Ki Hwan Kim

Central Pontine Myelinolysis in a Patient with Acute Lymphoblastic Leukemia after Hematopoietic Stem Cell Transplantation : A Case Report

We describe a 37-yr-old man who developed central pontine myelinolysis (CPM) after allogeneic hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia. After HSCT, desquamation developed on the whole body accompanied by hyperbilirubinemia. The liver biopsy of the patient indicated graft-versus-host disease-related liver disease, and the dose of methylprednisolone was increased. Then, the patient developed altered mentality with eye ball deviation to the left, for which electroencephalogram and magnetic resonance imaging (MRI) scans were done. Brain MRI scan demonstrated the imaging findings consistent with central pontine myelinolysis and extrapontine myelinolysis. He did not have any hyponatremia episode during hospitalization prior to the MRI scan. To the best of our knowledge, presentation of CPM after allogeneic HSCT is extremely rare in cases where patients have not exhibited any episodes of significant hyponatremia. We report a rare case in which hepatic dysfunction due to graft-versus-host disease has a strong association with CPM after HSCT.

Pleural Effusion in Multiple Myeloma: Characteristics and Practice Patterns

In many Asian countries battling with the double burden of increasing noninfectious diseases on top of infectious diseases, multiple myeloma (MM) patients presenting with pleural effusion (PE) pose a great diagnostic challenge. Thus, we aimed to analyze the clinical features and practice patterns of such patients. This is a multicenter retrospective study of newly diagnosed MM patients between January 2011 and December 2015. Among 575 MM patients diagnosed during the study period, 80 (13.9%) that were associated with PE were identified and analyzed. The most common cause of PE was parapneumonic (25%), followed by reactive (18.8%). Higher CRP levels and leukocytosis were indicators of parapneumonic PE. There were 7 (8.8%) with myelomatous PE and 2 (2.5%) with tuberculosis. Fifty-six patients underwent additional examinations to determine the exact cause of effusion; 28 patients received computed tomography (CT) of the chest, 5 patients underwent thoracentesis/biopsy, and 23 patients underwent both CT and thoracentesis/biopsy. On the other hand, 24 patients did not undergo additional analyses but were treated empirically. Real-world analyses of practice patterns in MM patients with PE showed the suboptimal use of invasive procedures to determine the exact cause of PE. Since reversible causes and tuberculosis pleurisy are not uncommon, invasive procedures should be actively incorporated as needed.

Diffuse Large B-Cell Lymphoma With Germinal Center B-Cell Phenotype Mimicking Primary Effusion Lymphoma

Case Report A 67-year-old woman presented with a 3-week history of abdominal distension. She had neither significant medical nor family history. Physical examination revealed abdominal distension without tenderness or rebound tenderness. No cervical, supraclavicular, axillary, or inguinal lymphadenopathy was noted, and there was no sign of hepatosplenomegaly. Computed tomography of the abdomen and chest showed bilateral pleural effusions, a large amount of ascites, diffuse peritoneal thickening with contrast enhancement, and diffuse mesenteric infiltration with omental cakes. Multiple but small ( 15 mm) scattered mediastinal, peritoneal, and retroperitoneal lymph nodes were also observed. [F]fluorodeoxyglucose positron emission tomography demonstrated small hypermetabolic lymph nodes in the mediastinal, peritoneal, and retroperitoneal spaces and hypermetabolism in both ovaries (Fig 1A). No significant abnormalities were identified on endoscopic examination of the stomach and colon. Serum chemistry showed abnormal levels of alkaline phosphatase (655 U/L) and creatinine (1.7 mg/dL). Serum lactate dehydrogenase, 2microglobulin, and cancer antigen 125 (CA-125) were also elevated at 1,990 U/mL, 8.52 mg/L, and 1,290 U/mL, respectively. Hepatitis B virus surface antigen, antibodies to hepatitis C virus, and ELISA for HIV-1 were all negative. Diagnostic laparoscopy revealed diffuse peritoneal infiltration. However, there were no abnormalities in either ovary, in discordance with nuclear imaging. Pathology (Fig 2A, hematoxylin and eosin stain) from the omental cake revealed poorly differentiated atypical large cells that stained positive for CD20 (Fig 2B), CD79a, leukocyte common antigen, and B-cell lymphoma 6 (BCL-6; Fig 2C). The cells were negative for CD3, CD5, CD10, CD30, pan-cytokeratin, BCL-2, multiple myeloma 1, and Kaposi sarcoma–associated virus/human herpes virus 8 (KSHV/ HHV-8). Stain for Ki-67 (Fig 2D) highlighted more than 80% of tumor cells. In situ hybridization for Epstein-Barr–encoded RNAs was negative. CMYC was not amplified. Cell block from ascites revealed the same atypical cells. A diagnosis of diffuse large BCL, germinal center B-cell phenotype (GCB-DLBCL) was made. Trephine biopsies of bone marrow showed diffuse infiltration of the marrow with lymphoma. Cerebrospinal fluid involvement was ruled out by lumbar puncture. Eight cycles of chemoimmunotherapy including cyclophosphamide, doxorubicin, vincristine, prednisolone, and rituximab (R-CHOP) every 3 weeks were planned. Symptoms, signs, and laboratory abnormalities dramatically improved within 1 week after the first cycle. After four cycles of R-CHOP, partial remission was achieved. Restaging bone marrow with immunohistochemical analysis of CD79a indicated no residual disease. Serum CA-125 and lactate dehydrogenase were reduced to 21 and 181 U/mL, respectively. [F]fluorodeoxyglucose positron emission tomography (Fig 1B) showed markedly reduced extent of lymphoma except for a few residual hypermetabolic mediastinal lymph nodes.

Costs and clinical outcomes of patients with diffuse large B-cell lymphoma in first remission: role of PET/CT surveillance

Background/Aims The role of [18F]-f luorodeoxyglucose positron emission tomography-computed tomography (PET/CT) in patients with diffuse large B-cell lymphoma (DLBCL) in first remission is unclear. Methods Medical costs within the first 3 years of treatment completion and clinical outcomes of 118 patients with DLBCL in first remission with and without surveillance PET/CT (PET/CT [+] group [n = 76] and PET/CT [–] group [n = 42], respectively) were retrospectively analyzed. Results In a propensity matched cohort with adjustment for International Prognostic Index risk and relapse, the PET/CT (+) group was shown to have similar medical costs as the PET/CT (–) group. Relapse-free survival (RFS) and overall survival (OS) were comparable between the two groups (median RFS not reached [NR] for both groups, p = 0.133; median OS NR, p = 0.542). Among 76 patients with surveillance PET/CT, 31 (40.8%) had findings suggestive of recurrence and 16 of these (51.6%) were later confirmed to have recurrent disease. Fifteen patients (48.4%) were confirmed to not have recurrence after follow-up CT or PET/CT evaluation (n = 10) and biopsy (n = 4). None of the patients with negative PET/CT findings had disease recurrence. Sensitivity, specificity, positive predictive value, and negative predictive value of PET/CT for detection of recurrence were 1, 0.75, 0.52, and 1, respectively. Conclusions Surveillance PET/CT resulted in similar clinical outcomes and medical costs compared to no surveillance PET/CT. Approximately half of patients with PET/CT findings of recurrence had no recurrence after follow-up imaging and biopsy, which would not have been carried out if PET/CT had not been performed in the first place.

Serum free light chain difference and beta-2 microglobulin levels are risk factors for thromboembolic events in patients with AL amyloidosis

&NA; AL amyloidosis might increase the risk of thromboembolism and other plasma cell dyscrasias. Therefore, we evaluated the features of thromboembolism in AL amyloidosis. The incidence of thromboembolism was substantial (12.3%); most events developed within the first year after the diagnosis, and arterial thromboembolism occurred frequently. In particular, patients with risk factors might require close monitoring for thromboembolism. Background: AL amyloidosis might increase the risk of thromboembolism and other plasma cell dyscrasias; however, only a few reports have described the clinical features of thromboembolism. The present study aimed to elucidate the clinical features of thromboembolic events and to identify the risk factors for these events. Materials and Methods: The medical records were retrospectively reviewed to define the clinically significant thromboembolic events. Results: A total of 106 patients with biopsy‐proven AL amyloidosis were included. During a median follow‐up of 18.1 months (range, 0.4‐166.9 months), 13 thromboembolism events were identified in 13 patients. Of the 13 patients, 9 (8.5%) experienced acute cerebral infarction, 2 (1.9%) experienced pulmonary embolism, and 2 (1.9%) experienced deep vein thrombosis. Patients with a higher serum free light chain (FLC) difference (≥ 172.4 mg/L) or &bgr;2‐microglobulin (&bgr;2MG) levels (≥ 2.78 mg/L) experienced significantly more thromboembolic events compared with those with a lower value according to multivariable analysis (for FLC difference: hazard ratio, 4.309; 95% confidence interval, 1.158‐16.032; P = .029; for &bgr;2MG: hazard ratio, 9.739; 95% confidence interval, 1.127‐84.174; P = .039). Most thromboembolic events (11 of 13; 84.6%) occurred within the first year after the AL amyloidosis diagnosis. Conclusion: The incidence of thromboembolism was substantial in those with AL amyloidosis. A greater FLC difference and for &bgr;2MG levels were risk factors for thromboembolic events.

The Derived Neutrophil-to-Lymphocyte Ratio Is an Independent Prognostic Factor in Transplantation Ineligible Patients with Multiple Myeloma

Background: The neutrophil-to-lymphocyte ratio (NLR) is an independent prognostic marker in solid and hematological cancers. While the derived NLR (dNLR) was shown to be non-inferior to the NLR in large cohorts of patients with different cancer types, it has not been validated as a prognostic marker for multiple myeloma (MM) to date. Methods: Between May 22, 2011 and May 29, 2014, 176 patients with MM from 38 centers who were ineligible for autologous stem cell transplantation were analyzed. The dNLR was calculated using complete blood count differential data. The optimal dNLR cut-off value according to receiver operating characteristic analysis of overall survival (OS) was 1.51. All patients were treated with melphalan and prednisone combined with bortezomib. Results: The complete response rate was lower in the high dNLR group compared to the low dNLR group (7 vs. 26.1%, respectively; p = 0.0148); the corresponding 2-year OS rates were 72.2 and 84.7%, respectively (p = 0.0354). A high dNLR was an independent poor prognostic factor for OS (hazard ratio 2.217, 95% CI 1.015–4.842; p = 0.0458). Conclusion: The dNLR is a readily available and cheaply obtained parameter in clinical studies, and shows considerable potential as a new prognostic marker for transplantation-ineligible patients with MM.

Abstract LB-241: Quantification of EGFR allele frequency predicts tumor response to EGFR tyrosine kinase inhibitors

Background: EGFR tyrosine kinase inhibitors (TKIs) are current standard treatments for non-small cell lung cancers (NSCLCs) with EGFR mutation. Current diagnostic tests for EGFR mutation include direct sequencing, pyrosequencing or real-time PCR based technology. We have developed a digital droplet PCR based analysis, GenesWell™ ddEGFR Mutation Test (IUO version 5.2. Gencurix Inc., Seoul, Korea). Methods: We have analyzed a total of 325 archived tissue from 233 lung cancer patients treated with gefitinib or erlotinib in the participating 3 hospitals from 2008 to 2013. Samples were analyzed with GenesWell™ ddEGFR Mutation Test and the results were compared with in-house results recorded in each institutional EMR. Results: Since we have analyzed left-over archived tissue, the amount of DNA was inappropriate for analysis in few cases (n=5, 1.5%), which had less than 2ng/uL concentration of DNA. ddEGFR test detected additional EGFR mutations in patients with EGFR wild-type (WT) (N=4), exon 19 deletion (19del) (N=4) and exon 21 L858R (L858R) (N=3) by in-house EGFR test. ddEGFR test detected EGFR mutations in cytology-base samples, such as pleural effusion or ascites. Small amount of sample from CSF and plasma was also detectable with ddEGFR test. Based on in-house EGFR mutation results, response rates (RRs) and disease control rates (DCRs) were as follows: 15.8% and 26.9% in WT, 71.4% and 91.8% in 19del, and 55.9% and 91.2% in L858R. Similarly, RRs and DCRs were as follows, based on ddEGFR results: 13.4% and 43.9% in wild-type (WT), 77.6% and 93.9% in 19del and 54.1% and 86.5% in exon 21 L858R (L858R). Mean allele frequencies were 48.6 (0 - 180.5) in PR, 27.4 (0 - 287.5) in SD, and 9.5 (0-159.6) in PD (P-value, PR vs SD: .0078, PR vs PD: