We have recently observed 3 children with AML treated with daunorubicin (DNR), ara-c and thioguanine (TG) who during remission developed marked hepatomegaly (H) in the absence of jaundice or significant tranaaminaaemia. Liver scans revealed diffuse non-homogeneous reduction in uptake suggesting leukemic infiltration. Liver biopsies showed no significant infiltration, but instead thickening of the walls of the central veins, and intense centrilobular congestion and hemorrhage, a pattern resembling VOD caused by plant alkaloid poisoning. One child had a large R. pleural effusion requiring chest drainage for 1 month. All 3 children have been since maintained only on TG. H and abnormal liver scans have improved but remain abnormal 8-10 months later. One child in relapse was re-treated with all 3 druga and developed an exacerbation of the liver disease and pleural effusion. The erythrocytes of the newborn infant posseas a variety of metabolic characteriatics that serve to distinguish them from the red cells of n o r m 1 adults. In an attempt to define the functional significance of w r a of t h e m differencea the red cell. of nnrborn infanta were etudied at reduced oxyeen tenaions rather than in room air. in order to m r e closely mimic the intrauterine wvironrant. Red cells from 10 adults and 10 infants were incubated for 3 hours in room air, 5X 02. 2X 02, and in nitrogen, and measureuntm of glycolysim, glycolytic interudiates, and re8ponae to mnadione (7.5 ug/ml) were performed. Glucose conmumption and pymvate and lactate production roae in a similar fashion in both group#. In the adult. the incream in glucoae conrumption cns araociated with an increme in the levels of trio-phosphataa and 2.3-DPG. A 16 year old girl developed hypercalcemia (14.4 mgmfdl) at the time of exacerbation of acute lymphoblastic leukemia which required intensive therapy, including mithramycin, to reduce calcium levels. Parathormone (PTH) was inappropriately elevated to 82 p1Eqlml with a calcium level of 13.7 mgmldl.To determine if ectopic PTH production by leukemic cella was occurring in thia patient, bone marrow (952 lymphoblasta) was cultured in vitro in a liquid culture aystem containing 15% fetal calf serum. No measurable PTH was present at 0 time or at 20 hours, however, 247p1Eq/ml PTH was measured at 68 hours. PTH levels increased in the culture aystem with levels of 349 p1Eqlml at 10 days and 533 plEqlml at 13 da3a. PTH was undetectable when no viable cella remained in culture at 17 days. PTH production was similar when the cells were cultured in media with calcium levels ranging from 2.7 -5.9 mgmldl. This is the initial demonstration of autonomous PTH production in culture of lymphoblastic leukemia cells, and is another example of a non-endocrine cell produring a biologically active polypeptide hormone. Autonomous production of PTH should be considered in the etiology of hypercalcemia in acute lymphoblastic leukemia.
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