SACCSG HL-2018. Barriers and enablers of a harmonized treatment protocol for childhood and adolescent Hodgkin lymphoma in South Africa.

Introduction: Collaborative studies have contributed to improved survival of pediatric Hodgkin lymphoma in well-resourced settings, but few are documented in resource-constrained countries. The South Africa Children's Cancer Study Group initiated harmonization of management protocols in 2015. This article analyzes barriers and enablers of the process. Methods: Clinician-researchers at 11 state-funded pediatric oncology units completed preparatory questionnaires in June 2018. Parameters included infrastructure, access to therapeutic modalities and clinician numbers. A reassessment of 13 sites (two new pediatric oncology unit) in February 2021 ascertained changes in resources and identified challenges to full participation. Questions investigated the presence and quality of diagnostic radiology, availability of surgeons, cytology/pathology options and hematology laboratory facilities. Results: The response rate was 11/11 to survey 1 and 13/13 to survey 2. The anticipated pre-study barriers to participation of pediatric oncology units included time constraints and understaffing. PET-CT was unavailable to two centers. The majority of pediatric oncology units met the minimum criteria to participate. The interim survey confirmed chemotherapy and radiotherapy availability nearly 100% of the time. One site reported improved access to radiotherapy while another reported improved access to PET-CT. Barriers to participation included excessive times to obtain regulatory approvals, time constraints and lack of dedicated research staff. Enablers include the simple management algorithm and communication tools. Conclusion: This study demonstrates that multicenter collaboration and harmonization of management protocols are achievable in a middle-income setting. Minimal funding is required but full participation to run high-quality studies requires more financial investment. Focused funding and increased prioritization of research may address systemic barriers to full participation.

Childhood aplastic anaemia with paroxysmal nocturnal haemoglobinuria clones: A retrospective single-centre study in South Africa.

Background: Paroxysmal nocturnal haemoglobinuria (PNH) clones in children are rare but commonly associated with aplastic anaemia (AA) and myelodysplasia. Objective: This study aimed to determine the prevalence of PNH clones in paediatric patients with idiopathic AA, identify differences in clinical and laboratory features and outcomes, and determine the impact of clone size on clinical presentation. Methods: Patients with confirmed idiopathic AA who were tested for PNH between September 2013 and January 2018 at the Inkosi Albert Luthuli Central Hospital, Durban, KwaZulu-Natal, South Africa, were included. PNH clones were detected in neutrophils and monocytes by flow cytometry using fluorescent aerolysin, CD24, CD66b and CD14. Results: Twenty-nine children with AA were identified and 11 were excluded. Ten patients (10/18, 55.6%) had PNH clones ranging from 0.11% to 24%. Compared to the PNH-negative group, these children were older (median: 10 years vs 4 years, p = 0.02) and had significantly lower total white cell counts (median 1.7 × 109/L vs 3.2 × 109/L; p = 0.04). There was no difference in median absolute neutrophil count or haemoglobin concentration. Four patients in each group received immunosuppressive therapy (IST). At six months, all four patients with PNH clones had responded, compared to one in the PNH-negative group. Conclusion: More than half of children with AA had a PNH clone. The size of the clone did not impact clinical severity; however, IST use may positively impact prognosis. We recommend early initiation of IST in patients with AA to avoid delays associated with human leukocyte antigen typing.

Childhood aplastic anaemia with paroxysmal nocturnal haemoglobinuria clones: A retrospective single-centre study in South Africa

Background: Paroxysmal nocturnal haemoglobinuria (PNH) clones in children are rare but commonly associated with aplastic anaemia (AA) and myelodysplasia.Objective: This study aimed to determine the prevalence of PNH clones in paediatric patients with idiopathic AA, identify differences in clinical and laboratory features and outcomes, and determine the impact of clone size on clinical presentation.Methods: Patients with confirmed idiopathic AA who were tested for PNH between September 2013 and January 2018 at the Inkosi Albert Luthuli Central Hospital, Durban, KwaZulu-Natal, South Africa, were included. PNH clones were detected in neutrophils and monocytes by flow cytometry using fluorescent aerolysin, CD24, CD66b and CD14. Results: Twenty-nine children with AA were identified and 11 were excluded. Ten patients (10/18, 55.6%) had PNH clones ranging from 0.11% to 24%. Compared to the PNH-negative group, these children were older (median: 10 years vs 4 years, p= 0.02) and had significantly lower total white cell counts (median 1.7 × 109/L vs 3.2 × 109/L; p= 0.04). There was no difference in median absolute neutrophil count or haemoglobin concentration. Four patients in each group received immunosuppressive therapy (IST). At six months, all four patients with PNH clones had responded, compared to one in the PNH-negative group. Conclusion: More than half of children with AA had a PNH clone. The size of the clone did not impact clinical severity; however, IST use may positively impact prognosis. We recommend early initiation of IST in patients with AA to avoid delays associated with human leukocyte antigen typing.

Prognostic factors affecting survival in children and adolescents with HIV and Hodgkin lymphoma in South Africa.

South African children with Hodgkin lymphoma (HL) and human immunodeficiency virus (HIV) have low 5-year overall survival (OS) rates. In this retrospective multicenter study, 271 South African pediatric patients with HL were studied to determine OS and prognostic factors in those with HIV and HL. Univariate risk factor analysis was performed to analyze prognostic factors. The 29 HIV-infected patients were younger (p = .021), more likely to present with wasting (0.0573), stunting (0.0332), and Stage IV disease (p = .000) than HIV-uninfected patients. The 5- and 10-year OS of HIV-infected patients of 49% and 45% versus 84% and 79%, respectively for HIV-uninfected patients (p = .0001) appeared to be associated with hypoalbuminemia (<20 g/dL) and CD4 percentage of <15%. Causes of death in the HIV-infected group included disease progression (6/14), infection (4/14), unknown (3/14), and second malignancy (1/14). HIV-infected pediatric patients with HL experience increased mortality due to post-therapy opportunistic and nosocomial infections.

Treatment outcomes of children with Hodgkin lymphoma between 2000 and 2010: First report by the South African Children's Cancer Study Group.

BACKGROUND: Children with Hodgkin lymphoma (HL) have excellent survival rates in high-income countries, but there are minimal outcome data in South African patients. Differing approaches to treatment are used in centres across South Africa, and the South African Children's Cancer Study Group (SACCSG) embarked on a programme to audit outcomes to improve survival rates. PATIENTS AND METHODS: A multicentre study was conducted to analyse outcomes and prognostic factors of children with HL in South Africa. Ten dedicated South African paediatric oncology units participated in a retrospective data review. All patients with HL treated consecutively between January 2000 and December 2010 were included. Kaplan-Meier curves and Cox regression model were employed to determine survival rates and prognostic factors. RESULTS: Two hundred and ninety-four patients were eligible for inclusion. The median age at presentation was 9.6 years (range 2.9-18.8); 55.4% of the patients presented with Stage III and IV disease and 9.9% were human immunodeficiency virus (HIV) positive. First-line therapy consisted of adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) in 158 patients, vincristine, procarbazine/etoposide, prednisone and doxorubicin in 97 and adriamycin, bleomycin, vincristine and dacarbazine-chlorambucil, vinblastine, prednisone and procarbazine in 23 patients. The 5-year overall survival (OS) was 79% (95% confidence interval 73-84%). Multivariate analysis demonstrated that HIV infection (P = 0.018) and Ann Arbor Stage III and IV disease (P = 0.006) conferred a poor prognosis, while treatment with ABVD was associated with higher survival rates (P = 0.028). CONCLUSION: OS rates are encouraging for a middle-income country, although economic disparities continue to impact negatively on outcomes. Study results will form the basis for the development of national protocol and continued advocacy to rectify disparities.

A review of the use of blood and blood products in HIV-infected patients.

Despite numerous publications on the appropriate use of blood and blood products, few specifically consider the role of transfusion in the management of HIV. This review is a synthesis of conditions encountered in the management of HIV-infected patients where the transfusion of blood or blood products may be indicated. A consistent message emerging from the review is that the principles of transfusion medicine do not differ between HIV-negative and -positive patients. The aim of the review is to provide clinicians with a practical and succinct overview of the haematological abnormalities and clinical circumstances most commonly encountered in the HIV setting, while focusing on the rational and appropriate use of blood and blood products for HIV patients. Important ethical considerations in dealing with both the collection and transfusion blood and blood products in the HIV era have also been addressed.

The prevention and management of congenital syphilis: an overview and recommendations.

The continued occurrence of congenital syphilis is an indictment of the inadequate antenatal care services and poor quality of programmes to control sexually transmitted infections. More than 1 million infants are born with congenital syphilis each year. Despite national policies on antenatal testing and the widespread use of antenatal services, syphilis screening is still implemented only sporadically in many countries, leaving the disease undetected and untreated among many pregnant women. The weak organization of services and the costs of screening are the principal obstacles facing programmes. Decentralization of antenatal syphilis screening programmes, on-site testing and immediate treatment can reduce the number of cases of congenital syphilis. Antenatal syphilis screening and treatment programmes are as cost effective as many existing public health programmes, e.g. measles immunization. Diagnosis of congenital syphilis is problematic since more than half of all infants are asymptomatic, and signs in symptomatic infants may be subtle and nonspecific. Newer diagnostic tests such as enzyme immunoassays, polymerase chain reaction and immunoblotting have made diagnosis more sensitive and specific but are largely unavailable in the settings where they are most needed. Guidelines developed for better-resourced settings are conservative and err on the side of overtreatment. They are difficult to implement in, or inappropriate for, poorly-resourced settings because of the lack of investigative ability and the pressure on health facilities to discharge infants early. This paper offers recommendations for treating infants, including an approach based solely on maternal serological status and clinical signs of syphilis in the infant.