Annals of Hematology最新文献

This retrospective cohort study examined the association between radiotherapy and prognosis in follicular lymphoma (FL) patients, with stratification by age, Ann Arbor stage, primary tumor site, surgical status, and grade. Using data from the SEER database, we employed Cox proportional hazards and competing risk models to assess the impact of radiotherapy on overall survival (OS) and cancer-specific survival (CSS) in 7,551 FL patients. The association between radiotherapy and second primary cancer (SPC) was explored using Logistic regression model. At the end of the 60-month follow-up, 6,053 patients were alive, while 1,498 had died. The overall result showed that radiotherapy was associated with the better OS [hazard ratio (HR): 0.70, 95% confidence interval (95%CI): 0.59-0.83, P < 0.001] and CSS (HR: 0.67, 95% CI: 0.52-0.87, P = 0.002)) in FL patients. Radiotherapy was associated with improved OS and CSS in patients aged ≥ 60 years [OS: HR: 0.65, CI: 0.53-0.79; CSS: HR: 0.63, CI: 0.52-0.77], early Ann Arbor stage (OS HR: 0.51, CI: 0.40-0.65; CSS HR: 0.51, CI: 0.40-0.65), primary sites at lymph nodes (OS HR: 0.76, CI: 0.62-0.93; CSS HR: 0.76, CI: 0.62-0.93) and skin/soft tissue (OS HR: 0.35, CI: 0.16-0.81; CSS HR: 0.36, CI: 0.16-0.82), and in both surgical (OS HR: 0.70, CI: 0.52-0.93; CSS HR: 0.70, CI: 0.52-0.93) and non-surgical patients (OS HR: 0.71, CI: 0.56-0.89; CSS HR: 0.69, CI: 0.55-0.87). Radiotherapy showed no significant association with second primary cancer (SPC) risk. These findings suggest radiotherapy improves 5-year survival outcomes in FL patients during the rituximab era.

The efficacy and safety of total marrow irradiation (TMI) plus a reduced dose of melphalan as autologous stem cell transplantation (ASCT) preconditioning for multiple myeloma (MM) patients were evaluated. The 11 patients with MM had a median age of 57 (range: 46-75) years; six of them were at standard risk and five of them were at high risk based on the Mayo Stratification of Myeloma and Risk-adapted Therapy (mSMART) standard risk factors. Before ASCT, three patients achieved stringent complete response (sCR), two patients achieved complete remission (CR), and the rest of the patients had either partial response (PR) or progressive disease. Most of the 11 patients were pretreated with melphalan 120-140 mg/m² and TMI 12 Gy. The intravenous infusion median mononuclear cell count (MNC) was 8.13 (4.16-11.84) × 10⁸/kg, and the median CD34⁺ count was 4.74 (2.51-21.98) × 10⁶/kg. The minimal residual disease (MRD) in the grafts as determined by flow cytometry (FCM) and fluorescence in situ hybridization (FISH) were negative in 10 patients but positive in the progressive patient. All patients stopped maintenance therapy after transplantation, and further observation focused on the efficacy and tolerability of the transplantation. The neutropenic and thrombocytopenia durations were 11 (7-28) and 14 (8-70) days, respectively. The primary acute non-hematological toxicities were mild oral and gastrointestinal mucositis; there were no transplant-related deaths or serious complications. Of the eight patients who did not achieve sCR before transplantation, seven converted to sCR and one converted to VGPR after transplantation. The median follow-up period was 24 (10-57.5) months. Only one patient relapsed, and the progression-free survival (PFS) was 90.9%, while the overall survival (OS) was 100%. Our preliminary results suggest that melphalan 120-140 mg/m² plus TMI 12 Gy/6f as a conditioning regimen is safe and efficient for patients with MM.

Primary head and neck mucosa-associated lymphoid tissue lymphoma (HN-MALT) is a rare lymphoma with unknown incidence and prognosis. We allocated HN-MALT data from the Self-Surveillance, Epidemiology, and End Results database (2000-2021) into training and validation cohorts at a 7:3 ratio. A joinpoint regression analysis was used to examine sex-specific and age-group morbidities, and independent prognostic factors were identified through multivariate Cox analysis to construct a nomogram prediction model and verify the accuracy of prediction. A total of 2,517 patients with HN-MALT were randomly divided into training (1,762) and validation (755) groups. The incidence of HN-MALT in men and women decreased from 2007 to 2021, with an annual percent change (APC) of -3.04% (95%: -4.4 - -1.6, P < 0.05), while in the ≥ 60 years old group, the incidence decreased significantly from 2016 to 2021, with an APC of -8.20 (95%: -13.9 - -2.1, P < 0.05). The multivariate Cox analysis revealed that male, ≥ 60 years old, white, and divorced/separated/widowed were independent risk factors of the overall survival and lymphoma-specific survival. A nomogram prediction model was constructed based on the Cox regression results for multiple factors, the areas under the curve, the calibration curve, and decision curve analysis results of which indicated that the nomogram prediction model performed very well. HN-MALT cells exhibit distinctive clinical and pathological characteristics. Furthermore, we developed a nomogram model for the prognostic assessment to offer valuable guidance for clinical decision-making.

Central nervous system (CNS) involvement in Waldenström macroglobulinemia (WM) is a rare complication that can manifest as Bing-Neel syndrome (BNS) or as histological transformation (HT) to diffuse large B-cell lymphoma (DLBCL). We report data from a single-center cohort of 469 patients consecutively diagnosed with WM between 2000 and 2022. BNS was identified in 1.5% (n = 7) and HT with CNS involvement (CNS-HT) in 1.7% (n = 8) of patients. The cumulative incidence of BNS and CNS-HT at 15 years was 2.6% and 2.7%, respectively, with CNS-HT more likely to develop in closer proximity to the initial WM diagnosis. One patient with CNS-HT exhibited a preceding phase of BNS before transformation. In general, patients with BNS and CNS-HT presented with diverse neurological symptoms and clinical features. Parenchymal lesions were uniformly found in all patients with CNS-HT, while neuroimaging findings were less consistent in patients with BNS. Involvement of multiple extramedullary sites was observed in approximately half of the patients with both BNS and CNS-HT. Patients with CNS-HT had poor outcomes, with a median overall survival of 10 months following the onset of CNS involvement, whereas BNS was associated with a more favorable prognosis, particularly in patients treated with ibrutinib. This study is the first to present a comparative analysis of BNS and CNS-HT in WM, providing novel insights into their incidence, clinical features, and outcomes.

The advent of BTK inhibitors has been transformative in the management of patients with chronic lymphocytic leukemia or other B-cell lymphoproliferative disorders. However, emergence of BTK or PLCG2 mutations lead to resistance to these compounds and are now a growing concern in clinical practice. Assessing BTK mutations is now becoming a priority to guide the therapeutic decision at further relapse. To this end, targeted next-generation sequencing (NGS) is a valid tool, but lack of sensitivity and the required time for delivering results remain major challenges. Digital PCR could be more sensitive but is also limited by the number of mutations that can be screened. We here overcame these challenges by multiplexing digital PCR (mdPCR) in three assays that can cover 96% of ibrutinib-resistant cases. We investigated a cohort of 28 patients progressing on ibrutinib and for whom NGS revealed BTK mutations (C481S, C481F and C481R) and/or PLCG2 R665W mutation. Overall, 49 mutations were detected by NGS and 68 by mdPCR. We found mdPCR to bemore sensitive than NGS, particularly at low allelic frequencies, making it more suitable for the detection and quantification of small mutated clones. Thus, mdPCR offers high sensitivity, is expected to be more rapid and cost-effective than NGS in detecting resistance mutations to improve the therapeutic choice at relapse after exposure to BTK inhibitors.

The aim of this study was to develop and validate a nomogram predicting progression-free survival (PFS) for adult patients with positive acute lymphoblastic leukemia(Ph + ALL) who have undergone allogeneic hematopoietic stem cell transplantation(allo-HSCT) and tyrosine kinase inhibitor(TKI) treatment. Data were retrospectively collected from 176 adult patients diagnosed with Ph + ALL and treated with allo-HSCT and TKIs at The First Affiliated Hospital, Zhejiang University School of Medicine, between January 2015 and May 2023. 70% of the patients were randomly assigned to the training group(n = 124) and 30% of the patients were assigned to the validation group(n = 52). Univariate Cox regression analysis and Akaike Information Criterion(AIC) were utilized to identify significant predictive factors, leading to the development of a nomogram designed to forecast the probability of PFS at 6, 9, and 12 months post-transplantation. The final nomogram incorporated three key variables: presence of complex additional cytogenetic abnormalities (ACAs), minimal residual disease (MRD) status prior to allo-HSCT, and IKZF1 gene deletions. The calibration curves showed excellent consistency between the nomogram prediction and actual observation for 6-, 9- and 12-month PFS in the training set and validation set. The C-index of the training set was 0.726(95%CI: 0.635-0.816), which was no significantly different from the validation set(C-index = 0.774, 95%CI: 0.674-0.875, P > 0.05). This study may provide a simple and efficient prediction model for patients with Ph + ALL undergoing allo-HSCT and TKIs, which can accurately predict PFS subsequent to transplantation. This tool could potentially aid clinicians in decision-making processes and improve patient outcomes.

Early T-precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) is a rare and aggressive subtype of T-cell leukemia with poor prognosis and resistance to standard treatments. We report a 21-year-old male with ETP-ALL/LBL who, after an initial complete remission with the HOELZER protocol, experienced early relapse and was refractory to subsequent FLEND and BFM protocols. Following disease progression and complications, he was treated with a combination of daratumumab, venetoclax, azacitidine, and dexamethasone. This regimen achieved complete remission after one cycle. This case highlights the potential of this combination therapy as an effective treatment for refractory ETP-ALL/LBL, suggesting further research is warranted to validate its efficacy and safety.

Post-transplant cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are mainstay prophylactic treatment options for graft-versus-host disease (GVHD), widely used in haploidentical stem cell transplantation. Due to a lack of prospective studies, a number of retrospective comparisons have yielded different conclusions as to which prophylaxis regimen is superior. We performed a meta-analysis of these studies to get more informed and comprehensive decisions from clinicians. Nine studies were eligible, and a total of 1674 patients were included. The combined hazard ratio (HR), relative risk (RR), and weighted mean difference (WMD) results demonstrated that, compared with ATG, PTCy demonstrated better overall survival (OS) (HR 0.7, 95% CI 0.51-0.97), leukemia-free survival (LFS) (HR 0.66, 95% CI 0.53-0.81), and GVHD-free/relapse-free survival (GRFS) (HR 0.79, 95% CI 0.65-0.97); faster lymphocyte reconstitution, lower risk of relapse (HR 0.69, 95% CI 0.53-0.9) and fungal infection (RR 0.23, 95% CI 0.07-0.79). However, neutrophil engraftment was delayed in the PTCy regimen group (WMD 3.29, 95% CI 2.49-4.10). No statistically significant differences were observed in the time to platelet engraftment, bacterial infection, or viral infection, including cytomegalovirus, polyomaviruses BK/JC and Epstein-Barr virus. Nor was any statistically significant difference observed in the incidences of II-IV acute-GVHD (aGVHD) (HR 0.81, 95% CI 0.62-1.05), III-IV aGVHD (HR 0.67, 95% CI 0.22-2.19) or severe chronic-GVHD (cGVHD) (RR 1.22, 95% CI 0.51-2.88), or non-relapse mortality (NRM) outcomes (HR 0.67, 95% CI 0.4-1.11). Therefore, in haploidentical transplantation, PTCy accelerates lymphocyte reconstitution, significantly reduces the risk of recurrence and fungal infection, and improves the OS, LFS and GRFS, compared with ATG, with no significant difference in the efficacy of preventing acute or severe cGVHD, or the risk of bacterial or viral infection.

This study investigated the importance of comprehensive genetic diagnosis in pediatric B-cell acute lymphoblastic leukemia (B-ALL). We analyzed 175 B-ALL employing karyotyping, FISH, MLPA, targeted next-generation sequencing (t-NGS), and Optical Genome Mapping (OGM). This approach achieved an 83% classification rate, identifying 17 distinct genetic subtypes. Specifically, within B-other subtype, seven different subgroups were identified (ZNF384, IGH, DUX4, NUTM1 rearrangements, PAX5 alterations, PAX5 P80R, and IKZF1 N159Y). Secondary genetic alterations were observed, with copy number alterations (CNA) present in 60% of cases and mutations detected in 70.6%. While these alterations exhibited specific associations with certain genetic subtypes, CNAs did not appear to significantly impact the prognosis within these genetic groups. HeH, ETV6::RUNX1, ZNF384-r, and PAX5 P80R exhibited excellent outcomes, contrasting with the poor prognoses observed in KMT2A-r, hypodiploidy, and CRLF2-r (5-year overall OS were 50%, 50%, and 52%, respectively). These findings underscore the value of integrated genetic diagnostics for accurate subtyping, risk stratification, and guiding personalized treatment in pediatric B-ALL. Therefore, optimizing diagnostic workflows for routine clinical practice is crucial. Our study confirms the utility of conventional techniques (karyotyping and FISH), combined with t-NGS and OGM, for comprehensive genetic diagnosis.

Folates serve as key enzyme cofactors in several biological processes. Folic acid supplementation is a cornerstone practice but may have a "dark side". Indeed, the accumulation of circulating unmetabolized folic acid (UMFA) has been associated with various chronic inflammatory conditions, including cancer. Additionally, by engaging specific folate receptors, folates can directly stimulate cancer cells and modulate the expression of genes coding for pro-inflammatory and pro-fibrotic cytokines.This evidence could be extremely relevant for myelofibrosis (MF), a chronic myeloproliferative neoplasm typified by the unique combination of clonal proliferation, chronic inflammation, and progressive bone marrow fibrosis. Folate supplementation is frequently associated with conventional or investigational drugs in the treatment of MF-related anemia to tackle ineffective erythropoiesis. In this review, we cover the different aspects of folate metabolism entailed in the behavior and function of normal and malignant hematopoietic cells and discuss the potential implications on the biology of myelofibrosis.