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.
Relapse after allogeneic HSCT for relapsed ALL
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 because of 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 EFS.[70,71,72] 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.[71,72]
Reduced intensity approaches can also cure a percentage of patients when used as a second allogeneic transplant approach, but only if patients achieve a CR 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]
Treatment of extramedullary relapse
With improved success in treating children with ALL, the incidence of isolated extramedullary relapse has decreased. The incidence of isolated CNS relapse is less than 5%, and testicular relapse is less than 1% to 2%.[77,78,79] Age older than 6 years at diagnosis is an adverse prognostic factor for patients with an isolated extramedullary relapse. In the majority of children with isolated extramedullary relapses, submicroscopic marrow disease can be demonstrated using sensitive molecular techniques, and successful treatment strategies must effectively control both local and systemic disease. Patients with an isolated CNS relapse who show greater than 0.01% MRD in a morphologically normal marrow have a worse prognosis than patients with either no MRD or MRD less than 0.01%.