Intensive chemotherapy versus bone marrow transplantation in pediatric acute myeloid leukemia : a matter of controversies

tion situations and that a different outcome may be achieved if higher doses of CY are used or if CY is used in other diseases. Such differences may explain apparent divergences between observations in this report and other reports. Two of these other prospective studies included only patients with CML.2,4 First, CML patients are exposed to no or only to low-dose chemotherapy prior to transplantation. This may explain why BU may be less toxic in CML patients than in patients with AML. Second, BU is known to be an active drug in CML even at much lower doses. Its activity on AML cells may be different. Third, CML is probably the disease for which the graft-versus-leukemia (GVL) effect is the most potent. It can thus be hypothesized that the GVL effect in CMLmay be strong enough to overcome limitations of the antileukemic effect from the preparative regimen. Indeed, a recent encouraging report of nonmyeloablative preparative regimens in CMLsupports this hypothesis.5 The third trial reporting a different conclusion from ours may not be comparable, as only 51 such patients with AML in CR1 were randomized.3 A retrospective registry analysis from European Blood and Marrow Transplant group (EBMT) also failed to find a difference between BUCY and CYTBI.6 But this analysis includes many variables and markedly various doses of CY, and this may be critical. Indeed, a report in a pediatric population withAML in CR1 found a higher relapse rate in the BUCY group than in the CYTBI group, but this difference disappeared when the CY dose was increased up to 200 mg/kg.7 The long-term follow-up of our study also indicates that secondary neoplasia represent the major cause of late failures, and this may even increase with longer-term follow-up. The occurrence of secondary neoplasia emphasizes that close attention should be given to patients who may be considered cured from the initial disease. An evaluation of the quality of survival of long-term survivors is also important and is presently being addressed in a joint study of the 4 prospective trials that have been discussed.8 Finally, nonmyeloablative conditioning regimens have recently been developed with promising preliminary results indicating lower initial toxicity. But long-term results from this approach should be compared with the results achieved after a standard CYTBI preparation for patients with AML in CR1. Didier Blaise, Dominique Maraninchi, Mauricette Michallet, Josy Reiffers, Jean Pierre Jouet, Noël Milpied, Agnes Devergie, Michel Attal, Jean Jacques Sotto, Mathieu Kuentz, Norbert Ifrah, Charles Dauriac, Pierre Bordigoni, Nicole Gratecos, François Guilhot, Denis Guyotat, Eliane Gluckman, and Jean Paul Vernant