American Journal of Hematology最新文献

In our study, we identified a novel, ruxolitinib-sensitive, CCDC6::JAK2 fusion gene as a driver of atypical JAK2-unmutated MPN with a polycythemic phenotype. The CCDC6::JAK2 chimeric protein retains the CCDC6 coiled-coil domain and the JAK2 kinase domain. Dimerization of chimeric proteins through coiled-coil domains promotes JAK2 autophosphorylation leading to constitutive activation of the JAK/STAT signaling pathway.

Chronic kidney disease (CKD) is common and a major contributor to increased morbidity and early mortality in people with sickle cell anemia (SCA). Urine albumin-to-creatinine ratio (uACR) is recommended to identify patients with SCA-related CKD but its utility in predicting long-term kidney dysfunction remains unclear in this patient population. In two independent, longitudinal cohorts of patients with hemoglobin SS or Sβ⁰-thalassemia (USA: n = 268, median follow-up 6 years; France: n = 310, median follow-up 8.2 years) we investigated the utility of uACR, as well as other clinical and modifiable risk factors, for predicting a decline in kidney function as determined by the rate of estimated glomerular filtration rate (eGFR) decline. Using linear mixed-effects models, a higher baseline uACR independently predicted a faster rate of eGFR decline as well as a more rapid annual eGFR decline, defined as ≥ 3 mL/min/1.73m² (p ≤ 0.009). Furthermore, baseline uACR of ≥ 100 mg/g creatinine was independently associated with the rate of eGFR decline and rapid annual eGFR decline in both cohorts. Tobacco smoking was also associated with a faster rate of eGFR decline and was congruous between the two cohorts. In conclusion, we demonstrate that uACR is an important clinical tool that predicts a more rapid decline in kidney function and should be routinely monitored in people with SCA. Our data also support preventative care to reduce tobacco smoking for mitigating the risk of CKD progression in this high-risk population.

Polyfunctional cytomegalovirus (CMV)-specific T cells are critical for antiviral immunity in allogeneic hematopoietic cell transplantation (HCT) recipients. However, gaps remain in managing refractory CMV and optimizing virus-specific cellular therapy (VST). We conducted a comparative analysis of how timing and dosing of immunosuppressive agents, including post-transplant cyclophosphamide (PT-Cy), corticosteroids, mycophenolate mofetil (MMF), and calcineurin inhibitors (CNIs), shape CMV-specific T-cell polyfunctionality. CD4⁺ and CD8⁺ T-cell responses (IFN-γ plus ≥ 1 functional marker) were assessed following pp65 stimulation within 100 days post-HCT in the pre- and post-letermovir era. Among 243 patients, 31% exhibited polyfunctional CD4⁺ and CD8⁺ responses. PT-Cy did not significantly impair T-cell functionality. Cyclosporine was associated with higher frequencies of polyfunctional T cells compared to tacrolimus, even at concentrations above the therapeutic range. Intermediate (≥ 0.5 mg/kg) and high-dose (≥ 1 mg/kg) corticosteroids, especially within 2–4 weeks before testing, significantly suppressed T-cell responses, though rapid tapering preserved function. Prolonged administration of MMF (≥ 2000 mg) diminished T-cell polyfunctionality. These findings provide novel insights into the importance of timing and dosing of the immunosuppressive effects of PT-Cy, corticosteroids, MMF and CNIs on CMV-specific immunity. Adjusting immunosuppression in specific time windows may improve the management of refractory CMV infections and optimize VST in HCT recipients.

M. Malagola, L. Castagna, D. Matranga, et al., “Outcome of Patients With Acute Myeloid Leukemias or Myelodysplastic Syndromes After Relapsing From Allogeneic Stem Cell Transplantation: The GITMO AML/MDS-Relapse Registry Study.” American Journal of Hematology 100, no. 10 (2025): 1902–1905. https://doi.org/10.1002/ajh.70030.

In this article, the authorsʼ names were incorrect. The correct list is below:

Michele Malagola^1,2, Luca Castagna³, Domenica Matranga⁴, Vera Radici^1,2, Mirko Farina^1,2, Marco Galli^1,2, Eugenia Accorsi Buttini⁵, Vicky Rubini⁶, Caterina Alati⁷, Simona Bassi⁸, Alessandra Biffi⁹, Carlo Borghero¹⁰, Alessandro Busca¹¹, Chiara Nozzoli¹², Angelo Michele Carella¹³, Irene Cavattoni¹⁴, Raffaella Cerretti¹⁵, Patrizia Chiusolo¹⁶, Michele Cimminiello¹⁷, Angela Cuoghi¹⁸, Marco De Gobbi^19,20, Federico Vincenzo²¹, Piero Galieni²², Anna Paola Iori²³, Attilio Olivieri²⁴, Matteo Parma²⁵, Francesca Patriarca²⁶, Vincenzo Pavone²⁷, Alessandra Picardi²⁸, Eugenia Piras²⁹, Nicola Polverelli³⁰, Lucia Prezioso³¹, Benedetta Rambaldi³², Elvira Scalisi³³, Carmine Selleri³⁴, Cristina Skert³⁵, Alessandro Spina³⁶, Cristina Tecchio³⁷, Elena Oldani³², Eliana Degrandi³⁸, Domenico Russo^1,2, Massimo Martino⁷

We apologize for this error.

Compared to historical reports, both aGVHD and cGVHD appeared to have decreased in the recent transplant era, possibly due to the extension of T-cell depletion, the availability of effective second-line approaches in SR/D GVHD and improved anti-infectious prophylaxis and treatments.

Gilteritinib is a selective FLT3 inhibitor approved for the treatment of relapsed or refractory (R/R) FLT3-mutated acute myeloid leukemia (AML) following ≥ 1 prior line of therapy. However, data on its effectiveness in later-line settings is limited. We conducted a multicenter, retrospective study including 171 adult patients with R/R FLT3-mutated AML who received gilteritinib as third-line or beyond between August 2017 and March 2024 across centers in Italy, Spain, the United Kingdom, and Turkey. The primary endpoint was overall survival (OS). Secondary endpoints included overall response rate (ORR), composite complete remission (cCR), duration of response. Among the 171 patients, 84% carried FLT3-ITD mutations and 26% had received ≥ 3 prior lines of therapy. The cCR rate was 28%, and ORR was 47%. Patients who were younger and presented with relapsed (vs. refractory) disease had better outcomes. Prior exposure to venetoclax or allogeneic hematopoietic stem cell transplantation (HSCT) was associated with inferior response. Gilteritinib enabled HSCT in 12% of patients. Median OS was 7.1 months (95% CI, 5.9–10.1), and in Cox-regression analysis was significantly improved among responders and those who underwent HSCT (median OS: 21.5 months; 95% CI, 12.8–NR). Prior venetoclax exposure was associated with shorter survival (5.7 months; 95% CI, 5.1–8.8). On multivariate analysis, previous exposure to venetoclax and FLT3 inhibitors was the strongest predictor of reduced response rates. Despite heavy pretreatment, gilteritinib retained clinically relevant activity in later-line R/R FLT3-mutated AML. Its use beyond second-line may serve as a bridge to HSCT in selected patients. Resistance mechanisms, particularly following venetoclax, remain a therapeutic challenge. These data support the continued use of gilteritinib beyond second-line and highlight the need for prospective studies to optimize sequencing strategies.