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.
Evidence (chemotherapy for B-precursor ALL):
- In a St. Jude Children's Research Hospital study, which included 23 patients with late relapses treated with chemotherapy in CR2, the 2-year cumulative incidence of relapse was 49% for the 12 patients who were MRD-positive at the end of reinduction and 0% for the 11 patients who were MRD-negative. Whether transplantation benefits patients with late marrow relapse but a high level of MRD after reinduction treatment requires further study.