Session: 721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities: Poster I
Hematology Disease Topics & Pathways:
Biological, Diseases, Therapies, Clinically relevant, transplantation, stem cells
Using Transplant Registry of Japanese Data Center for Hematopoietic Cell Transplantation, we could analyze 5017 Japanese CBT pairs who were typed as HLA-A, -B, -C, -DRB1 alleles at the field 1 and 2 level, and transplanted single unit of cord blood for the first time. Patient age was ranged from 0 to 80 years old (median 50), Patient with AML was 1,113, ALL 884, MDS 514, other hematological malignancy 1,007 and non-hematological malignancy 374. 20 patients were transplanted in 1999-2004, 1,484 in 2005-2010 and 3,513 in 2011-2016. Donor HLA homo and patient HLA hetero combination (homo-hetero) was found in 39 pairs, hetero-homo in 40, homo-homo in 21, hetero-hetero with HLA allele match in HVG vector in 236, hetero-hetero with one allele mismatch in 569 and hetero-hetero with more than 2 allele mismatch in 4112 pairs.
Of note, all of 39 HLA homo-hetero pairs obtained neutrophil engraftment (500/μl) at 10-51 day (median 20) after transplantation except one early death pair. Platelet engraftment (20,000/μl) was also obtained in all evaluable 30 pairs. Acute GVHD with grade Ⅱ-Ⅳ and grade Ⅲ-Ⅳ occurred in 17 pairs and 3 pairs of 38 evaluable pairs respectively. Multivariate competing risk regression analysis including clinical factors revealed that homo-hetero pairs (n=39) showed a comparative neutrophil engraftment risk (HR=1.18 p=0.285) compared with HLA allele match hetero-hetero pairs (n=236), favorable risk compared with hetero-hetero pairs with HLA 1 allele mismatch (n=569) and favorable risk compared with hetero-hetero pairs with HLA more than 2 allele mismatch (n=4112). Also, these homo-hetero pairs showed comparative mortality (HR 0.95 P=0.85), platelet engraftment ((HR 1.10 p=0.597) and a tendency of higher risk of acute GVHD (grade 2-4) HR 1.63. p=0.065) compared with HLA allele match hetero-hetero pairs.
Further, we obtained detailed information on HLA alleles and haplotypes of HLA-homo. 37 of 39 homo-hetero donors had conserved extended HLA haplotypes (HP-1 n=18, HP=2 n=8, HP=3 n=7, HP-4 n=5, HP-5 n=1) which were ethnicity specific and highly conserved through the entire HLA region, and one of two patient heterogeneous HPs invariably shared the same HP as donor HLA-homo HP, and another non-shared patient HP was mismatched with 1 to 4 HLA alleles of HLA-A, -B, -C and -DRB1 loci in the GVH direction in 33 of these 37 pairs. The KIR2DL1 epitope was donor C1/C1 and patient C1/C1 in all homo-hetero pairs, making the KIR2DL ligand match combination.
In conclusion, CBTs from homo-hetero showed a favorable engraftment rate (100%), which confirmed our previous preliminary report for 6 homo-hetero CBTs. HLA alleles of HLA-homo donor were consisted of major conserved extended HLA haplotypes. Those results carry an important implication, namely the possibility that HLA-homo iPSC transplantation results in favorable engraftment, and banking of iPSC with major conserved extended HLA haplotypes is recommended, and patients possessing a single conserved common HLA haplotype have a higher chance of yielding HLA-homo iPSC and promising allo-iPS-T.
Disclosures: Ichinohe: Janssen Pharmaceutical K.K.: Honoraria; Mundipharma: Honoraria; Alexion Pharmaceuticals: Honoraria; Taiho Pharmaceutical Co.: Research Funding; Takeda Pharmaceutical Co.: Research Funding; Otsuka Pharmaceutical Co.: Research Funding; MSD: Research Funding; Pfizer: Research Funding; Ono Pharmaceutical Co.: Research Funding; Kyowa Hakko Kirin Co.: Research Funding; CSL Behring: Research Funding; JCR Pharmaceuticals: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria; Zenyaku Kogyo Co.: Research Funding; Sumitomo Dainippon Pharma Co.: Research Funding; Repertoire Genesis Inc.: Research Funding; Nippon Shinyaku Co.: Research Funding; Eisai Co.: Research Funding; Chugai Pharmaceutical Co.: Research Funding; Astellas Pharma: Research Funding; Novartis.: Honoraria.
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