Childhood leukaemia and lymphoma: African experience supports a role for environmental factors in leukaemogenesis

Abstract

Major differences exist in the nature of leukaemia and lymphoma in low-income African children compared to those in the high-income countries. These include the absence of the peak incidence of acute lymphoblastic leukaemia (ALL) in under-five-year olds that characterizes the disease in high-income countries. Conversely, chloroma association with acute myelogenous leukaemia (CA-AML/AMML) and Burkitt’s lymphoma (BL) are rare in the high-income countries. This report describes clinical and laboratory as well as epidemiological features of childhood leukaemia and lymphoma reported betwen 1982 and 1984 in the city of Ibadan, Nigeria. The observed pattern of distribution of childhood haematological malignancies in the city is more consistent with the observations of Ludwik Gross’s experiments on environmental influences, such as malnutrition and infections, animal leukaemogenesis, and mirroring the consequences of the primordial pressures that have shaped human genetics and pathophysiology.

Neonatal leukaemia

“…A second case presented with haemophagocytic lymphohistiocytosis and pancytopenia; the leukaemic phase of BPDCN with 46,XX,t(2;17;8)(p23;q23;p23) and CLTC-ALK fusion manifest at 2 months of age with the fusion gene then demonstrated to have been present at birth (Tokuda et al, 2014). (Table IV) Spontaneous remission of leukaemia, reminiscent of that occurring in the majority of cases of TAM, is a well-recognised feature of cases of neonatal leukaemia associated with t(8;16)/ KAT6A-CREBBP; some such cases subsequently relapse (Dinulos et al, 1997;Wong et al, 2008;Coenen et al, 2013;Barrett Acute myelomonocytic (Pui et al, 1987) or acute monocytic/monoblastic leukaemia (Bresters et al, 2002) *In addition there are a number of other reports of neonatal leukaemia with t(11;19) without the 19p13 breakpoint or the fusion gene being fully specified. (Terui et al, 2008) and cryptic insertion of CREBBP into chromosome 16 (Barrett et al, 2017) Mainly acute monoblastic or acute monocytic leukaemia (Schouten et al, 1983;Bernstein et al, 1987;Zandecki et al, 1988;Hanada et al, 1991;Sainati et al, 1996;Classen et al, 2005;Terui et al, 2008;Sung et al, 2010;Coenen et al, 2013;(cases 17, 19, 23, 43) (Sainati et al, 1996;Classen et al, 2005;Terui et al, 2008;Wu et al, 2011a).…”

“…Other subtypes of AML that are more characteristic of older children and adults can, likewise, present as neonatal leukaemia, specifically t(8;21)(q22;q22.1); RUNX1-RUNX1T1 (Nanda et al, 2012) and t(8;16)(p11.2;p13.3)/KAT6A-CREBBP and variants (Table III). Cases with t(8;16) (Schouten et al, 1983;Bernstein et al, 1987;Zandecki et al, 1988;Hanada et al, 1991;Sainati et al, 1996;Dinulos et al, 1997;Classen et al, 2005;Wong et al, 2008;Wu et al, 2011a;Coenen et al, 2013;Barrett et al, 2017), together with those with t(1;22), are the most common subtypes of neonatal AML after cases with rearrangement of KMT2A. It is of interest that two neonates with t (8;16)-associated neonatal leukaemia had underlying Noonan syndrome (Wong et al, 2008;Barrett et al, 2017).…”

Haematological cancers in African children: progress and challenges

“…Worldwide, acute myeloid leukaemia (AML) represents 20-25% of acute leukaemias. Early reports, including an analysis of childhood cancer in Nigeria in the 1980's, suggest that 50% of acute leukaemia in Africa was AML (Williams et al, 2014). More recent reports from African hospital cancer registries report 20-25% of acute leukaemia cases as AML, which matches international experience (Kersten et al, 2013).…”

Pattern of childhood acute leukemia presentation at a tertiary hospital in Nigeria: a five-year review

“…We found no association between socioeconomic status and acute leukemia diagnosis although Williams et al reported an association between high socioeconomic class and prevalence of acute leukemia. 9 Eden in his review reflected on the importance of geneticenvironmental interaction in the aetiology of childhood leukemia. 5 The common clinical features patients presented with were pallor, fever, hepatomegaly and lymphadenopathy which are similar to other reports.…”

“…The common presentations of acute leukemia include fever, fatigue, pallor, bleeding, infection, lymphadenopathy and hepatosplenomegaly. 8,9,10 Majority of the presenting clinical features are as a result of infiltration of organs, bone marrow and extramedullary sites. The initial presentation of leukemia is usually nonspecific which may include anorexia, fatigue and irritability with progressive bone marrow failure leading to pallor, bleeding, fever and infection.…”