Burkitt's lymphoma: The prevalence of HIV/AIDS and the outcome of treatment.

The prevalence of HIV in Burkitt's lymphoma (BL) patients and the outcome of treatment in Cameroon were unknown. Records of all patients diagnosed with BL at three Cameroon Baptist Convention hospitals were reviewed to ascertain the recorded HIV status and outcome of treatment. Of 979 patients diagnosed with BL, 717 were tested for HIV and 11 (1.5%) were HIV-positive. Three of eight patients treated with both cyclophosphamide (CPM)-based chemotherapy and antiretrovirals were alive at 62, 96 and 111 months, respectively. The HIV rate was comparable to that of 1% for the general population of children aged <15 years. Low-cost high-frequency CPM was the only available treatment option for BL and was associated with 37.5% long-term survival in a resource-limited setting.

Kaposi's sarcoma: Good outcome with doxorubicin, bleomycin and vincristine sulphate (ABV) chemotherapy and highly active antiretroviral therapy.

There is little published information on effective treatment of Kaposi's sarcoma (KS) in children in low-income countries. We prospectively treated 12 patients with an institutional review board-approved protocol consisting of four monthly courses of doxorubicin (Adriamycin), bleomycin and vincristine sulphate (ABV), with highly active antiretroviral therapy (HAART) plus co-trimoxazole prophylaxis for those who were HIV-positive, with additional vincristine if remission was not achieved after 4 months. Maintenance HAART plus co-trimoxazole was given to all HIV-positive patients. A fine-needle aspirate and CD4+ count were done if possible, and staging was performed according to Mitsuyasu. Eight of ten HIV-positive patients with stage III - IVB disease, and both HIV-negative patients with stage I disease, were in remission after 473 - 1 490 (mean 939) days. One patient died after absconding during treatment, and one died from neutropenia-related pulmonary infection. ABV with or without HAART is an effective treatment option for children with KS.

Burkitt's lymphoma patients in Northwest Cameroon have a lower incidence of sickle cell trait (Hb AS) than healthy controls.

Contradictory findings have been reported from Africa with regard to the risk of developing Burkitt's lymphoma (BL) in sickle cell trait (AS)carriers. Haemoglobin electrophoresis was performed in 78 BL patients in the Northwest region of Cameroon, and in 78 nearest-neighbourcontrols of the same age, sex and tribe from the same village. AS was confirmed in 4 of 78 (5.13%) BL patients and in 11 of 78 (14.10%)controls (χ2, p=0.052; Fisher's exact, one-tailed, p=0.050). Sickle cell trait carriers had a marginal statistically reduced risk of developing BL.

Endemic Burkitt Lymphoma: Long-term Outcome in 87 Patients Who Presented With Paraplegia in Cameroon.

The reported long-term outcome of endemic Burkitt lymphoma (eBL) patients who present with paraplegia is largely unknown. Records of BL patients treated with comparable short-interval cyclophosphamide chemotherapy schedules between 2004 and 2014 at three Baptist mission hospitals in Cameroon were reviewed. Survivors were followed up and examined at home or in hospital. Eighty-seven of 948 (9.2%) patients had paraplegia at diagnosis. The survival rate in eBL patients with paraplegia at diagnosis was 33% (n = 29) after follow-up of between 2 and 96 (median 40) months. Seven patients (24%) had neurological sequelae and needed rehabilitation. There was no relationship between the duration of symptoms (<2, 2-4, >4 weeks) and the survival rate or the risk to have neurological sequelae. The survival rate and risk for sequelae were similar in patients with confirmed St. Jude stage III and IV diseases.

Epidemiology of Burkitt's lymphoma in Northwest Province, Cameroon, 2003-2010.

BACKGROUND: Burkitt's lymphoma (BL) is an aggressive non-Hodgkin's lymphoma endemic to regions of Africa. Cases are thought to be typically found in low-lying, humid regions where malaria is rife. AIMS AND OBJECTIVES: To investigate the clinical characteristics of BL, its incidence and relationship with malarial incidence in Northwest (NW) Province, Cameroon. METHODS: Data on BL were collected from the three tertiary referral centres for BL treatment in NW Province, Cameroon. Data on malaria were collected from the Delegation of Public Health in Bamenda, NW Province. Data were collected between March and May 2010. RESULTS: 471 cases of BL were identified. The St Jude's stage of patients at presentation was as follows: stage I, 14.4% (43/299); stage II, 8.4% (25/299); stage III, 69.9% (209/299); stage IV, 7.4% (22/299). The incidences of BL per 100,000 children <15 years of age from 2005 to 2009 were as follows: 2005, 3.01 (29); 2006, 2.02 (20); 2007, 2.45 (25); 2008, 2.38 (25); 2009, 3.06 (33). The average incidence in NW Province was 2.58. In the Ndop plain, Ngo-Ketunjia, the incidences of BL were as follows: 2005, 10.3 (10); 2006, 3.00 (3); 2007, 1.95 (2); 2008, 2.84 (3); 2009, 4.60 (5). The average incidence was 4.54/100,000 children <15 years of age. Statistical analysis demonstrated a sinusoidal distribution of malaria cases throughout the year (P<0.00), with a peak incidence on 10 April. Conversely, no sinusoidal distribution of BL cases was demonstrated throughout the year (P = 0.09). CONCLUSION: No relationship was demonstrated between an acute malarial infection and BL. Significant clustering was found, with the low-lying Ndop plain of Ngo-Ketunjia having an incidence of BL nearly twice that elsewhere in the region. The study demonstrates that the incidence of BL in NW Province, Cameroon remains one of the highest documented in the world.

The Cameroon 2008 Burkitt lymphoma protocol: improved event-free survival with treatment adapted to disease stage and the response to induction therapy.

Treatment of endemic Burkitt lymphoma (BL) with cyclophosphamide (CPM) and intrathecal methotrexate (IT MTX) can cure 50% of patients. In this study, induction therapy with CPM and IT MTX was followed by consolidation chemotherapy adapted for stage, clinical response, and abdominal ultrasound findings. One hundred and twenty-nine consecutive patients with BL, 77 male and 52 female with a median age of 7.9 years, were treated in mission hospitals in Cameroon. The diagnosis rested on fine-needle aspirate (79%), biopsy, bone marrow, cerebrospinal fluid, abdominal ultrasound, and clinical examination. Six percent had St Jude stage I, 13% stage II, 72% stage III, and 12% stage IV disease. The abdomen (76%) and face (50%) were mainly involved. Induction chemotherapy was CPM 40 mg/kg and IT MTX 12.5 mg and IT hydrocortisone 12.5 mg on days 1, 8, and 15. Stage I and II patients received CPM 60 mg/kg on day 29, and stage III patients CPM 60 mg/kg on days 29 and 43 if in remission on day 28. Stage IV patients and patients not in remission received CPM 60 mg/kg on days 29, 43, and 57 and 1.0 g/m(2) MTX intravenous (IV) and vincristine 1.5 mg/m(2) IV on day 29. Event-free survival (EFS) at mean 365 days was 61% (n = 79) and 100% in stage I, 85% in stage II, 60% in stage III, and 27% in stage IV patients. Deaths (n = 24) were disease or treatment related and 26 patients relapsed (mean 135 days). Risk-adapted treatment achieved 61% 1-year EFS.

The incidence, clustering and characteristics of Burkitt lymphoma in the Northwest province of Cameroon.

The epidemiology of Burkitt lymphoma (BL) has never been documented in Cameroon. Data were collected from 16 hospitals, the Delegation of Public Health and the regional pathologist in the Northwest province of Cameroon on all BL cases. The incidence of BL in this region is 5.9/100,000 children aged <15 years/year - the second highest incidence documented to date. Significant clustering was also identified in Ndop, a low-lying region with a high malaria endemicity, at 21.5 cases/100,000 children aged <15 year/year (P < 0.001).

The effect of vitamin A status in children treated for cancer.

Chemotherapy for cancer can cause immunocompromise. The authors speculated that children with cancer and low vitamin A plasma levels were more susceptible to cancer treatment-related complications than children who are not vitamin A deficient. A cohort of 49 children with cancer were followed from diagnosis until death or for at least 5 years. Plasma retinol levels were determined at diagnosis. Complications of treatment were recorded. Children with low retinol levels at diagnosis tended to have more chance to develop febrile neutropenia (p = .052). Children with fever had lower mean vitamin A levels at diagnosis than those who did not suffer febrile episodes. In a childhood population with a high prevalence of vitamin A deficiency, routine vitamin A assessment and supplementation in children with cancer appears indicated.

Rescue chemotherapy for patients with resistant or relapsed endemic Burkitt's lymphoma.

Patients with endemic Burkitt's lymphoma who failed primary treatment with the Malawi 2002 or 2003 Burkitt's lymphoma treatment protocols, consisting of high frequency cyclophosphamide 40 mg/kg and intrathecal methotrexate, were offered rescue chemotherapy. Twenty-eight patients (14 boys and 14 girls; age range 3-13 years) with resistant disease (n=8) or relapse (n=20) presented to the Queen Elizabeth Central Hospital, Blantyre, Malawi. Treatment consisted of cyclophosphamide 60 mg/kg and vincristine 1.5 mg/m(2) i.v. on Days 1, 8 and 15, plus intrathecal methotrexate on the same days in those patients treated for a relapse. The majority of patients (81%) had St Jude stage III or IV disease. Twenty patients (71%) achieved a complete clinical remission. Day 8 treatment was delayed in eight children and Day 15 treatment in five patients, both for a median of 7 days, mainly due to neutropenia. Ten patients relapsed after 42-311 days (median 105 days). Ten patients (36%) remained in remission for 353-712 days (median 487 days). Patients whose first relapse occurred after 6 months as well as those with limited disease had the best outcome. This simple 15-day chemotherapy schedule salvaged 36% of patients and significantly increased the overall cure rate of our Burkitt's lymphoma patients.

Improved outcome in South African children of mixed ethnicity treated for all.

A historical cohort study with an analytical component was conducted to determine whether risk-appropriate chemotherapy can improve survival in children of mixed ethnicity with ALL. Eighty-one coloured children treated for ALL in South Africa were divided into 2 groups: group A (n = 39), treated prior to 1992, and group B (n = 42), treated after 1992. A comparison was made of survival, treatment complications, and supportive measures. The two groups were comparable. The mean nadirs of the white cell count (p < .01), platelet count (p = .01), and hemoglobin value (p < .01) were significantly lower in group B. The survival rate of 37% in group A improved to 66% in group B (p = .025). The results show that a risk-adapted regimen increased survival in children of mixed ethnicity in the Western Cape, despite increased hematological toxicity and episodes of febrile neutropenia.

Isoniazid pharmacokinetics in children treated for respiratory tuberculosis.

AIMS: To define the pharmacokinetics of isoniazid (INH) in children with tuberculosis in relation to the N-acetyltransferase 2 (NAT2) genotype. METHODS: The first order elimination rate constant (k) and area under the concentration curve (AUC) were calculated in 64 children <13 years of age (median 3.8) with respiratory tuberculosis from INH concentrations determined 2-5 hours after a 10 mg/kg INH dose. The NAT2 genotype was determined; 25 children were classified as homozygous slow (SS), 24 as heterozygous fast (FS), and 15 as homozygous fast (FF) acetylators. RESULTS: The mean (SD) k values of the genotypes differed significantly from one another: SS 0.254 (0.046), FS 0.513 (0.074), FF 0.653 (0.117). Within each genotype a median regression of k on age showed a significant decrease in k with age. The mean (SD) INH concentrations (mg/l) two hours after INH administration were SS 8.599 (1.974), FS 5.131 (1.864), and FF 3.938 (1.754). A within genotype regression of 2-hour INH concentrations on age showed a significant increase with age. A within genotype regression of 3-hour, 4-hour, and 5-hour concentrations on age also showed a significant increase with age in each instance. In ethnically similar adults, mean (SD) 2-hour INH concentrations (mg/l) for each genotype were significantly higher than the children's: SS 10.942 (1.740), FS 8.702 (1.841), and FF 6.031 (1.431). CONCLUSIONS: Younger children eliminate INH faster than older children and, as a group, faster than adults, and require a higher mg/kg body weight INH dose to achieve serum concentrations comparable to adults.

Incidence of acute lymphoblastic leukaemia in white and coloured children in the Western Cape.

UNLABELLED: Objectives. To record the age-specific incidence rate (ASIR) for diagnosed acute lymphoblastic leukaemia (ALL) in coloured and white children aged 0 - 12 years in the Western Cape (WC). DESIGN: A retrospective population-based study using the 1991 population census to calculate the mean annual childhood population and the ASIR for ALL in the 0 - 4, 5 - 9 and 10 - 12-year age groups in rural and Cape Town metropolitan areas for the period 1983 - 1999. Odds ratios were calculated using EpiInfo 2000. SETTING: Registry records of the paediatric cancer units at Tygerberg and Red Cross War Memorial Children's hospitals where all children with ALL in the WC were initially treated. SUBJECTS: All white and coloured children aged 0 - 12 years diagnosed as having ALL from 1983 - 1999. OUTCOME MEASURES: The ASIR by age and ethnic group in rural and metropolitan patients in the WC. RESULTS: The estimated annual childhood population in 1991 was 709 151 with 80.4% coloured and 19.6% white children, of whom 60% were resident in the Cape Town metropolitan area and 40% in the rural area of the WC. Of 246 children with ALL diagnosed in the period 1983 - 1999, 144 were male and 102 female. The ASIR in coloured children aged 0 - 4 years was 17.1/10(6) in the rural and 30.5/10(6) in the metropolitan area, compared with 55.7/10(6) and 56.2/10(6) respectively in white children. In the 5 - 9-year age group the ASIR in coloured children was 10.0/10(6) in the rural and 16.6/10(6) in the metropolitan area compared with 27.6/10(6) and 26.7/10(6) respectively in white children. The 10 - 12-year age group had comparable incidence rates in both populations and geographical areas. Only one case occurred within a 20 km radius of the Koeberg nuclear reactor. CONCLUSIONS: White children have an ASIR for ALL comparable to rates of diagnosis in the USA, while only half as many coloured children aged 0 - 9 years were diagnosed in both the rural and metropolitan areas. This contrast may indicate significant underdiagnosis of ALL in coloured children over the period in question. The change in health policy since 1994, which has improved access to primary health care, may improve the rate of diagnosis among coloured and black children.

Haemophilia patients aged 0-18 years in the Western Cape.

OBJECTIVES: To record the number of haemophilicas aged 0-18 years in the Western Cape (WC), what event led to the diagnosis, the level of clotting factor, treatment, functional status of their joints and impact of the disease on the family. DESIGN: A prospective study of patients registered with the South African National Haemophilia Registry and new patients, utilising the patients' paediatricians, hospital records, patient and guardian interviews, physical examination and provincial nurse haemophilia co-ordinators. SETTING: Haemophilia care centres at the three WC academic hospitals, regional hospitals and homes of patients. Two elective medical students, MHH and JJH, collected the information. SUBJECTS: All boys with confirmed haemophilia A or B in the WC. OUTCOME MEASURES: Events that led to diagnosis, degree of haemophilia, use of clotting factor, functional status, and effect on family. RESULTS: Of 78 patients (59 haemophilia A, 19 haemophilia B) identified, 49 could be studied. Forty-three per cent had severe, 29% moderate and 22% mild disease (6% unknown). Family history was present in 49%, but led to diagnosis in only 12%. The most common first symptoms were subcutaneous and mucosal bleeding. Delay in diagnosis varied from 0 to 9 months. Twenty-nine per cent of guardians were suspected of child abuse. RSA produced clotting factor was used 'on demand' in 73% of patients, for periodic prophylaxis in 20% and as continuous prophylaxis in 7%. Joints were functionally restricted in 43% of patients. The majority of guardians (59%) said the disease had a major impact on the family. CONCLUSIONS: The diagnosis of haemophilia in children with a positive family history was often delayed. Haemophilia causes significant morbidity in our patients and their families.

Long term survival of children with Burkitt lymphoma in Malawi after cyclophosphamide monotherapy.

BACKGROUND: Between 1991 and 1997, limited funding at times restricted available treatment for children with Burkitt lymphoma (BL) to cyclophosphamide (CPM) monotherapy at Lilongwe Central Hospital, Malawi. Our objective was to assess long-term survival in Malawian children with Burkitt lymphoma (BL) who had received one or more treatments with intravenous CPM at 40 mg/kg/dose at 14-day intervals. PROCEDURE AND RESULTS: The study population consisted of 92 children in whom BL had been confirmed on fine needle aspirates (FNA), a home address had been documented on discharge from hospital, and the treatment records could be verified. Only the clinical site(s) of disease had been recorded. The M:F ratio was 1.4 and median age 8 years. A clinical officer on motorcycle attempted to locate the given addresses and interview parents or other sources. In 19 patients, the address was incorrect. Of 73 evaluable patients, 40 children are alive at a mean follow-up time of 59 (range: 29-104) months. The survival rate was 63.5% in 52 children with BL of the head only, and 33.3% in 21 children with primary disease involving the abdomen or other sites. Survivors had received a median number of 6 (range: 1-12), non-survivors 4 (range: 1-12), and untracable children 3 (range: 1-11) courses of CPM. CONCLUSIONS: We confirmed that CPM could cure children with facial and abdominal BL. The unavoidable bias in the selection of patients and the variable amount of CPM given, precludes accurate survival estimates. A prospective study with proper staging, assessment of FNA, marrow and cerebrospinal fluid with modern techniques, a standard treatment protocol, and adequate follow-up will better define the current therapeutic value of CPM monotherapy. CPM can be purchased at about 3 US dollars per 500 mg.

Infants exposed to alcohol prenatally: outcome at 3 and 7 months of age.

To investigate early recognition of the consequences of alcohol exposure in utero, we studied 79 infants at the ages of 3 and 7 months. Twenty-nine of them were exposed to varying levels of maternal alcohol intake and 50 had no exposure and formed a control group. Special attention was paid to fetal alcohol syndrome-related facial features, neurological development and behavioural performance of the infants. To monitor facial features, pictures were taken at 3 and 7 months of age. Significant differences in facial features were found between the alcohol-exposed and non-exposed children at 3 months only. An age-adequate neurological examination showed no significant difference at 3 months but a significant difference at 7 months of age between the alcohol-exposed infants and the controls. Mothers reported more misbehaviour in the exposed than in the non-exposed group. These results indicate that it is possible to recognise alcohol-related defects within the 1st year of life thus allowing early intervention.

Prognostic value of day 14 blast percentage and the absolute blast index in bone marrow of children with acute lymphoblastic leukemia.

The product of the percentage blasts on the bone marrow aspirate (BMA) and the biopsy cellularity has been termed the "absolute blast index aspirate" (ABI-aspirate) and is used to measure disease response on day 7 of induction therapy. The authors compared the event-free survival (EFS) in high-risk and standard-risk patients as identified by the ABI-aspirate and the BMA percentage blasts on day 14 of induction therapy. Both indices identified high-risk cases. EFS of patients categorized as high-risk by these 2 methods and the high-risk criteria used by the authors' service (WCC of > 20 x 10(9)/L, age < 2 and > 8 years and a peripheral blood blast count of > 1.0 x 10(9)/L on day 8 of induction) did not differ. There was concordance between patients identified as high risk by all 3 methods. The results confirmed the prognostic value of the ABI-aspirate and the BMA percentage blasts on day 14 of induction therapy, but these methods were not superior to the high-risk criteria currently in use.

Viral isolates during febrile neutropaenia in children with cancer.

We prospectively studied South African children with cancer for viral isolates during episodes of febrile neutropaenia. Viruses were found in seven (31.8 per cent) and bacteria in five (22.7 per cent) of 22 episodes. The most common isolate was the herpes simplex virus and the most common source was from nasopharyngeal aspirates. There was no dual detection of viral and bacterial isolates. This study emphasizes the important contribution of viruses to febrile neutropaenia.