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Leukaemia and sudden death
Leukemia Research Vol. 22, No. 3, p. 289, 1998. 0 1998 Published bv Elsevier Science Ltd. All riebts reserved Printed in &eat Britain 0145-2126/98 $19.00 + 0.M)
Pergamon PII: SO145-2126(97)00167-7
LETTER TO THE EDITORS LEUKAEMIA
AND SUDDEN DEATH the second stage of labour, and infections from faulty leucopoiesis [5]. Before antibiotics were discovered the infection risk would be of overriding importance. But today the risk shared by ALL and JML might be of minor importance compared with the ‘JML only’ risk of dying from anoxia at two critical junctures: after separation of the placenta (unexplained stillbirth during the second stage of labour), or after falling asleep when, unbeknown to anyone, the first common cold to follow loss of passive immunity was having its first effect, namely, slight nasal obstruction (unexplained sudden death). According to this hypothesis, abnormally high levels of HbF and other signs of faulty erythropoiesis should have associations with three causes of infant mortality: SIDS, pneumonia and JML. Therefore, routine testing of HbF levels at, say, 1 and 4 weeks of age, followed by checking of all deaths in the next 1I months, should be sufficient to test the null hypothesis of no such associations, and might be the means of diagnosing JML before there was any flooding of the bloodstream with malignant cells.
Neither the increase in young cases of acute lymphatic leukaemia (ALL) which accompanied a world-wide decrease in infant mortality, nor the sudden infant death syndrome (SIDS), which first attached attention during this period, have been satisfactorily explained. But it is possible that both problems might be resolved by routine monitoring of blood levels of fetal haemoglobin (HbF) during the neonatal period. Here is the reasoning behind this suggestion. By 1975, haematologists had discovered that in the still rare cases of juvenile myeloid leukaemia (JML) there were high levels of HbF and other signs of faulty erythropoieses [ 11; epidemiologists had discovered that births in the first half of the calendar year were followed by ‘too many’ infant leukaemias and ‘too few’ cot deaths [2], and paediatricians had discovered that sudden unexplained deaths of infants not only had a peak incidence between 1 and 6 months (and were commoner in the winter than the summer) but also had associations with household infections, breast feeting and a short second stage of labour [3]. In addition to these observations there was both evidence that childhood cancers have in utero origins, and evidence that, in cases of leukaemia, loss of immunological competence occurs much earleir than other, more obvious signs of disease [4]. These findings make it reasonable to suspect that ALL might be the result of mutations in embryonic equivalents of lymph nodes (whose side effects include faulty leucopoiesis), and that JML might be the result of mutations in embryonic equivalent or red marrow (whose side effects include both faulty leucopoiesis and faulty erythropoiesis). In other words, for ALL there might be one competing cause of death (infections) and for JML there might be three; it ufero deaths from maldevelopment of erythrocytes; stillbirths from insufficient haemoglobin to cope with tbe anoxic conditions of
References 1. Lee, G. R. et al. Wintrobe’s Clinical Haematology, Vol. 75, 9th edn. Lea & Febiger, Philadelphia, 1993,pp. 1986. 2. Stewart, A. M., Infant leukaemia and cot deaths. Btitish Medical Journal, 1975, ii, 605. 3. Carpenter, R. G. and Emery, J. L., Identification and follow-up of infants at risk of sudden death. Nature 1974, 250, 729. 4. Stewart, A. M. and Kneale, G. W., The immune system and cancers of foetal origin. Cancer Immunology and Immunotherapy 1982, 14, 110. 5. Stewart, A. M., Childhood cancers and competing causes of death. Leukemia Research 1995, 19, 2, 103. A. M. Stewart Department of Public Health and Epidemiology, The Medical School, Edgbaston, Birmingham B15 2TT, UK
Correspondence to: A. M. Stewart, Departmentof Public Health and Epidemiology, The Medical School, Edgbaston, Birmingham B15 2TT, UK.
289
Pergamon PII: SO145-2126(97)00167-7
LETTER TO THE EDITORS LEUKAEMIA
AND SUDDEN DEATH the second stage of labour, and infections from faulty leucopoiesis [5]. Before antibiotics were discovered the infection risk would be of overriding importance. But today the risk shared by ALL and JML might be of minor importance compared with the ‘JML only’ risk of dying from anoxia at two critical junctures: after separation of the placenta (unexplained stillbirth during the second stage of labour), or after falling asleep when, unbeknown to anyone, the first common cold to follow loss of passive immunity was having its first effect, namely, slight nasal obstruction (unexplained sudden death). According to this hypothesis, abnormally high levels of HbF and other signs of faulty erythropoiesis should have associations with three causes of infant mortality: SIDS, pneumonia and JML. Therefore, routine testing of HbF levels at, say, 1 and 4 weeks of age, followed by checking of all deaths in the next 1I months, should be sufficient to test the null hypothesis of no such associations, and might be the means of diagnosing JML before there was any flooding of the bloodstream with malignant cells.
Neither the increase in young cases of acute lymphatic leukaemia (ALL) which accompanied a world-wide decrease in infant mortality, nor the sudden infant death syndrome (SIDS), which first attached attention during this period, have been satisfactorily explained. But it is possible that both problems might be resolved by routine monitoring of blood levels of fetal haemoglobin (HbF) during the neonatal period. Here is the reasoning behind this suggestion. By 1975, haematologists had discovered that in the still rare cases of juvenile myeloid leukaemia (JML) there were high levels of HbF and other signs of faulty erythropoieses [ 11; epidemiologists had discovered that births in the first half of the calendar year were followed by ‘too many’ infant leukaemias and ‘too few’ cot deaths [2], and paediatricians had discovered that sudden unexplained deaths of infants not only had a peak incidence between 1 and 6 months (and were commoner in the winter than the summer) but also had associations with household infections, breast feeting and a short second stage of labour [3]. In addition to these observations there was both evidence that childhood cancers have in utero origins, and evidence that, in cases of leukaemia, loss of immunological competence occurs much earleir than other, more obvious signs of disease [4]. These findings make it reasonable to suspect that ALL might be the result of mutations in embryonic equivalents of lymph nodes (whose side effects include faulty leucopoiesis), and that JML might be the result of mutations in embryonic equivalent or red marrow (whose side effects include both faulty leucopoiesis and faulty erythropoiesis). In other words, for ALL there might be one competing cause of death (infections) and for JML there might be three; it ufero deaths from maldevelopment of erythrocytes; stillbirths from insufficient haemoglobin to cope with tbe anoxic conditions of
References 1. Lee, G. R. et al. Wintrobe’s Clinical Haematology, Vol. 75, 9th edn. Lea & Febiger, Philadelphia, 1993,pp. 1986. 2. Stewart, A. M., Infant leukaemia and cot deaths. Btitish Medical Journal, 1975, ii, 605. 3. Carpenter, R. G. and Emery, J. L., Identification and follow-up of infants at risk of sudden death. Nature 1974, 250, 729. 4. Stewart, A. M. and Kneale, G. W., The immune system and cancers of foetal origin. Cancer Immunology and Immunotherapy 1982, 14, 110. 5. Stewart, A. M., Childhood cancers and competing causes of death. Leukemia Research 1995, 19, 2, 103. A. M. Stewart Department of Public Health and Epidemiology, The Medical School, Edgbaston, Birmingham B15 2TT, UK
Correspondence to: A. M. Stewart, Departmentof Public Health and Epidemiology, The Medical School, Edgbaston, Birmingham B15 2TT, UK.
289