Annals of Hematology最新文献

Translocations involving immunoglobin (IG) are common in B-cell neoplasms. These IG translocations lead to the disposition of the enhancer or promoter of an IG locus, typically IGH, to a proto-oncogene, resulting in the elevated expression of the cancer gene. IG fusions play an important role in the diagnosis, prognostication, and therapy selection of B-cell lymphomas. A t(14;22)(q32;q11) translocation involving IGH and IGL is rare in lymphomas. We report herein clinicopathological characteristics, response to treatment, and outcomes of a first splenic marginal zone lymphoma case with a t(14;22)(q32;q11) translocation involving IGH and IGL treated with rituximab, ibrutinib, and obinutuzumab. Studies of additional cases are needed to elucidate the potential role of the t(14;22) translocation in lymphomagenesis and prognostication.

While Azacitidine combined with HAG (HHT, low-dose cytarabine, G-CSF) regimen has shown promise in treating older and unfit patients with acute myeloid leukemia (AML), its efficacy in younger patients remains understudied. This study evaluates the effectiveness and safety of Azacitidine combined with the HAG regimen in a broader patient cohort, including newly diagnosed and relapsed/refractory AML patients. This single-center, prospective cohort included patients with acute myeloid leukemia admitted to our center from June 2019 to Oct 2022 for induction chemotherapy with the HAGA regimen (Azacitidine combined with HAG). We focused on patients' remission rate, MRD (minimal residual disease) conversion and safety. 71 patients with newly diagnosed or R/R AML were enrolled in this study, with a median follow-up time of 20.5 months. After two cycles of HAGA, patients received 3 cycles intermediate-dose Cytarabine and 1 cycle HAGA regimen as consolidation therapies. The CRc (composite complete remission) rate of HAGA regimen as induction chemotherapy for the overall cohort was 85.9% (61/71), which included 71.8% (51/71) CR and 14.1% (10/71) CRi. The CRc with MRD-negative rate was 76.1%. Median OS (overall survival) and DFS (disease free survival) were not yet reached, and the estimated 24-month OS rate was 65.4% (95%CI: 48.4-78.0%), the estimated 24-month DFS rate 66.0% (95%CI: 48.1-79.0%). Only one patient died in induction. The HAGA regimen can be a new option in addition to intense chemotherapy for newly diagnosed or R/R AML, and with high safety.

Allogeneic haematopoietic stem cell transplant is a routine procedure for several haematological disorders though infections are the main cause of morbidity and mortality. Rare infections, such as protozoan reactivations, can be life-threatening and clinicians should be aware of these possibilities. Herein, we present a case of neuro-toxoplasmosis post haploidentical haematopoietic stem cell transplant.

Sequential combination bypass therapy (SCBT) is an effective treatment option for haemophilia patients with inhibitors; however, its safety, efficacy, and cost have largely have yet to be systematically evaluated. To address this question, we retrospectively analyzed the medical records of 14 haemophilia patients with high titer inhibitors who underwent surgery. The patients with high inhibitors were treated with two SCBT regimens by optimizing doses of the recombinant activated factor VII (rFVIIa) and prothrombin complex concentrate (PCC). The effectiveness and safety of the two SCBT regimens were evaluated. In addition, rFVIIa and PCC factor consumption and costs were also compared. The median age of the 14 patients was 30.00 (27.25-42.75) years. They all underwent major surgeries, with 85.71% (12/14) was orthopedic surgeries related to hemophilic arthropathy. Four patients were treated using regimen 1 and ten with regimen 2. Results showed that regimen 2 exhibited a higher haemostatic efficiency (90% vs. 75% intraoperative and 90% vs. 50% postoperative) and a 28.0% reduction in economic costs (863,604.68 RMB vs. 621,756.62 RMB). All patients after surgery had no prothrombin time extension, 7.14% had fibrinogen and platelet count decreases, and 57.14% had D-dimer increases that returned to baseline within 5-7 days after SCBT. The study shows that regimen 2 as an optimized SCBT regimen is an efficient approach to secure haemostasis for haemophilia patients with high titer inhibitors in the perioperative period, rather than regimen 1. The findings can help design future clinical studies and provide more reliable data and implementation advice.

For patients (pts) with relapsed or refractory multiple myeloma (RRMM) after previous autologous hematopoietic cell transplantation (AHCT), novel agents, cellular and immunotherapies are increasingly available. Options for second-line treatment mostly include triplet regimens based on proteasome inhibitors, immunomodulatory drugs and anti-CD38 monoclonal antibodies and since recently also CAR T cells. The importance of autologous salvage transplantation (retransplantation, Re-AHCT) has significantly decreased in recent years due to the availability of many new treatment options. Therefore, we performed a retrospective analysis of 171 pts cases with RRMM who received Re-AHCT between 2002 and 2021. With a median follow-up of 74.7 months, the 5-year rates of progression-free survival (PFS) and overall survival (OS) were 18% (median 20.6 months) and 57% (median 65.0 months), respectively, the 100-day mortality rate was 4%. Multivariate analysis identified R-ISS stage and duration of previous response (DoR) as independent prognostic factors for PFS and OS. While the revealed high-risk population (R-ISS stage II/III, DoR ≤ 24 months) was associated with a significantly worse PFS (HR 2.728) and OS (HR 3.129), the low-risk group (R-ISS I, DoR > 24 months) achieved a median PFS and OS of 45.0 months and 80.2 months, respectively. Therefore, Re-AHCT could remain an option in such prognostically favorable pts with RRMM even in the era of novel therapies especially when more potent treatment modalities are not available.

Catheter-related bloodstream infections represent one of the most prevalent complications in patients with peripherally inserted central venous catheters (PICCs). The application of antibiotic lock therapy (ALT), particularly in patients with hematological malignancies, has not been well documented. We aim to share our experience on ALT for these patients and to evaluate its effectiveness and safety. All cases of patients with hematological malignancies who had PICC from January 2018 to October 2024 were retrospectively reviewed. Microbiologic data of PICC-related bloodstream infections (PRBSIs) were collected. A comparison was made between patients managed with ALT and those without it. Factors affecting PICC removal were also explored. A total of 45 patients experienced 67 episodes of PRBSIs, yielding an incidence rate of 2.98 per 1,000 PICC days. The median time of PRBSI onset was 42 days. Predominant pathogens included Gram-negative bacilli (49.3%) and Gram-positive cocci (35.8%). The catheter salvage rate was significantly higher at 76.5% when ALT was combined with systemic antibiotic therapy (SAT), compared to 51.5% for SAT alone (p = 0.033). 3 death events (3/34) compared with 4 death events (4/33) occurred in each therapeutic regimen (p = 0.709). Elevated procalcitonin levels (> 2ng/ml) and inadequate empirical therapy were risk factors for PICC removal; conversely, ALT served as a protective factor against it. ALT in combination with systemic antibiotics is a safe and effective approach for managing PRBSIs in patients with hematological malignancies, helping to avoid unnecessary catheter removal and could be considered in clinical practice when catheter retention is desired.

Recent advances in measurable residual disease (MRD) technology have significantly enhanced predictive accuracy for outcomes in various hematologic malignancies, serving as a crucial surrogate endpoint. However, in mantle cell lymphoma (MCL), identifying the optimal timing for MRD assessment and understanding the prognostic implications of MRD dynamics remain challenging, primarily due to limited extensive MRD data. Our study encompassed 102 patients with MCL, all presenting with clonal B-cell involvement in bone marrow as determined by multiparametric flow cytometry (MFC). MRD evaluations were conducted every two cycles. 75.5% (77/102) achieved MRD negativity during induction therapy. We found the MRD status at the end of four cycles treatment had the best predictive ability for survival (HR = 3.2, C-index = 0.664). 32 of 77 patients (41.6%) had a rapid tumor burden reduction and achieved MRD negativity within two cycles treatment. Notably, this swift shift to MRD negativity was observed more frequently in patients classified as MIPI high-risk. However, this rapid clearance of MRD did not confer any prognostic benefit to these patients. Subgroup analyses revealed that MRD negativity held prognostic value in almost all categories, except for those with blastoid/pleomorphic morphology. MRD assessment serves as a valuable complement to the traditional response evaluation, particularly benefiting for patients attaining partial remission. These findings highlighted the importance of MRD detection during response evaluation of MCL therapy and determined that after four treatment cycles is the best MRD detection timepoint.

Lymphoid leukemias represent a significant global health burden, leading to substantial morbidity and mortality. The intricate interplay between leukemic cells and their surrounding tumor microenvironment (TME) is pivotal in disease initiation, progression, and therapeutic resistance. Comprising a dynamic milieu of stromal, immune, and leukemic cell populations, the TME orchestrates a complex network of signaling pathways and molecular interactions that foster leukemic cell survival and proliferation while evading immune surveillance. The crosstalk between these diverse cellular components within the TME not only fuels tumor progression but also confers resistance to conventional therapies, including the development of multi-drug resistance (MDR). Recognizing the pivotal role of the TME in shaping disease outcomes, novel therapeutic approaches targeting this dynamic ecosystem have emerged as promising strategies to complement existing anti-leukemic treatments. As a result, drugs that target the TME have been developed as complementary strategies to those that directly attack tumor cells. Thus, a detailed understanding of the TME components and their interactions with tumor cells is critical. Such knowledge can guide the design and implementation of novel targeted therapies for lymphoid leukemias.

Therapies that effectively suppress graft-versus-host disease (GVHD) without compromising graft-versus-leukemia/lymphoma (GVL) effects is important in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematopoietic malignancies. Geranylgeranylacetone (GGA) is a main component of teprenone, a gastric mucosal protectant commonly used in clinical practice. In preclinical models, GGA suppresses proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α), which are associated with GVHD as well as induces thioredoxin-1 (Trx-1), which suppresses GVHD while maintaining GVL effects. Here, we investigated whether the addition of teprenone to standard GVHD prophylaxis could reduce the cumulative incidence of severe acute GVHD (aGVHD) without attenuating GVL effects. This open-label, randomized clinical trial enrolled 40 patients (21 control and 19 teprenone group) who received allo-HSCT between May 2022 and February 2023 in our institution. Patients in the teprenone group received 50 mg of teprenone orally thrice daily for 21 days from the initiation of the conditioning regimen. The cumulative incidence of severe aGVHD by day 100 after allo-HSCT was not significantly different in the two groups (27.9 vs. 16.1%, p = 0.25). The exploratory studies revealed no obvious changes in Trx-1 levels, but the alternations from baseline in IL-1β and TNF-α levels at day 28 after allo-HSCT tended to be lower in the teprenone group. In conclusion, we could not demonstrate that teprenone significantly prevented the development of severe aGVHD. Discrepancy with preclinical model suggests that appropriate dose of teprenone may be necessary to induce the expression of antioxidant enzymes that suppress severe aGVHD. Clinical Trial Registration number:jRCTs 061210072.

Objectives: This study aimed to provide an overview of temporal trends in incidence and mortality of non-Hodgkin lymphoma (NHL) from 1992 to 2021 at global, regional, and national levels, with a special focus on their associations with age, period and cohort.

Methods: Data were obtained from the Global Burden of Disease Study 2021. We presented temporal trends in NHL incidence and mortality for the world and 204 countries and territories from 1992 to 2021. An age-period-cohort (APC) model was adopted to estimate net drifts (overall annual percentage change), local drifts (annual percentage change in each age group), longitudinal age curves (expected longitudinal age-specific rate), and period (cohort) relative risks.

Results: The global age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) for NHL were 7.14 (95% uncertainty interval [UI]: 6.58, 7.66) and 3.19 (95% UI: 2.93, 3.44) per 100,000 population in 2021, respectively. From 1992 to 2021, the global net drift of incidence rate was 0.11% (95% confidential intervals [CI]: 0.07%, 0.15%) per year, ranging from - 0.60% (95% CI: -0.66%, -0.54%) in high socio-demographic index (SDI) region to 1.51% (95% CI: 1.46%, 1.57%) in middle SDI region, with 100 countries and territories presenting increasing trends. Similar patterns can be found in the net drift of mortality rate, with 19 countries and territories showing upward trends. Age effects illustrated that incidence and mortality risks progressively increased with advancing age across different SDI regions. Period effects on incidence presented rising risks in high-middle, middle and low-middle SDI regions, whereas on mortality exhibited persistent downward trends in high and high-middle SDI regions. High-middle and middle SDI regions presented initially unfavourable and then favourable trends in incidence and mortality risks across successive birth cohorts. A strong heterogeneity was found in age, period and cohort effects on incidence and mortality across countries.

Conclusions: Despite observing an increasing temporal trend in NHL incidence, coupled with a declining trend in mortality, NHL represented a substantial public health challenge worldwide. Temporal trends in NHL were not completely commensurate with socioeconomic development and varied widely across countries. Timely intervention should be conducted, especially for middle-aged and aged individuals.