A hybrid protocol CLAG-M, a possible player for the first-line therapy of patients with mixed phenotype acute leukemia. A Polish Adult Leukemia Group experience.

Introduction: Mixed-phenotype acute leukemia (MPAL) is a rare disease with poor prognosis. So far, no standard approach has been established as the "know-how" of MPAL is based only on retrospective analyses performed on small groups of patients. Materials and methods: In this study, a retrospective analysis of the outcomes of adult MPAL patients included in the PALG registry between 2005 and 2024 who received the CLAG-M hybrid protocol as induction or salvage therapy was performed. Results: Sixteen of 98 MPAL patients received CLAG-M: eight as first-line and eight as salvage therapy. In the first line, two patients achieved partial response (PR), and six achieved complete remission (CR), of whom four successfully underwent allogeneic hematopoietic stem cell transplantation (alloHSCT). Two patients who did not undergo alloHSCT promptly relapsed. Within the whole group, the overall response rate (ORR) was 75% (n = 12/16). With the median follow-up of 13 months, six out of eight patients remain in CR, however, two of them died due to acute graft versus host disease. Out of eight patients who received CLAG-M in the second line, four patients (50%) obtained CR. AlloHSCT was conducted in seven cases, six of which were in CR. Only two patients remained in CR at the time of the last follow-up. Tolerance to treatment was good. The median times for severe neutropenia and thrombocytopenia were 22 days (range, 16-24) and 17 days (range, 12-24), respectively. Overall, grade 3-4 infections were observed in 12 cases, and all infections presented successful outcomes. Conclusions: CLAG-M is an effective first-line salvage regimen for MPAL with an acceptable safety profile. Early achievement of CR with prompt alloHSCT allows for satisfactory disease control.

Sinus bradycardia as a rare adverse event in patients receiving cyclosporine A after allogeneic hematopoietic stem cell transplantation.

Cyclosporine A (CSA) is a commonly used immunosuppressive agent for the prophylaxis of graft-versus-host disease following allogeneic hematopoietic stem cell transplantation (alloHSCT). While tachycardia is a known adverse effect of CSA, bradycardia remains a phenomenon rarely described in the literature. We conducted a retrospective evaluation of the incidence of bradycardia in patients after alloHSCT treated with CSA between January 2020 and February 2023 at our center. Out of 206 patients, sinus bradycardia following the administration of CSA was observed in 6 (2.9%), comprising 3 women and 3 men, with the median age of 55 years (range: 20-65). The underlying diseases were myeloid malignancies in 4 and aggressive lymphoma in 2 patients. The patients received grafts from a matched unrelated (n=5) or a haploidentical family donor (n=1) following various conditioning regimens. Coexisting cardiovascular disorders were found in 5 of the 6 patients. All patients experienced symptomatic bradycardia within 1-4 days (median 2 days) after CSA introduction, which persisted until CSA withdrawal. One patient required treatment with atropine. All patients continued their immunosuppressive therapy with tacrolimus, which was well-tolerated Our study indicates CSA as a causative factor of sinus bradycardia in a small percentage of alloHSCT patients receiving CSA as graft-versus host disease (GvHD) prophylaxis. Importantly, these patients did not experience any cardiac complications when switched to tacrolimus. Although further research on the effects of CSA on heart automatation is needed, our single-center experience can help prompt diagnosis and therapeutic intervention in daily clinical practice.

Two Doses of BNT162b2 mRNA Vaccine in Patients after Hematopoietic Stem Cell Transplantation: Humoral Response and Serological Conversion Predictors.

Vaccination against SARS-CoV-2 is currently the best tool in the fight against the COVID-19 pandemic. However, there are limited data on its efficacy and safety after hematopoietic stem cell transplantation (HCT). We present the results of a prospective analysis of the humoral response to two doses of BNT162b2 mRNA vaccine in 93 adult patients, including 29 after autologous HCT (autoHCT) and 64 after allogeneic HCT (alloHCT). Positive anti-SARS-CoV-2 antibodies were detected before vaccination in 25% of patients despite a negative medical history of COVID-19. Seroconversion after vaccination was achieved in 89% of patients after alloHCT and in 96% after autoHCT, without grade 3/4 adverse events. Post-vaccination anti-SARS-CoV-2 antibody level correlated with the time from transplant and absolute B-cell count at the vaccination. In univariate analysis restricted to the alloHCT group, short time since transplantation, low B-cell count, low intensity conditioning, GvHD, and immunosuppressive treatment at the vaccination were associated with lack of seroconversion. In the multivariate model, the only negative predictor of seroconversion remained treatment with calcineurin inhibitor (CNI). In conclusion, the BNT162b2 mRNA vaccine is highly immunogenic in patients after HCT, but treatment with CNI at the time of vaccination has a strong negative impact on the humoral response.