Adult T-cell acute lymphoblastic leukemia: biologic profile at presentation and correlation with response to induction treatment in patients enrolled in the GIMEMA LAL 0496 protocol

Between 1996 and 2000, 90 newly diagnosed adult patients with T-acute lymphoblastic leukemia (T-ALL) were registered in the Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) Leucemia Acuta Limfoide (LAL) 0496 protocol. Cases were centrally processed for morphology, immunophenotype, cytogenetics, molecular biology, and multidrug resistance (MDR). Twenty-two patients were females and 68 were males. Four percent of cases were pro-T, 47% pre-T, 39% cortical T, and 10% mature T-ALL. Fifty-six percent of patients with pro-T + pre-T-ALL achieved complete remission (CR) compared with 91% for cortical + mature cases (P = .002). CD34 expression was associated with a significantly lower CR rate: 54% versus 84% (P = .009). Thirty-one (36.5%) of 85 patients had an abnormal karyotype, the most common abnormality (15%) being a partial del(6q). The cytogenetic profile did not impact on CR achievement. MDR1 function, present in 26% of cases, correlated significantly with CR achievement (P = .004). A highly significant (P = .001) difference in CR rate was observed between patients who did not express the CD13/CD33/CD34 antigens and were MDR functionally negative (96%) compared with patients positive for at least one of these markers (57%). Multivariate analysis showed an impact on CR achievement for CD33 expression and MDR1 function. An extensive biologic workup of adult T-ALL cases at presentation is recommended in order to design tailored therapeutic strategies aimed at improving CR rates.     

Custom dynamic stent for esophageal strictures in children

Background

Esophageal stenting represents a new strategy to avoid multiple dilations owing to stenosis relapse. Our custom stent improves esophageal motility unlike the widespread self-expandable plastic esophageal stents. The aim of the study was to confirm the efficacy of treatment with silicone custom stents in esophageal stenosis (ES) in pediatric patients.

Methods

A silicone stent of 7-, 9-, or 12.7-mm external diameter is built coaxially on a nasogastric tube that guarantees the correct position. The 2 ends are tailored to allow food passage between stent and esophageal wall. All patients received dexamethasone (2 mg/kg per day) for 3 days and ranitidine/proton-pump inhibitors. Study approval was obtained from our ethical board.

Results

From 1988 to 2010, 79 patients with ES, mean age 35.4 months (3-125 months), underwent esophageal hydrostatic/Savary dilations and custom-stent placement, left in place for at least 40 days. Stenting was effective in 70 (88.6%) of 79 patients. Fifty percent of the patients with effective treatment received only one dilation for stent placement. Fourteen patients received more stents successfully. There was one stent-related major complication.

Conclusion

Our custom stent improves treatment in ES. In caustic injuries, ES stenting represents the first option. In postsurgical ES, we stent after at least 5 dilations.     

Stainless steel bands in endodontics: effects on cuspal flexure and fracture resistance

AIMS: This study investigated the effect of stainless steel bands on cuspal flexure and fracture resistance of extracted maxillary premolars. METHODOLOGY: Twenty extracted maxillary premolars (10 matched pairs) with mesio-occluso-distal (MOD) cavities and endodontic access were subjected to occlusal loading tests (100 N) using a servo-hydraulic testing machine. Cuspal deflections were measured by an extensometer, with and without the band present. Ten teeth (one of each pair) then had the band removed, and all teeth were subjected to loading until fracture. RESULTS: Mean cuspal flexure of teeth with bands was one-half of flexure without bands (P < 0.001). Teeth with bands fractured at higher load than their matched pairs with the band removed (P < 0.001), with mean loads at fracture of 1282 N and 729 N, respectively. CONCLUSIONS: The study showed that stainless steel bands used in endodontics reduce the cuspal flexure of maxillary premolars and increase their fracture resistance.     

CD56 expression is an indicator of poor clinical outcome in patients with acute promyelocytic leukemia treated with simultaneous all-trans-retinoic acid and chemotherapy.

PURPOSE: Preliminary reports suggest that leukemic cell expression of CD56, a neural cell adhesion molecule, is associated with adverse clinical outcome in either acute myeloid leukemia with t(8;21) or acute promyelocytic leukemia (APL). We investigated the prognostic relevance of CD56 in a series of patients with APL who were treated homogeneously with all-trans-retinoic acid (ATRA) and chemotherapy. PATIENTS AND METHODS: Clinicobiologic presenting features and therapeutic results were analyzed in a series of 100 patients with genetically proven APL who were treated, according to the example of the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto multicenter trial, with ATRA plus idarubicin (AIDA) and for whom data on CD56 expression were available at diagnosis. RESULTS: Fifteen patients (15%) showed expression of CD56 in greater than or equal to 20% blasts at diagnosis and were considered as CD56(+). No differences were found regarding age, sex, WBC and platelet counts, incidence of coagulopathy, hemoglobin and fibrinogen levels, promyelocytic leukemia/retinoic acid receptor (PML/RAR) alpha fusion type, or complete remission (CR) rate in the comparison of the CD56(+) and CD56(-) populations. Conversely, compared with patients who were CD56(-), patients with CD56(+) APL had shorter CR duration (P =.04) and overall survival (P =.002). In the multivariate analysis, CD56 positivity and initial WBC count greater than 10 x 10(9) cells/L retained statistical significance in overall survival (P =.04 and P =.02, respectively). CONCLUSION: The expression of CD56 is significantly associated with inferior CR duration and survival in patients with APL who were treated with modern frontline treatment that included ATRA and simultaneous chemotherapy. Combined with other well-established prognostic factors such as WBC count, CD56 expression at diagnosis might be used to build prognostic scores for risk-adapted therapy in APL.     

Junctional adhesion molecule‐A is down‐regulated in anaplastic thyroid carcinomas and reduces cancer cell aggressiveness by modulating p53 and GSK3 α/β pathways

Junctional adhesion molecule A (JAM‐A) is a transmembrane protein that contributes to different biological process, including the epithelial to mesenchymal transition (EMT). Through an EMT profiler array, we explored the molecular players associated with human thyroid cancer progression and identified JAM‐A as one of the genes mostly deregulated. The quantitative real‐time polymerase chain reaction and immunohistochemistry analyses showed that downregulation of JAM‐A occurred in anaplastic thyroid carcinoma (ATC) compared with normal thyroid (NT) and papillary thyroid carcinoma (PTC) tissues and correlated with extrathyroid infiltration, tumor size, and ATC histotype. In ATC cell lines, JAM‐A restoration suppressed malignant hallmarks of transformation including cell proliferation, motility, and transendothelial migration. Accordingly, knockdown of JAM‐A enhanced thyroid cancer cell proliferation and motility in PTC cells. Through the proteome profiler human phospho‐kinase array, we demonstrated that higher expression of JAM‐A was associated with a significant increased level of phosphorylation of p53 and GSK3 α/β proteins. In conclusion, our findings highlight a novel role of JAM‐A in thyroid cancer progression and suggest that JAM‐A restoration could have potential clinical relevance in thyroid cancer treatment.