Potential for Cure by Chemotherapy Only, without Allogeneic Stem Cell Transplantation, in Pediatric Relapsed Acute Myeloid Leukemia?.

Relapse occurs in 30–40% of newly diagnosed acute myeloid leukemia (AML) patients, with long-term survival in 20–30% of them. Allogeneic stem cell transplantation (allo-SCT) is generally recommended as part of treatment of relapsed AML. Formal evidence for this recommendation is lacking, despite the evidence for a graft-versus-leukemia effect in AML. At initial diagnosis of high-risk AML, allo-SCT seems no better than chemotherapy only. Therefore, the need for allo-SCT in relapsed AML (as a high-risk situation) may be questioned, at least as general recommendation. We therefore studied the Dutch children and adolescents with AML that relapsed between 1980 and 1998, with a focus on patients reported to be alive without disease after treatment with chemotherapy only for the relapsed AML. We also summarised the relevant literature. Since autologous SCT has been reported to provide similar results as intensive chemotherapy, and lacks the graft-versus-leukemia effect, these patients were included in the “chemotherapy only” group. The Dutch patients were treated according to different treatment protocols, that all included cytarabine and an anthracycline, and in half of patients etoposide. A total of 113 relapsed AML cases were identified, of which 90 were treated with curative intent, with a second complete remission (CR2) in 57 of them. Overall probability of survival at 10 years is 16%(SE3%), with 18 disease-free survivors. Allo-SCT was performed in 16 out of the 57 CR2 patients, with 8 (50%) long-term survivors. Ten out of the 41 patients treated without allo-SCT (including 9 patients that underwent autologous SCT) survived (24%). However, allo-SCT as time-dependent covariable was not an independent favorable prognostic factor. The 10 long-term survivors treated at relapse without allo-SCT (7 chemotherapy only, 3 plus auto-SCT) did not have unique or similar clinical or AML cell biological features and included 6 patients with relapse within 12 months from CR1. Some of these 10 patients had been treated in the nineties with relatively intensive chemotherapy at initial diagnosis. In the literature, 6 papers describe the outcome of cohorts of pediatric relapsed AML patients (Stahnke 1998; Webb 1999; Aladlidi 2003, Wells 2003, Abrahamsson 2006, Rubnitz 2007). Overall probabilities of survival at 2 to 5 years ranged from 12% to 34%. A total of 77 patients were fully treated with chemotherapy only, and 27 out of them survived, i.e. 35%. In conclusion, treatment without allo-SCT of patients with relapsed AML seems curative in 20–40% of these patients, which is surprisingly high. However, patient selection may have occurred, and some patients may have been treated less optimally at initial diagnosis according to current standards. Results of the ongoing international study Relapsed AML 2001/01 will contribute to this discussion in the near future. Especially important is the question which type of patients with relapsed AML might be cured without allo-SCT. The Dutch and literature data suggest that randomised studies proving the role of allo-SCT in (subgroups of) relapsed AML are required. Experimental allogeneic SCT procedures, such as haplo-identical and mismatched unrelated donor SCT, should be carefully balanced against the chance of cure by chemotherapy only in patients in good quality second complete remission of AML.