Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Recurrent Childhood AML and Other Myeloid Malignancies
Despite second remission induction in over one-half of children with acute myeloid leukemia (AML) treated with drugs similar to drugs used in initial induction therapy, the prognosis for a child with recurrent or progressive AML is generally poor.[1,2] Approximately 50% to 60% of relapses occur within the first year following diagnosis, with most relapses occurring by 4 years from diagnosis. The vast majority of relapses occur in the bone marrow, with central nervous system (CNS) relapse being very uncommon. Length of first remission is an important factor affecting the ability to attain a second remission; children with a first remission of less than 1 year have substantially lower rates of remission than children whose first remission is greater than 1 year (50%–60% vs. 70%–90%, respectively).[2,3,4] Survival for children with shorter first remissions is also substantially lower (approximately 10%) than that for children with first remissions exceeding 1 year (approximately 40%).[2,3,4]
Regimens that have been successfully used to induce remission in children with recurrent AML have commonly included high-dose cytarabine given in combination with other agents, such as mitoxantrone, fludarabine and idarubicin,[5,6,7], L-asparaginase, etoposide, and clofarabine.[9,10,11] The standard-dose cytarabine regimens used in the United Kingdom Medical Research Council AML 10 study for newly diagnosed children with AML (cytarabine and daunorubicin plus either etoposide or thioguanine) have, when used in the setting of relapse, produced remission rates similar to those achieved with high-dose cytarabine regimens.
Chronic eosinophilic leukemia (CEL) is a chronic myeloproliferative disorder of unknown etiology in which a clonal proliferation of eosinophilic precursors results in persistently increased numbers of eosinophils in the blood, bone marrow, and peripheral tissues. In CEL, the eosinophil count is greater than or equal to 1.5 × 109 /L in the blood. To make a diagnosis of CEL, there should be evidence for clonality of the eosinophils or an increase in blasts in the blood or...
In a report of 379 children with AML who relapsed after initial treatment on BFM protocols, a second complete remission (CR2) rate was 63% and overall survival was 23%.[Level of evidence: 3iiiA] The most significant prognostic factors associated with a favorable outcome after relapse included achieving CR2, a relapse greater than 12 months from initial diagnosis, no allogeneic bone marrow transplant in first remission, and favorable cytogenetics (t(8;21), t(15;17), and inv(16)). The Therapeutic Advances in Childhood Leukemia and Lymphoma (TACL) Consortium also identified duration of previous remission as a powerful prognostic factor, with 5-year OS rates of 54% ± 10% for patients with greater than 12 months first remission duration compared with 19% ± 6% for patients with shorter periods of first remission.
The selection of further treatment following the achievement of a second remission depends on prior treatment as well as individual considerations. Consolidation chemotherapy followed by HSCT is conventionally recommended, though there are no controlled prospective data regarding the contribution of additional courses of therapy once CR2 is obtained. Unrelated donor HSCT has been reported to result in 5-year probabilities of leukemia-free survival of 45%, 20%, and 12% for patients with AML transplanted in second complete remission, overt relapse, and primary induction failure, respectively.[Level of evidence: 3iiA] The optimum type of preparative transplant regimen and source of donor cells has not been determined, although alternative donor sources, including haploidentical donors, are being studied. Importantly, however, there are no data that suggest total-body irradiation (TBI) is superior compared with busulfan-based myeloablative regimens.[16,17]