Effects Of Noninherited Maternal Antigen On The Occurrence Of Acute Graft-Versus Host Diseae After Unmanipulated Haploidentical Blood and Marrow Transplantation

Exposure to non-inherited maternal antigen (NIMA) in fetal and neonatal life has a lifelong immunological consequence. In haploidentical transplantation, the mismatched haplotype of the donor can originate from either the mother or the father. The aim of this prospective study is to investigate the effects of NIMA and non-inherited paternal antigen (NIPA) on transplant outcomes in patients who underwent unmanipulated haploidentical blood and marrow transplantation (HBMT).

Two hundred and eleven patients with hematological disease, including AML, ALL, CML, MDS, SAA, and others, who received haploidentical blood and marrow allgrafts were enrolled in this study. The stem cell source was G-CSF mobilized BM combined with PB. The conditioning regimen was modified BUCY plus ATG with 10mg/kg in total dosage. MTX, CSA, and MMF were used for prophylaxis of graft-versus-host disease.

The median patient follow-up was 343 days (range, 7-573 days). The median time for neutrophil and platelet engraftment was 12 days (range 7-25 days) and 16 days (range 6-410 days), respectively. The cumulative incidence of grade 2-4 actue GVHD at day 100 after HBMT was 41.7%±3.8% The cumulative incidence of chronic GVHD at 1 year was 53.4%±4.1%. The 1-year probability of relapse, TRM, LFS, and OS at 1 year was 11.3%±2.3%, 8.3%±1.9%, 79.6%±3.0%, and 85.0%±2.8%, respectively. Among the 211 patients, multivariate analysis showed that high risk patients had a high relapse rate (HR: 3.699, 95%CI, 1.598-8.565, P=0.002) and low LFS (HR: 2.452, 95%CI, 1.322-4.546, P=0.004). Duration from diagnosis to transplantation (more than 6 months vs. less than or equal to 6 moths) was associated with a high incidence of TRM (HR: 3.175, 95%CI, 1.251-8.059, P=0.015). Young recipient age (HR: 0.969, 95%CI, 0.946-0.993, P=0.012) were associated with a low incidence of grade 2-4 actue GVHD. Multiple analysis also showed that patients who received allografts from NIMA mismatched donor and father donor had lower incidences of grade 2-4 actue GVHD compared to those of patients receiving allografts from mother (HR: 0.576, 95%CI, 0.334-0.996, P=0.048, and HR: 0.378, 95%CI, 0.126-1.137, 0.087, respectively). For subgroup patients who received allografts from sibling donors, multivariate analysis showed that sibling transplantations mismatched for NIMA had a significantly lower incidence of grade 2-4 acute GVHD than those with NIPA mismatched donors (HR: 0.257, 95%CI, 0.083-0.796, P=0.018). No effects of NIMA mismatch on relapse, TRM, LFS, and OS were found in the current study.

Our results suggest that HBMT from a NIMA mismatched donor can offer low indicence of grade 2-4 acute GVHD. In unmanipulated haploidentical settings, mother donor transplantation may be associated with high incidence of grade 2-4 acute GVHD. These data suggest a NIMA mismatched donor not a mother donor should be preffered as donor for unmanipulated haploidentical blood and marrow transplantation.

No relevant conflicts of interest to declare.