Contributions
Abstract: S796
Type: Oral Presentation
Presentation during EHA22: On Sunday, June 25, 2017 from 08:30 - 08:45
Location: Room N105
Background
By definition “haplo-identical” donors share genotipically 4/8 antigens with recipients. However, casual phenotypical homozygosity in the non-shared haplotype makes the real degree of disparity less than 4/8 in a few donor/recipient couples.
Aims
Since 2010, patients who lacked a HLA-identical donor have been transplanted from a haploidentical donor in our two Italian institutions. In this large series of patients we aim to verify the real degree of antigen disparity between donors and recipients and whether it impacts on transplantation outcome.
Methods
All haplotransplants performed in two Italian istitutions from August 2010 to July 2016 (n =318) were included. All patients received a myeloablative regimen (MA) followed by unmanipulated bone marrow and high dose post-transplant cyclophosphamide (PT-CY), combined with cyclosporine and mycophenolate. Donors and recipients were typed, until 2015, using DNA method (SSO and SBT) for HLA A, B, C, DRB1, DQ and DPB at a high resolution level, as defined by EFI standards and by NGS at allelic level in 2016 for the same loci. When applicable (72,3% of patients) members of the immediate family where typed to definitively establish HLA genotype and haplotype identity. Differences at loci A, B, C, DRB1 in both GvH and HvG direction were evaluated. We evaluated overall survival (OS) and non-relapse mortality (NRM) according to the amount of overall mismatches; also, we analyzed cumulative incidence of grade II – IV aGVHD, moderate-severe chronic GvHD and relapse (CIR) according to the degree of HLA mismatches in the GVH direction and graft rejection rate according to the degree of HLA mismatches in the HVG direction. For analysis purpose, the whole patient population was divided into 2 groups: 0-1-2 antigen mismatches versus 3-4 antigen mismatches. The same distinction was mantained when analyzing only GVH or HVG directed mismatches. Acute GvHD was calculated at day 100, the other parameters were calculated at the second year of follow up. OS was estimated using the Kaplan-Meier approach while cumulative incidence was calculated for aGvHD, cGvhD, relapse and NRM.
Results
Median age of patients was 48 years (17-74). Diagnoses included acute myeloid leukemia (130), acute lymphoblastic leukemia (64), lymphoid and plasma cell malignancies (43), myeloproliferative neoplasms (48) and myelodisplastic syndrome (33). 144 patients (45%) were transplanted in advanced phase of disease. With a median follow up of 562 days (range 6-2241 days), 2-year OS was 55,7%. Concerning the proportion of “true” haploidentical D/R pairs, 231 out of 318 (72%) couples showed 4/8 mismatches at HLA A, HLA B, HLA C and HLA DRB1 loci. Neither OS nor NRM showed significant correlation with the degree of overall mismatches at 2 years (0-2 mm: 54.2% vs 3-4 mm:58.8%, p=0.58 and 0-2 mm:18.2% vs 3-4 mm:19.1%, p=0.93, respectively). Considering only GVH directed mismatches, no difference was highlighted between low or high HLA mismatch burden in cumulative incidence of aGVHD (12.6% vs 23.9%, p=0.13), cGVHD at 1 year (12.2% vs 14.8%, p=0.84) and relapse (33.3% vs 24%, p=0.26). In this series graft rejection rate was 6.6%; no correlation was observed with the amount of HLA mismatch in the HVG direction.
Conclusion
In this series, about one third of haploidentical donor/recipient pairs differ for less than 4 /8 HLA antigens. Furthermore, in the setting of a MA conditioning with PT-CY the real degree of HLA mismatching observed had no impact on OS, NRM, CI of Relapse and acute and chronic GvHD .
Session topic: 22. Stem cell transplantation - Clinical
Keyword(s): HLA, Haploidentical stem cell transplantation, Allogeneic hematopoietic stem cell transplant
Abstract: S796
Type: Oral Presentation
Presentation during EHA22: On Sunday, June 25, 2017 from 08:30 - 08:45
Location: Room N105
Background
By definition “haplo-identical” donors share genotipically 4/8 antigens with recipients. However, casual phenotypical homozygosity in the non-shared haplotype makes the real degree of disparity less than 4/8 in a few donor/recipient couples.
Aims
Since 2010, patients who lacked a HLA-identical donor have been transplanted from a haploidentical donor in our two Italian institutions. In this large series of patients we aim to verify the real degree of antigen disparity between donors and recipients and whether it impacts on transplantation outcome.
Methods
All haplotransplants performed in two Italian istitutions from August 2010 to July 2016 (n =318) were included. All patients received a myeloablative regimen (MA) followed by unmanipulated bone marrow and high dose post-transplant cyclophosphamide (PT-CY), combined with cyclosporine and mycophenolate. Donors and recipients were typed, until 2015, using DNA method (SSO and SBT) for HLA A, B, C, DRB1, DQ and DPB at a high resolution level, as defined by EFI standards and by NGS at allelic level in 2016 for the same loci. When applicable (72,3% of patients) members of the immediate family where typed to definitively establish HLA genotype and haplotype identity. Differences at loci A, B, C, DRB1 in both GvH and HvG direction were evaluated. We evaluated overall survival (OS) and non-relapse mortality (NRM) according to the amount of overall mismatches; also, we analyzed cumulative incidence of grade II – IV aGVHD, moderate-severe chronic GvHD and relapse (CIR) according to the degree of HLA mismatches in the GVH direction and graft rejection rate according to the degree of HLA mismatches in the HVG direction. For analysis purpose, the whole patient population was divided into 2 groups: 0-1-2 antigen mismatches versus 3-4 antigen mismatches. The same distinction was mantained when analyzing only GVH or HVG directed mismatches. Acute GvHD was calculated at day 100, the other parameters were calculated at the second year of follow up. OS was estimated using the Kaplan-Meier approach while cumulative incidence was calculated for aGvHD, cGvhD, relapse and NRM.
Results
Median age of patients was 48 years (17-74). Diagnoses included acute myeloid leukemia (130), acute lymphoblastic leukemia (64), lymphoid and plasma cell malignancies (43), myeloproliferative neoplasms (48) and myelodisplastic syndrome (33). 144 patients (45%) were transplanted in advanced phase of disease. With a median follow up of 562 days (range 6-2241 days), 2-year OS was 55,7%. Concerning the proportion of “true” haploidentical D/R pairs, 231 out of 318 (72%) couples showed 4/8 mismatches at HLA A, HLA B, HLA C and HLA DRB1 loci. Neither OS nor NRM showed significant correlation with the degree of overall mismatches at 2 years (0-2 mm: 54.2% vs 3-4 mm:58.8%, p=0.58 and 0-2 mm:18.2% vs 3-4 mm:19.1%, p=0.93, respectively). Considering only GVH directed mismatches, no difference was highlighted between low or high HLA mismatch burden in cumulative incidence of aGVHD (12.6% vs 23.9%, p=0.13), cGVHD at 1 year (12.2% vs 14.8%, p=0.84) and relapse (33.3% vs 24%, p=0.26). In this series graft rejection rate was 6.6%; no correlation was observed with the amount of HLA mismatch in the HVG direction.
Conclusion
In this series, about one third of haploidentical donor/recipient pairs differ for less than 4 /8 HLA antigens. Furthermore, in the setting of a MA conditioning with PT-CY the real degree of HLA mismatching observed had no impact on OS, NRM, CI of Relapse and acute and chronic GvHD .
Session topic: 22. Stem cell transplantation - Clinical
Keyword(s): HLA, Haploidentical stem cell transplantation, Allogeneic hematopoietic stem cell transplant