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The present study is to investigate whether extranodal (EN) metabolic tumor volume (MTV) would have a specific clinical meaning for survival in EN diffuse large B cell lymphoma (DLBCL) patients. Two hundred forty DLBCL patients with EN involvement received 18F-fluorodeoxygenase (FDG) positron emission tomography/computed tomography (PET/CT) were enrolled. Survival analysis revealed that low EN MTV (PFS [progression-free survival], HR = 0.278, 95% CI = 0.127-0.807, p = 0.001; OS [overall survival], HR = 0.320, 95% CI = 0.145-0.703, p = 0.003), low total MTV (PFS, HR = 0.194, 95% CI = 0.085-0.445, p < 0.001; OS, HR = 0.213, 95% CI = 0.092-0.491, p < 0.007), and high National Cancer Center Network-International Prognostic Index score (PFS, HR = 3.152, 95% CI = 1.732-5.734, p < 0.001; OS, HR = 2.457, 95% CI = 1.363-4.430, p = 0.003) were independently associated with survivals in the patients. Our data showed that EN MTV is a useful and novel prognostic parameter for predicting survival in DLBCL patients with EN involvement.

Background Systemic inflammatory response can be associated with the prognosis of diffuse large B cell lymphoma (DLBCL). We investigated the systemic factors significantly related to clinical outcome in relapsed/refractory DLBCL. Methods In 242 patients with DLBCL, several factors, including inflammatory markers were analyzed. We assessed for the correlation between the survivals [progression-free survival (PFS) and overall survival (OS)] and prognostic factors. Results In these patients, a high derived neutrophil/lymphocyte ratio (dNLR) (PFS, HR=2.452, P=0.002; OS, HR=2.542, P=0.005), high Glasgow Prognostic Score (GPS) (PFS, HR=2.435, P=0.002; OS, HR=2.621, P=0.002), and high NCCN-IPI (PFS, HR=2.836, P=0.003; OS, HR=2.928, P=0.003) were significantly associated with survival in multivariate analysis. Moreover, we proposed a risk stratification model based on dNLR, GPS, and NCCN-IPI, thereby distributing patients into 4 risk groups. There were significant differences in survival among the 4 risk groups (PFS, P

FLT3 mutations are the most common genomic alteration detected in acute myeloid leukemia (AML) with a worse clinical prognosis. The highly frequent FLT3 mutations, together with the side effects associated with clinical prognosis, make FLT3 promising treatment targets and have provoked the advancement of FLT3 inhibitors. Recently, numerous FLT3 inhibitors were actively developed, and thus the outcomes of this aggressive subtype of AML were significantly improved. Recently, midostaurin and gilteritinib were approved as frontline treatment of AML and as therapeutic agents in the recurred disease by the United States Food and Drug Administration. Recently, numerous promising clinical trials attempted to seek appropriate management in frontline settings, in relapsed/refractory disease, or after stem cell transplantation in AML. This review follows numerous clinical trials about the usefulness of FLT3 inhibitors as frontline therapy, as relapsed/refractory conditioning, and as maintenance therapy of stem cell transplantation. The cumulative data of FLT3 inhibitors would be important clinical evidence for further management with FLT3 inhibitors in AML patients with FLT3 mutations.

Background We investigated whether distancemax, that is, the degree of distance between the upper aerodigestive tract (UAT) mass and the farthest pathologic lymph node, was significantly associated with survival in patients with limited-stage UAT natural killer/T cell lymphoma (NKTCL). Methods A total of 157 patients who received chemotherapy (CTx) with/without radiotherapy (RTx) were enrolled. Results In the survival analysis, an elevated lactate dehydrogenase level [progression-free survival (PFS): hazard ratio (HR), 2.948; 95% confidence interval (CI), 1.606‒5.404; P

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.

// Moo-Kon Song 1 , Joo-Seop Chung 2 , Ho-Young Yhim 3 , Sung-Nam Lim 4 , Seong-Jang Kim 5 , Yeon-Hee Han 6 , Hye-Kyung Shim 7 , Sung-Hoon Jung 8 , Je-Jung Lee 8 and Deok-Hwan Yang 8 1 Department of Hemato-Oncology, Hanyang University Hanmaeum Changwon Hospital, Changwon, Korea 2 Department of Hematology-Oncology, Pusan National University Hospital, Busan, Korea 3 Department of Hematology, Chonbuk National University Hospital, Jeonju, Korea 4 Department of Hematology, Busan Haeundae Paik Hospital, Busan, Korea 5 Department of Nuclear Medicine, Pusan National University Hospital, Busan, Korea 6 Department of Nuclear Medicine, Chonbuk National University Hospital, Jeonju, Korea 7 Department of Nuclear Medicine, Busan Haeundae Paik Hospital, Busan, Korea 8 Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Korea Correspondence to: Deok-Hwan Yang, email: // Keywords : extranodal natural killer/T-cell lymphoma, tumor necrosis, complete resection, prognosis Received : March 31, 2017 Accepted : May 10, 2017 Published : May 23, 2017 Abstract Tumor necrosis (TN) is associated with worse prognosis in several solid cancers. Whether TN predicts poor outcome in natural killer cell / T cell lymphoma (NKTCL) is unclear. We investigated the clinical impact of TN on survival and other novel prognostic parameters in upper aero-digestive tract (UAT) NKTCL of 100 patients with limited stage. TN was significantly associated with poor performance status ( p = 0.049), high Korean Prognostic Index score ( p = 0.024), high C-reactive protein/albumin ratio ( p = 0.003), higher maximum standard uptake value on positron emission tomography/computed tomography (PET/CT) ( p = 0.008) and higher metabolic tumor volume (MTV) on PET/CT ( p < 0.001). In univariate and multivariate analyses, progression-free survival and overall survival were independently associated with High MTV status ( p = 0.001, p = 0.032), TN ( p = 0.018, p = 0.009), local tumor invasiveness ( p = 0.007, p = 0.035), complete resection ( p = 0.020, p = 0.028) and regional lymph node involvement ( p < 0.001, p < 0.001). TN and complete resection are concluded to be novel independent prognostic factors in patients with UAT NKTCL.

Bortezomib-melphalan-prednisone (VMP) showed superior efficacy versus MP as first-line treatment for transplantation-ineligible multiple myeloma (MM). This study investigated the efficacy of VMP for Korean patients with MM. Overall, 177 MM patients received 9 cycles of VMP in this prospective, multicenter, observational study. The primary endpoint was 2-year progression-free survival (PFS). Thirty-nine (22%) patients were aged ≥ 75 years and 83 (47.4%) patients had International Staging System stage III. A median of 5 cycles were delivered. Overall response rate (ORR) was 72.9%, and complete response (CR) rate was 20.3%. With a median follow-up of 11.9 months, median PFS was 17 months. The 2-year PFS and overall survival (OS) rates were 29.2% and 80.0%, respectively. Median OS was not reached. PFS was significantly different depending on performance status (Eastern Cooperative Oncology Group < 2 vs. ≥ 2; p = 0.0002), β2-microglobulin level (< 5.5 vs. ≥ 5.5 mg/L; p = 0.0481), and cumulative dose of bortezomib (< 35.1 vs. ≥ 35.1 mg/m2; p < 0001). The common adverse events (AEs) were in line with the well-known toxicity profiles associated with VMP. In conclusion, VMP is a feasible and effective front-line treatment for transplant-ineligible older patients with MM in Korea. Continuing therapy with prompt adjustment of treatment according to AEs may be important to improve outcomes of elderly patients.

Acute myeloid leukemia (AML) is a heterogenous hematopoietic neoplasm with various genetic abnormalities in myeloid stem cells leading to differentiation arrest and accumulation of leukemic cells in bone marrow (BM). The multiple genetic alterations identified in leukemic cells at diagnosis are the mainstay of World Health Organization classification for AML and have important prognostic implications. Recently, understanding of heterogeneous and complicated molecular abnormalities of the disease could lead to the development of novel targeted therapeutic agents. In the past years, gemtuzumab ozogamicin, BCL-2 inhibitors (venetovlax), IDH 1/2 inhibitors (ivosidenib and enasidenib) FLT3 inhibitors (midostaurin, gilteritinib, and enasidenib), and hedgehog signaling pathway inhibitors (gladegib) have received US Food and Drug Administration (FDA) approval for the treatment of AML. Especially, AML patients with elderly age and/or significant comorbidities are not currently suitable for intensive chemotherapy. Thus, novel therapeutic planning including the abovementioned target therapies could lead to improve clinical outcomes in the patients. In the review, we will present various important and frequent molecular abnormalities of AML and introduce the targeted agents of AML that received FDA approval based on the previous studies.

Tumor necrosis (TN) can lower responsiveness to chemotherapy and confer basic resistance to anti-cancer therapy. We investigated the association of TN with poor clinical features and outcome in diffuse large B cell lymphoma (DLBCL). We examined the presence or absence of TN in 476 DLBCL patients of who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Eighty-nine (18.7 %) patients had TN at diagnosis. Patients with TN had a progression-free survival (PFS) and overall survival (OS) of 39.3 and 46.7 %, whereas patients without TN had a PFS and OS of 73.4 and 82.6 %. Adverse clinical factors of poor Eastern Cooperative Oncology Group performance status ≥ grade 2 (p = 0.005), elevated lactate dehydrogenase ratio >1 (p

In tumor microenvironment, the programmed death 1 (PD-1) immune checkpoint has a crucial role of mechanism of T cell exhaustion leading to tumor evasion. Ligands of PD-1, programmed death ligand 1/2 (PD-L1/L2) are over-expressed in tumor cells and participate in prolonged tumor progression and survivals. Recently, clinical trials for patients who failed to obtain an optimal response prior to standardized chemotherapy in several solid cancers have been focused on targeting therapy against PD-1 to reduce disease progression rates and prolonged survivals. Since various inhibitors targeting the immune checkpoint in PD-1/PD-L1 pathway in solid cancers have been introduced, promising approach using anti-PD-1 antibodies were attempted in several types of hematologic malignances. In diffuse large B cell lymphoma (DLBCL) as the most common and aggressive B cell type of non-Hodgkin’s lymphoma, anti-PD-1 and anti-PD-L1 antibodies were studies in various clinical trials. In this review, we summarized the results of several studies associated with PD-1/PD-L1 pathway as an immune evasion mechanism and described clinical trials about targeting therapy against PD-1/PD-L1 pathway in DLBCL.

Even though local stage (Ann Arbor stage I/II) marginal zone lymphoma (MZL) is well controlled with local treatment-based therapy, no data exist on the role of additional chemotherapy after local treatment for stage I/II MZL. Patients with biopsy-confirmed Ann Arbor stage I/II MZL (n = 210) were included for analysis in this study. Of these, 180 patients (85.7 %) were stage I and 30 (14.3 %) were stage II. Most patients (n = 182, 86.7 %) were treated with a local modality including radiation therapy or surgery and 28 (13.3 %) received additional systemic chemotherapy after local treatment. The overall response rate was 98.3 % (95 % CI 96-100 %), with 187 complete responses and 20 partial responses. In the local treatment group, the mean progression-free survival (PFS) was 147.4 months (95 % CI 126.7-168.1 months) and the overall survival (OS) was 188.2 months (95 % CI 178.8-197.7 months). In the additional chemotherapy group, the mean PFS was 103.4 months (95 % CI 84.9-121.9 months) and the OS was 137.3 months (95 % CI 127.9-146.7 months). There was no difference between the two groups in OS (p = 0.836) and PFS (p = 0.695). Local stage MZL has a good clinical course and is well controlled with a local treatment modality without additional chemotherapy.

Because of relapse after horse ATG (hATG) therapy, rabbit ATG (rATG) would be a realistic alternative as second line immunosuppressive therapy (IST) in severe aplastic anemia (SAA) patients. We investigated whether intensified intravenous (IV) CsA therapy with rATG would increase the response of IST in SAA patients. Sixty-one of the 123 patients received IV CsA therapy with rATG during initial 2 weeks then changed to oral form (IV CsA group), while other 62 patients just received oral CsA therapy with rATG (oral CsA group). Hematologic response rates at 3 and 6 months were not different between IV CsA group and oral CsA group (p = 0.795, p = 0.079). However, CsA levels during initial 15 days were higher in response-achieved group than response-not-achieved group. Intensive IV CsA group maintained CsA level ≥300 ng/ml during 15 days had higher responses at 6 months than non-intensive IV CsA group and oral CsA group (p = 0.009, p = 0.021). Intensive IV CsA group (HR = 3.239, 95% CI = 1.095–8.997, p = 0.013) independently predicted favorable the hematologic response at 6 months of IST. Early intensified CsA therapy was important to achieve favorable outcomes in IST including rATG.

We evaluated the incidence, clinical characteristics, and prognostic impact of calreticulin (CALR) mutations in essential thrombocythemia (ET) and primary myelofibrosis (PMF) patients. In all, 48 ET and 14 PMF patients were enrolled, and the presence of CALR mutations was analyzed by direct sequencing. Patients were classified into three subgroups according to Janus kinase 2 (JAK2) V617F and CALR mutation status, and their clinical features and prognosis were compared. CALR mutations were detected in 15 (24.2%) patients, and the incidence increased to 50.0% in 30 JAK2 V617F mutation-negative cases. These included 11 patients with three known mutations (c.1092_1143del [seven cases], c.1154_1155insTTGTC [three cases], and c.1102_1135del [one case]) and 4 patients with novel mutations. ET patients carrying CALR mutation were younger, had lower white blood cell counts, and experienced less thrombosis during follow-up than those carrying JAK2 V617F mutation, while both patient groups showed similar clinical features and prognosis. In ET patients without JAK2 V617F mutation, CALR mutation did not significantly affect clinical manifestation and prognosis. In conclusion, CALR mutation analysis could be a useful diagnostic tool for ET and PMF in 50% of the cases without JAK2 V617F mutations. The prognostic impact of CALR mutations needs further investigation.

Approximately 10-25 % of patients with diffuse large B cell lymphoma (DLBCL) at the time of diagnosis exhibit bone marrow involvement (BMI). After introduction of rituximab, immunohistochemistry (IHC) markers lost to prognostic value in DLBCL patients. However, the specimens used have mainly been diagnostic tissues, not bone marrow (BM). It would thus be useful to determine the prognostic value of specific IHC markers of pathologic BM in DLBCL patients with BMI in the rituximab era. In the present study, a total of 580 DLBCL patients were analyzed 67 of whom had BMI. CD10, Bcl-6, MUM-1, Bcl-6 and Ki-67 dyeing on pathologic BM were applied. Bcl-2 positivity was more frequent in discordant BMI (P = 0.039) and high Ki-67 expression was more frequent in concordant BMI (P = 0.016). High Ki-67 expression independently predicted poor prognosis between the negative BMI group and each of the following BMI-positive groups: entire BMI (PFS, P < 0.001; OS, P < 0.001), concordant BMI (PFS, P = 0.024; OS, P = 0.007), and discordant BMI (PFS, P = 0.033; OS, P = 0.026). We found that Ki-67 expression in pathologic BM is a novel significant prognostic parameter of worse prognosis in DLBCL patients with BMI in the rituximab era.

Purpose This study was conducted to evaluate outcomes in adult patients with Burkitt lymphoma (BL) or Burkitt-like lymphoma treated with an rituximab plus hyper-CVAD (R-hyper-CVAD) regimen by focusing on tolerability and actual delivered relative dose intensity (RDI). Materials and methods Patients ≥ 20 years of age and pathologically diagnosed with BL or Burkitt-like lymphoma were treated with at least one cycle of R-hyper-CVAD as the first-line treatment in this study. Eligible patients' case report forms were requested from their physicians to obtain clinical and laboratory data for this retrospective study. Results Forty-three patients (median age, 51 years) from 14 medical centers in Korea were analyzed, none of which were infected with human immunodeficiency virus. The majority of patients had advanced diseases, and 24 patients achieved a complete response (75.0%). After a median follow-up period of 20.0 months, 2-year event-free and overall survival rates were 70.9% and 81.4%, respectively. Eleven patients (25.6%) were unable to complete the R-hyper-CVAD regimen, including six patients due to early death. The RDIs of adriamycin, vincristine, methotrexate, and cytarabine were between 60% and 65%, which means less than 25% of patients received greater than 80% of the planned dose of each drug. Poor performance status was related to the lower RDIs of doxorubicin and methotrexate. Conclusion R-hyper-CVAD showed excellent treatment outcomes in patients who were suitable for dose-intense chemotherapy. However, management of patients who are intolerant to a dose-intense regimen remains problematic due to the frequent occurrence of treatmentrelated complications.

We retrospectively examined the outcomes of 56 patients with diffuse large B-cell lymphoma (DLBCL) who underwent autologous stem cell transplant (ASCT) with BEAM/BEAC (carmustine, etoposide, cytarabine, melphalan/cyclophosphamide) or busulfan (Bu)-containing conditioning regimens. The Bu group had lower disease-related mortality and more frequent achievement of complete remission (CR) after ASCT from partial remission (PR) or refractory status before ASCT compared with the BEAM/BEAC group. The estimated 2-year EFS (59.3% vs. 15.0%) and overall survival (OS) (70.2% vs. 42.0%) in pre-ASCT rituximab-exposed patients with DLBCL were higher in the Bu group. In patients with high-risk DLBCL exposed to rituximab with first remission, the Bu group had better EFS (p = 0.004) and OS (p = 0.053) rates, while survival rates for relapsed/refractory patients did not differ between groups. Bu regimens are highly effective for preparing patients with DLBCL with previous exposure to rituximab for ASCT, especially in high-risk patients who achieved a first remission.

Chimeric antigen receptor (CAR) T-cell therapy has shown promising clinical impact against hematologic malignancies. CD19 is a marker on the surface of normal B cells as well as most B-cell malignancies, and thus has a role as an effective target for CAR T-cell therapy. In numerous clinical data, successes with cell therapy have provided anticancer therapy as a potential therapeutic option for patients who are resistant to standard chemotherapies. However, recent growing evidence showed the limitations of the treatment such as antigen-positive relapse due to poor CAR T-cell persistence and antigen-negative relapses associated with CAR-driven mutations, alternative splicing, epitope masking, low antigen density, and lineage switching. The understanding of the resistance mechanisms to the cell therapy has developed novel potential treatment strategies, including dual-targeting therapy (dual and tandem CAR), and armored and universal CAR T-cell therapies. In this review, we provide an overview of resistance mechanisms to CD19 CAR T-cell therapy in B-cell malignancies and also review therapeutic strategies to overcome these resistances.

Dear Editor, Src homology 2 B3 (SH2B3), previously named LNK, has been reported as a new genetic abnormality in BCR-ABL negative myeloproliferative neoplasms (MPN) [1,2,3]. In western patients, the mutational hot spot of SH2B3 is located in exon 2, within a pleckstrin homology (PH) domain. However, SH2B3 mutations in Korean MPN patients can occur in several other regions of the SH2B3 gene, including exons 7 and 8 [4]. In this study, we performed sequencing analyses of SH2B3 in Korean patients with BCR-ABL1 negative MPN and compared the results with previous studies. In total, 75 patients were enrolled in the study, comprising 32 patients with essential thrombocytosis (ET), 25 patients with polycythemia vera (PV), 10 patients with primary myelofibrosis (PMF), and eight patients with unclassifiable MPN. All patients were diagnosed between June 2007 and March 2012 at Pusan National University Hospital in Busan, Korea. The patients comprised 40 males and 35 females with a median age of 57.3 yr. This research was reviewed and approved by full committee review of the Institutional Review Board at Pusan National University Yangsan Hospital (No. 05-2014-058). We designed the primers and performed the mutation analyses by direct sequencing of the following loci: SH2B3 exons 2, 7, and 8; Janus kinase 2 (JAK2) exon 12 and V617F mutation; and casitas B-lineage lymphoma proto-oncogene (CBL) exons 8 and 9. Alterations in the CBL gene have been identified in AML, MPN, and chronic myelomonocytic leukemia patients [5]. We identified two different SH2B3 mutations (2.7%) in exon 8 (Fig. 1 and Table 1). A novel p.Q571* (c.1711C>T) mutation which results in a premature stop codon and the known p.I568T (c.1703T>C) missense mutation were identified. In addition, two patients have a known polymorphism, p.A356T (c.1606G>A) [4]. The JAK2 V617F mutation was detected in 48 of 75 patients (64.0%); however, no mutation of JAK2 exon 12 or CBL exons 8 or 9 was identified. One of the two patients with a SH2B3 mutation also harbored a JAK2 V617F mutation (Table 1). Fig. 1 Nucleotide sequence and chromatogram of SH2B3 mutations in Korean patients with BCR-ABL1 negative myeloproliferative neoplasm. (A) Nonsense mutation (c.1711C>T; p.Q571*), (B) missense mutation (c.1703T>C; p.I568T). Table 1 The characteristics of two patients with SH2B3 mutations The mutations in SH2B3 were described in approximately 6.1-25.0% of patients with chronic phase MPN in western countries [1,2,3,6]. In this study, the frequency of SH2B3 mutation was 2.7%, and the mutations were found only in exon 8. Recently, Ha et al. [4] demonstrated that mutational frequency of the SH2B3 gene was 7.1% in exons 7 and 8 in 42 Korean patients with chronic phase MPNs. They reported that three types of SH2B3 mutation accompanied by JAK2 V617F mutation, including p.Q423* located on exon 7, and p.R551W and p.I568T located on exon 8; the p.I568T mutation was also detected in this study. Including this data, mutations of SH2B3 are discovered in exon 7 and 8 in the Korean population, and no mutation was identified in exon 2 of SH2B3 gene. The SH2B3 is known to bind JAK2 and perform a critical role in negative regulation of downstream signal transduction [7]. Pardanani et al. reported the co-occurrence frequency of SH2B3 mutations and the JAK2 V617F mutation and found that SH2B3 mutations occur at similar frequencies in both JAK2 V617F negative and positive patients [6]. The effect of co-occurrence of SH2B3 and JAK2 V671F is still unknown, but an animal model study suggested that a more severe phenotype may result in cases with both mutations [8]. In this study, there were no significant differences in prognosis in patients with SH2B3 mutation according to the presence of JAK2 V617F mutation (Table 1). Therefore, the clinical significance might be investigated in a large-scale study. This study has some limitations, such as the small investigation size and the low detection sensitivity of the direct sequencing method. In addition, since we did not search the entire coding region, there is a possibility of SH2B3 mutations in other regions outside exons 2, 7, and 8. For further study of SH2B3, mutational analysis of either the entire coding region or additional exons needs to be considered. In conclusion, racial differences can cause variances not only in the prevalence but also in the mutational hot spot region of SH2B3. Our study suggests that SH2B3 mutations occur infrequently, and exon 8 in SH2B3 may be the most frequent mutational area in BCR-ABL negative MPN patients in Korea.

This research was supported by the 2012 clinical research grant from Pusan National University Hospital. Authors' Disclosures of Potential Conflicts of Interest: No potential conflicts of interest relevant to this article were reported.

Recent studies have shown that metabolic tumor volume (MTV) by positron emission tomography/computed tomography (PET/CT) is an important prognostic parameter in patients with non‐Hodgkin's lymphoma. However, it is unknown whether doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) alone in early stage Hodgkin's lymphoma would lead to similar disease control as combined modality therapy (CMT) using MTV by PET/CT. One hundred and twenty‐seven patients with early stage Hodgkin's lymphoma who underwent PET/CT at diagnosis were enrolled. The MTV was delineated on PET/CT by the area ≥SUV (max), 2.5 (standardized uptake value [SUV]). Sixty‐six patients received six cycles of ABVD only. The other 61 patients received CMT (involved‐field radiotherapy after 4–6 cycles of ABVD). The calculated MTV cut‐off value was 198 cm(3). Clinical outcomes were compared according to several prognostic factors (i.e. age ≥50 years, male, performance status ≥2, stage II, B symptoms, ≥4 involved sites, extranodal site, large mediastinal mass, CMT, elevated erythrocyte sedimentation rate and high MTV). Older age (progression‐free survival [PFS], P = 0.003; overall survival [OS], P = 0.007), B symptoms (PFS, P = 0.006; OS, P = 0.036) and high MTV (PFS, P = 0.008; OS, P = 0.007) were significant independent prognostic factors. Survival of two high MTV groups treated with ABVD only and CMT were lower than the low MTV groups (PFS, P

Little is known on racial differences in patients with diffuse large B-cell lymphoma (DLBCL). The aim of this retrospective study is to compare characteristics, prognostic factors and outcomes of Asian and Western patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP).Patient-level data was collected from 8 centers. All patients were diagnosed with DLBCL and treated with R-CHOP. Patients were divided into Asian and Western, according to the country of report. Comparisons and univariate/multivariate survival analyses were performed.712 patients, 455 Asian and 257 Western patients were included. Westerners were more likely to present with elevated LDH (64% vs. 48%, p0.01) and advanced stage (58% vs. 49%, p0.01). After a median follow-up of 36 months, there was no difference in progression-free (PFS; p=0.33) or overall survival (OS; p=0.69). There were no PFS or OS differences between races when evaluating separately each age-adjusted International Prognostic Index category. In the multivariate analyses, performance status and stage were associated with PFS and OS in both races.There are no differences in prognostic factors, PFS and OS between Asian and Western patients with DLBCL treated with R-CHOP.

This study investigated whether metabolic tumor volume (MTV) by PET/CT as indicator of extent of lymphoma burden would be a prognostic factor in stage I(E)/II(E) extranodal natural killer/T cell lymphoma (ENKTCL). Eighty patients with stage I(E)/II(E) ENKTCL in the upper aerodigestive tract underwent PET/CT at diagnosis were enrolled and 32 patients received upfront radiotherapy (RTx). MTV was measured on PET/CT images by the extranodal region above SUV, 2.5. Receiver operating curve analyses indicated that an MTV of 35.2 cm(3) was the ideal cut-off to distinguish between low and high MTV groups. Clinical outcomes were compared according to several prognostic factors (age, stage, high performance status [PS], high International Prognostic Index, elevated lactate dehydrogenase [LDH], local tumor invasiveness [LTI], high MTV and up-front RT). High PS, elevated LDH, LTI, high MTV and upfront RT were associated with survivals. In multivariate analysis, high MTV (PFS, HR=4.170, 95% CI=1.714-10.147, p=0.002; OS, HR=4.102, 95% CI=1.617-10.408, p=0.003) and up-front RT (PFS, HR=0.410, 95%CI=0.178-0.946, p=0.037; OS, HR=0.365, 95% CI=0.152-0.872, p=0.023) were significant independent prognostic factors. Upfront RTx and extent of tumor burden, as measured by the MTV, had significant prognostic value in patients with ENKTCL.

There has been controversy surrounding Waldeyer’s ring (WR), especially focused on the question of whether it should be regarded as a nodal or an extranodal site. We conducted retrospective analyses of marginal zone B cell lymphomas involving WR (WR-MZLs) to observe their clinical features and prognosis, with specific regard to the nodal-or-extranodal question. A total of 52 patients with histological diagnosis of WR-MZL were retrospectively analyzed. The most common involvement site was the tonsil (40.4 %). Ann Arbor stage III/VI disease was present in 48.1 % (25 of 52). The response rate of the 27 stage I/II patients was 88.9 %, with 21 complete remissions and three partial remissions. The median time to progression (TTP) was 3.7 years (95 % CI 2.5–4.9 years). The estimated 5-year TTP and overall survival rates were 39.4 and 90.5 %, respectively. In a comparison with the historical data regarding extra-WR MALT lymphoma and nodal MZL (N-MZL), MALT lymphoma showed better TTP results than did WR-MZL and N-MZL (P

Our objective was to evaluate the non-germinal center (GC) profile as a marker for response and survival in DLBCL and to compare the characteristics of patients with GC and non-GC DLBCL treated with rituximab-containing regimens. In this patient-level meta-analysis, retrospective data from 712 newly diagnosed DLBCL patients treated with chemoimmunotherapy from 7 centers were analyzed. GC and non-GC profiles were defined according to the Hans algorithm. Although the non-GC profile showed a trend towards worse overall survival (HR 1.24, 95% CI 0.92-1.66; p=0.15) and progression-free survival (HR 1.29, 95% CI 0.96-1.73; p=0.09), it did not retain its value in the multivariate survival analysis. Additionally, the non-GC profile was independently associated with worse complete response rates (OR 0.55, 95% CI 0.37-0.83; p

Primary gastrointestinal (PGI) diffuse large B cell lymphoma (DLBCL) is a relatively common disease. Recent studies indicate that measurement of maximum standardized uptake value (SUV(max)) on pretreatment for (18)F‐fluorodeoxyglucose PET is an important prognostic factor in PGI DLBCL. However, there is still an association between initial tumor burden and prognosis. Thus, in the present study, we investigated whether tumor volume by PET could have a potential prognostic value to predict the outcome. From 2006 to 2009, 165 Stage I E/II E PGI DLBCL patients were enrolled in the study. One hundred and five patients received cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (R‐CHOP) only, whereas 60 patients underwent surgery plus R‐CHOP. Metabolic tumor volume (MTV) was defined initial tumor burden as target GI lesion above SUV, 2.5 by PET as a contouring border. Over a median follow‐up period of 36.6 months, receiver operating characteristic (ROC) analysis indicated that the best cut‐off values for MTV and SUV(max) were 160.1 cm(3) and 12.0, respectively. The estimated area under the ROC curve was higher for MTV than SUV(max). Thus, MTV was a better predictor for survival than SUV(max). In patients with a low MTV (160.1 cm(3)), survival was longer in those who underwent surgery plus R‐CHOP than in those treated with R‐CHOP alone (P

Purpose: Primary thyroid marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type (pTY-MZL) is an extremely uncommon form of lymphoma. Due to its rarity, the natural history and optimal treatment modality for this disease have yet to be clearly established. Methods: A total of 27 patients with histologically confirmed pTY-MZL were retrospectively analyzed. Results: The median age of our subjects was 53 years (range 25–82). This study involved 17 females (63.0%) and 10 males (37.0%). Twenty-four out of 27 patients (88.9%) initially presented with localized disease, defined by Ann Arbor stage I/II. Bone marrow involvement was detected in 8.3% of the patients (2 patients), and 91.7% of the patients (25 of 27) were categorized into the low or low-intermediate risk group, according to the International Prognostic Index criteria. Accompanying Hashimoto’s thyroiditis was detected in 72% of the patients, whereas thyroglobulin antibody levels were elevated in 70% of the patients. Twenty-six patients were treated with surgery, radiotherapy or chemotherapy, and 25 patients achieved complete remission. During the follow-up period, only 2 patients evidenced progression, and no deaths occurred over the course of the study. Conclusion: pTY-MZL tends to be an indolent disease. However, unlike other mucosa-associated lymphoid tissue site MZLs, pTY-MZL was well controlled via several treatment modalities, and the patients’ responses were sustained for a prolonged period.

BACKGROUND/AIMS Autologous stem cell transplantation (ASCT) has become the treatment of choice for patients with multiple myeloma (MM). Studies have shown that maintenance treatment with interferon-alpha is associated with improved survival rates following ASCT. However, despite these recent advances in regimes, relapses are inevitable; thus, the prediction of relapse following ASCT requires assessment. METHODS We retrospectively analyzed 39 patients who received ASCT between 2003 and 2008. All patients received chemotherapy with vincristine, adriamycin, and dexamethasone (VAD), and ASCT was performed following high-dose melphalan conditioning therapy. We evaluated the influence of the post-transplant day +14 (D+14) bone marrow plasma cell percent (BMPCp) (≥ 2 vs. < 2%), international scoring system (ISS) stage (II vs. III), response after 3 cycles of VAD therapy (complete response [CR] vs. non-CR), deletion of chromosome 13q (del[13q]) (presence of the abnormality vs. absence), and BMPCp at diagnosis (≥ 50 vs. < 50%) on progression-free survival (PFS) and overall survival (OS). RESULTS During the median follow-up of 28.0 months, the median PFS and OS were 29.1 and 42.1 months, respectively. By univariate analysis, ISS stage III at diagnosis, BMPCp ≥ 50% at diagnosis, CR after 3 cycles of VAD therapy, del (13q) by fluorescence in situ hybridization, and BMPCp ≥ 2% at post-transplant D+14 were correlated with PFS and OS. A multivariate analysis revealed that a post-transplant D+14 BMPCp ≥ 2% (PFS, hazard ratio [HR] = 4.426, p = 0.008; OS, HR = 3.545, p = 0.038) and CR after 3 cycles of VAD therapy (PFS, HR = 0.072, p = 0.014; OS, HR = 0.055, p = 0.015) were independent prognostic parameters. CONCLUSIONS Post-transplant D+14 BMPCp is a useful parameter for predicting the outcome for patients with MM receiving ASCT.

Juvenile xanthogranuloma(JXG) is the variant of non-Langerhans' cell histiocytosis. The orange-yellow background coloration with clouds of paler yellow deposits is the most characteristic dermoscopic finding of JXG. Other dermoscopic features include erythematous border, subtle pigment network and white linear streak. The objective of this study was to present the structural correlation between dermoscopic features and histopathological findings of JXG and to find the different dermoscopic features in various stages of JXG. Eleven patients with histologically proven JXG were examined with polarized light dermoscopy. Histopathological findings were assessed and dermoscopic features including setting sun appearance, clouds of paler yellow globules, whitish streak, and branched and linear vessels were evaluated. Among 11 patients, five patients were in early evolutionary stage, four patients in fully developed stage and two in late regressive stage. The setting sun appearance was found in all patients in different stages except one in late regressive stage (90.9%). The clouds of paler yellow globules were present in nine patients (81.8%) and were constant features in fully developed stage and late regressive stage. The whitish streak was present in four patients (36.4%) and telangiectasia in 10 patients (81.8%). The setting sun appearance may hold diagnostic value in early evolutionary stage to fully developed stage, but not in late regressive stage. The clouds of paler yellow globules are more predominant in fully developed stage and late regressive stage. In addition to the use of dermoscopy as an accurate diagnostic tool for differential diagnosis, it could be applied in evaluation of histopathological maturation of JXG.

Dear Editor Plasmacytoma, a neoplastic proliferation of plasma cells, is a type of plasma cell dyscrasia that may manifest as multiple myeloma, primary amyloidosis, or monoclonal gammopathy of unknown significance. Extramedullary plasmacytoma rarely involves the mediastinum [1]. Simultaneous detection of mediastinal plasmacytoma and myelomatous pleural effusion accompanying myeloma is very rare. Furthermore, an amylase-producing multiple myeloma appears to be a fairly unusual phenomenon. This is a rare case of simultaneous extramedullary plasmacytoma and myelomatous pleural effusion with increased salivary-type amylase levels without evidence of pancreatic or salivary gland involvement. This is the first reported case of mediastinal plasmacytoma and myelomatous pleural effusion as an initial presentation accompanying a salivary-type amylase-producing multiple myeloma in Korea. A 65-yr-old man was admitted with an anterior chest mass associated with dyspnea and nausea. Physical examination showed a 9×9 cm suprasternal mass with diffuse borders. Chest computed tomography (CT) showed an anterior mediastinal mass with anterior chest wall invasion and right pleural effusion and subsequent bilateral involvement. Provisional diagnosis of mediastinal lymphoproliferative disorder with malignant pleural effusion was made. The pleural effusion was tapped and found to be an exudate with an unusually high level of pleural fluid amylase, 5,809.7 IU/L, >4.4 times the serum value. Cytospin analysis of pleural effusion showed a proliferation of medium-sized oval cells with eccentric nuclei, abundant basophilic cytoplasm, and perinuclear halo, resembling plasma cells (Fig. 1). Fig. 1 Histologic examination of the pleural fluid (A), mediastinal mass (B and C), and bone marrow (D, E, and F). (A) Cytospin analysis of pleural fluid shows increased plasma cells with eccentric nuclei and abundant basophilic cytoplasm, consistent with myelomatous ... The patient underwent an ultrasonography-guided biopsy of the anterior chest wall mass. Histologically, the tumor was characterized by a well-circumscribed proliferation of plasma cells that was positive for CD138 and lambda light chain on immunohistochemical stains (Fig. 1). The patient's mediastinal plasmacytoma was diagnosed at this time. There were no osteolytic regions on cranial, spinal, and pelvic radiographs. Serum protein electrophoresis and immunoelectrophoresis were unremarkable, but urine protein electrophoresis demonstrated a monoclonal peak in the beta immunoglobulin region, and urinary immunoelectrophoresis including IgD and IgE revealed an abnormal arc in the lambda light chain. Bone marrow aspiration and biopsy demonstrated hypercellular marrow with moderate neoplastic plasma cell proliferation (35%), consistent with plasma cell myeloma (Fig. 1). Immunohistochemical staining of the bone marrow specimen also showed neoplastic plasma cells positive for CD138, lambda light chain, and CD56. Chromosome analysis of the bone marrow specimen revealed 41,X,-Y,i(1)(q10),-4,-10,-16,-22[6]/42,idem,+add(16)(q24)[7]/46,XY[17]. Due to lack of bone marrow specimens, initial FISH profile for myeloma including IgH/CCND1 rearrangement, IgH/MAF rearrangement, IgH/FGFR3 rearrangement, 1q21 abnormalities, TP53 loss, and 13q14 loss was not performed. Karyotypic results showing hypodiploidy and 1q abnormalities could be suggestive of poor prognosis of tumor progression and advanced disease status. To study the increased amylase level in the pleural fluid, serum and urine amylase levels were measured. Amylase levels were up to 1,312.1 IU/L (reference range, 36-128 IU/L) in serum and 7,507.5 IU/L (reference range, 0-1,500 IU/L) in urine. Abdominal ultrasonography and CT revealed no significant pancreatic abnormality. The serum lipase level was within reference range. Amylase isoenzyme electrophoresis of serum and urine predominantly showed salivary-type total amylase (97.1% and 92.7%, respectively) (Fig. 2). Unfortunately, amylase isoenzyme electrophoresis of pleural effusion was not performed. Fig. 2 Amylase isoenzyme electrophoreses of serum and urine shows that the level of the salivary-type isoenzyme is the highest, consistent with salivary-type amylase-producing myeloma. On the basis of these findings, the patient was finally diagnosed as having salivary-type amylase-producing mediastinal plasmacytoma with myelomatous pleural effusion. He received two courses of induction chemotherapy consisting of intravenous thalidomide, cyclophosphamide, and dexamethasone. For the management of the mediastinal mass and myelomatous pleural effusion, radiotherapy was administered. After chemotherapy with radiotherapy, urine amylase (2,042.6 IU/L) and lambda light chain (504 mg/L) levels were markedly decreased. Extramedullary plasmacytoma in multiple myeloma is associated with aggressive disease, leading to shorter overall survival and progression-free survival [2]. Because the human salivary amylase gene (AMY1) is located in chromosome 1p21 [3, 4], the chromosome 1p deletion in our patient resulted in the structural deletion of chromosome 1p21, and such structural alteration might cause an uncontrolled production of amylase by plasma cells, leading to an elevated amylase level. Duplication of all or part of the 1q chromosome and whole arm translocation of 1q in multiple myeloma are associated with tumor progression and advanced disease [5, 6]. Our patient had high amylase levels in the serum, urine, and pleural fluid. After induction chemotherapy and radiotherapy for mediastinal plasmacytoma and myelomatous pleural effusion, amylase levels in the serum and urine were markedly decreased. This finding suggests that the neoplastic plasma cells directly produced salivary-type amylase in this case. This evidence supports the hypothesis that salivary-type amylase levels in serum, urine, and other fluids are indicative of myeloma disease progression and treatment response [7]. A recent research revealed that patients with amylase-producing myeloma commonly present with salivary-type amylase isoenzyme production, high tumor mass, extensive extramedullary spread, extensive bone destruction, and poor prognosis; therefore, in these patients, a simple test such as serum amylase level may represent a reliable disease activity index and provide additional prognostic information [7]. To our knowledge, salivary-type amylase-producing multiple myeloma presenting with mediastinal plasmacytoma and myelomatous pleural effusion as seen in our patient is extremely rare. Although the precise mechanism of development of hyperamylasemia in myeloma is not well understood, chromosome 1p deletion in this patient can result in a functional change in the AMY1 gene located on chromosome 1p21. In patients with salivary-type amylase-producing multiple myeloma, a simple test such as estimating serum amylase levels may provide reliable disease activity and prognostic information.

Although numerous studies about primary extranodal diffuse large B cell lymphoma (DLBCL) were reported sporadically, the literature of clinical value of immunophenotype and bulky diameter in rituximab era is limited. Ninety-six patients with primary extranodal DLBCL receiving R-CHOP therapy were analyzed to evaluate whether immunophenotype and size of bulky disease are significantly important. The International Prognostic Index was still an important prognostic factor for progression-free survival (PFS) and overall survival (OS; p = 0.003, p = 0.027). Difference of survival between germinal center (GC) type and non-GC type was not different (PFS: p = 0.192; OS: p = 0.197). In two separated groups according to extranodal maximum tumor diameter (EN-MTD) 7.5 cm as cutoff value for survival, the group of EN-MTD ≥7.5 cm had lower PFS and OS than

This study analyzed the outcomes of myelodysplastic syndrome patients treated with azacitidine. Between August 2006 and June 2008, a total of 126 patients were treated with azacitidine at a dose of 75 mg/m(2)/day subcutaneously for 7 days, which was repeated every 28 days. The median age of the patients was 64 (range, 20-82) years. Forty-three patients (33.4%) were classified as intermediate-2 and high risk according to International Prognostic Scoring System (IPSS), while 61 patients (47.3%) were classified as high and very high risk according to WHO Prognostic Scoring System (WPSS). Sixty patients (47.6%) exhibited a response at the median of 3 (range, 1-5) cycles. A complete response was observed in 21 patients (16.7%), a partial response in six patients (4.8%), and total hematologic improvement in 61 patients (48.4%). For the IPSS risk group, the median survival for the patients with intermediate-1 was 20.0 months, for intermediate-2 was 14.9 months, and for high risk was 6.3 months (p = 0.008). For the WPSS risk group, the median survival duration was 21.3 months for the very low and low risk patients, 16.5 months for intermediate risk patients, and 14.9 months for the high and very high risk patients (p = 0.003). The patients with higher than normal lactate dehydrogenase (LDH) levels at the time of diagnosis showed a poor survival (p = 0.003). The median survival duration for the patients with high LDH levels was 13.9 months, while that for the patients with normal LDH levels was 20.6 months. The multivariate analyses revealed that high LDH levels [hazard ratio (HR) 4.384, p < 0.001] and high and very high WPSS risk group (HR 3.855, p = 0.014) were significantly associated with a worse survival, whereas a response to azacitidine was identified as a good prognostic factor for survival (HR 0.224, p = 0.019). In conclusion, while the pretreatment risk group and initial LDH levels were both confirmed as important prognostic factors to predict the outcomes for patients treated with azacitidine, more effective therapies are still needed to prevent disease progression.

A high absolute lymphocyte count (ALC) at diagnosis is known as a surrogate marker of favorable prognosis in newly diagnosed multiple myeloma (MM). Recent studies showed tumor sensitization and enhanced cytotoxicity of bortezomib. We hypothesized that a high ALC before bortezomib treatment would contribute to tumor sensitization and activated cytotoxicity of bortezomib in relapsed MM. Ninety-seven relapsed MM patients who underwent bortezomib-dexamethasone (Vel-Dex) therapy were analyzed. Median follow-up duration was 21 months and median age was 61 years. Complete response (CR) and very good partial response (VGPR) after 2 cycles of Vel-Dex therapy were higher in the high-ALC group (≧1.1 × 109/l) (CR + VGPR 50.0% in the high-ALC group vs. 10.4% in the low-ALC group, p = 0.001), and stable disease (SD) rate was lower in the high-ALC group (SD 11.8% in the high-ALC group vs. 44.8% in the low-ALC group, p < 0.001). In the univariate analysis, the low-ALC group before therapy was associated with shorter progression-free survival (PFS) [hazard ratio (HR), 2.780; 95% confidence interval (95% CI) 1.703–4.536, p < 0.001]. Multivariate analysis revealed that a low ALC represented an independent predictive factor for PFS (HR 1.937, 95% CI 1.168–3.212, p = 0.010). A low ALC just before Vel-Dex therapy was associated with a poor prognosis in relapsed MM.

To evaluate the prognostic value of the metabolic tumor volume measured on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging and other clinical factors in patients treated for locally advanced head-and-neck cancer (HNC) at a single institution.Between June 2005 and August 2008, 59 patients with HNC that underwent pretreatment FDG-PET studies received neoadjuvant chemotherapy and radiation therapy. Metabolically active tumor regions were delineated on the pretreatment PET scans by a fixed SUV of 2.5. We evaluated the relationship of the 18F-fluorodeoxyglucose-PET maximum standardized uptake value (SUV) and the metabolic tumor volume (MTV) with the progression-free survival (PFS) and overall survival (OS).The MTV and lymph node metastasis were predictive of the PFS and OS. The lymph node status did not correlate with the MTV. A higher MTV of 9.3 cm(3) was significantly associated with an increased risk of recurrence (2.19-fold, p = 0.006) and death (1.62-fold, p = 0.051). Separation of patients with tumor volumesor= 9.3 cm(3) and no lymph node disease vs. any other combination was strongly predictive of the PFS and the OS.MTV and lymph node status were prognostic values associated with survival. Quantitative measurement of tumor volume separates patients with a good prognosis from those with a poorer prognosis. A subset of patients with relatively small tumors and no lymph node involvement did very well.

Imatinib-induced macrocytic anemia was known to result from c-kit inhibition in chronic myeloid leukemia (CML). However, recent studies showed that the prevalence of anemia is increased with high trough imatinib level and increased doses of imatinib influence decreased proliferation of burst forming units-erythroids (BFU-Es). The aim of this study was to evaluate the continuously increased mean cell volume (MCV) level's correlation with cytogenetic response and the favorable outcome in early chronic phase (CP)-CML patients. Clinical importance of MCV level was evaluated to correlate with cytogenetic response and compared with Sokal score, a known excellent prognostic parameter of cytogenetic response (CCR) in 84 early CP-CML patients. The patients with early and continuously increased MCV level irrespective of anemia achieved higher CCR after 12 months of imatinib therapy than patients with non-CCR (p=0.011). When the value was compared with low Sokal score, elevated MCV was independent predictor of CCR (RR=12.925, p=0.002 vs. RR=35.445, p0.001). Furthermore, the patients with early and continuously increased MCV level had a higher probability of maintaining CCR than non-increased level (p=0.019). Increased MCV level was surrogate marker of achievement and durability to CCR for early CP-CML patients in the present study.

Background Used as individual agents, topical antibiotics and benzoyl peroxide are known to be effective in treatment of acne. Clindamycin phosphate 1% with benzoyl peroxide 5% (CDP/BPO) is a new combination gel, made by rationale, in that combination drug is more effective than either ingredients used alone. Adapalene 0.1% (ADA) is the third-generation retinoid, shown to be as effective as other topical retinoid with well tolerability. Objectives To compare the efficacy and tolerability in combination of CDP/BPO in comparison with ADA in Asian patients with mild to moderate acne vulgaris. Methods Total of 69 patients, including 31 patients for CDP/BPO group and 38 for ADA group, with mild to moderate acne vulgaris were enrolled for a 12-week prospective, randomized, open-label comparative study of topical agents. Efficacy was assessed by lesion counts, acne grading system, and global improvement. Adverse events were also evaluated in scale of 0 (none) to 3 (severe). Results Both CDP/BPO and ADA were effective in reducing lesion counts and acne severity scale and showed significant global improvement. However, CDP/BPO offered greater efficacy against inflammatory lesions than ADA. Both drugs were well tolerated with minimal adverse drug reactions. Conclusion Combination formulation of CDP/BPO and ADA were shown to be both effective in decreasing total, inflammatory, and non-inflammatory lesion counts along with well tolerability in Asian patients with mild to moderate acne vulgaris. Conflicts of interest None declared

Background Basal cell carcinoma (BCC) is by far the most common cancer in white populations. In addition, recent reports have demonstrated an increasing incidence of BCC in Korea. We have observed a significant number of early-onset BCC cases in which the disease occurred in patients younger than 50 years. Objective To investigate the clinicopathological characteristics of early-onset BCC in an Asian population, specifically in Koreans. Methods One hundred and five patients with early-onset BCC were enrolled from a total of 1047 BCC patients who underwent surgery between January 1997 and December 2014 (942 patients over the age of 50 years were designated as the control group). Results Early-onset BCC accounted for 10.03% of all 1047 cases and the incidence over time displayed an incremental trend. The early-onset group displayed similar results as the control group, with a predominance of female BCC patients and the majority of tumours displaying the following characteristics: small in size, occurring in sun-exposed areas and belonging to the noduloulcerative clinical subtype and nodular histopathological subtype. In comparison with a previous study in a Western population, the incidence of the disease in non-exposed areas of the body, as well as the proportion of tumours of the superficial histological subtype, were lower in Asian patients. Conclusion Although the clinicopathological characteristics of BCC are well-known, these characteristics have not been determined for early-onset BCC in an Asian population. Therefore, this study is the first report on early-onset BCC in Asians, specifically in a Korean patient group.

Bone marrow involvement (BMI) in diffuse large B cell lymphoma (DLBCL) was naively regarded as an adverse clinical factor. However, it has been unknown which factor would separate clinical outcomes in DLBCL patients with BMI. Recently, metabolic tumor volume (MTV) on positron emission tomography/computed tomography (PET/CT) was suggested to predict prognosis in several lymphoma types. Therefore, we investigated whether MTV would separate the outcomes in DLBCL patients with BMI. MTV on PET/CT was defined as an initial tumor burden as target lesion ≥ standard uptake value, 2.5 in 107 patients with BMI. Intramedullary (IM) MTV was defined as extent of BMI and total MTV was as whole tumor burden. 260.5 cm(3) and 601.2 cm(3) were ideal cut-off values for dividing high and low MTV status in the IM and total lymphoma lesions in Receiver Operating Curve analysis. High risk NCCN-IPI (p

Background.DNA methyltransferase 3A(DNMT3A) mutation was recently introduced as a prognostic indicator in normal karyotype (NK) AML and we evaluated the incidence and prognostic impact ofDNMT3Amutations in Korean NK AML patients.Methods. Total 67 NK AML patients diagnosed during the recent 10 years were enrolled.DNMT3Amutations were analyzed by direct sequencing and categorized into nonsynonymous variations (NSV), deleterious mutations (DM), and R882 mutation based onin silicoanalysis results. Clinical features and prognosis were compared with respect toDNMT3Amutation status.Results. Three novel (I158M, K219V, and E177V) and two known (R736H and R882H) NSVs were identified and the latter three were predicted as DMs.DNMT3ANSVs, DMs, and R882 mutation were identified in 14.9%–17.9%, 10.3%–10.4%, and 7.5% of patients, respectively.DNMT3Amutations were frequently detected inFLT3ITD mutated patients (P= 0.054, 0.071, and 0.071 in NSV, DMs, and R882 mutation, resp.) but did not affect clinical features and prognosis significantly.Conclusions. Incidences ofDNMT3ANSVs, DMs, and R882 mutation are 14.9%–17.9%, 10.3%–10.4%, and 7.5%, respectively, in Korean NK AML patients.DNMT3Amutations are associated withFLT3ITD mutations but do not affect clinical outcome significantly in Korean NK AML patients.

Therapy-induced autoimmunity may mediate the destruction of cancer cells. Previous studies have demonstrated that presence of autoimmune thyroid disorder is associated with favorable outcome in patients with solid cancer. Patients with diffuse large B cell lymphoma (DLBCL) who achieved complete response on positron emission tomography/computed tomography (PET/CT) after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy were enrolled in this study. The patients with and without diffuse thyroid uptake (DTU) were classified by PET/CT. A total of 270 patients were enrolled in this study. DTU related to autoimmune thyroiditis was present in 61 patients. The median time to DTU detection was 5.7 months (range, 0–21.3 months). High International Prognostic Index (IPI) score (progression-free survival [PFS], p = 0.001; overall survival [OS], p = 0.008), bulky mass ≥10 cm (PFS, p = 0.001; OS, p = 0.001), bone marrow involvement (PFS, p < 0.001; OS, p = 0.001), and DTU after R-CHOP therapy (PFS, p < 0.001; OS, p = 0.001) were significantly associated with PFS and OS. High IPI score (PFS, p = 0.003; OS, p = 0.014), BM involvement (PFS, p = 0.009; OS, p = 0.039), and DTU after R-CHOP therapy (PFS, p = 0.002; OS, p = 0.002) were independently associated with PFS and OS. DTU after R-CHOP therapy independently predicted favorable outcomes in patients with DLBCL.

Rituximab improved prognosis in diffuse large B cell lymphoma (DLBCL). However, activity of rituximab may be reduced by conformational change in CD20 by statin-induced cholesterol depletion. Conformation change in CD20 could impair the binding of rituximab and significantly decrease the killing effect of lymphoma cells. R-CHOP therapy could counteract the prognostic gap between GC type and non-GC type. We investigated whether statin use could have different clinical impacts on immunohistochemical DLBCL subtypes in the rituximab era. We analyzed data from 409 patients with de novo DLBCL who received R-CHOP therapy. During median follow-up time of 38.6 months, 3-year progression-free survival (PFS) and overall survival (OS) in the GC type were similar to those in the non-GC type (PFS, p = 0.125; OS, p = 0.201). Moreover, survivals were comparable between patients with statin therapy and those without the statin therapy (PFS, p = 0.282; OS, p = 0.273). We also analyzed whether statin therapy would have clinical significance by immunophenotypes in patients treated with R-CHOP therapy. The non-GC type with statin therapy had inferior PFS and OS compared to other groups (PFS, p = 0.008; OS, p = 0.006). In multivariate analysis, statin therapy had significant negative impacts on survivals of the non-GC type independent of other clinical factors (PFS, hazard ratio/HR: 1.553, 95% CI: 1.058–2.279, p = 0.024; OS, HR = 1.532, 95% CI: 1.041–2.255, p = 0.023). Therefore, statin therapy negatively affected the clinical outcome of the non-GC phenotype, but it was beneficial to R-CHOP therapy in DLBCL.

Introduction Fluorescence in-situ hybridization (FISH)-detected abnormalities, including del(17p), del(13q), and t(4;14), have been associated with inferior prognosis. However, there are few data about the prognostic significance of cytogenetic abnormalities for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients with extramedullary plasmacytoma (EMP). Patients and Methods Between April 2004 and December 2012, 290 MM patients underwent ASCT at 3 centers. FISH data for bone marrow samples obtained at diagnosis were available for 58 patients who had EMP at diagnosis or during treatment. Results The t(11;14), t(4;14), del(13q), and 1q gain abnormalities were seen in 14.9%, 6.3%, 25.6%, and 42.9%, respectively. No t(14;16) or del(17p) cytogenetic abnormality was detected in the examined patients. Patients with t(11;14) had a lower response rate compared to patients with other cytogenetic abnormalities. EMP-specific relapse was higher in patients with t(11;14) than in patients with other cytogenetic abnormalities (42.9% vs. 10%-33.3%). Each of the 4 cytogenetic abnormalities predicted shorter median progression-free survival (6-12 months vs. 27-37 months) and shorter overall survival (16-22 months vs. 68 months or not reached) compared to no cytogenetic abnormality. The t(11;14) translocation was an important prognostic factor for both progression-free survival (hazard ratio, 25.154; P P = .024) in the multivariate analysis. Conclusion In the current study, t(11;14), t(4;14), del(13q), and 1q gain were associated with worse survival in MM patients with EMP. The role of t(11;14) as a prognostic parameter for ASCT in MM patients with EMP should be confirmed with a large, well-designed study.

We evaluated the clinical outcomes and relapse patterns of 80 patients with primary sinonasal tract diffuse large B-cell lymphoma (SN-DLBCL) treated with rituximab-cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) chemotherapy at 22 institutions. A total of 59 (73.8%) patients received R-CHOP chemotherapy alone, whereas 21 (26.3%) were treated with R-CHOP followed by involved field radiotherapy (IFRT). In 73 patients with Ann Arbor stage I-II disease, no significant difference was found in the response rate or overall survival (OS) between R-CHOP alone (n = 52) and R-CHOP followed by IFRT (n = 21). Among 11 relapsed patients in this study, the most common pattern of relapse was local (n = 8, 11.8%), whereas central nervous system (CNS) relapse was observed in only one (1.9%) patient. These results suggest that patients with primary SN-DLBCL treated with R-CHOP have a relatively low CNS relapse rate and better OS compared to previous studies before the introduction of R.

We aimed to compare the characteristics of skeletal and soft tissue plasmacytomas and to analyze clinical outcomes and prognostic factors of autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients with plasmacytoma. We retrospectively reviewed data from 93 myeloma patients with detectable extramedullary (EM) plasmacytoma at diagnosis or during the course of the disease, who underwent ASCT. Soft tissue plasmacytoma occurred more frequently in male patients and had higher levels of serum β2-microglobulin and lactate dehydrogenase and high frequency of advanced disease according to International Staging System compared to the skeletal plasmacytoma group. Both soft tissue and skeletal plasmacytoma groups showed similar plasmacytoma relapse patterns after ASCT and relapsed with EM plasmacytoma slightly more frequently in the bone compared to soft tissue sites. Compared to patients with skeletal plasmacytoma, patients with soft tissue plasmacytoma had worse median progression-free survival (PFS) (12 vs. 28 months) (P = 0.001) and overall survival (OS) (37 vs. 67 months) (P = 0.037) after ASCT. In a multivariate analysis, soft tissue plasmacytoma was an only independent poor prognostic factor for both PFS (HR, 2.398; 95% CI, 1.304-4.410) and OS (HR, 2.811; 95% CI, 1.107-7.135) after ASCT. These results demonstrate that, even though ASCT achieved a strong response in myeloma patients with soft tissue plasmacytoma, the presence of EM disease still contributed to a poor prognosis after ASCT compared to skeletal plasmacytoma, and these poor outcomes were not overcome by ASCT.

Summary We investigated the prognostic value of the magnetic resonance imaging (MRI) pattern of bone marrow involvement in patients with multiple myeloma (MM) eligible for autologous stem cell transplantation (ASCT). 126 patients with untreated MM indicated for ASCT underwent spine MRI and cytogenetic analysis at diagnosis. All patients received ASCT after induction therapy of VAD (vincristine, doxorubicin, dexamethasone; n = 55) or a thalidomide-based regimen (TCD; n = 71). Thalidomide maintenance therapy was performed in 68 patients. The MRI pattern was normal in 27, focal in 47, and diffuse/variegated in 52 patients. Patients with the diffuse/variegated pattern showed significantly higher stage (P = 0·038), higher β-2 microglobulin level (P = 0·001) and severe anaemia (P = 0·015). However, the cytogenetics were not different among the MRI patterns (P = 0·890). Progression-free survival (PFS) was lower in the diffuse/variegated pattern (P = 0·002) than other patterns, but not overall survival (OS) (P = 0·058). Thalidomide maintenance therapy was correlated only with PFS (P = 0·001). High-risk cytogenetics were associated with both poorer PFS (P

As part of an effort to develop a more effective and safe treatment for relapsed or refractory non-Hodgkin's lymphoma (NHL), we conducted a phase II study of the oxaliplatin, etoposide, and ifosfamide (IFETOx) regimen. Patients with relapsed or refractory NHL and a performance status of 0-2 were eligible. The IFETOx consisted of etoposide at 100 mg/m(2) on days 1-3, oxaliplatin at 130 mg/m(2) on day 2, and ifosfamide 5,000 mg/m(2) on day 2, every 21 days. The primary endpoint was the overall response rate (ORR) for IFETOx regimen. A total of 23 eligible patients were enrolled. The median age was 58 years (range 19-76 years), and the male-to-female ratio was 15:8. The disease status was as follows: 15 patients had relapsed and 8 patients were refractory to treatment. The ORR for IFETOx chemotherapy was 65.2 %. In the 15 patients who responded to the protocol treatment, five underwent hematopoietic stem cell transplantation. The 2-year probability of progression-free survival and overall survival rates were 51.4 and 56.1 %, respectively. Grade 3/4 neutropenia was observed in 73.9 % of the patients. No significant renal impairment was observed. In conclusion, IFETOx chemotherapy shows a tolerable toxicity profile and efficacy as a salvage treatment regimen for relapsed or refractory NHL.