Breaking barriers: supporting hematopoietic stem cell transplant program through collaborative radiation therapy service from a physically distant center.

BACKGROUND: Total body irradiation (TBI) for hematopoietic stem cell transplant (HSCT) has certain distinct advantages, such as uniform dose distribution and lack of drug resistance, but it is not widely available in resource-constrained settings. To overcome the limitations of in-house radiotherapy services in hematology centers, we evaluated the feasibility of conducting HSCT programs in coordination with two physically distant centers using a reduced-intensity TBI protocol. METHODS: Thirty-two patients with a median age of 20.5 years were included in the study. Fifteen patients were diagnosed with aplastic anemia, 10 patients with acute myeloid leukemia (AML), 3 patients with acute lymphocytic leukemia (ALL), and 4 patients with other hematological conditions. Conditioning regimens used were fludarabine plus cyclophosphamide in 29 cases, fludarabine-cytarabine ATG in 2 cases, and busulfan plus fludarabine in 1 case. The TBI dose was 3 Gy in 28 cases and 2 Gy in 4 cases. Patients were followed monthly after TBI, and the major toxicities were recorded. RESULTS: The median follow-up was 22 months. The most common acute complication was acute graft-versus-host disease (GVHD), which occurred in 15.6% of patients. The major late complications were chronic GVHD (9.3%), Cytomegalovirus (CMV) infection (34.3%), and CMV-induced secondary graft failure (6.2%). Seventy-five percent of patients were alive, 21.9% were dead, and 1 patient was lost to follow-up. CONCLUSIONS: HSCT based on TBI is feasible even if the center lacks a radiotherapy facility by coordinating with a remote radiotherapy facility. without compromising the patient's outcome.

The differential needs and expectations from general practitioners in oncology between high-income countries and low- and-middle-income countries: results from a survey of Canadian and Nepali oncologists.

Background: To address the shortage of oncologists in the wake of the rapidly increasing global cancer burden, general practitioners of oncology (GPOs) have been added to cancer care teams worldwide. GPOs are family physicians with additional training in oncology and their roles differ by both country and region. In this study, we aimed to learn about the roles and expectations of GPOs from the perspective of oncologists in Canada and Nepal. Methods: A survey was designed and administered to Canadian and Nepali Oncologists between February and November 2022 using Research Electronic Data Capture, a secure web-based software platform hosted at Queen's University in Kingston, Ontario, Canada. Participants were recruited through personal networks/social media in Nepal and the survey was distributed through an email list provided by the Canadian Association of Medical Oncologists. Results: The survey received 48 responses from Canadian and 7 responses from Nepali oncologists. Canadian respondents indicated that in terms of educational content delivery, clinics with oncologists followed by didactic lectures by oncologists were thought to be the most effective, followed by a small group learning and online education. Nepali oncologists also indicated didactic lectures by oncologists and small group learning would be the most effective teaching techniques, followed by online education and clinics with oncologists. Critical knowledge domains and skills most relevant for GPO training identified by Canadian respondents were managing pain and other common symptoms of cancers, as well as treatment of common side effects, followed by goals of care discussion, post-treatment surveillance for recurrence, and the management of long-term complications from treatment. Respondents from Nepal, however, suggested an approach to diagnosis to patient with increased risk of cancer, and cancer staging were the most critical knowledge domains and skills. The majority of oncologists in both countries thought a training program of 6-12 months was optimal. Conclusion: We found many similarities in oncologist's opinions of GPOs between the two countries, however, there were also some notable differences such as the need to provide cancer screening services in Nepal. This highlights the need to tailor GPO training programs based on local context.

Report on hematopoietic cell transplantations performed in 2018/2019 focusing on the trends of selection of stem cell sources in the Asia-Pacific region: APBMT Activity Survey.

The number of hematopoietic stem cell transplantations (HCTs) is increasing annually worldwide, and the Asia-Pacific (AP) region is no exception. We report on the absolute number of HCTs in 2018 and 2019 and the trends in graft selection and disease indication in the past few decades. In 2018, 24,292 HCTs were performed in the AP region, of which 8,754 (36.0%) were autologous and 15,538 (64.0%) were allogeneic. Among the allogeneic HCTs, 10,552 (67.9%) of the recipients were related to their donors, whereas 4,986 (32.1%) were unrelated. In 2019, 27,583 HCTs were reported, of which 17,613 (63.9%) were allogeneic and 9,970 (36.1%) were autologous. Although, in 2010, there was a nearly equal number of related and unrelated HCTs, the difference has shown an annual increase, with more than double (2.05) the number of related than unrelated HCTs in 2019. Recent trends in the AP region show that peripheral blood has overwhelmingly surpassed the bone marrow as a graft source for both related and unrelated HCTs, with the haploidentical donor type being preferred; however, their trends in each country/region were quite different among countries/regions. In 2019, the main conditions requiring HCT were acute myelogenous leukemia (n=6,629 [24.0%]), plasma cell disorders (PCD) (n=4,935 [17.9%]), malignant lymphoma (ML) (n=4,106 [14.9%]), acute lymphoblastic leukemia (AML) (n=3,777 [13.7%]), myelodysplastic syndrome or myelodysplastic/myeloproliferative neoplasm (n=1,913 [6.9%]), severe aplastic anemia (n=1,671 [6.1%]), and hemoglobinopathy (n=910 [3.3%]). PCD and ML were the main indications for autologous HCT, and the number of PCD cases has grown more prominent than the corresponding of ML. The increased number of allogeneic transplants for hemoglobinopathy remains prominent, as well as that of AML and acute lymphocytic leukemia for the past 5 years. There was a significant regional variation in the number of facilities performing HCTs, ranging from one in Mongolia and Nepal to 313 in Japan, and differing regional densities varying from 0.1 in Indonesia and Pakistan to 24.7 in Japan. The total transplant density per 10 million population in each country/region also differed (0.2 in Indonesia and 627 in New Zealand). This annual Activity Survey aims to help all participating countries/regions understand the changes in HCT, serve as an asset in promoting HCT activities in the AP region, and be used as a reference for comparison with other registries from Europe and the United States.

Therapy-related Acute Myeloid Leukemia in Non-Hodgkin Lymphoma Survivors: Risk, Survival Outcomes and Prognostic Factor Analysis.

BACKGROUND: Therapy-related acute myeloid leukemia (tAML) is a serious complication in patients with Non-Hodgkin lymphoma (NHL) exposed to chemotherapy or radiation. This extensive database study aims to quantify the risk of tAML in NHL and determine the impact of tAML on the overall survival (OS) of patients with NHL. MATERIALS AND METHODS: Patients diagnosed with NHL and de novo AML from 2009 to 2018 were identified from the Surveillance, Epidemiology, and End Results database. Multiple primary standardized incidence ratio (SIR) sessions of the SEER*Stat software were used to calculate SIR and the absolute excess risk of tAML. Overall survival (OS) was evaluated using Kaplan-Meier curves and compared using log-rank tests. Multivariate analysis was used to study the role of each covariate on OS in patients with tAML. RESULTS: The SIR of tAML was 4.89 (95% CI 4.41-5.41), with a higher incidence of tAML observed for age <60 years, NHL prior to 2013 and within 5 years of diagnosis, and those who received chemotherapy. NHL patients with tAML had lower OS than those without tAML (5-year OS 59% vs. 13%, p < 0.001). Patients with tAML showed worse OS than de novo AML in univariate analysis (5-year OS 13% vs. 25%, p = 0.001) but not in multivariate analysis (HR 0.93, 95% CI 0.82-1.04, p = 0.21). Age ≥60 years and lack of chemotherapy were associated with poor OS in tAML subcategory. CONCLUSION: Age, time since NHL diagnosis, and receipt of chemotherapy directly influence the risk of development of tAML in NHL survivors.

Outcome of ALL With ALL-BFM-95 Protocol in Nepal.

PURPOSE: Data on survival outcomes in patients with acute lymphoblastic leukemia (ALL) originating from Nepal are limited. We aim to present the real-world data on treatment outcomes of patients with de novo ALL treated with pediatric ALL-Berlin-Frankfurt-Muenster (BFM)-95 protocol in Nepal. PATIENTS AND METHODS: We used the medical records of 103 consecutive patients with ALL treated in our center from 2013 to 2016 to evaluate the overall survival (OS) and relapse-free survival (RFS) and analyzed the effects of clinicopathologic factors on survival outcomes in patients with ALL. RESULTS: The 3-year OS and RFS in the entire cohort was 89.4% (95% CI, 82.1 to 96.7) and 87.3% (95% CI, 79.8 to 94.7), with a mean OS and RFS of 79.4 months (95% CI, 74.2 to 84.5) and 76.6 months (95% CI, 70.8 to 82.4), respectively. Patients with prednisone good response (PGR) showed better mean OS and RFS, whereas complete marrow response on day 33 was associated with better mean OS alone. Patients with Philadelphia (Ph)-positive ALL showed worse mean RFS compared to those with Ph-negative status. On multivariate analysis, PGR (hazard ratio [HR], 0.11; 95% CI, 0.03 to 0.49; P = .004) and sagittal vein thrombosis (SVT; HR, 5.95; 95% CI, 1.30 to 27.18; P = .02) were the only independent predictors of OS and RFS, respectively. Adverse events on BFM-95 protocol included SVT (4.9%), peripheral neuropathy (7.8%), myopathy (20.4%), hyperglycemia (24.3%), intestinal obstruction (7.8%), avascular necrosis of femur (6.8%), and mucositis (46%). CONCLUSION: BFM-95 protocol appears to be a safe and effective strategy in adolescent and young adults and adult Nepalese population with ALL with a low toxicity profile.

Hemophagocytic Lymphohistiocytosis: an Under-recognized and Life-threatening Condition.

Diagnosis of hemophagocytic lymphohistiocytosis is a challenge in Nepal because of limited resources and the high prevalence of tropical febrile illness mimicking hemophagocytic lymphohistiocytosis. We retrospectively reviewed medical records of 21 patients who were diagnosed with hemophagocytic lymphohistiocytosis from 2010 to 2015 at a single center in Nepal. Two patients had a mutation in their perforin gene and underwent successful haploidentical stem cell transplantation. Marrow hemophagocytosis was found only in 57% of the patients. Five patients had hematological malignancy and were treated with disease-specific chemotherapy. Seven patients developed hemophagocytic lymphohistiocytosis secondary to an infection, including visceral leishmaniasis, scrub typhus, and Epstein Barr virus. EBV-associated hemophagocytic lymphohistiocytosis was refractory to hemophagocytic lymphohistiocytosis 94 protocol, including the addition of rituximab. Malignancy and infection-associated hemophagocytic lymphohistiocytosis was more common. The most common clinical presentations included fever, splenomegaly, hyponatremia, liver function derangement, hyperfibrinogenemia, hyperferritinemia, and cytopenia. With a mortality of 29% in our study cohort, hemophagocytic lymphohistiocytosis should be considered a lethal disease, and clinicians should maintain a high index of suspicion to diagnose this disease. Keywords: Hemophagocytic lymphohistiocytosis; infection; malignancy.

Clinical, Laboratory and Radiological Features of Paragonimiasis Misdiagnosed as Pulmonary Tuberculosis.

Background: Paragonimiasis presents with nonspecific symptoms and radiologic findings, allowing for the possibility of misdiagnosis. Diagnosis is generally delayed due to lack of suspicion and presentation similar to pulmonary tuberculosis. Methods: A prospective observational study was carried out on 20 subjects at Civil Service Hospital of Nepal from March 2015 to June 2019 who presented with eosinophilia and pulmonary symptoms, and were treated empirically with Anti-tubercular therapy for suspicion of pulmonary tuberculosis. Results: The median age of the patient was 34 years. Mean blood absolute eosinophil count was 16678/ul. Fever was present in 80% (n=16). Cough was present in 90% (n=18). Pleural effusion was noticed in 100% (n=20). Chest computed tomography showed ground-glass opacities in 65% (n=13) of patients. Pleural fluid eosinophilia (>10%) was evident in all patients. Pleural fluid LDH was elevated in 85% (n=17) of patients. Similarly, ADA was high (>40U) in 75% (n= 15) of patients, and pleural fluid sugar was low in 80% (n=16) of patients. All patients (100%) gave a history of crab or snail consumption. Paragonimus egg was detected in five (25%) patients. Twenty patients fulfilled definite or probable diagnostic criteria of paragonimiasis. Ninety-five (n=19) patients responded to praziquantel. Conclusion: Unavailability of serologic tests or failure to demonstrate parasitic egg under the microscope should not discourage physicians to consider the diagnosis of paragonimiasis when marked eosinophilia, high LDH levels, and low glucose levels are identified in pleural fluid of a patient with a history of raw crab or snail consumption.

Training General Practitioners in Oncology: A Needs Assessment Survey From Nepal.

PURPOSE: Nepal lacks enough cancer care providers to address the growing burden of cancer in the country. One way of addressing this issue is to train general practitioners (GPs) in oncology (GPOs) so that they can task-share and task-shift oncology care. However, limited information is available regarding the current level of oncology expertise of Nepali GPs and whether they perceive a need for, and have an interest in, such a GPO training program if available in Nepal. METHODS: A survey was distributed to GPs in Nepal to collect data on current oncology training and clinical practice and evaluate levels of interest and need for a GPO training program. The survey was distributed electronically from February to July 2021. RESULTS: The survey obtained 71 individual responses from GPs in Nepal. The majority of respondents were male (87%), and most worked as consultants or senior consultants (63%). Only 6% of respondents had a mandatory oncology rotation during their GP training, and only 15% indicated that their GP training had adequately prepared them to care for patients with cancer. Ninety-six percent of respondents perceived a need for a GPO training program in Nepal, with 94% indicating an interest in enrolling in such a program and 71% indicating that they were very interested. CONCLUSION: The findings indicate an urgent need for and an encouraging interest in establishing a GPO training program in Nepal. These findings will be used to guide the development and implementation of this type of program.

ASTCT Clinical Practice Recommendations for Transplantation and Cellular Therapies in Multiple Myeloma.

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. The American Society for Transplantation and Cellular Therapy convened an expert panel to formulate clinical practice recommendations for role, timing, and sequencing of autologous (auto-HCT), allogeneic (allo-HCT) and CAR T-cell therapy for patients with newly diagnosed (NDMM) and relapsed/refractory MM (RRMM). The RAND-modified Delphi method was used to generate consensus statements. Twenty consensus statements were generated. The panel endorsed continued use of auto-HCT consolidation for patients with NDMM as a standard-of-care option, whereas in the front line allo-HCT and CAR-T were not recommended outside the setting of clinical trial. For patients not undergoing auto-HCT upfront, the panel recommended its use in first relapse. Lenalidomide as a single agent was recommended for maintenance especially for standard risk patients. In the RRMM setting, the panel recommended the use of CAR-T in patients with 4 or more prior lines of therapy. The panel encouraged allo-HCT in RRMM setting only in the context of clinical trial. The panel found RAND-modified Delphi methodology effective in providing a formal framework for developing consensus recommendations for the timing and sequence of cellular therapies for MM.

Hematopoietic Stem Cell Transplantation in Nepal: International Partnership, Implementation Steps, and Clinical Outcomes.

Blood and marrow transplantation (BMT) is rarely available in many low- to middle-income countries (LMICs). In 2012, Civil Service Hospital, a government hospital in Kathmandu, partnered with the University of Illinois at Chicago to consult on the establishment of BMT in their hospital, train staff, and promote educational activities. The implementation of BMT occurred in 3 phases over 4 years and included regular onsite visits, training of personnel in Chicago, continuous remote communication, and co-organization of educational events in Kathmandu. The Nepalese government funded the construction of a state-of-the art BMT unit and stem cell laboratory inside Civil Hospital. Autologous (auto) hematopoietic stem cell transplantation (HSCT) was started in 2016, and allogeneic (allo) HSCT from matched related donors (MRDs) or haploidentical (haplo) donors was initiated in 2017. The cost of transplantation was $5200 for auto-HSCT, $10,000 for MRD HSCT, and $13,300 for haplo HSCT. The major socioeconomic determinants reported by Nepalese BMT providers were the cost of transplantation, loss of revenue of the patient and/or caregiver, and cost of transportation. All patients (n = 66) received peripheral blood stem cell grafts, and all allo-HSCT recipients were given post-transplantation cyclophosphamide as graft-versus-host disease (GVHD) prophylaxis. Among recipients of auto-HSCT (n = 30), with a median follow-up of 1029 days (range, 130 to 1653 days), 87% were alive, and transplantation-related mortality (TRM) was 10%. Among allo-HSCT recipients (n = 36), all patients engrafted, and at a median follow-up of 204 days (range, 12 to 1131 days), 75% of them were alive (MRD, 71%; haplo, 83%), with a TRM of 19%. Only 3 of 36 patients developed acute GVHD grade II-IV. The median overall survival in auto-HSCT recipients was 1610 days and was not reached in allo-HSCT recipients. The long-lasting partnership with University of Illinois at Chicago helped build capacity and allowed the Civil Service Hospital team to establish a BMT program in Nepal that has high quality standards at an affordable cost for the majority of patients.

Highlights from ecancer Choosing Wisely Nepal 2022: critical appraisal skills for evidence-based practice, 24th-25th September 2022, Kathmandu, Nepal.

The ecancer Kathmandu 2022 workshop on the 24th-25th September 2022 was the first ecancer conference organised in Nepal, a Southeast Asian nation sandwiched between India and China. It was focused on critical appraisal skills for evidence-based practice and was organised in partnership with the Karnali Academy of Health Sciences and the Civil Service Hospital from Nepal, and the Queen's Global Oncology Program from Canada. The workshop emphasised the need for critical thinking in understanding clinical research, and also motivated the delegates to undertake meaningful clinical research relevant to the local setting. The sessions highlighted the features of a good clinical research, identify pitfalls in the reporting of clinical trials, implementation of the research into locally relevant practice and development of local clinical guidelines. Furthermore, the faculty also discussed how to write a good scientific paper, the do's and don'ts of a systematic review and meta-analysis, the role of peer-review and how to do one properly and what do editors look for in evaluating papers submitted for publication. The audience learned the importance of finding a good mentor and fostering local and international collaboration. The local faculty also highlighted their own personal journeys and how mentorship and global collaboration played an important role in their own academic career. The enthusiastic panel discussion was a highlight of the programme where the delegates learned about several important topics from the faculties, such as work-life balance, the role of mentorship in building careers and building networks.

Trends in disease indications for hematopoietic stem cell transplantation in the Asia-Pacific region: A report of the Activity Survey 2017 from APBMT.

The Asia-Pacific Blood and Marrow Transplantation Group (APBMT) has been conducting annual surveys on the activity of hematopoietic stem cell transplants since 2007. The APBMT Data Center collected the following data in 2017. A total of 21,504 transplants were registered from 733 transplant centers of 20 countries/regions in the Asia-Pacific (AP) region. Five countries/regions comprised 89.4% of all transplants - China (6,979), Japan (5,794), South Korea (2,626), India (2,034), and Australia (1,789). The number of centers in these five countries/regions also comprised 88.9% of all centers: Japan (373), China (123), India (66), Australia (45), and South Korea (44). The overall ratio between autologous and allogeneic transplants was 37.0% and 63.0%, respectively, but the ratios varied significantly among countries/regions. Autologous transplants have surpassed allogeneic transplants in Thailand, Australia, Vietnam, New Zealand, Singapore, and Iran. In contrast, the proportion of allogeneic transplants comprised over 70% of all transplants in Pakistan, China, and Hong Kong. These ratios were compared by the Data Center among countries/regions that performed more than 50 transplants. The proportion of related and unrelated transplants also differed among countries/regions. The number of unrelated transplants was more than related ones in Japan (2,551 vs. 1,202) and Australia (329 vs. 291), whereas more than 80% of all transplants were related transplants in Malaysia (90.9%), India (89.5%), Iran (87.2%), Vietnam (85.7%), China (80.9%), and Thailand (80.6%). All transplant activities were related transplants in Pakistan, the Philippines, Myanmar, and Nepal, and no allogeneic transplants were performed in Bangladesh and Mongolia. Regarding the indications for transplants, acute myeloid leukemia (AML) was the most common disease for allogeneic transplant (4,759, 35.1% of allogeneic transplants), while plasma cell disorder (PCD) was the most common disease for autologous transplant (3,701, 27.3% of all autologous transplants). Furthermore, the number of transplants for hemoglobinopathy has steeply increased in this region compared with the rest of disease indications (677, 3.1% of all transplants). APBMT covers a broad area globally, including countries/regions with diverse disease distribution, development of HSCT programs, population, and economic power. Consistent and continuous activity surveys considering those elements in each country/region revealed the HSCT field's diverse characteristics and background factors in this region.

Oncology training programmes for general practitioners: a scoping review.

INTRODUCTION: Due to the increasing global burden of cancer and the shortage of trained medical oncologists, training General Practitioners (GPs) in Oncology (known as GPOs) has been proposed as a means to potentially ease some burden on medical oncologists with heavy workloads, especially in low-and-middle-income countries (LMICs), by task-sharing and task-shifting. We undertook a scoping review to identify and characterise the existing training programmes and curricula for GPOs globally. DESIGN: We searched three major electronic databases: EMBASE, Medline/PubMed and Education Source for articles that described a medical oncology training programme for GPs. All study types were eligible in this review. We followed a two-stage standardised screening process using two independent reviewers to evaluate the eligibility of the articles. RESULTS: Five peer-reviewed articles were included in our review and grey literature scans identified an additional seven GPO training programmes for a total of 12 programmes and their curricula. All of the included studies were from high-income countries. The duration of programmes varied from comprehensive programmes structured over 2 years (n = 2) to shorter duration medical oncology training activities (n = 2), a short, 1.5-day workshop and a 10-hour course. In the grey literature, GPO training programme durations ranged from 2 weeks to 13 months. A mixture of delivery methods was employed including didactic lectures and clinical rotations. CONCLUSION: This scoping review identified a small number of heterogeneous studies and grey literature sources that described and/or evaluated medical oncology training programmes for GPs. The information synthesised here can be used to foster the collaboration needed for the continued development of GPO programmes that could help address the problem of lack of workforce to meet the rising burden of cancer, especially in LMICs.

The 2016 APBMT Activity Survey Report: Trends in haploidentical and cord blood transplantation in the Asia-Pacific region.

This report describes the results of the Asia-Pacific Blood and Marrow Transplantation Group (APBMT) Activity Survey 2016, focusing on the trends of haploidentical and cord blood (CB) transplants in the Asia-Pacific region. Mongolia and Nepal submitted their first activity data in this survey, and the number of countries/regions participating in the activity survey grew to 20. The annual number of transplants exceeded 20,000 for the first time in 2016, and the total number of centers increased to 686. About 87.9% of all hematopoietic stem cell transplantations (HSCTs) were performed in China, Japan, Korea, India, and Australia with China performing the highest number. Beginning with the 2016 survey, APBMT modified the survey forms and initiated the collection of the exact number of haploidentical transplants. The total number of such transplants was 3,871, and 66.0% of those were performed in China. Meanwhile, cord blood transplants in this region remained high (1,612), and 81.8% of them (1,319) were performed in Japan. The number of facilities and transplants, the ratio of haploidentical transplants to related transplants, the ratio of CB transplants to unrelated transplants, and proportions of haploidentical and CB transplants per capita significantly differed among countries/regions in the Asia-Pacific region. Data collection and analysis revealed the transition and diversity of transplants in this region. This report also shows a dramatic increase in haploidentical transplants as seen in other parts of the world, while revealing uniquely that the activity of cord blood transplant remains high in this region.