MST1R as a potential new target antigen of chimeric antigen receptor T cells to treat solid tumors.

Although chimeric antigen receptor T cell (CAR-T) is a promising immunotherapy in hematological malignancies, there remain many obstacles to CAR-T cell therapy for solid tumors. Identifying appropriate tumor-associated antigens (TAAs) is especially critical for success. Using a bioinformatics approach, we identified common potential TAAs for CAR-T cell immunotherapy in solid tumors. We used the GEO database as a training dataset to find differentially expressed genes (DEGs) and verified candidates using the TCGA database, obtaining seven common DEGs (HM13, SDC1, MST1R, HMMR, MIF, CD24, and PDIA4). Then, we used MERAV to analyze the expression of six genes in normal tissues to determine the ideal target genes. Finally, we analyzed tumor microenvironment factors. The results of major microenvironment factor analyses showed that MDSCs, CXCL1, CXCL12, CXCL5, CCL2, CCL5, TGF-ß, CTLA-4, and IFN-γ were significantly overexpressed in breast cancer. The expression of MST1R was positively correlated with TGF-ß, CTLA-4, and IFN-γ. In lung adenocarcinoma, MDSCs, Tregs, CXCL12, CXCL5, CCL2, PD-L1, CTLA-4, and IFN-γ were significantly overexpressed in tumor tissues. The expression of MST1R was positively correlated with TGF-ß, CTLA-4, and IFN-γ. In bladder cancer, CXCL12, CCL2, and CXCL5 were significantly overexpressed in tumor tissues. MST1R expression was positively correlated with TGF-ß. Our results demonstrate that MST1R has the potential as a new target antigen for treating breast cancer, lung adenocarcinoma, and bladder cancer and may be used as a progression indicator for bladder cancer.

Neutrophil-to-lymphocyte ratio and risk of lung cancer mortality in a low-risk population: A cohort study.

Neutrophil-to-lymphocyte ratio (NLR) is associated with poor prognosis in patients with lung cancer, but the predictive role of NLR on the risk of developing lung cancer is unknown. We investigated the association between NLR and lung cancer mortality in lung cancer-free adults. A cohort study was performed with 527,124 Korean adults who were free of lung cancer and were followed for up to 16 years. Vital status and lung cancer-related deaths were ascertained through national death records. Hazard ratios (HRs) and 95% confidence intervals (CIs) for lung cancer mortality were estimated using a Cox proportional hazards model. During 4,567,495.8 person-years of follow-up, 574 lung cancer deaths were identified. A higher NLR was positively associated with lung cancer mortality. The multivariable-adjusted HR (95% CI) for lung cancer mortality comparing quintiles 2, 3, 4 and 5 of NLR to the lowest quintile were 1.26 (0.96-1.67), 1.23 (0.93-1.63), 1.33 (1.01-1.75) and 1.47 (1.13-1.92), respectively. The highest risk of lung cancer mortality was also observed in the highest NLR quintile among never-smokers and low-risk individuals after adjusting for lung function and other possible confounders. Platelet-to-lymphocyte ratio showed an inverse J-shaped association with lung cancer mortality in men but the trends in women, low-risk individuals or never-smokers were neither linear nor U-shaped. In this large cohort of young and middle-aged individuals, NLR was independently associated with increased risk of lung cancer mortality in low-risk individuals, indicating a role of systemic inflammation in lung cancer mortality in our study population.

Efficacy and safety of Viscum album extract (Helixor-M) to treat malignant pleural effusion in patients with lung cancer.

PURPOSE: Manifestations of malignant pleural effusions (MPEs) are alleviated by local therapies as well as by systemic treatment. After 2009, when commercial use of talc was discontinued in Korea, we have used Helixor-M, which is derived from the European mistletoe (Viscum album), as an alternative sclerosing agent for pleurodesis. We aimed to evaluate the efficacy and safety of Helixor-M for controlling MPE. METHODS: Between 2009 and 2015, we consecutively enrolled 52 patients with lung cancer, who underwent pleurodesis to treat MPE and were analyzed retrospectively. On day 1, 100 mg of Helixor-M was instilled via pleural catheter. If the procedure was not effective, it was repeated every other day up to five times, and the dose increased each time by 100 mg. The primary study outcome was reappearance of pleural effusion at 1 month after the last pleurodesis procedure. RESULTS: The median age of patient was 63 years, and 77% of the 52 patients were male. About 85% of pleural effusions were found to be malignant by cytogenetic analysis. Forty-two (81%) patients were evaluable for recurrence of MPE. The 1-month recurrence rate was 48% (20/42). Among the 20 patients who developed recurrent MPE, 6 required therapeutic thoracentesis. Thirteen (25%) patients experienced procedure-related pain requiring medication. Eight (15%) had fever > 38 °C. CONCLUSIONS: Our results suggest that a pleurodesis with Helixor-M was an effective and tolerable procedure for controlling MPE in lung cancer patients.

Expression Pattern of Smad4/GATA3 as a Predictor of Survival in Invasive Ductal Carcinoma of the Breast.

BACKGROUND: Smad4 and GATA3 proteins are known prognostic markers in various cancers. Smad4 is a mediator linked to both tumour suppression and progression. GATA3 is a regulator of development and morphogenesis of the mammary gland. We assessed and compared the predictive performance of Smad4 and GATA3 for clinical outcomes in patients with breast cancer. METHODS: The combined expression pattern based on Smad4+/- and GATA3+/- was evaluated by immunostaining using breast cancer tissue microarray, and the relationships between protein expression and clinicopathological variables were analysed. RESULTS: Smad4 expression was only associated with an ill-defined tumour border, whereas GATA3 was associated with several good prognostic factors. On analysis of combined markers, there was a significant difference in the expression of fascin (an important factor for cancer invasiveness) between the Smad4+/GATA3- and Smad4-/GATA3+ groups. Smad4+/GATA3- was correlated with worse clinicopathological parameters, relapse-free survival (RFS), and overall survival (OS), compared to Smad4-/GATA3+. CONCLUSION: Combined markers of Smad4/GATA3 showed a superior performance compared to single markers for predicting RFS and OS in patients with breast cancer.

Invasion Depth Measured in Millimeters is a Predictor of Survival in Patients with Distal Bile Duct Cancer: Decision Tree Approach.

BACKGROUND: AJCC staging system is unreliable for predicting survival in distal bile duct (DBD) cancer patients, due to inter-observer variation. Measured depth of invasion (DOI) is suggested to be more accurate to predict patients' clinical outcome in extra-hepatic cholangiocarcinomas, but its significance in DBD cancer and cutoff values are still debatable. This study aimed to identify the optimal cutoff value of DOI in relation to prognosis in DBD cancer patients. METHODS: Data of 179 patients with DBD adenocarcinoma treated in three institutions were investigated. Under microscopic review, DOI was measured. The relationships between the clinicopathological parameters and the groups based on DOI (≤3; 3-10; >10 mm) were evaluated, and the survival times of each group based on DOI and T classification were compared. RESULTS: Deeply invading tumors exhibited a greater tendency toward the infiltrative type, high histological grade, AJCC stage, and pancreatic, duodenal, lymphovascular and perineural invasion. The measured DOI was significantly correlated with worse relapse-free and overall survival (all p < 0.05). In multivariate analyses, the DOI remained as one of the prognostic factors (all p < 0.05), while T classification was not a significant prognostic factor. The new prognostic models (low, intermediate, and high risk) that applied DOI and nodal metastasis showed significant difference in recurrence and survival rate (all p < 0.05). CONCLUSIONS: On the basis of the proposed cutoff value, the DOI could be clear and meaningful, overcoming the vagueness of the T classification for predicting clinical outcomes in patients with DBD carcinoma.

Imatinib withdrawal syndrome and longer duration of imatinib have a close association with a lower molecular relapse after treatment discontinuation: the KID study.

The aim of the Korean Imatinib Discontinuation Study was to identify predictors for safe and successful imatinib discontinuation. A total of 90 patients with a follow-up of ≥12 months were analyzed. After a median follow-up of 26.6 months after imatinib discontinuation, 37 patients lost the major molecular response. The probability of sustained major molecular response at 12 months and 24 months was 62.2% and 58.5%, respectively. All 37 patients who lost major molecular response were retreated with imatinib therapy for a median of 16.9 months, and all achieved major molecular response again at a median of 3.9 months after resuming imatinib therapy. We observed newly developed or worsened musculoskeletal pain and pruritus in 27 (30%) patients after imatinib discontinuation. Imatinib withdrawal syndrome was associated with a higher probability of sustained major molecular response (P=0.003) and showed a trend for a longer time to major molecular response loss (P=0.098). Positivity (defined as ≥ 17 positive chambers) of digital polymerase chain reaction at screening and longer imatinib duration before imatinib discontinuation were associated with a higher probability of sustained major molecular response. Our data demonstrated that the occurrence of imatinib withdrawal syndrome after imatinib discontinuation and longer duration of imatinib were associated with a lower rate of molecular relapse. In addition, minimal residual leukemia measured by digital polymerase chain reaction had a trend for a higher molecular relapse. (Trial registered at ClinicalTrials.gov: NCT01564836).

High Ki67/BCL2 index is associated with worse outcome in early stage breast cancer.

AIMS: Breast cancers are heterogeneous, making it essential to recognise several biomarkers for cancer outcome predictions. Ki67 proliferation index and B cell lymphoma 2 (BCL2) proteins are widely used as prognostic indicators in many types of malignancies. While Ki67 is a marker of normal or tumour cell proliferation, BCL2 plays a central role in antiproliferative activities. A combination of these two biomarkers with contrary purposes can provide enhanced prognostic accuracy than an analysis using a single biomarker. METHODS: We evaluated Ki67 and BCL2 expression with 203 cases of breast cancer. The relative expression of each biomarker named as Ki67/BCL2 index was divided into two groups (low vs high) with the use of area under receiver operating characteristic curves. RESULTS: There were significant correlations between Ki67/BCL2 index and clinicopathological findings such as age, tumour stage, size and necrosis, histological grade, extensive intraductal component, lymphatic and vascular invasion, oestrogen receptor, progesterone receptor, human epithelial growth factor receptor 2 and p53 expression (all p<0.05). In univariate and multivariate analyses, high Ki67/BCL2 index correlated with shorter disease-free survival and overall survival in patients with early stage invasive ductal carcinoma (all p<0.05). CONCLUSIONS: The Ki67/BCL2 index should be considered as a prognostic predictor in patients with early stage invasive ductal carcinoma.

Chromosome 13 deletion and hypodiploidy on conventional cytogenetics are robust prognostic factors in Korean multiple myeloma patients: web-based multicenter registry study.

This study was designed to evaluate the prevalence of chromosomal abnormalities and to identify the specific abnormalities associated with poor prognosis. A total of 2,474 patients whose conventional cytogenetics were available at the time of diagnosis were evaluated via a nationwide registry. Normal metaphase cytogenetics was observed in 2,012 patients (81.3%). Among the 462 patients with chromosomal abnormalities, there were 161 (34.8%) patients with hyperdiploidy, 197 (42.6%) with pseudodiploidy, 79 (17.1%) with hypodiploidy, and 25 (5.5%) with near-tetraploidy. Deletion 13 (Δ13) in metaphase was observed in 167 patients (6.8%). Fluorescent in situ hybridization (FISH) was carried out in 967 patients (39.1%), and 66 (13.7%) out of 482 and 63 (10.3%) out of 611 patients were positive for t(4;14) and del(17p), respectively. With a median follow-up duration of 25.1 months, the median overall survival (OS) was 51.2 months (95% confidence interval, 46.5-55.9 months). In univariate analysis, the following four chromosomal abnormalities were significantly associated with a poor survival outcome: Δ13, hypodiploidy, del(13q) in FISH, and del(17p) in FISH. In the subsequent multivariate analysis, in which del(13q) and del(17p) in FISH were excluded due to a relatively low number of patients, Δ13 and hypodiploid status were independently associated with a poor survival outcome after adjusting for important clinical factors, including age, sex, performance, beta2-microglobulin, albumin, and lactate dehydrogenase (LDH). Using conventional metaphase cytogenetics, we confirmed that both Δ13 and hypodiploid status were robust poor prognostic factors. The metaphase karyotyping should remain the primary cytogenetic tool and an essential investigation for risk stratification in newly diagnosed multiple myeloma patients.

Comparison of surgical outcomes of transoral robotic and endoscopic thyroidectomy: A systematic review and network meta-analysis.

This study aimed to compare surgical outcomes of transoral robotic thyroidectomy (TORT) and transoral endoscopic thyroidectomy vestibular approach (TOETVA), concurrently compared with conventional transcervical thyroidectomy (CTT). A network meta-analysis, comprising 23 studies, was performed in this study. The operative time of the CTT group was significantly shorter than that of the TOETVA and TORT groups. The hospital stay of the TOETVA group was significantly longer than that of the CTT group. Rates of transient recurrent laryngeal nerve palsy and total complications were higher in association with TOETVA than with TORT. No significant differences were found between the three groups in intraoperative blood loss, retrieved lymph nodes, postoperative pain, and other complications. Cosmetic satisfaction was significantly superior with TORT and TOETVA than with CTT. Compared with CTT, TOETVA and TORT showed superior cosmesis but no significant difference in surgical outcomes except for operative time and hospital stay.

Long-term functional swallowing and speech outcomes after transoral robotic surgery for oropharyngeal cancer.

Objectives: Transoral robotic surgery (TORS) has emerged as a minimally invasive approach for oropharyngeal cancer, aiming to improve functional preservation and reduce morbidity. However, the long-term effects on speech and swallowing, crucial aspects of quality of life, remain unclear. This study investigates the long-term functional swallowing and speech outcomes of TORS for oropharyngeal cancer. Methods: We retrospectively reviewed 41 patients diagnosed with oropharyngeal squamous cell carcinoma who underwent TORS from 2010 to 2018. Tongue mobility, articulation, verbal diadochokinesis, reading speed, and modified barium swallowing tests were performed 2-3 years post-operatively to assess long-term speech and swallowing function. Results: The mean age was 57.7 ± 9.9 years, and the male to female ratio was 34:7. The palatine tonsil was the most common tumor site (73.2%), followed by the base of tongue (22.0%). Concurrent neck dissection was performed in 97.6% of patients, and adjuvant radiation or chemoradiation was administered to 36 patients (87.8%). Tongue mobility, articulation, verbal diadochokinesis, and reading speed were comparable to normal population. Modified barium swallowing tests revealed acceptable outcomes in most patients; only one patient (2.4%) required a percutaneous endoscopic gastrostomy tube. Notably, no permanent tracheostomies were necessary. Conclusions: Long-term speech and swallowing functions were preserved in most patients treated with TORS for oropharyngeal cancer. TORS is an excellent treatment modality for oropharyngeal cancer in terms of functional outcomes.

Early dose reduction of dasatinib does not compromise clinical outcomes in patients with chronic myeloid leukemia: A comparative analysis of two prospective trials.

Dasatinib is a potent second-generation tyrosine kinase inhibitor (TKI) used as a first-line treatment option for patients with chronic myeloid leukemia (CML). Currently, dose modification due to adverse events (AEs) is common in patients treated with dasatinib. This study compared the outcomes of two sequential prospective trials that enrolled patients with newly diagnosed chronic phase of CML (CP-CML) and initiated dasatinib at a starting dose of 100 mg daily. In the PCR-DEPTH study, CP-CML patients who started dasatinib 100 mg daily were enrolled and followed up, while in the DAS-CHANGE study, when patients achieved early molecular response with any grade of AEs were enrolled and treated with dasatinib 80 mg once daily. A total of 102 patients (PCR-DEPTH) and 90 patients (DAS-CHANGE) were compared. Although the median value of the relative dose intensity (RDI) of dasatinib was significantly higher in PCR-DEPTH than in DAS-CHANGE (99.6 % vs. 80.1 %, p <0.001), the MMR rate at 12months showed a trend toward superiority in DAS-CHANGE compared to PCR-DEPTH (77.1 % vs 65.2 %, p = 0.084). The frequencies of MR4.0 at 24 and 36 months were higher in DAS-CHANGE than in PCR-DEPTH (44.4 % vs 28.8 %, p = 0.052 and 63.6 % vs 40.3 %, p= 0.013, respectively). RDIs were not different according to the MMR, MR4.0 or MR4.5 in analyses using a pooled population. Our results suggest that early dose reduction of dasatinib does not compromise efficacy in patients achieving EMR at 3 months and could be an interventional strategy for improving long term outcomes.

Comparison of treatment strategies for patients with intestinal diffuse large B-cell lymphoma: surgical resection followed by chemotherapy versus chemotherapy alone.

The aim of this retrospective cohort study was to analyze the impact of surgery on the outcomes and qualities of life (QOL) in patients with intestinal diffuse large B-cell lymphoma (DLBCL). We assessed 345 patients with either localized or disseminated intestinal DLBCL and compared them according to treatment: surgical resection followed by chemotherapy versus chemotherapy alone. In patients with localized disease (Lugano stage I/II), surgery plus chemotherapy yielded a lower relapse rate (15.3%) than did chemotherapy alone (36.8%, P < .001). The 3-year overall survival rate was 91% in the surgery plus chemotherapy group and 62% in the chemotherapy-alone group (P < .001). The predominant pattern in the chemotherapy group was local relapse (27.6%). When rituximab was used with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP), there was no improvement of the outcomes in patients treated with primary surgical resection. The QOL of patients who underwent surgery and chemotherapy was lower than chemotherapy alone, but its difference was acceptable. Multivariate analysis showed that surgical resection plus chemotherapy was an independent prognostic factor for overall survival. Surgical resection followed by chemotherapy might be an effective treatment strategy with acceptable QOL deterioration for localized intestinal DLBCL. This study was registered at www.clinicaltrials.gov as #NCT01043302.

Predictive factors for successful imatinib cessation in chronic myeloid leukemia patients treated with imatinib.

Although recent studies have suggested that cessation of imatinib (IM) in chronic myeloid leukemia patients can be associated with sustained response, further validation is needed to explore predictive factors. In a prospective, multicenter study, chronic phase patients were eligible for cessation of IM therapy after more than 3 years if they had no detectable BCR-ABL1 transcript for at least 2 years. A total of 48 patients with a median age of 47 years (19-74 years) were enrolled. Twenty patients received IM for post-transplant relapse. After a median follow-up of 15.8 months (1.4-28.2 months) after IM discontinuation, nine of the non-transplant group lost undetectable molecular residual disease (UMRD) and major molecular response (MMR), whereas none of the 20 patients in the transplant group experienced UMRD loss. Probabilities for sustained MMR and UMRD were 64.4% and 66.3% in the non-transplant group, respectively. Of nine patients re-treated with IM, eight patients re-achieved MMR at a median of 1.7 months (0.9-2.8 months). Seven of these patients re-achieved UMRD at a median of 5.6 months (2.8-12.1 months). Previous transplantation, IM duration, and UMRD duration were significantly associated with sustained molecular responses. Our data strongly suggest that immunological control contributes to sustained suppression of residual leukemia cell expansion and that IM can be safely discontinued in patients with post-transplant relapse.

Low gamma-butyrobetaine dioxygenase (BBOX1) expression as a prognostic biomarker in patients with clear cell renal cell carcinoma: a machine learning approach.

Gamma-butyrobetaine dioxygenase (BBOX1) is a catalyst for the conversion of gamma-butyrobetaine to l-carnitine, which is detected in normal renal tubules. The purpose of this study was to analyze the prognosis, immune response, and genetic alterations associated with low BBOX1 expression in patients with clear cell renal cell carcinoma (RCC). We analyzed the relative influence of BBOX1 on survival using machine learning and investigated drugs that can inhibit renal cancer cells with low BBOX1 expression. We analyzed clinicopathologic factors, survival rates, immune profiles, and gene sets according to BBOX1 expression in a total of 857 patients with kidney cancer from the Hanyang University Hospital cohort (247 cases) and The Cancer Genome Atlas (610 cases). We employed immunohistochemical staining, gene set enrichment analysis, in silico cytometry, pathway network analyses, in vitro drug screening, and gradient boosting machines. BBOX1 expression in RCC was decreased compared with that in normal tissues. Low BBOX1 expression was associated with poor prognosis, decreased CD8+ T cells, and increased neutrophils. In gene set enrichment analyses, low BBOX1 expression was related to gene sets with oncogenic activity and a weak immune response. In pathway network analysis, BBOX1 was linked to regulation of various T cells and programmed death-ligand 1. In vitro drug screening showed that midostaurin, BAY-61-3606, GSK690693, and linifanib inhibited the growth of RCC cells with low BBOX1 expression. Low BBOX1 expression in patients with RCC is related to short survival time and reduced CD8+ T cells; midostaurin, among other drugs, may have enhanced therapeutic effects in this context.

Effectiveness of pegfilgrastim prophylaxis in preventing febrile neutropenia during R-FC chemoimmunotherapy for chronic lymphocytic leukemia: A multicenter prospective phase II study.

Background: A chemotherapy of rituximab, fludarabine and cyclophosphamide (R-FC) has been accepted as a promising frontline chemotherapy in selected patients with chronic lymphocytic leukemia (CLL). Although R-FC regimen is a relatively dose-dense regimen and neutropenia incidence is more than 50%, primary prophylactic pegfilgrastim was not fully recommended in the clinical field. Therefore, the study evaluated the prophylactic effectiveness of pegfilgrastim to reduce the incidence of febrile neutropenia associated with R-FC of patients with CLL. Patients and methods: A single-arm, multicenter, prospective phase II study was designed to assess the efficacy of prophylactic pegfilgrastim. Thirty-four CLL patients were enrolled and analyzed for neutropenia and other related factors, and comparative analysis was performed with historical cohort. Results: Compared with our historical cohort, incidence of grade 3-4 neutropenia and febrile neutropenia was remarkably reduced during any cycle of chemotherapy (14.7% vs. 48.2% of study cohort vs. historical cohort during C1, 5.9% vs. 65.8% during C2, 12.9% vs. 80.6% during C3, 10% vs. 84.6% during C4, 3.4% vs. 83.6% during C5, and 10.7% vs. 85.7% during C6, p <0.001). Also, cumulative incidence of disrupted chemotherapy was noticeably reduced in study cohort on any cycles of R-FC regimen (8.8% vs. 22.2% of study cohort vs. historical cohort on C2, 9.7% vs. 25.2% on C3, 13.4% vs. 26.9% on C4, 13.8% vs. 45.2% on C5, 17.9% vs. 47.3% on C6, p=0.007). In addition, treatment-related mortality was 5.9%, which significantly reduced compared to 9.6% of our historical cohort (HR 0.64, 95% CI 0.42-0.79, P = 0.032). Conclusion: Primary prophylactic pegfilgrastim is effective in the prevention of neutropenia/febrile neutropenia, and infection-related mortality during R-FC regimen in patients with CLL.

Intensified First Cycle of Rituximab Plus Eight Cycles of Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone with Rituximab Chemotherapy for Advanced-Stage or Bulky Diffuse Large B-Cell Lymphoma: A Multicenter Phase II Consortium for Improving Survival of Lymphoma (CISL) Study.

PURPOSE: This phase II, open-label, multicenter study aimed to investigate the efficacy and safety of a rituximab intensification for the 1st cycle with every 21-day of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP-21) among patients with previously untreated advanced-stage or bulky diffuse large B-cell lymphoma (DLBCL). MATERIALS AND METHODS: Ninety-two patients with stage III/IV or bulky DLBCL from 21 institutions were administered 8 cycles of R-CHOP-21 with an additional one dose of rituximab intensification on day 0 of the 1st cycle (RR-CHOP). The primary endpoint was a complete response (CR) rate after 3 cycles of chemotherapy. RESULTS: Among the 92 DLBCL patients assessed herein, the response rate after 3 cycles of chemotherapy was 88.0% (38.0% CR+50.0% partial response [PR]). After the completion of 8 cycles of chemotherapy, the overall response rate was observed for 68.4% (58.7% CR+9.8% PR). The 3-year progression-free survival rate was 64.0%, and the 3-year overall survival rate was 70.4%. Febrile neutropenia was one of the most frequent grade 3 adverse events (40.0%) and 5 treatment-related deaths occurred. Compared with the clinical outcomes of patients who received R-CHOP chemotherapy as a historical control, the interim CR rate was higher in male patients with RR-CHOP (20.5% vs. 48.8%, p=0.016). CONCLUSION: Rituximab intensification on days 0 to the 1st cycle of the standard 8 cycles R-CHOP-21 for advanced DLBCL yielded favorable response rates after the 3 cycles of chemotherapy and acceptable toxicities, especially for male patients. ClinicalTrials.gov ID: NCT01054781.

Allogeneic hematopoietic stem cell transplant for adults over 40 years old with acquired aplastic anemia.

Although younger age is associated with favorable prognosis in adults undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) for aplastic anemia (AA), other pretransplantation factors may be more important than age. We retrospectively analyzed the impact of older age on transplantation outcomes and survival in a total of 225 adult patients with AA who underwent allo-HSCT: 57 patients >40 years old (older patient group [OPG]) and 168 patients ≤40 years old (younger patient group [YPG]). Age at allo-HSCT ≤40 years, time from diagnosis to allo-HSCT ≤6 months, and matched related donor (MRD) were favorable prognostic factors in all study patients. Risk analysis of survival in the OPG showed that age >50 years was the only poor prognostic factor. Survival did not differ significantly between the YPG and patients <50 years old in the OPG. In conclusion, patients between the ages of 41 and 50 years with severe AA and MRDs should undergo allo-HSCT as early as possible to optimize survival.

Laparoscopic lymphadenectomy for isolated lymph node recurrence in gynecologic malignancies.

STUDY OBJECTIVE: To assess the feasibility and efficacy of laparoscopic lymphadenectomy in patients with isolated lymph node recurrences (ILNR) who underwent initial surgery because of gynecologic malignancy. DESIGN: Retrospective study (Canadian Task Force classification II-3). SETTING: University teaching hospital. PATIENTS: Six patients with ILNR (1 cervical, 4 ovarian, and 1 peritoneal) diagnosed between March 2003 and July 2010. INTERVENTION: Laparoscopic lymphadenectomy. MEASUREMENTS AND MAIN RESULTS: Median (range) patient age was 59.5 (24-70) years, and body mass index was 21.7 (21.0-24.6). There was no unplanned conversion to laparotomy. Operating time was 337.5 (200-400) minutes, hemoglobin change was 0.9 (0.4-2.6) g/dL, and hospital stay was 8.5 (5-19) days. The number of harvested lymph nodes was 20 (5-27), and of positive lymph nodes was 4 (1-24). One patient had common iliac vein laceration, with complete hemostasis achieved using intracorporeal suture. Postoperative lymphedema occurred in 1 patient, and was managed conservatively. All patients received adjuvant chemotherapy after laparoscopic lymphadenectomy. CONCLUSION: Laparoscopic lymphadenectomy in patients with ILNR is feasible and might be an alternative therapeutic strategy.

Prognostic significance of BLK expression in R-CHOP treated diffuse large B-cell lymphoma.

BACKGROUND: The aim of the present study was to evaluate the prognostic significance of B-cell lymphocyte kinase (BLK) expression for survival outcomes in diffuse large B-cell lymphoma (DLBCL) patients treated with R-CHOP. METHODS: We retrospectively analyzed the medical records of 89 patients from two tertiary referral hospitals. The expression of BLK, SYK, and CDK1 were evaluated in a semiquantitative method using an H-score, and the proportions of BCL2 and C-MYC were evaluated. RESULTS: A total of 89 patients received R-CHOP chemotherapy as a first-line chemotherapy. The expression rates of BLK in tumor cells was 39.2% (n = 34). BLK expression status was not significantly associated with clinical variables; however, BLK expression in tumor cells was significantly associated with the expression of both C-MYC and BCL2 (p = .003). With a median follow-up of 60.4 months, patients with BLK expression had significantly lower 5-year progression-free survival (PFS) and overall survival rates (49.8% and 60.9%, respectively) than patients without BLK expression (77.3% and 86.7%, respectively). In multivariate analysis for PFS, BLK positivity was an independent poor prognostic factor (hazard ratio, 2.208; p = .040). CONCLUSIONS: Here, we describe the clinicopathological features and survival outcome according to expression of BLK in DLBCL. Approximately 39% of DLBCL patients showed BLK positivity, which was associated as a predictive marker for poor prognosis in patients who received R-CHOP chemotherapy.

Safety and efficacy of nilotinib in adult patients with chronic myeloid leukemia: a post-marketing surveillance study in Korea.

Background: Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea. Methods: An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph+ CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response. Results: During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients). Conclusion: This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph+ CML in routine clinical practice settings.