Comparison of clinical efficacy between HLA-mismatched related and HLA-matched unrelated donor hematopoietic stem cell transplantation for hematopoietic malignancies
Authors: Yu Sijian , Fan Zhiping , Xu Dan , Huang Fen , Zhang Yu , Wei Yongqiang , Zhou Hongsheng , Jiang Qianli , Dai Min , Xu Na , Sun Jing , Liu, MD Qifa 
Published: October 2019

Abstract

Objective
To compare the clinical efficacy of HLA-mismatched related donor (MRD) and HLA-matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT) for hematopoietic malignancies, 175 patients with hematopoietic malignancies undergoing allogeneic HSCT (allo-HSCT) (83 from MRD and 92 from MUD) from October 2002 to December 2012 were enrolled in this retrospective study.

Methods
Of the 175 patients, 67 were female, and 108 were male. The median age was 27.0 (range 11-53) years. Primary diseases included acute lymphoblastic leukemia (ALL, n=56), acute myelogenous leukemia (AML, n=46), acute leukemias of ambiguous lineage (ALAL, n=13), chronic myeloid leukemia (CML, n=47), myelodysplastic syndrome (MDS, n=7), lymphoma (n=5) and aplastic anemia (AA, n=1). Fifty-seven patients were in the status of no remission (NR), and 118 were complete remission (CR) at the time of transplantation. Genomic molecular typing was used for HLA-A, -B and -DRB in most donors and recipients before May 2008, and then it was used for HLA-A, -B, -DRB, -DRQ and Cw. Hematopoietic engraftment, graft versus host disease (GVHD), relapse, overall survival (OS) and disease-free survival (DFS) were compared between MRD and MUD group.

Results
Eighty-three patients received MRD transplantation, including sibling (n=47), parents (n=29), children (n=5) and others (n=2), and 93 received MUD transplantation. Of HLA 6/6 typing, 18 were one allele, 19 two alleles, 1 three alleles-mismatched; of HLA 10/10 typing, 4 were one allele, 17 two alleles, 9 three alleles, 7 four alleles, and 8 five alleles- mismatched in MRD group. Forty-one patients were HLA 6/6 and 51 we HLA 10/10-matched in MUD group. There was no significant difference between MRD and MUD group regarding age, gender, disease type and disease status pre-transplantation (all P>0.05). Except for 4 and 3 patients who died of regimen-related toxicity (RRT), respectively, in MRD and MUD group, other patients obtained hematopoietic engraftment.
The median time to neutrophil and platelet engraftment was 11 (range, 9 to 22) days and 13 (range, 10 to 40) days in MRD group, and it was 12 (range, 10 to 29) days and 14 (range, 10 to 60) days in MUD group (P>0.05, P>0.05). The incidence of I-IV0 acute GVHD (aGVHD) was 68.7% and 48.9% in MRD and MUD group (P<0.01), but there was no significant difference in the incidence of III-IV0 aGVHD between the two groups (14.5% vs. 8.7%, P>0.05). The incidence of chronic GVHD (cGVHD) was 22.9% and 41.3% in MRD and MUD group (P<0.05), but there was no significant difference in the incidence of extensive cGVHD between the two groups (7.2% vs. 12.0%, P>0.05).The mortality of GVHD was 14.5% and 18.6% in MRD and MUD group (P>0.05).
With a median follow up of 51 months (range 1 day-130 months) post-transplantation, the 10- year OS and DFS were 47.2%±6.1% and 42.9%±6.1% in MRD group, compared with 55.1%±5.5% and 45.8%±5.4% in MUD group(P=0.236, P=0.686, respectively). The 10-year cumulative incidence of relapse was 24.8%±6.0% and 39.1%±6.1% in MRD and MUD group (P=0.230).

Conclusions
Although the incidence of cGVHD was higher in MRD group, there was no significant difference in the incidence of I-IV0 aGVHD, III-IV0 aGVHD and extensive cGVHD between MRD and MUD group. Hematopoietic engraftment, cumulative relapse rate, OS and DFS also did not differ significantly between the two groups. These results suggest that MRD is equivalent to MUD in efficacy and safety. Without HLA-matched related donors, MRD is superior to MUD because donor source is unlimited and choice of treatment could be made promptly according to disease status.

Disclosures:
Liu: It was supported by Science and Technology Program of Guangzhou of China (11A72121174).: Research Funding; It was supported by National Public Health Grand Research Foundation (Grant No. 201202017), National Natural Science Foundation of China (Grant No.81000231, No.81270647).: Research Funding; It was supported by 863 Program (No. 2011AA020105).: Research Funding.