Therapy for childhood acute myeloid leukemia: Role of allogeneic bone marrow transplantation

Abstract

Acute myeloid leukemia (AML) has one of the lowest survival rates of childhood cancers. The first significant improvement in AML therapy started with the introduction of the now standard regimen of 3 days of anthracyclines and 7 days of cytarabine (Ara-C), the so-called 3+7 combinations. Several different therapeutic approaches have been taken in attempts to improve the outcome, including intensification of therapy both for remission induction and in the postremission phase. Intensification of postremission therapy included multiple courses of high-dose chemotherapy and/or myeloablative therapy followed by stem- cell rescue from either allogeneic or autologous sources. Furthermore, risk-tailored therapy is now possible, by cytogenetic risk stratification, promptness of remission induction, and identification of distinct clinical subgroups such as children with Down syndrome. This approach is rapidly changing potential therapeutic strategies for children with AML. It is in this changing mileu that we address the proper role of stem-cell transplantation, a modality that is changing (like chemotherapy) with expanding stem-cell sources and approaches to decrease transplant-related toxicity.

Pediatric Oncology Group (POG) studies of acute myeloid leukemia (AML): a review of four consecutive childhood AML trials conducted between 1981 and 2000

“…[28][29][30] Thus, the question of when and whom to transplant in AML remains unsettled. 31,32 Cytogenetic characteristics have emerged as the most important predictor of outcome in childhood AML in our studies and in others. After data of patients with Down's syndrome and with APL were excluded, the best outcome was observed for patients with an inv(16) þ t(16;16) with 5-year EFS of 60% and OS of 76% and the next best outcome was in patients with a t(8;21) or with a normal karyotype (see Table 3a and b).…”

Randomized use of cyclosporin A (CsA) to modulate P-glycoprotein in children with AML in remission: Pediatric Oncology Group Study 9421

“…2,3 Since only 15% to 20% of children with AML have suitable related donors, other strategies are necessary to improve overall survival. 4,5 Several adult and pediatric studies explored the benefits of modifying induction therapy in AML. Some included substituting idarubicin or mitoxantrone for daunorubicin, [6][7][8][9] increasing the dose or duration of cytarabine, [10][11][12] and administering the second course of induction chemotherapy on days 10 to 14.…”