Burkitt Lymphoma: A Potentially Curable Childhood Tumour: Experience in Ile-Ife, Nigeria (1986-2014)

Background: Burkitt lymphoma (BL) is the commonest tumour among Nigerian children. It is reported to be highly responsive to readily available cytotoxic drugs; yet, the outcome of therapy remains abysmal. Objectives: To review the epidemiology of BL in terms of risk factors, age incidence, regional distribution, disease sub-types, examine the available treatment regimens locally and internationally and report on the outcome of treatment in Nigeria under different conditions. Methods: A comprehensive literature review on the epidemiology of BL was undertaken and results of publications and clinical trials of BL were evaluated. Results: Three major sub-types of Burkitt lymphoma are recognised in the world literature; the classic endemic BL (eBL) in sub-Saharan Africa, EBV-independent sporadic BL (sBL) found in population outside the endemic areas and the HIV-related BL (HIV-BL), which is found in regions with high incidence of HIV infection. All the sub-types have common cytogenetic abnormalities: t (8, 14), t (8, 22), and t (2, 8). The COM regimen incorporating cyclophosphamide, oncovin and methotrexate (with the intrathecal cytarabine and methotrexate), was found to be very effective for eBL. Treatment outcome was dismal for the self-financed patients treated with COM regimen between 1986 and 2000 (Group A) compared to the internationally sponsored patients treated between 2000 and 2014 (Group B). While 16.8% of Group A patients had no chemotherapy, 9.8% were lost to toxic deaths and 88% defaulted; most of the patients in group B had full chemotherapy; the Event-Free Survival (EFS) rates at 12 and 24 months were 58.3% and 53.4%, respectively. Conclusions: COM regimen with intrathecal cytarabine and methotrexate is very effective for eBL

Blood pressure indices and disease severity in patients with sickle cell anaemia

Background: Individuals with sickle cell anaemia (SCA) have lower systemic blood pressures compared to individuals with haemoglobin Hb AA phenotype.Objective: To evaluate blood pressure indices of individuals with SCA in steady state, in comparison with haematological and clinical markers of disease severity.Methodology: Seventy-nine (79) individuals with SCA (subjects) in steady state and 50 age-matched individuals with Hb AA (controls) were prospectively studied. Height, blood pressure (BP), weight, creatinine clearance (by 24-hour urine collection), full blood count (FBC) and reticulocyte count were obtained from all subjects and controls. Body mass index (BMI), corrected reticulocyte count, mean arterial pressure (MAP) and pulse pressure (PP) were calculated using standard protocols.The frequency of vaso-occlusive crises in the last one year and number of blood transfusions in the last two years were obtained from subjects.Data was analyzed using descriptive and inferential statistics and p ≤0.05 was used to define the level of statistical significance.Results: The systolic (105.52±11.75mmHg and 113.20±7.94mmHg respectively; P = 0.01), diastolic (62.59±9.33mmHg and 75.40±5.70mmHg respectively; P=0.03) and mean arterial pressures (76.90±8.81mmHg and 88.00±5.51mmHg respectively;P =0.04) were significantly lower in subjects when compared with controls. ; pulse pressure (PP) was however significantly higher in subjects than controls (42.92±10.91mmHg and 37.80±7.43mmHg respectively (P = 0.03). In female subjects, the white cell count was negatively correlated with systolic BP (r = -0.39;P = 0.01) and PP (r = -0.33; P = 0.03).Conclusion: Lower systolic and pulse pressures may predict worsening disease severity in individuals with sickle cell anaemia.Keywords: Sickle cell anaemia,disease severity,blood pressure indice

Lymphomas in sub-Saharan Africa - what can we learn and how can we help in improving diagnosis, managing patients and fostering translational research?

Approximately 30 000 cases of non-Hodgkin lymphoma (NHL) occur in the equatorial belt of Africa each year. Apart from the fact that Burkitt lymphoma (BL) is very common among children and adolescents in Africa and that an epidemic of human immunodeficiency virus (HIV) infection is currently ongoing in this part of the world, very little is known about lymphomas in Africa. This review provides information regarding the current infrastructure for diagnostics in sub-Saharan Africa. The results on the diagnostic accuracy and on the distribution of different lymphoma subsets in sub-Saharan Africa were based on a review undertaken by a team of lymphoma experts on 159 fine needle aspirate samples and 467 histological samples during their visit to selected sub- Saharan African centres is presented. Among children (age), BL accounted for 82% of all NHL, and among adults, diffuse large B-cell lymphoma accounted for 55% of all NHLs. Among adults, various lymphomas other than BL, including T-cell lymphomas, were encountered. The review also discusses the current strategies of the International Network of Cancer Treatment and Research on improving the diagnostic standards and management of lymphoma patients and in acquiring reliable clinical and pathology data in sub- Saharan Africa for fostering high-quality translational research

Clinicopathological Features Of Nigerians With Myelodysplastic Syndromes

Aim: Myelodysplastic syndromes are a group of haematologic disorders characterized by varying degrees of cytopenias and a propensity to leukaemic transformation. The aim of this study is to determine the prevalence, clinical and laboratory characteristics and the outcome of management in Nigerians with this disorder. Methods: Ten patients who have full clinical and laboratory information were retrospectively studied. Data extracted included demographic parameters, clinical features at presentation, haematological parameters, including bone marrow cytology (and cytogenetic findings, where available), management instituted and outcome of such therapy. Results: Ten patients with de novo MDS were managed and followed-up for a median period of 3 months. The majority (90.0%) were aged 50 years or above with a median age of 65 years. All presented with symptoms of cytopenias such as anaemia (100%), neutropenia (50.0%), and thrombocytopenia (10.0%). Patients had mainly supportive management such as blood product supports. One patient, however, in addition received growth factor and cytotoxic chemotherapy, while one received cytotoxic drugs alone. These were however not adequate due to financial constraints. Eight deaths were recorded (88.9%), either cytopenia related (five) or renal failure (three). Cause of death in one was not known as he died at home. The mean survival was 50.5 ± 96.1 weeks (range=2.1-308.4 weeks) Conclusion: It could be concluded that though clinical and laboratory features of Nigerians with MDS are similar to what is obtained from other parts of the world, non-availability of both specific and supportive drugs, and poor socio-economic status of most patients contributed significantly to the poor outcome recorded in this report

Determinants of Overall and Progression-Free Survival of Nigerian Patients with Philadelphia-Positive Chronic Myeloid Leukemia

Objective. The tyrosine kinase inhibitors have markedly changed the disease course for patients with Ph+ and/or BCR-ABL1+ chronic myeloid leukemia (CML). This study was embarked upon to assess the long-term effects of imatinib therapy on survival in adult Nigerian patients with CML. Methods. All adult patients on imatinib (400–600 mg) seen from July 2003 to December 2010 were assessed. Male/female distribution was 171/101, with a median age of 38 (range, 20–75) years. Overall survival (OS) and progression-free survival (PFS) were determined using the Kaplan-Meier techniques. Results. Of all the 272 patients, 205 were in chronic phase, 54 in accelerated phase, and five in blastic phase, at commencement of imatinib. As at December 2010, 222 were alive. OS at 1 and 5 years was 94% and 63%, while PFS was 89% and 54%, respectively. Similarly, amongst the 205 patients in chronic phase, OS at 1 and 5 years was 97% and 68%, while PFS was 92% and 57%. Conclusion. Imatinib’s place as first-line therapy in the treatment of CML has further been reinforced in our patients, with improved survival and reduced morbidity, comparable with outcomes in other populations

Chronic Myeloid Leukemia in Nigerian Patients: Anemia is an Independent Predictor of Overall Survival

Objectives The advent of the tyrosine kinase inhibitors has markedly changed the prognostic outlook for patients with Ph + and/or BCR-ABL1 + chronic myeloid leukemia (CML). This study was designed to assess the overall survival (OS) of Nigerian patients with CML receiving imatinib therapy and to identify the significant predictors of OS. Methods All patients with CML receiving imatinib from July 2003 to June 2013 were studied. The clinical and hematological parameters were studied. The Kaplan-Meier technique was used to estimate the OS and median survival. P -value of <0.05 was considered as statistically significant. Results The median age of all 527 patients (male/female = 320/207) was 37 (range 10-87) years. There were 472, 47, and 7 in chronic phase (CP), accelerated phase, and blastic phase, respectively. As at June 2013, 442 patients are alive. The median survival was 105.7 months (95% confidence interval [CI], 91.5-119.9); while OS at one, two, and five years were 95%, 90%, and 75%, respectively. Multivariate Cox regression analysis revealed that OS was significantly better in patients diagnosed with CP ( P = 0.001, odds ratio = 1.576, 95% CI = 1.205-2.061) or not in patients with anemia ( P = 0.031, odds ratio = 1.666, 95% CI = 1.047-2.649). Combining these variables yielded three prognostic groups: CP without anemia, CP with anemia, and non-CP, with significantly different median OS of 123.3, 92.0, and 74.7 months, respectively (χ 2 = 22.042, P = 0.000016). Conclusion This study has clearly shown that for Nigerian patients with CML, the clinical phase of the disease at diagnosis and the hematocrit can be used to stratify patients into low, intermediate, and high risk groups

Comparative Assessment of Echocardiographic Patterns Among Chronic Myeloid Leukemia Patients on Tyrosine Kinase Inhibitor and Healthy Controls.

PURPOSE: Chronic myeloid leukemia (CML) is one of the common hematological malignancies in Nigeria. Cardiac abnormalities are associated with CML irrespective of treatment with tyrosine kinase inhibitors such as imatinib, which is available gratis in Nigeria. OBJECTIVE: To assess the prevalence and patterns of cardiac dysfunction among patients with CML irrespective of treatment with imatinib using transthoracic echocardiography, and 12-lead surface electrocardiography. PATIENTS AND METHODS: CML patients without Imatinib, CML patients with imatinib, and apparently healthy (age- and sex-matched) controls were 70 each in the study. Various echocardiographic parameters were measured and data obtained were analyzed, and the level of significance was taken as p \u3c 0.05. RESULTS: Of 70 CML patients with imatinib, 54.3% were men and 45.7% were women, while the CML group without imatinib had 62.9% men and 37.1% women, non-CML control had 54.3% men and 45.7% women. The average hematocrit was significantly lower in the CML group without Imatinib compared with the other groups (p CONCLUSION: Cardiac abnormalities are present in CML patients with or without Imatinib treatment, with significant prevalence than what is seen in the non-CML control group

Immunohistochemical characterization of small round blue cell tumors of childhood at Ile-Ife, Nigeria: A 10-Year retrospective study

Background: Immunostains when used in correlation with clinical site of tumours and morphology permits accurate and specific diagnosis of these undifferentiated tumours. Materials and Methods: A ten-year retrospective research of the histopathological and immunohistochemical features of small round blue cell tumours (SRBCT) in OAUTHC was analyzed. Pathology reports of all SRBCT and their blocks were retrieved and recut slides reviewed to determine each tumour types. Acute myelocytic lymphoma/leukeamias and Glioblastoma multiformis were excluded from SRBCT of childhood. Eighty four (84) cases that fulfilled the inclusion criteria were analyzed using immunohistochemistry. Results: The age range of presentation was 0-15 years (Mean 5.98±3.964 year S.D.). Retinoblastoma and Wilms' tumours were the commonest histological sub-types with a percentage of 20.0% each followed by Burkitt lymphoma (17.6%), rhabdomyosarcoma (9.8%) which was the only soft tissue sarcoma found. The least represented was supra-tentorial CNS-PNET (1.2%). Eighty four blocks of SRBCT were subjected to different panels of immunohistochemistry. Of all these tumours 36 cases had a change in diagnosis: 23 cases had an initial, pre-immunohistochemical umbrella diagnosis ranging from NHL, SRBCT to no pathological diagnosis at all. Seven (7) cases with initial diagnosis ranging from Ewing's sarcoma (1 case), retinoblastoma (1 case) to rhabdomyosarcoma (5 cases) were finally confirmed with immunostains as Burkitt lymphoma (BL) while one case of BL was finally confirmed as rhabdomyosarcoma. The last five of the 36 cases were totally non-neoplastic lesions but had histology diagnosis ranging from NHL, spinal cell sarcoma to periosteal osteosarcoma. The immunostains done on these 5 cases revealed erythroid hyperplasia with dyserythropoiesis, cellular neurofibroma, fibrous dysplasia, reactive follicular hyperplasia and normal retinal tissue. Conclusion: Application of immunohistochemistry does indeed enhance the diagnostic accuracy of these undifferentiated tumors