Blood, Vol. 91 No. 3 (February 1), 1998:
pp. 1091-1092
CORRESPONDENCE
Busulfan Alone as Cytoreduction Before Autografting for Chronic
Myelogenous Leukemia
 |
LETTER |
To the Editor:
A number of prospective randomized studies have recently been designed
to address the question of whether autografting prolongs survival for
patients with chronic myelogenous leukemia (CML) in chronic
phase,1,2 but there is no general agreement as to the
optimal approach to cytoreduction before transfusion of autologous stem
cells. We believe that the use of high-dose busulfan alone, as used in
patients subjected to second allograft procedures,3 may be
a good compromise between maximal cytoreduction and minimal regimen-related toxicity.
A heterogeneous group of 37 patients with CML in different phases of
CML were autografted at the Hammersmith Hospital in London over a
5-year period by using busulfan alone as cytoreduction (Table
1). The regimen consisted
of 4 mg/kg/d busulfan orally for 4 consecutive days (total, 16 mg/kg).
A loading dose of 1,000 mg oral phenytoin was administered 1 day before
the start of chemotherapy and phenytoin was continued at a dose of 300 mg/d for 7 days to prevent epileptic seizures. Neither busulfan nor
phenytoin levels were monitored. Autologous cells were infused 48 hours
after the last dose of busulfan. All patients had some degree of
stomatitis, but no other major toxicities4 were encountered
(Table 2). Specifically, no patient had
busulfan-related pulmonary toxicity, hepatic veno-occlusive disease, or
epileptic seizures, and no patient experienced persisting alopecia.
We did not formally compare the use of busulfan alone with that of
other more intensive cytoreduction regimens. However, the complete/major cytogenetic response rate at 3 months postautograft was
20% (6 patients) and the median survival postautograft was 3.4 years
(95% confidence interval [CI]: 1.7 to 5.9) (Table 1). Thus, we can
be reasonably confident that the use of this cytoreduction regimen
produced results at least as good as those achieved with the
combinations of busulfan plus cyclophosphamide or cyclophosphamide plus
total body irradiation.
The principal reason why busulfan alone might be preferable to more
intensive regimens is simply the fact that it may achieve the same
level of cytoreduction with less toxicity. Conversely, the fact that
the cells used for the autograft usually contain at least some
Ph+ progenitor cells such that relapse must originate at
least partly from the autografted material5 might mean
that the attempt at complete marrow ablation with maximal chemotherapy
or chemoradiotherapy was not justified. Moreover, busulfan alone is
relatively easy to administer and administration will become even more
straightforward when the intravenous preparations now being developed
become available for routine use.
We conclude that if one chooses to autograft a patient with CML, then
busulfan alone is a reasonable cytoreduction regimen associated with
minimal toxicity which should still permit the possibility of a
subsequent allograft or second autograft
procedure.
Stephen G. O' Brien
John
M. Goldman
Department of Haematology
Imperial College School
of Medicine
Hammersmith Hospital London, UK
| |
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