Cauda equina lymphoma mimicking non-neoplastic hypertrophic neuropathy of the cauda equina: A case report.

Spinal cauda equina lymphoma (CEL) is very rare, with only about 14 cases reported in the English medical literature. Magnetic resonance image findings and the gross appearance of CEL at surgery are similar to those of non-neoplastic hypertrophic neuropathy of the cauda equina (HNCE); however, their prognosis and treatment are very different. We report a case of CEL and discuss the differences from non-neoplastic HNCE.

Clinicopathologic and genetic features of the starry-sky pattern in double-expressor diffuse large B-cell lymphoma.

Double expressor lymphoma (DEL) is a subset of diffuse large B-cell lymphoma (DLBCL) characterized by the co-expression of MYC and BCL2 proteins with a poor prognosis. However, there are no standard criteria for evaluating the morphologic features of DEL. We aimed to analyze the prognostic value of the starry-sky pattern (SSP) and its correlation with clinicopathologic and genetic features in 153 DEL cases. The SSP was significantly associated with aggressive parameters, including c-MYC overexpression, CD5 expression, higher IPI, and age-adjusted IPI. In the univariate survival analyses, the presence of SSP was associated with unfavorable progression-free survival (PFS) (p = 0.040), and tended towards an adverse overall survival (OS) (p = 0.061). However, when c-MYC was overexpressed, SSP was significantly correlated with inferior OS (p = 0.019). In the multivariate survival analysis, SSP was also associated with poor PFS (p = 0.048). Additionally, next-generation sequencing data revealed SSP was significantly associated with the KMT2D mutation and had different genetic mutation profiles from non-SSP. In conclusion, SSP may represent morphologic characteristics of aggressiveness in DEL.

High prevalence of hepatitis B and hepatitis C virus infections in Korean patients with hematopoietic malignancies.

We performed a large case-control study (3,932 cases, 15,562 controls) to investigate the association of hepatitis B virus (HBV) and hepatitis C virus (HCV) with hematopoietic malignancies in Korea, where HBV is endemic. HBV was present in 636 control patients (4.1%), 333 lymphoma patients (12.4%), and 75 leukemia patients (6.0%). HCV infection was present in 173 control patients (1.1%), 76 lymphoma patients (2.8%), and 18 leukemia patients (1.4%). Co-infection of HBV and HCV was present in one (0.007%) control patient, seven lymphoma patients (0.3%), and one leukemia patient (0.08%). HBV infection was associated with increased risks for most subtypes of B and T/NK-cell lymphomas, Hodgkin's lymphoma, and acute myeloid leukemia. HCV infection was associated with increased risks for diffuse large B cell lymphoma, extranodal marginal zone B cell lymphoma, peripheral T cell lymphoma, and acute lymphoid leukemia B cell early pre-B type. HBV seems to have a more important role than HCV in the pathogenesis of specific hematologic malignancies in Korea.

Prognostic factors and clinical outcomes of high-dose chemotherapy followed by autologous stem cell transplantation in patients with peripheral T cell lymphoma, unspecified: complete remission at transplantation and the prognostic index of peripheral T cell lymphoma are the major factors predictive of outcome.

High-dose chemotherapy followed by autologous stem cell transplantation (HDT/ASCT) offers a rescue option for T cell lymphoma patients with poor prognosis. However, the effectiveness of HDT/ASCT in patients with various peripheral T cell subtypes, optimal transplant timing, and the prognostic factors that predict better outcomes, have not been identified. We retrospectively investigated the clinical outcomes and prognostic factors for HDT/ASCT in 64 Korean patients with peripheral T cell lymphoma, unspecified (PTCL-U) between March 1995 and February 2007. The median age at transplantation was 44 years (range: 15-63 years). According to the age-adjusted International Prognostic Index (a-IPI) and the prognostic index of PTCL (PIT), 8 patients (12.5%) were in the high-risk group and 16 (26.6%) had the 2-3 PIT factors, respectively. After a median follow-up of 29.7 months, the 3-year overall survival (OS) and progression-free survival (PFS) rates were 53.0% +/- 7.5% and 44.3% +/- 7.0%, respectively. Univariate analysis showed that poor performance status, high lactate dehydrogenase (LDH) levels, high a-IPI score, high PIT classes, failure to achieve complete response (CR) at transplantation, and nonfrontline transplantation were associated with poor OS. Multivariate analysis showed that failure to achieve CR at transplantation (hazard ratio [HR] 2.23; 95% confidence interval [CI] 1.78-7.93) and 2-3 PIT factors (HR 3.76; 95% CI 1.02-5.42) were independent prognostic factors for OS. Failure to achieve CR at transplantation and high PIT are negative predictable factors for survival following HDT/ASCT in patients with PTCL-U.

POEMS Syndrome: Bone Marrow, Laboratory, and Clinical Findings in 24 Korean Patients.

POEMS syndrome is a rare paraneoplastic syndrome, which includes polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes due to plasma cell (PC) neoplasm. Diagnosis of this disease is challenging because of its rarity and complex clinical manifestations. We attempted to identify the key clinical features and characteristic bone marrow (BM) findings of POEMS syndrome, by reviewing the medical records and BM analyses of 24 Korean patients. Frequent clinical manifestations included polyneuropathy (100%), monoclonal gammopathy (100%), organomegaly (92%), extravascular volume overload (79%), and endocrinopathy (63%). The BM analyses revealed mild PC hyperplasia (median PCs: 5.5%) and frequent megakaryocytic hyperplasia (88%), megakaryocyte clusters (88%), and hyperlobation (100%). Flow cytometry of BM aspirates using CD138/CD38/CD45/CD19/CD56 showed normal (67%, 4/6) or neoplastic PC immunophenotypes (33%, 2/6). A diagnosis of POEMS syndrome must be considered when a patient suspected of having PC dyscrasia shows the above clinical presentation and BM findings.

Protective role of CYP1A1*2A in the development of multiple myeloma.

We had previously reported the association of the NQO1*2/*2 polymorphism with a decreased risk for multiple myeloma (MM) in Koreans (odds ratio, OR, 0.24; 95% confidence interval, CI, 0.01-0.68). The associations of polymorphisms of other metabolizing enzymes (CYP1A1, GSTM1 and GSTT1) with the MM risk were investigated in 116 Korean MM patients and 176 Korean controls using TaqMan allelic discrimination and multiplex polymerase chain reaction. The ORs for CYP1A1*1/*2A and CYP1A1*1/*2B genotypes were 0.43 (95% CI, 0.19-0.98) and 0.51 (95% CI, 0.26-0.98), respectively, which was significantly associated with a decreased MM risk. With regard to CYP1A1 alleles, the OR for the CYP1A1*2A allele was 0.57 (95% CI, 0.326-0.995), which was also significantly associated with a decreased MM risk. However, null types of GSTM1 and GSTT1 polymorphisms were not associated with the MM risk. These results were different from those of a previous report on Caucasians which suggested the association of the GSTT1 polymorphism with an increased MM risk and no association of CYP1A1 with the MM risk. The associations of polymorphisms of metabolizing enzymes with the risk for MM differed between Koreans and Caucasians, suggesting an ethnic variation in the susceptibility to MM.

Significantly better prognosis for patients with primary plasma cell leukemia than for patients with secondary plasma cell leukemia.

Plasma cell leukemia (PCL) is a rare variant of multiple myeloma (MM). Patients may either present de novo (primary PCL), or PCL may occur during the course of MM (secondary PCL). We compared the laboratory and clinical findings of both primary and secondary PCL and MM to elucidate their natural history and the relationship among these entities. Ten cases of PCL (7 cases of primary PCL and 3 cases of secondary PCL) and 20 sex- and age-matched cases of MM were compared. The patients with primary PCL showed significantly lower platelet and neutrophil counts in peripheral blood and higher cellularity in bone marrow than patients with MM (p = 0.002, < 0.001 and 0.027, respectively). Immunophenotypic studies showed a different expression of HLA-DR and CD117 antigens among the 3 groups. There was a significant difference in survival between the 3 groups (median survival of primary PCL, secondary PCL and MM = 22.2, 1.3 and 36.4 months, respectively; p = 0.048). The patients with primary PCL showed better prognosis than those with secondary PCL. Primary PCL might be a differently developed disease from MM. In diagnosing PCL, it is important to differentiate primary PCL from secondary PCL for the prediction of prognosis.

Randomized phase II study of gemcitabine plus cisplatin versus etoposide plus cisplatin for the treatment of locally advanced or metastatic non-small cell lung cancer: Korean Cancer Study Group experience.

BACKGROUND: Several randomized trials have demonstrated superior response rates and survivals for new agent platinum doublets than for older platinum doublets in advanced non-small cell lung cancer (NSCLC), however, few trials have been performed in Asian populations. Thus, we conducted a randomized study to compare gemcitabine-cisplatin (GP) with etoposide-cisplatin (EP) in Korean patients with advanced NSCLC. METHODS: Patients with histologically confirmed, locally advanced or metastatic NSCLC were randomized to receive either gemcitabine 1250 mg/m2 on days 1 and 8 plus cisplatin 75 mg/m2 on day 1, or etoposide 100 mg/m2 on days 1-3 plus cisplatin 75 mg/m2 on day 1. Treatment was repeated every 21 days in both groups. The primary endpoint was response rate. RESULTS: Between May 2000 and December 2001, 83 patients at 9 Korean centers were enrolled in this study. The GP arm showed a significantly higher response rate (52.6% versus 19.4%; P = 0.002), a longer time to progression (4.3 months in both arms; P = 0.018) and a marginally significant prolongation of overall survival (18.3 months versus 10.9 months; P = 0.059) than the EP arm. Grades 3 and 4 thrombocytopenia (18% versus 0%) was more common in the GP arm whereas grades 3 and 4 neutropenia was more common in EP arm (48.7% versus 71.8%). Other toxicities were comparable in both arms. CONCLUSION: GP provided a significantly higher response rate and a longer time to progression than EP and should be considered a standard treatment in advanced NSCLC in Korean population.

Characteristics of unexpected protein bands in multiple myeloma patients after autologous stem cell transplantation.

OBJECTIVES: The aim of this study is to investigate the characteristics of unexpected protein bands (UPBs) in patients with multiple myeloma (MM). DESIGN AND METHODS: Individuals diagnosed with MM (n=193) were enrolled. Their medical records and IFE patterns were reviewed. RESULTS: Of the patients that underwent ASCT, 54% developed UPBs. The median time for UPB appearance and duration was 1.8 and 5.7months, respectively. IFE revealed 74.1% of UPBs to be of the immunoglobulin G type and 72.2% to be of the κ-type. At UPB appearance, 42.6% of patients were defined as sCR or CR, and 50.0% of the patients satisfying the CR criteria had an abnormal FLC ratio. Of the patients who developed UPBs, five relapsed. Among these, four patients showed disappearance of the previous IFE oligoclonality and reappearance of the original paraprotein at relapse. CONCLUSIONS: Close follow-up of UPBs is critical for evaluating MM therapeutic response and disease progression. The presence of monoclonal bands may indicate relapse of disease, but in the vast majority of cases with UPBs, it does not; instead, it most likely represents a transient phenomenon caused by the immune response.

Clinical characteristics, pathological distribution, and prognostic factors in non-Hodgkin lymphoma of Waldeyer's ring: nationwide Korean study.

BACKGROUND/AIMS: In Asia, the incidence of non-Hodgkin lymphoma (NHL) has increased in recent decades. Waldeyer's ring (WR) is the most common site of NHL involving the head and neck. In this study, the pathological distribution of WR-NHL and its clinical features were analyzed retrospectively. METHODS: From January 2000 through December 2010, we analyzed the medical records of 328 patients from nine Korean institutions who were diagnosed with WR-NHL. RESULTS: The study group comprised 197 male and 131 female patients with a median age of 58 years (range, 14 to 89). The rate of localized disease (stage I/II) was 64.9%, and that of low-risk disease (low/low-intermediate, as defined by the International Prognostic Index) was 76.8%. Diffuse large B-cell lymphoma (DLBCL; 240 patients, 73.2%) was the most common pathologic subtype, followed by peripheral T-cell lymphoma (14 patients, 4.3%) and nasal NK/T-cell lymphoma (14 patients, 4.3%). WR-NHL occurred most frequently in the tonsils (199 patients, 60.6%). Extranodal involvement was greater with the T-cell subtype (20 patients, 42.5%) compared with the B-cell subtype (69 patients, 24.5%). Multivariate analyses showed that age ≥ 62 years, T-cell subtype, and failure to achieve complete remission were significant risk factors for overall survival. CONCLUSIONS: DLBCL was found to have a higher incidence in Korea than those incidences reported by other WR-NHL studies. T-cell lymphoma occurred more frequently than did follicular lymphoma. T-cell subtype, age ≥ 62 years, and complete remission failure after first-line treatment were significant poor prognostic factors for overall survival according to the multivariate analysis.

Langerhans cell histiocytosis followed by Hodgkin's lymphoma.

A 22-year-old man was referred to our institution due to lower back pain and was diagnosed with Langerhans cell histiocytosis of the thoracic and lumbar spine. The patient achieved complete remission with radiotherapy and chemotherapy. One year later, right cervical lymphadenopathy was observed and Hodgkin's lymphoma was confirmed on biopsy. The patient was treated with chemotherapy and autologous stem cell transplantation, and experienced no further symptoms. Further, no evidence of recurrence was observed on follow-up imaging. This report discusses the association between Langerhans cell histiocytosis and Hodgkin's lymphoma.

The Efficacy and Safety of DA-3030 (Recombinant Human Granulocyte Colony-Stimulating Factor) in Neutropenia after the Remission Induction Chemotherapy in Patients with Acute Myelogenous Leukemia.

PURPOSE: This study was conducted to determine the efficacy and safety of DA-3030 (a recombinant methionyl human granulocyte colony-stimulating factor, rhG-CSF), after remission induction chemotherapy, in patients with acute myelogenous leukemia (AML). MATERIALS AND METHODS: After the remission induction chemotherapy, with idarubicin (12 mg/m2/day for 3 days) and cytarabine (200 mg/m2/day for 7 days), 26 patients with newly diagnosed AML were assigned to receive DA-3030 (200mug/m2/day), starting 24 hours after the completion of the remission induction chemotherapy, until their neutrophil count recovered to greater than 1, 000/muL for 3 consecutive days. RESULTS: The median time from the initiation of the chemotherapy to the neutrophil recovery of 1, 000/muL was 21 days (range, 12~41). Treatment with DA-3030 was not associated with significant adverse side effects. The most frequently reported side effects were musculo-skeletal pain (13%) and headache (13%). CONCLUSION: The DA-3030 is a safe rhG-CSF for the treatment of neutropenia after remission induction chemotherapy in patients with AML.

Preliminary Results of Paclitaxel, Cisplatin and Concurrent High-Dose Radiation Therapy for Locally Advanced Non-Small-Cell Lung Cancer.

PURPOSE: To investigate the feasibility, toxicity and response rate, of concurrent chemoradiation therapy with paclitaxel/cisplatin in stage III locally advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Between May 1999 and December 2000, 80 patients with stage III NSCLC were enrolled in a prospective protocol. Radiotherapy was given to a total dose of 70.2 Gy (daily fraction of 1.8 Gy for 5 days), over an 8 week period, on the gross tumor volume, combined with chemotherapy. The concurrent chemotherapy consisted of paclitaxel (40 mg/m2) and 20 mg/m2 cisplatin per week for 8 consecutive weeks. All patients received 3-D conformal radiotherapy using CT-simulated planning. Acute toxicities were evaluated by the RTOG scale. The median follow-up period was 16 months, ranging from 3 to 29 months. RESULTS: Of the 80 patients, 71 received treatment per protocol, with minor variation of protocol delivery. The median age of the patients was 60 years. Karnofsky Performance status were 100 and 90 in 62 patients, and 80 and 70 in 9, respectively. Weight loss of less than 5% for 6 months was observed in 22 patients. The response to treatment was evaluated from the radiological findings. Complete and partial responses were observed in 8 and 51 patients, respectively. Ultimately, 82% of patients (included complete responses: 8 cases) obtained more than a partial response. Although, radiation induced esophagitis was the most common treatment related toxicity, occurring in 44 patients (69%), severe radiation esophagitis like, grade 3, was observed in only 3 patients, and the most acute toxicities had completely recovered 1 month following treatment. The overall 2-year actuarial and progression free survivals were 56 and 45%, respectively. CONCLUSION: This combined modality has activity with manageable toxicity and 23 months in mean survival time in patients with stage III NSCLC. A longer follow up will be required to realise the expected higher survival of these results.

Concurrent Etoposide/Cisplatin Combination Chemotherapy (EP) and Thoracic Radiotherapy after Two Cycles of EP for Limited Stage Small Cell Lung Cancer.

PURPOSE: s: Although the standard management of limited stage small cell lung cancer is concurrent platinum-based chemotherapy with thoracic radiotherapy (TRT), the optimal timing of the TRT remains controversial. We investigated the feasibility of concurrent chemoradiation for the patients with limited stage small cell lung cancer after 2 cycles of combination chemotherapy with Etoposide/Cisplatin (EP). MATERIALS AND METHODS: EP consisted of Etoposide 100 mg/m2 on day 1 to 3 and Cisplatin 70 mg/m2 on day 1. Six cycles were given to the responders every 4 weeks. Total 55 Gy (1.8 Gy once-daily or 1.2 Gy twice-daily, 5 days per week) of TRT were given to the patients who showed at least a partial response after 2 cycles of EP. The other patients were treated by the physician's decision. The patients with complete remission were recommended to receive prophylactic cranial irradiation. RESULTS: Fifty patients were enrolled. Thirty-five (70%) of them showed responses (2 complete remissions and 33 partial remissions) after 2 cycles of EP. Thirty-three of the responders were given TRT starting with the 3rd cycle of EP. The nonresponders were treated with salvage chemotherapy and TRT. After completion of treatment for 50 patients, the overall response rate was 86% (29 complete remissions, 14 partial remissions). One patient (2%) showed stable disease, and 6 (12%) showed a progressive disease. The median progression free survival was 326 days and the median survival time was 410 days. One-, 2-, 3-, 4- and 5-year survival rates were 62%, 24%, 14%, 9% and 6%, respectively. As hematologic toxicities during chemoradiation, 35.1% with grade III/IV neutropenia and 18.9% with grade III/IV thrombocytopenia were noted. Grade II/III radiation pneumonitis and radiation esophagitis were noted in 5/1 and 13/1 patients (15.2%/ 3.0% and 39.4%/3.0%), respectively. One patient died of septicemia during chemoradiation. CONCLUSION: The concurrent EP and TRT after 2 cycles of EP was feasible in limited stage small cell lung cancer. Further study is required for the indentification of optimum timing of TRT during combination chemotherapy.

A case of treatment-related myelodysplastic syndrome and acute myelogenous leukemia following high-dose chemotherapy with autologous stem cell transplantation for non-Hodgkin's lymphoma.

Treatment-related myelodysplastic syndrome (t-MDS) and acute myelogenous leukemia (t-AML) are now well established as complications of cytotoxic chemotherapy. We experienced a 28-yr-old female patient who developed t-MDS/t-AML with characteristic chromosomal abnormalities including 11q23 chromosomal rearrangement following high-dose chemotherapy with autologous stem cell transplantation (ASCT) for non-Hodgkin's lymphoma. The patient was admitted with bulky abdominal masses of B cell lineage non-Hodgkin's lymphoma. After 2 cycles of systemic chemotherapy of the Vanderbilt regimen, the patient underwent ASCT with high dose chemotherapy of the BEAC regimen. She also received radiation of 48 Gy for the residual periportal lymphadenopathy. The initial cytogenetic analysis of the infused mononuclear cells revealed a normal karyotype. Twenty two months after the ASCT, pancytopenia was noted and her bone marrow aspirate showed dysplastic hemopoiesis with myeloblasts up to 12% of nonerythroid nucleated cells. The patient was diagnosed as t-MDS (refractory anemia with an excess of blasts). Cytogenetic analysis showed complex chromosomal abnormalities including 11q23 rearrangement, which is frequently found in topoisomerase II inhibitor-related hematologic malignancies. Four months later, it was noted that the t-MDS had evolved into an overt t-AML. Cytogenetic analysis showed an evolving pattern with more complex abnormalities. The patient was treated with combination chemotherapy, but her leukemic cells were resistant to the therapy.