Lower Incidence of Cytomegalovirus Reactivation Following Post-Transplantation Cyclophosphamide HLA-Mismatched Unrelated Donor Transplantation.

The use of haploidentical or HLA-mismatched unrelated donors (MMUD) allows allogeneic hematopoietic cell transplantation in individuals without suitable matched donors. Post-transplantation cyclophosphamide (PTCy) is used routinely for prevention of graft-versus-host disease in recipients of haploidentical transplants, and its use has been recently explored in MMUD transplantation. We compared the incidence of cytomegalovirus (CMV) reactivation and rate of lymphocyte recovery between PTCy MMUD and alternative transplantation modalities. Single-center retrospective study of 22 consecutive PTCy MMUD recipients transplanted between April 2017 and January 2019. Patients undergoing anti-thymocyte globulin (ATG) MMUD (n = 37) and PTCy haploidentical transplantation (n = 19) between January 2015 and July 2018 served as historical controls. We assessed the incidence of CMV (any viremia) and clinically significant CMV reactivation (cs-CMVi; defined as CMV disease or CMV viremia leading to preemptive treatment) in these 3 groups. Immune reconstitution was assessed by absolute lymphocyte count (ALC) at days 30, 90, 180, and 360 after transplantation. Statistical analyses included Kaplan-Meier plots with a log-rank test, Kruskal-Wallis test, and Fisher's exact test where appropriate, and logistic regression analyses. For PTCy MMUD, PTCy haploidentical and ATG MMUD groups, the 100-day and 200-day incidence of CMV (any viremia) were 41%, 63%, and 77% (P = .02), and 64%, 68%, and 86% (P = .049), respectively. The rate of cs-CMVi was also lower in PTCy MMUD compared to PTCy haploidentical and ATG MMUD (14% versus 53% and 54% at day 100 [P = .01] and 25% versus 53% and 58% at day 200 [P = .03]). There was a trend toward lower 200-day incidence of cs-CMVi in PTCy MMUD compared to ATG MMUD, even after excluding letermovir-treated patients from the analysis (25% versus 58% [P = .06]). The association between PTCy MMUD and lower risk of cs-CMVi remained significant even after adjusting for letermovir prophylaxis (odds ratio = 0.23, 95% confidence interval, 0.07-0.81 [P = .02]). Day 30 ALC was lower in PTCy MMUD compared to PTCy haploidentical and ATG MMUD (0.14, 0.33, 0.44 × 109/L, respectively [P = .005) but similar across groups at other time points. PTCy MMUD transplantation was associated with lower incidence of CMV events, independent of the use of CMV prophylaxis. Larger studies are needed.

Clinical presentation and outcomes of COVID-19 following hematopoietic cell transplantation and cellular therapy.

BACKGROUND: One year into the pandemic, published data on hematopoietic cell transplantation (HCT) recipients with coronavirus disease 2019 (COVID-19) remain limited. METHODS: Single-center retrospective cohort study of adult HCT recipients with polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. RESULTS: Twenty-eight consecutive transplantation and cellular therapy patients (autologous, n = 12; allogeneic, n = 15; chimeric antigen receptor T-cell therapy [CAR-T], n = 1) with COVID-19 were identified. The median age was 57 years. The median time from HCT to COVID-19 diagnosis was 656 days (interquartile range [IQR], 33-1274). Patients were followed for a median of 59 days (IQR, 40-88). Among assessable patients (n = 19), 10 (53%) had documented virological clearance; median time to clearance was 34 days (range, 21-56). Out of 28, 12 (43%), 6 (21%), and 10 (36%) patients had mild, moderate, and severe/critical disease, respectively. Overall mortality was 25%, nearly identical for autologous and allogeneic HCT, and exclusively seen in hospitalized patients, older than 50 years of age with severe COVID-19. None of the patients with mild (n = 12) or moderate (n = 6) COVID-19 died whereas 7/10 patients (70%) with severe/critical COVID-19 died (P = .0001). Patients diagnosed with COVID-19 within 12 months of HCT exhibited higher mortality (57% vs 14%; P = .04). All-cause 30-day mortality (n = 4) was 14%. A higher proportion of patients who died within 30 days of COVID-19 diagnosis (3/4) were receiving ≥2 immunosuppressants, compared with patients who survived beyond 30 days after COVID-19 diagnosis (2/24; 75% vs. 8%; P = .01). CONCLUSIONS: Mortality in COVID-19 HCT patients is higher than that of the age-comparable general population and largely dependent on age, disease severity, timing from HCT, and intensity of immunosuppression.

Pretransplant Levels of C-Reactive Protein, Soluble TNF Receptor-1, and CD38+HLADR+ CD8 T Cells Predict Risk of Allograft Rejection in HIV+ Kidney Transplant Recipients.

INTRODUCTION: HIV-positive (HIV+) kidney transplant recipients exhibit a 2- to 3-fold increased risk of allograft rejection. Dysregulated immune activation in HIV infection persists despite successful antiretroviral therapy and is associated with non-AIDS morbidity, including renal disease. We hypothesized that the pathological levels of inflammation and immune activation associated with chronic HIV infection could have clinical utility in the prediction of rejection in HIV+ kidney recipients. METHODS: Prospective cohort study of 22 HIV-negative (HIV-; donor) to HIV+ (recipient) kidney transplant recipients who underwent biomarker assessment pretransplant and were subsequently followed for development of acute rejection. Plasma levels of markers of inflammation (soluble tumor necrosis factor receptor 1 [sTNF-R1] and C-reactive protein [CRP]) and microbial translocation (soluble CD14 and lipopolysaccharide) were measured by enzyme-linked immunosorbent assay or chromogenic endpoint assay. Levels of activated (CD38+HLADR+) CD4+ and CD8+ T cells, and T regulatory cells (CD4+CD25highFoxP3+) were measured by flow cytometry. RESULTS: Among the biomarkers evaluated, only the pretransplant levels of sTNF-R1, CRP, and frequencies of CD38+HLADR+ CD8 T cells, were found to be at significantly higher levels among patients who experienced biopsy-proven acute rejection. Confirming our hypothesis, patients with high pretransplant levels of sTNF-R1 or activated CD8+ T cells had a significantly increased 200-day cumulative incidence of biopsy-proven acute rejection (0 vs. 38% for both; P = 0.01). Similarly, pretransplant CRP levels higher than 5 µg/ml were associated with increased risk of acute rejection within the first 6 months post-transplant (0 vs. 43%; P = 0.01). CONCLUSION: Biomarker-based identification of HIV+ recipients at increased risk for rejection might facilitate individualized induction immunosuppression regimens in this vulnerable patient population.