A 76-year-old woman with stage IIIB squamous cell lung carcinoma developed pancytopenia following maintenance therapy with durvalumab. She was diagnosed with squamous cell lung carcinoma (T4N2M0, stageIIIB) in December 2023. Following a favorable response to chemoradiotherapy, maintenance therapy with durvalumab was initiated in June 2024. Thrombocytopenia was observed starting in August, and platelet count had decreased to 22,000/µl in October, leading to the discontinuation of durvalumab. However, the condition progressed to pancytopenia. Bone marrow biopsy revealed hypocellular marrow without dysplasia, fibrosis, or hemophagocytosis. Additional findings included paroxysmal nocturnal hemoglobinuria-type blood cells and fatty marrow replacement on spinal MRI. Based on these comprehensive findings, the patient was diagnosed with aplastic anemia (AA) in January 2025. Immunosuppressive therapy combining antithymocyte globulin, cyclosporine A, and eltrombopag was initiated in February 2025, resulting in a favorable response. AA is a relatively rare immune-related adverse event, and reports of AA induced by durvalumab are extremely limited. This case highlights the importance of considering AA in the differential diagnosis of persistent thrombocytopenia or pancytopenia during immune checkpoint inhibitor therapy.

Anti-thymocyte globulin (ATG) and post-transplantation cyclophosphamide (PTCy) are both used as in-vivo lymphodepleting treatment in allogeneic hematopoietic stem cell transplantation (HSCT), particularly in the matched unrelated donor (MUD) setting.

Although anti-thymocyte globulin (ATG) is commonly used as prophylaxis against graft-versus-host disease (GVHD) following allogeneic haematopoietic stem cell transplantation (alloSCT), there is considerable inter-patient variability in ATG exposure. The impact of ATG exposure in outcomes following reduced intensity conditioning (RIC)-alloSCT remains unknown. We explored the impact of post-transplant ATG exposure (PT-ATG-exp) in 68 adults with haematological malignancies undertaking first RIC-alloSCT with ATG (Thymoglobulin, total dose 4.5mg/kg, day -3 to -1 alloSCT). Post-transplant ATG exposure was determined by area under the curve (AUC) through analysis of sera collected at standardised timepoints. Post-transplant ATG exposure range was highly variable [46-420 arbitrary units (AU) per day/mL]. Day 0 ATG concentration and day 0-14 ATG AUC highly correlated with PT-ATG-exp (R = 0.93 and 0.99, respectively, P < 0.001). Using a Cox proportional hazards model, patients with PT-ATG-exp between 80-135 AU per day/mL had inferior 2-year GRFS compared to the remainder of the cohort [25% (95% CI, 11%-56%) vs 54% (95% CI, 40%-73%), P = 0.02; HR 2.01 (95% CI, 1.04-3.86, P = 0.04] due to higher incidence of grade III-IV acute GVHD [33% (95% CI, 16%-51%) vs 12% (95% CI, 4%-24%), P = 0.034; HR 2.95 (95% CI, 0.99-8.83, P = 0.05)]. Recipients with the highest PT-ATG-exp (quartile 4: 185-420 AU per ml/day) had the lowest incidence of grade III-IV acute GVHD (0% at 180-days) but also lowest median CD3[+] chimerism (85%) and highest incidence of mixed donor chimerism (CD3[+]: 93% and CD3[-]: 33%) at day 100. In this analysis, PT-ATG-exp influenced post-transplant outcomes including GVHD incidence and donor chimerism following in RIC-alloSCT.

Park and colleagues recently reported, in a single-centre Korean cohort of 391 adult patients with myelodysplastic neoplasms (MDS) receiving fludarabine-busulfan conditioning and antithymocyte globulin (ATG)-based prophylaxis, that matched sibling donor (MSD) recipients experienced a substantially higher 5-year cumulative incidence of relapse (34.3%) than recipients of unrelated (UD; 16.4%) or haploidentical (HID; 16.8%) donors, with reduced acute and chronic graft-versus-host disease (GVHD) in the MSD arm. The authors conclude that under ATG-based prophylaxis, MSD may no longer be the optimal donor choice in MDS. We respectfully argue that this conclusion is constrained by two structural features of the cohort. First, ATG dose is severely confounded with donor type: 61.3% of MSD recipients received 10 mg/kg ATG versus 0% of HID recipients, a dose pattern that inverts standard clinical practice and overlaps a range in which independent evidence indicates impaired disease control without offsetting GVHD benefit. Second, the GVHD- non-relapse mortality pattern in the cohort is more consistent with a cumulative immunosuppression-intensity hypothesis than with a primary donor-source effect. We propose that the most clinically actionable inference is to re-examine ATG dosing in MSD transplants for MDS, rather than to displace MSD as a preferred donor.

Anti-thymocyte globulin (ATG) has been a standard prophylaxis for graft-versus-host disease (GVHD). However, the pharmacokinetics of ATG in vivo vary significantly, and weight-based fixed dosing may not optimize efficacy while minimizing toxicity. We investigated the clinical results of a therapeutic-drug-monitoring (TDM)-based, dose-optimized ATG strategy versus weight-based fixed dosing in haploidentical haematopoietic stem cell transplantation (NCT05166967). Patients were randomly assigned in a 1:1 ratio to receive a targeted dose of ATG or a fixed dose of 10 mg/kg. The primary endpoint was the 365-day graft-versus-host disease-free and relapse-free survival (GRFS). From January 1, 2022, to January 16, 2024, 204 patients were enrolled, with 102 patients in each group. The 365-day GRFS was higher in the targeted dose group (66.7%) than in the fixed dose group (50.0%; hazard ratio [HR], 0.666; 95% confidence interval [CI], 0.4456 to 0.9954; P = 0.048). The cumulative incidence of moderate to severe chronic GVHD at day 365 was significantly lower in the targeted dose group (9.8%; 95% CI, 5.0 to 16.5) compared with the fixed dose group (22.5%; 95% CI, 15.0 to 31.1; P = 0.026). Fewer grade 3-5 infections were reported in the targeted dose group (44.1%) than in the fixed dose group (70.6%; P < 0.001). More patients in the targeted dose group achieved optimal ATG exposure (P = 0.007) and superior CD4[+] T-cell reconstitution (P = 0.002). These findings support the clinical utility of a TDM-based individualized ATG dosing strategy that balances efficacy and toxicity for GVHD prophylaxis in allogeneic stem cell transplantation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05166967.

Background: Black patients awaiting transplantation are more likely to be immunologically sensitized than White, Hispanic, or Asian patients. In Nigeria, the situation is compounded by multiple blood transfusions before and during dialysis, including patients on the waiting list for kidney transplantation. Tailored immunosuppressive regimens and allocation policies are being explored to address the unique genetic and immunological profiles of Black patients and improve outcomes. Comparing practice in the selected Nigerian center with international and local guidelines on induction immunosuppression is the main crux of this review. This review focused on current practices in induction regimen for kidney transplantation in immunologically high-risk patients in a Nigerian transplant setting, explores its outcome and compares this practice and its outcome with practice in other centers and international kidney transplant guidelines. Keyword searches of academic databases - PUBMED, SCOPUS, AJOL, Cochrane, ISI, Google scholar and IBSS databases were conducted. Manual searches of other relevant journals and reference lists of primary articles. Anti-thymocyte globulin remains the choice of induction agent, with the same dose used for both non sensitized and highly sensitized patients. Induction regimen used in the index center was given for a shorter duration of 3-5 days when compared to standard guideline recommendations of 21 doses over 28 days. However, the 3-month and 12-month graft outcome obtained was 90% and 90%, respectively, in the index center; and this was comparable to the outcome in centers where the standard protocol was employed. There is no change in the choice of immunosuppressive agent for kidney transplant in Nigeria and other centers and guidelines reviewed. With ongoing efforts to reduce the widening gap in transplant care by having an individualized approach to care, this narrative explores current practices in a resource-constrained setting as compared to guideline recommendations and provides a basis for future studies.