Describing the evolution of myeloid-derived leucocytes in treated B-lineage paediatric acute lymphoblastic leukaemia with a data-driven granulocyte-monocyte-blast model.

Acute lymphoblastic leukaemia (ALL) is associated with a compromised myeloid system. Understanding the state of granulopoiesis in a patient during treatment, places the clinician in an advantageous position. Mathematical models are aids able to present the clinician with insight into the behaviour of myeloid-derived leucocytes. The main objective of this investigation was to determine whether a proposed model of ALL during induction therapy would be a usable descriptor of the system. The model assumes the co-occurrence of the independent leukaemic and normal marrow populations. It is comprised of four delay-differential equations, capturing the fundamental characteristics of the blood and bone marrow myeloid leucocytes and B-lineage lymphoblasts. The effect of treatment was presumed to amplify cell loss within both populations. Clinical data was used to inform the construction, calibration and examination of the model. The model is promising-presenting a good foundation for the development of a clinical supportive tool. The predicted parameters and forecasts aligned with clinical expectations. The starting assumptions were also found to be sound. A comparative investigation highlighted the differing responses of similarly diagnosed patients during treatment and further testing on patient data emphasized patient specificity. Model examination recommended the explicit consideration of the suppressive effects of treatment on the normal population production. Additionally, patient-related factors that could have resulted in such different responses between patients need to be considered. The parameter estimates require refinement to incorporate the action of treatment. Furthermore, the myeloid populations require separate consideration. Despite the model providing explanation, incorporating these recommendations would enhance both model usability and predictive capacity.

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.

Childhood cancer survival rates in two South African units.

INTRODUCTION: Childhood cancer is relatively rare, but there is a very good chance of cure. While overall survival rates of >70% are reported from developed countries, survival is much less likely in developing countries and unknown in many countries in Africa. OBJECTIVE: To analyse survival rates of childhood cancers in two South African paediatric oncology units. METHODS: This retrospective review included all children (0 - 15 years) admitted with a malignancy at two paediatric oncology units (Universitas Hospital Academic Complex in Bloemfontein, Free State, and Tygerberg Hospital in Cape Town, Western Cape) between 1987 and 2011. The protocols used in the units were similar, and all the diagnoses were confirmed histologically. RESULTS: There were 3 241 children, 53.5% of whom were males. Median follow-up was 17 months. The most common cancers were leukaemia (25.0%), brain tumours (19.5%), lymphoma (13.0%) and nephroblastoma (10.0%). The prevalences of neuroblastoma and retinoblastoma were similar at 5.8% and 5.7%, respectively. Overall survival was calculated to be 52.1%. Lymphoma and nephroblastoma had the highest survival rates at 63.9% and 62.6%, respectively. Brain tumours had the lowest survival rate at 46.4%. A comparison between ethnic groups showed white children to have the highest survival rate (62.8%); the rate for children of mixed racial origin was 53.8% and that for black children 48.5%. CONCLUSIONS: Overall survival rates for children admitted to two paediatric cancer units in South Africa were lower than data published from developed countries, because many children presented with advanced disease. New strategies to improve cancer awareness are urgently required.

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.

Children with cancer and HIV infection: what is different about them?

BACKGROUND: Children with HIV and cancer show an excess of non-Hodgkin lymphoma and leiomyosarcoma when compared with children with malignancy but without HIV. This study aimed at: (1) comparing the distribution of various cancers in South African children with malignancies and HIV versus children with malignancies but without HIV and (2) comparing the outcomes after therapy. PROCEDURE: This is a retrospective comparative study of 84 black children with cancer and HIV, consecutively admitted at Tygerberg Children's Hospital, Cape Town and Universitas Hospital, Bloemfontein, between 1995 and 2010, compared with 570 HIV-negative black children with malignant diseases, consecutively admitted at the 2 hospitals, between 2002 and 2010. Variables studied included age, sex ratio, number of cases of each malignancy, length of follow-up, treatment abandonment, and mortality. The statistical significance was tested with the Student t test and χ test for P≤0.05. Kaplan-Meyer survival curves were constructed. RESULTS: The most frequent cancer was Kaposi sarcoma (39.3%), seen exclusively in children with HIV. Burkitt lymphoma was found more often (20.2%) in the HIV-positive group than in the HIV-negative one (2.8%, P<0.0001). Leiomyosarcoma, described as the second most frequent neoplasm encountered in HIV-positive children, was found in this series only once. The survival figures are much worse in the HIV-positive group: 26.2% versus 47.7% (P<0.0001), mainly due to drug toxicity. CONCLUSIONS: Kaposi sarcoma and Burkitt lymphoma occurred more often in children with HIV. These children have a lower tolerance of chemotherapy, even when combined with HAART.

The South African Paediatric Tumour Registry - 25 years of activity.

The South African Children's Tumour Registry was established 25 years ago as it was essential to collect data on malignant disease in the paediatric population that can be used for statistical research in an efficient and sustainable way. The Registry is a useful and significant repository of specific paediatric data, along with the recently revitalised National Cancer Registry, to serve the needs of the cancer research community.

Kaposi sarcoma in South African children.

BACKGROUND: The incidence of Kaposi's sarcoma (KS) in sub-Saharan Africa, increased tens of times since the onset of the AIDS epidemic. There is, however, very little literature concerning the clinical features of this disease, its management and outcome in HIV-positive children in Africa. This study describes retrospectively the clinical presentation of the malignancy, its management and outcome, in a series of HIV-positive children. PATIENTS AND METHODS: Seventy children with KS and HIV infection were admitted consecutively from January 1998 to December 2009 in South African hospitals. Clinical data were extracted from tumor registries and patient records and analyzed. RESULTS: The average age in this series was 73 months. The males/females ratio was 1.59:1. Skin lesions were present in 36 out of 63 cases (57.14%), followed by lymph node lesions (28 cases, 44.44%). The mean CD4+ lymphocyte count was 440 (SD = 385). The average CD4+ percentage was 12.20% (SD = 9.13). Only 14 patients (20%) were taking combined antiretrovirals at the time of diagnosis; a further 35 were given HIV treatment after diagnosis. Thirty-two patients (45.71%) survived only 4 months on average; 10 were lost to follow-up; and 28 (40%) were alive, with an average follow-up of 16 months. Antiretrovirals improved survival (P = 0.001). CONCLUSIONS: The often present skin lesions facilitated the diagnosis; lymphadenopathy was less frequently seen than skin lesions. Antiretroviral drugs were associated with higher survival rate. The mortality remains high in spite of antiretrovirals and cytostatics.