Relapse after allogeneic HSCT for relapsed ALL

For patients with B-ALL who relapse after allogeneic HSCT and can be successfully weaned from immune suppression and have no GVHD, tisagenlecleucel and other 4-1BB CAR T-cell approaches have resulted in EFS rates exceeding 50% at 12 months.[148] For patients with T-ALL who relapse or for patients with B-ALL who are unable to undergo CAR T-cell therapy, 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.[149] Among the highly selected group of patients able to undergo a second ablative allogeneic HSCT, approximately 10% to 30% will achieve long-term EFS.[149-154]; [82,155][Level of evidence C1] Prognosis is more favorable in patients with longer duration of remission after the first HSCT and in patients with CR at the time of the second HSCT.[151,152,156] In addition, one study showed an improvement in survival after second HSCT if acute GVHD occurred, especially if it had not occurred after the first transplant.[157]

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.[158][Level of evidence B4] Donor leukocyte infusion has limited benefit for patients with ALL who relapse after allogeneic HSCT.[159]; [160][Level of evidence C1]

Whether a second allogeneic transplant is necessary to treat isolated CNS and testicular relapse after HSCT is unknown. A small series has shown survival in selected patients using chemotherapy alone or chemotherapy followed by a second transplant.[161][Level of evidence C1]