Sickle cell allele HBB-rs334(T) is associated with decreased risk of childhood Burkitt lymphoma in East Africa.

Burkitt lymphoma (BL) is an aggressive B-cell lymphoma that significantly contributes to childhood cancer burden in sub-Saharan Africa. Plasmodium falciparum, which causes malaria, is geographically associated with BL, but the evidence remains insufficient for causal inference. Inference could be strengthened by demonstrating that mendelian genes known to protect against malaria-such as the sickle cell trait variant, HBB-rs334(T)-also protect against BL. We investigated this hypothesis among 800 BL cases and 3845 controls in four East African countries using genome-scan data to detect polymorphisms in 22 genes known to affect malaria risk. We fit generalized linear mixed models to estimate odds ratios (OR) and 95% confidence intervals (95% CI), controlling for age, sex, country, and ancestry. The ORs of the loci with BL and P. falciparum infection among controls were correlated (Spearman's ρ = 0.37, p = .039). HBB-rs334(T) was associated with lower P. falciparum infection risk among controls (OR = 0.752, 95% CI 0.628-0.9; p = .00189) and BL risk (OR = 0.687, 95% CI 0.533-0.885; p = .0037). ABO-rs8176703(T) was associated with decreased risk of BL (OR = 0.591, 95% CI 0.379-0.992; p = .00271), but not of P. falciparum infection. Our results increase support for the etiological correlation between P. falciparum and BL risk.

Local evidence in sub-Saharan Africa; the CANCaRe Africa experience-Lessons learned and shared thoughts about the way forward.

Collaborative research generating local evidence is key to closing the research and survival gap between sub-Saharan Africa and high-income countries. Lessons learned by CANCaRe Africa, the Collaborative African Network for Childhood Cancer Care and Research while pioneering such research are being discussed together with recommendations for the future.

Reflections on 20 years of the Wilms Africa project: Lessons learned and the way forward.

Wilms tumour (WT) is one of the common and curable childhood cancer types included in the Global Initiative for Childhood Cancer (GICC) to monitor progress. Local evidence is key to finding effective and sustainable solutions to local challenges to improve care and survival. Local evidence generated by the Wilms Africa project is summarised with recommendations for the future.

Surgical aspects and outcomes after nephrectomy for Wilms tumour in sub-Saharan Africa: A report from Wilms Africa Phase II-CANCaRe Africa.

BACKGROUND: Wilms tumour (WT) is one of the common and curable cancer types targeted by the Global Initiative for Childhood Cancer. Tumour excision is essential for cure. This analysis focuses on surgical outcomes of patients with WT in sub-Saharan Africa. METHODS: We implemented a risk-stratified WT treatment guideline as a multicentre, prospective study across eight hospitals and six countries. Eligibility criteria were age 6 months to 16 years, unilateral WT, surgery performed after preoperative chemotherapy and diagnosed between 1 January 2021 and 31 December 2022. Data collection included a specific surgical case report form (CRF). RESULTS: The study registered 230 patients, among whom 164 (71.3%) had a nephrectomy. Ninety-eight percent of patients had a completed surgical CRF. Out 164 patients, 50 (30.5%) had distant metastases. Median tumour diameter at surgery was 11.0 cm. Lymph node sampling was done in 122 (74.3%) patients, 34 (20.7%) had intraoperative tumour rupture, and for 18 (10.9%), tumour resection involved en bloc resection of another organ. Tumour size at surgery was significantly correlated with tumour rupture (p < .01). With a median follow-up of 17 months (range: 2-33), 23 (14.0%) patients have relapsed. Twenty-two (13.4%) patients abandoned treatment post nephrectomy. Two-year event-free survival was 60.4% ± 4.7% with treatment abandonment as an event. CONCLUSION: Survival post nephrectomy is challenged by treatment abandonment, treatment-related mortality and relapse. Large tumours after preoperative chemotherapy were associated with a higher risk of tumour rupture. Earlier diagnosis and access to radiotherapy are expected to improve survival.

Prevention of treatment abandonment remains an important challenge to increase survival of Wilms tumor in sub-Saharan Africa: A report from Wilms Africa-CANCaRe Africa.

BACKGROUND: The Wilms Africa studies implemented an adapted Wilm's tumor (WT) treatment protocol in sub-Saharan Africa in two phases. Phase I began with four sites and provided out-of-pocket costs. Phase II expanded the number of sites, but lost funding provision. Objective is to describe the outcomes of Phase II and compare with Phase I. METHODS: Wilms Africa Phase I (n = 4 sites; 2014-2018) and Phase II (n = 8 sites; 2021-2022) used adapted treatment protocols. Funding for families' out-of-pocket costs was provided during Phase I but not Phase II. Eligibility criteria were age less than 16 years and newly diagnosed unilateral WT. We documented patients' outcome at the end of planned first-line treatment categorized as treatment abandonment, death during treatment, and disease-related events (death before treatment, persistent disease, relapse, or progressive disease). Sensitivity analysis compared outcomes in the same four sites. RESULTS: We included 431 patients in Phase I (n = 201) and Phase II (n = 230). The proportion alive without evidence of disease decreased from 69% in Phase I to 54% in Phase II at all sites (p = .002) and 58% at the original four sites (p = .04). Treatment abandonment increased overall from 12% to 26% (p < .001), and was 20% (p = .04) at the original four sites. Disease-related events (5% vs. 6% vs. 6%) and deaths during treatment (14% vs. 14% vs. 17%) were similar. CONCLUSION: Provision of out-of-pocket costs was important to improve patient outcomes at the end of planned first-line treatment in WT. Prevention of treatment abandonment remains an important challenge.

Effectiveness of a Wilms tumour treatment guideline adapted to local circumstances in sub-Saharan Africa: A report from Wilms Africa Phase II-CANCaRe Africa.

BACKGROUND: Wilms tumour (WT) is one of the cancer types targeted by the Global Initiative for Childhood Cancer (GICC). The objective of this study was to describe the outcomes of Wilms Africa Phase II in sub-Saharan Africa. METHODS: Wilms Africa Phase II used a comprehensive WT treatment protocol in a multi-centre, prospective study conducted in eight hospitals in Ethiopia (2), Ghana (2), Malawi, Cameroon, Zimbabwe and Uganda. Eligibility criteria were: age younger than 16 years, unilateral WT, diagnosed between 1 January 2021 and 31 December 2022. RESULTS: We included 230 WT patients, median age 3 years, 53% male. Median maximum tumour diameter at diagnosis was 13.6 cm and 33% of patients had metastatic disease. Nephrectomy was performed in 71% of patients, of whom 21% had a tumour rupture. Two-year event-free survival (EFS) was 41.3% ± 3.9% after a median follow-up of 17 months (range: 1-33 months), with treatment abandonment considered an event. Treatment abandonment occurred in 26% and death during treatment in 14%. Disease relapse occurred in 10%. Two-year EFS of the 26 patients who received radiotherapy was 64.5% ± 9.7% with no reported disease relapse. CONCLUSION: Patients continue to present late with advanced WT in sub-Saharan Africa, and their survival is below the 60% GICC target. Prevention of treatment abandonment and treatment-related mortality remain important. Earlier diagnosis and access to radiotherapy are expected to decrease disease-related mortality.

Transfusion Volume for Children with Severe Anemia in Africa.

BACKGROUND: Severe anemia (hemoglobin level, <6 g per deciliter) is a leading cause of hospital admission and death in children in sub-Saharan Africa. The World Health Organization recommends transfusion of 20 ml of whole-blood equivalent per kilogram of body weight for anemia, regardless of hemoglobin level. METHODS: In this factorial, open-label trial, we randomly assigned Ugandan and Malawian children 2 months to 12 years of age with a hemoglobin level of less than 6 g per deciliter and severity features (e.g., respiratory distress or reduced consciousness) to receive immediate blood transfusion with 20 ml per kilogram or 30 ml per kilogram. Three other randomized analyses investigated immediate as compared with no immediate transfusion, the administration of postdischarge micronutrients, and postdischarge prophylaxis with trimethoprim-sulfamethoxazole. The primary outcome was 28-day mortality. RESULTS: A total of 3196 eligible children (median age, 37 months; 2050 [64.1%] with malaria) were assigned to receive a transfusion of 30 ml per kilogram (1598 children) or 20 ml per kilogram (1598 children) and were followed for 180 days. A total of 1592 children (99.6%) in the higher-volume group and 1596 (99.9%) in the lower-volume group started transfusion (median, 1.2 hours after randomization). The mean (±SD) volume of total blood transfused per child was 475±385 ml and 353±348 ml, respectively; 197 children (12.3%) and 300 children (18.8%) in the respective groups received additional transfusions. Overall, 55 children (3.4%) in the higher-volume group and 72 (4.5%) in the lower-volume group died before 28 days (hazard ratio, 0.76; 95% confidence interval [CI], 0.54 to 1.08; P = 0.12 by log-rank test). This finding masked significant heterogeneity in 28-day mortality according to the presence or absence of fever (>37.5°C) at screening (P=0.001 after Sidak correction). Among the 1943 children (60.8%) without fever, mortality was lower with a transfusion volume of 30 ml per kilogram than with a volume of 20 ml per kilogram (hazard ratio, 0.43; 95% CI, 0.27 to 0.69). Among the 1253 children (39.2%) with fever, mortality was higher with 30 ml per kilogram than with 20 ml per kilogram (hazard ratio, 1.91; 95% CI, 1.04 to 3.49). There was no evidence of differences between the randomized groups in readmissions, serious adverse events, or hemoglobin recovery at 180 days. CONCLUSIONS: Overall mortality did not differ between the two transfusion strategies. (Funded by the Medical Research Council and Department for International Development, United Kingdom; TRACT Current Controlled Trials number, ISRCTN84086586.).

Immediate Transfusion in African Children with Uncomplicated Severe Anemia.

BACKGROUND: The World Health Organization recommends not performing transfusions in African children hospitalized for uncomplicated severe anemia (hemoglobin level of 4 to 6 g per deciliter and no signs of clinical severity). However, high mortality and readmission rates suggest that less restrictive transfusion strategies might improve outcomes. METHODS: In this factorial, open-label, randomized, controlled trial, we assigned Ugandan and Malawian children 2 months to 12 years of age with uncomplicated severe anemia to immediate transfusion with 20 ml or 30 ml of whole-blood equivalent per kilogram of body weight, as determined in a second simultaneous randomization, or no immediate transfusion (control group), in which transfusion with 20 ml of whole-blood equivalent per kilogram was triggered by new signs of clinical severity or a drop in hemoglobin to below 4 g per deciliter. The primary outcome was 28-day mortality. Three other randomizations investigated transfusion volume, postdischarge supplementation with micronutrients, and postdischarge prophylaxis with trimethoprim-sulfamethoxazole. RESULTS: A total of 1565 children (median age, 26 months) underwent randomization, with 778 assigned to the immediate-transfusion group and 787 to the control group; 984 children (62.9%) had malaria. The children were followed for 180 days, and 71 (4.5%) were lost to follow-up. During the primary hospitalization, transfusion was performed in all the children in the immediate-transfusion group and in 386 (49.0%) in the control group (median time to transfusion, 1.3 hours vs. 24.9 hours after randomization). The mean (±SD) total blood volume transfused per child was 314±228 ml in the immediate-transfusion group and 142±224 ml in the control group. Death had occurred by 28 days in 7 children (0.9%) in the immediate-transfusion group and in 13 (1.7%) in the control group (hazard ratio, 0.54; 95% confidence interval [CI], 0.22 to 1.36; P = 0.19) and by 180 days in 35 (4.5%) and 47 (6.0%), respectively (hazard ratio, 0.75; 95% CI, 0.48 to 1.15), without evidence of interaction with other randomizations (P>0.20) or evidence of between-group differences in readmissions, serious adverse events, or hemoglobin recovery at 180 days. The mean length of hospital stay was 0.9 days longer in the control group. CONCLUSIONS: There was no evidence of differences in clinical outcomes over 6 months between the children who received immediate transfusion and those who did not. The triggered-transfusion strategy in the control group resulted in lower blood use; however, the length of hospital stay was longer, and this strategy required clinical and hemoglobin monitoring. (Funded by the Medical Research Council and Department for International Development; TRACT Current Controlled Trials number, ISRCTN84086586.).

Towards zero percent treatment abandonment of patients with common and curable childhood cancer types in Blantyre, Malawi.

BACKGROUND: Treatment abandonment is a common cause of treatment failure in low-income countries (LIC). We implemented a comprehensive package of interventions aiming to enable all families to complete the treatment of their child. The objective of this study was to evaluate the impact of those interventions. PROCEDURE: In this prospective and historically controlled study, we included all children younger than 16 years with a newly diagnosed common and curable cancer type (acute lymphoblastic leukaemia [ALL], Hodgkin disease, Wilms tumour, retinoblastoma and Burkitt lymphoma) admitted to the Queen Elizabeth Central Hospital in Blantyre, Malawi, between 1 June 1 2019 and 1 June 1 2020. Interventions to enable treatment completion included full funding of costs to the family (treatment, transport, accommodation and food in the hospital) and tracking of patients if they did not attend treatment appointments. The outcomes of patients were compared with those of a similar historical cohort. RESULTS: The intervention cohort of 150 patients were compared to 264 historical control patients. Treatment abandonment decreased significantly from 19% (49/264) to 7% (10/150) (p < .001). The proportion of patients with Wilms tumour, retinoblastoma or ALL alive without evidence of disease at the end of treatment increased from 38% (57/149) to 53% (44/83) (p = .03). CONCLUSION: A simple and relatively low-cost comprehensive intervention package with no costs for families, significantly decreased treatment abandonment. This strategy may increase survival of children with common and curable cancers in LIC, especially when coupled with improvements in access to treatment and quality of treatment, including supportive care.

Early doxorubicin cardiotoxicity in Malawian children admitted to Queen Elizabeth Central Hospital, Malawi.

BACKGROUND: Doxorubicin is known to cause chemotherapy-induced cardiotoxicity. In resource-poor settings, monitoring for cardiotoxicity is not routinely done, and its incidence is unknown. The aim of this study was to determine the proportion of children who developed doxorubicin-induced cardiotoxicity within 1 year of having received treatment at paediatric oncology ward. METHODS: Children aged 3 months to 18 years with cancer were prospectively enrolled and followed up between January 2016 to June 2019. Transthoracic echocardiogram was done at baseline, 1 month, 6 months and a year after completion of therapy. Cardiotoxicity was defined as a decline in left ventricular ejection fraction (LVEF) of ≥10% to a final value of <50%. An overall incidence risk of developing cardiotoxicity was estimated. A one-way analysis of variance (ANOVA) was conducted to compare baseline LVEF with follow-up measurements. FINDINGS: Ninety-one children were enrolled, 74% (68/91) were male, and 67% (62/91) were aged 5 months to 14 years. Most patients received a doxorubicin cumulative dose between 100 and 200 mg/m2 and no cardiotoxicity was observed during the study period. However, of 77 children with at least one follow up, five children 6.54% (95% CI: 2.1-14.5) experienced LVEF reduction of >10%, though not to a final value of <50%. No deterioration of systolic function was found among 20 children who completed follow-up (F = 2.43, p-value = .07). INTERPRETATION: In this cohort of patients, most received a low cumulative doxorubicin dose and only 22% were available for evaluation at study end; no cardiotoxic events associated with doxorubicin administration were observed after 12 months.

Fever and neutropenia outcomes and areas for intervention: A report from SUCCOUR - Supportive Care for Children with Cancer in Africa.

BACKGROUND: Death during paediatric cancer treatment is common in sub-Saharan Africa. Using the infrastructure of Supportive Care for Children with Cancer in Africa (SUCCOUR), our objective was to describe fever and neutropenia (FN) characteristics and outcomes in order to identify potential areas for future intervention. METHODS: A multicentre prospective, observational cohort study was conducted in sub-Saharan Africa. Data were collected from September 2019 to March 2020. Children below 16 years with newly diagnosed cancer treated with curative intent were included. Data were abstracted in real time using standardised case report forms by trained personnel. Characteristics and outcomes of FN during the first 3 months of treatment were documented. RESULTS: A total of 252 patients were included (median age 6.0, range 0.2-15.0 years, 54% male). The most common cancer was Burkitt lymphoma (63/252, 25%). Among 104 FN episodes, 21 (21%) were associated with prolonged neutropenia (>1 week) and 32 (31%) were associated with profound neutropenia (absolute neutrophil count <0.1 × 109 /L). In 10/104 (10%) episodes, empiric antibiotics were started within 1 hour following fever onset and in 16/104 (15%) episodes, a blood culture was obtained before starting antibiotics. Malaria parasitaemia was detected in four of 104 (4%). A total of 11/104 (11%) patients died in the FN episodes. CONCLUSIONS: Although in most, FN was not associated with prolonged or profound neutropenia, 11% resulted in death. Areas to target include blood cultures prior to antibiotics and earlier initiation of empiric antibiotics. Future efforts should modify FN practices to reduce treatment-related mortality.

Early death and treatment-related mortality: A report from SUCCOUR - Supportive Care for Children with Cancer in Africa.

BACKGROUND: Deaths during paediatric cancer treatment are common in Africa. It is often difficult to distinguish between treatment-related and disease-related causes. To prevent these deaths, it is important to study them and identify the cause. The Supportive Care for Children with Cancer in Africa (SUCCOUR) programme enabled a study with the objective to identify the reasons for early death during treatment. METHODS: We conducted a multicentre prospective, observational cohort study in sub-Saharan Africa. Children younger than 16 years with newly diagnosed cancer treated with curative intent were included from 1 September 2019 until 30 March 2020. Data were abstracted in real time by trained personnel using standardised case report forms. The treating clinician's assessment of the cause of death and signs, symptoms and laboratory values of patients who died during the first 3 months of treatment (early death) were documented. RESULTS: We included 252 patients (median age 6.0, range 0.2-15.0 years, 54% male). The most common cancer was Burkitt lymphoma (63/252, 25%). Fifteen percent of patients (37/252) died during the first 3 months of treatment. Of these 37 patients, 33 (89%) died of a treatment-related cause. Treatment-related mortality of all patients in the first 3 months of treatment was 13% (33/252). CONCLUSION: Fifteen percent of patients had an early death during treatment and 13% had a treatment-related death. This suggests the need to improve supportive care. Implementation of supportive care pathways adapted to local circumstances may be helpful.

Treatment abandonment: A report from the collaborative African network for childhood cancer care and research-CANCaRe Africa.

BACKGROUND: 'Treatmentabandonment' is a common and preventable cause of childhood cancer treatment failure in low- and middle-income countries (LMIC). Risk factors and effective interventions in LMIC are reported. Poverty and costs of treatment are perceived as overriding causes in sub-Saharan Africa. The objective of this study was to study potential determinants of treatment abandonment, including aspects of treatment costs in sub-Saharan Africa, to be better informed for planned future interventions. METHODS: A multicentre, prospective, observational, cohort study was conducted in five hospitals in sub-Saharan Africa. Children younger than 16 years with newly diagnosed cancer treated as inpatient with curative intent were included. The occurrence of treatment abandonment and potential determinants including aspects of treatment costs were documented during the first 3 months of treatment. RESULTS: We included 252 patients (median age 6.0, range 0.2-15.0 years, 54% male). The most common cancer was Burkitt lymphoma (63/252, 25%). Seven percent of patients (18 of 252) abandoned treatment. Two thirds (65%, 163/252) of patients had to borrow money to reach the hospital for the diagnosis and start of treatment. Treatment abandonment occurred more frequently in families who had to borrow money (16/163, 10%) versus those who did not (2/89, 2%; p = .026). CONCLUSIONS: Limiting costs for families and improved counselling may reduce treatment abandonment. Development and implementation of interventions to reduce treatment abandonment are required in sub-Saharan Africa.

Incidence and predictors of hospital readmission in children presenting with severe anaemia in Uganda and Malawi: a secondary analysis of TRACT trial data.

BACKGROUND: Severe anaemia (haemoglobin < 6 g/dL) is a leading cause of recurrent hospitalisation in African children. We investigated predictors of readmission in children hospitalised with severe anaemia in the TRACT trial (ISRCTN84086586) in order to identify potential future interventions. METHODS: Secondary analyses of the trial examined 3894 children from Uganda and Malawi surviving a hospital episode of severe anaemia. Predictors of all-cause readmission within 180 days of discharge were identified using multivariable regression with death as a competing risk. Groups of children with similar characteristics were identified using hierarchical clustering. RESULTS: Of the 3894 survivors 682 (18%) were readmitted; 403 (10%) had ≥2 re-admissions over 180 days. Three main causes of readmission were identified: severe anaemia (n = 456), malaria (n = 252) and haemoglobinuria/dark urine syndrome (n = 165). Overall, factors increasing risk of readmission included HIV-infection (hazard ratio 2.48 (95% CI 1.63-3.78), p < 0.001); ≥2 hospital admissions in the preceding 12 months (1.44(1.19-1.74), p < 0.001); history of transfusion (1.48(1.13-1.93), p = 0.005); and missing ≥1 trial medication dose (proxy for care quality) (1.43 (1.21-1.69), p < 0.001). Children with uncomplicated severe anaemia (Hb 4-6 g/dL and no severity features), who never received a transfusion (per trial protocol) during the initial admission had a substantially lower risk of readmission (0.67(0.47-0.96), p = 0.04). Malaria (among children with no prior history of transfusion) (0.60(0.47-0.76), p < 0.001); younger-age (1.07 (1.03-1.10) per 1 year younger, p < 0.001) and known sickle cell disease (0.62(0.46-0.82), p = 0.001) also decreased risk of readmission. For anaemia re-admissions, gross splenomegaly and enlarged spleen increased risk by 1.73(1.23-2.44) and 1.46(1.18-1.82) respectively compared to no splenomegaly. Clustering identified four groups of children with readmission rates from 14 to 20%. The cluster with the highest readmission rate was characterised by very low haemoglobin (mean 3.6 g/dL). Sickle Cell Disease (SCD) predominated in two clusters associated with chronic repeated admissions or severe, acute presentations in largely undiagnosed SCD. The final cluster had high rates of malaria (78%), severity signs and very low platelet count, consistent with acute severe malaria. CONCLUSIONS: Younger age, HIV infection and history of previous hospital admissions predicted increased risk of readmission. However, no obvious clinical factors for intervention were identified. As missing medication doses was highly predictive, attention to care related factors may be important. TRIAL REGISTRATION: ISRCTN ISRCTN84086586 .

Outcome at the end of treatment of patients with common and curable childhood cancer types in Blantyre, Malawi.

BACKGROUND: The WHO Global Initiative for Childhood Cancer aims to increase survival to at least 60% for all children with cancer globally, with initial focus on six common curable cancer types. Frequent causes of treatment failure in low income countries (LICs) are treatment abandonment and death during treatment. Here, we report on the outcome at the end of treatment of patients with newly diagnosed common and curable cancer types, admitted in the Queen Elizabeth Central Hospital, Blantyre, Malawi. PROCEDURE: Outcome at end of treatment was documented and analyzed retrospectively for all children with a working diagnosis of a common and curable cancer type (ALL, Hodgkin disease, Wilms tumor, retinoblastoma, and Burkitt lymphoma) admitted over a 2-year period. Patients with a misdiagnosis were excluded. Outcomes were categorized as alive without evidence of disease, treatment abandonment, death during treatment, or persistent disease. RESULTS: We included 264 patients. Seven patients with a misdiagnosis were excluded. At the end of treatment, 53% (139 of 264) of patients were alive without evidence of disease, 19% (49 of 264) had abandoned treatment, 23% (61 of 264) had died during treatment, and 6% (15 of 264) had persistent disease. CONCLUSION: Survival of children with common and curable cancers is (significantly) below 50%. Almost half (42%) of the patients either abandoned treatment or died during treatment. Strategies to enable parents to complete treatment of their child and improved supportive care are needed. Such interventions may need to be given priority to improve the currently poor survival.

Improvement of overall survival in the Collaborative Wilms Tumour Africa Project.

INTRODUCTION: The Collaborative Wilms Tumour (WT) Africa Project implemented an adapted WT treatment guideline in six centres in sub-Saharan Africa. The primary objectives were to describe abandonment of treatment, death during treatment, event-free survival (EFS) and relapse following implementation. An exploratory objective was to compare outcomes with the baseline evaluation, a historical cohort preceding implementation. METHODS: The Collaborative WT Africa Project is a multi-centre prospective clinical trial that began in 2014. Funding was distributed to all participating centres and used to cover treatment, travel and other associated costs for patients. Patient characteristics, tumour characteristics and events were described. RESULTS: In total, 201 WT patients were included. Two-year EFS was 49.9 ± 3.8% when abandonment of treatment was considered an event. Relapse of disease occurred in 21% (42 of 201) of all included patients and in 26% (42 of 161) of those who had a nephrectomy. Programme implementation was associated with significantly higher survival without evidence of disease at the end of treatment (52% vs 68.5%, P = .002), significantly reduced abandonment of treatment (23% vs 12%, P = .009) and fewer deaths during treatment (21% vs 13%, P = .06). CONCLUSION: This collaborative implementation of an adapted WT treatment guideline, using relatively simple and low-cost interventions, was feasible. Two-year EFS was almost 50%. In addition, a significant decrease in treatment abandonment and an increase in survival at the end of treatment were observed compared to a pre-implementation cohort. Future work should focus on decreasing deaths during treatment and will include enhancing supportive care.

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

BACKGROUND: 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. METHODS: Children with KS at Queen Elizabeth Central Hospital, Blantyre, Malawi treated between August 2012 and March 2015 with six courses of vincristine, bleomycin and etoposide combination chemotherapy, including antiretroviral therapy (ART) if HIV infected, were studied and outcomes compared with previously reported results. FINDINGS: Fifty-six children were included; 38 (68%) were male; and 48 (86%) were HIV positive, of whom 36 (77%) were on ART at diagnosis. Median age at diagnosis was 8 years (interquartile range [IQR] 3-12) and median follow-up was 16.9 months (IQR 3.4-36.4). Quality of life improved in 45 (80%) children; the median Lansky Score increased from 80% pre-treatment to 100% post-treatment. Eighteen (32%) children had complete response to treatment. At 12 months, overall survival was 71% (95% confidence interval [CI] 56-82) and event-free survival (event = death, loss to follow-up or relapse) was 50% (95% CI 36-63). At 1 year, the risk of loss to follow-up was 13.4%. In a previous, same-site, randomized controlled study of vincristine monotherapy, vincristine and bleomycin, or oral etoposide, oral etoposide monotherapy had the best outcome with survival at 12 month of 66% (95% CI 46-80) and event-free survival of 52% (95% CI 33-68); however, loss to follow-up was not reported. CONCLUSION: Overall survival, event-free survival and quality of life appear to have improved with this three-agent combination chemotherapy; however larger, randomized studies are needed to determine optimal management.

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

BACKGROUND: 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. PROCEDURE: All participating centres obtained local Institutional Research Board (IRB) approval and implemented the adapted WT treatment guideline. End-of-treatment outcome was documented for 2 years. It was divided into alive without evidence of disease, treatment abandonment, death during treatment and persistent disease. The outcome of children enroled in the first 2 years of the prospective clinical trial has been compared to the outcome before the start of the project. RESULTS: One hundred twenty-two patients were included in the baseline evaluation (2011-2012) and 133 in the first 2 years of the collaborative clinical trial (2014-2015). The percentage of patients alive without evidence of disease at the end of treatment increased from 52% (63/122) to 68% (90/133; P = 0.01). Treatment abandonment decreased from 23% (28/122) to 13% (17/133; P = 0.03). Death during treatment decreased from 21% (26/122) to 13% (17/133; P = 0.07). CONCLUSION: This collaboration, using relatively simple and low-cost interventions, led to a significant decrease in treatment abandonment and increase in survival without evidence of disease at the end of treatment.