Hematology最新文献

Objectives: Currently, there is limited understanding regarding the prognostic significance of time to progression (TTP) after first remission in multiple myeloma (MM).

Methods: We conducted a retrospective analysis of clinical data from 209 patients with MM. These patients were categorized into ≤ 6 months, ≤ 12 months, ≤ 24 months, > 24 months, 6-12 months, and 12-24 months subgroups based on TTP.

Results: Patients in ≤ 12 months group exhibited shorter median overall survival (OS) and OS-1 compared to those in ≤ 24 months group (61.73 vs 96.10 months, P = 0.02; 54.00 vs 74.17 months, P = 0.048). ≤ 6 months group exhibited shorter median OS and OS-1 compared to 6-12 months group (33.63 vs 79.60 months, P = 0.022; 19.93 vs 65.17 months, P = 0.015). Patients in 6-12 months group had shorter median OS and OS-1 compared to those in 12-24 months group (79.60 vs 100.43 months, P < 0.001; 65.17 vs 77.17 months, P = 0.012).No significant difference in OS was observed between patients in 12-24 months and > 24 months groups. For patients who experienced progression within 12 or 24 months after remission, undergoing autologous hematopoietic stem cell transplantation (ASCT) after progression conferred a median OS and OS-2 advantage over receiving post-progression chemotherapy. Multivariable analysis confirmed that TTP was an independent predictor for OS in patients with MM.

Conclusion: Patients with MM who experience earlier disease progression within 12 months after remission have a worse prognosis, and post-progression ASCT can improve their survival outcomes.

Background: Relapsed/Refractory (R/R) diffuse large B-cell lymphoma (DLBCL) represents a subgroup with a high incidence and dismal prognosis. Currently, there is a lack of robust models for predicting R/R DLBCL. Therefore, we conducted a retrospective study to identify key determinants to be incorporated into a novel nomogram to enhance the identification of DLBCL patients at elevated risk of refractoriness/recurrence.

Methods: We included 293 newly-diagnosed DLBCL patients from Harbin Medical University Cancer Hospital, collected from 2008-2017. Patients were randomly divided into a training cohort (n = 206) and a validation cohort (n = 87) at a 7:3 ratio. The training cohort underwent univariable analysis to select variables for a binary logistic regression model. These variables were also prioritized using a random forest algorithm. The developed nomogram was evaluated with the receiver-operator characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) for its clinical utility.

Results: Univariable analysis pinpointed several factors significantly associated with refractoriness/recurrence, including pathological subtype, lactate dehydrogenase (LDH), International Prognostic Index (IPI), treatment, absolute lymphocyte count (ALC), lymphocyte/monocyte ratio (LMR), and prognostic nutritional index (PNI). Binary logistic regression highlighted pathological subtype, LDH, treatment, and ALC as key predictors, which were incorporated into the nomogram. The nomogram showed excellent calibration and accuracy in both cohorts, and comparative DCA and ROC analysis demonstrated its superior net benefit and area under the curve (AUC) compared to traditional indexes like IPI, R-IPI, and NCCN-IPI.

Conclusion: This nomogram serves as a valuable tool for predicting the likelihood of refractoriness or recurrence in DLBCL patients.

Background: Progressive multifocal leukoencephalopathy (PML) is characterized by demyelination in the central nervous system. It is caused by infection with human polyomavirus 2 and has a poor prognosis. Therapeutic strategies involve restoring immune function and/or discontinuing immunosuppressive treatment. Immune checkpoint inhibitors such as those targeting programmed death receptor-1 (PD-1) can alleviate PML by restoring T cell function. There are no case reports on the use of the PD-1 inhibitor, Sintilimab, for treating PML. Here, we report a case of successful treatment of PML with sintilimab following allogeneic hematopoietic stem cell transplantation.

Case presentation: A 35-year-old woman with high-risk acute myeloid leukemia underwent allogeneic hematopoietic stem cell transplantation after induced remission and developed PML 12 months after transplantation. She received five courses of 100 mg every 4 weeks with monitoring by magnetic resonance imaging (MRI) and viral load in the cerebrospinal fluid, showing clinical improvement, resolution of neurological symptoms, and reduced viral load. MRI showed initial exacerbation of lesions but significant improvement after five courses of treatment. No graft-versus-host disease occurred, but manageable immune reconstitution inflammatory syndrome was observed.

Conclusion: Sintilimab, a PD-1 inhibitor, might be used to treat PML in patients with hematologic malignancies undergoing allo-HSCT, which needs further investigation.

Background: Hemoglobin (Hb) Hekinan is a prevalent α-globin variant frequently missed in thalassemia screening centers using high-performance liquid chromatography (HPLC) or capillary electrophoresis. This study aims to investigate the hematological and molecular characteristics of Hb Hekinan in a large cohort.

Methods: Hb variants were identified using isoelectric focusing (IEF) and HPLC. Hb Hekinan was confirmed by direct DNA sequencing. Additional genetic determinants, including α-thalassemia, β-thalassemia and other variants, were detected using multiplex GAP-PCR, ARMS-PCR or direct DNA sequencing as appropriate.

Results: Among 61,997 Hb typing samples, 149 cases of Hb Hekinan were identified in Thai individuals and classified into 8 genotypic groups. These included 104 Hb Hekinan heterozygotes, 10 Hb Hekinan coexisting with α⁺-thalassemia, 3 Hb Hekinan with non-deletional α-variants, 6 Hb Hekinan with α⁰-thalassemia, 21 double heterozygote for Hb Hekinan and HbE, 3 Hb Hekinan with β-thalassemia trait, 1 triple heterozygotes (Hb Hekinan/α⁰-thalassemia/Hb E) and 1 quadruple heterozygote for Hb Hekinan/α⁺-thalassemia/Hb E/Hb Hope. Hb Hekinan was well-separated from Hb A using IEF but was frequently missed with HPLC. On HPLC, Hb Hekinan could only be identified when coexisting with α⁰-thalassemia. All cases presented with either normal Hb levels or mild anemia.

Conclusions: Hb Hekinan is a prevalent α-globin variant that is often undetected by HPLC but reliably identified using IEF. These findings highlight the importance of incorporating IEF for accurate diagnosis of Hb Hekinan. Most cases are clinically benign, even when interacting with other thalassemia syndromes or Hb variants.

Objective: This review aimed to examine if there is any difference in the risk of thrombosis and central line-associated bloodstream infection (CLABSI) with the use of peripherally inserted central catheter (PICC) and conventional central venous catheters (CVC) in hematological cancer patients.

Methods: We searched the online databases of PubMed, CENTRAL, Scopus, Web of Science, and Embase for all types of studies comparing the risk of thrombosis and CLABSI between PICC and CVC. The search ended on 23rd September 2024.

Results: Eight studies were included. One was a randomized trial while others were observational studies. Meta-analysis showed no statistically significant difference in the risk of thrombosis between PICC and CVC (OR: 1.69 95% CI: 0.75, 3.82 I²= 78%). However, these results were not stable on sensitivity analysis. The exclusion of two studies indicated a higher risk of thrombosis with PICC. Pooled analysis showed that the risk of CLABSI was significantly lower with PICC as compared to CVC (OR: 0.52 95% CI: 0.40, 0.66 I²= 0%). Results of subgroup analysis based on study design and diagnosis showed conflicting results.

Conclusions: There is conflicting evidence on the risk of thrombosis between PICC and CVC when used for hematological cancer patients. There could be a tendency of higher risk of thrombosis with PICC which needs to be confirmed by further studies. However, the use of PICC may reduce the risk of CLABSI in such patients. The quality of evidence is low owing to the predominance of observational studies with high inter-study heterogeneity.

Background: This study aimed to develop a prognostic model based on extracellular trap-related genes (NETRGs) for patients with cALL.

Methods: Data from the TARGET-ALL-P2 and TARGET-ALL-P3 cohorts in the Genomic Data Commons database, the transcriptome dataset GSE26713, the single-cell transcriptome dataset GSE130116 from the Gene Expression Omnibus database and 306 NETRGs identified were analysed. Differentially expressed genes (DEGs) were identified from GSE26713 and differentially expressed NETRGs (DE-NETRGs) were obtained by overlapping DEGs with NETRGs. Functional analyses were conducted. Key feature genes were identified through univariate and least absolute shrinkage and selection operator (LASSO) regression. Prognostic genes were determined via multivariate Cox regression analysis, followed by the construction and validation of a risk model and nomogram. Additional analyses included immune profiling, drug sensitivity, functional differences, cell-type-specific expression, enrichment analysis and RT-qPCR.

Results: A total of 1,270 DEGs were identified in GSE26713, of which 74 overlapped with NETRGs. Seven prognostic genes were identified using univariate, LASSO and multivariate Cox regression analyses. Survival analysis revealed lower survival rates in the high-risk group. Independent prognostic analysis identified risk scores and primary diagnosis as independent predictors of prognosis. Immune cell profiling showed significant differences in cell populations such as aDCs, eosinophils and Th2 cells between risk groups. Six cell subtypes were annotated, with prognostic genes predominantly expressed in myeloid cells. RT-qPCR revealed that PTAFR, FCGR2A, RETN and CAT were significantly downregulated, while TLR2 and S100A12 were upregulated in cALL.

Conclusion: TLR2, PTAFR, FCGR2A, RETN, S100A12 and CAT may serve as potential therapeutic targets.

Objective: To evaluate the short-term efficacy and safety of eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) in China.

Method: Data were retrospectively collected from patients with PNH who received at least 3 months of full-dose eculizumab. Changes in clinical and laboratory indicators after 1, 3, and 6 months of eculizumab therapy and at the end of follow-up were documented. The incidence rates of breakthrough hemolysis (BTH), extravascular hemolysis (EVH), and adverse events were recorded.

Result: A total of 48 patients, including 27 males, with a median age of 46 (12-78) years were included. Twenty-four (50%) patients had classic PNH and 24 (50%) had bone marrow failure (BMF)/PNH. Eighteen (37.5%) patients required blood transfusion. The median duration of follow-up was 6 (3-15) months. During the follow-up period, Lactate Dehydrogenase (LDH) levels were lower than those at baseline (<0.05) at all observation points. The patients showed a significant reduction in creatinine levels from baseline (P = 0.022 and P = 0.039, respectively) at 1 and 3 months. At the end of the follow-up, fifteen (83.3%) became transfusion-independent. No new thrombotic events were observed. The FACIT-Fatigue score significantly improved (P < 0.05). No significant differences were observed in the changes in hemoglobin or LDH levels between patients with classic PNH and those with BMF/PNH. BTH was observed in 17.4% of patients and EVH in 10.4%. Mild adverse events occurred in 22.9% of patients. No deaths or clonal evolution was observed.

Conclusion: Eculizumab can effectively control the hemolytic symptoms of PNH with good tolerance for Chinese patients.

Objective: This study was designed to compare treatment patterns, clinical trial participation, and clinical outcomes among patients with small lymphocytic lymphoma/chronic lymphocytic leukemia (CLL) or Mantle cell lymphoma (MCL) by site of care.

Methods: A nationwide electronic health record (EHR)-derived de-identified database was utilized for this study. Eligible patients were diagnosed with either CLL or MCL from 2013-2022 who received systemic therapy for their disease. Overall survival (OS) was analyzed using Kaplan Meier method, censoring patients without events at last observation in the database. Cox proportional hazards regression model was used to adjust for baseline covariates.

Results: A total of 6,372 patients with CLL and 3,411 with MCL met eligibility criteria for this analysis; 13.9% and 22.2%, respectively, were treated in academic settings. Academic settings were associated with higher patient volume and were more likely to treat MCL with CAR-T, enroll patients with CLL or MCL to clinical trials, and care for patients who were younger, White, and for CLL with higher rates of del(17p) mutations (all p < 0.01). Survival was significantly longer among patients treated in academic vs community settings (median OS not reached vs 80.5 months for CLL; 95.6 vs 68.7 months for MCL from start of first-line therapy).

Discussion: Patients who received care in academic settings differed from those treated in the community; care in academic settings was associated with significantly longer OS and higher trial participation. Further research is warranted to better understand the factors that may contribute to the observed outcomes.

Purpose: We report the case of a 6-year-old boy who presented with muscular hypertonia, impaired growth, and recurrent infections, who was diagnosed with purine nucleoside phosphorylase (PNP) deficiency with two novel mutations in the PNP gene. He underwent a hematopoietic stem cell transplantation (HSCT) from an unrelated donor, and we observed the clinical outcome.

Methods: We retrospectively analyzed the clinical manifestations and outcomes of this patient who underwent HSCT. We analyzed the results of whole exome sequencing (WES) on the patient.

Results: The patient experienced repeated serious respiratory and gastrointestinal infections since birth and presented with neurological symptoms. He was found to have two novel pathogenic mutations in the PNP gene through WES. One hemizygous variant was c.385dup (p.Ile129Asnfs*6) in exon 4. The other was a heterozygous deletion in exon 2-6. He underwent HSCT with clinical improvement.

Conclusions: We presented a patient with two novel mutations in the PNP gene and clinical improvement following an allo-HSCT.

Objectives: Whether intermediate-dose tertiary prophylaxis can improve quality of life and psychological health in adults with severe/moderate hemophilia A has not been determined. This research aims to explore the impact of intermediate-dose tertiary prophylaxis with recombinant human FVIII (rhFVIII) on quality of life, anxiety and depression in such individuals transitioned from on-demand treatment.

Methods: This retrospective analysis collected data from July 2019 to July 2022. Haemophilia Quality of Life Questionnaire for Adults (HAEMO-QoL-A), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7) were compared before and after prophylaxis. Additionally, functional independence and joint status were analyzed at the end of the 3-year prophylaxis period, as well as their correlations with HAEMO-QoL-A, PHQ-9, and GAD-7.

Results: The HAEMO-QoL-A total score decreased after prophylaxis (pre-prophylaxis: 88.90 ± 33.38 vs. post-prophylaxis: 79.59 ± 22.89) (P = 0.016). The mean PHQ-9 scores before and after prophylaxis were 4.44 ± 4.63 and 5.56 ± 4.30 (P = 0.058), respectively, while the mean GAD-7 scores were 3.15 ± 3.84 and 4.44 ± 3.99 (P = 0.016). Significant correlations were observed for HAEMO-QoL-A with functional independence (P < 0.001), mood and emotions with age (P = 0.032), PHQ-9 scores with knee joint rehabilitation scores (P = 0.047), and GAD-7 scores with treatment experience and ankle joint rehabilitation scores (P = 0.029, P = 0.039).

Conclusion: Intermediate-dose tertiary prophylaxis with rhFVIII can improve quality of life but not relieve anxiety and depression in adults with severe/moderate hemophilia A. Better functional independence correlates with improved quality of life. Gait and age also influence the quality of life to some extent. We need to undertake anxiety and depression screening and provide psychological treatment when necessary.