ACUTE LEUKEMIAS IMMUNOPHENOTYPES AT AGAKHAN UNIVERSITY HOSPITAL, NAIROBI.

OBJECTIVE: The aim was to determine relative frequencies of acute leukemia immunophenotypes using commonly expressed markers and to describe the clinicopathological characteristics. Design: This was a prospective cross-sectional study. SETTING: The study was based at Aga khan clinical laboratory department. SUBJECTS: One hundred and thirty two (132) consecutive blood and bone marrow specimens from patients suspected to have acute leukemia were analysed for cytomorphological characteristics and immunophenotyping. The clinical-pathological characteristics were also recorded. Immunological category was assigned using the EGIL criteria. RESULTS: There were 88 AML and 42 ALL patients analysed for immunophenotypes. Only tw cases of biphenotypic leukemia were found. The commonest overall AML morphological sub-type was AML-M2, 26 (29.5%). Majority of ALL cases were B-cell immunological sub-type (96.6%). Early pre-B phenotype constituted 62.07% and Common B-cell ALL 37.93%. There were only 4 cases of T-cell ALL. Majority of patients presented with anaemia with a median hemoglobin of 7.5g/dl (range 2-15g/dl). The median platelet count was 55 (range 4-462 x 10(9)/L). CONCLUSION: Immunophenotyping of acute leukemia is beneficial in accurate diagnosis of patients with these malignancies in this setup. T-cell ALL, AML-M6 and M7 are less frequent than what has been reported in most studies in Africa.

Clinico-pathologic characteristics and treatment outcomes in children with neuroblastoma at the Kenyatta National Hospital, Nairobi.

OBJECTIVE: To determine clinical-pathologic characteristics, treatment modalities and treatment outcomes of children diagnosed with neuroblastoma. DESIGN: Cross-sectional descriptive study based on secondary data from patient records. SETTING: Records department of Kenyatta National Hospital (KNH), a tertiary teaching and referral hospital based in Nairobi. SUBJECTS: Children aged 15 years and below, admitted with the diagnosis of neuroblastoma, between January 1997 and December 2005. MAIN OUTCOME MEASURES: Presenting clinical features, diagnostic modalities including laboratory and imaging data, treatment modalities, response to treatment and patient survival. RESULTS: Twenty six patients were eligible for the study; 13 males and 13 females giving a M:F ratio of 1:1. The age range was 5 days to 12 years, with a median age of five years. Abdominal swelling (53.8%), inability to walk due to bone pains, (50%), and cranial or periorbital swelling, (38.5%) were the commonest presenting features. Diagnosis of neuroblastoma was based on tissue biopsy in 50% (95% CI 40.6-79.8%) of the patients, and on fine needle aspiration cytology of mass or bone marrow in the rest. Bone marrow involvement was present in 16, (75%). Anaemia, was common with 72.7% patients having a haemoglobin (HB) <8 g/dl at presentation. Immunohistochemistry and cytological grading were done in two, (8%), patients. Urinary vanilly 1 mandelic acid (VMA), screening was positive in 50% (95% CI 29.9%-70.1%). The most frequently involved organs were abdomen (88.9%), and skeleton, (84.6%). Majority of patients, (92.3%), presented with advanced stage IV disease. Three patients died before commencement of treatment. All treated patients (100%), received cytotoxic therapy. Only two patients (8.6%) had surgery as part of treatment while one, (4.3%) was treated with radiotherapy. The initial treatment regimen was similar for all the patients. Although most patients had a complete initial response to treatment, early relapse, treatment failure, death or loss to follow up of patients with progressive disease were common. Overall survival (OS) at one year and two years were 19.2% (95% CI 6.6-39.4%) and 7.7% (95% CI 0.9%-25.1%) respectively. Only one patient was alive, (also free of disease), five years after diagnosis. CONCLUSION: Although other clinical-pathologic findings of the patients were similar to those reported elsewhere, virtually all study patients presented with advanced stage IV disease, which would be associated with poor prognosis irrespective of quality of care. Priority must therefore be on ensuring early diagnosis and referral of patients with neuroblastoma before any other interventions can be expected to positively impact on outcome. The limited role of surgery and radiotherapy observed over the study period may be attributed to late presentation of the patients. Pathologic evaluation of important information could have been availed at minimal extra cost. To be at par with current internationally accepted treatment approaches that have been associated with improved survival, there is need to base choice of regimens for individual patients on clinical and readily accessible pathologic markers.

Immunophenotyping of acute leukaemias by flow cytometry: a review.

OBJECTIVE: To provide an overview of the utility of flow cytometry for phenotyping of acute leukaemias and selection-of monoclonal antibodies. DATA SOURCES: The literature review was obtained through internet, journals and chapters in the relevant books. DATA SELECTION: Relevant articles and chapters on immunophenotyping of acute leukaemias were selected from respected international journals and books in the field of haematology and were reviewed. DATA EXTRACTION AND SYNTHESIS: Complete articles relevant to the topic were selected and reviewed and the necessary information extracted for this review. CONCLUSIONS: Flow cytometry has been used extensively in recent years to characterise haemopoeitic malignancies and done routinely in the developed world. This technique has greatly improved the diagnosis and classification of haemopoeitic malignancies and has been recommended by World Health Organisation classification (WHO) of tumours of haemopoeitic and lymphoid tissue. Application of flow cytometry for the diagnosis of leukaemias has been recently introduced in Kenya and is currently being undertaken in research using limited but appropriate panels of monoclonal antibodies. It is hoped that findings of this research will inform the use of flow cytometry as an ancillary diagnostic technique in our resource-constrained set up.

Disseminated histoplasmosis diagnosed on bone marrow aspirate cytology: report of four cases.

Histoplasmosis, caused by two varieties of dimorphic fungi, Histoplasma capsulatum variant capsulatum and Histoplasma capsulatum variant duboisii is a systemic fungal infection. It has a worldwide distribution and is shown to be more prevalent in North America and Central America. Both variants occur in Africa. Disease spectrum ranges from asymptomatic primary infection to disseminated disease in immunocompromised patients. Since the upsurge of acquired immune deficiency syndrome (AIDS) and despite the availability of high active anti-retroviral therapy (HAART) many patients still present with opportunistic infections of which histoplasmosis is one. Four cases are presented; two infants and two adults. All had disseminated disease with multiple organ involvement and the disease was not suspected clinically. Diagnosis was made incidentally on bone marrow aspirate cytology. The two adult cases were HIV positive, one with CD4 counts of 132 cells/microlitre and was not on HAART. The other was on HAART but the CD4 had not been determined. One of the infants tested HIV negative and the others status was unknown. A high index of suspicion is required for diagnosis as the disease may mimic tuberculosis(TB) and other causes of hepatosplenomegaly such as visceral leishmaniasis. Laboratory diagnosis includes culture, direct staining, antigen and antibody detection. Antibody detection may give false negative in the immunocompromised patient. The infection responds well to antifungal agents (amphotericin B is the drug of choice) and life long maintenance therapy may be required in AIDS especially if CD4 counts remain less than 150 cells/microlitre. Histoplasmosis should be a differential diagnosis in immunosuppressed patients with unexplained fever, weight loss, hepatosplenomegaly and chest findings especially if not responding to anti-TB treatment.