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Treatment of Recurrent Childhood ALL

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    For patients with either an early or late relapse who are treated with chemotherapy and have a second relapse, there is evidence that an unrelated SCT may result in long-term disease-free survival.[43][Level of evidence: 3iiA] Patients with long first and second remission have the lowest relapse risk, but there is a high rate of nonrelapse mortality.

    For patients with T-cell ALL who have marrow relapses, outcomes with chemotherapy alone have generally been poor,[5] and these patients are usually treated with allogeneic SCT in CR2, regardless of time to relapse.

    Stem cell transplantation

    For patients proceeding to allogeneic SCT, total-body irradiation (TBI) appears to be an important component of the conditioning regimen. Two retrospective studies and a randomized trial suggest that transplant conditioning regimens that include TBI produce higher cure rates than chemotherapy-only preparative regimens.[32,44,45] TBI is often combined with either cyclophosphamide or etoposide. Results with either drug are generally equivalent,[46] although one study suggested that if cyclophosphamide is used, higher-dose TBI may be necessary.[47] The potential neurotoxic effects of TBI should be considered, particularly for very young patients. The use of post-HSCT intrathecal chemotherapy chemoprophylaxis does not appear to offer benefit;[48] however, this is controversial.[49,50,51]

    In addition to the conditioning regimen, disease status at the time of transplantation also appears to be an important predictor of outcome. Several studies have demonstrated that the level of MRD at the time of transplant is an important predictor of survival in patients in CR2.[22,52,53,54]

    There is no apparent difference in outcome between children and adolescents transplanted in second remission.[55][Level of evidence: 3iiA]

    Outcomes following matched unrelated donor and umbilical cord blood transplants have improved significantly over the past decade and may offer outcome similar to that obtained with matched sibling donor transplants.[36,56,57,58,59]; [60][Level of evidence: 2A]; [61][Level of evidence: 3iiiA] Rates of clinically extensive graft-versus-host disease (GVHD) and treatment-related mortality remain higher with unrelated than with matched sibling transplants.[37,56,62] However, there is some evidence that matched unrelated donor transplantation may yield a lower relapse rate, and National Marrow Donor Program and Center for International Blood and Marrow Transplant Research (CIBMTR) analyses have demonstrated that rates of GVHD, treatment-related mortality, and OS have improved over time.[63]; [64,65][Level of evidence: 3iiA]

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