Clinical Profile and Treatment of Multiple Myeloma at a Tertiary Hospital in Kenya: A Five-Year Retrospective Review.

Background: Multiple myeloma (MM) is a chronic B-cell malignancy that involves proliferation of neoplastic clonal plasma cells in the bone marrow with circulating monoclonal immunoglobulins or constituent chains in serum or urine or both. It is a rare cancer with a lifetime risk of 0.76% and an age-adjusted incidence rate of 2.5-7.2 per 100,000 in high-income countries. There is a paucity of local data on the morbidity and treatment of MM. Methods: This was a single-centre descriptive retrospective study at the Kenyatta National Hospital (KNH). The study population included inpatients and outpatients with a documented diagnosis of MM managed between 1st January 2014 and 31st December 2018. Demographic data, pathology reports, laboratory results, and clinical findings were transcribed and uploaded to a database, and data analysis was done using Stata 16® software. Results: A total of 207 patient files were reviewed. The median age at presentation was 60 years with a slight male preponderance. Bone pain was the predominant complaint in 59% (139/207) of patients, with 17% of patients presenting with paraparesis or paraplegia. For patients who underwent imaging, osteolytic bone lesions were identified in 90.6% (126/139). Anaemia was present in 71% (147/207) patients, hypercalcemia in 55.4%, and renal dysfunction in 38.2%. There were 25 different treatment regimens prescribed, with 13 patients (7%) being on bortezomib-based triplet therapy. Conclusions: MM in KNH is a disease of the middle aged, affecting men and women almost equally and presenting mainly with bone pain and anaemia. Although there seems to be a general improvement in diagnosis and care, access to novel and less toxic agents for treatment is still wanting.

Determinants of an integrated cervical cancer screening services in primary healthcare: sharing lessons from Kisumu, Kenya.

Background: The successful integration of cervical cancer screening service (CCASS) into primary healthcare's routine services depends on locality-specific and context-based service determinants. Objective: This paper aims to identify the abovementioned determinants and discusses how health administrators can manage their influence on CCASS delivery at the primary healthcare level. Methods: We conducted in-depth face-to-face interviews using a structured questionnaire with CCASS nurse providers and managers in four randomly selected primary health facilities. Information on the method(s) of screening utilised, the challenges faced, and the changes observed in CCASS provision were collected. Service managers were asked how they managed unplanned CCASS disruption, factors influencing CCASS replication, and aftercare support to cancer-affected women. Nurse providers were interviewed on the management of CCASS awareness and critical changes required to sustain CCASS service effectiveness. We used a constant interactive and inductive approach for data analysis. Results: Nine thematic categories of CCASS determinants were identified: 'cultural', 'socioeconomic', 'individual', 'health system', 'evidence-based operations', 'outcome-based resourcing', 'workflow improvement and standardisation', 'inclusive partner's management', 'utilisation'. These determinants were grouped into three domains: 'conceptual', 'outcomes', and 'growth' domains, to correspond to clusters of determinants that are likely to influence the CCASS lifecycle in its formative, continuous delivery or productivity, and reproductive phases. Conclusions: The findings show that sustaining an efficient integrated CCASS delivery at the PHC level requires phase-appropriate continuous adaptive improvements of service determinants within that locality. Results: Nine thematic categories of CCASS determinants were identified: 'cultural', 'socioeconomic', 'individual', 'health system', 'evidence-based operations', 'outcome-based resourcing', 'workflow improvement and standardisation', 'inclusive partner's management', 'utilisation'. These determinants were grouped into three domains: 'conceptual', 'outcomes', and 'growth' domains, to correspond to clusters of determinants that are likely to influence the CCASS lifecycle in its formative, continuous delivery or productivity, and reproductive phases. Conclusions: The findings show that sustaining an efficient integrated CCASS delivery at the PHC level requires phase-appropriate continuous adaptive improvements of service determinants within that locality.

Molecular Profiling of Kenyan Acute Myeloid Leukemia Patients.

Acute myeloid leukemia (AML) is an infrequent disease, and it is associated with high morbidity and mortality. It harbors a unique configuration of cytogenetic abnormalities and molecular mutations that can be detected using microscopic and molecular methods respectively. These genetic tests are core elements of diagnosis and prognostication in high-income countries. They are routinely incorporated in clinical decision making, allowing for the individualization of therapy. However, these tests are largely inaccessible to most patients in Kenya and therefore no data has been reported on this group of patients. The main purpose of this study is to describe the cytogenetic and molecular abnormalities of acute myeloid leukemia patients seen at the hemato-oncology unit of Kenyatta National Hospital. A cross-sectional descriptive study was carried out over a 3-month period on ten patients with a diagnosis of AML. Social demographics and clinical data were collected through a study proforma. A peripheral blood sample was collected for conventional metaphase G-banding technique and next generation sequencing. Particularly, targeted DNA sequencing (Illumina myeloid panel) and whole exome sequencing (WES) were performed. Cytogenetic analysis failed in 10/10 cases. Targeted sequencing was successfully obtained in 8 cases, whereas WES in 7. Cytogenetic studies yielded no results. There were 20 mutations detected across 10 commonly mutated genes. All patients had at least one clinically relevant mutation. Based on ELN criteria, NGS identified three patients with high-risk mutations, affecting TP53 (n = 2) and RUNX1 (n = 1). One patient was classified as favorable (PML-RARA) while 4 were standard risk. However, WT1 mutations associated with unfavorable prognosis were recorded in additional 2 cases. WES showed concordant results with targeted sequencing while unveiling more mutations that warrant further attention. In conclusion, we provide the first molecular profiling study of AML patients in Kenya including application of advanced next generation sequencing technologies, highlighting current limitations of AML diagnostics and treatment while confirming the relevance of NGS in AML characterization.

Baseline blood count levels increase odds of cytopenia among CML patients in Kenya: a case control study.

BACKGROUND: Imatinib is the gold standard for the treatment of all phases of Philadelphia positive Chronic Myeloid Leukemia (CML). During treatment, patients may develop cytopenia. We aimed to study the baseline characteristics and factors associated with cytopenia at a Nairobi Hospital. METHODS: This was a retrospective case-control study of patients aged ≥18 years on follow-up at the Glivec International Patient Access Program (GIPAP) clinic from 2007 to 2015. The cases consisted of CML patients on imatinib who developed cytopenia. The controls were CML patients on imatinib who did not develop cytopenia. Baseline socio - demographic, clinical, hematologic, and molecular data were retrieved from patients' files. Chi square or fishers' exact tests were used to analyze for differences between cytopenia and no cytopenia. Binary logistic regressions were employed to identify relationships. Univariate and multivariate analyses were done to identify independent predictors of cytopenia. Odds ratios (OR) were presented including the 95% confidence intervals and respective p values. RESULTS: A total of 201 patients were studied consisting of ninety-four (94) patients with cytopenia and 107 with no cytopenia. Among the entire population, males were 52, and 42% were aged 36-50 years. Sex, age, marital status, occupation and education level were similar between the cytopenia and no cytopenia groups. Among the 201 patients, 70% had symptoms for > 12 months before diagnosis, 78.6% had B symptoms at baseline, 80% had a moderate splenomegaly at baseline. Among patients with cytopenia, 40 and 37.4% developed cytopenia within 3 months and 3-6 months respectively after imatinib initiation. Baseline neutrophilia, neutropenia, anaemia, thrombocytosis, thrombocytopenia was found in 68, 11, 11, 23.5 and 11% respectively. Baseline hemoglobin, neutrophil and platelet level were significantly different between the cytopenia and the no cytopenia group. On univariable analysis, baseline anemia with hb < 7.9 g/dL (p = 0.002), neutropenia (p = 0.001), neutrophilia > 100,000/mm3 (p = 0.002) and thrombocytopenia (p = 0.001) increased the odds of developing cytopenia. On multivariable analysis, baseline anaemia (p value < 0.002), neutropenia (p value < 0.001), thrombocytopenia (p value, < 0.001) and thrombocytosis (p value, 0.033) increased the odds of developing cytopenia. CONCLUSION: Odds of cytopenia were higher in presence of baseline cytopenia and thrombocytosis. Clinicians should have a high index of suspicion for these patients.

Correction to: Immune landscape in Burkitt lymphoma reveals M2-macrophage polarization and correlation between PD-L1 expression and non-canonical EBV latency program.

[This corrects the article DOI: 10.1186/s13027-020-00292-w.].

Immune landscape in Burkitt lymphoma reveals M2-macrophage polarization and correlation between PD-L1 expression and non-canonical EBV latency program.

BACKGROUND: The Tumor Microenviroment (TME) is a complex milieu that is increasingly recognized as a key factor in multiple stages of disease progression and responses to therapy as well as escape from immune surveillance. However, the precise contribution of specific immune effector and immune suppressor components of the TME in Burkitt lymphoma (BL) remains poorly understood. METHODS: In this paper, we applied the computational algorithm CIBERSORT to Gene Expression Profiling (GEP) datasets of 40 BL samples to draw a map of immune and stromal components of TME. Furthermore, by multiple immunohistochemistry (IHC) and multispectral immunofluorescence (IF), we investigated the TME of additional series of 40 BL cases to evaluate the role of the Programmed Death-1 and Programmed Death Ligand-1 (PD-1/PD-L1) immune checkpoint axis. RESULTS: Our results indicate that M2 polarized macrophages are the most prominent TME component in BL. In addition, we investigated the correlation between PD-L1 and latent membrane protein-2A (LMP2A) expression on tumour cells, highlighting a subgroup of BL cases characterized by a non-canonical latency program of EBV with an activated PD-L1 pathway. CONCLUSION: In conclusion, our study analysed the TME in BL and identified a tolerogenic immune signature highlighting new potential therapeutic targets.

Molecular switch from MYC to MYCN expression in MYC protein negative Burkitt lymphoma cases.

MYC is the most altered oncogene in human cancer, and belongs to a large family of genes, including MYCN and MYCL. Recently, while assessing the degree of correlation between MYC gene rearrangement and MYC protein expression in aggressive B-cell lymphomas, we observed few Burkitt lymphoma (BL) cases lacking MYC protein expression despite the translocation involving the MYC gene. Therefore, in the present study we aimed to better characterize such cases. Our results identified two sub-groups of MYC protein negative BL: one lacking detectable MYC protein expression but presenting MYCN mRNA and protein expression; the second characterized by the lack of both MYC and MYCN proteins but showing MYC mRNA. Interestingly, the two sub-groups presented a different pattern of SNVs affecting MYC gene family members that may induce the switch from MYC to MYCN. Particulary, MYCN-expressing cases show MYCN SNVs at interaction interface that stabilize the protein associated with loss-of-function of MYC. This finding highlights MYCN as a reliable diagnostic marker in such cases. Nevertheless, due to the overlapping clinic, morphology and immunohistochemistry (apart for MYC versus MYCN protein expression) of both sub-groups, the described cases represent bona fide BL according to the current criteria of the World Health Organization.

Prevalence and Predictors of Cisplatin-Induced Peripheral Neuropathy at the Kenyatta National Hospital.

PURPOSE: To determine the prevalence, predictors, and/or risk factors of chemotherapy-induced peripheral neuropathy in patients undergoing chemotherapy with cisplatin at Kenyatta National Hospital, Nairobi, Kenya. METHODS: This was a cross-sectional analysis of patients who underwent chemotherapy with cisplatin for at least 2 months at Kenyatta National Hospital oncology units. Peripheral neuropathy was determined by history and physical examination per the protocol. Data are presented in tables. Descriptive inferential statistics such as means, medians, and proportions were determined where applicable. RESULTS: We recruited 67 patients who were undergoing chemotherapy with cisplatin. Fifty-six patients (83.6%) had peripheral neuropathy. Forty-five patients (81%) had mild-grade (grades 1 and 2) peripheral neuropathy. Only two patients (3.1%) had grade 4 neuropathy. Almost all patients who were overweight or obese developed peripheral neuropathy. CONCLUSION: Peripheral neuropathy among patients receiving cisplatin is quite prevalent at Kenyatta National Hospital (83.6% prevalence rate). However, most of the patients had a mild grade of neuropathy, which is largely consistent with literature elsewhere.

Improving Access to Cancer Testing and Treatment in Kenya.

PURPOSE: In response to the increasing cancer burden in Kenya, this study identified barriers to patients seeking access to cancer testing and treatment and to clinicians in delivering these services. Policy recommendations based on findings are presented. METHODS: This qualitative study used semistructured key informant interviews. Purposive sampling was used to recruit 14 participants: seven oncology clinicians and seven support and advocacy leaders for patients with cancer. Qualitative analysis was used to identify themes. RESULTS: Seven barriers to cancer testing and treatment were identified: high cost of testing and treatment, low level of knowledge about cancer among population and clinicians, poor health-seeking behaviors among population, long distances to access diagnostic and treatment services, lack of decentralized diagnostic and treatment facilities, poor communication, and lack of better cancer policy development and implementation. CONCLUSION: Kenyans seeking cancer services face significant barriers that result in late presentation, misdiagnosis, interrupted treatment, stigma, and fear. Four policy recommendations to improve access for patients with cancer are (1) improve health insurance for patients with cancer; (2) establish testing and treatment facilities in all counties; (3) acquire diagnosis and treatment equipment and train health personnel to screen, diagnose, and treat cancer; and (4) increase public health awareness and education about cancer to improve diagnoses and treatment. Effective cancer testing and treatment options can be developed to address cancer in a resource-constrained environment like Kenya. An in-depth look at effective interventions and policies being implemented in countries facing similar challenges would provide valuable lessons to Kenya's health sector and policymakers.

The American Society of Clinical Oncology's Efforts to Support Global Cancer Medicine.

Despite much progress in the management of malignant diseases, the number of new cases and cancer-related deaths continues to rise around the world. More than half of new cases occur in economically developing countries, where more than two thirds of cancer deaths are expected. However, implementation of all necessary steps to accomplish the dissemination of state-of-the-art prevention, diagnosis, and management will require increased allocation of resources, and, more importantly, harmonization of the efforts of hundreds of national and international public health agencies, policy-setting bodies, governments, pharmaceutical companies, and philanthropic organizations. More than 30% of the members of the American Society of Clinical Oncology (ASCO) reside and practice outside US borders, and more than half of attendees at all of the scientific congresses and symposia organized by ASCO are international. As cancer has become an increasingly global disease, ASCO has evolved as a global organization. The ASCO Board of Directors currently includes members from France, Brazil, and Canada. In 2013, the ASCO Board of Directors identified a number of strategic priorities for the future. Recognizing the importance of non-US members to the society, their first strategic priority was improving the society's service to non-US members and defining these members' identity in the international oncology community. This article reviews current ASCO activities in the international arena and its future plans in global oncology.

Oesophageal cancer and Kaposi's sarcoma in Malawi: a comparative analysis.

Given that oesophageal cancer (OC) is common in Malawi and its outcome is so dismal, would it be pragmatic to promptly mitigate the effects of smoking, alcohol and aflatoxins rather than seek a higher degree of local evidence for their role in OC? We retrospectively analysed a total of 13,217 OC and Kaposi's sarcoma (KS) cases as recorded in the Malawi National Cancer Registry from 1985 to February, 2006. We found no OC clustering to suggest a role for culturally variable habits like smoking, alcohol, maize use and maize storage in the country. It may be that drinking and eating hot foods physically damages the oesophageal mucosa, this is in line with work recently reported from Asia. We also found that OC numbers have risen in line with KS (and HIV) suggesting a link between these conditions.

The need for a national cancer policy in Malawi.

Cancer is causing a lot of suffering and death in Africa but is not considered a major health problem in Africa. This needs to change. Cancer should be given equal emphasis to HIV/AIDS, tuberculosis (TB) and Malaria. A national cancer policy is required in Malawi to develop and improve evidence-based cancer prevention, early diagnosis, curative and palliative therapy. A national cancer policy is crucial to ensure a priotised, clear, coordinated and sustained fight against cancer. When no policy exists, events are likely to be random, stakeholders and practitioners in the fight against cancer may not agree on how to proceed, may duplicate efforts or may neglect areas that would have greater nationwide impact resulting in poor quality activities and haphazard development.