Hematological Oncology最新文献

Vincristine, etoposide, prednisone, and doxorubicin (OEPA)/cyclophosphamide, vincristine, prednisone, and dacarbazine (COPDAC) regimen represents a preferred chemotherapy backbone for response-adapted treatment of pediatric Hodgkin Lymphoma (HL). Epidemiological, demographic, and clinical characteristics differ between children with HL from developing and developed countries. Administration of OEPA/COPDAC in low-middle-income countries (LMIC) has been associated with high treatment-related mortality (TRM), hindering its wide adoption. In this comprehensive analysis, we evaluated OEPA/COPDAC-associated adverse events and their impact on treatment delivery in 301 Egyptian patients with pediatric HL aged 2.5–17.9 years. The mean age at presentation was 10.1 years (72% of patients ≤ 13 years) with a male-to-female ratio of 2.6:1. The three treatment groups (TG) were represented. Nodular Sclerosis classic HL (59.8%) represented the most common histopathological subtype. Adverse events were reported during 49.8% of the administered cycles. Eighty-nine and 76.4% of the patients encountered toxicity during OEPA1 and OEPA2 cycles respectively. The frequency of toxicity during COPDAC cycles ranged from 16% to 29.4%. Grade 3/4 decreased neutrophils were the most commonly occurring AE during OEPA cycles (range 71%–85%). Profound neutropenia occurred in 27.9% and 13.8% during OEPA1 and OEPA2 respectively. Profound neutropenia significantly differed across age groups. Treatment-related mortality (TRM) occurred in 1% of the patients. Ninety-eight percent of the scheduled chemotherapy cycles were successfully administered. Treatment modification due to toxicity was required in 9.3% of patients whereas 121 hospital admissions (891 days) were reported. Recurrent toxicity that is, toxicity in > 50% of administered cycles and consequently hospital admission significantly differed across age groups. Our findings support that low TRM is achievable in LMIC centers with adequate infrastructure and treatment capabilities. We additionally provide real-life data on the associated treatment modification and hospital admission.

Diffuse large B-cell lymphoma (DLBCL) is a prevalent subtype of non-Hodgkin's lymphoma (NHL). Ferroptosis is a novel form of cell death involved in multiple tumor development. However, the relationship between ferroptosis-related genes and DLBCL has not been extensively studied. The GSE95290 dataset was downloaded from the Gene Expression Omnibus (GEO) database and merged with genes associated with ferroptosis to screen differentially expressed genes (DEGs). Hub genes were identified by constructing a protein-protein interaction (PPI) network. The messenger RNA (mRNA) expressions of hub genes were subsequently detected in vitro using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). The impact of voltage dependent anion channel 1 (VDAC1) on the proliferation, apoptosis, and ferroptosis of DLBCL was evaluated using Cell Counting Kit-8, flow cytometry, and relevant ferroptosis assays, respectively. Six highly expressed hub genes were identified, all of which could be used as diagnostic biomarkers for DLBCL. In vitro studies revealed that suppressing VDAC1 expression inhibited DLBCL cell proliferation and promoted apoptosis. Furthermore, knockdown of VDAC1 promoted ferroptosis in DLBCL cells and xenograft tumor models, resulting in elevated levels of malondialdehyde (MDA) and iron and increased protein levels of Acyl-CoA synthetase long-chain family 4 (ACSL4) and cyclooxygenase-2 (COX2). Conversely, glutathione (GSH) and superoxide dismutase (SOD) levels were reduced, accompanied by decreased protein levels of glutathione peroxidase 4 (GPX4) and ferritin heavy chain1 (FTH1). VDAC1 knockdown induces ferroptosis in DLBCL, which provides new insights into the pathogenic mechanisms of DLBCL.

Overproduction of vascular endothelial growth factor (VEGF) seems to contribute to the pathogenesis, still unclear, of POEMS Syndrome. Our study retrospectively reviewed the clinical and VEGF data from a multicenter Italian cohort of patients affected by POEMS syndrome who underwent to autologous peripheral blood stem cell transplantation (aPBSCT) in order to find an impact on clinical improvement or outcome. Patients with VEGF levels higher than 758 pg/mL were at higher risk of relapse, with sensible difference in PFS (p = 0.007). VEGF could be used as a marker of relapse and as a marker of disease intensity in patients with POEMS.

This study aims to focus on GM at species level, exploring the causal associations with different kinds of lymphoma to provide some information on potential intervention directions in lymphoma. Data of GM taxa were extracted from the genome-wide association study conducted by the MiBioGen and Dutch Microbiome Project (DMP), and those of lymphomas were obtained from the FinnGen consortium. Inverse variance weighted (IVW) method and Bonferroni multiple correction were utilized to assess the causal associations of GM species with different kinds of lymphoma. The effect size was expressed by odds ratios (ORs) with 95% confidence intervals (CIs). Reverse causal association analysis has also been performed. Additionally, scatter plots and leave-one-out test were conducted for sensitivity analysis. After correction, the IVW estimates suggested that elevated relative abundance of species Faecalibacterium_prausnitzii had a negatively causal association with increased odds of Hodgkin's lymphoma (HL) (OR = 0.584, 95% CI: 0.516–0.662). Relative abundance of species Gordonibacter_pamelaeae, Holdemania_filiformis, Sutterella_wadsworthensis and Coprococcus_sp_ART55_1 was negatively associated with follicular lymphoma (FL) odds, whereas that of species Bifidobacterium_catenulatum and Coprococcus_comes were positively associated with FL odds (all p < 0.05). Relative abundance of species Akkermansia_muciniphila and Coprococcus_sp_ART55_1 had a negatively causal association with non-follicular lymphoma (NFL) odds, respectively, while that of Bacteroides_uniformis had a positive one (all p < 0.05). Relative abundance of species Flavonifractor_plautii was negatively linked to diffuse large B-cell lymphoma (DLBCL) risk (OR = 0.471, 95% CI: 0.344–0.645). Relative abundance of species Eggerthella_unclassified was positively associated with T/NK cell lymphoma (TNK) risk while that of Ruminococcus_lactaris was negatively associated with TNK risk (all p < 0.05). Elevated relative abundance of Parabacteroides_unclassified was associated with higher risk of non-Hodgkin's lymphoma (NHL) (OR = 1.955, 95% CI: 1.654–2.312). The relative abundance of species Holdemania_filiformis was negatively associated with mantle cell lymphoma (MCL) risk (OR = 0.637, 95% CI: 0.544–0.746). The relative abundance of species Rothia_mucilaginosa and Lachnospiraceae_bacterium_3_1_46FAA had positively causal association with marginal zone lymphoma (MZL) risk, while that of species Alistipes_senegalensis had a negative one (all p < 0.05). This study identified 16 GM species that have potential causal associations with different kinds of lymphoma, which provided some new idea for further exploration on prevention and treatment targets in lymphoma.

The negative impact of invasive pulmonary aspergillosis (IPA) in acute myeloid leukemia (AML) is well known whereas its clinical relevance in acute lymphoid leukemia (ALL) is still unclear. We have carried out a prospective multicentric observational study within the Rete Ematologica Lombarda to describe the incidence of IPA in acute leukemia (AL) patients, focusing on differences between AML and ALL. Between 2018 and 2020, 207 AL patients (AML: 165, ALL: 42) were evaluated. During induction, proven/probable and possible IPA were diagnosed in 32/207 patients (15.4%), equally divided into proven/probable and possible (16 each, 7.7%). IPA diagnosis was made in 23/165 (13.9%) AML and in 9/42 (21.4%) ALL patients (p = 0.2374). Proven/probable IPA were more frequent in ALL than in AML (ALL: 7/42, 16.6% vs. AML: 9/165, 5.4%; p = 0.0235). OS was similar in patients with or without proven/probable IPA (not reached vs. 63 months, p = 0.588), while OS was significantly reduced in possible IPA (22 months vs. not reached, p = 0.0167). More than 15 days of neutropenia duration and lack of antimold prophylaxis were associated with IPA. Achieving complete remission was protective, whereas age over 60 years and, with a borderline significance, possible IPA were associated with risk of death. In conclusion, Ph-negative ALL should be considered at the same high risk for IPA as AML. Antimold prophylaxis should be probably extended also to ALL.

B-cell non-Hodgkin lymphoma (NHL) in one of the most serious extrahepatic manifestations of chronic hepatitis C virus (HCV) infection. No prospective studies have been conducted in the United States (US) on the impact of direct-acting antivirals (DAAs) in HCV-infected patients with indolent B-cell NHL not requiring chemotherapy. In this prospective study, we evaluated the general characteristics of US patients with HCV-associated indolent B-cell NHL and the oncologic impact of only DAA treatment without systemic cancer therapy in those patients. We enrolled patients seen at our center during 2014–2021; we analyzed only chemotherapy-naïve patients treated with DAAs. Patients who required immediate conventional treatment for lymphoma were excluded from the study. The primary endpoints were sustained virologic response at 12 weeks (SVR12) and lymphoproliferative disease response, classified as complete response, partial response, stable disease, or progressive disease. The secondary endpoints were overall response rate (ORR) of NHL, duration of response (DOR), overall survival (OS), and progression-free survival (PFS). Nine patients met the study criteria and were analyzed. Most patients were male (n = 6), White (n = 6), younger than 65 years (n = 6), and non-cirrhotic (n = 8); had HCV genotype 1 (n = 5); and had been infected for more than 30 years (n = 7). All patients achieved SVR12. Six patients (67%) had complete response, and 3 (33%) had progressive disease. The ORR was 67%. The median DOR was 51 months (range 16–81 months). The 5-year DOR, OS, and PFS rates were 100%, 83%, and 67%, respectively. HCV-associated NHL is a late extrahepatic complication of HCV. Infected patients with indolent NHL have an excellent virologic responses to DAAs and most of them experienced a favorable oncologic response after HCV eradication without chemotherapy.

Primary lymphoma of the female genital tract (PLFGT) is a rare disease. The incidence is gradually increasing each year. There have been few reports about PLFGT, and most of them have involved individual cases and small-sample retrospective analyses. The pathogenesis of PLFGT is still under exploration and may be associated with hormones, inflammation/infection, and immunodeficiency. Diffuse large B-cell lymphoma (DLBCL) is the most common pathological type. The majority of the patients presented with vaginal bleeding, abdominal pain, an abdominal mass, and other nonspecific symptoms. Lymphoma-associated B symptoms are quite rare. These patients initially visited gynecological departments, possibly leading to misdiagnosis due to nonspecific features. The treatment strategies for and prognosis of PLFGT differ substantially from those of other gynecologic malignancies. Thus, interdisciplinary cooperation among gynecologists, pathologists, and hematologists is essential.

This study, including 412 patients newly diagnosed with myelodysplastic neoplasm (MDS), investigated the clinical, molecular, and prognostic features of MDS with moderate-to-severe bone marrow fibrosis (MF). Among the patients with MDS, 347 (84%) had MF grade 0–1 (MF0–1), and 65 (16%) had MF grade 2–3 (MF2–3). Patients with MDS with MF2–3 showed similar overall survival (OS) (16.6 vs. 21.3 months; p = 0.34) but demonstrated inferior progression-free survival (PFS) (6.6 vs. 15.2 months; p = 0.02) and a higher risk of leukemia transformation (35.4 vs. 16.4%; p < 0.001) compared to those with MF0–1. In the MDS with excess blast (MDS-EB) subtypes, individuals with MF2-3 exhibited shorter OS (4.8 vs. 11.7 months; p = 0.01) and PFS (3.1 vs. 7.9 months; p = 0.006) than those in patients with MF0-1. However, individuals with MF0-1 and MF2-3 showed similar OS and PFS rates among the patients with the MDS non-excess blast (MDS-nonEB) subtypes. Additionally, we reclassified the patients with MDS according to the 2022 World Health Organization (WHO) classification. Patients with MDS with fibrosis (MDS-f) had a shorter OS (5.6 vs. 13.8 months; p = 0.01) and PFS (3.1 vs. 7.9 months; p = 0.006) than MDS with increased blasts (MDS-IB) subtypes. Our study reveals the unique features of patients with MDS-MF2-3 and validates the refinements made in the 5th edition of the WHO proposal.