Humoral serological response to the BNT162b2 vaccine after allogeneic haematopoietic cell transplantation.

OBJECTIVES: To assess the humoral immune response to the BNT162b2 vaccine after allogeneic haematopoietic cell transplantation (HCT). METHODS: This is a prospective cohort study. The SARS-CoV-2 IgGII Quant (Abbott©) assay was performed 4-6 weeks after the second BNT162b2 vaccine for quantitative measurement of anti-spike antibodies. RESULTS: The cohort included 106 adult patients. Median time from HCT to vaccination was 42 (range 4-439) months. Overall, 15/106 (14%, 95% confidence interval (CI) 7-21%) were seronegative despite vaccination, 14/52 patients on immunosuppression (27%, 95%CI 19-35%) compared to only 1/54 patients off immunosuppression (1.8%, 95%CI 1-4%) (p 0.0002). The proportion of seronegative patients declined with time; it was 46% (6/13) during the first year, 12.5% (3/24) during the second year and 9% (6/69) beyond 2 years from transplant. Patients with acute graft-versus-host disease (GVHD) (odds ratio (OR) 3.3, 95%CI 0.97-11.1, p 0.06) and moderate to severe chronic GVHD (OR 5.9, 95%CI 1.2-29, p 0.03) were more likely to remain seronegative. Vaccination was well tolerated by most patients. However, 7% (7/106) reported that GVHD-related symptoms worsened within days following vaccination. CONCLUSION: A significant proportion of allogeneic HCT recipients receiving immunosuppression demonstrated an inadequate humoral response to the BNT162b2 vaccine. These patients should be recognized and instructed to take appropriate precautions. Recipients who were off immunosuppression had a humoral response that was comparable to that of the general population.

Efficacy of folinic acid rescue following MTX GVHD prophylaxis: results of a double-blind, randomized, controlled study.

The use of methotrexate (MTX) for graft-versus-host disease (GVHD) prophylaxis is associated with increased rates of organ-specific toxicities. Despite limited data, the European Society for Blood and Marrow Transplantation-European LeukemiaNet working group recommend the use of folinic acid (FA) rescue to reduce MTX toxicity after allogeneic hematopoietic cell transplantation (allo-HCT). In a multicenter, double-blind, randomized, controlled trial, we explored whether FA rescue reduces MTX-induced toxicity. We enrolled patients undergoing allo-HCT with myeloablative conditioning with peripheral blood stem cell grafts, with GVHD prophylaxis consisting of cyclosporine and MTX. Patients were randomized to receive FA or placebo starting 24 hours after each MTX dose and continuing over 24 hours in 3 to 4 divided doses. The primary end point was the rate of grades 3 and 4 oral mucositis. After enrollment of 52 patients (FA, n = 28; placebo, n = 24), preplanned interim analysis revealed similar rates of grade 3 and 4 (46.6% vs 45.8%; P = .97) and grades 1 to 4 (83.3% vs 77.8%; P = .65) oral mucositis. With a median follow-up of 17 (range, 4.5-50) months, there was no difference in the rates of acute and chronic GVHD, disease relapse, nonrelapse mortality, and overall survival. These interim results did not support continuation of the study. We conclude that FA rescue after MTX GVHD prophylaxis does not decrease regimen-related toxicity or affect transplantation outcomes. This study was registered at clinicaltrials.gov as #NCT02506231.

Pilot study: fluvoxamine treatment for depression and anxiety disorders in children and adolescents with cancer.

OBJECTIVE: To evaluate the safety, tolerability, and benefit of fluvoxamine for the treatment of major depressive disorder or anxiety disorders in children and adolescents with cancer. METHOD: The study was conducted from 2001 to 2004 at a pediatric hematology-oncology center. Fifteen children and adolescents with cancer were treated with fluvoxamine 100 mg/day in an open prospective 8-week trial. Safety and tolerability were evaluated at baseline and at weeks 4 and 8 by blood tests and the Side Effects Checklist. Clinical benefit was assessed with the Clinical Global Impressions-Improvement, the Children's Depression Rating Scale-Revised, and the Pediatric Anxiety Rating Scale. RESULTS: Fluvoxamine was well tolerated by all subjects. Psychiatric symptoms improved significantly. CONCLUSIONS: In this open trial, fluvoxamine appeared to be well tolerated and was associated with a promising reduction in the depression and anxiety symptoms of pediatric patients with cancer.