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Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Recurrent Childhood AML and Other Myeloid Malignancies

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Isolated CNS Relapse

Isolated CNS relapse occurs in 3% to 5% of pediatric AML patients.[27,28] Factors associated with an increased risk of isolated CNS relapse include the following:[27]

  • Age younger than 2 years at initial diagnosis.
  • M5 leukemia.
  • 11q23 abnormalities.
  • CNS involvement at initial diagnosis.

The outcome of isolated CNS relapse when treated as a systemic relapse is similar to that of bone marrow relapse. In one study, the 8-year OS for a cohort of children with an isolated CNS relapse was 26% ± 16%.[27]

Recurrent Acute Promyelocytic Leukemia (APL)

Despite the improvement in outcomes for patients with newly diagnosed APL, approximately 10% to 20% of patients relapse.

An important issue in children is the prior exposure to anthracyclines, which can range from 400 mg/m2 to 750 mg/m2.[29] Thus, regimens containing anthracyclines are often not optimal for children with APL who suffer relapse. For children with recurrent APL, the use of arsenic trioxide as a single agent or regimens including all-trans retinoic acid should be considered, depending on the therapy given during first remission. Arsenic trioxide is an active agent in patients with recurrent APL, with approximately 85% of patients achieving remission after treatment with this agent.[30,31,32,33] Data are limited on the use of arsenic trioxide in children, although published reports suggest that children with relapsed APL have a response to arsenic trioxide similar to that of adults.[30,32,34] Because arsenic trioxide causes QT interval prolongation that can lead to life-threatening arrhythmias,[35] it is essential to monitor electrolytes closely in patients receiving arsenic trioxide and to maintain potassium and magnesium values at midnormal ranges.[36] The use of anti-CD33/calicheamicin monoclonal antibody as a single agent resulted in 91% (9 of 11 patients) molecular remission after two doses and in 100% of patients (13 of 13) after three doses, thus demonstrating excellent activity of this agent in relapsed APL.[37]

Retrospective pediatric studies have reported 5-year event-free survival (EFS) rates after either autologous or allogeneic transplantation approaches to be similar at approximately 70%.[38,39] When considering autologous transplantation, a study in adult patients demonstrated improved 7-year EFS (77% vs. 50%) when both the patient and the stem cell product had negative promyelocytic leukemia/retinoic acid receptor alpha fusion transcript by polymerase chain reaction (molecular remission) before transplant.[40] Another study demonstrated that among seven patients undergoing autologous HSCT and whose cells were minimal residual disease (MRD)-positive, all relapsed in less than 9 months after transplantation; however, only one of eight patients whose autologous donor cells were MRD-negative relapsed.[41] Another report demonstrated that the 5-year EFS was 83.3% for patients who underwent autologous HSCT in second molecular remission and was 34.5% for patients who received only maintenance therapy.[42] Such data support the use of autologous transplantation in patients who are MRD-negative in second complete remission who have poorly matched allogeneic donors.

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