Evaluation of platelet cross-matching in the management of patients refractory to platelet transfusions.

BACKGROUND: Cross-match-compatible platelets are used to support thrombocytopenic patients who are refractory to randomly selected platelets. However, few studies have addressed the efficacy of using this strategy for patients requiring intensive platelet transfusion therapy. The aim of this study was to determine the effectiveness of cross-match-compatible platelets in an unselected group of patients refractory to platelets from random donors. MATERIALS AND METHODS: A total of 406 cross-match-compatible platelet components were administered to 40 evaluable patients who were refractory to random-donor platelets. A solid-phase red cell adherence method was used for platelet cross-matching. The corrected count increment was used to monitor the effectiveness of each platelet transfusion. Multivariate analysis was performed to detect whether any variables could predict the response to transfusion. RESULTS: Statistically significant improvements were found in the mean corrected count increment when comparing cross-match-compatible platelets with randomly selected and incompatible platelets (p<0.001 for each). Compatible platelet transfusions were associated with a good response in 72.9% of cases while incompatible platelets were associated with a poor response in 66.7% of transfusion events (p<0.001). In the presence of clinical factors or alloimmunisation, compatible platelets were associated with good responses in 67.9% and 28.0% respectively vs 100% and 93.3% in their absence (p=0.009, p<0.001). Multivariate analysis revealed that cross-matching and alloimmunisation were the strongest predictors of transfusion response at 1 hour, while ABO compatibility, type of units received, followed by alloimmunisation then clinical factors were predictors at 24 hours. DISCUSSION: Platelet cross-matching using the solid-phase red cell adherence technique is an effective and rapid first-line approach for the management of patients refractory to platelet transfusions.

Gravin gene expression in acute myeloid leukemia.

Acute leukemias are caused by genetic and epigenetic mechanisms involving tumor suppressor genes and oncogenes. Aberrant DNA methylation patterns are the most frequent molecular alterations detected in acute myeloid leukemia (AML). Gravin is down-regulated in several solid tumors and is implicated in tumorigenesis. To explore its role in the molecular pathogenesis and its possible prognostic importance in AML, we have evaluated the expression levels of the gravin gene in 83 acute myeloid leukemia patients as compared with controls using quantitative real-time polymerase chain reaction (qRT-PCR). Mean gravin expression was 0.53 ± 1.34 and 8.81 ± 11.6 for patients and controls, respectively, and was found to be about 16-fold lower than controls. Gravin gene expression was lower than controls in 83.1 % (69/83) and was similar to controls in 16.9 % (14/83) of cases (p < 0.0001). It was found that there was no significant correlation between gravin expression and laboratory prognostic markers (p > 0.05). Gravin expression was highest in complete remission (1.065 ± 1.79) and lowest in relapse (0.019 ± 0.03) with a statistical difference (p = 0.004). Patients with gravin expression below median level had higher risk to develop relapse (OR = 8.689, 95 % CI = 2.464-30.638; p < 0.0001). No statistical correlation was reported between gravin expression and survival times (OS, DFS) (p = 0.482, 0.409, respectively), and this was confirmed in multivariate analysis. Gravin gene expression was found to be decreased in acute myeloid leukemia, and the degree of its decreased expression has been found to be correlated with poor prognosis.

Cytokeratin 20 and vascular endothelial growth factor as molecular markers in Egyptian patients with colorectal cancer.

PURPOSE: To investigate the expression of cytokeratin 20 (CK20) and vascular endothelial growth factor (VEGF) in the peripheral blood of colorectal cancer (CRC) patients, and correlate the findings with the pathologic data of the patients. METHODS: This study was carried out on 50 subjects, 40 patients with histologically confirmed colorectal carcinoma undergoing elective surgery and 10 healthy individuals matched for age and sex. Total RNA extraction followed by real time quantitative RT-PCR and real time TaqMan quantitative assay for peripheral blood expression of CK20 and VEGF was done for both patients and controls. RESULTS: (1) Statistically significant high levels of CK20,VEGF, CEA (p = 0.000 each) and CA19-9 (p = 0.002) in CRC patients when compared with controls; (2) Statistically significant increase in the expression of CK20 in advancing CRC stage C (p = 0.001) and with LN metastasis (p = 0.000); (3) Statistically significant increase in the expression of VEGF in advancing CRC stage C (p = 0.002), pathologic grade (p = 0.038), and with LN metastasis (p = 0.004); and (4) statistically positive correlation between CK20 and VEGF expressions, and also between these markers and CEA level. CONCLUSION: CK20 and VEGF expressions in peripheral blood of CRC patients are promising molecular markers for CRC progression and metastasis.

Mutations of p53 gene in breast cancer in the Egyptian province of Dakahliya.

BACKGROUND: Breast cancer is the most common malignancy among females worldwide. Molecular analysis of p53 is likely to have value in diagnosis, prognosis, and treatment of breast cancer. OBJECTIVE: To study the frequency and spectrum of p53 gene mutations in breast cancer patients residing Al Dakahliya district in the north of Egypt. MATERIALS AND METHODS: Thirty patients with cancer breast as well as 10 controls were evaluated for p53 status by flow-cytometry, PCR-SSCP, and sequencing analysis. RESULTS: P53 mutations were evident in five breast cancer patients (17%) including two missense mutations (A218 T and R279 G) in exon 6, 8; nonsense mutations (S297stop and Y159stop) in exon 8, 5, respectively, and frame shift mutation (M133 fs) in exon 5. p53 mutations were associated with invasive ductal carcinoma, large tumor size, and advanced disease stage CONCLUSION: p53 gene mutations is potentially responsible for pathogenesis and clinical aggressiveness of breast cancer in our locality.

Expression of lung resistance protein and multidrug resistance-related protein (MRP1) in pediatric acute lymphoblastic leukemia.

Multidrug resistance (MDR) is a phenomenon by which cells become resistant to unrelated chemotherapeutic agents. The prognostic value that lung resistance protein (LRP) and multidrug resistance-related protein 1 (MRP1) have in the setting of pediatric acute lymphoblastic leukemia (ALL) is controversial. The aim of this study was to investigate the expression of LRP and MRP1 and effect on clinical outcome and prognosis. The mRNA expression of LRP and MRP1 were analyzed in leukemic blasts of 34 pediatric ALL patients. LRP and MRP1 mRNA expression were detected in 41.2% and 35.3%, respectively. Eleven (91.7%) of 12 patients without LRP achieved CR compared with 9 (50.0%) of 18 with LRP expression. Similarly, 11 (100%) of 11 patients without MRP1 expression achieved CR compared with 9 (47.4%) of 19 with MRP1 expression and higher LRP expression rate or MRP1 expression rate was present in patients with relapse than MDR genes negative patients. The expression of either of two genes was associated with poorer 2-year survival. Also, patients expressing both genes had poorer outcomes and had worse 2-year survival. We suggest that MDR expression affects complete remission and survival rates in ALL patients. Thus, diagnosis appears to provide prognostic information for pediatric ALL.