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.

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.

Plasma Cell Leukemia: A Review of 3 Cases Managed in Kenya.

Plasma Cell Leukemia (PCL) is a rare and aggressive form of plasma cell dyscrasia that can arise either de novo (primary plasma cell leukemia) or evolve from previously diagnosed and treated multiple myeloma (secondary PCL). We highlight three clinical cases with very different presentations as a reminder of this diagnosis. The cases also highlight the diversity and variability that cover a patient's journey that is highly dependent on accessibility based on financial capability and social support. The clinical presentation is more aggressive due to the higher tumour burden and more proliferative tumor cells with cytopenias being profound and more organomegaly. The diagnosis is made based on at least 20% of total white blood cells being circulating plasma cells with a peripheral blood absolute plasma cell count of at least 2 × 109/l. Treatment with novel agents followed by autologous stem cell transplant in those who are transplant eligible leads to better outcomes.

Cytopenia among CML Patients on Imatinib in Kenya: Types, Grades, and Time Course.

BACKGROUND: Imatinib mesylate is the gold standard for the treatment of all phases of Philadelphia-positive chronic myeloid leukemia. Patients on imatinib treatment may develop cytopenia due to drug toxicity. This study aimed to determine the types, grades, and time course of cytopenia in CML patients on imatinib at a Nairobi hospital. METHODS: This was a cross-sectional descriptive study of adult patients aged ≥18 years followed up at the Glivec International Patient Access Program (GIPAP) clinic from 2007 to 2015. Patients who developed cytopenia within 12 months of initiating imatinib were eligible. Clinical and hematologic data were retrieved from the patients' charts and entered into a study proforma. Measures of central tendency such as mean, median, mode, standard deviation, and variance were used for analysis. RESULTS: Sixty three percent (63.6%) of the 94 patients developed a monocytopenia, with anemia seen in 34%, neutropenia in 27.6%, and thrombocytopenia in 8% of the 94 patients. Anemia plus neutropenia was the most common bicytopenia at 12.7%. Pancytopenia was seen in only 5 of the 94 patients. Most of the cytopenia was grades 2 and 3. Anemia was present at baseline while neutropenia and thrombocytopenia developed within 12 months of imatinib initiation. Anemia resolved during the first 12 months of therapy while neutropenia and thrombocytopenia resolved within 24-36 months of treatment. CONCLUSION: Monocytopenia, especially anemia, was the most common type of cytopenia. The cytopenia was predominantly grade 2, developed in majority of the patients within 6 months after imatinib initiation, and had resolved by 24-36 months after imatinib initiation.