Outcomes of Human Leukocyte Antigen-Matched Related Donor and Haploidentical Allogeneic Hematopoietic Cell Transplantation Recipients by Immune Profiles of Recipients and Donors

Abstract

Haploidentical (Haplo) allogeneic HCTs (alloHCT) have been used more frequently over the last decade as survival is similar to HLA-matched related donor (MRD) alloHCTs. We aimed to identify donor and recipient immune signatures before alloHCT that are associated with clinically meaningful outcomes in MRD vs Haplo alloHCT recipients. This retrospective cohort study of 165 MRD (n = 132) and Haplo (n = 33) alloHCT recipients and their related donors between 2007-2019 with paired peripheral blood samples immunophenotyped for T-cell, B-cell, NK cell and dendritic cell (DC) subsets. Immune cells were quantified before alloHCT in donors and recipients; calculations of immune cell ratios were classified as high, intermediate, and low and analyzed with alloHCT outcomes. Haplo donors were younger than MRD donors (median: 35 vs 51 years), whereas Haplo recipients were older than MRD recipients (median: 68 vs 54 years), were more likely to have a Karnofsky Performance Score ≤ 70 (76% vs 57%), 3+ comorbidities (54% vs 47%), and were in complete remission prior to alloHCT (58% vs 42%). In MRD alloHCT, a lower ratio of CD4+ to CD8+ effector memory cells in the donor was associated with lower 4-yr overall survival (OS; 25% vs 61%; P = .009), lower 4-yr progression free survival (PFS; 25% vs 58%; P = .014) and higher incidence of 1-yr transplant-related mortality (TRM; 39% vs 7%; P = .009) in recipients. A higher ratio of CD8+ effector memory to total NK cells measured in MRD recipients was associated with a higher incidence of grade II-IV aGvHD (63% vs 37%; P = .004) but was not statistically significant for III-IV aGvHD (23% vs 12%). In Haplo alloHCT, a lower ratio of total T-regulatory to CD4+ central memory cells in the donor was associated with lower 4-yr PFS (22% vs 60%; P = .0091). A higher ratio of CD4+ effector memory to CD8+ effector memory cells measured in Haplo recipients pre-alloHCT was associated with lower 4-yr OS (25% vs 88%; P = .0039). In both MRD and Haplo recipients, a higher ratio of CD4+ naïve to CD4+ central memory cells was associated with a higher incidence of grade II-IV aGvHD (64% vs 38%; P = .04). Evaluation of pre-alloHCT immune signatures of the donor and recipient may influence clinically meaningful patient outcomes in both MRD and Haplo transplants.

Keywords: Allogeneic transplant; Flow cytometry; Haploidentical transplant; Immune profiles; Matched related donor.

Figure 1.. Significant immune cell ratios by MRD vs Haplo and Patient vs Donor cells for HCT outcomes.

Larger dots represent a lower p-value with the largest representing p<0.01. Blue dots represent improved outcomes whereas red dots represent worse outcomes. Darker blue or reds dots represent an intermediate ratio between immune cell populations as opposed to a higher immune cell ratio associated with HCT outcomes. aGvHD – acute graft-versus-host disease, CM – central memory, DC – dendritic cells, EM – effector memory, NK – natural killer cells, NS – not significant, OS – overall survival, PFS – progression free survival, Treg – T regulatory cells, TRM – transplant-related mortality.

Figure 2.

In MRD recipients, the ratio of CD4+ effector memory to CD8+ effector memory cells in the donor associated with A) 4-year Overall Survival, B) 4-year Progression-Free Survival, and C) and 1-year incidence of Transplant-Related Mortality

Figure 3.

In Haplo recipients, the ratio of CD19+ naïve to CD19+ memory B-cells in the patient was associated with A) 4-year Overall Survival, B) 4-year Progression-Free Survival, C) grade II-IV acute GvHD, and D) not associated with grade III-IV acute GvHD.

Figure 4.

In Haplo recipients, the donor to recipient CD4+ naïve to CD8+ naïve ratio was associated with A) 4-year Overall Survival and B) Progression-Free Survival.

Figure 5.

In MRD recipients, the donor to patient CD4+ effector memory to CD8+ effector memory ratio was associated with A) Transplant-Related Mortality and B) grade III-IV acute GvHD.