Standard Treatment Options for Recurrent Childhood ALL
Treatment of bone marrow relapse
Standard treatment options for reinduction therapy when cancer has recurred in the bone marrow include the following:
Standard treatment options for postreinduction therapy when cancer has recurred in the bone marrow include the following:
- Chemotherapy (for B-precursor ALL).
- Stem cell transplantation.
Initial treatment of relapse consists of induction therapy to achieve a CR2. Using either a four-drug reinduction regimen (similar to that administered to newly diagnosed high-risk patients) or an alternative regimen including high-dose methotrexate and high-dose cytarabine, approximately 85% of patients with a marrow relapse achieve a CR2 at the end of the first month of treatment.; [Level of evidence: 2A]; [Level of evidence: 2Di] Patients with early marrow relapses have a lower rate of achieving a morphologic CR2 (approximately 70%) than do those with late marrow relapses (approximately 95%).[17,24]
- A United Kingdom-based randomized trial of patients with relapsed ALL compared reinduction with a four-drug combination using idarubicin versus mitoxantrone. [Level of evidence: 1iiA]
- A significant improvement in OS in the mitoxantrone arm (69% vs. 45%, P = .007) due to decreased relapse was reported.
The potential benefit of mitoxantrone in relapsed ALL regimens requires further investigation.
Other combinations of agents have been reported to induce remissions in patients with multiple-relapsed or refractory ALL. The combination of clofarabine, cyclophosphamide, and etoposide was reported to induce remission in 44% to 56% of patients with refractory or relapsed disease.; [Level of evidence: 2A]
Patients with relapsed T-cell ALL have much lower rates of achieving CR2 with standard reinduction regimens than do patients with B-precursor phenotype. Treatment of children with first relapse of T-cell ALL in the bone marrow with single-agent therapy using the T-cell selective agent, nelarabine, has resulted in response rates of approximately 50%. The combination of nelarabine, cyclophosphamide, and etoposide has produced remissions in patients with relapsed/refractory T-cell ALL.
Postreinduction therapy (second complete remission)
Post-CR2 therapy for patients who experience a bone marrow relapse (either isolated or combined) while on therapy or within 6 months of discontinuing therapy generally includes hematopoietic stem cell transplantation (HSCT).[30,31]
For B-precursor patients with an early marrow relapse, allogeneic transplant from a human leukocyte antigen (HLA)-identical sibling or matched unrelated donor that is performed in second remission has been reported in most studies to result in longer leukemia-free survival than a chemotherapy approach.[7,23,32,33,34,35,36,37,38] However, even with transplantation, the survival rate for patients with early marrow relapse is less than 50%.
For patients with a late marrow relapse of B-precursor ALL, a primary chemotherapy approach after achievement of CR2 has resulted in survival rates of approximately 50%, and it is not clear whether allogeneic transplantation is associated with superior cure rate.[9,39,40,41]; [Level of evidence: 3iiA] End-reinduction MRD levels may help to identify patients with a high risk of subsequent relapse if treated with chemotherapy alone (no SCT) in CR2.