ABSTRACT
Richter transformation (RT) is an aggressive lymphoma occurring in patients with chronic lymphocytic leukaemia. Here we investigated the anti-CD3/anti-CD19 T-cell-engager blinatumomab after R-CHOP (i.e. rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients with untreated RT of diffuse large B-cell lymphoma histology (NCT03931642). In this multicentre phase 2 study, patients without complete response (CR) after two cycles of R-CHOP were eligible to receive an 8-week blinatumomab induction via continuous vein infusion with stepwise dosing until 112 µg/day. The primary endpoint was the CR rate after blinatumomab induction and secondary endpoint included safety, response duration, progression-free and overall survival. Thirty-nine patients started the first cycle of R-CHOP, 25 of whom received blinatumomab. After blinatumomab induction, five (20%) patients achieved CR, four (16%) achieved partial response, and six (24%) were stable. Considering the entire strategy, the overall response rate in the full-analysis-set was 46% (n = 18), with CR in 14 (36%) patients. The most common treatment-emergent adverse events of all grades in the blinatumomab-safety-set included fever (36%), anaemia (24%), and lymphopaenia (24%). Cytokine release syndrome (grade 1/2) was observed in 16% and neurotoxicity in 20% of patients. Blinatumomab demonstrated encouraging anti-tumour activity (the trial met its primary endpoint) and acceptable toxicity in patients with RT.
Subject(s)
Antibodies, Bispecific , Antineoplastic Combined Chemotherapy Protocols , Cyclophosphamide , Doxorubicin , Lymphoma, Large B-Cell, Diffuse , Prednisone , Rituximab , Vincristine , Humans , Male , Female , Antibodies, Bispecific/administration & dosage , Antibodies, Bispecific/adverse effects , Antibodies, Bispecific/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Middle Aged , Cyclophosphamide/therapeutic use , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Rituximab/administration & dosage , Rituximab/therapeutic use , Rituximab/adverse effects , Doxorubicin/therapeutic use , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Aged , Prednisone/therapeutic use , Prednisone/administration & dosage , Prednisone/adverse effects , Vincristine/therapeutic use , Vincristine/adverse effects , Vincristine/administration & dosage , Lymphoma, Large B-Cell, Diffuse/drug therapy , Adult , Aged, 80 and over , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Treatment OutcomeABSTRACT
The low incidence of vincristine-induced peripheral neuropathy (VIPN) in Kenyan children may result from low vincristine exposure. We studied vincristine exposure in Kenyan children and dose-escalated in case of low vincristine exposure (NCT05844670). Average vincristine exposure was high. Individual vincristine exposure was assessed with a previously developed nomogram. A 20% dose increase was recommended for participants with low exposure and no VIPN, hyperbilirubinemia, or malnutrition. None of the 15 participants developed VIPN. Low vincristine exposure was seen in one participant: a dose increase was implemented without side effects. In conclusion, the participants did not develop VIPN despite having high vincristine exposure.
Subject(s)
Feasibility Studies , Peripheral Nervous System Diseases , Vincristine , Humans , Vincristine/adverse effects , Vincristine/administration & dosage , Female , Male , Kenya , Child, Preschool , Child , Peripheral Nervous System Diseases/chemically induced , Infant , Antineoplastic Agents, Phytogenic/adverse effects , Antineoplastic Agents, Phytogenic/administration & dosage , Neoplasms/drug therapy , Follow-Up Studies , AdolescentABSTRACT
Prostate cancer is a prevalent carcinoma among males, and conventional treatment options are often limited. Cytotoxic chemotherapy, despite its drawbacks, remains a mainstay. We propose a targeted co-delivery approach using nanoscale delivery units for Oncolytic measles virus (OMV) and vincristine (VC) to enhance treatment efficacy. The HA-coated OMV + VC-loaded TCs nanoformulation is designed for targeted oncolytic activity in prostate cancer. The CD44 expression analysis in prostate cancer cell lines indicates a significantly high expression in PC3 cells. The optimization of nanoformulations using Design of Expert (DOE) is performed, and the preparation and characterization of HA-coated OMV + VC-loaded TCs nanoformulations are detailed showing average particle size 397.2 ± 0.01 nm and polydispersity index 0.122 with zeta potential 19.7 + 0.01 mV. Results demonstrate successful encapsulation efficiency with 2.4 × 106 TCID50/Ml and sustained release of OMV and VC from the nanoformulation for up to 72 h. In vitro, assays reveal potent anticancer activity at 10 ± 0.71% cell viability in PC3 cells compared to 73 ± 0.66% in HPrEC and significant morphological changes at 90 µg/ml in dose and time-dependent manner. The co-formulation showed positive cell death 49.5 ± 0.02% at 50 µg PI/ml in PBS and 54.3% cell cycle arrest at the G2/M phase, 8.1% G0/G1 and 5.7% at S phase, with significant mitochondrial membrane potential (MMP) at 50 µg/ml, as assessed by flow cytometry (FACS). The surface-integrating ligand approach enhances the targeted delivery of the oncolytic virus and chemotherapeutic drug, presenting a potential alternative for prostate cancer treatment and suggested that co-administering VC and OMV in a nanoformulation could improve therapeutic outcomes while reducing chemotherapeutic drug doses.
Subject(s)
Oncolytic Virotherapy , Oncolytic Viruses , Prostatic Neoplasms , Vincristine , Humans , Male , Prostatic Neoplasms/therapy , Prostatic Neoplasms/drug therapy , Vincristine/pharmacology , Vincristine/administration & dosage , Oncolytic Virotherapy/methods , Cell Line, Tumor , Measles virus/drug effects , Cell Survival/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/administration & dosage , Drug Delivery Systems , Nanoparticles/chemistry , PC-3 CellsABSTRACT
BACKGROUND: The metabolic tumour area (MTA) was found to be a promising predictor of prostate cancer. However, the role of MTA based on 18F-FDG PET/CT in diffuse large B-cell lymphoma (DLBCL) prognosis remains unclear. This study aimed to elucidate the prognostic significance of MTA and evaluate its incremental value to the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) for DLBCL patients treated with first-line R-CHOP regimens. METHODS: A total of 280 consecutive patients with newly diagnosed DLBCL and baseline 18F-FDG PET/CT data were retrospectively evaluated. Lesions were delineated via a semiautomated segmentation method based on a 41% SUVmax threshold to estimate semiquantitative metabolic parameters such as total metabolic tumour volume (TMTV) and MTA. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off values. Progression-free survival (PFS) and overall survival (OS) were the endpoints that were used to evaluate the prognosis. PFS and OS were estimated via KaplanâMeier curves and compared via the log-rank test. RESULTS: Univariate analysis revealed that patients with high MTA, high TMTV and NCCN-IPI ≥ 4 were associated with inferior PFS and OS (P < 0.0001 for all). Multivariate analysis indicated that MTA remained an independent predictor of PFS and OS [hazard ratio (HR), 2.506; 95% confidence interval (CI), 1.337-4.696; P = 0.004; and HR, 1.823; 95% CI, 1.005-3.310; P = 0.048], whereas TMTV was not. Further analysis using the NCCN-IPI model as a covariate revealed that MTA and NCCN-IPI were still independent predictors of PFS (HR, 2.617; 95% CI, 1.494-4.586; P = 0.001; and HR, 2.633; 95% CI, 1.650-4.203; P < 0.0001) and OS (HR, 2.021; 95% CI, 1.201-3.401; P = 0.008; and HR, 3.869; 95% CI, 1.959-7.640; P < 0.0001; respectively). Furthermore, MTA was used to separate patients with high NCCN-IPI risk scores into two groups with significantly different outcomes. CONCLUSIONS: Pre-treatment MTA based on 18F-FDG PET/CT and NCCN-IPI were independent predictor of PFS and OS in DLBCL patients treated with R-CHOP. MTA has additional predictive value for the prognosis of patients with DLBCL, especially in high-risk patients with NCCN-IPI ≥ 4. In addition, the combination of MTA and NCCN-IPI may be helpful in further improving risk stratification and guiding individualised treatment options. TRIAL REGISTRATION: This research was retrospectively registered with the Ethics Committee of the Third Affiliated Hospital of Soochow University, and the registration number was approval No. 155 (approved date: 31 May 2022).
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Cyclophosphamide , Doxorubicin , Fluorodeoxyglucose F18 , Lymphoma, Large B-Cell, Diffuse , Positron Emission Tomography Computed Tomography , Prednisone , Rituximab , Vincristine , Humans , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/diagnostic imaging , Lymphoma, Large B-Cell, Diffuse/mortality , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Positron Emission Tomography Computed Tomography/methods , Vincristine/therapeutic use , Vincristine/administration & dosage , Cyclophosphamide/therapeutic use , Cyclophosphamide/administration & dosage , Middle Aged , Female , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Prednisone/administration & dosage , Prednisone/therapeutic use , Doxorubicin/therapeutic use , Doxorubicin/administration & dosage , Prognosis , Aged , Retrospective Studies , Adult , Rituximab/therapeutic use , Aged, 80 and over , Young Adult , Tumor Burden/drug effects , ROC Curve , Radiopharmaceuticals , AdolescentABSTRACT
OBJECTIVE: Raising awareness of acquired hemophilia A (AHA) and early diagnosis is critical to reduce the associated mortality rate. We aimed to characterize acquired hemophilia in Chinese patients and evaluate the effectiveness of immunotherapy. METHODS: The clinical characteristics, laboratory test data, therapeutic approaches, and outcomes of 20 patients with AHA who were admitted to Xi'an Central Hospital between January 2012 and December 2020 were retrospectively studied. RESULTS: Nine of the patients (45%) were treated by single glucocorticoid administration; three (15%) with cyclophosphamide (CP) in combination with a glucocorticoid; four individuals (20%) received a combination therapy of rituximab with CP and glucocorticoid or rituximab with CP, vincristine, and a glucocorticoid; three (15%) by injection of human immunoglobulin in combination with a glucocorticoid; and one (5%) with CP alone. Six patients (30%) achieved total remission and 11 (55%) partial remission (PR), but three (15%) did not enter remission, indicating an objective response rate of 85%. CONCLUSION: Combination therapy with rituximab or intravenous human immunoglobulin achieves superior results in some patients with AHA. Immunosuppression and the administration of coagulation factors can rapidly control the disease and are efficacious, but >50% of patients only achieved PR. These findings suggest that the complete elimination of inhibitors requires prolonged immunosuppression therapy.
Subject(s)
Cyclophosphamide , Hemophilia A , Immunotherapy , Rituximab , Humans , Hemophilia A/immunology , Hemophilia A/drug therapy , Hemophilia A/therapy , Male , Retrospective Studies , Middle Aged , Female , Aged , Adult , Rituximab/therapeutic use , Rituximab/administration & dosage , Cyclophosphamide/therapeutic use , Cyclophosphamide/administration & dosage , Immunotherapy/methods , Treatment Outcome , Glucocorticoids/therapeutic use , Glucocorticoids/administration & dosage , Immunoglobulins, Intravenous/therapeutic use , Immunoglobulins, Intravenous/administration & dosage , Vincristine/therapeutic use , Vincristine/administration & dosage , Drug Therapy, Combination , Immunosuppressive Agents/therapeutic useABSTRACT
INTRODUCTION: Ewing sarcoma (ES), is a rare cancer affecting children, adolescents and adults. After VIDE (vincristine-ifosfamide-doxorobucin-etoposide) induction chemotherapy, Busulfan-Melphalan (BuMel) high-dose chemotherapy followed by autologous hematopoietic stem cells transplantation improved outcomes in unfavourable localized ES, but with more toxicities than conventional chemotherapy (VAI: Vincristine-dactinomycin-Ifosfamide). We evaluated whether the risk of acute toxicity associated with BuMel compared to VAI varied according to age in patients recruited in the R2Loc and R2Pulm randomised trials of the Euro-E.W.I.N.G.99 and Ewing-2008 trials. METHODS: We included patients with a localized high-risk disease, or pulmonary or pleural metastasis. We analysed the risk of severe toxicity according to randomised treatment group (VAI versus BuMel) and age group (<12 years, 12-17 years, 18-24 years, ≥25 years). We evaluated the heterogeneity of treatment effects by age group using interaction terms in logistic multivariable models. RESULTS: The analysis included 243 patients treated with VAI and 205 with BuMel. Overall, BuMel was associated with a higher risk of severe acute toxicity than VAI particularly haematological, gastrointestinal, liver, sinusoidal occlusive syndrome, and infections. Severe haematological toxicity and lower general condition were significantly more frequent in younger patients, whatever treatment. We did not observe any significant heterogeneity in terms of the excess risk of severe toxicities associated with BuMel compared to VAI according to age group. CONCLUSION: The excess of acute toxicity associated with BuMel compared to VAI does not vary significantly with age, suggesting the feasibility of BuMel across all age groups.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Busulfan , Hematopoietic Stem Cell Transplantation , Melphalan , Sarcoma, Ewing , Transplantation, Autologous , Humans , Hematopoietic Stem Cell Transplantation/methods , Hematopoietic Stem Cell Transplantation/adverse effects , Sarcoma, Ewing/drug therapy , Sarcoma, Ewing/therapy , Busulfan/administration & dosage , Busulfan/adverse effects , Child , Adolescent , Young Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Melphalan/administration & dosage , Melphalan/adverse effects , Melphalan/therapeutic use , Male , Female , Age Factors , Adult , Etoposide/administration & dosage , Etoposide/adverse effects , Bone Neoplasms/drug therapy , Bone Neoplasms/secondary , Vincristine/adverse effects , Vincristine/administration & dosage , Vincristine/therapeutic use , Child, Preschool , Ifosfamide/administration & dosage , Ifosfamide/adverse effects , Treatment OutcomeABSTRACT
PURPOSE: To study the inner and outer retinal functions using a full-field electroretinogram (ERG) before and after intravenous chemotherapy (IVC) in children with retinoblastoma (RB). METHODS: Of the 11 eyes, seven had RB and four were normal. All children were examined under anesthesia using a handheld ERG machine with a standard protocol - light-adapted single-flash ERG (fERG), photopic single-flash 3.0- and 30-Hz flickers, and photopic negative response (PhNR) amplitudes at 72 ms (P72). The amplitudes and peak times were compared before and after IVC. RESULTS: Post-chemotherapy tumor regressed in all seven eyes. Of the seven eyes, the fERG peak time (a-wave) was delayed in two eyes (29%), whereas the b-wave was delayed in six eyes (86%). The fERG amplitude height for a- and b-waves decreased in five eyes (71%) and six eyes (86%), respectively. In addition, photopic flicker 30-Hz b-wave peak time delayed in five eyes (71%), whereas the b-wave amplitude height decreased in six eyes (86%). Simultaneously, the P72 amplitude height decreased in six eyes (86%), whereas the P-ratio increased in all seven eyes (100%). In comparison, the ERG responses improved in three of the four contralateral normal eyes. Overall, the cone function improved in two eyes (29%), whereas cone bipolar cell and retinal ganglion cell (RGC) function improved in one eye (14%) each. CONCLUSION: Comparison of light-adapted ERG changes before and after IVC showed reduced amplitudes and delayed peak times for both a and b waveforms, as well as reduced PhNR amplitude attributable to bipolar and RGC injury.
Subject(s)
Electroretinography , Retinal Neoplasms , Retinoblastoma , Humans , Retinoblastoma/drug therapy , Retinoblastoma/physiopathology , Retinoblastoma/diagnosis , Electroretinography/methods , Retinal Neoplasms/drug therapy , Retinal Neoplasms/physiopathology , Retinal Neoplasms/diagnosis , Male , Female , Child, Preschool , Infant , Retina/physiopathology , Antineoplastic Combined Chemotherapy Protocols , Child , Vincristine/therapeutic use , Vincristine/administration & dosage , Follow-Up Studies , Antineoplastic Agents/administration & dosageABSTRACT
Infection is a major cause of treatment-related morbidity and mortality in pediatric acute lymphoblastic leukemia (ALL). Most children with ALL who develop life-threatening bacterial infections do so during induction therapy. We describe a rare case of ALL presenting simultaneously with Streptococcus agalactiae group B Streptococcus bacteremia and meningitis in a 3-year-old girl. She received appropriate antimicrobial therapy and a 2-drug early induction regimen consisting of vincristine and dexamethasone, leading to slow neurologic recovery and a favorable initial response to anti-neoplastic therapy as evidenced by minimal residual disease of 1.12% on day 15 of induction.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Dexamethasone , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Streptococcal Infections , Streptococcus agalactiae , Humans , Female , Child, Preschool , Streptococcal Infections/drug therapy , Streptococcal Infections/microbiology , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/complications , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Dexamethasone/therapeutic use , Dexamethasone/administration & dosage , Meningitis, Bacterial/drug therapy , Meningitis, Bacterial/microbiology , Meningitis, Bacterial/diagnosis , Vincristine/administration & dosage , Vincristine/therapeutic use , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Bacteremia/drug therapy , Bacteremia/microbiologyABSTRACT
A 44-year-old HIV-positive man diagnosed with diffuse large B-cell lymphoma in 2021 achieved complete remission with six cycles of R-CHOP therapy but had a relapse in November 2022. ESHAP therapy failed to induce remission, leading to complete remission with four cycles of Pola-BR therapy. Post-failure of autologous stem cell harvest, cord blood transplantation (CBT) was performed in June 2023. Notably, this case used recently approved intramuscular antiretroviral therapy (ART) with cabotegravir and rilpivirine, addressing gastrointestinal complications during CBT. This innovative use of intramuscular ART in the treatment of malignancy represents a first in the field, offering a pioneering approach to HIV-related lymphoma.
Subject(s)
Cord Blood Stem Cell Transplantation , HIV Infections , Lymphoma, Large B-Cell, Diffuse , Humans , Male , Adult , Cord Blood Stem Cell Transplantation/adverse effects , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/therapy , HIV Infections/drug therapy , HIV Infections/complications , Lymphoma, AIDS-Related/drug therapy , Lymphoma, AIDS-Related/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Injections, Intramuscular , Prednisone/therapeutic use , Prednisone/administration & dosage , Doxorubicin/therapeutic use , Doxorubicin/administration & dosage , Vincristine/therapeutic use , Vincristine/administration & dosage , Cyclophosphamide/therapeutic use , Cyclophosphamide/administration & dosage , Rituximab/therapeutic use , Rituximab/administration & dosage , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/administration & dosage , Anti-Retroviral Agents/therapeutic use , Anti-Retroviral Agents/administration & dosageABSTRACT
Health-related quality of life (HRQoL) data are important indicators of health status in patients with lymphoma. The objective of this analysis was to assess the impact of treatment with Sandoz rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) on HRQoL in treatment-naïve adult patients with diffuse large B-cell lymphoma (DLBCL) included in the prospective, real-world REFLECT study. REFLECT is the first prospective study to assess HRQoL in patients with DLBCL treated with a rituximab biosimilar. HRQoL was assessed via the patient-reported European Organization for Research and Treatment of Cancer Core Quality of Life questionnaire at baseline, mid-treatment (month 3), end of treatment (month 6), and follow-up (months 9 and 12). Subgroup analyses were performed to evaluate the influence of baseline characteristics on HRQoL, and associations between baseline HRQoL and treatment response. HRQoL was assessed in 169 patients. Mean global health status score remained stable from baseline (54.8) to mid-treatment (month 3; 54.7), before steadily improving through to end of treatment (month 6; 61.4), and follow-up month 9 (64.9) and month 12 (68.8). Similar trends were observed across most functional and symptom subscales. Higher cognitive, physical, or role functioning, and less appetite loss, diarrhea, fatigue, or pain at baseline, were all associated with an improved likelihood of reaching a complete versus partial response at the end of treatment. Overall, these findings confirm the HRQoL benefits of R-CHOP therapy in treatment-naïve adult patients with DLBCL, and suggest that baseline HRQoL may be predictive of treatment response.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Cyclophosphamide , Doxorubicin , Lymphoma, Large B-Cell, Diffuse , Prednisone , Quality of Life , Rituximab , Vincristine , Humans , Lymphoma, Large B-Cell, Diffuse/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Rituximab/administration & dosage , Rituximab/therapeutic use , Vincristine/administration & dosage , Vincristine/therapeutic use , Cyclophosphamide/administration & dosage , Cyclophosphamide/therapeutic use , Doxorubicin/administration & dosage , Doxorubicin/therapeutic use , Prednisone/administration & dosage , Prednisone/therapeutic use , Male , Female , Middle Aged , Prospective Studies , Aged , Adult , Germany , Aged, 80 and over , Follow-Up StudiesABSTRACT
BACKGROUND: Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is one of the first line treatments for diffuse large B-cell lymphoma (DLBCL). Rituximab comprises most of the treatment cost for this regimen; therefore, biosimilars, such as rituximab-abbs are crucial to provide affordable care. Although rituximab-abbs was studied primarily in follicular lymphoma, the Food and Drug Administration (FDA) approved this drug for all indications of the reference product on the basis of extrapolation. Effectiveness and safety data surrounding the use of rituximab-abbs in DLBCL is lacking. OBJECTIVE: To evaluate the effectiveness and safety of rituximab-abbs and reference product rituximab as R-CHOP treatment for patients with DLBCL. PATIENTS AND METHODS: This noninferiority (NI) study compared the 2-year overall survival (OS), overall response rate (ORR), and incidence of adverse events (AEs) between rituximab-abbs and its reference product (RP) in R-CHOP among adult patients with newly diagnosed DLBCL. The study inclusion period was from 1 January 2019 to 31 December 2020. Analyses were performed on the basis of a noninferiority lower limit of 10% for OS and ORR, and an upper limit of 10% for serious AEs. RESULTS: There were 240 patients who received RP rituximab, while 295 patients received rituximab-abbs. The cohort had a mean age of 63.7±12.2 years and 43% were female. The 2-year OS was 81.0% and 79.6% (NI p < 0.01) while the ORR was 80.0% and 69.6% (NI p < 0.01), among the rituximab-abbs and rituximab groups, respectively. The incidence of infusion reaction AEs (NI p < 0.01) and noninfusion reaction AEs (NI p < 0.01) also met noninferiority. CONCLUSIONS: We demonstrated that rituximab-abbs was noninferior to rituximab in both effectiveness and safety among patients receiving R-CHOP for DLBCL in this study. Long-term follow-up would be needed to confirm these results.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Cyclophosphamide , Doxorubicin , Lymphoma, Large B-Cell, Diffuse , Prednisone , Rituximab , Vincristine , Humans , Rituximab/therapeutic use , Rituximab/adverse effects , Rituximab/administration & dosage , Lymphoma, Large B-Cell, Diffuse/drug therapy , Female , Middle Aged , Male , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Doxorubicin/therapeutic use , Doxorubicin/adverse effects , Doxorubicin/administration & dosage , Cyclophosphamide/therapeutic use , Cyclophosphamide/adverse effects , Cyclophosphamide/administration & dosage , Aged , Prednisone/therapeutic use , Prednisone/administration & dosage , Prednisone/adverse effects , Vincristine/therapeutic use , Vincristine/adverse effects , Vincristine/administration & dosage , Adult , Biosimilar Pharmaceuticals/therapeutic use , Biosimilar Pharmaceuticals/adverse effects , Biosimilar Pharmaceuticals/administration & dosage , Treatment Outcome , Aged, 80 and overABSTRACT
BACKGROUND: The Children's Oncology Group defines intermediate-risk rhabdomyosarcoma as unresected FOXO1 fusion-negative disease arising at an unfavourable site or non-metastatic FOXO1 fusion-positive disease. Temsirolimus in combination with chemotherapy has shown promising activity in patients with relapsed or refractory rhabdomyosarcoma. We aimed to compare event-free survival in patients with intermediate-risk rhabdomyosarcoma treated with vincristine, actinomycin, and cyclophosphamide alternating with vincristine and irinotecan (VAC/VI) combined with temsirolimus followed by maintenance therapy versus VAC/VI alone with maintenance therapy. METHODS: ARST1431 was a randomised, open-label, phase 3 trial conducted across 210 institutions in Australia, Canada, New Zealand, and the USA. Eligible patients were those aged 40 years or younger with non-metastatic FOXO1-positive rhabdomyosarcoma or unresected FOXO1-negative rhabdomyosarcoma disease from unfavourable sites. Two other groups of patients were also eligible: those who had FOXO1-negative disease at a favourable site (excluding orbit) that was unresected; and those who were aged younger than 10 years with stage IV FOXO1-negative disease with distant metastases. Eligible patients had to have a Lansky performance status score of 50 or higher if 16 years or younger and a Karnofsky performance status score of 50 or higher if older than 16 years; all patients were previously untreated. Patients were randomised (1:1) in blocks of four and stratified by histology, stage, and group. Patients received intravenous VAC/VI chemotherapy with a cyclophosphamide dose of 1·2 g/m2 per dose per cycle with or without a reducing dose of intravenous weekly temsirolimus starting at 15 mg/m2 or 0·5 mg/kg per dose for those who weighed less than 10 kg. The total duration of therapy was 42 weeks followed by 6 months of maintenance therapy with oral cyclophosphamide plus intravenous vinorelbine for all patients. Temsirolimus was withheld during radiotherapy and for 2 weeks before any major surgical procedure. The primary endpoint was 3-year event-free survival. Data were analysed with a revised intention-to-treat approach. The study is registered with ClinicalTrials.gov (NCT02567435) and is complete. FINDINGS: Between May 23, 2016, and Jan 1, 2022, 325 patients were enrolled. In 297 evaluable patients (148 assigned to VAC/VI alone and 149 assigned to VAC/VI with temsirolimus), the median age was 6·3 years (IQR 3·0-11·3); 33 (11%) patients were aged 18 years or older; 179 (60%) of 297 were male. 113 (77%) of 148 patients were FOXO1 negative in the VAC/VI group, and 108 (73%) of 149 were FOXO1 negative in the VAC/VI with temsirolimus group. With a median follow-up of 3·6 years (IQR 2·8-4·5), 3-year event-free survival did not differ significantly between the two groups (64·8% [95% CI 55·5-74·1] in the VAC/VI group vs 66·8% [57·5-76·2] in the VAC/VI plus temsirolimus group (hazard ratio 0·86 [95% CI 0·58-1·26]; log-rank p=0·44). The most common grade 3-4 adverse events were anaemia (62 events in 60 [41%] of 148 patients in the VAC/VI group vs 89 events in 87 [58%] of 149 patients in the VAC/VI with temsirolimus group), lymphopenia (83 events in 65 [44%] vs 99 events in 71 [48%]), neutropenia (160 events in 99 [67%] vs 164 events in 105 [70%]), and leukopenia (121 events in 86 [58%] vs 132 events in 93 [62%]). There was one treatment-related death in the VAC/VI with temsirolimus group, categorised as not otherwise specified. INTERPRETATION: Addition of temsirolimus to VAC/VI did not improve event-free survival in patients with intermediate-risk rhabdomyosarcoma defined by their FOXO1 translocation status and clinical factors. Novel biology-based strategies are needed to improve outcomes in this population. FUNDING: The Children's Oncology Group (supported by the US National Cancer Institute, US National Institutes of Health).
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Cyclophosphamide , Rhabdomyosarcoma , Sirolimus , Vincristine , Humans , Male , Female , Child , Adolescent , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Sirolimus/analogs & derivatives , Sirolimus/administration & dosage , Sirolimus/therapeutic use , Rhabdomyosarcoma/drug therapy , Rhabdomyosarcoma/mortality , Rhabdomyosarcoma/pathology , Child, Preschool , Vincristine/administration & dosage , Vincristine/adverse effects , Young Adult , Cyclophosphamide/administration & dosage , Adult , Dactinomycin/administration & dosage , Irinotecan/administration & dosage , Irinotecan/therapeutic use , Infant , Progression-Free Survival , Forkhead Box Protein O1/geneticsABSTRACT
BACKGROUND: Despite the excellent outcomes achieved in the treatment of pediatric Burkitt lymphoma (BL) in high-income countries (HICs), outcomes remain poor in low- and middle-income countries (LMICs). Efforts to improve BL outcomes in Tanzania included the creation of National Treatment Guidelines in 2016. However, disease outcomes in Tanzania following the creation of these guidelines have not been reported to date. PROCEDURE: Historical records from 2016 to 2021 for patients 0-18 years of age with a diagnosis of BL and seen at Bugando Medical Centre (BMC), in Mwanza, Tanzania, were curated into an electronic database and analyzed descriptively. Patients in this cohort were treated per the Tanzanian National Treatment Guidelines, which include six cycles of cyclophosphamide, vincristine, and methotrexate (COM) chemotherapy with intrathecal methotrexate and cytarabine. RESULTS: In total, 92 BL patients' records were eligible for analysis. Patients in this cohort were most commonly Murphy stage II (28%) or stage III (34%). Nearly all, 91%, met International Network for Cancer Treatment and Research (INCTR) high-risk criteria at presentation. Forty-two percent of patients did not receive a biopsy and were treated with a presumed diagnosis of BL alone. A 1-year event-free survival of 29.6% (95% confidence interval [CI]: 20.3%-39.5%) and a 1-year overall survival of 38.5% (95% CI: 28%-48.9%) were observed. A high rate of treatment abandonment (34%) was also observed. CONCLUSION: In a historical cohort of pediatric patients with BL treated per the 2016 Tanzanian National Treatment Guidelines, we observed poor outcomes and a high rate of abandonment. These outcomes appear inferior to those achieved in the INCTR clinical trial that informed the guidelines' creation, and highlights the importance of "real-world" outcomes data in LMICs. These data reinforce the idea that continued clinical research and capacity building efforts are necessary to improve BL outcomes in LMICs.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Burkitt Lymphoma , Cyclophosphamide , Vincristine , Humans , Burkitt Lymphoma/drug therapy , Burkitt Lymphoma/therapy , Child , Female , Child, Preschool , Male , Tanzania , Adolescent , Retrospective Studies , Infant , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Infant, Newborn , Cyclophosphamide/administration & dosage , Cyclophosphamide/therapeutic use , Vincristine/administration & dosage , Vincristine/therapeutic use , Methotrexate/administration & dosage , Methotrexate/therapeutic use , Practice Guidelines as Topic , Survival Rate , Standard of Care , Cytarabine/administration & dosage , Follow-Up Studies , PrognosisABSTRACT
A 69-year-old woman was previously treated with antibiotics for suspected pyelonephritis due to fever but showed limited improvement. Contrast-enhanced CT revealed heterogeneous areas of decreased contrast enhancement in both kidneys, along with an elevated soluble level of the IL-2 receptor (5,090 U/ml), and thus the patient was referred to our department for further evaluation. A percutaneous renal biopsy performed due to suspected malignant lymphoma confirmed lymphoma cell infiltration into the renal interstitium. Immunohistochemical staining was positive for MYC/BCL2/BCL6, leading to the diagnosis of stage IVB primary renal triple expressor diffuse large B cell lymphoma (DLBCL). Due to acute kidney injury, continuous hemodiafiltration (CHDF) was initiated, followed by rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. The patient's renal function improved rapidly, and complete response was achieved after six cycles of R-CHOP. Although DLBCL is a common lymphoma, the primary renal subtype is extremely rare and poses both diagnostic and therapeutic challenges. This case highlights the potential clinical implications of combining CHDF with chemotherapy to achieve complete response despite an initial poor prognosis based on the patient's overall clinical condition and pathology.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Doxorubicin , Kidney Neoplasms , Lymphoma, Large B-Cell, Diffuse , Prednisone , Vincristine , Humans , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/therapy , Lymphoma, Large B-Cell, Diffuse/pathology , Female , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Doxorubicin/administration & dosage , Vincristine/administration & dosage , Vincristine/therapeutic use , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Kidney Neoplasms/therapy , Prednisone/administration & dosage , Prednisone/therapeutic use , Cyclophosphamide/administration & dosage , Rituximab/administration & dosage , Rituximab/therapeutic use , Renal Dialysis , Treatment Outcome , HemodiafiltrationABSTRACT
Mantle cell lymphoma (MCL) accounts for 3-10% of non-Hodgkin's lymphomas (NHL). We identified 14 patients with mantle cell lymphoma, with an average number of 3.5 new cases/year. A male predominance was observed with a sex ratio equal to 6. The average age of our patients was 64.4±14.1 years, with an average diagnostic delay of 6.57 months. Regarding the clinical presentation, adenopathy was the most reported physical sign (78.6%) followed by B symptoms (57.1%). Disseminated stages were the most frequent in our series: stages IV (78.5%) and III (7.1%) versus stages I (0%) and II (7.1%). The extra-ganglionic localizations observed were hepatic 5 cases (31.1%), pulmonary 04 cases (25%), medullary 4 cases (25%), pleural 2 cases (12.5%) and prostate 1 case (6.2%). All diagnosed cases are mantle cell lymphomas, of which 12 cases (85.7%) are classical and 2 cases (14.3%) indolent. The high-risk group is, according to international prognostic index (MIPI) MCL prognostic score, the most represented in our series: 0-3 = 6 cases (42.9%), 6-11 = 8 cases (57.1%). The therapeutic protocol chosen 1st line: 9 patients treated with R-DHAP, three with R-CHOP, one with DHAOX and one with R-CVP. Second line: two patients treated with R-DHAP, one after R-CHOP and the other after R-CVP. Two patients received autologous hematopoietic stem cell transplant at the end of the treatment. The evolution was marked by the death of 7 patients, 3 lost to follow-up and 4 still followed. Additionally, the study highlights characteristics and treatment patterns of mantle cell lymphoma, emphasizing its predominance in males, delayed diagnosis, frequent dissemination, and high-risk classification, with chemotherapy as the primary treatment modality and a challenging prognosis contributing to a comprehensive understanding of mantle cell lymphoma presentation and management.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Lymphoma, Mantle-Cell , Neoplasm Staging , Humans , Lymphoma, Mantle-Cell/therapy , Lymphoma, Mantle-Cell/pathology , Lymphoma, Mantle-Cell/diagnosis , Lymphoma, Mantle-Cell/epidemiology , Lymphoma, Mantle-Cell/drug therapy , Morocco , Male , Middle Aged , Female , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Aged, 80 and over , Adult , Prognosis , Retrospective Studies , Delayed Diagnosis , Cyclophosphamide/administration & dosage , Vincristine/administration & dosageABSTRACT
Panniculitis is an inflammation that occurs in subcutaneous adipose tissue. Panniculitis includes physical panniculitis (e.g., traumatic) and infectious panniculitis (e.g., bacterial, fungal, subcutaneous panniculitis-like T cell lymphoma [SPCTL], etc.). Accurate diagnosis is crucial due to similar clinical presentation of all types of panniculitis. Here, we report a case of SPCTL which was initially diagnosed with traumatic panniculitis. A 15-year-old male patient was admitted to a previous hospital due to a progressively enlarged right flank and inguinal mass after an abdominal bruise. He was initially diagnosed with traumatic panniculitis, but the mass expanded throughout the chest and abdomen accompanied by a fever of over 11 months. Computed tomography (CT) revealed a subcutaneous mass in the anterior chest and abdominal wall. Fludeoxyglucose F18 (FDG) uptake was observed at those lesions using FDG-positron emission tomography (PET). A biopsy of the mass lesion was performed, during which SPCTL was diagnosed based on pathological examination. He was initially treated with prednisolone and cyclosporine A for two weeks. His fever went down, but subcutaneous mass in the chest and abdominal wall persisted. Therefore, he received a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen. After 6 courses of CHOP, CT revealed no disease evidence. He remained in complete remission at 30 months of therapy.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Cyclophosphamide , Disease Progression , Doxorubicin , Lymphoma, T-Cell , Panniculitis , Vincristine , Humans , Male , Panniculitis/diagnosis , Panniculitis/etiology , Panniculitis/drug therapy , Panniculitis/pathology , Adolescent , Lymphoma, T-Cell/diagnosis , Lymphoma, T-Cell/pathology , Lymphoma, T-Cell/diagnostic imaging , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Vincristine/administration & dosage , Prednisone/administration & dosage , Tomography, X-Ray Computed , Positron-Emission Tomography , Fluorodeoxyglucose F18 , Treatment Outcome , Biopsy , Diagnosis, DifferentialABSTRACT
BACKGROUND: Adding ibrutinib to standard immunochemotherapy might improve outcomes and challenge autologous stem-cell transplantation (ASCT) in younger (aged 65 years or younger) mantle cell lymphoma patients. This trial aimed to investigate whether the addition of ibrutinib results in a superior clinical outcome compared with the pre-trial immunochemotherapy standard with ASCT or an ibrutinib-containing treatment without ASCT. We also investigated whether standard treatment with ASCT is superior to a treatment adding ibrutinib but without ASCT. METHODS: The open-label, randomised, three-arm, parallel-group, superiority TRIANGLE trial was performed in 165 secondary or tertiary clinical centres in 13 European countries and Israel. Patients with previously untreated, stage II-IV mantle cell lymphoma, aged 18-65 years and suitable for ASCT were randomly assigned 1:1:1 to control group A or experimental groups A+I or I, stratified by study group and mantle cell lymphoma international prognostic index risk groups. Treatment in group A consisted of six alternating cycles of R-CHOP (intravenous rituximab 375 mg/m2 on day 0 or 1, intravenous cyclophosphamide 750 mg/m2 on day 1, intravenous doxorubicin 50 mg/m2 on day 1, intravenous vincristine 1·4 mg/m2 on day 1, and oral prednisone 100 mg on days 1-5) and R-DHAP (or R-DHAOx, intravenous rituximab 375 mg/m2 on day 0 or 1, intravenous or oral dexamethasone 40 mg on days 1-4, intravenous cytarabine 2 × 2 g/m2 for 3 h every 12 h on day 2, and intravenous cisplatin 100 mg/m2 over 24 h on day 1 or alternatively intravenous oxaliplatin 130 mg/m2 on day 1) followed by ASCT. In group A+I, ibrutinib (560 mg orally each day) was added on days 1-19 of R-CHOP cycles and as fixed-duration maintenance (560 mg orally each day for 2 years) after ASCT. In group I, ibrutinib was given the same way as in group A+I, but ASCT was omitted. Three pairwise one-sided log-rank tests for the primary outcome of failure-free survival were statistically monitored. The primary analysis was done by intention-to-treat. Adverse events were evaluated by treatment period among patients who started the respective treatment. This ongoing trial is registered with ClinicalTrials.gov, NCT02858258. FINDINGS: Between July 29, 2016 and Dec 28, 2020, 870 patients (662 men, 208 women) were randomly assigned to group A (n=288), group A+I (n=292), and group I (n=290). After 31 months median follow-up, group A+I was superior to group A with 3-year failure-free survival of 88% (95% CI 84-92) versus 72% (67-79; hazard ratio 0·52 [one-sided 98·3% CI 0-0·86]; one-sided p=0·0008). Superiority of group A over group I was not shown with 3-year failure-free survival 72% (67-79) versus 86% (82-91; hazard ratio 1·77 [one-sided 98·3% CI 0-3·76]; one-sided p=0·9979). The comparison of group A+I versus group I is ongoing. There were no relevant differences in grade 3-5 adverse events during induction or ASCT between patients treated with R-CHOP/R-DHAP or ibrutinib combined with R-CHOP/R-DHAP. During maintenance or follow-up, substantially more grade 3-5 haematological adverse events and infections were reported after ASCT plus ibrutinib (group A+I; haematological: 114 [50%] of 231 patients; infections: 58 [25%] of 231; fatal infections: two [1%] of 231) compared with ibrutinib only (group I; haematological: 74 [28%] of 269; infections: 52 [19%] of 269; fatal infections: two [1%] of 269) or after ASCT (group A; haematological: 51 [21%] of 238; infections: 32 [13%] of 238; fatal infections: three [1%] of 238). INTERPRETATION: Adding ibrutinib to first-line treatment resulted in superior efficacy in younger mantle cell lymphoma patients with increased toxicity when given after ASCT. Adding ibrutinib during induction and as maintenance should be part of first-line treatment of younger mantle cell lymphoma patients. Whether ASCT adds to an ibrutinib-containing regimen is not yet determined. FUNDING: Janssen and Leukemia & Lymphoma Society.
Subject(s)
Adenine , Antineoplastic Combined Chemotherapy Protocols , Cyclophosphamide , Lymphoma, Mantle-Cell , Piperidines , Rituximab , Transplantation, Autologous , Vincristine , Humans , Lymphoma, Mantle-Cell/therapy , Lymphoma, Mantle-Cell/drug therapy , Adenine/analogs & derivatives , Adenine/administration & dosage , Adenine/therapeutic use , Piperidines/administration & dosage , Piperidines/therapeutic use , Middle Aged , Male , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Vincristine/administration & dosage , Vincristine/therapeutic use , Rituximab/administration & dosage , Rituximab/therapeutic use , Adult , Cyclophosphamide/administration & dosage , Cyclophosphamide/therapeutic use , Aged , Europe , Hematopoietic Stem Cell Transplantation/methods , Prednisone/administration & dosage , Prednisone/therapeutic use , Doxorubicin/administration & dosage , Young Adult , Dexamethasone/administration & dosage , Dexamethasone/therapeutic use , Adolescent , Israel , Treatment OutcomeABSTRACT
Importance: Options for adults with relapsed or refractory B-cell acute lymphoblastic leukemia or lymphoma (B-ALL) are limited, and new approaches are needed. Inotuzumab ozogamicin (InO) has been combined with low-intensity chemotherapy, with modest improvements over historical controls, and dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) treatment is safe and active for newly diagnosed ALL. Objective: To assess the safety and clinical activity of DA-EPOCH and InO in adults with relapsed or refractory B-ALL. Design, Setting, and Participants: This single-center, single-arm, nonrandomized, phase 1 dose-escalation trial included adults with relapsed or refractory CD22+ B-ALL and was conducted between September 2019 and November 2022. At least 5% blood or marrow blasts or measurable extramedullary disease (EMD) was required for enrollment. Interventions: DA-EPOCH was given on days 1 to 5, while InO was given on day 8 and day 15 of a 28-day cycle. Three dose levels were studied using a bayesian optimal interval design. Main Outcomes and Measures: The primary outcome was the maximum tolerated dose of InO when combined with DA-EPOCH, defined as the highest dose level that produced a rate of dose-limiting toxicity below 33%. Secondary objectives included response rates, survival estimates, and descriptions of toxic effects. Results: A total of 24 participants were screened and enrolled (median age, 46 [range, 28-76] years; 15 [62%] male). The median number of lines of prior therapy was 3 (range, 1-12). Three of 11 participants (27%) treated at the highest dose level (InO, 0.6 mg/m2, on day 8 and day 15) experienced dose-limiting toxicity, making this the maximum tolerated dose. No deaths occurred during the study, and only 1 patient (4%; 95% CI, 0.1%-21%) developed sinusoidal obstructive syndrome after poststudy allograft. The morphologic complete response rate was 84% (95% CI, 60%-97%), 88% (95% CI, 62%-98%) of which was measurable residual disease negative by flow cytometry. Five of 6 participants with EMD experienced treatment response. The overall response rate was 83% (95% CI, 63%-95%). Median overall survival, duration of response, and event-free survival were 17.0 (95% CI, 8.4-not reached), 15.0 (95% CI, 6.7-not reached), and 9.6 (95% CI, 4.5-not reached) months, respectively. Conclusions: In this study, adding InO to DA-EPOCH in adults with relapsed or refractory B-ALL was feasible, with high response rates and sinusoidal obstructive syndrome occurring rarely in a heavily pretreated population. Many patients were able to proceed to poststudy consolidative allogeneic hematopoietic cell transplant and/or chimeric antigen receptor T-cell therapy. Further investigation of this combination is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT03991884.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Cyclophosphamide , Doxorubicin , Etoposide , Inotuzumab Ozogamicin , Prednisone , Vincristine , Humans , Inotuzumab Ozogamicin/administration & dosage , Male , Female , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Adult , Etoposide/administration & dosage , Etoposide/adverse effects , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Cyclophosphamide/administration & dosage , Cyclophosphamide/therapeutic use , Cyclophosphamide/adverse effects , Vincristine/administration & dosage , Vincristine/adverse effects , Vincristine/therapeutic use , Prednisone/administration & dosage , Prednisone/adverse effects , Prednisone/therapeutic use , Aged , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/mortality , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/pathology , Maximum Tolerated Dose , Dose-Response Relationship, DrugABSTRACT
Primary cardiac lymphoma is an exceedingly rare malignant tumor, with diffuse large B-cell lymphoma (DLBCL) being the most prevalent histological subtype. This disease has non-specific clinical manifestations, making early diagnosis crucial. However, DLBCL diagnosis is commonly delayed, and its prognosis is typically poor. Herein, we report the case of a 51-year-old male patient with DLBCL who presented with recurrent chest tightness for 4 months as the primary clinical symptom. The patient was admitted to the hospital and diagnosed with acute myocardial infarction and left ventricular hypertrophy with heart failure. Echocardiography revealed a progression from left ventricular thickening to local pericardial thickening and adhesion in the inferior and lateral walls of the left ventricle. Finally, pathological analysis of myocardial biopsy confirmed the diagnosis of DLBCL. After treatment with the R-CHOP chemotherapy regimen, the patient's chest tightness improved, and he was discharged. After 2 months, the patient succumbed to death owing to sudden ventricular tachycardia, ventricular fibrillation, and decreased blood pressure despite rescue efforts. Transthoracic echocardiography is inevitable for the early diagnosis of DLBCL, as it can narrow the differential and guide further investigations and interventions, thereby improving the survival of these patients.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Echocardiography , Heart Neoplasms , Hypertrophy, Left Ventricular , Lymphoma, Large B-Cell, Diffuse , Myocardial Infarction , Vincristine , Humans , Lymphoma, Large B-Cell, Diffuse/pathology , Lymphoma, Large B-Cell, Diffuse/complications , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/drug therapy , Male , Middle Aged , Heart Neoplasms/complications , Heart Neoplasms/pathology , Heart Neoplasms/diagnosis , Myocardial Infarction/etiology , Myocardial Infarction/diagnosis , Fatal Outcome , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hypertrophy, Left Ventricular/etiology , Vincristine/administration & dosage , Vincristine/therapeutic use , Doxorubicin/administration & dosage , Doxorubicin/therapeutic use , Rituximab/therapeutic use , Rituximab/administration & dosage , Cyclophosphamide/therapeutic use , Cyclophosphamide/administration & dosage , Prednisone/therapeutic use , Prednisone/administration & dosageABSTRACT
DISEASE OVERVIEW: Plasmablastic lymphoma (PBL) is a rare CD20-negative aggressive lymphoma with a poor prognosis under standard treatment options. Though PBL is associated with human immunodeficiency virus infection and other immunosuppressed states, it can also affect immunocompetent individuals. DIAGNOSIS: The diagnosis requires a high clinical suspicion and pathological confirmation. EBER expression and MYC gene rearrangements are frequently detected. The differential diagnosis includes EBV+ diffuse large B-cell lymphoma, extracavitary primary effusion lymphoma, ALK+ DLBCL, and HHV8+ large B-cell lymphoma, among others. RISK STRATIFICATION: Age ≥60 years, advanced clinical stage, and high intermediate and high International Prognostic Index scores are associated with worse survival. MANAGEMENT: Combination chemotherapy regimens, such as EPOCH, are recommended. The addition of bortezomib, lenalidomide, or daratumumab might improve outcomes. Including PBL patients and their participation in prospective clinical trials is warranted.