Background: Anti-transcriptional intermediary factor 1 gamma (anti-TIF1γ) is an autoantibody that has gained increasing recognition as a paraneoplastic marker expressed in patients with dermatomyositis and occult malignancy. Its presence in patients without dermatomyositis but occult malignancy is less well established. The management of synchronous malignancies, such as concurrent lymphoproliferative and solid tumor neoplasms in patients also remains a major therapeutic challenge. Case Description: A female in her 60s presented with persistent weakness and systemic illness was found to have anti-TIF1γ antibodies during work-up for suspected myositis. Ultimately, the patient did not meet diagnostic criteria for an inflammatory myositis. However, recognizing the association between anti-TIF1γ with malignancy prompted a work-up that identified synchronous aggressive Epstein-Barr virus-positive marginal zone lymphoma (MZL) and stage IIA colon adenocarcinoma. While remission of her MZL was achieved with bendamustine-rituximab, her metastatic colonic adenocarcinoma was therapy-resistant in the setting of KRASG12D mutation, resulting in decision to transition her to palliative care after failed response to multiple chemotherapy regimens. Conclusions: This case details the clinical relevance of anti-TIF1γ as a rare but clinically important marker of immune dysregulation while highlighting the diagnostic and therapeutic challenges of managing a patient with aggressive, synchronous primary malignancies.
Background: Chronic lymphocytic leukemia (CLL) is a chronic lymphoproliferative disorder characterized by gradual accumulation of monoclonal lymphocytes. End-stage renal disease (ESRD) patients with CLL can be candidates for kidney transplant but despite potential benefits, significant challenges exist. Due to risk of CLL progression and organ infiltration, many of these patients are excluded from the transplant list. CLL infiltration of the transplanted kidneys is not reported to be common but when present signifies poor prognosis and poses a challenge for treatment. Case Description: A 71-year-old male with CLL and chronic kidney disease (CKD) progressed to ESRD due to factors unrelated to CLL and received kidney transplantation. His CLL was stable prior to transplantation without requiring any treatment. After transplantation, despite stability of his blood counts and adenopathy, he developed acute kidney injury. Biopsy of the transplanted kidneys revealed CLL infiltration without any signs of graft rejection. He was then treated with venetoclax and obinutuzumab following which the renal function improved and there was no residual CLL in subsequent kidney biopsies. He continues to do well 4 years post-transplant with normal renal function and no evidence of CLL recurrence. Conclusions: Our case highlights the possibility of CLL progression after kidney transplantation. Newer targeted therapies can be effective in treating CLL progression and additional research is required to better characterize the frequency of kidney infiltration and to identify optimal treatment strategies.
Background: Infra-diaphragmatic Hodgkin's lymphoma (IDHL) is a rare disease. The prognostic impact of infra-diaphragmatic localization of this lymphoma is controversial. We aim to evaluate the clinic-pathologic features and outcome of IDHL. Methods: Between 2007 and 2020, all patients with histologically confirmed stage I/II IDHL were retrospectively evaluated including clinical presentation, initial lab work, radiological findings, response to initial treatment and their outcome in comparison to stage I/II supra-diaphragmatic HL (SDHL). Results: Among 991 Hodgkin's lymphoma (HL) staged I/II, there were 35 IDHL (3.5%) patients with male to female ratio 2.5:1, median age of 10.1 years, 34.3% (12/35) of cases were histologically nodular lymphocytic predominant HL (NLPHL) while 37.1% (13/35) were classical HL (CHL) of mixed cellularity (MC) type, 34.3% (12/35) of patients presented with B symptoms. In 57% of cases erythrocyte sedimentation rate (ESR) was less than 30, 20% (7/35) of patients relapsed. Overall survival (OS) was 87.8% while relapse free survival (RFS) was 76.2% at 5 years, OS and RFS of the patients with adequate interim positron emission tomography/computed tomography (PET/CT) response were higher than those with inadequate response at 5 years (P<0.001). OS according to diaphragmatic site was statistically significant (P=0.016) (88.1% for infra, vs. 98.2% for supra-diaphragmatic) while RFS according to diaphragmatic site was also statistically significant (P<0.001) (76.2%) for infra, versus (93%) for supra-diaphragmatic at 5 years. Conclusions: Although IDHL cases do not carry high risk features still this category of the patients has lower OS and RFS in comparison to supra-diaphragmatic cases at initial presentation making infra-diaphragmatic site by itself a bad prognostic factor.
Atherosclerosis occurs due to hyperlipidemia and lipid oxidation and is a major cause of death worldwide.This study was conducted to assess the correlation between the TyG index and CIMT and to estimate the predictive value of the TyG index as an early marker of subclinical atherosclerosis.This cross-sectional study was done at JLN Medical college, Ajmer tertiary care centre of central Rajasthan, North India, from December 2019 to June 2021 on 137 Non- Diabetic Males and Females of Age >18 and < 65 years patients. Detailed history, thorough clinical examination and relevant investigations were done to collect data. TyG index and CIMT were calculated. Participants were divided into two groups: Group 1- CIMT>0.9mm (having subclinical atherosclerosis) and Group 2- CIMT≤0.9mm.Mean age and BMI of participants in group 1 and group2 was 50.94yrs; 45.87yrs(P < 0.001), 28.97kg/m2; 26.56 kg/m2 (P = 0.002) respectively. Mean FBS and TG of group 1 and group 2 was 101.33mg/dl; 87.80mg/dl (P < 0.001), 210mg/dl; 156.15mg/dl (P value < 0.001) respectively. The mean TyG index in group 1 was 4.97 and in group 2 was 4.74 (P < 0.001). By receiver operating characteristic (ROC) curve analysis, the cut off value for TyG index is 4.87 (sensitivity = 94.4%, specificity = 94.2%, AUC = 0.887; P value < 0.001).We observed significant positive correlation between CIMT & TyG index (Pearson coefficient +0.675; p value < 0.001). TyG index is a reliable marker for predicting subclinical atherosclerosis at an early stage.
Background and Objective: Diffuse large B cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults. More than half of patients with new DLBCL diagnoses are cured with front line immunochemotherapy, yet subsets of patients identified by pathologic testing are at higher risk of relapse. However, these pathologic classification systems remain imperfect and their implications for treatment are uncertain. We aim to discuss recent work in this area and explore its potential applications for improving patient treatment in the clinic.
Background: Mantle cell lymphoma (MCL) accounts for 7% of adult mature B cell non-Hodgkin lymphomas (NHLs). Paraneoplastic focal segmental glomerulosclerosis (FSGS) is an exceedingly rare association of MCL. There is limited evidence on the outcomes of lymphoma associated paraneoplastic renal syndromes who are treated with Bruton tyrosine kinase inhibitors. We describe a rare case of MCL associated FSGS who was successfully treated with a chemotherapy free regimen of single agent ibrutinib and continues to be in sustained complete remission with respect to lymphoma and FSGS-related proteinuria at a follow-up of 2 years. Case Description: A 73-year-old gentleman presented with 2-month history of bilateral pedal oedema with frothy urine. Examination revealed generalized lymphadenopathy with hepatosplenomegaly. Twenty-four-hour urine protein was 11 grams/total volume, suggesting nephrotic syndrome. There were atypical circulating lymphocytes in the blood. Flowcytometry and cytogenetic studies from bone marrow aspirate and histopathology of lymph node biopsy confirmed the diagnosis of MCL. Kidney biopsy revealed FSGS. The patient was treated with ibrutinib 560 mg once daily considering his age and preference for oral therapy. At the end of two years of follow-up the patient is in complete remission for both MCL and FSGS. Conclusions: Our case highlights that FSGS can be a rare paraneoplastic renal manifestation of MCL. Bruton tyrosine kinase inhibitors can be safely used effectively in patients with paraneoplastic lymphoma associated FSGS.
Background:Primary central nervous system lymphoma (PCNSL) is a rare and aggressive primary brain tumor. While high dose methotrexate (HDMTX) regimens remain standard of care, it remains unclear if optimization of HDMTX doses and the addition of rituximab provide clinical benefit. Over the last 30 years, standard care given at Memorial Sloan Kettering Cancer Center (MSKCC) has evolved, allowing the comparison of patients receiving different numbers of HDMTX doses and those treated with and without rituximab. The purpose of this study was to describe outcomes based on treatment pattern changes.Methods:This single-center, retrospective, IRB-approved study at MSKCC included patients with immunocompetent PCNSL, age ≥18 years and diagnosed between 1/1983-12/2017. Overall survival (OS) was modeled from date of last HDMTX for analyses associating HDMTX and OS. Multivariable Cox regression models estimated hazard ratios (HR) and corresponding 95% confidence intervals (CI).Results:There were 546 patients identified with newly diagnosed PCNSL. Median overall survival (mOS) of the entire population was 4.7 years (95% CI: 3.8-5.7 years); 3.3 years (95% CI: 2.7-3.9 years) in patients diagnosed prior to 2006 and 8.1 years (95% CI: 6.6-11.1 years) in patients diagnosed 2006 onwards. Patients receiving ≥6 doses of HDMTX had improved survival compared to those receiving <6 doses of HDMTX (mOS: 7.8 vs. 4.3 years; P=0.001). Patients receiving induction rituximab had improved OS compared to those who did not receive rituximab (mOS: 10.5 vs. 3.2 years; P<0.0001). Patients receiving ≥6 doses of HDMTX and rituximab had greatest mOS at 13 years, with a 70% reduction in death (HR =0.30; 95% CI: 0.19-0.47) adjusting for treatment era, sex, and recursive partitioning analysis (RPA) classes comprising age and karnofsky performance score (KPS).Conclusions:OS for PCNSL has improved significantly over the last few decades. Patients seem to benefit with ≥6 doses of HDMTX and the addition of rituximab, an effect independent of treatment era, age, and KPS.
: Diffuse large B-cell lymphoma (DLBCL) is a disease of older adults, and these patients experience higher rates of relapsed and refractory disease than younger patients. While treatment options in this setting have expanded, this population represents an area of unmet need as they are frequently ineligible for curative or aggressive therapies based on medical comorbidities or functional status, and often excluded from clinical trials. However, it is important to recognize that this is a diverse group of patients, and treatment choices need to be considered on an individual basis. Herein, we discuss an approach to the treatment of older patients with relapsed aggressive lymphoma, including utilization of geriatric assessments to categorize patients based on their fitness. The role of cellular therapy, including autologous stem cell transplant (ASCT) and chimeric antigen receptor T-cell products are reviewed, as well as a discussion of novel, targeted agents available in the relapsed setting with a focus on the available data for older patients for these treatments. For patients who are not fit enough for these therapies, we discuss palliative treatments that are available. We also highlight several emerging classes of drugs that may offer new treatment options in the future and offer our current approach for the management of these patients based on their fitness.
Background and Objective: Commonly used cellular therapies in lymphomas include stem cell transplantation, both autologous and allogeneic, as well as chimeric antigen receptor T-cell (CAR-T) cell therapies. Many patients diagnosed with lymphoma are older, with a wide range of function and comorbidities. The use of transplantation has been described in patients in their 60s and 70s with success. CAR-T therapies are increasingly being explored in older patients as well. Methods: We performed a literature review to describe the outcomes of older individuals undergoing cellular therapies. Key Content and Findings: Autologous transplantation has been extensively described in patients in their 60s. It has also been described in several smaller series in patients over the age of 70 years. Transplant related mortality (TRM) can be as low as 5% at 1 year in selected patients in their 70s. The use of allogeneic transplantation (alloHSCT) for lymphoma has been less extensively described in elderly patients, but rates of TRM of 11–25% have been described in several series. CAR-T cell therapy can be used in selected patients who would otherwise not be eligible for curative intent therapies with transplantation. Rates of TRM with CAR-T therapies are frequently less than 5% in elderly patients. There does not appear to be an upper age limit to CAR-T therapies. Geriatric assessment and other simplified risk scores may help to improve outcomes with elderly patients undergoing cellular therapy. Conclusions: Cellular therapy is feasible in elderly patients with lymphoma with acceptable TRM rates.
Background and Objective: Mantle cell lymphoma (MCL) is a rare form of B cell Non-Hodgkin Lymphoma that predominantly affects the elderly and remains incurable. High-dose chemotherapy with rituximab followed by autologous stem cell transplant has improved outcomes in younger and fit patients. A chemo-immunotherapy based regimens with or without maintenance rituximab is considered a front-line therapy option in elderly patients. The introduction of novel agents including Bruton tyrosine kinase inhibitors (BTKis) have steadily improved the outcomes of older MCL patients in relapsed setting. In this review article, we discuss the management approach of elderly mantle cell patients in the initial and relapsed settings. Methods: We conducted literature search in Medline, Ovid databases to identify relevant studies on older MCL patients with keywords listed in the body of the article. No filters for publication dates or text language. No exclusion criteria. Key Content and Findings: MCL is a heterogenous disease, with an indolent form at one end that can be observed. At the other end of the spectrum is highly proliferative disease which has very aggressive course. Rituximab with Bendamustine has been shown to be non-inferior compared to the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, and vincristine) and is the preferred first-line treatment for most patients. BTKis are approved in second-line setting for patients with relapsed disease. Their efficacy, oral availability, better safety profile, make them a preferred second line agent. Chimeric antigen receptor T cell therapy, receptor tyrosine kinase like orphan receptor 1 (ROR1) antibody drug conjugates and bispecific antibodies have further broadened the treatment options for the elderly patients. Conclusions: Recent advances in the understanding of the biology of this disease and the development of well tolerated therapeutic options have led to improvement in the outcomes of elderly, unfit patient patients. This has shifted the focus of treatment in the frontline gradually towards combinations of chemotherapy and small molecules inhibitors, potential chemotherapy-free options and combining small molecules in combination with anti-CD20 antibody for induction and maintenance. Further follow-up therapies are needed in assessing the treatment in relapsed setting in patients who progress on small molecules in first line.
