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.

PVR (CD155) Expression as a Potential Prognostic Marker in Multiple Myeloma.

Poliovirus receptor (PVR, CD155) is upregulated during tumor progression, and PVR expression is associated with poor prognosis in cancer patients; however, prognostic implications for PVR in multiple myeloma (MM) have not been investigated. PVR plays an immunomodulatory role by interacting with CD226, CD96, and TIGIT. TIGIT is a checkpoint inhibitory receptor that can limit adaptive and innate immunity, and it binds to PVR with the highest affinity. We used immunohistochemistry, ELISA, qPCR, and flow cytometry to investigate the role of PVR in MM. PVR was highly expressed in patients with MM, and membrane PVR expression showed a significant correlation with soluble PVR levels. PVR expression was significantly associated with the Revised-International Staging System stage, presence of extramedullary plasmacytoma and bone lesion, percentage of bone marrow plasma cells (BMPCs), and ß2-microglobulin levels, suggesting a possible role in advanced stages and metastasis. Furthermore, TIGIT expression was significantly correlated with the percentage of BMPCs. Patients with high PVR expression had significantly shorter overall and progression-free survival, and PVR expression was identified as an independent prognostic factor for poor MM survival. These findings indicate that PVR expression is associated with MM stage and poor prognosis, and is a potential prognostic marker for MM.

Changes in facial temperature measured by digital infrared thermal imaging in patients after transnasal sphenopalatine ganglion block: Retrospective observational study.

Sphenopalatine ganglion block (SPGB) is a technique developed in the 1990s for the management of head and neck pain patients. Recently, transnasal sphenopalatine ganglion block (TN-SPGB) has been widely used for these patients; however, no objective methods exist for validating the success of TN-SPGB. In this study, we measured the changes in facial temperature before and 30 minutes after TN-SPGB by using digital infrared thermal imaging (DITI) to validate its success.The medical records of patients, who underwent TN-SPGB and facial DITI between January 2016 and December 2017, were reviewed. TN-SPGB and facial DITI were performed 36 times in 32 patients. The changes in facial temperatures measured at the forehead (V1), maxillary area (V2), and mandibular area (V3) by using DITI before and 30 minutes after TN-SPGB were recorded and compared. The temperatures on the ipsilateral and contralateral sides of these areas were also compared. The comparison between pain relief group and pain maintenance group was analyzed.After TN-SPGB, the temperature decreased significantly on both sides of V1 (P = .0208, 0.0181). No significant differences were observed between the ipsilateral and contralateral sides (P > .05). There was no correlation between changes in temperature and changes in pain score in the pain regions after the procedure (P > .05).The temperature decreased significantly in V1 area at 30 minutes after TN-SPGB compared with the temperature before TN-SPGB. Based on these results, we propose using DITI to measure temperature changes as an objective method for verifying the success of TN-SPGB.

Efficacy and safety of blinatumomab treatment in adult Korean patients with relapsed/refractory acute lymphoblastic leukemia on behalf of the Korean Society of Hematology ALL Working Party.

Blinatumomab, a bispecific T cell-engaging antibody, has demonstrated efficacy for relapsed or refractory acute lymphoblastic leukemia (ALL). In this study, we evaluated the efficacy and toxicity of blinatumomab in adult Korean patients with relapsed or refractory Philadelphia-negative B cell precursor ALL. A total of 50 patients received blinatumomab treatment between June 2016 and August 2017 in Korea. The median number of prior therapy was one (range, 1-4). Among the 49 evaluable patients, 22 (44.9%) achieved complete response (CR) or CR with incomplete blood count recovery, and 16 of whom subsequently underwent allogenic stem cell transplantation. Although no statistically significant differences were observed, patients with extramedullary disease and poor performance status had lower responses to blinatumomab treatment. In addition, the use of high-dose dexamethasone prior to blinatumomab treatment did not affect the response to blinatumomab. The median event-free survival and overall survival of the responders were 7.5 and 8.1 months, respectively. For non-hematologic toxicities, the most common toxicity was infection. The incidences of severe cytokine release syndrome and neurologic toxicity each was 4%. In conclusion, blinatumomab was an effective and tolerable therapy in adult Korean patients with relapsed or refractory Philadelphia-negative B cell precursor ALL.

Autologous stem cell transplantation with busulfan, cyclophosphamide, and etoposide as an intensifying frontline treatment in patients with peripheral T cell lymphomas: a multicenter retrospective trial.

The effectiveness of high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) as a frontline treatment in peripheral T cell lymphomas (PTCLs) is still unclear. We retrospectively investigated the clinical outcomes of HDT/ASCT as an intensifying frontline treatment in 31 patients with newly diagnosed PTCLs. The conditioning regimen of HDT/ASCT consisted of busulfan, cyclophosphamide, and etoposide (BuCyE). At diagnosis, five (16.1 %) patients were classified as high risk according to the prognostic index for PTCL (PIT). The disease status of the patients before HDT/ASCT consisted of 23 patients (74.2 %) with complete response (CR) and eight patients (25.8 %) with partial response (PR). Six (75 %) out of eight patients with PR at pretransplantation were improved in terms of the response to CR after HDT/ASCT. At a median follow-up of 32.4 months, the 3-year probability of overall survival (OS) and progression-free survival (PFS) was 64.5 ± 8.6 %. Transplant-related mortality occurred in three patients (9.7 %), due to septic shock, hemorrhage, and delayed pneumonia, respectively. Bone marrow involvement of PTCL at diagnosis was a poor prognostic factor for OS. In conclusion, frontline HDT/ASCT with a conditioning regimen of BuCyE may be an effective and tolerable intensifying therapeutic option to improve outcomes in patients with PTCLs.

Phase II trial of rituximab plus CVP combination chemotherapy for advanced stage marginal zone lymphoma as a first-line therapy: Consortium for Improving Survival of Lymphoma (CISL) study.

We conducted a multicenter, phase II trial to investigate the efficacy and safety of rituximab plus CVP (R-CVP) combination therapy for patients with previously untreated stage III or IV marginal zone lymphoma (MZL). The treatment consisted of rituximab 375 mg/m(2), cyclophosphamide 750 mg/m(2) and vincristine 1.4 mg/m(2) (maximum 2.0 mg) being given intravenously on day 1 and oral prednisolone 100 mg on days 1-5. The treatment was repeated every 3 weeks and this was continued for six or eight cycles. Forty-two patients were enrolled from 13 institutes in Korea. Among them, two patients were dropped after the first and second cycles of chemotherapy, respectively, without evaluation. The 40 patients received a total of 287 cycles of R-CVP chemotherapy. The overall response rate was 88% (95% CI, 77-98%) with 24 complete responses (60%). The median duration of response was 28.3 months. After a median follow-up of 38.2 months, the estimated 3-year progression-free survival and overall survival were 59% and 95%, respectively. There were 30/287 cycles (11%) and 5/287 cycles (2%) of grade 3 or 4 neutropenia and febrile neutropenia, respectively. The R-CVP regimen can be an effective and tolerable first-line immunochemotherapy regimen for advanced stage MZL.

Phase II study of paclitaxel, cisplatin, and 5-fluorouracil combination chemotherapy in patients with advanced gastric cancer.

This phase II study evaluated the efficacy and safety of combination chemotherapy with paclitaxel, cisplatin, and 5-fluorouracil (5-FU) in advanced gastric cancer. Patients with histologically confirmed gastric adenocarcinoma were eligible for the study. Paclitaxel (175 mg/m(2)) and cisplatin (75 mg/m(2)) were given as a 1-hr intravenous infusion on day 1, followed by 5-FU (750 mg/m(2)) as a 24-hr continuous infusion for 5 days. This cycle was repeated every 3 weeks. Forty-five eligible patients (median age, 56 yr) were treated in this way. Of the 41 patients in whom efficacy was evaluable, an objective response rate (ORR) was seen in 51.2% (95% CI, 0.35-0.67), a complete response in two, and a partial response in 19 patients. The median progression free survival was 6.9 months (95% CI, 5.86-7.94 months), and the median overall survival was 12.7 months (95% CI, 9.9-15.5). The main hematological toxicity was neutropenia and greater than grade 3 neutropenia was observed in twelve patients (54%). Febrile neutropenia developed in three patients (6.8%). The major non-hematological toxicities were asthenia and peripheral neuropathy, but most of patients showed grade 1 or 2. In conclusion, combination chemotherapy with paclitaxel, cisplatin, and 5-FU is a promising regimen, and was well tolerated in patients with advanced gastric cancer.

Newly developed multiple myeloma in a patient with primary T-cell lymphoma of bone.

Primary non-Hodgkin's lymphoma of bone (PLB) is rare, and generally presents as a single extensive and destructive bone lesion. Histopathologically, most cases present as diffuse large B-cell lymphoma, and T-cell lymphoma is rare. By contrast, multiple myeloma is a disease defined as the neoplastic proliferation of a single clone of plasma cells producing a monoclonal immunoglobulin. We report a case of multiple myeloma that developed during treatment of PLB in a type of T-cell. A 48-yr-old man was diagnosed as T-cell PLB, stage IE, 18 months ago. The patient received the chemoradiotherapy and salvage chemotherapy for PLB. However, the lymphoma progressed with generalized bone pain, and laboratory findings showed bicytopenia and acute renal failure. On bone marrow biopsy, the patient was diagnosed as having multiple myeloma newly developed with primary T-cell lymphoma of bone. In spite of chemotherapy, the patient died of renal failure.

Relationship between dendritic cells and activated eosinophils in induced sputum of asthmatics.

It has been suggested that dendritic cells (DCs) are critical antigen presenting cells for eosinophilic airway inflammation in a mouse model of asthma, and cysteinyl leukotrienes may play a role in DC trafficking in asthmatics. We investigated whether the number of DCs is increased in the induced sputum of both atopic and nonatopic asthmatics and is related to activated eosinophil count in the sputum. Sputum was induced by inhalation of hypertonic saline in 9 atopic and 12 nonatopic asthmatics and 10 nonatopic normal controls, and differential cell counts were performed. DCs and activated eosinophils were identified by immunocytochemistry with monoclonal antibodies (anti-CD1a and EG2, respectively). There were significantly higher percentages of eosinophils, EG2+ cells, and CD1a+ DC in the sputum of atopic and nonatopic asthmatics compared with normal controls, respectively. In asthmatics, the percentage of CD1a+ DC was significantly correlated with that of EG2+ cells (Rs=0.62, p=0.004). We demonstrated that the increased number of DCs was evident in the induced sputum of both atopic and nonatopic asthmatics, and the DC number was related to the activated eosinophil count, which suggests that DCs may contribute to the ongoing eosinophilic inflammation in asthmatic airways, and vice versa.