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Malignancies after marrow transplantation for aplastic anemia and fanconi
anemia: a joint Seattle and Paris analysis of results in 700 patients
HJ Deeg, G Socie, G Schoch, M Henry-Amar, RP Witherspoon, A Devergie, KM Sullivan, E Gluckman and R Storb
Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
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 anemia
treated with allogeneic marrow transplantation at the Fred Hutchinson
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 estimate of
14% (95% confidence interval, 4% to 24%) at 20 years. Five cases were
lymphoid malignancies (two acute lymphoblastic leukemias and three
lymphoproliferative disorders) occurring 1.4 to 14.6 months (median, 3
months) posttransplant, and 18 were solid tumors (17 squamous cell and one
mucoepidermoid carcinoma) presenting 30 to 221 months (median, 99 months)
posttransplant. Thus, the hazard for lymphoid malignancies declined rapidly
posttransplant, while the hazard for solid tumors increased progressively
with time posttransplant. Risk factors for solid tumors identified in
univariable analysis included the underlying diagnosis of Fanconi anemia (P
= .0002), azathioprine therapy for chronic graft-versus-host disease (GVHD)
(P < .0001), irradiation (total body or thoracoabdominal) as part of the
conditioning regimen (P = .0002), chronic GVHD (P = .0099), acute GVHD (P =
.0135), and male sex (P = .0499). In multivariable, stepwise proportional
hazards models, azathioprine therapy (P < .0001) and the diagnosis of
Fanconi anemia (P < .0001) were significant factors for all patients.
Irradiation was a significant factor (P = .004) only if the time-dependent
variable azathioprine was not included in the analysis. If only non-Fanconi
patients were considered, azathioprine (P = .0043), age (P = .025), and
irradiation (P = .042) were significant factors. Results in patients with
Fanconi anemia and malignancies other than solid tumors were not subjected
to an analysis because of the small number of events. It is of note,
however, that no case of myeloproliferative disorder was observed. In
summary, the highest risk of developing a solid tumor was associated with
the diagnosis of Fanconi anemia. Better prevention of GVHD or omission of
azathioprine as GVHD therapy (or both) may reduce the risk of late tumor
development. Similarly, nonirradiation conditioning regimens may reduce the
tumor risk, at least in patients without Fanconi anemia. Interactions
between potential risk factors are complex, and further observation and
additional analyses will be of interest.
Volume 87,
Issue 1,
pp. 386-392,
01/01/1996
Copyright © 1996 by The American Society of Hematology
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