Clinical significance of surface antigen expression in children with acute myeloid leukemia: results of study AML-BFM-87

Immunophenotyping using a panel of 15 antibodies was performed in 267 (87%) and cytogenetic analysis in 196 (64%) of 307 children under 17 years of age enrolled in the AML-BFM-87 study. Treatment consisted of cytosine arabinoside, daunorubicin, etoposide induction and a 6-week seven-drug consolidation chemotherapy, followed by two blocks of high- dose cytosine arabinoside with or without cranial irradiation and maintenance therapy for 1 year. Five-year event-free survival for patients with immunophenotypic data was .43 +/- .03 SE. The diagnostic value of the pan-myeloid reagents CD13, CD33, and CDw65 for the recognition of childhood acute myeloid leukemia (AML) was high with a sensitivity of 98% (positivity of at least one of these antigens), whereas, with the exception of CD41 for French American British (FAB) subtype M7, the expression of single cell-surface antigens showed no correlation with morphologic or cytogenetic subgroups. On the other hand, characteristic subgroups of AML defined by morphologic features and karyotypes could be described by low or high rates of surface antigen expression compared with those of other patients. These immunophenotypic features most probably associated with specific entities include expression of CD34 or CD13 and absence of CD14 or CD4 in M2 with Auer rods/t(8;21); absence of HLA-DR, CD34, and CD14, but expression of CD33 in M3/t(15;17); positivity of either CD34 or CD13 and either CD14 or CD2 for M4Eo/inv(16); and absence of either CD34 or CD13 and expression of either CD33 or CDw65 and either CD15 or CD4 for M5/t(9;11). In FAB M0, negativity of one or two of the three panmyeloid- associated markers (CD13/33/w65) was common; and cytogenetic results frequently showed random abnormalities. Expression of lymphoid-, progenitor- and most myeloid-associated antigens had no influence on the prognosis, whereas the outcome was significantly better for children with M2 with Auer rods, M3, or M4Eo or for those with the associated karyotypes t(8;21);t(15;17) and inv(16) than for other patients.     

Pharmacological challenges in chronic pancreatitis

Drug absorption in patients with chronic pancreatitis might be affected by the pathophysiology of the disease.The exocrine pancreatic insufficiency is associated with changes in gastrointestinal intraluminal pH,motility disorder,bacterial overgrowth and changed pancreatic gland secretion.Together these factors can result in malabsorption and may also affect the efficacy of pharmacological intervention.The lifestyle of chronic pancreatitis patients may also contribute to gastrointestinal changes.Many patients limit their food intake because of the pain caused by eating and in some cases food intake is more or less substituted with alcohol,tobacco and coffee.Alcohol and drug interaction are known to influence the pharmacokinetics by altering either drug absorption or by affecting liver metabolism.Since patients suffering from chronic pancreatitis experience severe pain,opioids are often prescribed as pain treatment.Opioids have intrinsic effects on gastrointestinal motility and hence can modify the absorption of other drugs taken at the same time.Furthermore,the increased fluid absorption caused by opioids will decrease water available for drug dissolution and may hereby affect absorption of the drug.As stated above many factors can influence drug absorption and metabolism in patients with chronic pancreatitis.The factors may not have clinical relevance,but may explain inter-individual variations in responses to a given drug,in patients with chronic pancreatitis.