-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

2183 Expanding the Donor Pool, the Number of Antigen Mismatches Has No Impact in the Outcomes of Haploidentical Stem Cell Transplantation with Peripheral Blood Stem Cells and Dual T Cell Depletion

Program: Oral and Poster Abstracts
Session: 732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Poster I
Hematology Disease Topics & Pathways:
Clinical Practice (Health Services and Quality), Biological therapies, Treatment Considerations, Transplantation (Allogeneic and Autologous)
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Tommy Alfaro, MD1*, Nihar Desai, MBBS, MD, DM2*, Carol Chen3*, Maria Queralt Salas4*, Igor Novitzky-Basso, MD5*, Wilson Lam, MD6, Ivan Pasic, MD5*, Arjun Datt Law, MD, MBBS, DM7, Fotios Michelis, MD8*, Jeffrey H. Lipton, MD, PhD9, Armin Gerbitz, MD, PhD3*, Rajat Kumar, MD PhD5, Dennis Dong Hwan Kim, MD, PhD10, Jonas Mattsson, MD, PhD11* and Auro Viswabandya, MD12

1Hans Messner Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Centre, La Union, Ca, Costa Rica
2Princess Margaret Cancer Center, Lucknow, India
3Hans Messner Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
4Hematopoietic Cell Transplantation Unit, Hospital Clínic de Barcelona, ICAMS, Barcelona, Spain
5Hans Messner Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada, Toronto, ON, Canada
6Department of Medicine, University of Toronto, Toronto, ON, Canada
7Princess Margaret Cancer Centre, Toronto, ON, CAN
8Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada
9Princess Margaret Cancer Centre, Toronto, ON, Canada
10Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
11Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada
12Princess Margaret Cancer Centre, TORONTO, ON, CAN

Background:

The use of Haploidentical donors has expanded the donor pool, specially for ethnic minorities. We intend to assess the impact of antigen mismatches (mm) in a cohort of patients receiving peripheral blood stem cells (PBSC) and GVHD prophylaxis with ATG and PTCY in combination.

Methods:

We analyzed the outcomes of 185 patients who underwent haploidentical stem cell transplant between August 2016 and November 2023 at Princess Margaret Hospital. The GVHD prophylaxis regimen comprised rabbit-ATG, PTCy, and CsA. T-cell replete peripheral blood stem cell (PBSC) grafts were infused on day 0.

Results:

We created two groups with 5-6/10 antigen mismatches (n=154) and 7-9/10 antigen mismatches (n=31). The median age of recipients was 57 years for those having 5-6 mismatches and 53 years for those with 7-9 mismatches, p=0.45. Males constituted 58.4% in the 5-6 mismatch group and 61.3% in the 7-9 mismatch group (p=0.84). Acute myeloid leukemia (AML) was the most common indication for transplant in both groups. Conditioning intensity was similarly distributed among the groups, for GVHD prophylaxis, 76.4% received a total ATG dose of 4.5 mg/kg, and 23.5% received 2 mg/kg in both groups combined with PTCY 50 mg/kg on D+3, +4. Cytomegalovirus (CMV) serostatus, the proportion of cryopreserved grafts, and median CD34+ cell dose was also similar across groups. The median follow-up time was 15 months, ranging from 5.6 to 38.4 months.

At two years, OS was 57.2% (95% CI 48.7-64.8) for the 5-6 mm group and 55.2% (95% CI 35.4-71.2) for the 7-9 mm group (p=0.676), with median survival times of 48.26 months and 57.62 months, respectively, p=0.676.

The cumulative incidence of relapse (CIR) at two years was 19.6% (95% CI 13.5-26.6) and 24% (95% CI 10.3-40.9) for the respective groups, p=0.37.

Non-relapse mortality (NRM) at 1 year for the 5-6 mm group and the 7-9 mm group was 25.7% (95% CI 19-32.8) versus 23.2% (95% CI 10-39.5) respectively, p=0.571.

At 100 days, rates of acute graft-versus-host disease (GVHD) for all grades were 37.1% (95% CI 29.4-44.7) for the 5-6 mm group and 41.9% (95% CI 24.3-58.6) for the 7-9 mm group, p=0.72. For acute GVHD grades III-IV, the rates at 100 days were 10.1% (95% CI 5.8-15.8) for the 5-6 mm group and 10.5% (95% CI 2.5-25.2) for the 7-9 mm group, p=0.49.

Chronic GVHD all grades at one year was 21.9% (95% CI 15.7-28.9) for the 5-6 mm group and 18% (95% CI 6-34.5) for the 7-9 mm group, with two-year rates of 22.8% (95% CI 16.4-29.9) and 27% (95% CI 11.4-45.3), respectively, p=0.93. Chronic GVHD moderate-severe at one year was 16.1% (95% CI 10.6-22.6) for the 5-6 mm group and 7.7% (95% CI 1.2-22.2) for the 7-9 mm group, with two-year rates of 16.1% (95% CI 10.6-22.6) and 22.3% (95% CI 7.6-41.6), respectively, p=0.858. At two years, the graft versus host disease/relapse free survival (GRFS) rate for the 5-6 mm group was 53% (95% CI 44.5-60.8), while for the 7-9 mm group, it was 47% (95% CI 27.7-64.1), p=0.70.

ANC engraftment rates at 30 and 60 days were 96% (95% CI 91.1-0.983) for the 5-6 mm group and 93.5% (95% CI 72.3-98.6) for the 7-9 mm group, p=0.49. Platelet engraftment at 30 days was 58.6% (50.2-66) for the 5-6 mm group and 61.3% (41.4-76.2) for the 7-9 mm group (p=0.59), with 60-day rates of 85.6% (95% CI 78.6-90.5) and 78% (95% CI 57.4-89.4), respectively, p=0.59. Primary graft failure rates at 30 days were 2.6% (95% CI 0.9-6.1) for the 5-6 mm group and 3.2% (95% CI 0.2-14.4) for the 7-9 mm group (p=0.07), and at 60 days, they were 4.6% (95% CI 2-8.7) versus 12.9% (95% CI 4-27.3), p=0.07.

Median days to develop BSI were 15 (range 13-48) for the 5-6 mm group and 38 (range 13-NA) for the 7-9 mm group, p=0.64. The incidence of clinically significant CMV infection (≥500 copies) at 100 days was 13% (95% CI 8.2-18.8) for the 5-6 mm group and 22.6% (95% CI 9.8-38.6) for the 7-9 mm group, p=0.16. Clinically significant EBV infection (≥30000 copies) at 100 days was 25.3% (95% CI 18.7-32.4) for the 5-6 mm group and 16.1% (95% CI 5.7-31.2) for the 7-9 mm group, p=0.20.

Conclusion:

The combination of PTCY and ATG for GVHD prophylaxis effectively neutralizes the impact of antigen mismatches in PBSC haploidentical transplants, with favorable outcomes regardless of mismatch extent. This approach highlights the safety and viability of utilizing alternative donors, significantly broadening the donor pool and enhancing transplant accessibility.

Disclosures: Novitzky-Basso: Takeda: Honoraria. Lipton: Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding. Kim: Paladin: Honoraria, Research Funding; Ascentage: Consultancy; Pfizer: Honoraria, Research Funding; Novartis: Honoraria, Other: Advisory board, Research Funding.

*signifies non-member of ASH