Sexual dysfunction is a frequent long-term complication following allogeneic hematopoietic stem cell transplantation (HSCT). This multicenter, prospective, randomized controlled trial evaluated the feasibility and efficacy of a multimodal intervention targeting sexual function and early detection of genital chronic graft-versus-host disease (cGVHD) in adult recipients of HSCT. Participants were randomized 1:1 to the intervention or usual care. The intervention included repeated questionnaires, genital assessments, and nurse-led consultations. Sexual function was assessed using the Female Sexual Function Index or the International Index of Erectile Function, with secondary outcomes including sexual health, sexual distress, and feasibility measures. Overall sexual function did not differ significantly between groups for women (difference (diff) 3.3, P = 0.391) or men (diff 0.9, P = 0.761). Significant improvements favoring the intervention group were observed in women’s sexual pain (diff −2.1, P = 0.019) and, for both sexes, in sexual pain (diff −13.6, P = 0.030), communication with professionals (diff −15.5, P = 0.017), and partnership quality (diff −22.8, P = 0.040). The incidence of genital cGVHD was 25.0% among male (n = 11) and 28.1% (n = 9) among females. We conclude that the multimodal intervention was feasible, led to improved sexual health, and facilitated earlier recognition of genital cGVHD, supporting the integration of interdisciplinary sexual health assessments into routine post-HSCT care.
Myelofibrosis (MF), the most severe Philadelphia chromosome-negative myeloproliferative neoplasm, is driven by mutations in JAK2, CALR, or MPL, with CALR mutations accounting for 30–35% of cases. Mutant CALR forms an aberrant complex with the thrombopoietin receptor, resulting in constitutive JAK–STAT signalling and is expressed on the malignant cell surface as a tumour-specific neoantigen absent from normal tissues, making it an attractive therapeutic target. Allogeneic haematopoietic cell transplantation (allo-HCT) remains the only curative treatment but is limited to selected patients with adequate fitness and a suitable donor. This review summarises the rapidly evolving landscape of CALR-directed therapies, including peptide vaccines, the Fc-silenced monoclonal antibody INCA033989, bispecific T-cell engagers, antibody-drug conjugates, and the CAR T-cell therapy RPG4, and explores their potential impact on transplant decision-making. INCA033989 has generated the most mature clinical data, demonstrating improvements in splenomegaly, constitutional symptoms, anaemia and early markers of disease modification, whereas cytotoxic approaches such as CAR T-cell therapy offer the prospect of deeper clonal eradication. Collectively, these therapies have the potential to redefine the role and timing of allo-HCT and expand treatment opportunities in the peri-transplant setting, including the targeted eradication of measurable residual disease following transplantation.
The presence of mutations in basic leucine zipper (bZIP) region of the CEBPA gene in patients with acute myeloid leukemia (AML) is defined as a favorable risk marker according to the guidelines. A total of 173 CEBPA-mutated AML patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) were retrospectively recruited, compared with 345 control patients selected by propensity score matching. Patients carrying CEBPAmut had a better 5-year PFS than CEBPAwt group (60.8% vs. 55.0%, P = 0.016). Failure to achieve complete remission after first induction chemotherapy, the presence of CEBPA mutation before allo-HSCT and the absence of maintenance therapy were proven to be statistically significant factors for worse survival (all P < 0.001). Surprisingly, survival analysis revealed that patients with nontypical in-frame bZIP mutations or harboring both FLT3-ITD and CEBPA mutations had a favorable outcome of PFS (CEBPAin-frame bZIP 59.9% vs. CEBPAno in-frame bZIP 63.3% vs. CEBPAwt 55.0%, P = 0.045; CEBPAmut/FLT3-ITDmut 75.9% vs. CEBPAmut/FLT3-ITDwt 57.3% vs. CEBPAwt 55.0%, P = 0.02). Conversely, the presence of GATA2 mutations showed no benefit. Our findings suggest that CEBPAmut patients with nontypical in-frame shift in bZIP region or with the co-mutation of FLT3-ITD could benefit from allo-HSCT.
