Serum levels of CD8 antigen in childhood lymphoid malignancies: a possible indicator of increased suppressor cell activity in poor-risk patients

Serum concentrations of CD8 antigen were measured at diagnosis with an enzyme-linked immunoassay in children with acute lymphoblastic leukemia (n = 344) or non-Hodgkin's lymphoma (n = 65). All patients had detectable levels of the serum antigen, which in its soluble nonreduced form appeared to be a 52-Kd homodimer as compared with the 66-Kd surface membrane component on most thymocytes and on a subset of functionally distinct T cells (suppressor/cytotoxic). Increased serum levels of CD8 in leukemia patients were significantly related to recognized high-risk prognostic features: high leukocyte count, large liver and spleen size, high serum lactic dehydrogenase level, T-cell immunophenotype, presence of a mediastinal mass, pseudodiploid karyotype, DNA index less than 1.16, and chromosomal translocation. Children with serum CD8 levels greater than or equal to 450 U/mL were more likely to fail treatment than were those with lower levels (P = .002), even in the group with non-T-cell leukemia (P = .003). In a multivariate analysis, serum CD8 antigen contributed independent prognostic information beyond that conveyed by age, leukocyte count, and race (P = .02). High serum CD8 antigen levels also correlated with advanced stages of disease in children with non-Hodgkin's lymphoma or B- cell leukemia. Children with higher serum CD8 antigen levels (greater than or equal to 700 U/mL) had a poorer treatment outcome (P = .003), even after results were adjusted for disease stage and serum lactic dehydrogenase level (P = .05). Measurement of serum levels of CD8 antigen not only has important prognostic value in childhood lymphoid malignancies but also could be useful in assessing the immunoregulatory role of T cells in patients with cancer.     

Adhesion of malaria-infected red blood cells to chondroitin sulfate A under flow conditions

Adhesion of parasitized red blood cells (PRBCs) to microvascular endothelial cells (ECs) is a distinctive feature of Plasmodium falciparum malaria and is a central event in the development of life- threatening complications such as cerebral malaria. PRBCs adhere to several EC-expressed molecules in vitro, but the relative importance of these interactions in vivo remains unclear. Chondroitin sulfate A (CSA) is the most recent EC surface-associated molecule to be implicated in the adhesive process. Accordingly, we have studied adhesion of PRBCs to CSA in vitro using a parallel-plate flow chamber. Under controlled flow conditions, PRBCs adhered to CSA in a concentration-dependent manner at wall-shear stresses up to 0.2 Pa, a value that is within the physiological range for venules. Once adhered, PRBCs remained stationary (rather than rolling) and continued to remain stationary even when the wall-shear stress was raised to supravenular levels. The adhesive interaction was strong and a proportion of adherent PRBCs could withstand detachment at stresses up to 2.5 Pa. Soluble CSA at pharmacological concentrations prevented adhesion of flowing PRBCs in a concentration-dependent manner but failed to reverse established adhesion. Adhesion of PRBCs to CSA could contribute to the pathogenesis of malaria, and soluble CSA may have a useful therapeutic effect.     

Cytogenetic features and serum lactic dehydrogenase level predict a poor treatment outcome for children with pre-B-cell leukemia

Leukemic cells from 89 (24%) of 369 children with newly diagnosed acute lymphoblastic leukemia (ALL) were found to have a pre-B immunophenotype. By comparison with blasts having the common ALL phenotype, the pre-B cells were more likely to have a DNA index less than 1.16 (P = 0.02), a pseudodiploid karyotype (P less than 0.001), and a chromosomal translocation (P = 0.001). Increased serum lactic dehydrogenase levels (P = 0.001) were also characteristic of pre-B ALL; otherwise, the clinical and laboratory features of the two groups were similar. A nonrandom chromosomal translocation, t(1;19)(q23;p13.3), was identified in blast cells from 16 (23%) of the 70 patients with pre-B ALL and adequate chromosome banding studies; different translocations were found in 11 of the remaining patients. The presence of any chromosomal translocation in the pre-B group was significantly related to a higher leukocyte count, an increased level of serum lactic dehydrogenase, an increased percentage of S-phase cells, black race, and a blast cell DNA index less than 1.16. Four presenting features were found to confer an increased risk of treatment failure among pre-B patients: pseudodiploidy, chromosomal translocation, black race, and higher serum lactic dehydrogenase level. In a multivariate analysis, pseudodiploidy emerged as the strongest factor for predicting relapse in pre-B ALL. The frequent association of chromosomal abnormalities of known adverse prognostic significance and high serum lactic dehydrogenase levels with pre-B-cell ALL explains, at least in part, the poor treatment outcome reported for children with this subtype of leukemia.     

Lack of significant association of an insertion/deletion polymorphism in the angiotensin converting enzyme (ACE) gene with tropical calcific pancreatitis

Background  

The genetic basis of tropical calcific pancreatitis (TCP) is different and is explained by mutations in the pancreatic secretory trypsin inhibitor (SPINK1) gene. However, mutated SPINK1 does not account for the disease in all the patients, neither does it explain the phenotypic heterogeneity between TCP and fibro-calculous pancreatic diabetes (FCPD). Recent studies suggest a crucial role for pancreatic renin-angiotensin system during chronic hypoxia in acute pancreatitis and for angiotensin converting enzyme (ACE) inhibitors in reducing pancreatic fibrosis in experimental models. We investigated the association of ACE gene insertion/deletion (I/D) polymorphism in TCP patients using a case-control approach. Since SPINK1 mutations are proposed a modifier role, we also investigated its interaction with the ACE gene variant.     

Aplasie médullaire associée à la ticlopidine

Ticlopidine induced bone marrow aplasia. The authors report two cases of bone marrow aplasia observed 2 months after initiation of a treatment with ticlopidine. The outcome was favorable after discontinuation of therapy. The frequency of this severe drug-induced complication seems to have been underestimated. The absolute necessity of a careful haematological survey during the first 3 months of therapy is pointed out.     

Prognostic importance of chromosome number in 136 untreated children with acute lymphoblastic leukemia

Leukemia cell karyotypes were determined at diagnosis for 136 of 159 consecutive patients with acute lymphoblastic leukemia (ALL) who were followed for up to 35 mo. Ninety patients (67%) had abnormal karyotypes. Five chromosome categories were designated, based on the distribution of modal numbers: hyperdiploid greater than 50 (n = 41), hyperdiploid 47-50 (n = 18), pseudodiploid (n = 28), normal (n = 46), and hypodiploid (n = 3). Treatment response was assessed for the categories in terms of time to failure (induction failure, first relapse, or death). Children in the hyperdiploid greater than 50 category had the best responses to treatment, with only 2 failures, and those in the pseudodiploid category had the poorest (p less than 0.001). The remaining 3 chromosome categories had intermediate responses and formed a third prognostic group. This same influence of chromosome number on time to failure was evident within the 2 clinical prognostic groups: high risk, signified by a leukocyte count greater than 100 X 10(9)/liter, meningeal leukemia, mediastinal mass, or the presence of blasts that formed rosettes with sheep erythrocytes at 37 degrees C, and standard risk, indicated by the absence of these features. The influence of chromosome number on time to failure was also the same within the historically favorable prognostic group that had common ALL. Results of a multivariate analysis indicated that chromosome number was the strongest single predictor of outcome (p less than 0.001) and was the only variable that added significant prognostic information to leukocyte count (p less than 0.001). The combination of chromosome number and leukocyte count should more clearly distinguish patients with ALL at low or high risk of relapse.