Role of ancillary techniques in diagnosis, therapy and prognosis of a case of precursor B-cell acute lymphoblastic leukemia in an elderly patient

The chromosomal abnormality of Philadelphia chromosome is mostly seen in Chronic Myeloid Leukemia (CML). But it is observed that the Philadelphia chromosome (Ph), t(9,22), is the most common cytogenetic abnormality in adult patients with acute lymphoblastic leukemia (ALL), occurring in about 20% to 30 % of all cases. Patients with Ph-positive ALL have breaks in the minor breakpoint region, m?BCR (exons 1?2) lead to a short fusion proteins (p190) and is most frequently associated with Ph chromosome- positive ALL. They have an increased risk for central nervous system (CNS) involvement, an aggressive clinical course and poor prognosis. Historically, they had an inferior outcome when compared with their Ph-negative counterparts. Adult Ph+ patients achieve Complete Remission rates comparable to Ph? ALL patients with standard chemotherapy, but the remissions are short and survival poor. The addition of tyrosine kinase inhibitors (TKIs) including imatinib has dramatically improved outcomes. We are presenting this case report of t(9;22), p190 BCR-ABL1 positive ALL in an elderly female patient of south Gujarat.

Effect of whole-brain radiotherapy and TKIs on suvival of patients with brain metastases from non-small cell lung cancer stratified by EGFR mutation status / 中国肿瘤临床

Objective: To compare overall survival (OS) and intracranial progression-free survival (iPFS) effects of whole-brain radiotherapy (WBRT) and tyrosine kinase inhibitors (TKIs) in NSCLC patients with brain metastases (BM) stratified by EGFR mutation status (mutant, wild-type). Methods: We performed a retrospective analysis of 215 NSCLC BM patients diagnosed in January 2013 to January 2015 with known EGFR status and followed up to December 1, 2016. Stratified Kaplan-Meier curves and multivariate Cox models were used to evaluate the effects of WBRT (defined as≥30 Gy, "W") and TKIs (after BM, "T") on OS and iPFS independently and jointly. Two-sided P>0.20 was considered non-significant (ns). Results: In patients with BM, the mean age was 58 years, 52% were female, and 93% had adenocarcinoma. Those with EGFR mutations (114 patients) had "W" (35 patients) and "T" (87 patients) with adjusted hazard ratios (HRs) (P) of 1.135 (ns) and 0.202 (P<0.001) for OS, respectively, and 1.122 (ns) and 0.275 (P<0.001) for iPFS, respectively. "W+T" (22 patients), "T only" (65 patients), "W only"(13 patients), and "neither" (14 patients) had OS-median survival time (MST) of 14.1, 15.3, 7.1, and 4.3 months, respectively; their iPFS-MST were 14.1, 13.4, 6.8, and 4.5 months, respectively. Their adjusted HRs (P) were 0.196 (P=0.003), 0.114 (P<0.001), 0.434 (ns), 1.000 (ref) for OS, respectively, and 0.272 (P=0.012), 0.200 (P<0.001), 0.622 (ns), 1.000 (ref) for iPFS, respectively. Compared with "T only," "W+T" was not associated with better survival and "W only" had adjusted HRs (P) of 3.804 (P=0.025) for OS and 3.114 (P=0.032) for iPFS. The EGFR wild-type (101 patients) used "W" in 43 patients with OS-MST of 11.3 (7.1) and iPFS of 11.2 (4.8) months; the adjusted HRs (P) of "W"were 0.539 (P=0.105) for OS and 0.485 (P=0.048) for iPFS. Conclusions: In EGFR-mutant NSCLC BM patients, TKIs are associated with improved survival, whether, WBRT alone or combined are not. In cases of EGFR wild-type, WBRT confers the improved the iPFS.

Novel EGFR-TK Inhibitor EKB-569 Inhibits Hepatocellular Carcinoma Cell Proliferation by AKT and MAPK Pathways

Epidermal growth factor receptor (EGFR)-targeted therapies have been effective in some cancers, but not in hepatocellular carcinoma (HCC). The aim of this study was to investigate the drug potential to overcome multi-drug resistance in HCC cells. Thirteen drug-sensitive HCC cells were assessed using the CCK-8 assay. G0-G1 arrest was measured by FACS. Western blot analysis was used to detect the key enzymes in both the Ras/Raf and PI3K pathways. When establishing the IC50 of HCC to several drugs, including EKB-569, sorafenib, erlotinib, gefitinib, pazopanib, and brivanib, SK-Hep1 cells treated with EKB-569 have shown the highest (72.8%-86.4%) G0-G1 arrest and decreased the phosphorylation of AKT and ERK at the protein level. We found that EKB-569 had higher efficacy in HCC, compared to first generation, reversible EGFR-TK inhibitors. Furthermore, the combination of sorafenib and EKB-569 showed a synergistic effect to inhibit proliferation of SNU-475, previously the most resistant cell to EGFR-TKIs. Therefore, novel EKB-569 in combination with sorafenib may be able to overcome HCC resistance to EGFR-TK inhibitors.