Bishesh Sharma Poudyal

Cheaper Options in the Prevention of Chemotherapy-Induced Nausea and Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is a common challenge in oncology practice for which there are expensive guideline-based treatment options. Although supportive care in cancer adds significantly to the overall cost, the discussion of unaffordability of anticancer treatment frequently only revolves around the targeted drugs and immunotherapies. In this review, we highlight the available cost-saving strategies and recent updates in preventing CINV in patients with cancer. This is the first work, to our knowledge, to review specifically the less expensive alternatives in CINV prevention, which is particularly important for those working in resource-limited settings. Whereas patients in these settings often cannot afford expensive antiemetics, we now have the science to offer cheaper, more affordable options without necessarily compromising efficacy.

Antifungal prophylaxis with Amphotericin B deoxycholate emulsified in lipids for acute myeloid leukemia patients treated in low economy countries

1Clinical Haematology and Bone Marrow Transplant Unit, Civil Service Hospital, Kathmandu, Nepal, 2Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Japan, 3Department of Pharmacology, 4Department of Pathology and Clinical Haematology Unit, Civil Service Hospital, Kathmandu, Nepal, 5Intensive Care Unit, Tribhuwan University Teaching Hospital, Kathmandu, Nepal, and 6 Division of Hematology/Oncology, Department of Medicine, UI Cancer Center and Center for Global Health, University of Illinois at Chicago, Chicago, IL, USA

Cerebral venous thrombosis presenting with intracerebral hemorrhage in a patient with paroxysmal nocturnal hemoglobinuria

Cerebral venous thrombosis (CVT) is an uncommon cause of stroke. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare type of hemolytic anemia, frequently associated with thrombophilia. PNH may rarely present with CVT. Approximately, one-third of the patients with CVT develop cerebral hemorrhage. Here, we present a rare combination of CVT presenting with intracerebral hemorrhage in a patient with PNH. High index of suspicion is needed to avoid misdiagnosis. Patient was successfully managed with anticoagulation therapy.

Factor XIII deficiency: the first case reported from Nepal

The initial hemostatic plug is not sufficient to prevent blood loss unless it is stabilized by the action of plasma factor XIII. Congenital or acquired factor XIII deficiency must be considered when a patient has a major bleeding disorder and all of the initial screening laboratory tests are normal, including prothrombin time, activated partial thromboplastin time, platelet count, and bleeding time. Here we report the case of a child with congenital factor XIII deficiency, who presented with bleeding from umbilical stump and spontaneous hematoma in the left buttock.

Perioperative management of two cases of hemophilia with spontaneous intracerebral hemorrhage undergoing emergency craniotomy in resource constrained setup of Nepal

Patients with hemophilia are prone to develop spontaneous intracranial hemorrhage. It carries a significant risk of morbidity and mortality. In this case series, we report two cases of hemophilia who suffered spontaneous intracerebral hemorrhage with features of raised intracranial pressure and were successfully managed perioperatively. The patients were managed with early intensive care unit management, measures to reduce intracranial pressure, perioperative clotting factor administration, airway management and surgery to decrease the raised intracranial pressure. Both patients improved following surgery and were discharged home. Perioperative multidisciplinary management of hemophilia is discussed in this series.

Prevalence of factor V G1691A, factor II G20210A, methylenetetrahydrofolate reaductase C677T and endothelial protein C receptor 23 bp insertion polymorphisms in indigenous population of Nepal

Dear Editor, Nepal is a tiny country situated between China and India with a population of approximately 29 million people of diverse ethnicities and religions. It is a high altitude mountainous and landlocked country. The majority of Nepali population is of Indo-Aryan origin, the remaining are Tibetans in northern Nepal and Mongoloid inhabitants in the central belt. The prevalence of thrombophilic polymorphisms varies widely in different populations. Study of these common polymorphisms is essential to adopt a strategy for thrombophilia screening in a specific population. Except for a single case report, there are no studies on the frequency of common thrombophilia markers in Nepali population [1]. The present study was undertaken to analyze the prevalence of the common polymorphisms which are associated with thrombosis either singly or in association with another thrombophilia marker, i.e., factor V Leiden (FVL), prothrombin (PT) G20210A, methylenetetrahydrofolate (MTHFR) C677T, and endothelial protein C receptor (EPCR) 23 bp insertion polymorphism in indigenous Nepali population. A total of 78 normal healthy donor blood samples from Nepal (45 males, 33 females; age range 21–44 years) were analyzed. These individuals were of Tibetan/Asian–Mongoloid origin and were randomly selected for the present study. None of the subjects had any previous history of arterial or venous thrombosis. The study was approved by the institute ethics boards of both the participating institutes. After obtaining an informed consent, blood was collected in 2 ml trisodium citrate vacutainers (BD Biosciences, CA, USA) and transported to Mumbai in refrigerated containers within 48 h of collection. DNA was extracted from whole blood, using PureLinkTM Genomic DNA Kits (Life Technologies, Invitrogen, CA, USA). FVL mutation was analyzed by an in-house allele-specific PCR followed by resolution of the amplicons in 2 % agarose gel. The PT and MTHFR polymorphisms were analyzed by PCRRFLP technique followed by resolution in 10 % PAGE as described earlier [2, 3] and EPCR 23 bp insertion polymorphism was analyzed by resolution of the PCR amplicons in 10 % polyacrylamide gel [4]. The prevalence of these polymorphisms is shown in Table 1. Among 78 individuals, each one (1.3 %) had FVL G1691A mutation and PT G20210A polymorphism in heterozygous state. The prevalence of MTHFR C677T was quite high, i.e., 31/78 (40 %), out of which, only one was homozygous, i.e., T677T. None of the subjects had the presence of EPCR 23 bp insertion polymorphism. This study is the first of its kind to determine the frequency of the common polymorphic markers associated with thrombosis in Nepali population. Both FVL mutation and PT G20210A polymorphisms have been found to be quite low in Asian population as compared to European countries [5] and the same has been observed in Nepali population. The PT 20210 G/A polymorphism is associated with elevated levels of factor II in plasma which in turn A. Patil :K. Ghosh : S. Shetty (*) National Institute of Immunohaematology (ICMR), 13th Floor, KEM Hospital, Parel, Mumbai 400 012, India e-mail: shrimatishetty@yahoo.com

Challenges and Results of Laparoscopic Splenectomy for Hematological Diseases in a Developing Country

Introduction Though, in developed countries, laparoscopy is now a gold standard for splenectomy, we are lacking in this aspect in the eastern world. Splenectomy has mostly been performed by open surgery in our region. This is our effort to introduce laparoscopic splenectomy in our country. Methods This is a retrospective cohort study done in patients presenting to hematology and surgery department of our hospital who underwent laparoscopic splenectomy for hematological diseases from January 2013 to December 2016. Results There were 50 patients (38 females, 12 males). The diagnoses were idiopathic thrombocytopenic purpura in 31, (steroid/azathioprine-resistant, steroid dependent), hereditary spherocytosis in 9, alpha-thalassemia in 3, beta-thalassemia in 2, autoimmune hemolytic anemia in 4, and isolated splenic tuberculosis in 1. Average platelet counts preoperatively were 62000 ± 11000/mm3 (range 52000-325000/mm3). The mean operative time was 130 ± 49 minutes (range 108-224 min). The mean postoperative stay was 4 ± 2.11 days (range 3-9 days). Laparoscopic splenectomy could be completed in 45 (90%) patients. Conclusion Laparoscopic splenectomy could be successfully contemplated in patients with hematological diseases, especially if spleen is normal or only mildly enlarged, and is an advantageous alternative to open splenectomy. Absence of ideal resources has not limited our progress in minimal access approach.

First Global Blood & Marrow Transplant [GlobalBMT] Conference in Kathmandu with experiences from Nepal, India, Singapore and Sri Lanka

The First GlobalBMT Conference organized on November 5, 2017 in Kathmandu fulfilled one of the educational goals of the active collaboration between the University of Illinois at Chicago Center for Global Health and Civil Service Hospital in Kathmandu (Nepal). This collaboration, that over the years has facilitated the establishment of the first BMT Center in Nepal, is aimed at improving the care of hematologic patients in this country, building capacity in BMT, as well as collaborating on projects related to cost-effectiveness and affordability of BMT in low-middle-income countries (LMICs). To this purpose, the main objective of this first GlobalBMT Conference was to gather physicians from BMT centers in South-East Asia to discuss relevant topics in BMT from the perspective of this part of the world and to find common views on standard practices and specific needs.

TKI-induced pure red cell aplasia: first case report of pure red cell aplasia with both imatinib and nilotinib

Tyrosine-kinase inhibitors (TKIs) represent the only hopes for long-term survival for patients with chronic myeloid leukaemia (CML) and gastrointestinal stromal tumours. Thus, uninterrupted use of TKIs is of importance in such patients. Pure red cell aplasia (PRCA) is a rare disorder, not previously known to be associated with TKIs. We present, to the best of our knowledge, the first case of a patient with CML who developed PRCA secondary to both imatinib and nilotinib. Although PRCA was controlled on withdrawal of TKI, TKI continuation in the patient with CML is important. So we treated him with prednisone, but his haemoglobin started to drop on resumption of imatinib. He was changed to nilotinib but again developed PRCA, which did not improve with steroids. We treated him with cyclosporine and were able to reintroduce nilotinib at a reduced dose without further complications. This case report makes physicians aware of this rare complication of TKIs and also provides encouragement that PRCA could be controlled and TKI continued.

Inspiration amidst the challenges: the first report of successful bone marrow transplantation in the Himalayan country Nepal

Since the first successful haematopoietic stem cell transplant (HSCT) in the late 1950s, HSCT has been established as a standard of care in many benign and malignant haematological disorders (Copelan, 2006; Appelbaum, 2007). In 2006 alone, a total of 50 417 HSCTs were performed worldwide, the majority of which were in Europe (48%) and the Americas (36%) (Gratwohl et al, 2010). Nepal, unknown to many until the recent devastating earthquake, is a small low-income country in South Asia sandwiched between India and China. The health care system of Nepal is overwhelmed with communicable diseases, such as diarrhoea, typhoid and tuberculosis. Under such circumstances, haematological disorders receive the least attention and priority from the government. The dire lack of health facilities, manpower and health insurance, the rapidly increasing cost of novel treatment, poverty, illiteracy and challenging geography frustrates even the most optimistic of physicians. Amidst those adversities and challenges, we started our first HSCT services in November 2012 [India and China started in late 1980s (Advani & Saikia, 1987; Lu et al, 1990)] through our private efforts at Nobel Hospital, Kathmandu. Between November 2012 and May 2014, five multiple myeloma (MM) patients and one patient with relapsed diffuse large B cell lymphoma (DLBCL) were eligible for autologous SCT. One MM patient had his transplant deferred due to inadequate stem cell collection. We report, for the first time, our outcomes and experiences with these five patients (four MM, one DLBCL) who underwent HSCT in Nepal. Three MM patients received bortezomib, doxorubicin and dexamethasone induction regimen while one received lenalidomide-dexamethasone. All achieved a very good partial response and were considered for HSCT. The stage IIIB DLBCL patient, who had an International Prognostic Index score of 3, opted for CHOP chemotherapy due to unaffordability of rituximab and achieved partial remission as assessed by computerized tomography. He was planned for radiotherapy but relapsed. He then received three cycles of ifosfamide, carboplatin and etoposide (ICE), achieving complete remission (CR). He was then scheduled for autologous HSCT (Table I). All MM patients were followed-up monthly. Protein electrophoresis, immunofixation electrophoresis and light chain ratio evaluation was done every 3 months. All patients achieved CR at 3 months. Three patients maintained CR at 1 year of follow-up. The DLBCL patient was followed monthly for 2 months and every 2 months thereafter. Patient was in CR for 7 months but then relapsed at 8 months posttransplant with an additional disseminated tuberculosis infection. He succumbed to infection at 9 months post-transplant. Our experience shows that HSCT services are feasible even in low-economy countries. We used standard category 1 induction regimens for our MM patients; rituximab was not given to the DLBCL patient for financial reasons. MM patients tolerated the standard conditioning regimen of melphalan although this was complicated by mucositis and febrile neutropenia, which were manageable. After 1 year of follow-up, three patients are still in CR. Our DLBCL patient relapsed immediately after completing the sixth cycle of chemotherapy and thus was a candidate for HSCT (Gugliemi et al, 1998). He achieved CR after 3 cycles of ICE and therefore we pursued HSCT. Cost is an important issue in the feasibility of HSCT in low-income countries. Autologous HSCT costs approximately