Comparison of rabbit ATLG and ATG for GVHD prophylaxis in hematological malignancies with haploidentical hematopoietic stem cell transplantation.

Rabbit anti-human T lymphocyte globulin (ATLG) and anti-thymocyte globulin (ATG) are commonly used for graft-versus-host disease (GVHD) prophylaxis in allogeneic hematopoietic stem cell transplantation (HSCT). Yet, their efficacy and safety have seldom been compared in hematological malignancies with haploidentical HSCT. A retrospective analysis with 28 ATLG (total dosage, 20-30 mg/kg) and 18 ATG (total dosage, 8-10 mg/kg) patients were performed. The cumulative incidences of chronic GVHD and relapse were comparable between both groups. ATLG showed a trend towards a lower acute GVHD incidence (28.6% vs. 44.4%, P = 0.242) and 3-year non-relapse mortality (10.7% vs. 27.8%, P = 0.160), and had a significantly higher 3-year overall survival (OS, 64.3% vs. 33.3%, P = 0.033) and GVHD-free and relapse-free survival (GRFS, 32.1% vs. 11.1%, P = 0.045) compared with ATG. Multivariate Cox regression analysis demonstrated ATLG was independently associated with a favorable OS (hazard ratio [HR] = 0.37, 95% confidence interval [CI]: 0.16-0.86, P = 0.020) and GRFS (HR = 0.51, 95%CI: 0.26-1.00, P = 0.051). Furthermore, ATLG had a lower risk of fever (25.0% vs. 61.1%, P = 0.014) and hemorrhage cystitis (7.1% vs. 38.9%, P = 0.008) than ATG-T. In conclusion, ATLG confers more survival benefit and a better safety profile than ATG and can be used in hematological malignancies with haploidentical HSCT. Prospective designed trials with a larger sample size are warranted to confirm the results in the future.

Successful Treatment of Severe Steroid-Resistant Engraftment Syndrome Following Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia with Emapalumab: A Case Report.

Engraftment syndrome (ES) is an early complication of hematopoietic stem cell transplantation (HSCT) characterized by fever and additional clinical manifestations including rash, diarrhea, lung infiltrates, weight gain, and neurological symptoms. Steroid-resistant ES following HSCT significantly affects the efficacy of transplantation and may even result in patient mortality. As ES essentially represents a cytokine storm induced by engrafted donor cells with interferon-gamma (IFN-γ) playing a central role, we hypothesized that emapalumab (an anti-IFN-γ monoclonal antibody) may be an effective approach to treat steroid-resistant ES. Here, we present a case report of a 14-year-old female patient who received a second haploidentical HSCT due to a relapse of acute myeloid leukemia. Nine days after the transplantation, the patient developed a fever and exhibited a poor response to antimicrobials (ceftazidime/avibactam). A few days later, the patient presented with a new-onset rash, weight gain, and impaired liver function, leading to a diagnosis of ES. Initial immunosuppressive (tacrolimus and mycophenolate mofetil) treatment failed to control the disease. On day 16 post-transplantation, the patient received two infusions of 50 mg of emapalumab. Following the initiation of emapalumab treatment, the patient's fever returned to normal and ES was effectively controlled. This case report demonstrated that emapalumab had a possible efficacy for steroid-resistant ES and provided a novel therapeutic strategy to treat this clinical complication.