P. B. Hesseling

Spectrum and presentation of pediatric malignancies in the HIV era: Experience from Blantyre, Malawi, 1998–2003

Data on childhood cancers in Africa are sparse, particularly since the spread of HIV. We aimed to document the frequency of pediatric cancers presenting to a large central hospital in Malawi, detailing the presenting features, initial investigations, and HIV status of these children.

The 2000 Burkitt lymphoma trial in Malawi.

We previously reported 57% 12‐month event free survival (EFS) in Malawian children with stage I to III Burkitt lymphoma (BL) with an intermediate dose chemotherapy protocol lasting 77 days. This protocol was shortened to 42 days and evaluated in children with stage I to IV disease for EFS and toxicity.

Malnutrition and neutropenia in children treated for Burkitt lymphoma in Malawi.

Infection in neutropenic children is a major cause of morbidity and mortality in children treated for cancer. In developing countries, children with cancer are often malnourished at diagnosis. In Blantyre, Malawi, children with Burkitt lymphoma are treated with a local protocol with limited toxicity. The aim of this study was to evaluate the incidence and outcome of febrile neutropenia during this treatment and the association with malnutrition at diagnosis.

Endemic Burkitt lymphoma: a 28-day treatment schedule with cyclophosphamide and intrathecal methotrexate

Abstract Background: Endemic Burkitt lymhoma (eBL) is the most common childhood cancer in equatorial Africa and there is a need for affordable, effective treatment. Aim: To record the morbidity of treatment and event-free survival after 1 year using relatively high doses of cyclophosphamide at short intervals combined with intrathecal methotrexate. Methods: Forty consecutive patients with a mean age of 6.9 (range 2–15) years were treated at Queen Elizabeth Central Hospital, Blantyre between 10th April and 17th November 2006. The initial diagnosis was made clinically and confirmed by fine-needle aspiration in 73%. Abdominal ultrasound, bone marrow aspirate and CSF analysis were undertaken routinely. Chemotherapy consisted of cyclophosphamide, 40 mg/kg on day 1 and 60 mg/kg on days 8, 18 and 28. Intrathecal methotrexate 12.5 mg and hydrocortisone 12.5 mg were administered on days 1, 8, 18 and 28. Allopurinol was commenced before chemotherapy, and a high urinary output was maintained to prevent tumour lysis. Results: St Jude stage distribution was stage I, 1; II, 9; III, 24; and IV, 6. An equal number (70%) presented with abdominal and facial disease, and 15% with paraplegia. Twenty patients (50%) were below the 5th NCHS centile for weight-for-age. Two patients died during treatment, three had chemotherapy-resistant disease and 35 (88%) achieved complete clinical remission by day 28. Sixteen required antibiotic treatment for presumed infection and nine received a blood transfusion. Relapse occurred in 16 patients after 65–311 days (median 137). Nineteen patients (48%) have been in continued remission for 265–670 days (median 454). Conclusion: This short, inexpensive treatment schedule (<50 US

Practical recommendations for the management of children with Endemic Burkitt Lymphoma (BL) in a resource limited setting

) cured almost 50% of eBL patients in a setting of very limited resources.

Meeting the challenge of hematologic malignancies in sub-Saharan Africa.

Treatment recommendations for endemic Burkitt lymphoma (BL) in settings with only minimum requirements for curative treatment (PODC setting 1) are described. The reported cure rate for endemic BL is usually <50%. Facilities within setting 1 differ. Three treatment schedules are proposed based on: (1) when accurate staging is not possible, (2) when staging is possible and for (3) relapses and poor responders to primary therapy. A literature review and personal experience were used to formulate the recommendations. Recorded 1‐year event free survival was 48% for treatment 1, 61% for treatment 2, and 35% for the rescue treatment. Pediatr Blood Cancer 2013; 60: 357–362.

The Cameroon 2008 Burkitt Lymphoma Protocol: Improved Event-Free Survival with Treatment Adapted to Disease Stage and the Response to Induction Therapy

Cancer is a leading cause of death and disability in sub-Saharan Africa and will eclipse infectious diseases within the next several decades if current trends continue. Hematologic malignancies, including non-Hodgkin lymphoma, leukemia, Hodgkin lymphoma, and multiple myeloma, account for nearly 10% of the overall cancer burden in the region, and the incidence of non-Hodgkin lymphoma and Hodgkin lymphoma is rapidly increasing as a result of HIV. Despite an increasing burden, mechanisms for diagnosing, treating, and palliating malignant hematologic disorders are inadequate. In this review, we describe the scope of the problem, including the impact of endemic infections, such as HIV, Epstein-Barr virus, malaria, and Kaposi sarcoma-associated herpesvirus. We additionally describe current limitations in hematopathology, chemotherapy, radiotherapy, hematopoietic stem cell transplantation, and supportive care and palliation. We review contemporary treatment and outcomes of hematologic malignancies in the region and outline a clinical service and research agenda, which builds on recent global health successes combating HIV and other infectious diseases. Achieving similar progress against hematologic cancers in sub-Saharan Africa will require the sustained collaboration and advocacy of the entire global cancer community.

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

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/m2 MTX intravenous (IV) and vincristine 1.5 mg/m2 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.

Childhood cancer in Africa

Patients with endemic Burkitts lymphoma who failed primary treatment with the Malawi 2002 or 2003 Burkitts 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 Burkitts lymphoma patients.

High-dose intense chemotherapy in South African children with B-cell lymphoma: Morbidity, supportive measures, and outcome

The majority of children with cancer live in low‐ and middle‐income countries (LMICs) with little or no access to cancer treatment. The purpose of the paper is to describe the current status of childhood cancer treatment in Africa, as documented in publications, dedicated websites and information collected through surveys. Successful twinning programmes, like those in Malawi and Cameroon, as well as the collaborative clinical trial approach of the Franco‐African Childhood Cancer Group (GFAOP), provide good models for childhood cancer treatment. The overview will hopefully influence health‐care policies to facilitate access to cancer care for all children in Africa. Pediatr Blood Cancer 2014;61:587–592.