Acta Haematologica最新文献

Introduction: Distress negatively affects cancer outcomes. The National Comprehensive Cancer Network (NCCN) recommends screening patients for distress by a self-reported scale (0-10) and referring those with scores ≥4 to supportive services (SSs). Little is known about the prevalence of distress and healthcare utilization in classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs): polycythemia vera (PV), essential thrombocythemia (ET), myelofibrosis (MF).

Methods: We retrospectively identified MPN patients at our center to measure the proportions of patients with distress ≥4 evaluated by a SS (chaplaincy, integrative oncology, palliative medicine, psychiatry, psychology, and social work [SW]) or had acute care utilization (ACU; ≥ 1 ED visit or hospitalization) within 6 months of electronic distress screening (EDS). We also obtained sociodemographic, disease characteristics, and symptom score data to stratify variables associated with distress.

Results: Among 141 patients (44 PV, 49 ET, and 48 MF), the median age was 63 years (range, 25-89). Most patients identified as female (62%), white (77%), and completed EDS within 3 months of diagnosis (55%). Of 75/141 (53%) who reported distress ≥4, only 25/75 (33%) were evaluated by SS, and 23/75 (31%) had ACU within 6 months of EDS. Patients with distress ≥4 evaluated by SS had significantly higher ACU (48% vs. 14%; p = 0.009). Distress was associated with higher symptom scores and more ED visits but not gender, race, ethnicity, diagnosis, relationship status, or insurance.

Conclusion: Despite consensus recommendations, most patients with distress ≥4 were not evaluated by SS. Future work should identify ways to better use patient-reported outcomes to promote early intervention.

Introduction: The treatment protocols of adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) have evolved, with the advent of pediatric-based regimens, measurable residual disease monitoring, and mutation analysis. Among the latter, previous reports have identified FLT-3 mutations in up to 5% of pediatric patients; however, the full clinical significance of these mutations in the non-pediatric population is still uncertain.

Methods: Our cohort includes AYA patients with ALL treated with the NY-II and BFM protocols at different time periods, allowing analysis of prognostic factors and survival outcomes. Additionally, we analyzed DNA samples for FLT-3 mutations, focusing on the potential prognostic implications and treatment responses within our cohort.

Results: No significant differences were found in overall survival or progression-free survival between the two treatment protocols. However, a higher rate of hematopoietic stem-cell transplantation was noted in the NY-II patients. Older age and high WBC count at presentation were identified as adverse prognostic factors using multivariate analysis. FLT-3 mutations were identified in 4 patients (5%) of the cohort, with only 1 patient having FLT-3 internal tandem duplication mutation and 3 patients having FLT-3-tyrosine kinase domain mutations.

Conclusions: The low rate and variability of FLT-3 mutations in an Israeli cohort precludes broad conclusions regarding their prognostic significance. In our cohort, age and WBC count but not treatment protocol or FLT-3 mutations influenced survival.

Background: Recent advancements in cellular therapies, particularly chimeric antigen receptor T-cells (CAR-T) and T-cell-engaging bispecific antibodies have significantly altered the therapeutic landscape for multiple myeloma. There are two US FDA approved CAR-T products targeting BCMA available for commercial use at this time. Though these innovative therapies have demonstrated considerable efficacy in heavily pretreated multiple myeloma patients, many challenges remain, including accessibility, potential toxicities such as cytokine release syndrome and neurotoxicity and development of resistance through targeted antigen loss and T-cell exhaustion and various other mechanisms. CRISPR edited allogeneic CAR-T cells, CAR-NK cells, and structural makeover of autologous CART with safety switches are being studied to address current limitations in cellular therapy. Additionally, newer target antigens such as GPRC5D, FcRH5, armored CAR-T cells that resist immunosuppressive cytokines such as TGF-β are being investigated.

Summary: This review summarizes safety and efficacy of currently available CART, discusses challenges with these therapies, and ongoing research efforts aimed at addressing resistance, mitigate treatment-related toxicities, and refining for broader applicability and prolonged efficacy.

Key messages: CART cell therapy has shown significant benefit in treatment of multiple myeloma. Many challenges persist. Novel strategies with structural modifications are being incorporated to overcome the limitations.

Background: Managing cancer-associated thrombosis (CAT) is a significant clinical challenge due to several factors such as increased bleeding tendency, frailty, and drug-drug interactions. For many years, the drug of choice for treating CAT was low molecular weight heparin (LMWH). Recently, direct oral anticoagulants (DOACs) entered to the therapeutic milieu of CAT. However, due to the large diversity among patients with CAT in clinical and laboratory characteristics, not all patients will equally benefit from treatment with DOACs. Furthermore, several subgroups of patients with CAT have specific characteristics that influence the anticoagulant decision-making process.

Summary: In this review, we present four different theoretical clinical case scenarios, each representing a different challenge that is associated with thrombosis management; brain metastasis, malignancies of the gastrointestinal tract, drug-drug interactions (DDIs), and thrombocytopenia. By reviewing current literature, we suggest our clinical approach for managing these cases in the era of DOACs.

Key messages: (1) The management of patients with brain tumors and CAT is challenging due to increased risk for both intracranial hemorrhage and recurrent venous thromboembolism. Both LMWH and DOACs are optional treatment in this setting. (2) There are conflicting data regarding the bleeding risk in patients with GI malignancies. Treatment with LMWH should be considered specifically in patients with advanced disease and unresectable tumors. (3) There is a paucity of data regarding DDI in patients with CAT. However, caution should be exercised when prescribing DOACs to patients receiving concurrent medications that either affect DOAC metabolism or influence bleeding risk. (4) The management of patients with CAT and thrombocytopenia depends on the severity of thrombocytopenia and the timing of the thrombotic event.

Introduction: Changes in the number and functional capacity of T lymphocytes have been reported in chronic lymphocytic leukemia (CLL) patients. The aim of this study was to examine the prognostic significance of T-lymphocyte subgroups in CLL patients.

Methods: Eighty-three previously untreated patients were retrospectively enrolled and flow cytometry results at diagnosis were examined. No difference was found in T-lymphocyte parameters according to age, gender, and disease stage.

Results: The CD4 and CD7 percentages, CD4/MBC (malignant B cell), CD8/MBC, and CD7/MBC values at diagnosis were significantly lower in patients with a progressive disease. T-lymphocyte percentages were significantly lower in deceased patients. In the univariate regression model, T-lymphocyte percentages, T-lymphocyte/MBC ratios, HLA-DR+ percentage, Rai stage (intermediate + high risk), Binet stage (B+C), and beta-2 microglobulin level had significant effects on both progression-free survival (PFS) and overall survival (OS); treatment status (yes) had a significant effect only on PFS, while age at diagnosis (≥65 years) had a significant effect only on OS. In the multivariate regression model, Rai stage, CD7/MBC ratio, and treatment status (yes) had a significant effect on PFS; Rai stage and CD8/MBC ratio had a significant effect on OS.

Conclusion: Lower T-lymphocyte/MBC ratios at diagnosis could be a marker for higher risk of CLL progression.

Background: Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) are novel chimeric antigen receptor (CAR)-T cell therapies targeting B-cell maturation antigen (BCMA), and both have recently gained approval by the US Food Drug Administration (FDA) for the treatment of relapsed and refractory multiple myeloma (RRMM).

Summary: These therapies offer unprecedented responses in RRMM but present new challenges including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), non-ICANS neurotoxicity, cytopenias, infections, and hypogammaglobulinemia.

Key messages: In the evolving CAR-T landscape, a primary objective is to develop innovative strategies for managing associated toxicities. Through meticulous exploration of underlying mechanisms and tailored interventions, we aim to enhance safety and enable broader outpatient utilization. Refinement of protocols, biomarker identification, and robust monitoring are imperative for sustained efficacy. This comprehensive approach guarantees the continuous advancement and optimization of CAR-T therapy.

Introduction: We aimed to identify the clinical characteristics and risk factors for chronic immune thrombocytopenia (ITP) in patients with systemic lupus erythematosus (SLE).

Methods: We retrospectively reviewed patients diagnosed with SLE-associated ITP between January 2000 and December 2021. Patient characteristics were analyzed according to the progression of chronic thrombocytopenia. No response was defined as a platelet count <30 × 109/L or less than double the baseline count after treatment. Factors associated with chronic ITP were evaluated by logistic regression analysis.

Results: Among the 121 patients with SLE-associated ITP, 27 progressed to chronic ITP lasting more than 1 year after initial diagnosis. The median initial platelet count was significantly lower in patients with chronic thrombocytopenia than in those without the disease (16 vs. 51 × 109/L). Patients who did not achieve a response within 1 month of treatment exhibited a high probability of progressing to chronic ITP (55.6 vs. 22.3%, p < 0.001). Multivariable analysis revealed that severe thrombocytopenia at baseline (<20 × 109/L) (adjusted odds ratio [aOR] = 13.628, 95% confidence interval [CI] = 3.976-46.791) and no response within 1 month (aOR = 9.171, 95% CI = 2.776-30.298) were significantly associated with the risk of progression to chronic ITP in patients with SLE. Approximately one-quarter of the patients with SLE-associated ITP progressed to chronic ITP.

Conclusion: Severe thrombocytopenia and failure to achieve a response within 1 month were risk factors for the development of chronic ITP in those patients.

Introduction: Treatment of patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (r/r BCP-ALL) remains a significant clinical challenge. Many new strategies are changing the treatment landscape of r/r BCP-ALL in recent years. Blinatumomab has improved outcomes in r/r BCP-ALL, though high treatment costs and extended hospital stays are significant concerns. We considered that shortening the duration of blinatumomab administration during induction therapy might solve these problems.

Methods: We retrospectively analyzed 19 patients with r/r BCP-ALL treated with different durations of blinatumomab, where 10 patients received blinatumomab for 14 days (Bli 14D group) and 9 received it for a longer duration (LT group, 21-28 days).

Results: The overall response rate (ORR) was 63.2% (12/19) of patients in total, and the ORRs in 14D and LT groups were almost the same (60% and 66.6%, respectively). The median overall survival was not reached in either groups. The median event-free survival time was 4.1 months in LT group and not reached in D14 group. The most common adverse events were consistent with previous reports, including cytokine release syndrome, neurologic toxicity, and hematological toxicity.

Conclusion: A 14-day blinatumomab administration may be a promising and well-tolerated regimen in r/r BCP-ALL, offering the same ORR and survival rates.