Therapeutic Advances in Hematology最新文献

Background: Cytomegalovirus (CMV) infection can lead to significant morbidity and mortality in pediatric hematopoietic stem cell transplant recipients. Early detection of CMV infection is crucial for managing its impact.

Aim: This study aims to evaluate the effectiveness of QuantiFERON-CMV^® (QF-CMV) and QuantiFERON-Monitor^® (QFM) tests in predicting CMV infection and graft-versus-host disease (GvHD) in pediatric hematopoietic stem cell transplant recipients to enhance patient outcomes and support personalized prevention strategies.

Methods: The QF-CMV and QFM tests were used to predict CMV pp65 antigen and GvHD in 24 pediatric hematopoietic stem cell transplant recipients.

Results: Data showed that positive CMV antigenemia (CMV-Ag) increased the risk of GvHD by 21.2%. QF-CMV and QFM were associated with CMV-Ag, with QF-CMV inversely predicting GvHD. Lymphocyte and neutrophil counts were positively linked to both tests.

Conclusion: The findings suggest that QF-CMV and QFM tests could predict GvHD and CMV infection risk and help identify high-risk patients, contributing to personalized prevention strategies and improving CMV treatment. Despite the small sample size, this study is an essential proof of concept due to the unique patient population of pediatric bone marrow stem cell transplant recipients. Further multicenter studies are needed to validate these results.

Background: Adult T-cell leukemia/lymphoma (ATL) is a neoplasm with a high prevalence in certain regions such as southwestern Japan, the Caribbean, sub-Saharan Africa, South America, and Australia. In Colombia, the seroprevalence of human T-cell lymphotropic virus type 1 (HTLV-1) has been reported in specific populations, but there is limited information about the clinical course and management of ATL in the country.

Objectives: To describe the clinical characteristics, treatment patterns, and outcomes of patients diagnosed with HTLV-1-positive ATL in a high-complexity healthcare institution in Colombia and compare these findings with reports from other geographic regions.

Design: Observational retrospective cohort study conducted in a single high-complexity healthcare institution in Cali, Colombia, including patients diagnosed between 2011 and January 2022.

Methods: This study presents an observational retrospective cohort of patients diagnosed with HTLV-1-positive ATL and managed at a high-complexity institution in Cali, Colombia. Eligible patients were adults diagnosed with ATL and HTLV-1 seropositivity, receiving treatment between 2011 and January 2022. Demographic, clinical, and treatment-related variables were collected and analyzed using descriptive and survival analyses.

Results: Thirty-three patients diagnosed with ATL between 2011, and January 2022 were identified and included in the study. Most patients were female (52%) with a median age of 54 years. Acute presentation was the most common (64%), and most patients were identified at Ann Arbor stage 4. Treatment mainly consisted of various chemotherapy protocols, with cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (CHOP)-like regimens being the most frequently used. However, the overall response rate to chemotherapy was low, and most patients experienced complications and toxicities associated with treatment.

Conclusion: This study provides insights into the clinical course and management of ATL in a Colombian population. The findings highlight the predominance of acute presentations, advanced disease stages at diagnosis, and challenges in achieving a complete response with conventional chemotherapy. Further research is needed to improve treatment strategies, identify prognostic markers, and develop more effective therapies for ATL patients in Colombia.

This report describes the cases of two patients with mycosis fungoides and Sézary syndrome (MF/SS) who achieved clinical benefit with mogamulizumab combination therapies. Case 1 is a 56-year-old male with stage IIIB (T4NxM0B1) MF, which later progressed into SS, with ongoing skin symptoms (erythema, lichenified skin, and pruritis) and axillary and inguinal lymphadenomegaly. Skin-directed and systemic therapies failed to achieve a long-lasting response in this patient. Mogamulizumab (1 mg/kg once weekly for 4 weeks; once every 2 weeks thereafter) yielded temporary improvement in skin symptoms, but progression in the skin was confirmed after ~2 months. Subsequently, the combination of mogamulizumab with psoralen plus ultraviolet light A (PUVA) yielded a partial response; however, PUVA was discontinued due to phototoxicity and mogamulizumab was continued as monotherapy. At the latest evaluation, clinical improvement in the skin and reduced lymphadenomegaly were evident with ongoing mogamulizumab monotherapy; the patient is awaiting allogeneic hematopoietic stem cell transplantation. Case 2 is an 80-year-old male with stage IIIB (T4NxM0B1) granulomatous variant MF who presented with diffuse erythema with desquamation, ectropion, and inguinal lymphadenopathy. Treatment with oral prednisone and bexarotene failed to achieve adequate, long-lasting responses. Mogamulizumab (1 mg/kg once weekly for 4 weeks; once every 2 weeks thereafter) monotherapy yielded an initial improvement, characterized by less intense erythema, but the improvement was not sustained. Mogamulizumab was supplemented with oral prednisone and then PUVA; this combination resulted in improvement in the skin. PUVA was stopped due to unavailability, and methotrexate (10 mg once weekly) was initiated alongside continued mogamulizumab; this led to improvement in erythema. The patient continued mogamulizumab plus methotrexate with improving clinical status, prior to their death, which was deemed to be unlikely to be related to treatment. Our experience suggests that, in principle, mogamulizumab can be used in combination with other therapies; however, further research is needed.

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).