Matched Sibling Versus Haploidentical Hematopoietic Transplant for Adult Patients with Acute Lymphoblastic Leukemia

Introduction:

Matched sibling donor hematopoietic stem cell transplant (MSD-HSCT) had an established role in the post-remission therapy for adult patients with acute lymphoblastic leukemia (ALL), while the role of haploidentical related donor (HRD) HSCT had not been fully defined. Moreover, the outcome of HRD-HSCT has improved gradually recent years which get very close to the outcome of MSD-HSCT. We set this study to compare the outcome between MSD and HRD HSCT for adult patients with ALL, and further to evaluate the role of HRD-HSCT in the post-remission therapy of adult ALL.

Methods:

Between March 2008 and June 2015, a total of 130 adult patients with ALL were assigned to receive MSD or HRD HSCT in our center. The strategy of donor selection between MSD and HRD was as follows: If a fully MSD was available, patients were assigned to undergo MSD-HSCT. If an MSD was unavailable, patients were assigned to receive HRD-HSCT. High resolution DNA typing of HLA-A, -B, -C, DRB1, and -DQB1 were performed in all patients and donors in our center. All patients received myeloablative conditioning mainly involving BuCy without total body irradiation. Anti-T-lymphocyte globulin (ATG-F; Fresenius, Bad Homburg, Germany) (2.5 mg/kg per day IV on days -5 to -2) was also administered to patients receiving HRD-HSCT. 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:

According to MSD availability, 42 patients were assigned to receive MSD-HSCT and 88 patients were assigned to receive HRD-HSCT. The median age of patients in the MSD cohort (36 years, range 16-51 years) was significantly older than those in the HRD cohort (24 years, range 14-50 years, P<0.001). The sex distribution of patients was also unbalanced between these two cohorts (Male/Female ratio: MSD 0.50 vs HRD 1.59, P=0.003). No significant difference of other clinical characteristics was observed between these two cohorts (P>0.05). The median follow-up time was 20.5 months (range 0.34-99.5 months) in the whole cohort.

Engraftment

Three patients in the HRD cohort died within 30 days after HSCT (day 11, day 21, and day 26). Among the 129 patients surviving beyond 15 days, all patients achieved myeloid recovery. The median time and the cumulative 15-day incidences of myeloid engraftment were 12 days (range, 8-17 days) and 95.2% in the MSD cohort, and 13 days (range, 9-29 days) and 73.6% in the HRD cohort, respectively. Myeloid recovery in the HRD cohort was significantly delayed compared with URD cohort (P=0.001).

Among the 127 patients surviving beyond 30 days, 5 patients in the HRD cohort experienced primary platelet engraftment failure. The median time and the cumulative 30-day incidences of platelet engraftment were 12 days (range, 7-36 days) and 95.2% in MSDs, and 15 days (range, 8-53 days) and 89.4% in HRDs, respectively. Patients receiving HSCT from HRDs experienced significantly delayed platelet recovery compared with those receiving HSCT from URDs (P<0.001).

Long-term Outcomes

There was a trend of higher 5-year relapse rate for patients receiving MSD-HSCT (49.1%) in comparison with those receiving HRD-HSCT (31.2%, P=0.053). While the non-relapse mortality (NRM) rates were significantly higher in the HRD cohort (23.9%) compared with MSD cohort (2.4%, P=0.004). The opposite effects from relapse rate and NRM rate resulted to a comparable survival rates between these two cohorts: The estimated 5-year overall survival (OS) rates were 52.3% and 52.5% for MSD and HRD HSCT (P=0.510), respectively. And the estimated 5-year relapse free survival (RFS) rates were 48.5% and 44.9% for MSD and HRD HSCT (P=0.626), respectively. After adjusting for patient age and sex, OS (P=0.180) and RFS (P=0.282) were still not significantly affected by donor type. In multivariate analysis, cGVHD had beneficial effects on RFS (HR=0.385, P=0.003) while beyond CR1 at transplant had adverse effects on RFS (HR=2.145, P=0.009).

Conclusion:

These data suggested that HRD-HSCT could achieve similar survival rates to MSD-HSCT for adult patients with ALL. HRD-HSCT could be a frontline alternative as post-remission therapy for adult ALL patients who lack a matched sibling donor.