Significant Risk of Graft-versus-Host Disease with Exposure to Checkpoint Inhibitors before and after Allogeneic Transplantation.

Investigators are using checkpoint inhibitors (CPIs) to treat aggressive hematologic malignancies in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) and in some patients with relapsed disease after allo-HSCT. CTLA-4 inhibitors and PD-1 inhibitors are 2 main types of CPIs, which work through activation of the immune system. On one hand, CPIs can achieve graft-versus-tumor effect, and on the other hand, there is a risk of graft-versus-host disease (GVHD). After a comprehensive literature review, we included data (n = 283) from 24 studies (11 original manuscripts and 13 case reports or case series) and evaluated the results to assess the safety and efficacy of CPI use in conjunction with allo-HSCT. Among the 283 patients, 107 received CPI before allo-HSCT, and 176 received CPI after allo-HSCT. The most common indication for CPI use was for Hodgkin lymphoma. The CPIs used in various studies included ipilimumab, nivolumab, and pembrolizumab. Among the patients exposed to CPI before allo-HSCT, 56% developed acute GVHD and 29% developed chronic GVHD. Investigators reported 20 deaths, 60% of which were GVHD-related. The overall mortality risk with GVHD is 11%. In this group, investigators noted an objective response rate (ORR) in 68% of patients, with complete remission (CR) in 47%, partial remission (PR) in 21%, and stable disease in 11%. Among the patients who received a CPI after allo-HSCT for disease relapse, 14% developed acute GVHD and 9% developed chronic GVHD. Investigators reported 40 deaths, 28% of which were GVHD-related. The mortality risk with GVHD is approximately 7%. Investigators reported ORR in 54% of patients, with CR in 33%, PR in 21%, and disease stabilization in 5%. After careful evaluation of collective data, we found that CPI use both before and after allo-HSCT can be highly effective, but exposure can lead to a significantly increased risk of GVHD-related morbidity and mortality in this patient population. Despite limited availability of data, there is need for extreme caution while making decisions regarding the use of CPIs. Detailed discussions and prospective well-designed clinical trials are needed to explore this issue further.

Treating Diffuse Large B Cell Lymphoma in the Very Old or Frail Patients.

OPINION STATEMENT: R-CHOP has been the standard of care for diffuse large B cell lymphoma (DLBCL), curing approximately 60% of patients for more than 2 decades. However, the optimal treatment of patients who are too frail to tolerate this regimen and/or are not candidates for anthracycline therapy continues to be debated. MInT and GELA trials established addition of rituximab to CHOP in DLBCL but excluded patients older than 80 years. Multiple regimens have been tried with varying success in the very elderly, including R-mini-CHOP, R-mini CEOP, R-split CHOP, pre-phase strategies, and R-GCVP. However, there has not been a randomized trial among these strategies. Although addition of novel agents including ibrutinib, brentuximab vedotin, lenalidomide, and many others on the horizon holds promise in this population, none have been tested in a randomized setting or have results awaited. There is also a lack of a validated and easy to use clinical tool in this population to predict patients who will not tolerate R-CHOP. Identifying patients who will not tolerate R-CHOP early with the help of tools like CGA, along with integrating biology-based treatment (ibrutinib, lenalidomide in activated B cell type DLBCL) is being investigated in this population.

Double Vision: Isolated Third Cranial Nerve Palsy After Cardiac Catheterization.

Neurological complications after cardiac catheterization are rare. We report an unusual case of isolated third cranial nerve palsy in a 72-year-old male patient whose past medical history was significant for diabetes mellitus and coronary artery disease (CAD). He presented for elective cardiac catheterization for stable angina, which revealed multivessel CAD and no intervention was done. Two hours after the procedure, the patient suddenly started complaining of new-onset double vision in his left eye. Ophthalmologic exam revealed ptosis of the left eye lid, sluggish pupillary reflex and impaired adduction of the left eye along with exotropia of the left eye on primary gaze, all findings consistent with the left third nerve palsy. Rest of the neurological exam and neuroimaging (CT angiogram of head and MRI brain) were normal. Embolic phenomenon has been described as a possible mechanism in such patients leading to small vessel ischemic disease and cerebral microinfarction. Neuro-ophthalmologic complications after cardiac catheterization are rare but devastating for the patients. These should be recognized promptly, and patients should undergo neuroimaging to evaluate for any identifiable causes. These patients should be treated with aspirin and statin therapy and evaluated by ophthalmology for correction with prism lenses if symptoms persist.

A Systematic Review of Transfusion-Transmissible Infections Among Blood Donors and Associated Safety Challenges in Pakistan.

The blood transfusion (BT) system in Pakistan is fragmented, demand-driven and depends on weakly regulated transfusion practices. There is a considerable possibility that transfusion-transmissible infections (TTIs) are contributing to the current epidemic of hepatitis B virus (HBV) and hepatitis C virus (HCV) (affecting 7.4% of the general population) in the country. To study this issue, we conducted a systematic review to identify articles related to TTIs and transfusion safety in Pakistan from January 1, 2010 to January 31, 2020. A review of 33 articles met the final criteria for qualitative synthesis. Analysis of these studies showed a cumulative frequency of HBV 2.04%, HCV 2.44%, HIV 0.038%, syphilis 1.1% and malaria 0.11%. The frequency of coinfections among blood donors varied from 0.0099% to 0.35%. The highest number of coinfections were HCV and syphilis, followed by HCV and HBV infections. Syphilis and malaria were tested in only 38% and 46% of all the blood donations in one study. The rate of voluntary non-remunerated donations (VNRDs) was less than 13%, and male donors were 95% to 100% in these studies. There was a significant difference in the frequency of HBV and HCV in VNRDs (0.48%) as compared to replacement donors (RDs) (4.15%). In short, this review shows a high frequency of TTIs, especially HBV, HCV and syphilis in the blood donor population in Pakistan. There is a high dependency on RDs, minimal use of healthy voluntary blood donation practices, inadequate screening of high-risk donors, repeated collections of the blood from RDs, poor quality of screening methods and limited knowledge of donor health. Without standardized safe transfusion practices, there will be an ongoing increase in transmission of TTIs, especially HBV, HCV, syphilis, and HIV leading to a significant adverse public health impact.

Associations between particulate matter air pollution, presence and progression of subclinical coronary and carotid atherosclerosis: A systematic review.

BACKGROUND AND AIMS: Long-term exposure to particulate matter (PM) air pollution has been linked with increased cardiovascular events and mortality, however, studies had shown inconsistent associations between PM exposure and subclinical atherosclerosis. METHODS: We performed an updated systematic literature review to identify studies evaluating the associations between PM and subclinical atherosclerosis, measured using presence/progression of coronary artery calcium (CAC) or carotid intima-media thickness (CIMT) in adult populations. Quality was assessed using the Newcastle-Ottawa scale. RESULTS: Eighteen studies were included: 5 cohorts and 13 cross-sectional. Amongst 7 studies that evaluated the associations between PM and prevalence of CAC, 4 reported significantly higher odds of detectable CAC>0 or CAC>400 with increased PM exposure. Nine studies evaluated the association between exposure to at least one of the particulates and CIMT; of these, 6 reported significant independent associations. Two studies evaluated PM2.5 and CAC progression, with 1 reporting a greater progression of CAC with increased exposure to PM, while 3 out of 4 studies evaluating CIMT progression showed no significant difference in CIMT progression with a higher PM2.5 exposure. Additionally, 3 studies found significant associations between proximity to major roadways and measures of subclinical atherosclerosis. Among null studies, most displayed non-significant trends towards higher atherosclerosis burden with higher PM exposure. CONCLUSIONS: Overall, available observational studies support a positive association between PM exposure and subclinical atherosclerosis. Further longitudinal studies are needed to better establish this relationship and assess the efficacy of previously identified interventions on mitigation of clinical cardiovascular disease.

Special considerations for the treatment of multiple myeloma according to advanced age, comorbidities, frailty and organ dysfunction.

Multiple Myeloma (MM) is primarily a disease of old age with a median age of sixty-nine years at diagnosis. The development of novel therapies for induction and use of autologous stem cell transplantation has resulted in improved clinical outcomes and better quality of life for MM patients. Elderly patients, comprising the majority of MM population, have a higher incidence of age-related comorbidities, frailty and organ dysfunction which complicates the coordination of treatment and limits the selection of therapies. Even in the era of multiple chemotherapeutic options, the clinical heterogeneity of the myeloma patients' demands personalized treatments which often require dose-adjustments or dose delays. The use of reduced-dose regimens and various comorbidity indices has improved clinical outcome and regimen tolerability in MM patients with renal, neurological and bone abnormalities. We focus on advancements in the treatment of multiple myeloma with the goal to guide clinicians towards patient-specific management.

Extrapyramidal Symptoms with Administration of Lenalidomide Maintenance Therapy for Multiple Myeloma.

Lenalidomide is commonly used as induction or maintenance therapy in multiple myeloma. We report a case of 71-year-old female presenting with tardive dyskinesia-like symptoms one month after starting her lenalidomide maintenance therapy after high-dose chemotherapy and autologous hematopoietic stem cell rescue. Her symptoms evolved over days to pronounced uncontrollable limb movements, tongue smacking, lip-smacking, abnormal sounds, and tongue biting. The patient categorically denied any exposure to other drugs which are known to cause symptoms of tardive dyskinesia. The patient underwent a thorough evaluation, stopped the lenalidomide, and received therapy to control her symptoms with a gradual improvement over a six-week period. There is a paucity of literature on the association of lenalidomide with tardive dyskinesia. Common central nervous system-related side effects include peripheral neuropathy, dizziness, dysgeusia, headache, tremor, somnolence, and memory impairment. Very few studies in the existing literature have reported an association of tardive dyskinesia with lenalidomide therapy. Here, we present a case of an elderly female with multiple myeloma who developed severe tardive dyskinesia while she was on lenalidomide maintenance therapy.