For patients with T-cell ALL and marrow relapse, outcomes with chemotherapy alone have generally been poor, and these patients are usually treated with allogeneic SCT in CR2, regardless of time to relapse.
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.[29,38,39] TBI is often combined with either cyclophosphamide or etoposide. Results with either drug are generally equivalent, although one study suggested that if cyclophosphamide is used, higher-dose TBI may be necessary. The potential neurotoxic effects of TBI should be considered, particularly for very young patients.
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.[20,42,43]
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.[33,44,45,46,47]; [Level of evidence: 2A]; [Level of evidence: 3iiiA] Rates of clinically extensive graft-versus-host disease (GVHD) and treatment-related mortality (TRM) remain higher with unrelated than with matched sibling transplants.[34,44,50] 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, TRM, and OS have improved over time.; [52,53][Level of evidence: 3iiA] Another CIBMTR study suggests that outcome after one or two antigen mismatched cord blood transplants may be equivalent to that for a matched family donor or a matched unrelated donor. In certain cases in which no suitable donor is found or an immediate transplant is considered crucial, a haploidentical transplant utilizing large doses of stem cells may be considered. For T cell-depleted CD34-selected haploidentical transplants in which a parent is the donor, patients receiving maternal stem cells may have a better outcome than those who receive paternal stem cells.[Level of evidence: 3iiA] There are a number of new options under study for preventing subsequent relapse after transplantation, including withdrawal of immune suppression or donor lymphocyte infusion and targeted immunotherapies, such as monoclonal antibodies and natural killer cell therapy.
For patients relapsing after an allogeneic HSCT for relapsed ALL, a second ablative allogeneic HSCT may be feasible. However, many patients will be unable to undergo a second HSCT procedure due to failure to achieve remission, early toxic death, or severe organ toxicity related to salvage chemotherapy. Among the highly selected group of patients able to undergo a second ablative allogeneic HSCT, approximately 10% to 30% may achieve long-term event-free survival (EFS).[58,59,60] Prognosis is more favorable in patients with longer duration of remission after the first HSCT and in patients with complete remission at the time of the second HSCT.[59,60] Reduced intensity approaches can also cure a percentage of patients when used as a second allogeneic transplant approach, but only if patients achieve a complete remission confirmed by flow cytometry.[Level of evidence: 2A] Donor leukocyte infusion has limited benefit for patients with ALL who relapse after allogeneic HSCT.; [Level of evidence: 3iiiA] Whether a second allogeneic transplant is necessary to treat isolated CNS and testicular relapse is unknown, and a small series has shown survival in selected patients using chemotherapy alone or chemotherapy followed by a second transplant.[Level of evidence: 3iA]