George Chagaluka

Management of children with a Wilms tumor in Malawi, sub-Saharan Africa.

Wilms tumor has a survival rate of 85% to 90% in well-resourced countries. Malawi is a country in Sub-Saharan Africa with very limited resources. We evaluated the outcome of a treatment guideline including preoperative chemotherapy, supportive care, and strategies to enable parents to complete treatment. Between 2006 and 2011, 95 patients were initially diagnosed with a Wilms tumor; 11 were later excluded due to misdiagnosis. In 31% of patients, metastases were detected at presentation. Treatment outcomes in 8 patients with bilateral tumors and 3 patients who were referred after nephrectomy are analyzed separately. Treatment failed in 51% of 73 remaining patients. Reasons for failure were: 1) incomplete treatment (7%); 2) treatment-related deaths (15%); and 3) disease-related deaths (28%) with 11% unresectable tumors or metastases after preoperative chemotherapy and 17% relapse of disease. Projected survival is 46%. Challenges remain to improve survival for children with Wilms tumor in Malawi. Earlier diagnosis would reduce disease-related deaths as numbers of unresectable disease and relapse are high. Effective strategies, including social support, to enable parents to complete treatment need to be continued. Improved supportive care and nutritional support and possibly less intense preoperative chemotherapy are needed to reduce treatment-related deaths.

Kaposi’s sarcoma in children: An open randomised trial of vincristine, oral etoposide and a combination of vincristine and bleomycin

INTRODUCTION Kaposis sarcoma (KS) is a common childhood cancer in places where HIV is endemic and access to antiretroviral therapy (ART) is delayed. Despite this there are no randomised trials to compare and assess chemotherapeutic regimens. METHOD An open label, randomised trial comparing intravenous vincristine alone, vincristine and bleomycin and oral etoposide, was carried out in children with Kaposis sarcoma in the Queen Elizabeth Central Hospital, Blantyre, Malawi. HIV infected children were given ART after 2-3 courses of chemotherapy if they were not already on treatment. Neither HIV nor widespread KS are curable and treatment is aimed at disease reduction and improved quality of life. Tumour reduction was assessed by measuring the size of sentinel KS nodules and quality of life (QoL) by using the Lansky score. Follow up was until death or for one year. FINDINGS 92 children were enrolled of whom 46% were naïve to ART; 10 (11%) were HIV negative. Survival was not influenced by age or gender but was better in the oral etoposide and the vincristine and bleomycin groups. P=0.0045. The group receiving oral etoposide had a better quality of life. Toxicity was not significant, and any drop in haemoglobin or white cell count could have been causally related to HIV infection rather than cytotoxic therapy. CONCLUSION Oral etoposide is a safe, effective treatment to contain KS and improve QoL which can be achieved without many visits to the hospital and intravenous injections.

The efficacy and toxicity of SIOP preoperative chemotherapy in Malawian children with a Wilms tumour

In Malawi, preoperative chemotherapy for Wilms tumour is a logical strategy, but detailed information on toxicity and efficacy in such a resource limited setting has been unavailable.

The use of anthracyclines in the treatment of endemic Burkitt lymphoma

Burkitt lymphoma is the most common malignancy in children in Malawi, the worlds poorest country, where there is a long history of treating this disease using a 28‐day cyclophosphamide‐based protocol. Stage III/IV disease has had poor outcomes. In an attempt to improve the outcome for higher stage disease, anthracyclines were added to the existing protocol. The disease‐free (DFS) and overall survival (OS) of 58 children with cytologically confirmed Burkitt lymphoma admitted during 2012–2014 and treated using this protocol were calculated. Six (10%) children had stage I disease, ten (17%) stage II and 42 stage III or IV (73%). Overall 12‐month DFS (OS) was 68·5% (72·9%); for stage I disease 100% (100%), stage II 56·2% (60%), stage III/IV 66·3% (72·2%). The DFS was significantly improved from the previous protocol (P = 8 × 10−4). The addition of doxorubicin to stage III and IV disease resulted in a markedly improved DFS. Anthracyclines are deliverable in resource‐poor settings and possibly improve the survival of children with Burkitt lymphoma.

Outcome is unchanged by adding vincristine upfront to the Malawi 28-day protocol for endemic Burkitt lymphoma

We previously reported a 28‐day treatment protocol for children with endemic Burkitt lymphoma (BL) which included four doses of cyclophosphamide (CPM), intrathecal methotrexate and hydrocortisone (IT MTX/HC) at Queen Elizabeth Central Hospital (QECH) in Malawi which resulted in an Event‐Free Survival (EFS) of 50% at 1 year.

Treating childhood acute lymphoblastic leukemia in Malawi

Pediatric acute lymphoblastic leukemia (ALL) can now been cured in the vast majority of cases diagnosed in the developed world. However, the treatment regimes rely on good supportive care and multi-agent chemotherapy; and cannot be delivered in poor countries like Malawi. Therefore, many patients

Improved outcome at end of treatment in the collaborative Wilms tumour Africa project

The Collaborative Wilms Tumour (WT) Africa Project has implemented an adapted WT treatment guideline in sub‐Saharan Africa as a multi‐centre prospective clinical trial. A retrospective, baseline evaluation of end‐of‐treatment outcome was performed for a 2‐year period prior to the introduction of this guideline. The collaborative project aims to reduce both treatment abandonment and death during treatment to less than 10% for improving survival.

Haematological cancers in African children: progress and challenges

Cancer is increasingly important in low and middle‐income settings where infectious diseases are declining. Childhood cancers treated in well‐resourced centres have excellent outcomes with more than 80% survival. This success is not reflected in low‐income settings where challenges involve every step on the care pathway. Access to diagnosis, delayed presentation, advanced disease, co‐morbidities and underlying malnutrition make treatment difficult. Treatments are costly for impoverished families. Yet, the common haematological malignancies (Burkitt lymphoma, Hodgkin lymphoma, non Hodgkin lymphoma) are relatively easy to diagnose and, when managed with simple chemotherapy protocols, give limited but good results. As funding becomes available for cancer research we must ensure that the care and cure of these children is top of the agenda. There is already evidence of improved outcomes in middle‐income countries. For others there is a long journey ahead.

Survival of children with a Wilms tumor in Blantyre, Malawi

Abstract Wilms tumor (WT) has a survival rate above 90% in high income countries. Reported survival rates in sub-Saharan Africa are much lower and long-term outcome is not well known as follow-up is challenging. In Blantyre, Malawi, an adapted WT treatment guideline with preoperative chemotherapy, supportive care, and strategies to enable children and parents to complete treatment was introduced in 2006. Between 2006 and 2011, 73 children with a unilateral WT were treated. Follow-up, including home visits when needed, was done. Median follow-up time is 5 years (range 14–95 months). Two and five-year event free survivals are 46 and 42%. Causes of treatment failure are: 7% (5/73) abandonment of treatment, 15% (11/73) death during treatment and 30% (22/73) disease-related deaths (persistent disease and relapse). Long-term follow-up is challenging but necessary to be able to assess outcome and the true impact of interventions.

Triple therapy of vincristine, bleomycin and etoposide for children with Kaposi sarcoma: Results of a study in Malawian children

Kaposi sarcoma (KS) is the most common paediatric cancer in human immunodeficiency virus (HIV) endemic countries of sub‐Saharan Africa, but there is little research on management and outcomes.