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We assessed the efficacy and toxicity of etoposide, methylprednisolone, high-dose cytarabine, and oxaliplatin (ESHAOx) combination chemotherapy in patients with refractory or relapsed Hodgkin's lymphoma (HL). This was an open-label, non-randomized, multi-center phase II study. The ESHAOx regimen consisted of intravenous (i.v.) etoposide 40 mg/m2 on days 1 to 4, i.v. methylprednisolone 500 mg on days 1 to 5, i.v. cytarabine 2 g/m2 on day 5, and i.v. oxaliplatin 130 mg/m2 on day 1. Cycles (up to six) were repeated every 3 weeks. In an effort to identify prognostic markers, the serum levels of cytokines including tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and vascular endothelial growth factor (VEGF) were measured at the time of study entry. A total of 37 patients were enrolled, and 36 were available for evaluation of tumor response. The overall response rate was 72.2% (26/36) (complete response, 33.3% [12/36]; partial response, 38.9% [14/36]). The median time to progression was 34.9 months (95% confidence interval, 23.1-46.7 months). The most common grade 3 or 4 hematological adverse events were neutropenia (16/37, 43.2%), followed by thrombocytopenia (10/37, 27.0%). Grade 3 or 4 non-hematological adverse events were nausea (3/37, 8.1%), anorexia (2/37, 5.4%), mucositis (1/37, 2.7%), and skin rash (1/37, 2.7%). There were no treatment-related deaths. High levels of TNF-α and CRP were significantly associated with poorer overall survival (p = 0.00005 for TNF-α, p = 0.0004 for CRP, respectively). The ESHAOx regimen exhibited antitumor activity and an acceptable safety profile in patients with refractory or relapsed HL. Trial Registration: ClinicalTrials.gov. Registered February 21, 2011, https://clinicaltrials.gov/ct2/show/NCT01300156. [ABSTRACT FROM AUTHOR]

Both-side synchronous involvement has been reported to account for 7-24% of ocular adnexal marginal zone lymphoma (OAML). We conducted a retrospective analysis to identify the clinical features and treatment outcomes of synchronous bilateral OAML (SB-OAML) by treatment modality. We analyzed patients with a histologic diagnosis of SB-OAML, excluding metachronous bilateral involved OAML. We enrolled a total of 95 patients for this analysis, 36 males and 59 females; the median patient age was 42 years (range 16-77 years). Eleven (11.6%) patients had been treated with chemotherapy or chemo-immunotherapy (eight R-CVP, two CVP, and one R-CHOP). The median number of treatments was 6 (range 6-8); there were 9 complete responses (CRs; 81.8%) and 2 partial responses (PRs; 18.2%). Nearly all patients (88.4%) received radiotherapy in both eyes, and the median radiation dose was 27 Gy (range 20-40 Gy) to each eye; 68 CRs (80.9%) and 14 PRs (16.7%) were achieved. Ten-year progression-free survival (PFS) and overall survival (OS) rates were 79.8 and 91.1%, respectively. Radiotherapy continued to be an independent prognostic marker, with the hazard of progression (P = 0.036). Eleven patients (13.1%) had surgery for cataract treatment during follow-up, and patients who received low-dose radiation (< 30.3 Gy) experienced fewer cataract operations. SB-OAML was predominantly observed in young females, and they had good response and prognosis regardless of treatment modalities. Low-dose radiotherapy to both eyes showed a tendency of longer PFS than did chemotherapy and could decrease cataract operations. [ABSTRACT FROM AUTHOR]

Normal karyotype acute myeloid leukemia (NK-AML) with CCAAT/enhancer binding protein α (CEBPA) mutations is known to have a more favorable prognosis. However, direct comparison of the clinical significance according to consolidation therapy has not been widely performed in patients with NK-AML. A total of 404 patients with NK-AML who received intensive induction chemotherapy were included in the present study. Diagnostic samples from the patients were evaluated for CEBPA mutations by direct sequencing. CEBPA single (sm) or double mutation (dm) was observed in 27 (6.7 %) and 51 (12.6 %) patients, respectively. CEBPA (dm) was associated with GATA2 (mut), and it was less frequently associated with FLT3-ITD(pos), NPM1 (mut), and DNMT3A (mut) in comparison with CEBPA (wild) or CEBPA (sm) (all p values <0.05). On multivariate analysis, CEBPA (dm) (p = 0.007, OR 39.593) was an independent risk factor for achievement of complete remission (CR). With a median follow-up of 40.1 months, CEBPA (dm) showed a favorable overall survival (OS), event-free survival (EFS), and lower relapse incidence (RI) in comparison with CEBPA (wild) (all p values <0.005). Comparison of clinical outcome analyses (consolidation chemotherapy vs. allogeneic hematopoietic cell transplantation (HCT)) demonstrated the role of consolidation treatment in patients with CEBPA (dm). Allogeneic HCT was associated with lower EFS and RI and a trend of higher non-relapse mortality. However, there was no statistically significant difference in OS. In conclusion, CEBPA (dm) was associated with other molecular mutations. Consolidation chemotherapy alone may overcome higher relapse rates by reducing the treatment mortality and increasing survival after relapse events in patients with CEBPA (dm) in NK-AML. [ABSTRACT FROM AUTHOR]

According to a previous review, multiple mucosa-associated lymphoid tissue (MALT)-organs involving marginal zone B cell lymphomas (MZLs) are present in 10-30% of patients. However, the clinical features and specific relationships among involved organs are yet to be clearly identified. In this study, we conducted retrospective analyses of multiple MALT organs involving MZLs (MM-MZLs) to identify their clinical features, treatment, prognosis, and specific relationships among involved organs. For analysis, between June 1987 and June 2009, a total of 55 patients from 17 different institutions in Korea, all of whom were histologically diagnosed with MM-MZL, were included in this study. MM-MZL was defined as MZL involving more than 2 different MALT organs. Multiple involvements within one MALT organ (e.g. both side ocular lesions, multiple lung nodules, and multiple stomach lesions, etc.) were excluded from this study. The male/female ratio of the 55 patients was 41/14. The median age of our subjects was 59 years (range 30-82 years). MM-MZL without lymph node (LN) was detected only in 9 patients (36.2%). Bone marrow (BM) involvement was observed in 17 patients (30.9%). The most common site of involvement was the gastrointestinal (GI) tract (25 patients, 45.5%) followed by the lung (40%), Waldeyer's ring (WR) (27.3%), and ocular area (25.5%). Ocular MZLs were commonly accompanied with WR- or lung-MZLs. GI-MZLs were WR or GI-MZLs. Lung-MZLs were frequently observed with ocular and GI-MZLs. WR-MZLs were ocular or GI-MZLs. A total of 53 patients were treated, and 2 on watchful wait. As much as 48 patients received chemotherapy-based treatment. Among them, CR or PR was achieved in 38 patients (79.2%, 95% CI 67-91%). Median time to progression (TTP) was 2.3 years (95% CI 1.4-3.2 years). Cause-specific overall survival (OS) did not reach the median value. The 5-year OS rate was 84.9%. MM-MZLs tend to be an indolent disease, characterized by prolonged survival with frequent relapses. The majority of cases could be controlled effectively via chemotherapy-based treatment, and prolonged survival was achieved in those patients. The GI, lung, WR, and ocular area were commonly presented with other MALT site MZLs, and an organ-specific relationship appears to be relevant to MM-MZLs. [ABSTRACT FROM AUTHOR]

We performed a retrospective multicentre analysis to study the clinical features and treatment outcomes of B-lymphoblastic lymphoma (B-LBL) and T-lymphoblastic lymphoma (T-LBL) in Asian adult patients, and identify risk factors that predict relapse and poor prognosis. Fifty-five newly diagnosed patients (45 T-LBL and 10 B-LBL) were analysed. All patients were treated with intensive chemotherapy regimens including VPDL (vincristine, prednisolone, daunorubicin, L-asparaginase), CALGB (Cancer and leukemia group B), and Stanford/Northern California Oncology Group (NCOG). There was no difference of clinical features between B- and T-LBL except the frequent site of involvement. The overall response rate including complete response (28/55, 50.9%) and partial response (18/55, 32.7%) was 83.6%. Among 46 responders, 22 patients relapsed leading to 20 deaths. Partial responders showed more frequent relapse (10/18, 55.6%) than complete responders (11/28, 39.2%). The median progression-free survival (PFS) was 17 months (95% confidence interval, 11.5-22.5), and the 2-year overall survival was 52 ± 7% with a median follow-up of 50 months (range 8-152). Treatment outcome of T-LBL and B-LBL was not significantly different in terms of response and survival. The presence of pleural effusion was significantly prognostic for overall and PFS (p < 0.05). In conclusion, clinical features and treatment outcome of Asian adult LBL were comparable to previous results, and the prognosis is still poor despite intensive chemotherapy. [ABSTRACT FROM AUTHOR]

Abstract: Fourteen patients had primary ovarian lymphoma, while eighteen patients had secondary ovarian involvement. There was no significant difference in survival rates between primary and secondary involvement with diffuse large B-cell lymphoma (DLBCL), the most common subtype. The 5-year overall survivals of primary and secondary involvement with DLBCL were 70.0% and 59.3%, respectively. The localized bilateral ovarian involvement showed poorer survival compared to stage III/IV patients with secondary ovarian involvement. Treatment outcomes of secondary ovarian involvement in non-Hodgkin''s lymphoma were comparable to those of primary ovarian involvement, suggesting that ovarian involvement does not necessarily predict a worse prognosis for NHL patients. [Copyright &y& Elsevier]

Angiogenesis occurs in response to tissue ischemia and wound healing, and contributes to the pathogenesis of a variety of diseases, such as benign and malignant neoplasia. Several studies have measured bone marrow microvessel density (MVD) in MDS patients and acute myeloid leukemia (AML) patients transformed from MDS, and MVD was higher in MDS patients than controls, but was lower than in AML patients. Vascular endothelial growth factor (VEGF) is expressed in bone marrow blast cells, and an autocrine VEGF signaling mechanism has been established in MDS. Increased bone marrow angiogenesis and VEGF concentrations are adverse prognostic features in all of these patients. In this study, 69 patients were treated in two groups: hypomethylating agents or supportive care with oxymetholone ± pyridoxine. We evaluated the MVD and VEGF expression of paraffin-embedded bone marrow samples from patients. We also investigated the relationship between angiogenesis-related biomarkers including MVD, VEGF expression, and clinical factors. The patient median age was 65 years, and the median follow-up duration was 28 months. MVD assessment among subtypes of WHO MDS classification showed that the MVD of RCUD was significantly lower than in other types (p = 0.02). However, there was no significant difference in VEGF expression according to the subtype of MDS. Although MVD and VEGF expression did not differ between risk groups based on the IPSS, the low risk group tended to have lower expression of angiogenesis-related biomarkers. MDS patients receiving hypomethylating agents had significantly lower MVD expression in responders than in non-responders (6.13 ± 3.38 vs. 9.89 ± 2.10, respectively, p = 0.039). In a consecutive evaluation at the time of diagnosis and 3 months after the initial treatment, the group with a decrease or no change of MVD had a higher response rate compared to that in the group with an increase of MVD (92.9% vs. 58.8%, respectively, p = 0.045). Adverse prognostic factors included older age, MDS type other than RCUD, a higher IPSS risk group, and abnormal cytogenetics. Although angiogenesis-related markers did not demonstrate any significant prognostic association with survival, MVD (≥10 n/mm 2 ) and a strong expression of VEGF seemed to be associated with lower survival rate. These data suggested that the MVD value might be helpful in predicting responsiveness to treatment, especially in MDS patients treated with hypomethylating agents. Although angiogenesis-related markers including VEGF did not demonstrate a significant association with survival outcomes, we observed that high MVD and strong VEGF expression seemed to be associated with lower survival rate. Therefore, biologic markers related to angiogenesis might have a potential as prognostic factors for MDS patients. [ABSTRACT FROM AUTHOR]