High-dose BEAM chemotherapy with autologous haemopoietic stem cell transplantation for Hodgkin's disease is unlikely to be associated with a major increased risk of secondary MDS/AML
Cn. Harrison et al., High-dose BEAM chemotherapy with autologous haemopoietic stem cell transplantation for Hodgkin's disease is unlikely to be associated with a major increased risk of secondary MDS/AML, BR J CANC, 81(3), 1999, pp. 476-483
Hodgkin's disease is curable in the majority of patients, although a propor
tion of patients are resistant to or relapse after initial therapy. High-do
se therapy with autologous stem cell support has become the standard salvag
e therapy for patients failing chemotherapy, but there have been reports of
a high incidence of myelodysplasia/acute myeloid leukaemia (MDS/AML) follo
wing such treatment Patients who receive such therapy form a selected group
, however, who have already been subjected to other leukaemogenic factors,
such as treatment with alkylating agents. In order to ascertain the true ri
sk of MDS/AML, comparison must be made with other patients subjected to the
same risks but not undergoing transplantation. We report a retrospective c
omparative study of 4576 patients with Hodgkin's disease from the BNLI and
UCLH Hodgkin's databases, which includes 595 patients who have received a t
ransplant. Statistical analysis including Cox's proportional hazards multiv
ariate regression model with time-dependent covariates was employed. This a
nalysis reveals that the risk of developing MDS/AML was dominated by three
factors, namely quantity of prior therapy (relative risk [RR] 2.01, 95% con
fidence intervals [CI] 1.49-2.71, for each treatment block, P < 0.0001) and
whether the patient had been exposed to MOPP (RR 3.61, 95% CI 1.64-7.95, P
= 0.0009) or lomustine chemotherapy (RR 4.53, 95% CI 1,96-10,44, P = 0.001
). Following adjustment for these factors in the multivariate model the rel
ative risk associated with transplantation was 1.83 (95% CI 0.66-5.11, P =
0.25). This study provides no evidence of a significantly increased risk of
MDS/AML associated with BEAM therapy and autologous transplantation in Hod
gkin's disease. Concern over MDS/AML should not mitigate against the timely
use of this treatment modality. (C) 1999 Cancer Research Campaign.