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.

Versatile Usage of the Modified Lateral Mass Screw as an Alternative to Cervical Pedicle Screw Fixation.

OBJECTIVE: Posterior subaxial cervical screw fixation is commonly performed using the cervical pedicle screws (CPS) and lateral mass screws (LMS); however, their compatibility is low. Modified lateral mass screws (mLMS, also called paravertebral foramen screw) fixation was introduced as a salvage technique for LMS fixation and has features of both LMS and CPS techniques. In the present study, the use of mLMS as an alternative to CPS was analyzed based on clinical results. METHODS: Seventy-eight screws (38 CPSs and 40 mLMSs) were inserted into 12 patients. The misplacement of the screws was evaluated by computed tomography (CT). The failure of instrumentation and instability were evaluated using plain radiographs. RESULTS: The total number of CPS misplacements was 3 (10.5%); however, neurologic complications were not observed. mLMSs were used in the middle segments of the fusion in 10 patients and 2 patients had mLMS fixation for single-level fusion. An additional bridging implant was not required for connecting both CPSs and mLMSs. Instability was not observed during the observation period (4-51 months). Complete fusion was seen in 10 patients. CONCLUSIONS: The alternative mLMS fixation can decrease the risk of screw misplacement compared with CPS fixation alone and achieves adequate stability leading to fusion.

Optimization and validation of a fluorogenic dipeptidyl peptidase 4 enzymatic assay in human plasma.

During the development of a specific dipeptidyl peptidase 4 (DPP4) inhibitor to treat type 2 diabetes, a fluorogenic kinetic analysis for DPP4 enzymatic activity using Gly-Pro-Aminomethylcoumarin (AMC) as a substrate was optimized and validated for recombinant DPP4 and human plasma samples. The sensitivity, calibration curve, detection range, accuracy, precision, recovery efficiency, Km constant, short/long-term stability, and stability after freezing-thawing cycles were analyzed. DPP4 enzymatic activity (mU/min) was measured as the initial velocity (Vo) of the enzymatic reaction over time. The sensitivity of the Vo value was 14,488 mU/min for recombinant DPP4 and 17,995 mU/min for human plasma samples. The dynamic ranges of the calibration curve were linear and reliable between 1.11 × 104-1.86 × 106 mU/min of the mean Vo value and in the DPP4 concentration range of 23.4-3,000 ng/mL. The assay's accuracy and precision met acceptance criteria for all samples. Plasma DPP4 was stable under various storage temperatures, even after three freeze-thaw cycles. Our optimized, validated bioanalytic method for measuring DPP4 activity in plasma samples was successfully employed to evaluate the effect of evogliptin (DA-1229) tartrate, which irreversibly and dose-dependently inhibits DPP4 enzymatic activity, without the dilution effect of human plasma samples and irrespective of the co-treated metformin.

Phase II study of safety and efficacy of BEB (bendamustine, etoposide, and busulfan) conditioning regimen for autologous stem cell transplantation in non-Hodgkin lymphoma.

Autologous stem cell transplant (ASCT) is an effective treatment for non-Hodgkin lymphoma (NHL). However, recent supply issues and toxicity of carmustine have necessitated a new conditioning regimen. We conducted a multicenter, phase II study of BEB (busulfan, etoposide, and bendamustine) conditioning regimen for ASCT in patients with NHL. Thirty-one patients were enrolled and underwent ASCT with the BEB conditioning regimen. The most common subtype was diffuse large B-cell lymphoma (n = 23, 74.2%). Nine patients (29.0%) had a history of relapse, and 18 patients (58.1%) received more than 2 lines of chemotherapy before ASCT. A median number of 6.05 × 106/kg CD34 cells were infused, and all patients engrafted after a median period of 11 days. Thirteen patients (41.9%) experienced neutropenic fever, and 16 patients (51.6%) had grade 3 or 4 toxicities during ASCT. No one had a documented infection, veno-occlusive disease, or treatment-related death. Three-month complete remission rate was 81.8%. Median follow-up period of 15 months showed 6 patients (19.4%) relapsed or progressed and 3 patients died. The estimated 2-year progression-free survival and overall survival rate were 73.0% and 89.8%, respectively. Our results show that BEB conditioning regimens for ASCT are feasible with tolerable toxicity in patients with NHL.

Long-term Outcome of Angioplasty Using a Wingspan Stent, Post-Stent Balloon Dilation and Aggressive Restenosis Management for Intracranial Arterial Stenosis.

PURPOSE: To investigate the long-term outcome of stent angioplasty for symptomatic severe intracranial artery stenosis. METHOD: In this study 95 consecutive patients with intracranial atherosclerotic stenosis (>70%) underwent stent angioplasty using Wingspan stents. The primary endpoints were stroke or death within 30 days of the procedure and subsequent stroke attributed to the stented vessel. Disabling stroke was defined as stroke with a modified Rankin scale > 3. Secondary endpoints included transient ischemic attacks, contralateral stroke, nonstroke death, and other events. Patients underwent prestent balloon dilation with or without poststent balloon dilation, close restenosis follow-up, and selective retreatment, as required. RESULT: The mean follow-up duration was 34.9 ± 23.3 months. Primary endpoint events occurred in 23% of the patients. The median infarction volume was 2.6 ml, and 11 (68%) of 16 infarctions were <5 ml in volume. Disabling stroke occurred in 3% of patients. The primary endpoint rates were 17.9% within 30 days and 2.1% from 30 days to 1 year. Secondary endpoint events occurred in 27.3% of the patients. Mean stenosis was reduced from 76.8 ± 6.1% to 7.5 ± 13.4%. Of 80 patients who underwent angiographic follow-up, 11 (14%) experienced restenosis (≥50%) and 7 (9%) exhibited restenosis-related symptoms of transient ischemic attack. The rate of symptomatic restenosis was significantly higher in patients who underwent prestent balloon dilation alone than in patients who underwent prestent and poststent balloon dilation (p = 0.016). CONCLUSION: The postprocedural stroke rate was similar to that observed in the SAMMPRIS study. Symptomatic restenosis may be reduced by poststent dilation, close angiographic follow-up, and retreatment.

The effectiveness and safety of lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma in real-world clinical practice: a study of the Korean Multiple Myeloma Working Party (KMMWP-151 study).

Although lenalidomide plus dexamethasone (RD) is a therapeutic option for relapsed/refractory multiple myeloma (RRMM), limited real-world clinical data exist. The purpose of this study was to estimate efficacy and safety of RD in RRMM patients of the clinical practice. Data from patients at 25 university hospitals in South Korea between October 2009 and December 2016 were collected retrospectively. We report the effectiveness and safety of RD in 546 RRMM patients in routine clinical practice in South Korea. Patients (median age, 65 years) typically received median 7 cycles of RD, and 184 (33.7%) patients were treated with 10 or more cycles of RD. Patients with renal impairment (CLCr < 40 mL/min; 10.4%), comorbid conditions (≥ 2; 12.0%), and poor performance status (≥ 2; 25.1%) were included. The overall response rate was 64.2%: complete response (13.1%), very good partial response (VGPR 19.9%). With median follow-up duration of 18.6 months, median PFS and OS were 11.2 months and 25.2 months, respectively. In multivariate analysis, less than 2 comorbid conditions, normal LDH, failed one chemotherapy prior to RD, and ≥ 10 cycles of RD therapy had significantly prolonged PFS (P = 0.007, P = 0.011, P = 0.007, and P < 0.001, respectively). Adverse events were acceptable. RD is effective and safe in real-life clinical practice, including patients with comorbidities. RD is an effective and safe treatment in a real clinical setting which includes patients with comorbidities. Early and continual use of RD treatment may improve RRMM survival outcomes.

Mutation analysis in Korean patients with T-cell acute lymphoblastic leukemia.

Genomic studies have illuminated the alterations in pathways underlying T-cell acute lymphoblastic leukemia (T-ALL) pathogenesis, but detailed mutation data by next-generation sequencing have not been reported in Korean patients. We aimed to investigate mutation frequency, spectrum, and pattern in the Korean patients with T-ALL. We designed a multigene panel targeting 101 genes and validated it using 10 reference materials. The mutation analysis was done in a total of 10 patients with T-ALL. Clinical data and laboratory tests including immunophenotyping, cytogenetics, and molecular genetic tests were also investigated. All of the 10 patients harbored at least one mutation (range 1-6 per patient). A total of 34 clinically significant mutations including 15 novel mutations were identified in 23 genes. The median of variant allelic frequencies (VAFs) and blasts were counted upto 33% (range 5-91%) and 79% (range 38-90%), respectively. Recurrent mutations were involved in epigenetic regulators (60%), NOTCH1 signaling (40%), PI3K-AKT (40%), JAK-STAT (30%), and transcription factors (30%). We found that both NOTCH signaling and JAK-STAT signaling were positively associated with epigenetic regulators, while showed mutually exclusive patterns with PI3K-AKT pathway. This study showed that the frequency of mutations in epigenetic regulators in Korean patients was significantly higher than expected. Distribution of VAF as well as mutation spectrum is considerably heterogeneous in Korean patients with T-ALL. Although from a limited number of patients, this study provides the first detailed mutational portrait of T-ALL of Korean patients, and gives additional insight into molecular pathogenesis of the disease.

Dose Adjustment Helps Obtain Better Outcomes in Multiple Myeloma Patients with Bortezomib, Melphalan, and Prednisolone (VMP) Treatment

Objective: Multiple myeloma (MM) has a better survival outcome because of the development of drugs. However, equivalent outcomes cannot be expected from the same drug. Therefore, how the treatment schedule is managed is important. We analyzed VMP (bortezomib, melphalan, and prednisolone) data to determine an effective treatment strategy. Materials and Methods: We collected the data of 59 patients who were newly diagnosed with MM from January 2012 to April 2017 using electronic medical records. We analyzed baseline characteristics, responses, dose reductions, and survival. Results: The overall response rate was 86.5% [complete response (CR): 32.2%, very good partial response (VGPR): 37.3%]. The median progression-free survival was 33.6 months and the 5-year overall survival rate was 70%. There were significant better progression-free survival outcomes between CR and non-CR for each of the 4 cycles. Of the four patients who achieved CR after the first cycle, none have had disease progression as of yet. We divided patients into two groups according to the median dose (52.1 mg/m2) and we found no differences between the high-dose and low-dose groups. About 78% of patients completed 9-cycle schedules and 84% patients experienced dose reduction, mostly for reasons of non-hematologic toxicities. Conclusion: Active dose reduction helped to continue treatment and it increased the opportunity to be exposed to drugs. In the end, it resulted in improved outcome.

Pralatrexate in patients with recurrent or refractory peripheral T-cell lymphomas: a multicenter retrospective analysis.

Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of non-Hodgkin's lymphomas with poor clinical outcomes. Pralatrexate showed efficacy and safety in recurrent or refractory PTCLs. The purpose or this study was to investigate the efficacy and safety of pralatrexate in relapsed or refractory PTCLs in real-world practice. This was an observational, multicenter, retrospective analysis. Between December 2012 and December 2016, a total of 38 patients with relapsed or refractory PTCLs were treated with pralatrexate at 10 tertiary hospitals in Korea. Patients received an intravenous infusion of pralatrexate at a dose of 30 mg/m2/week for 6 weeks on a 7-week schedule. Modified dosing and/or scheduling was allowed according to institutional protocols. Median patient age was 58 years (range, 29-80 years) and the most common subtype was peripheral T-cell lymphoma, not otherwise specified (n = 23, 60.5%). The median dosage of pralatrexate per administration was 25.6 mg/m2/wk (range, 15.0-33.0 mg/m2/wk). In intention-to-treat analysis, 3 patients (7.9%) showed a complete response and 5 patients (13.2%) showed a partial response, resulting in an overall response rate (ORR) of 21.1%. The median duration of response was 7.6 months (range, 1.6-24.3 months). The median progression-free survival (PFS) was 1.8 months (95% confidence interval [CI], 1.7-1.8 months) and the median overall survival was 7.7 months (95% CI, 4.4-9.0 months). The most common grade 3/4 adverse events were thrombocytopenia (n = 13, 34.2%), neutropenia (n = 7, 23.7%), and anemia (n = 7, 18.4%). Our study showed relatively lower ORR and shorter PFS in patients with recurrent or refractory PTCLs treated with pralatrexate in real-world practice. The toxicity profile was acceptable and manageable. We also observed significantly lower dose intensity of pralatrexate in real-world practice.

Subacute endovascular recanalization of symptomatic cerebral artery occlusion: a propensity score-matched analysis.

BACKGROUND: The interval between the onset of cerebral vessel occlusion and recanalization has been shown to be an independent predictor of poor outcomes. However, endovascular recanalization of symptomatic cerebral vessel occlusion in the subacute period has not been well documented. We investigated the safety and efficacy of subacute recanalization of occluded cerebral vessels in patients with ischemic stroke or transient ischemic attacks (TIAs). METHODS: Between 2014 and 2015, 98 patients were admitted to the emergency room for ischemic stroke or TIA with a small infarct core, which was defined as modest early ischemic change on non-contrast CT or overt diffusion-perfusion mismatch. All patients underwent pre-transfemoral cerebral angiography and post-endovascular treatment. The patients were classified according to acute (onset-to-groin puncture time ≤6 hours) or subacute (onset-to-groin puncture time >6 hours) recanalization. Using propensity score analysis, recipients of acute and subacute recanalization underwent 1:1 matching. RESULTS: Following 1:1 propensity score matching, 32 patients who underwent acute and 32 who underwent subacute intra-arterial thrombolysis were matched. There were no significant differences in National Institutes of Health Stroke Scale at discharge, modified Rankin scale (mRS), the proportion of patients with an mRS value of 0-2, mortality at discharge, intracerebral bleeding, postprocedural infarct extension, newly detected infarction, and hyperintense acute reperfusion marker on follow-up images between the acute and subacute recanalization groups. CONCLUSIONS: In selected patients with clinically unstable cerebral artery occlusions, a diffusion-perfusion mismatch and small CT lesions, subacute and acute recanalization has comparable safety and efficacy rates.

Endovascular management of aneurysms associated with spinal arteriovenous malformations.

BACKGROUND: Spinal aneurysms are rare among spinal arteriovenous malformations (SAVMs). There are few reports of endovascular management of spinal aneurysms associated with SAVM. OBJECTIVE: To present endovascular management of aneurysms associated with SAVM. METHODS: Of 91 patients with SAVMs,eight (9%) presented with aneurysms. Of these, three were male and five were female with a median age of 18 years (range 11-38). We evaluated the presenting pattern, lesion level, type of the target aneurysm related to the presenting pattern and AVM nidus, and the result obtained after embolization or open surgery. Clinical status was evaluated by Aminoff-Logue (ALS) gait and micturition scale scores. RESULTS: The presenting patterns were subarachnoid hemorrhage (SAH, n=3) or mass effect caused by extrinsic (n=4) or intrinsic (n=1) cord compression. Aneurysms were located in four cervical, two thoracic, and two lumbar enlargement areas. There were two prenidal (arterial), three nidal, and three postnidal (venous) aneurysms. The mean diameter of the aneurysms was 9 mm (range 3-27). Glue embolization (n=6), open surgery (n=1), and combined surgery and embolization (n=1) was performed to obliterate the aneurysms. Obliteration of the target aneurysms resulted in improvement of symptoms and clinical stabilization of SAVMs in all patients during a mean of 55 months (range 7-228) of follow-up. CONCLUSIONS: Identification of a symptomatic aneurysm should be associated with clinical presentation pattern. Targeted obliteration of the aneurysm by embolization and/or surgery resulted in improvement of symptoms and stabilization of SAVM.

Therapeutic decision-making in elderly patients with acute myeloid leukemia: conventional intensive chemotherapy versus hypomethylating agent therapy.

Standards of care for elderly acute myeloid leukemia (AML) patients unfit for intensive chemotherapy remain undefined. We aimed to compare outcomes of hypomethylating agent (HMA) therapy and intensive chemotherapy (IC) in elderly AML patients and identify the subgroup of patients who are eligible for HMA therapy. We reviewed data on the outcomes of 86 AML patients aged ≥ 65 years, who had undergone treatment between 2010 and 2015. These treatments included IC (25 patients, 29.1%) or therapy using HMA including azacitidine or decitabine (61 patients, 70.9%). The overall response rates were 32 and 19.7%, respectively. Median overall survival (OS) (8 vs. 8 months) and progression-free survival (PFS) (6 vs. 7 months) durations were similar in the two groups. Patients in the HMA group with less than 10% peripheral blood (PB) blasts achieved significantly better OS duration than patients in the IC group (P = 0.043). Patients in the IC group with PB blasts and bone marrow blast of ≥ 10 and ≥ 50%, respectively, achieved better PFS durations than the corresponding patients in the HMA group (P = 0.038). Multivariate analysis identified the hematologic improvement-platelet (HI-P) as an independent prognostic factor for survival in the HMA group (P = 0.005). Our results showed that HMA therapy and IC were associated with similar survival duration in elderly AML patients. This study was noteworthy because it assessed prognostic factors that would help to select elderly patients who could expect actual benefits from undergoing the different therapeutic options available, especially HMA therapy.

Fosfomycin Biosynthesis via Transient Cytidylylation of 2-Hydroxyethylphosphonate by the Bifunctional Fom1 Enzyme.

Fosfomycin is a wide-spectrum phosphonate antibiotic that is used clinically to treat cystitis, tympanitis, etc. Its biosynthesis starts with the formation of a carbon-phosphorus bond catalyzed by the phosphoenolpyruvate phosphomutase Fom1. We identified an additional cytidylyltransferase (CyTase) domain at the Fom1 N-terminus in addition to the phosphoenolpyruvate phosphomutase domain at the Fom1 C-terminus. Here, we demonstrate that Fom1 is bifunctional and that the Fom1 CyTase domain catalyzes the cytidylylation of the 2-hydroxyethylphosphonate (HEP) intermediate to produce cytidylyl-HEP. On the basis of this new function of Fom1, we propose a revised fosfomycin biosynthetic pathway that involves the transient CMP-conjugated intermediate. The identification of a biosynthetic mechanism via such transient cytidylylation of a biosynthetic intermediate fundamentally advances the understanding of phosphonate biosynthesis in nature. The crystal structure of the cytidylyl-HEP-bound CyTase domain provides a basis for the substrate specificity and reveals unique catalytic elements not found in other members of the CyTase family.

Clinical features and treatment outcome of Epstein-Barr virus-positive nodal T-cell lymphoma.

The classification of mature NK-/T-cell lymphoma mainly originating from the T-cell lineage with predominantly nodal involvement and Epstein-Barr virus (EBV) positivity in a majority of tumor cells is unresolved. We analyzed the clinical features and treatment outcomes of such patients. Five patients with EBV-positive nodal T-cell lymphoma were surveyed during follow-up period. The median age was 53 years (range 33-88 years), and all patients showed nodal involvement. The patients mostly presented advanced clinical features, such as stage III or IV disease, elevated lactate dehydrogenase, and hemophagocytosis. Four patients received cyclophosphamide-containing chemotherapy at the time of diagnosis. However, three patients (75 %) showed disease progression during the early cycles of initial treatment. The median overall survival was 1.5 months (95 % CI 0.0-3.4 months). Patients with EBV-positive nodal T-cell lymphoma mainly show lymph node involvement, but also show aggressive clinical features and poor treatment outcomes, such as aggressive NK-cell leukemia. Therefore, we should consider EBV-positive nodal T-cell lymphoma to be a unique disease entity distinct from peripheral T-cell lymphoma not otherwise specified.

L-asparaginase-based regimens followed by allogeneic hematopoietic stem cell transplantation improve outcomes in aggressive natural killer cell leukemia.

Aggressive nature killer cell leukemia (ANKL) is a mature NK-T cell lymphoma with worse prognosis, but optimal treatment is unclear. Therefore, we analyzed the efficacy of L-asparaginase-based regimens for ANKL patients. Twenty-one patients who received dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) or etoposide, ifosfamide, dexamethasone, and L-asparaginase (VIDL) chemotherapy at Samsung Medical Center were selected. The overall response rate for all patients was 33% (7/21); 38% (5/13) in SMILE and 40% (2/5) in VIDL, respectively. The median progression-free survival was 3.9 months (95% CI 0.0-8.1 months) and median overall survival was 7.0 months (95% CI 2.3-11.7 months). Treatment response (P = 0.001), hematopoietic stem cell transplantation (HSCT) (P = 0.007) and negative conversion of Epstein-Barr virus (EBV) DNA titer after treatment (P = 0.004) were significantly associated with survival. Thus, L-asparaginase-based regimens followed by allogeneic HSCT seem to improve the outcome for ANKL patients.

Clinical Features and Survival of Patients With Follicular Lymphoma in Korea.

BACKGROUND: The incidence of follicular lymphoma (FL) varies according to geographic location. It is the second most common non-Hodgkin lymphoma in Western countries but has a very low incidence in Asia. Thus, no representative data are available for FL. Therefore, we gathered our own data to build a foundation for FL research. PATIENTS AND METHODS: We collected a total of 343 patient records. The median age was 53 years, and the ratio of male to female patients was 1.4:1. Most patients received chemotherapy with or without rituximab. RESULTS: The incidence of grade 1 and 2 FL was 64.9% (n = 205) and of stage III and IV was 51.2% (n = 171). The grade tended to be higher and the stage to be lower compared with Western data. In the chemotherapy group, the complete response rate was 76.0%, and the partial response rate was 17.1%. The median follow-up duration was 38.1 months. The estimated 5- and 10-year progression-free survival and overall survival rates were 68.3% and 84.9% and 63.0% and 71.3%, respectively. CONCLUSION: We could not find definitive differences between our Korean data and the Western data, although we found some trends in the baseline characteristics. Therefore, we hope to develop an understanding of FL and perform more qualitative studies in the future.

Modified one-day etoposide and cisplatin combination for previously untreated extensive-disease small-cell lung cancer: A retrospective evaluation of 36 cases.

The combination of etoposide and cisplatin (EP) remains one of the standard first-line treatments for extensive-disease small-cell lung cancer (ED-SCLC) We devised a one-day modified EP regimen for better tolerance and convenience by modifying the dose and schedule of conventional EP with administration over 3-5 consecutive days. The modified EP consists of two infusions of etoposide (120 mg/m2 each) and 60 mg/m2 of cisplatin on day 1 of a 21-day cycle and a maximum of 6 cycles of treatment. A total of 36 consecutive ED-SCLC patients were treated with the modified EP as first-line therapy and retrospectively reviewed to assess the efficacy and safety of this regimen. Of the 36 patients, 24 exhibited confirmed objective tumor response (overall response rate of 66%, with a complete response rate of 3% and a partial response rate of 63%). The median overall survival (OS) was 11.8 months [95% confidence interval (CI): 7.9-15.3] and the progression-free survival (PFS) was 7.3 months (95% CI: 5.2-9.7). The survival estimates at 1 year were 35 and 17% for OS and PFS, respectively. The chemotherapy treatment was well tolerated, with only one case of grade 4 non-hematological adverse events, no grade 4 hematological toxicities and no treatment-related deaths. The mean relative dose intensity of etoposide and cisplatin was measured to be 94.7 and 98.5% of the planned dose, respectively. Therefore, the modified EP warrants further clinical research regarding its effectiveness, toxicity profile and convenience of administration. Prospective randomized clinical trials are required to determine the therapeutic role of the modified EP as first-line treatment in patients with ED-SCLC.

Maximum standardized uptake value on positron emission tomography/computed tomography predicts clinical outcome in patients with relapsed or refractory diffuse large B-cell lymphoma.

BACKGROUND: Few clinical studies have clarified the prognostic factors that affect clinical outcomes for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after immunochemotherapy. METHODS: A total of 158 patients with relapsed or refractory DLBCL were enrolled. All patients underwent positron emission tomography/computed tomography (PET/CT) before and after salvage therapy. All enrolled patients previously received the ifosfamide, carboplatin, and etoposide regimen. Clinical outcomes were compared according to several factors (age ≥ 65 years, low age-adjusted International Prognostic Index [aa-IPI], maximum standardized uptake value [SUVmax] <6.0 on PET/CT, time to relapse ≥12 months, complete response after salvage therapy). A low aa-IPI, SUVmax <6.0, and time to relapse ≥ 12 months were independent prognostic factors for survival. RESULTS: In univariate analysis and multivariate analysis, SUVmax below 6.0 (P<0.001 for progression-free survival (PFS), P<0.001 for overall survival (OS)) and low aa-IPI (P<0.001 for PFS, P<0.001 for OS) were independent prognostic factors associated with favorable outcome. CONCLUSION: The aa-IPI and initial SUVmax were powerful prognostic factors in patients with relapsed or refractory DLBCL.