The 2000 Burkitt lymphoma trial in Malawi

Hesseling, Peter; Broadhead, Robin L.; Mansvelt, E. P. G.; Louw, Mercia; Wessels, G.; Borgstein, Eric; Schneider, Johann; Molyneux, Elizabeth

doi:10.1002/pbc.20254

Cited by 75 publications

(76 citation statements)

References 10 publications

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“…In this regard, 33% of 42 children with Burkitt lymphoma in Malawi were cured with a 42-day treatment regimen adapted to local conditions with a cost of US $250 per patient. 43 These patients were cured (defined as remission for at least 12 months, after which recurrence is uncommon in Burkitt lymphoma) despite the finding that 52% presented malnourished and 39% with an active parasitic infection (usually malaria). Whether the funds used for cancer care would have saved more lives had they been spent on other health problems is an important question, but it is encouraging that even in the poorest regions some children with cancer can be cured with existing resources under local conditions.…”

Section: Objectionsmentioning

confidence: 99%

Childhood cancer epidemiology in low‐income countries

Howard

Metzger

Wilimas

et al. 2007

Cancer

238

183

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Global studies of childhood cancer provide clues to cancer etiology, facilitate prevention and early diagnosis, identify biologic differences, improve survival rates in low-income countries (LIC) by facilitating quality improvement initiatives, and improve outcomes in high-income countries (HIC) through studies of tumor biology and collaborative clinical trials. Incidence rates of cancer differ between various ethnic groups within a single country and between various countries with similar ethnic compositions. Such differences may be the result of genetic predisposition, early or delayed exposure to infectious diseases, and other environmental factors. The reported incidence of childhood leukemia is lower in LIC than in more prosperous countries. Registration of childhood leukemia requires recognition of symptoms, rapid access to primary and tertiary medical care (a pediatric cancer unit), a correct diagnosis, and a data management infrastructure. In LIC, where these services are lacking, some children with leukemia may die before diagnosis and registration. In this environment, epidemiologic studies would seem to be an unaffordable luxury, but in reality represent a key element for progress. Hospital-based registries are both feasible and essential in LIC, and can be developed using available training programs for data managers and the free online Pediatric Oncology Networked Data Base (www.POND4kids.org), which allows collection, analysis, and sharing of data.

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Section: Objectionsmentioning

confidence: 99%

Childhood cancer epidemiology in low‐income countries

Howard

Metzger

Wilimas

et al. 2007

Cancer

238

183

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“…The 2000 Malawi BL protocol [16] The Pilot study left us with concerns about the cost of treatment, the duration of hospitalization, and the effect of the toxicity on patient survival and compliance with treatment. The good survival rate of patients with stage III disease who had not completed full treatment in the pilot study, encouraged us to proceed with another study in which only the first half of the Pilot Study chemotherapy would be given to all patients, including patients with stage IV disease (COP I, COMP I, COMP 2 for stages I and II over 35 days) (COP 1, COP 2, COMP I, COMP II for stages III and IV over 42 days as in Tables 1,2 for the Pilot Study).…”

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confidence: 99%

Burkitt lymphoma treatment: the Malawi experience

Hesseling

2009

J Afr Cancer

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L'objectif des études sur le lymphome de Burkitt (LB) au Malawi était de développer un traitement efficace et abordable dans une situation de ressources limitées. Dans l'étude du Malawi Pilot Study, 44 patients, atteints de LB de stades I, II et III de la classification de Saint-Jude, étaient traités par une chimiothérapie de densité moyenne basée sur la séquence et l'utilisation des médicaments selon le protocole LMB 89. Cinquante-sept pour cent du taux de survie globale étaient néanmoins associés aux décès liés à la toxicité du traitement chez 32 % des patients. Quarante des 92 patients, atteints de LB confirmé et qui ont été autorisés à quitter l'hôpital de leur vivant et traités par cyclophosphamide (CPM) seulement, étaient vivants lors de visite à domicile après 29-104 mois. Dans les études au Malawi, en 2002 (146 patients) et en 2003 (149 patients), le CPM à une dose de 40 mg/kg fut administré par voie intraveineuse ou par voie orale tous les sept jours × 3, additionné à du méthotrexate intrathécal, suivi par trois doses additionnelles de CPM tous les 14 jours en stades II et IV. La fourchette de survie, prévue selon la courbe de Kaplan-Meier, était de 45-52 %. Dans l'étude au Malawi en 2006 (40 patients), tous les stades étaient traités par CPM à une dose de 40 mg/kg au jour 1, suivi par CPM à une dose de 60 mg/kg aux jours 8, 18 et 28 et concomitante au méthotrexate interthécal. Dix-neuf (48 %) patients présentèrent une rémission continue après une médiane de 454 jours. Le coût de la chimiothérapie était de moins de 50 dollars US. Vingt-huit patients, avec une réponse incomplète à une chimiothérapie primaire ou qui présentaient une rémission, ont bénéficié d'un protocole de sauvetage par du CPM à une dose de 60 mg/kg, de la vincristine à une dose de 1,5 mg/m 2 , du méthotrexate intrathécal à une dose de 12,5 mg et de l'hydrocortisone à une dose de 12,5 mg aux jours 1, 8, 18 et 28. Ainsi, un taux de guérison global de 65 % peut être atteint par un traitement par le protocole du Malawi 2003 pour le LB suivi du protocole de sauvetage du Malawi en cas de nécessité. Mots clés Lymphome de Burkitt · Prise en chargeAbstract The objective of the Malawi Burkitt lymphoma (BL) studies was to develop effective and affordable treatment in a setting of limited resources. In the Malawi Pilot Study 44 BL patients with St Jude stages I, II and III were treated with medium intensity chemotherapy based on the sequence and drugs used in the LMB 89 protocol. The 57% overall survival rate was however associated with treatment toxicity related deaths in 32% of patients. Forty of ninety two patients with confirmed BL discharged from hospital alive and treated with cyclophosphamide (CPM) only, were found alive on home visit 29-104 months later. In the Malawi 2002 (146 patients) and 2003 (149 patients) studies i.v or oral CPM 40 mg/kg was given at 7-day intervals × 3 together with intrathecal methotrexate (MTX), followed in stages III and IV by 3 more doses of CPM at 14-day intervals. The projected Kaplan-Meier survival ranged from...

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“…Almost half the NHL in this cohort is now of the highly aggressive Burkitt's type with median overall survival of Ϸ8 months compared with 22 months for diffuse large B cell lymphoma (5). Burkitt's lymphoma (BL) also demands more widely available and cheaper treatment in the world's malarial belts, where it was first defined and remains endemic (6,7).…”

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confidence: 99%

Dopamine targets cycling B cells independent of receptors/transporter for oxidative attack: Implications for non-Hodgkin’s lymphoma

Meredith

Holder

Rosén

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Human B lymphocytes and derived lines from a spectrum of B cell malignancy were studied for expression of dopaminergic pathway components and for their cytostatic response to the catecholamine and related, potentially therapeutic compounds. Proliferating normal lymphocytes and dividing malignant clones rapidly arrested on exposure to dopamine in the low (<10 M) micromolar range. The antiparkinsonian drugs L-DOPA and apomorphine (particularly) were similarly antiproliferative. With the exception of D4, dopamine receptors D1-D5 were variably expressed among normal and neoplastic B cell populations, as was the dopamine transporter. Transcripts for D1 and D2 were frequently found, whereas D3 and D5 revealed restricted expression; dopamine transporter was detected in most cases. Nevertheless, pharmacological analysis disclosed that dopamine targeted cycling B cells independent of these structures. Rather, oxidative stress constituted the primary mechanism: the catecholamine's actions being mimicked by hydrogen peroxide and reversed by exogenous catalase, and evidence for the intracellular redox protein thioredoxin contributing protection. Among proliferating clones, growth arrest was accompanied by cell death in populations deplete in antiapoptotic Bcl-2: resting lymphocytes escaping low micromolar dopamine toxicity. Dysregulated bcl-2 expression, although preventing oxidative-induced caspase-dependent apoptosis, by itself conferred only minor protection against dopamine cytostasis. The selective impact of dopamine on lymphocytes that are in active cycle indicates an axis for therapeutic intervention not only in B cell neoplasia but also in lymphoproliferative disturbances generally. Rational tailoring of drug delivery systems already in development for Parkinson's disease could provide ideal vehicles for carrying the oxidative hit directly to the target populations.apoptosis ͉ oxidative stress ͉ Parkinson's disease ͉ Bcl-2 ͉ monoamines

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The 2000 Burkitt lymphoma trial in Malawi

Abstract: Thirty-three percent of children are in first remission at 12 months. The morbidity and mortality of treatment was high. The high relapse rate in all stages may be due to the low cumulative dose of CPM.

Cited by 75 publications

References 10 publications

Childhood cancer epidemiology in low‐income countries

Childhood cancer epidemiology in low‐income countries

Burkitt lymphoma treatment: the Malawi experience

Dopamine targets cycling B cells independent of receptors/transporter for oxidative attack: Implications for non-Hodgkin’s lymphoma

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