Haploidentical Hematopoietic Stem Cell Transplantation in Leukemia’s: Experience from a Cancer Center in India

There has been a surge in haploidentical hematopoietic stem cell transplantation (HSCT) in India recently. However, there is a paucity of data on haploidentical HSCT from India. The report is an analysis of data of haploidentical HSCT performed at our center. Analysis of patients with acute leukemia or chronic myeloid leukemia who underwent haploidentical HSCT during 2014–2019 was performed. The graft versus host disease (GVHD) prophylaxis was post-transplant Cyclophosphamide with Mycophenolate-mofetil and Cyclosporine. All patients were transfused peripheral blood stem cells from donors. Overall survival (OS) was calculated using the Kaplan–Meier method. Twenty-one patients underwent haploidentical HSCT. Fourteen-patients were males. The median age of patients was 15 years. Fludarabine with total body irradiation was the most common conditioning regimen (n = 15, 71.4%). The median duration for neutrophil and platelet engraftment was 14 days. Cumulative incidence of acute and chronic GVHD was 19%, and 38% respectively. The median follow-up was 26 months and the two-year OS was 38%. Twelve (57%) patients died during the study period, 8 patients (38%) died from transplant-related mortality (TRM), and 4 from disease relapse. Sepsis was the cause of death in six of the eight TRM. Nine out of 21 patients (42.8%) are leukemia-free on follow-up. Haploidentical HSCT is a promising modality of treatment in patients who have no suitable matched donors. Though the TRM remains high, good disease control was achieved in 42.8% of patients. Multi-drug resistant bacterial infection remains a challenge in performing haploidentical HSCT in developing countries.     

A modified olanzapine-based anti-emetic regimen for the control of nausea and vomiting in patients receiving weekly cisplatin

International Journal of Clinical Pharmacy - Background There is limited data on specific antiemetic protocols for control of chemotherapy-induced nausea/vomiting (CINV) caused by weekly cisplatin...     

High Recovery of Functional Islets Stored at Low and Ultralow Temperatures

BACKGROUND: Poor recovery of islets upon cryopreservation is the main hurdle in islet banking. Pancreatic islets have a poor antioxidative defense mechanism, and exposure of islets to low temperature leads to oxidative stress. AIM: We aimed to investigate whether known compounds such as metformin, γ aminobutyric acid (GABA), docosahexanoic acid (DHA), or eicosapentaenoic acid (EPA) alone or in combination are capable of reducing oxidative stress for better islet recovery upon storage at suboptimal temperatures. METHODS: Islets isolated from mouse pancreas were stored at low temperature (4°C) for 15 days and at ultralow temperature (-196°C) for 30 days with or without additives. After revival from cold storage, islets were assessed by using three methods: (1) specificity by dithizone (DTZ), (2) viability by fluorescein diacetate/propidium iodide (FDA/PI) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetra-zolium bromide (MTT) assay, and (3) functionality by glucose-stimulated insulin secretion (GSIS). The oxidative status of the islets stored at suboptimal temperatures was determined by both intracellular free radical release (fluorometric analysis) and lipid peroxidation (enzymatic determination). RESULTS: Supplementation with additives led to an improvement in islet survival upon storage at suboptimal temperatures, without depletion of insulin secretory activity, which was comparable to that of controls. The additives acted as cryoprotectants and antioxidants as revealed by high recovery of viable islets and reduction in total reactive oxygen species (ROS) and malonidealdehyde (MDA), respectively. CONCLUSIONS: Our results demonstrate for the first time that supplementation with EPA, DHA, and metformin may lead to higher islet recovery from -196°C storage, enabling proper islet banking.     

Prognostic Utility of the IPS 3 Score for Predicting Outcomes in Advanced Hodgkin Lymphoma

Background

The International Prognostic Scoring System (IPSS) consisting of 7 parameters (IPS7) has been the standard prognostic model used in advanced Hodgkin lymphoma (aHL). However, recent studies have questioned its discriminatory power. For retrospective analyses, its utility might be limited by missing parameters. A recent study has shown that the IPSS consisting of only 3 high-risk features (IPS3; stage IV, age 45 years or older, and hemoglobin <105 g/L) is a simple predictor of survival in aHL. However, there are limited data validating the IPS3.

DA-EPOCH-R in Aggressive CD 20 Positive B Cell Lymphomas: Real-World Experience

Recent reports have shown that excellent survival outcomes can be achieved in adult Burkitt’s lymphoma with the use of DA-EPOCH-R regimen. When compared to earlier intense pediatric-type protocols, this regimen is less toxic. There are limited reports available on the use of this regimen outside the context of clinical trials. We analyzed the outcomes of patients who were treated with the DA-EPOCH-R regimen [Burkitt’s lymphoma (BL), primary mediastinal B cell lymphoma (PMBCL) and HIV-positive patients with diffuse large B cell lymphoma (DLBCL)] at our center over a 3 year period. Baseline characters, responses, and toxicity data was captured from records. Event-free survival (EFS—from therapy initiation till occurrence of event (non-achievement of complete response or relapse) and overall survival (OS—from therapy initiation till death due to any cause) were estimated using Kaplan–Meier method. Among 41 patients [median age 40 years (18–76)], the following diagnoses were included-HIV negative patients (N = 29): BL (N = 24), PMBCL (N = 5); HIV positive patients (N = 12): BL (N = 8), and DLBCL (N = 4). Among those with BL, majority had stage III/IV disease (N = 21/32, 65%). At the completion of planned therapy, 33 had achieved CR (81%). One patient died due to toxicity. The actuarial EFS and OS at 2 years were 80 and 77% respectively for all patients. The OS at 2 years was 100% for PMBCL, 80% for BL and 50% for HIV-positive DLBCL. Majority of the failures in BL were in patients with advanced disease. DA-EPOCH-R can be used in real-world setting and allows treatment of older patients with BL.     

Effectiveness of olanzapine in patients who fail therapy with aprepitant while receiving highly emetogenic chemotherapy

Chemotherapy-induced nausea–vomiting (CINV) compromises the quality of life of patients with cancer. We present data on the effectiveness of olanzapine after failure of aprepitant in patients receiving highly emetogenic chemotherapy (HEC). A single-center prospective study was conducted, where patients ≥ 18 years who failed aprepitant, palonosetron, dexamethasone (APD) received olanzapine, palonosetron and dexamethasone (OPD) in the subsequent cycle of HEC. Failure of APD was defined as occurrence of ≥ grade 2 acute and/or delayed nausea ± vomiting. Response rates were compared with what was achieved in their previous cycle with the use of APD in the acute (0–24 h), delayed (24–120 h) and overall (0–120 h) periods after the start of HEC. Impact on life was assessed using the MD Anderson Symptom Inventory (MDASI). Fifty-five patients failed APD and received OPD in the subsequent cycle; 54 were evaluable for response. Complete response rate for OPD versus APD is 80 versus 20% (acute period), 90 versus 18% (delayed period) and 74 versus 5% (overall period), and no nausea rate for OPD versus APD is 57 versus 13% (acute), 59 versus 15% (delayed) and 48 versus 0% (overall period), p < 0.001 for all comparisons. MDASI scores showed significant improvement after switching to OPD. A mild increase in drowsiness noted in patients receiving OPD did not affect daily life in most patients. In patients receiving HEC and failing CINV prophylaxis with APD, switching to OPD regimen in the subsequent cycle greatly improves control of vomiting, increases “no nausea” rates and significantly reduces symptom severity scores.     

Regenerative therapy for hippocampal degenerative diseases: lessons from preclinical studies

Increase in life expectancy has put neurodegenerative diseases on the rise. Amongst these, degenerative diseases involving hippocampus like Alzheimer's disease (AD) and temporal lobe epilepsy (TLE) are ranked higher as it is vulnerable to excitotoxicity induced neuronal dysfunction and death resulting in cognitive impairment. Modern medicines have not succeeded in halting the progression of these diseases rendering them incurable and often fatal. Under such scenario, regenerative studies employing stem cells or their by‐products in animal models of AD and TLE have yielded encourageing results. This review focuses on the distinct cell types, such as hippocampal cell lines, neural precursor cells, embryonic stem cells derived neural precursor cells, induced pluripotent stem cells, induced neurons and mesenchymal stem cells, which can be employed to rescue hippocampal functions in neurodegenerative diseases like AD and TLE. Besides, the divergent mechanisms through which cell based therapy confer neuroprotection, current impediments and possible improvements in stem cell transplantation strategies are discussed. Authors are aware of the voluminous literature available on this issue and have made a sincere attempt to put forth the current status of research in the field of cell based therapy concurrently discussing the promise it holds for combating neurodegenerative diseases like AD and TLE in the near future. Copyright © 2015 John Wiley & Sons, Ltd.     

Mycotic aneurysm of internal carotid artery — A case report

Mycotic aneurysms are rare entities. Most of them occur in aorta or femoral artery. Mycotic aneurysm of extracranial carotid artery has been reported quite infrequently in the literature. Surgical intervention is mandatory. The ideal treatment is to excise the aneurysm and restore the circulation by interposition grafting by saphenous vein. However the limited access to extracranial internal carotid artery and the presence of infection at that site may not always allow the ideal management. Ligation of the aneurysm is a practical life-saving method in such cases. We are presenting our experience with one such patient who presented with a painful bleeding swelling in the throat and was successfully treated with ligation of internal carotid artery.