Who Is the Better Donor for Young Hematopoietic Transplant Recipients without Siblings: An Older-Aged Haploidentical Parental Donor or a Young Unrelated Donor?

Introduction:

Hematopoietic stem cell transplant (HSCT) outcomes from unrelated donor (URD) and haploidentical donor were very close in recent years, and both could be alternative donors for recipients without siblings. But when considering donor age, especially for young recipients (≤30 years) without siblings, whether outcomes can be improved with a young URD rather than older-aged haploidentical parental donors (HPD) is still unknown.

Methods:

Between 2008 and 2014, a total of 156 young adult patients with hematological malignancies without sibling donors were assigned to receive URD or HPD HSCT in our center. The strategy of donor selection between URD and HPD was as follows: If an HLA suitably matched URD (≥8 of 10 matching HLA-A, -B, -C, -DRB1, and -DQB1 allele loci and ≥5 of 6 matching HLA-A, -B, and -DRB1 antigen loci) was available, patients were assigned to undergo URD-HSCT. If an HLA suitably matched URD was unavailable, patients were assigned to receive HPD-HSCT. Among them, 10 recipients received HSCT from URDs older than 40 years were further excluded. The transplant procedure had been reported previously (Yi Luo et. al. Blood 2014). Briefly, all patients received myeloablative conditioning involving BuCy without total body irradiation. The GVHD prophylaxis consisted of cyclosporin A, methotrexate, and low-dose mycophenolate mofetil. Grafts were granulocyte-colony stimulating factor mobilized peripheral blood stem cells without ex vivo T-cell depletion.

Results:

The median age of the finally included 146 young recipients was 21 years (range, 15-30 years). Of whom, 67 received HSCT from HPDs and 79 received HSCT from URDs.The median donor age of the HPDs was 46 years (range, 40-53 years), in contrast to 28 years (range, 20-39 years) of the URDs.

Engraftment

All patients achieved myeloid recovery. The median time and the cumulative 15-day incidences of myeloid engraftment were 12 days (range, 8-16 days) and 97.4% in the URD cohort, and 13 days (range, 8-21 days) and 77.6% in the HPD cohort, respectively. Myeloid recovery in the HPD cohort was significantly delayed compared with URD cohort (P<0.001).

Two patients in the HPD cohort experienced primary platelet engraftment failure. The median time and the cumulative 30-day incidences of platelet engraftment were 13 days (range, 6-24 days) and 100% in URDs, and 15 days (range, 6-30 days) and 97.0% in HPDs, respectively. Patients receiving HSCT from HPDs experienced significantly delayed platelet recovery compared with those receiving HSCT from URDs (P<0.001).

aGVHD

The incidences of grades II-IV aGVHD were 45.5% in the URD cohort and 47.8% in the HPD cohort (P=0.78), respectively. The incidences of grades III-IV aGVHD were 14.3% in the URD cohort and 17.9% in the HPD cohort (P=0.55), respectively.

Long-term Outcomes

There was a trend of higher 5-year overall survival (OS) and relapse free survival (RFS) rates for patients transplanted from young URDs in comparison with HPDs (OS: 64.4% vs 59.6% (P=0.23) and RFS: 63.2% vs 49.6%; (P=0.20)),respectively. The relapse rate and non-relapse mortality (NRM) rate were comparable between two cohorts.

For standard risk patients, a significantly higher 5-year OS and RFS rate were observed for patients transplanted from young URDs compared with HPDs (OS: 76.3% vs 52.7% (P=0.03) and RFS: 73.2% vs 53.8%; (P=0.04)), respectively. The significantly lower survival rate in the HPD cohort to some extent could be explained by the higher NRM rate in the HPD cohort (HPD 30.8% vs URD 13.9%, P=0.07). While for high risk patients, long-term outcomes were comparable between two cohorts.

Conclusion:

These data favor a young URD over an older-aged HPD for young recipients without siblings in standard risk; while for those in high risk, transplant outcomes were comparable between a young URD and an old-aged HPD. Moreover, myeloid and platelet recovery were significantly delayed in HPD-HSCT compared with URD-HSCT.