Marc Hendricks

SIOP PODC: Recommendations for supportive care of children with cancer in a low-income setting†

These supportive care recommendations were prepared to guide doctors who practice in areas with significantly limited resources but who have sufficient infrastructure and training to treat children with cancer with curative intent. The success of any cancer treatment regimen depends largely on the availability and quality of supportive care and this also determines the intensity of treatment that can be delivered. We present practical recommendations on how to prevent infections, general nursing care, management of febrile neutropenia, nutritional assessment and support, treatment of co‐infections and the social support to help prevent failure to complete treatment in resource poor settings. Pediatr Blood Cancer 2013; 60: 899–904.

Malignancies in South African children with HIV.

Objectives: In 2008 the South African Children’s Cancer Study Group decided to review the epidemiology, management, and chemotherapy response of HIV-positive children with malignancy. Methods: This is a retrospective analysis of data collected from the records of HIV-positive children diagnosed with malignancy at 7 university-based pediatric oncology units serving 8 of the 9 provinces in South Africa. Results: Two hundred eighty-eight HIV-positive children were diagnosed with 289 malignancies between 1995 and 2009. Age at diagnosis ranged from 17 days to 18.64 years; median 5.79 years. Of the 220 HIV-associated malignancies, there were 97 Kaposi sarcomas, 61 Burkitt lymphomas, 47 other B-cell lymphomas including 2 primary central nervous system lymphomas, 12 Hodgkin lymphomas, and 3 leiomyosarcomas. Sixty-nine patients presented with non–AIDS-defining malignancies. More than 80% presented with advanced disease. Most patients (76.7%) were naive to antiretroviral therapy; 22.2% did not have access because it only became available in public hospitals in 2004. One hundred ninety-seven children were treated with curative intent; 91 received palliative care due to advanced malignancy and/or advanced HIV disease. Nearly one third had coexisting pathology, mostly tuberculosis. Overall survival for the whole group was 33.7%, but was 57.8% for those treated with antiretroviral therapy and chemotherapy. Conclusions: The study shows more Kaposi sarcoma and fewer primary central nervous system lymphomas among HIV-positive children than that is reported in the developed world, but confirms a higher incidence of non-Burkitt B-cell lymphoma than in HIV-negative children. The high number of non–AIDS-defining malignancies underscores the prevalence of HIV-AIDS in South Africa. The overall survival should improve with universal access to antiretrovirals and earlier diagnosis.

Childhood cancer in Africa

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.

SIOP PODC adapted treatment recommendations for standard-risk medulloblastoma in low and middle income settings

Effective treatment of children with medulloblastoma requires a functioning multi‐disciplinary team with adequate neurosurgical, neuroradiological, pathological, radiotherapy and chemotherapy facilities and personnel. In addition the treating centre should have the capacity to effectively screen and manage any tumour and treatment‐associated complications. These requirements have made it difficult for many low and middle‐income countries (LMIC) centres to offer curative treatment. This article provides management recommendations for children with standard‐risk medulloblastoma (localised tumours in children over the age of 3–5 years) according to the level of facilities available. Pediatr Blood Cancer 2015;62:553–564.

Serum ferritin is a cost-effective laboratory marker for hemophagocytic lymphohistiocytosis in the developing world.

Hemophagocytic lymphohistiocytosis (HLH) is a rare disease in children and presents many diagnostic difficulties. Without prompt intervention, the disease typically runs a rapidly fatal course. Diagnostic criteria were proposed by the Histiocyte Society in 1991 and have since been modified. Included in these criteria is a ferritin level >500 mcg/L2. Although not diagnostic, a high ferritin level is highly suggestive of HLH. Serum ferritin assays are more accessible and cost-effective compared with other biochemical markers, particularly in resource-limited settings. Fifteen patients with HLH were treated at Red Cross War Memorial Children’s Hospital between 1991 and 2010. Hyperferritinemia was a consistently reliable finding (93%) compared with either serum fibrinogen or triglycerides, which were elevated in only half of the patients. It is our contention that analysis of a complete blood count and serum ferritin (in addition to clinical criteria and tissue examination of marrow and/or cerebrospinal fluid) is probably the single most cost-effective and clinically helpful means to make the diagnosis of HLH when laboratory access is limited.

Kawasaki disease preceding haemophagocytic lymphohistiocytosis: Challenges for developing world practitioners

Kawasaki disease (KD) is a recognised precipitant of haemophagocytic lymphohistiocytosis (HLH). Although KD has been previously described in the developing world, there are no reported cases of KD preceding HLH. We report a case of a child with a persistent rash and unremitting fever consistent with the diagnosis of KD, who was found to have HLH, after intravenous gamma globulin failed to produce a clinical response. The diagnosis was made using the revised diagnostic criteria for HLH from the Histiocyte Society (1994). She fulfilled six of the eight clinical and laboratory criteria needed to make the diagnosis. Pediatr Blood Cancer 2010;54:1023–1025

The evolving management of Burkitt's lymphoma at Red Cross Children's Hospital

BACKGROUND Treatment for Burkitts lymphoma at Red Cross Childrens Hospital has evolved from the use of aggressive surgery and less intensive chemotherapy to a conservative surgical approach with more intensive chemotherapy. METHODS The study was a retrospective folder review of patients diagnosed with Burkitts lymphoma at RCCH between 1984 and 2004. RESULTS Ninety-two children were treated for Burkitts lymphoma at RCCH between 1984 and 2004. There were 10 patients with group A or fully resected disease, 52 with group B or extensive localised disease, and 30 with dissemination to the bone marrow and/or central nervous system or group C disease. Protocol 1 (less intensive chemotherapy based on the COMP regimen) was used from 1984, with protocol 2 (more intensive chemotherapy based on the LMB regimen) introduced in 1988 for group C disease, 1991 for group B disease and 1996 for group A disease. Overall 5-year survival increased from 20% with protocol 1 to 66% with protocol 2 for group C disease, and from 76.5% with protocol 1 to 88.2% with protocol 2 for group B disease. There were more admissions for neutropenic fever in patients on protocol 2 and more episodes of mucositis, and these patients required more red cell and platelet transfusions. With a more conservative surgical approach, biopsy largely replaced attempts to partially resect the tumour at primary surgery, and there was a consequent decline in surgical complications. CONCLUSIONS Intensive chemotherapy with protocol 2 has resulted in improved survival for group C and group B patients, but with more morbidity. Protocol 1, which is less intensive with less morbidity, remains a viable strategy for group A and group B disease in resource-poor settings.

Chest radiographic pulmonary changes reflecting extrapulmonary involvement in paediatric HIV disease

Respiratory infections are the commonest cause of pulmonary change on chest radiographs of HIV-infected children. However, HIV-related neurological, oropharyngeal, oesophageal, cardiac and haematological abnormalities may also manifest with pulmonary changes and must be considered in the interpretation of the chest radiograph in HIV-infected children.

Experience with B-cell lymphoma at a South African centre in the HIV Era

BACKGROUND In South Africa most cases of Burkitt lymphoma (BL) are sporadic, and constituted the majority of paediatric B-cell lymphomas (BCL) prior to the HIV epidemic. The purpose of the study was to review the results for HIV-negative children with BCL, to assess the effect of HIV-AIDS and to determine the optimum treatment for HIV-positive children. METHODS The study was a retrospective folder review of patients with BCL at Red Cross Childrens Hospital between 1991 and 2011. RESULTS One hundred and fourteen patients with BCL were diagnosed; 98 with BL, 14 with Diffuse Large B-cell lymphoma (DLBCL) and two with other forms of BCL. The proportion of DLBCL was 6.5% among HIV-negative and 36.4% among HIV-positive patients. Ninety-one HIV-negative patients were treated with LMB-based regimens. Event free survival (EFS) was 79%, with EFS for Groups A, B and C of 100%, 82.5% and 67.5%. Twenty-two HIV-positive patients were diagnosed since 2003, increasing the average number of cases from 4.3 per year to 6.9 per year. All had access to anti-retrovirals and 15 were treated with curative intent. EFS for the whole group was 58.4%. Since 2009 we have used LMB-based regimens achieving complete remission in six patients without excessive toxicity. CONCLUSION Results for HIV-negative patients are acceptable, but there is a need to improve outcomes for patients with combined bone marrow and CNS disease. HIV-AIDS has increased the number of BCLs with a higher proportion of DLBCL, and portends a poorer prognosis. Early evidence suggests we can achieve comparable outcomes without excessive toxicity by employing LMB-based regimens.

Emergence of vancomycin-resistant Enterococcus at a tertiary paediatric hospital in South Africa

BACKGROUND During 2013, the haematology/oncology unit at a tertiary level paediatric hospital in South Africa experienced the emergence of infection with vancomycin-resistant Enterococcus (VRE). OBJECTIVE To describe the clinical and molecular aspects of the cases identified. METHODS VRE isolates identified from blood culture specimens processed at the National Health Laboratory Service were screened for the presence of the vancomycin resistance genes vanA, B and C1, 2 and 3. Further characterisation of these isolates was carried out using pulsed-field gel electrophoresis (PGFE) and multilocus sequence typing (MLST). Clinical records of infected patients were reviewed to identify possible risk factors, while surveillance with rectal swabs was performed to identify VRE-colonised patients. RESULTS Four patients with haematological malignancies were identified with VRE bloodstream infections. Patients were immunocompromised at the time of the bloodstream infection (BSI), with receipt of vancomycin prior to VRE-BSI, and infections were treated with linezolid. Colonisation with VRE was found in 8 of 55 patients screened. Infected and colonised patients were isolated in the unit during their admission and strict contact precaution infection control practices were instituted. The vanA gene was identified in all of the isolates but one. PFGE and MLST results showed a degree of genetic relatedness between certain isolates obtained from rectal swab and blood culture samples, suggesting possible patient-to-patient transmission or persistence of the isolates in the unit. CONCLUSION Strict infection control practices are necessary to prevent infection and transmission of resistant organisms among vulnerable patients.