Publications by authors named "Janakiram M"

Background: In patients with diabetes and monoclonal gammopathy of uncertain significance (MGUS), the impact of glucagon-like peptide-1 (GLP-1) receptor agonists on the natural history of MGUS is unknown. We aimed to assess the association of GLP-1 receptor agonist use in the progression of MGUS to multiple myeloma in patients with diabetes.

Methods: This is a population-based cohort study of veterans diagnosed with MGUS from 2006 to 2021 with a prior diagnosis of diabetes.

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  • - A patient experienced movement and neurocognitive toxicity after receiving ciltacabtagene autoleucel, which did not improve with standard immunosuppression treatments.
  • - The patient's symptoms responded positively to a combination of dopaminergic therapies, including carbidopa/levodopa, ropinirole, and amantadine.
  • - This case marks the first documented instance of effective symptomatic treatment for a well-known neurotoxic syndrome associated with this therapy.
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  • Ciltacabtagene autoleucel (cilta-cel) CAR-T therapy was approved in 2022 for treating patients with multiple myeloma who have not responded to other treatments.
  • Out of 255 patients, 236 received the therapy, and many of them didn't qualify for earlier trials, but the results were still positive.
  • Most patients experienced some side effects, but many showed good responses to the treatment, with a significant percentage remaining cancer-free after one year.
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Multiple myeloma (MM) is a hematological malignancy of bone marrow (BM) plasma cells with excessive clonal expansion and is associated with the overproduction of light-chain or monoclonal immunoglobulins (Igs). MM remains incurable, with high rates of relapses and refractory disease after first-line treatment. Cancer stem cells (CSCs) have been implicated in drug resistance in MM; however, the evidence for CSCs in MM is not adequate, partly due to a lack of uniformity in the definitions of multiple myeloma stem cells (MMSCs).

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Introduction: Chimeric antigen receptor (CAR) T-cell therapy (CAR T therapy) is a treatment option for patients with relapsed or refractory multiple myeloma that has led to unprecedented treatment outcomes. Among CAR T therapies available, ciltacabtagene autoleucel (cilta-cel) is a good candidate for outpatient administration due to its generally predictable safety profile. There are multiple advantages of outpatient administration of cilta-cel, including reduced healthcare burden, expanded access, and patient autonomy.

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Among patients receiving CD19 or B-cell maturation antigen (BCMA) CAR T therapy, inflammation pre- and post-CAR T infusion is implicated in the development of toxicities including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and likely contributes to prolonged cytopenias. Clonal hematopoiesis (CH), the clonal expansion of hematopoietic stem cells harboring somatic mutations, has been associated with inflammasome upregulation. Herein, we examined the prevalence of pre-CAR T CH in a predominantly transplant-naïve cohort of recipients with non-Hodgkin lymphoma (NHL) or multiple myeloma (MM), and assessed the relationship between the presence of CH mutations and CAR T-related outcomes including CRS, ICANS, prolonged cytopenia, progression-free survival (PFS), and overall survival (OS).

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Little is known about risk factors for central nervous system (CNS) relapse in mature T-cell and natural killer cell neoplasms (MTNKNs). We aimed to describe the clinical epidemiology of CNS relapse in patients with MTNKN and developed the CNS relapse In T-cell lymphoma Index (CITI) to predict patients at the highest risk of CNS relapse. We reviewed data from 135 patients with MTNKN and CNS relapse from 19 North American institutions.

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Article Synopsis
  • Melphalan is the most commonly used conditioning regimen before autologous stem cell transplant (ASCT), but the best timing for its administration (either day 1 or day 2) is still debated for optimal safety and effectiveness.
  • A study analyzed outcomes of 366 patients receiving high-dose melphalan on D-1 vs. D-2, focusing on neutrophil and platelet engraftment times, hospital readmissions, and long-term survival rates.
  • Results showed similar engraftment times and overall survival rates after 2 years for both groups, but the D-1 group had a higher rate of hospital readmissions within 30 days post-transplant.
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Background Biomedical waste (BMW) management is an important practice that has to be followed by all healthcare workers (HCW) in health centres. COVID-19 had become a global threat, and the spread of the infection had increased drastically. Healthcare workers were already involved in managing COVID-19 patients.

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Over the past two decades, there have been significant advances in the treatment of multiple myeloma which has led to an improvement in overall survival.1,2 However, a notable proportion of patients continue to experience early mortality (EM), defined as 2 years from the time of diagnosis. This raises the possibility that improvements in myeloma survival have not extended equally to all groups.

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We evaluated patients with relapsed multiple myeloma with renal impairment (RI) treated with standard of care idecabtagene vicleucel (ide-cel), as outcomes with chimeric antigen receptor (CAR) T-cell therapy are unknown in this population. RI was defined as creatinine clearance (CrCl) <50 mL/min. CrCl of <30 mL/min or dialysis dependence were defined as severe RI.

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Autologous stem cell transplantation (ASCT) is a standard of care treatment for patients with multiple myeloma (MM). However, only 20% to 30% of patients with MM for whom the procedure is indicated undergo ASCT. Barriers to ASCT may be informational, financial, logistic, or cultural and may affect patients and treating oncologists.

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Most patients with multiple myeloma experience disease relapse after treatment with a B-cell maturation antigen-targeted therapy (BCMA-TT), and data describing outcomes for patients treated with sequential BCMA-TT are limited. We analyzed clinical outcomes for patients infused with standard-of-care idecabtagene vicleucel, an anti-BCMA chimeric antigen receptor (CAR) T-cell therapy, at 11 US medical centers. A total of 50 patients with prior BCMA-TT exposure (38 antibody-drug conjugate, 7 bispecific, 5 CAR T) and 153 patients with no prior BCMA-TT were infused with ide-cel, with a median follow-up duration of 4.

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Allogeneic natural killer (NK) cell adoptive transfer has shown the potential to induce remissions in relapsed or refractory leukemias and lymphomas, but strategies to enhance NK cell survival and function are needed to improve clinical efficacy. Here, we demonstrated that NK cells cultured ex vivo with interleukin-15 (IL-15) and nicotinamide (NAM) exhibited stable induction of l-selectin (CD62L), a lymphocyte adhesion molecule important for lymph node homing. High frequencies of CD62L were associated with elevated transcription factor forkhead box O1 (FOXO1), and NAM promoted the stability of FOXO1 by preventing proteasomal degradation.

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Patients with multiple myeloma (MM) are at a high risk for developing cardiovascular complications. Global longitudinal strain (GLS) can detect early functional impairment before structural abnormalities develop. It remains unknown if reduced GLS is associated with reduced survival in patients with MM.

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Article Synopsis
  • Adult T-cell leukemia/lymphoma (ATLL) has poor treatment outcomes, but allogeneic stem-cell transplantation (allo-SCT) shows promise, despite limited data.
  • In a study involving 100 ATLL patients, 17 underwent allo-SCT with notable improvements in 3-year progression-free survival (31%) and overall survival (35%), compared to autologous SCT (ASCT) which had a higher relapse incidence.
  • Factors such as achieving a complete response, a high Karnofsky score, and ethnicity influenced survival outcomes, indicating that allo-SCT may offer long-term survival benefits for select ATLL patients.
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Ibrutinib is effective in the treatment of relapsed/refractory (R/R) marginal zone lymphoma (MZL) with an overall response rate (ORR) of 48%. However, factors associated with response (or lack thereof) to ibrutinib in R/R MZL in clinical practice are largely unknown. To answer this question, we performed a multicenter (25 US centers) cohort study and divided the study population into three groups: "ibrutinib responders"-patients who achieved complete or partial response (CR/PR) to ibrutinib; "stable disease (SD)"; and "primary progressors (PP)"-patients with progression of disease as their best response to ibrutinib.

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Adult T-cell leukemia and lymphoma (ATLL) is an intractable T-cell neoplasia caused by a retrovirus, namely human T-cell leukemia virus type 1 (HTLV-1). Patients suffering from ATLL present a poor prognosis and have a dearth of treatment options. In contrast to the sporadic expression of viral transactivator protein Tax present at the 5' promoter region long terminal repeats (LTR), HTLV-1 bZIP gene (HBZ) is encoded by 3'LTR (the antisense promoter) and maintains its constant expression in ATLL cells and patients.

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Over the past decade, therapeutic options in multiple myeloma (MM) have changed dramatically. Given the unprecedented efficacy of novel agents, the role of hematopoietic cell transplantation (HCT) in MM remains under scrutiny. Rapid advances in myeloma immunotherapy including the recent approval of chimeric antigen receptor (CAR) T-cell therapy will impact the MM therapeutic landscape.

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Human T cell lymphotropic virus types 1 and 2 (HTLV-1/2) are delta retroviruses. HTLV-1 may lead to complications, including adult T cell leukemia-lymphoma (ATLL) and HTLV-1-associated myelopathy. Immunosuppression may result in progression from an asymptomatic carrier state to ATLL.

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Article Synopsis
  • Bortezomib-based triplet regimens, VRD (bortezomib, lenalidomide, dexamethasone) and VCD (bortezomib, cyclophosphamide, dexamethasone), are commonly used for treating newly diagnosed multiple myeloma in patients eligible for transplantation, but their relative effectiveness is debated.
  • A study comparing long-term outcomes of these regimens found that while patients receiving VCD were generally worse off initially, the efficacy between VRD and VCD in terms of response rates before and after autologous stem cell transplantation was similar.
  • However, patients treated with VRD had better overall and progression-free survival rates post-transplant, suggesting
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