Annals of Hematology最新文献

Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are severe myeloid disorders associated with significant morbidity and mortality. Because of patient and disease factors, many older adults are treated as outpatients with less-intensive therapy. Optimal supportive care strategies to minimize bleeding and infectious complications in this patient population have not been systematically evaluated. We conducted a survey of Canadian hematologists to explore current practice in the use of tranexamic acid (TXA) and prophylactic antimicrobials in patients with MDS/AML treated with less-intensive therapy, and to evaluate equipoise for future trials. Survey items were generated through a combination of literature review and discussion with content experts. The survey was disseminated to 304 potential respondents with a response rate of 52%. Prophylactic platelet transfusions were used by 95%, while prophylactic TXA was used by 57%; the most frequent reason for not using TXA was uncertainty about benefit or harm. Use of prophylactic antimicrobials varied by chemotherapy regimen. If antimicrobial prophylaxis was used, the most frequently prescribed antibacterials were fluroquinolones (90%) and trimethoprim/sulfamethoxazole (21%); the most commonly used antifungals were fluconazole (66%) and voriconazole (36%). The most common reason for not using prophylactic antimicrobials was insufficient evidence of benefit. Most respondents agreed that clinical trials are needed to define the use of TXA and prophylactic antimicrobials in this patient population. Among survey respondents, there was variation in the use of supportive care strategies to address bleeding and infection risk in older adults with MDS/AML. The results of this survey will help to inform clinical trials to assess the benefits and risks of these prophylactic strategies.

Up to one-third of patients with classical Hodgkin lymphoma (cHL) are not responsive to first-line therapy or eventually relapse. Immune checkpoint inhibitors (ICIs) have been successfully employed to treat relapsed/refractory cHL (r/r cHL) but place patients at risk of financial toxicity. Early-phase trials and observational data suggest that low doses of ICIs may achieve similar results to those obtained with high doses. In this study, we report a single-center experience using low-dose nivolumab (LD-Nivo) in different combinations for r/r cHL, including monotherapy, LD-Nivo plus brentuximab vedotin (BV), and LD-Nivo plus chemotherapy. The primary outcome was to assess the efficacy of LD-nivo in patients with r/r cHL. We included 23 consecutive patients (median age 27 years; 57% female). LD-Nivo was prescribed in 40, 100, and 140 mg fixed doses Q2W. Survival analysis was performed employing the Kaplan-Meier method. 73% of patients achieved an overall response, 43% complete response, and 30% partial response. One-year overall survival was 94.4% (95% CI, 0.84-1), and the 1-year progression-free survival was 89.4% (95% CI, 0.77-1). OS and PFS were similar accross combinations. The median dose of nivolumab was 0.78 mg/kg (range, 0.62-1.11), and the median number of cycles until a response was documented was 6 (range, 2-9). During follow-up, 18 patients received transplantation (11 autologous, 6 allogeneic). No statistically significant differences in survival or response were detected between nivolumab combinations or doses. Adverse events were observed in 61% of the patients, with none grade 3-4. LD-Nivo demonstrated promising results in relapsed/refractory HL, highlighting its potential as a cost-effective treatment option. Further research is needed to validate these findings and guide clinical practice.

This study aimed to investigate the prognostic relevance of cytogenetic risk in 9826 adults with acute myeloid leukemia (AML) who underwent allogeneic hematopoietic cell transplantation (HCT) during the first or second complete remission. The 5-year probabilities of overall survival (OS) were 66%, 61%, and 47% (P < 0.001), the cumulative incidences of relapse were 14%, 19%, and 32% (P < 0.001), and the cumulative incidences of non-relapse mortality (NRM) were 23%, 23%, and 25% (P = 0.208) in patients with favorable (n = 1418), intermediate (n = 6747), and poor cytogenetic risk (n = 1661), respectively. The significant effect of cytogenetic risk on OS was strong in all subgroups stratified by age, sex, performance status, disease status, donor type, conditioning intensity, graft-versus-host disease prophylaxis, and transplantation period (P < 0.001 for all). The evaluation of trends in posttransplant outcomes for patients in each cytogenetic risk category indicated that the risk of relapse declined in patients with favorable and intermediate cytogenetics and that the risk of NRM decreased in those with intermediate and poor cytogenetics. Therefore, patients with intermediate cytogenetics experienced the best OS improvement. These results confirm cytogenetic risk as a universal prognostic factor in patients with AML undergoing allogeneic HCT while highlighting the requirement for further improvements in posttransplant OS by reducing NRM in patients with favorable cytogenetics and by reducing relapse in patients with poor cytogenetics.

PD-1 inhibitors have shown unconventional response patterns in classic Hodgkin lymphoma (cHL). These include the phenomenon of pseudoprogression, highlighting the need for specialized response criteria such as the LyRIC, which stringened definitions for disease progression with introduction of indeterminate response category. Despite their potential utility, these provisional criteria are currently underutilized and require further refinement through clinical practice data collection. In this retrospective study LyRIC criteria were systematically used for response assessments in 180 patients with refractory cHL treated with nivolumab. Median follow-up was 60 months. Indeterminate response (IR) was a frequent phenomenon in study population: at 3 months of therapy 63 (35%) patients had an indeterminate response (IR1 7%, IR2 23%, IR3 6%). Among them 18 (29%) achieved an objective response with continued monotherapy. There were no differences in OS or TTNT depending on the type of IR. IR was the best achieved response in 45 (25%) patients. Patients with IR had favorable prognosis with no difference in OS, PFS and TTNT comparing to patients with PR when subsequent therapy was initiated due to disease progression. Patients with IR may achieve prolonged disease control or a deeper response upon continuing treatment. These findings support the broader implementation and adjustment of LyRIC criteria in clinical practice to enhance decision-making in cHL patients treated with immunotherapy.

This study describes the health-related quality of life (HRQoL) and symptom-specific functional impairment of patients with paroxysmal nocturnal hemoglobinuria (PNH) in a real-world setting. US-based adults with PNH treated with a parenterally administered complement inhibitor (PACI) for ≥ 6 months completed an online, cross-sectional, observational survey; a subset of patients also participated in semi-structured qualitative interviews. The survey included the PROMIS^® 29 + 2 Profile v2.1 (PROMIS 29 + 2) to measure HRQoL. The FACIT-Fatigue, Neuro-QOL Item Bank v2.0 Cognitive Function Short Form, and PROMIS Item Bank v1.0 Dyspnea Functional Limitations 10a Short Form measured symptom-specific functional impairment. For each patient with PNH who completed the online survey, 3 age- and sex-matched adults from the general population (GP) also completed the survey. The HRQoL and functional impairment of the PNH sample were compared to that of the GP sample. The association between HRQoL/functional impairment and fatigue severity for the PNH sample was also investigated. Compared to the age- and sex-matched GP sample, patients treated with PACIs for PNH had significantly worse HRQoL and greater functional impairment for all measured domains (p < 0.05). Within the PNH sample, statistically significant associations (p < 0.05) were observed between fatigue severity and HRQoL/functional impairment for all outcomes except the PROMIS 29 + 2 Sleep Disturbance domain. Interview participants described fatigue-related impairments in their physical, social, and cognitive functioning. Despite receiving treatment for PNH, patients experienced deficits in HRQoL and functional impairment, suggesting that opportunities to improve patient-relevant outcomes through treatment should be identified.

Indolent B-cell non-Hodgkin lymphomas(B-NHL) encompass a heterogeneous category of lymphomas characterized by a wide range of pathological subtypes. With the application of chemoimmunotherapy with rituximab (R-chemo), the prognosis of patients has improved considerably, with a 10-year survival rate of 60-80%. Despite these advancements, a significant number of patients still experience disease progression during or shortly after initial treatment. Those who progress within the first 24 months (POD24) continue to face a notably worse prognosis. This study aims to explore the significance of POD24 in predicting the prognosis of different subtypes of indolent B-cell NHL through a comprehensive literature review. The investigation extends to examining the existing prognostic assessment tools and evaluating the interrelationship between POD24 and these tools. By synthesizing relevant research findings, this study seeks to contribute to the current understanding of the role POD24 plays in prognostic evaluation and its potential implications in guiding clinical decision-making for patients with indolent B-cell NHL.

Early immune reconstitution, particularly of natural killer (NK) cells with strong graft-versus-leukemia effects, is crucial for the prognosis of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective study examined 122 pediatric patients with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) who underwent T-cell replete allo-HSCT at the Children's Hospital of Soochow University from 2019 to 2021. Peripheral blood lymphocyte counts on days 30 and 60 post-transplant were analyzed, focusing on NK cell recovery and its impact on overall survival (OS), relapse-free survival (RFS), non-relapse mortality (NRM), relapse, graft-versus-host disease, and CMV reactivation. Patients were categorized into high and low NK cell groups by the median NK cell counts at day 30 (NK30) and day 60 (NK60) after HSCT. Patients with high NK30 and NK60 levels had significantly better 3-year OS rates compared to their respective low NK count groups (86.8% ± 4.7% versus 67.6% ± 7.0%, P = 0.046; 95.7% ± 3.0% versus 63.7% ± 8.7%, P < 0.001, respectively). NK60 was found to be an independent predictor for 3-year OS and RFS in multivariate analysis. Early NK reconstitution was also related to lower NRM rates. However, this correlation disappeared in patients with ALL and those undergoing haploidentical transplantation. In addition, A positive association between early T cell and NK cell reconstitution was found in our study. Higher NK cell counts on days 60 can predict superior OS, RFS and lower NRM in pediatric AML allo-HSCT patients.

Vacuoles, E1 enzyme, X-linked, auto inflammatory, somatic (VEXAS) syndrome is an inflammatory disorder caused by somatic UBA1 variants and is characterized by late-onset systemic autoimmune inflammation and blood abnormalities. Glucocorticoids ameliorate symptoms effectively. However, other treatment options have limited efficacy and a transient effect. Herein, we describe a case of a 69-year-old male patient with VEXAS syndrome with skin, lung and hematologic involvement. He was treated with glucocorticoids and after the failure with anti IL-1 he began treatment with azacitidine with excellent hematological and clinical response. Azacitidine may be a suitable option for treating VEXAS syndrome, especially due to the relationship between inflammatory symptoms and response to azacitidine.

Background: Recent breakthrough advances in the treatment of DLBCL, such as the antibody-drug conjugate polatuzumab vedotin, have yielded clinical survival benefit over rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) for the first time in 20 years since the advent of the rituximab era. We thus examine the outcomes of standard immunochemotherapy for DLBCL in our multi-ethnic Asian population, so as to determine the real-world clinical need to adopt new therapeutics in this disease entity.

Methods: We conducted a retrospective study involving patients (n = 1071) diagnosed with DLBCL at the National Cancer Centre Singapore from 2010 to 2022, and treated with first-line rituximab-based regimens. The median follow-up duration was 48 months. Survival analyses were performed using the Kaplan-Meier method and multivariate Cox proportional models.

Results: The cohort consisted of 590 male and 481 female patients with a median age of 63.8 years (range, 19.3-93.6). Most were stage III-IV at diagnosis (60.9%) and of non-germinal center B-cell like (non-GCB) subtype by Han's criteria (56.5%). The vast majority received R-CHOP(-like) regimens (n = 997, 93.1%), including rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (EPOCH-R) (n = 95), achieving a 5-year progression-free survival (PFS) and overall survival (OS) of 64.5% and 74.7% respectively. Male sex (p = 0.0294), age > 60 years (p < 0.0001), poor ECOG scores (2-4) (p < 0.0001), advanced stage (III-IV) (p < 0.0001), presence of B-symptoms (p = 0.0305), and raised LDH (p = 0.0161) were independent predictors of OS, 4 of which are risk factors in the International Prognostic Index (IPI). In the intermediate to high-risk subgroup (IPI scores 2-5; n = 752), the 5-year PFS and OS were only 59.0% and 69.8% respectively. EBV status, MYC and/or BCL2/BCL6 rearrangements, were not significantly associated with survival outcomes. EPOCH-R was used more frequently than R-CHOP in patients with MYC rearrangements (n = 82, p < 0.0001), including those with MYC/BCL2 double-hit genetics (n = 31, p < 0.0001). Notably, neither regimen significantly affected survival outcomes, both in MYC-rearranged (PFS: HR 0.60, p = 0.1704; OS: HR 0.49, p = 0.0852), and in MYC/BCL2 double-hit DLBCL (PFS: HR 1.30, p = 0.6433; OS: HR 1.02, p = 0.9803).

Conclusion: Our study demonstrates that our local population has similar clinicopathological and prognostic characteristics of DLBCL as compared to global findings. It also highlights the limitations of R-CHOP(-like) regimens in contemporary DLBCL management and therefore an ongoing need for improved therapeutic strategies.