Allogeneic hematopoietic cell transplantation from alternative sources for adult Philadelphia chromosome-negative ALL: what should we choose when no HLA-matched related donor is available?

The best outcome for patients with Ph chromosome-negative ALL (Ph(-) ALL) can be obtained by HLA-matched related donor (mRD) allogeneic hematopoietic cell transplantation (allo-HCT) in first CR. However, only 30% of patients have a mRD. Three alternative sources, unrelated donor (URD), cord blood, and haploidentical related donor (haplo-RD), are available. URD allo-HCT is an old-established alternative source, and recent data have shown that URD allo-HCT can result in OS comparable with that with mRD allo-HCT for patients with Ph(-) ALL in first CR (OS at 4 years: mRD 65% vs URD 62%). Unrelated cord blood transplantation can also be indicated for patients with Ph(-) ALL in first CR (OS at 4 years: 57%), especially for young patients without an HLA-matched URD or patients who are in urgent need for allo-HCT. Limited data for haplo-RD allo-HCT for ALL showed utility in CR (OS at 3 years: up to 65%) but a survival rate of only 5-7% in non-CR. As there are no confirmed data about the utility of allo-HCT from an alternative source for adolescent and young adults who are eligible for pediatric protocols or for elderly patients with reduced-intensity conditioning. Further investigation, including investigation of minimal residual disease detection, may reveal subgroups of patients who can receive benefits from allo-HCT. Selection of the best source based on the patient status and appropriate timing is warranted.