Therapeutic Advances in Hematology最新文献

Background: The occurrence of adverse events after immunochemotherapy in patients with diffuse large B-cell lymphoma (DLBCL) frequently affects the course of chemotherapy, leading to a further decline in quality of life and survival.

Objectives: The primary objective of this study was to investigate the association between Chinese visceral adiposity index (CVAI), lipid accumulation product (LAP) index and skeletal muscle mass index (SMI) at initial diagnosis and the risk of haematological toxicity following immunochemotherapy in patients with DLBCL.

Design: Retrospective, single-centre study.

Methods: CVAI, LAP and SMI were calculated by combining clinical data of the patients. This study included 213 patients, of whom 117 (55%) patients experienced grades 3-4 haematological toxicity after immunochemotherapy. Participants were divided into four groups (Q1, Q2, Q3, Q4) based on the quartiles of CVAI, LAP and SMI.

Results: In the fully adjusted model, the risk of grades 3-4 haematological toxicity in group with the highest CVAI and LAP was reduced by 75.1% (OR: 0.249, 95% CI: 0.102-0.606, p = 0.002) and by 77.3% (OR: 0.227, 95% CI: 0.095-0.542, p = 0.001) compared to the group with the lowest CVAI and LAP. For SMI, the risk of grades 3-4 haematological toxicities in the group with the highest SMI was reduced by 62.9% compared with the lowest SMI group in the unadjusted model. The multivariable-adjusted restricted cubic spline curves and subgroup interaction analyses further confirmed the robustness of these findings.

Conclusion: The results indicate that DLBCL patients with relatively high CVAI, LAP and SMI at initial diagnosis have a lower risk of severe haematological toxicity following chemotherapy. Therefore, CVAI, LAP and SMI at initial diagnosis are reliable and effective biomarkers for predicting severe haematological toxicity after immunochemotherapy in DLBCL patients.

Trial registration: This is a retrospective study, and no registration on ClinicalTrials.gov.

Background: Macrofocal multiple myeloma (MFMM) is characterized by clonal plasma cells comprising less than 20% of the bone marrow, multiple lytic bone lesions, and the absence of anemia, renal insufficiency, and hypercalcemia. This subtype of multiple myeloma (MM) has a relatively low incidence. Prognostic staging and cytogenetic guidance for MFMM are often insufficient due to the low tumor burden in the bone marrow. Large cohort studies on this subgroup during the era of novel agents are limited.

Objectives: We aim to describe the clinical characteristics and prognostic markers of MFMM patients undergoing treatment with novel agents.

Methods: Consecutive cases of MM patients diagnosed at Peking University People's Hospital and Fu Xing Hospital of Capital Medical University from 2011 to 2023 were screened. A propensity score matching was conducted with a 2:1 ratio, matching classic MM patients to MFMM patients based on clinical variables of age and year of diagnosis.

Results: We identified 91 cases (4%) of MFMM and 182 matched classic MM among 2291 MM patients. The MFMM cohort had a higher proportion of male patients, those with <90% clonal plasma cells in the bone marrow by multiparameter flow cytometry, and patients with extramedullary disease, along with a lower proportion of patients with high-risk cytogenetics or advanced disease staging. MFMM patients demonstrated better overall responses compared to the control cohort (p = 0.027) in those not receiving upfront autologous stem cell transplantation (ASCT). During a median follow-up of 42.8 months for the entire cohort, the MFMM cohort exhibited significantly superior progression-free survival (PFS) and overall survival (OS) compared to the control cohort. In multivariate analysis of the entire cohort, exposure to immunomodulatory drugs and ASCT consolidation in frontline therapy were independently associated with improved PFS and OS. For the MFMM cohort, a Ki-67 index ⩾20% was associated with inferior PFS, providing valuable prognostic information in a group where staging and cytogenetic guidance are often inadequate.

Conclusion: We concluded that treatment strategies for MFMM patients should align with those for standard MM, and a Ki-67 index ⩾20% in biopsy samples of plasmacytoma is associated with inferior PFS.

Background: Anti-CD38 monoclonal antibodies (mAbs) have significantly changed the multiple myeloma treatment landscape. This meta-analysis compared the efficacy and safety of anti-CD38 mAb-based therapy versus standard therapy in newly diagnosed multiple myeloma (NDMM) patients.

Methods: We performed a comprehensive literature search on PubMed, the Cochrane Database, and ClinicalTrials.gov. The primary outcomes were progression-free survival (PFS) and minimal residual disease (MRD) status. Dichotomous outcomes were pooled using risk ratio (RR) along with the 95% confidence interval (CI) in RevMan 5.4. Subgroup analysis and meta-regression analysis were performed. The RoB 2.0 tool was used to assess the risk of bias.

Results: Our meta-analysis included 11 randomized controlled trials. There were 5270 patients; 3040 TEs and 2230 TIEs. Anti-CD38 mAbs significantly improved MRD negativity (RR 1.94, 95% CI: 1.59-2.37; p < 0.00001) and PFS (RR 0.51, 95% CI: 0.45-0.58; p < 0.00001). Subgroup analyses revealed better outcomes for both the TE (MRD: RR 1.52, 95% CI: 1.37-1.68; PFS: RR 0.43, 95% CI: 0.34-0.54) and TIE (MRD: RR 3.49, 95% CI: 2.65-4.61; PFS: RR 0.55, 95% CI: 0.47-0.64) populations. Meta-regression revealed that Eastern Cooperative Oncology Group (ECOG) score 0 significantly influenced MRD status (β = -0.015, p < 0.05), whereas ECOG scores 1 and 2 lacked statistical significance. Subgroup analysis revealed that PFS was significantly different between standard (RR 0.47) and high (RR 0.81) cytogenetic risk groups.

Conclusion: In NDMM patients, anti-CD38 mAb-based therapy significantly improved MRD status, and PFS compared with standard therapy alone, in both TE and TIE patients, suggesting a favorable benefit-risk profile.

Background: More real-world data are needed to complement existing phase III studies on the efficacy and safety of recombinant factor IX Fc fusion protein (rFIXFc) in people with haemophilia B.

Objectives: We report final data from the B-SURE study, evaluating the real-world usage and effectiveness of rFIXFc in France.

Methods: Previously treated patients (all ages/severities) received on-demand or prophylactic rFIXFc during B-SURE. Annualised bleeding rate (ABR), injection frequency (IF) and factor consumption (FC) were prospectively evaluated for patients on rFIXFc prophylaxis (primary endpoints). Six months of retrospective factor IX (FIX) data were collected for comparison; patients with ⩾3 months of treatment pre- and post-switch to rFIXFc were analysed.

Design: B-SURE was a 24-month, prospective, non-interventional, real-world study across haemophilia treatment centres in France.

Results: Ninety-one male patients enrolled across 21 centres (34% <18 years, 89% severe haemophilia B). Eighty-four patients received prophylaxis at rFIXFc initiation; mean prospective observation period was 21.5 months. Sixty-eight of 84 patients had prior FIX prophylaxis; on rFIXFc prophylaxis, these patients achieved low median ABR (1.2), IF (47.45 injections/year) and mean FC (2844 IU/kg/year). Compared with previous FIX, mean ABR was reduced by 40% (n = 63); mean IF and FC were reduced by 38.20 injections/year and 1008 IU/kg/year (n = 57). In patients with prior FIX on-demand (n = 15), mean ABR reduced by 84% on rFIXFc prophylaxis (n = 14), mean IF reduced by 2.13 injections/year and mean FC increased by 381.8 IU/kg/year (n = 15). Most physicians and patients were satisfied/highly satisfied with rFIXFc prophylaxis. rFIXFc was well tolerated with no new safety concerns.

Conclusion: Findings support the safety and effectiveness of rFIXFc, with reduced IF and FC while maintaining/improving bleed protection. Trial registration: NCT03655340.

Background: Heat stroke (HS), a potentially fatal heat-related illness, is often accompanied by disseminated intravascular coagulation (DIC) early, resulting in a poorer prognosis. Unfortunately, diagnosis by current DIC scores is often too late to identify DIC. This study aims to investigate the predictors and predictive model of DIC in HS to identify DIC early.

Methods: This retrospective study analyzed clinical data of patients with HS in a tertiary hospital from January 1, 2008 to December 31, 2020. Univariate and multivariate logistic regression analyses were employed to identify the risk factors for DIC in HS. The predictive models based on these risk factors were constructed and externally validated, and their predictive efficacy was evaluated using receiver operating characteristic curves.

Results: A total of 219 HS patients, including 49 with DIC, were included. The independent risk factors for DIC were identified as follows: neutrophil percentage (Neu%), lymphocyte count, lymphocyte percentage (Lym%), creatine kinase-MB (CKMB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and rhabdomyolysis (RM). After logarithmization, the final predictive model based on the logarithm of lactate dehydrogenase (InLDH; odds ratio (OR) = 9.266, 95% confidence interval (95%CI; 4.379-19.607), p < 0.0001) and the logarithm of neutrophil-lymphocyte ratio (InNLR; OR = 3.393, 95%CI (1.834-6.277), p < 0.0001) was constructed with the largest area under the curve (0.928). A nomogram incorporating InLDH and InNLR was developed and showed excellent discrimination and calibration capabilities.

Conclusion: Nine independent risk factors were identified for the occurrence of DIC in HS patients. The predictive model based on InLDH and InNLR can effectively predict the incidence of DIC. A nomogram based on InLDH and InNLR was developed to facilitate early identification and timely treatment of DIC in HS patients.

Background: Treatment outcomes for acute promyelocytic leukemia (APL) have improved with all-trans-retinoic acid and arsenic trioxide, yet relapse remains a concern, especially in pediatric patients. The prognostic value of minimal residual disease (MRD) post-induction and the impact of arsenic levels during induction on MRD are not fully understood.

Objectives: To evaluate the relationship between post-induction MRD levels and relapse-free survival (RFS) in pediatric APL patients, and to investigate the correlation between blood arsenic concentration levels during induction therapy and MRD status.

Design: A retrospective analysis of pediatric APL patients enrolled in a clinical trial from September 2011 to July 2020.

Methods: We assessed the relationship between RFS and post-induction MRD levels using the log-rank test. The optimal MRD cut-off was determined using the "surv_cutpoint" function in the survminer R package. Arsenic concentration levels were monitored in 16 patients on days 7 and 14 of induction therapy, and Spearman correlation was used to analyze the relationship between arsenic concentrations and MRD levels.

Results: Among 176 pediatric APL patients, with a median follow-up of 6 years, 4 relapsed. Patients with MRD >3.1% had significantly lower RFS compared to those with MRD ⩽3.1% (94.6% vs 100%, p = 0.023). In addition, a negative correlation was found between blood arsenic concentration levels and post-induction MRD levels. Lower arsenic concentrations were associated with higher MRD levels, with significant correlations observed for trough concentrations (R = -0.666, p = 0.005) and peak concentrations (R = -0.499, p = 0.049) on day 7.

Conclusion: Our study highlights the prognostic significance of post-induction MRD assessment in pediatric APL. We also demonstrate a negative correlation between blood arsenic concentration levels and MRD, suggesting that lower arsenic concentrations during induction therapy may contribute to a higher MRD burden. These findings may inform strategies to optimize treatment and improve outcomes in pediatric APL.Trial registration: www.clinicaltrials.gov (NCT02200978).

Background: Medical resources, especially blood products, were in short supply during the COVID-19. Less intensive therapy with hypomethylating agents/venetoclax (VEN) seems an effective treatment option for patients with acute myeloid leukemia (AML).

Objectives: To retrospectively analyze the efficacy and safety of VEN combined with azacitidine (AZA) in young adult patients with newly diagnosed (ND) AML.

Design: This was a retrospective study.

Methods: The clinical data of 25 AML patients treated with the VEN + AZA regimen from January 2021 to December 2023 at our center were collected, compared with a randomized historical study cohort that was administered intensive chemotherapy (IC) from January 2018 to December 2019.

Results: No rate of complete remission/complete remission with incomplete count recovery differences observed between the two arms reached statistical significance. Compared to traditional IC, minimal residual disease (MRD)-negative remission was achieved more quickly in patients treated with VEN + AZA regimens (after cycle 1: 8% in the IC group vs 56% in the VEN group, p = 0.0004; after cycle 2: 16% in the IC group vs 72% in the VEN group, p = 0.0001), especially in those AML patients who had a poor prognosis. The dependency of transfusion of red blood cell (RBC) and platelets during induction treatment was significantly lower in the VEN + AZA group (RBC: p = 0.0269; platelet: p = 0.0054). Compared with the standard IC, the incidence rate of non-hematological adverse events in VEN + AZA group was significantly decreased (infection: 100% vs 20%, p = 0.0001; gastrointestinal side effects: 48% vs 12%, p = 0.0055). The total hospitalization cost of the VEN group was significantly less than that of the IC group (p = 0.0395).

Conclusion: In conclusion, our study indicated that VEN + AZA with a higher MRD-negative remission rate and less toxic appeared to be a therapy option for young patients with ND AML. However, further well-designed studies with larger numbers of patients are needed to confirm the benefits of VEN + AZA in this population.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) stands as a cornerstone in the treatment of hematological malignancies, recognized for its remarkable efficacy. However, the persistent challenge of graft-versus-host disease (GVHD) continues to represent a significant barrier, often being the leading cause of nonrelapse mortality after allo-HSCT. To address this limitation, hematopoietic stem cell microtransplantation (MST) has emerged as a novel therapeutic strategy that synergistically combines chemotherapy, allo-HSCT, and cellular immunotherapy. This innovative approach is designed to retain the patient's immune function, promote the establishment of microchimerism, and achieve a potent graft-versus-tumor (GVT) response, all while significantly minimizing the risk of GVHD. MST has primarily been applied in the treatment of hematological malignancies, where it has demonstrated promising outcomes, including marked improvements in complete remission rates, overall survival rates, and progression-free survival rates. Moreover, MST facilitates hematopoietic recovery, decreases the likelihood of infections, and reduces the incidence of GVHD, thus contributing to an improved quality of life for patients. A deeper and more comprehensive understanding of MST's mechanisms could enhance its clinical utility and integration into standard treatment protocols. This review aims to explore the underlying mechanisms, current clinical applications, and challenges of MST, shedding light on its potential role in advancing the management of hematological malignancies.

Waldenström macroglobulinemia is an indolent B-cell lymphoma which although remains incurable, there are a lot of treatment options. Today, Bruton tyrosine kinase inhibitors have a central role in the management of the disease either as monotherapy or combination with other regimens, due to their efficacy, ease of administration, and safety profile. However, there is still active clinical investigation to further increase their efficacy and improve safety profile. Combinations based on BTK inhibitors may offer advantages. Second- and third-generation BTK inhibitors are also evaluated in combinations aiming to improve the depth of response, overcome genetic factors associated with poorer outcomes and reduce toxicity and duration of therapy.