irradiation (total bo dy or thoracoabdominal) as part of the conditioning regimen (P =.0002) , chronic GVHD (P =.0099), acute GVHD (P =.0135), and male sex (P=.049 9). In multivariable, stepwise proportional hazards models, azathiopri ne therapy (P < .0001) and the diagnosis of Fanconi anemia (P <.0001) were significant factors for all patients, Irradiation was a significa nt factor (P =.004) only if the time-dependent variable azathioprine w as not included in the analysis. If only non-Fanconi patients were con sidered, azathioprine (P =.0043), age (P=.025), and irradiation (P =.0 42) were significant factors. Results in patients with Fanconi anemia and malignancies other than solid tumors were not subjected to an anal ysis because of the small number of events. It is of note, however, th at no case of myeloproliferative disorder was observed. In summary, th e highest risk of developing a solid tumor was associated with the dia gnosis of Fanconi anemia. Better prevention of GVHD or omission of aza thioprine as GVHD therapy (or both) may reduce the risk of late tumor development, Similarly, nonirradiation conditioning regimens may reduc e the tumor risk, at least in patients without Fanconi anemia. Interac tions between potential risk factors are complex, and further observat ion and additional analyses will be of interest. (C) 1996 by The Ameri can Society of Hematology.