Sickle cell disease (SCD) is debilitating, with age-dependent complications such as stroke and liver disease, leading to significant morbidity and early mortality in young adults. Hematopoietic stem cell transplantation (HCT) is curative treatment for SCD, but transplantation-related risks often deter its use, especially in patients with severe comorbidities. A subset of severe SCD patients with significant end-organ dysfunction may benefit from a combined approach of HCT and solid organ transplantation (SOT). To the best of our knowledge, this report presents, for the first time, the utilization of dual orthotopic liver transplantation and haploidentical HCT (haplo-HCT) for severe SCD with advanced liver cirrhosis. Employing nonmyeloablative conditioning regimen and post-transplantation cyclophosphamide (PTCy). Both patients undergo orthotopic liver transplantation followed by haplo-HCT from the same related donors, achieve stable allograft function, full donor engraftment, and successful immunosuppression withdrawal through immune tolerance induction. Dual haplo-HCT and living donor liver transplantation (LDLT) is feasible in eligible SCD patients with end-stage liver disease.

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) remains a high-risk entity despite advances in tyrosine kinase inhibitors (TKIs), immunotherapy, and cellular therapies. Relapse driven by clonal evolution, central nervous system (CNS) sanctuary disease, and TKI resistance, particularly T315I mutations, continues to limit durable disease control. Asciminib, a first-in-class allosteric BCR::ABL1 (STAMP) inhibitor, has demonstrated efficacy and favorable tolerability in chronic myeloid leukemia, but its optimal role in Ph+ ALL remains to be defined. We report a three-patient case series of Ph+ acute leukemia treated with asciminib across diverse high-risk clinical settings, including multiply relapsed disease, CNS involvement, T315I-mutated leukemia, post-CAR-T-cell relapses, and transplant bridging. Clinical outcomes are contextualized through a comprehensive review of emerging clinical trial data, real-world cohorts, and mechanistic studies evaluating asciminib in Ph+ ALL. Across all cases, asciminib was incorporated as part of combination or consolidation strategies rather than as monotherapy in active disease. Asciminib contributed to molecular disease control, CNS leukemia clearance, and successful bridging to allogeneic transplantation or cellular therapy, with acceptable tolerability and no major vascular toxicity. Integration of published evidence demonstrates that asciminib exhibits consistent biological activity in Ph+ ALL, with improved durability when used in rational combinations, particularly with immunotherapy or ATP-competitive TKIs. Preclinical data further support asciminib’s compatibility with antibody-based and cellular therapies through preservation of immune effector function. Asciminib represents a versatile but context-dependent therapeutic option in Ph+ ALL. Its greatest clinical value appears to lie in rational combination regimens, maintenance strategies, and bridging to definitive therapies rather than single-agent salvage. Emerging structural biomarkers and ongoing clinical trials are expected to further refine patient selection, sequencing, and optimal integration of asciminib, particularly in CNS-involved disease and post-CAR-T cell relapse.

Background Cytomegalovirus (CMV) infection is a major contributor to morbidity and mortality in recipients of hematopoietic stem cell transplant (HSCT), solid organ transplant (SOT), and chimeric antigen receptor T-cell (CAR-T) therapy. While antiviral agents remain the cornerstone of treatment, CMV-specific immunoglobulins (CMVIG) have been utilized as adjunct therapy with variable outcomes. This study aims to evaluate the virological response and tolerability of CMVIG in cases of severe or refractory CMV viremia, with or without CMV disease. Methods: We conducted a single-center retrospective case series of adult recipients of SOT, allogeneic HSCT, and/or CAR-T cell therapy who developed CMV viremia or disease and received at least one dose of CMVIG between May 2017 and May 2023 at our center. Virological improvement within 14 days of starting CMVIG and tolerability of CMVIG are the primary outcome of this study. Results: A total of 33 patients were included. Of these, 29 underwent transplantation [SOT: 48.2%, HSCT: 51.7%], and five underwent CAR-T cell therapy (one post-HSCT). High-risk CMV serostatus was present in 12%. CMV viremia was documented in 32 patients (97%), and tissue-invasive disease was present in 11 patients (33.3%). Virological response, was observed in 65.6% of the cohort. The median time to undetectable CMV viral load following CMVIG initiation was 28 days. CMVIG was well-tolerated. All-cause mortality at 90 days remained high (57%). Conclusion: In this case series, CMVIG demonstrated a virological response rate of 65.6% in patients with severe or refractory CMV infection. While CMVIG was well-tolerated with minimal adverse events, the high mortality rate despite virological response suggests that CMVIG may be insufficient for this critically ill population. Our findings should be interpreted as observational data from a small case series, and prospective controlled trials are needed to establish the true benefit of CMVIG in combination with standard antiviral therapy.