-
Journal of Investigative Medicine High... 2024Pfizer/BioNTech (BNT162b2) is a messenger RNA (mRNA) vaccine that is highly effective in preventing the most severe outcomes of COVID-19 infection. Nucleoside-modified...
Pfizer/BioNTech (BNT162b2) is a messenger RNA (mRNA) vaccine that is highly effective in preventing the most severe outcomes of COVID-19 infection. Nucleoside-modified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines induce effective stimulation of T follicular helper (TFH) cells, leading to a robust germinal center B cell response. Side effects from the BNT162b2 vaccination, including significant lymphadenopathy, have been reported previously. Here, we present a case of angioimmunoblastic lymphoma (AITL), a rare, peripheral T-cell lymphoma with RHOA-G17v-mutated gene developing in a patient following BNT162B2 vaccine with a plausible explanation. A 60-year-old Asian female received her first dose of Pfizer BNT162B2 mRNA vaccine in August 2021. Right after her vaccination, she developed right axillary lymphadenopathy. She received her second vaccine dose in September 2021. Thereafter, she developed lymph node (LN) enlargement in her neck and groin. She underwent left posterior cervical and left groin LN excisional biopsy in April 2022 due to persistent palpable lymphadenopathy. Biopsy results then demonstrated benign follicular hyperplasia. For progressive B symptoms, a right axillary LN biopsy was done, which demonstrated AITL, with molecular studies revealing mutation in TET-2, IDH-2, and RHOA-G17v genes. Progression of AITL following BNT162B2 mRNA vaccine is limited in literature. Our case demonstrates a plausible correlation between the diagnosis of AITL following mRNA vaccination due to the malignant transformation of the TFH cells in patients who have a predisposing mutation of RHOA-17v. Given the rarity of AITL and the heterogeneity of molecular findings, more studies are needed to establish such an association.
Topics: Humans; Female; BNT162 Vaccine; Middle Aged; rhoA GTP-Binding Protein; Immunoblastic Lymphadenopathy; COVID-19; COVID-19 Vaccines; Lymphoma, T-Cell, Peripheral; SARS-CoV-2
PubMed: 38761096
DOI: 10.1177/23247096241231645 -
Blood Cancer Journal May 2024
Topics: Humans; Antigens, CD19; Lymphoma, Large B-Cell, Diffuse; Immunotherapy, Adoptive; Male; Female; T-Lymphocytes; Middle Aged; Receptors, Chimeric Antigen; Treatment Outcome; Aged; Adult
PubMed: 38760376
DOI: 10.1038/s41408-024-01065-z -
Blood Cancer Journal May 2024Autologous stem cell transplantation (autoHCT) is considered standard of care for newly diagnosed multiple myeloma (MM). Although most patients eventually progress after...
Autologous stem cell transplantation (autoHCT) is considered standard of care for newly diagnosed multiple myeloma (MM). Although most patients eventually progress after autoHCT, a small proportion achieve a durable response. In this retrospective study we included 1576 patients, 244 (15%) of whom were long-term responders (LTR), defined as having a progression-free survival (PFS) of ≥8 years after transplant. Patients in the LTR group were younger than the non-LTR group (median age 58.4 vs. 59.5 years; p = 0.012), less likely to have high-risk cytogenetics (4% vs. 14%; p < 0.001), more often had <50% bone marrow plasma cells (67% vs. 58%; p = 0.018) and R-ISS stage I disease (43% vs. 34%). More patients in the LTR group received post-transplant maintenance (63% vs. 52%; p = 0.002). Patients in the LTR group had higher rates of complete response (CR) at day100 (41% vs. 27%; p < 0.001) and at best post-transplant response (70% vs. 37%; p < 0.001), compared to the non-LTR group. Patients in the LTR groups had a median PFS of 169.3 months and the median overall survival (OS) had not been reached. The leading cause of death in the LTR was disease progression. In conclusion, 15% of patients in the cohort were LTR after upfront autoHCT, with distinct characteristics and a median PFS of more than 14 years.
Topics: Humans; Multiple Myeloma; Middle Aged; Hematopoietic Stem Cell Transplantation; Male; Female; Transplantation, Autologous; Aged; Retrospective Studies; Adult; Remission Induction; Treatment Outcome
PubMed: 38760362
DOI: 10.1038/s41408-024-01062-2 -
Technology in Cancer Research &... 20241q21 gain/Amp is one of the most common cytogenetic abnormalities. There are controversies about its effects on prognosis and may be associated with inferior outcomes in...
OBJECTIVE
1q21 gain/Amp is one of the most common cytogenetic abnormalities. There are controversies about its effects on prognosis and may be associated with inferior outcomes in patients with newly diagnosed multiple myeloma (NDMM). To explore the optimal induction treatment, we analyzed and compared the efficacy of combinations of bortezomib-lenalidomide-dexamethasone (VRD) and only bortezomib-based triplet regimens without lenalidomide (only bortezomib-based) as induction therapy in patients with NDMM with 1q21 gain/Amp.
METHODS
Seventy-six NDMM patients with 1q21 gain/Amp who were admitted to our center from 2016 to 2022 were retrospectively analyzed in this study. The progression and efficacy of the patients were observed.
RESULTS
Within our study group, the overall survival rate stood at 75.0%, and the progression-free survival (PFS) rate reached 40.8% in NDMM patients with 1q21 gain/Amp. The best outcome assessment was that 17.1% achieved complete response (CR) and 44.7% achieved very good partial response (VGPR). Patients in the VRD group had a deeper response (VGPR: 63.6% 37.0%, = 0.034), lower disease progression rate (31.8% 70.3%, = 0.002), longer sustained remission (median 49.7 months 18.3 months, = 0.030), and longer PFS (median 61.9 months 22.9 months, = 0.032) than those treated with only bortezomib-based induction therapy. No significant differences were found among patients with partial response or better (86.4% 77.8%, = 0.532) or CR (27.3% 13.0%, = 0.180). Multivariate analysis showed that only bortezomib-based induction therapy (= 0.003, HR 0.246, 95% CI 0.097-0.620), International Staging System stage III (= 0.003, HR 3.844, 95% CI 1.588-9.308) and LMR <3.6 (= 0.032, HR 0.491, 95% CI 0.257-0.940) were significantly associated with adverse PFS.
CONCLUSIONS
When compared with the sequential administration of bortezomib and lenalidomide or only bortezomib-based protocols, NDMM patients with 1q21 gain/Amp may benefit more from VRD as initial treatments.
Topics: Humans; Bortezomib; Lenalidomide; Multiple Myeloma; Female; Male; Antineoplastic Combined Chemotherapy Protocols; Middle Aged; Aged; Chromosomes, Human, Pair 1; Adult; Retrospective Studies; Prognosis; Treatment Outcome; Chromosome Aberrations; Aged, 80 and over; Dexamethasone
PubMed: 38759699
DOI: 10.1177/15330338241252605 -
Medicine May 2024This study aimed to investigate changes in hand sensation (finger tactile threshold and two-point discrimination) and function in patients with malignant lymphoma,... (Observational Study)
Observational Study
This study aimed to investigate changes in hand sensation (finger tactile threshold and two-point discrimination) and function in patients with malignant lymphoma, particularly during the early stages of chemotherapy with vincristine. Eighteen patients with malignant lymphoma were enrolled in this study. Data on the Common Terminology Criteria for Adverse Events Version 4.0, the visual analog scale for hand numbness, the Semmes Weinstein monofilament test, static and moving two-point discrimination (2PD), grip strength, pinch strength, and the Purdue Pegboard test were collected at 3 time points: before the start of chemotherapy (T0), after the first cycle of chemotherapy (T1), and after the second cycle of chemotherapy (T2). No significant changes were observed in Semmes Weinstein monofilament test at T0, T1, or T2 in either hand. However, the static 2PD was significantly worse for the right ring, little, and left middle fingers, whereas the moving 2PD was significantly worse for the right ring, left index, middle, and ring fingers. Furthermore, the visual analog scale scores for hand numbness and left-hand grip strength worsened significantly. Right-hand grip strength, pinch strength of both hands, and Purdue Pegboard test showed no significant deterioration. Chemotherapy with vincristine may affect hand sensation and function in patients with malignant lymphoma by exacerbating finger 2PD and hand numbness. Additionally, during the early stages of vincristine chemotherapy, it is important to monitor for a decrease in grip strength specifically in the left hand.
Topics: Humans; Vincristine; Male; Female; Hand Strength; Middle Aged; Lymphoma; Hand; Aged; Adult; Antineoplastic Agents, Phytogenic; Hypesthesia
PubMed: 38758870
DOI: 10.1097/MD.0000000000038207 -
Journal of Clinical Immunology May 2024Deficiency of Adenosine Deaminase 2 (DADA2) patients presenting with primary immunodeficiency are at risk of uncontrolled EBV infection and secondary malignancies...
Deficiency of Adenosine Deaminase 2 (DADA2) patients presenting with primary immunodeficiency are at risk of uncontrolled EBV infection and secondary malignancies including EBV-related lymphoproliferative disorders (LPD). This paper describes the first case of EBV related diffuse large B-cell lymphoma in a patient with DADA2 and uncontrolled EBV infection. Consideration should be given to monitoring for EBV viraemia and to preventative EBV specific therapy in DADA2 and patients with at risk primary immunodeficiencies. A type I interferon (IFN) gene signature is associated with DADA2 though its association with immune dysregulation is unclear.
Topics: Humans; Lymphoma, Large B-Cell, Diffuse; Epstein-Barr Virus Infections; Adenosine Deaminase; Herpesvirus 4, Human; Intercellular Signaling Peptides and Proteins; Male; Female; Hereditary Autoinflammatory Diseases
PubMed: 38758417
DOI: 10.1007/s10875-024-01712-x -
Cancer Immunology, Immunotherapy : CII May 2024Isatuximab, an anti-CD38 antibody, has been widely used in treatments for patients with relapsed/refractory multiple myeloma (MM). Despite its high efficacy, not all...
BACKGROUND
Isatuximab, an anti-CD38 antibody, has been widely used in treatments for patients with relapsed/refractory multiple myeloma (MM). Despite its high efficacy, not all patients achieve a lasting therapeutic response with isatuximab.
OBJECTIVE
We tried to identify biomarkers to predict the effectiveness of isatuximab by focusing on the host's immune status before treatment.
METHODS
We retrospectively analyzed the cases of 134 relapsed/refractory MM patients in the Kansai Myeloma Forum database who had received only a first isatuximab treatment.
RESULTS
Among the 134 patients, an isatuximab, pomalidomide and dexamethasone (Isa-PD) regimen, isatuximab, carfilzomib and dexamethasone (Isa-KD) regimen and isatuximab and/or dexamethasone (Isa-D) regimen were used in 112, 15 and 7 patients, respectively. The median age at treatment, number of prior treatment regimens, and progression-free survival (PFS) were 71, 6, and 6.54 months, respectively. Multivariate analysis showed that the PFS under the Isa-PD regimen was longer in patients with higher lymphocyte/monocyte ratio (LMR ≥ 4), fewer prior treatment regimens (< 6), and no use of prior daratumumab treatment. The OS under the Isa-PD regimen was longer in patients with higher white blood cell counts (WBC counts ≥ 3000/μL) and higher LMR. The PFS under the Isa-D regimen was longer in patients with fewer prior treatment regimens in univariate analysis, but no parameters were correlated with PFS/OS under the Isa-KD regimen.
CONCLUSION
We found that the patients with higher LMR (≥ 4) could obtain longer PFS and OS under the Isa-PD regimen. Other cohort studies of isatuximab treatment might be necessary to substantiate our results.
Topics: Humans; Multiple Myeloma; Female; Male; Thalidomide; Aged; Middle Aged; Retrospective Studies; Antineoplastic Combined Chemotherapy Protocols; Lymphocytes; Monocytes; Antibodies, Monoclonal, Humanized; Adult; Aged, 80 and over; Prognosis
PubMed: 38758239
DOI: 10.1007/s00262-024-03711-8 -
International Journal of Oncology Jun 2024Cellular senescence has a complex role in lymphocyte carcinogenesis and drug resistance of lymphomas. Senescent lymphoma cells combine with immunocytes to create an... (Review)
Review
Cellular senescence has a complex role in lymphocyte carcinogenesis and drug resistance of lymphomas. Senescent lymphoma cells combine with immunocytes to create an ageing environment that can be reprogrammed with a senescence‑associated secretory phenotype, which gradually promotes therapeutic resistance. Certain signalling pathways, such as the NF‑κB, Wnt and PI3K/AKT/mTOR pathways, regulate the tumour ageing microenvironment and induce the proliferation and progression of lymphoma cells. Therefore, targeting senescence‑related enzymes or their signal transduction pathways may overcome radiotherapy or chemotherapy resistance and enhance the efficacy of relapsed/refractory lymphoma treatments. Mechanisms underlying drug resistance in lymphomas are complex. The ageing microenvironment is a novel factor that contributes to drug resistance in lymphomas. In terms of clinical translation, some senolytics have been used in clinical trials on patients with relapsed or refractory lymphoma. Combining immunotherapy with epigenetic drugs may achieve better therapeutic effects; however, senescent cells exhibit considerable heterogeneity and lymphoma has several subtypes. Extensive research is necessary to achieve the practical application of senolytics in relapsed or refractory lymphomas. This review summarises the mechanisms of senescence‑associated drug resistance in lymphoma, as well as emerging strategies using senolytics, to overcome therapeutic resistance in lymphoma.
Topics: Humans; Drug Resistance, Neoplasm; Tumor Microenvironment; Cellular Senescence; Lymphoma; Lymphocytes; Signal Transduction; Carcinogenesis; Senotherapeutics; Aging
PubMed: 38757347
DOI: 10.3892/ijo.2024.5653 -
Cureus May 2024Castleman disease (CD) is a rare lymphoproliferative disorder characterized by abnormal lymph node enlargement. We present the first documented case of a stroma-rich...
Castleman disease (CD) is a rare lymphoproliferative disorder characterized by abnormal lymph node enlargement. We present the first documented case of a stroma-rich variant of hyaline vascular Castleman disease in Saudi Arabia. A 24-year-old Saudi female known to have acetylcholine receptor antibody-positive myasthenia gravis (MG) presented with shortness of breath, oral thrush, and an acute myasthenia gravis exacerbation, necessitating intensive care unit (ICU) admission. During her hospitalization, she was found to have a large pelvic mass. The mass was surgically excised. The diagnosis of stroma-rich hyaline vascular Castleman disease was rendered after histopathological examination. The patient's symptoms improved after the surgery. This case underscores the importance of considering Castleman disease in complex clinical presentations, especially in the context of autoimmune and paraneoplastic diseases. Recognition and timely intervention are crucial for patient management. Additionally, the report adds to the global literature on Castleman disease, emphasizing the need for further research into its clinical manifestations and associations.
PubMed: 38756713
DOI: 10.7759/cureus.60435 -
BMC Gastroenterology May 2024The diagnosis of intestinal tuberculosis is challenging even nowadays. This study aims to report the positivity rates of new diagnostic methods such as... (Observational Study)
Observational Study
INTRODUCTION
The diagnosis of intestinal tuberculosis is challenging even nowadays. This study aims to report the positivity rates of new diagnostic methods such as immunohistochemistry and Real-Time Polymerase Chain Reaction in patients with intestinal tuberculosis, as well as describe the pathological and endoscopic features of intestinal tuberculosis in our population.
METHODS
This was a retrospective observational study conducted in patients diagnosed with intestinal tuberculosis, between 2010 to 2023 from the Hospital Nacional Daniel Alcides Carrion and a Private Pathology Center, both located in Peru. Clinical data was obtained, histologic features were independently re-evaluated by three pathologists; and immunohistochemistry and real-time Polymerase Chain Reaction evaluation were performed. The 33 patients with intestinal tuberculosis who fulfilled the inclusion criteria were recruited.
RESULTS
Immunohistochemistry was positive in 90.9% of cases, while real-time Polymerase Chain Reaction was positive in 38.7%. The ileocecal region was the most affected area (33.3%), and the most frequent endoscopic appearance was an ulcer (63.6%). Most of the granulomas were composed solely of epithelioid histiocytes (75.8%). Crypt architectural disarray was the second most frequent histologic finding (78.8%) after granulomas, but most of them were mild.
CONCLUSION
Since immunohistochemistry does not require an intact cell wall, it demonstrates higher sensitivity compared to Ziehl-Neelsen staining. Therefore, it could be helpful for the diagnosis of paucibacillary tuberculosis.
Topics: Humans; Tuberculosis, Gastrointestinal; Peru; Male; Female; Retrospective Studies; Adult; Real-Time Polymerase Chain Reaction; Middle Aged; Immunohistochemistry; Aged; Young Adult; Granuloma; Mycobacterium tuberculosis; Adolescent; Sensitivity and Specificity
PubMed: 38755577
DOI: 10.1186/s12876-024-03235-6