Acta Haematologica最新文献

Introduction: Accurate prediction of survival in patients with acute myelogenous leukemia (AML) is challenging. Therefore, we developed a predictive survival model using endocrine-related gene expression to identify an endocrine signature for accurate stratification of AML prognosis.

Methods: RNA matrices and clinical data for AML were downloaded from a training dataset (Gene Expression Omnibus) and two validation datasets (the Cancer Genome Atlas and Therapeutically Applicable Research to Generate Effective Treatments).

Results: In relation to the survival outcome, a risk model was constructed by incorporating seven endocrine-related genes. The model exhibited favorable predictive efficacy in estimating 5-year survival rates, as demonstrated by both the training and validation cohorts. Multivariable analysis revealed that the endocrine signature demonstrated autonomous prognostic significance in the aforementioned cohorts. Prediction accuracy for 5-year overall survival increased using a nomogram combining endocrine risk score and classical prognostic factors compared with using classical prognostic factors alone. The model predictions were confirmed using AML cell lines.

Conclusion: The endocrine-related prognostic model established in this study improves AML survival prediction accuracy.

Introduction: Ruxolitinib is approved for treatment of myelofibrosis. We evaluated ruxolitinib in patients with anemia (hemoglobin <10 g/dL) or thrombocytopenia (platelet count ≤100 × 109/L) at diagnosis.

Methods: This was a retrospective, secondary analysis of a Cardinal Health Oncology Provider Extended Network medical chart review of adults with myelofibrosis diagnosed between 2012 and 2016 who received first-line ruxolitinib.

Results: 176 patients received first-line ruxolitinib and were included in this analysis. At diagnosis, 120 patients had hemoglobin concentrations <10 g/dL and 59 had a platelet count ≤100 × 109/L. Most patients (95%) with thrombocytopenia also had anemia. Median time of observation after diagnosis was 21.4 months. Among patients with anemia or thrombocytopenia, ruxolitinib dose at end of study was ≥10 mg twice daily (bid) in 88.3% and 83.1%, respectively. Ruxolitinib treatment was ongoing in 76.1% of patients overall and was rarely discontinued for anemia or thrombocytopenia (n = 2 total, 1.1%). Per the treating physician, 79.7% of patients had improved symptoms and 62.7% improved spleen size.

Conclusion: Most patients with myelofibrosis and anemia or thrombocytopenia at diagnosis tolerated and maintained a ruxolitinib dose ≥10 mg bid for nearly 2 years, resulting in clinical benefit. This real-world evidence supports observations from prospective clinical trials of ruxolitinib in myelofibrosis.

Background: Recent advancements in artificial intelligence (AI) hold significant promise for transforming hemophilia care. Summary: This review explores the impact of AI on critical aspects of hemophilia management, including bleeding risk prediction, biomarker identification, personalized treatment strategies, and patient education. Key Messages: We discuss the application of machine learning models in predicting bleeding risks among children with hemophilia engaging in physical activities, the use of AI in analyzing factor VIII protein structures to determine disease severity, and the development of AI-powered chatbots and digital platforms for patient education and self-management, particularly in resource-limited settings. Furthermore, we address the challenges inherent in implementing AI technologies in clinical practice, such as data privacy concerns, model interpretability, and the need for robust validation. By highlighting current advancements and future directions, we underscore the potential of AI to enhance personalized care and improve outcomes for individuals with hemophilia.

Introduction: Acute promyelocytic leukemia (APL) is genetically characterized by the fusion of promyelocytic leukemia (PML) gene with retinoic acid receptor alpha (RARα) resulting from a t(15;17)(q24;q21) chromosomal translocation. An infrequent but recurrent finding in APL is the formation of an isochromosome of the derivative chromosome 17; ider(17)(q10)t(15;17) or ider(17q). This rearrangement in APL results in an additional copy of the PML-RARα fusion gene as well as loss of 17p/TP53. Due to the infrequent occurrence of the ider(17q), the prognostic impact of this genetic finding is not well known. Case Presentation(s): Here, we describe the clinical characteristics and outcomes of our case series of 5 patients with ider(17q) APL treated at the University of Maryland and Johns Hopkins University.

Conclusion: In our series, patients with APL with ider(17q) did not have a worse prognosis.

Introduction: Distinguishing disseminated intravascular coagulation (DIC) from the coagulopathy of liver disease represents a common clinical challenge. Here, we evaluated the utility of two diagnostic tools frequently used to differentiate between these conditions: factor VIII (FVIII) levels and the International Society on Thrombosis and Hemostasis (ISTH) DIC score.

Methods: To this end, we conducted a retrospective chart review of patients with DIC, liver disease, or both. Multiple logistic regression was performed, and receiver operating characteristic curves were generated to calculate the area under curve (AUC) for distinguishing DIC in the setting of liver disease.

Results: Among 123 patients with DIC, liver disease, or liver disease plus DIC, FVIII levels did not differ significantly. ISTH scores were lower in patients with DIC than in liver disease with or without DIC. Addition of several laboratory parameters to the ISTH score, including mean platelet volume, FV, FVIII, international normalized ratio, and activated partial thromboplastin time, improved AUC for distinguishing DIC in liver disease from liver disease alone (AUC = 0.76; p < 0.0001).

Conclusion: We conclude that FVIII levels do not distinguish DIC from liver disease, and ISTH DIC scores are not predictive of DIC in patients with liver disease. Inclusion of additional lab variables within the ISTH DIC score may aid in identifying DIC in patients with liver disease.

Background: Advances in novel therapies have improved outcomes for multiple myeloma (MM) patients and the use of allo-SCT has decreased. Current guidelines no longer support allo-SCT as consolidation therapy for newly diagnosed MM, even in high-risk cases.

Summary: Allo-SCT is now typically considered only within clinical trials for young, high-risk patients with relapsed or refractory MM (RRMM). It has not proven favorable despite its historical use. CAR T-cell therapy and bispecific antibodies have shown promise in treating triple- and penta-exposed/refractory MM, yet relapse remains common with poor survival rates. The efficacy of allo-SCT following BCMA-directed therapy and other new T-cell-directed therapies is unclear. Allo-SCT might be a viable option for eligible patients who relapse after these therapies, or where such options are unavailable. Advancements in reduced-intensity conditioning regimens have led to lower toxicity and transplant-related (TR) morbidity, lower graft-versus-host disease (GvHD), and TR mortality. Expanded use of alternative donors, like haploidentical donors, has yielded comparable outcomes. Better post-transplant GvHD regimens and maintenance strategies to prevent relapse have been developed.

Key messages: This review analyzes available literature to better understand the safety, efficacy, and current role of allo-SCT in managing MM. Newer regimens are needed as routine use of allo-SCT cannot be recommended.

Background: High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) has become part of standard of care (SOC) in newly diagnosed multiple myeloma. In this review, we provide a historical perspective on ASCT since its introduction in the 1990s.

Summary: Overall survival (OS) benefit for HDT followed by ASCT was demonstrated in studies comparing HDT with ASCT to standard-dose therapy (SDT) before the era of novel agents. Conditioning is done with melphalan 200 mg/m2. Lower doses (MEL140, MEL150) for older patients with comorbidities are safe and have comparable results. The addition of busulfan to melphalan improves progression-free survival (PFS) but not OS. HDT with ASCT after induction with novel agents prolongs PFS but not OS compared to SDT alone. The benefit is more evident in patients with high-risk cytogenetics. Mobilization can be achieved with granulocyte colony-stimulating factor alone, but is improved with the addition of chemotherapy. Plerixafor reduces mobilization failure and enables sufficient stem cell collection after induction with novel agents. ASCT is safe with a low rate of mortality (1%), and selected patients can be managed as outpatients.

Key messages: HDT followed by ASCT remains part of SOC due to its PFS benefit and relatively low toxicity.