Utility of a Reverse Phase Protein Array to Evaluate Multiple Biomarkers in Diffuse Large B-Cell Lymphoma.

PURPOSE: Diffuse large B-cell lymphoma (DLBCL), the most common non-Hodgkin lymphoma, is a heterogeneous lymphoma with different clinical manifestations and molecular alterations, and several markers are currently being measured routinely for its diagnosis, subtyping, or prognostication by immunohistochemistry (IHC). Here, the utility of a reverse-phase-protein-array (RPPA) as a novel supportive tool to measure multiple biomarkers for DLBCL diagnosis is validated. EXPERIMENTAL DESIGN: The expression of seven markers (CD5, CD10, BCL2, BCL6, MUM1, Ki-67, and C-MYC) is analyzed by RPPA and IHC using 37 DLBCL tissues, and the correlation between the two methods is determined. To normalize tumor content ratio in the tissues, the raw RPPA values of each marker are adjusted by that of CD20 or PAX-5. RESULTS: The CD20-adjusted data for CD5, MUM1, BCL2, Ki-67, and C-MYC has better correlation with IHC results than PAX-5-adjusted data. Receiver operating characteristic (ROC) analysis reveals that CD5, MUM1, BCL2, and C-MYC exhibit a better sensitivity and specificity >0.750. Furthermore, the CD20-adjusted C-MYC value strongly correlates with that of IHC, and has a particularly high specificity (0.882). CONCLUSIONS AND CLINICAL RELEVANCE: Although further investigation using a large number of DLBCL specimens needs to be conducted, these results suggest that RPPA could be applicable as a supportive tool for determining lymphoma prognosis.

Renal dysfunction in patients with radioactive iodine-refractory thyroid cancer treated with tyrosine kinase inhibitors: A retrospective study.

In 2014/2015, tyrosine kinase inhibitors (TKIs) were introduced as a secondary treatment for refractory differentiated thyroid cancer (DTC) in Japan. While renal dysfunction is an adverse event of TKI, data on this adverse event in TKI-treated DTC remains insufficient. Here, we investigated renal function in patients undergoing TKI treatment for DTC and evaluated the efficacy of dose reduction/withdrawal for cases of renal dysfunction.A total of 73 cases of radioactive iodine-refractory DTC treated with sorafenib (n = 22) or lenvatinib (n = 51) were included. Patient data evaluated were TKI treatment period, estimated glomerular filtration rate (eGFR) before and after TKI therapy, incidence and degree (maximum value at time of TKI treatment) of proteinuria, and albumin levels before and after TKI therapy were compared.The mean ΔeGFR was -6.75% with lenvatinib and +5.90% with sorafenib. It was not significant (P = .15). The mean Δalbumin was -8.90% and -5.85% with lenvatinib and sorafenib, respectively; there was no significant difference between the lenvatinib and sorafenib groups (P = .77). According to our program of TKI dose reduction and withdrawal, all patients except 2 with diabetes were successfully continuing treatment.Overall, the present results demonstrated that renal function is negatively affected by long-term TKI treatment for RAI-refractory DTC. However, heightened proteinuria, decreased eGFR and albumin levels, and significant but apparently reversible renal dysfunction were more frequent with lenvatinib than sorafenib.

Treatment outcomes of differentiated thyroid cancer with distant metastasis improve by tyrosine kinase inhibitors.

In patients with distant metastasis, treatment for differentiated thyroid cancer (DTC) includes complete total thyroidectomy, followed by radioactive iodine (RAI) therapy for metastatic lesions. Tyrosine kinase inhibitor (TKI) treatment is the final treatment option for metastatic lesions, which is incurable with surgery/RAI therapy. The present study examined whether treatment outcomes for DTC in patients with distant metastasis improved following TKI treatment. This study included 147 patients (median age, 71; range, 33-91 years) who underwent surgery in our hospitals and were diagnosed with distant metastasis. Disease progression was observed in 70 patients, of whom 56 were treated with TKI (TKI group); 14 refused TKI treatment or showed no treatment indication [untreated (UT) group]. Disease progression and treatment outcomes were assessed using imaging evaluations. The present study investigated thyroglobulin doubling time (Tg-DT) and Tg antibody presence/absence and their relation to disease progression. Overall survival following disease progression between the two groups was compared. The study included 22 cases of sorafenib, 49 of lenvatinib, and 15 involving TKIs. The mean dosing period for sorafenib was 153 days and for lenvatinib was 462 days. In the TKI group, 16, 26, and 9 patients exhibited partial responses (PRs), stable disease (SD), and progressive disease (PD), respectively, whereas 5 patients were not evaluable. The disease control rate (DCR) (PR+SD) was 75.0%. A total of 16 patients died in the TKI group, whereas 10/14 patients in the UT group died. Survival curves for the groups were significantly different. TKI treatment improved the prognosis of patients with distant metastasis and PD.

Efficacy and tolerability of initial low-dose lenvatinib to treat differentiated thyroid cancer.

Some patients with differentiated thyroid cancer (DTC) may require an initial low dose (LD) of lenvatinib. However, few studies have investigated the efficacy of LD lenvatinib. We compared the efficacy and tolerability of lenvatinib at an initial LD to those of the standard initial dose of 24 mg in patients with DTC.In this cross-sectional study, records of patients with DTC treated with lenvatinib were retrospectively reviewed. Patients were divided into 2 groups based on the initial dose of lenvatinib: a full-dose (FD) group that received an initial dose of 24 mg/d and a LD group that received an initial dose of less than 24 mg/d. Categorical variables were compared with the Fisher exact test and continuous variables with Student t test. A progression-free survival (PFS) curve was constructed with the Kaplan-Meier method. A probability (P) value of < .05 was considered statistically significant.Thirty-six patients with DTC were treated with lenvatinib (30 in the FD group and 6 in the LD group). The response rates were 43% and 33% in the FD and LD groups, respectively. The median PFS duration was 696 [95% confidence interval (CI): 318-not available (NA)] days in the FD group. The median PFS of the LD group was not reached (95% CI: 124-NA) (P = .293). Treatment interruptions were required in 25 (83%) patients in the FD group and 4 (67%) in the LD group (P = .573). Dose reductions were required in 28 (93%) patients in the FD group and 4 (67%) in the LD group (P = .121). There were no significant differences in the incidences of common adverse events between the 2 groups.The LD group also required dose reduction and interruption frequently. Since these findings are only the short-term results of a limited number of cases, a large number of cases and long-term observations are needed to determine whether an initial LD is effective for patients with DTC in poor general condition.

Lenvatinib as a novel treatment for anaplastic thyroid cancer: A retrospective study.

Anaplastic thyroid cancer (ATC) is associated with an extremely poor prognosis and is resistant to the majority of chemotherapies. In 2015, lenvatinib was approved for treating ATC in Japan. The present study aimed to evaluate the overall survival (OS) of patients with ATC treated with lenvatinib. A total of 23 patients with a definitive histological diagnosis of ATC who were treated at Kanagawa Cancer Center (Yokohama, Kanagawa. Japan) were enrolled. Surgical treatment was possible in 10 patients (including one debulking surgery), and lenvatinib treatment was postoperatively started. The remaining 13 patients were not eligible for debulking surgery; thus, lenvatinib was promptly approved as a life-saving treatment. The therapeutic effect was determined according to the Response Evaluation Criteria In Solid Tumors criteria (ver.1.1). The patients exhibited a lenvatinib response rate of 17.4% and a disease control rate of 43.5%. However, lenvatinib was associated with a 100% incidence of treatment-related adverse events (AEs), with hypertension being the most common AE (91.3%). Additionally, dose interruptions and reductions were required due to the development of tumor fistulas or other tumor-related AEs, and 9 (39.1%) patients discontinued treatment due to grade 3 or higher AEs. The median OS time was 166 days. Overall, the present study demonstrated the effectiveness of lenvatinib against ATC, which is often chemotherapy-resistant. Successful treatment of fistulas developing due to tumor necrosis at the site of the primary lesion is crucial for improving the patient outcome. The response to lenvatinib in patients with ATC varies on a case-by-case basis and requires further investigation in future studies.

Primary uterine lymphoma: The Yokohama Cooperative Study Group for Hematology (YACHT) study.

AIM: Primary malignant lymphomas arising from the female genital tract are very rare, with an incidence rate of 0.5%. Because of its rarity, its clinical characteristics, prognosis and optimal treatment are still unclear. Here, we retrospectively evaluated female patients with uterine lymphoma. METHODS: Between January 2000 and October 2016, 4362 patients were newly diagnosed with malignant lymphoma by the participating institutions of YACHT. Among these 4362 patients, we retrospectively evaluated 14 adult patients with primary uterine lymphoma. RESULTS: The median follow up time was 41 months. The median age at diagnosis was 68 years. Of 14 patients, 10 (72%) were diagnosed with diffuse large B-cell lymphoma. Seven patients presented with vaginal bleeding and three with abdominal pain. Eleven patients (79%) had advanced stages at diagnosis. Three patients (21%) had ovarian involvement and 2 (14%) had vaginal involvement. Induction chemotherapy regimens were R-CHOP in seven patients (50%), CHOP in three (21%) and other regimens in four (29%). Among 14 patients, 12 patients (86%) achieved a complete response and 2 (14%) experienced disease progression. Three patients (21%) showed relapse. Five patients (36%) died because of malignant lymphoma. The 3-year overall survival rate was 57.9%. Soluble interleukin-2 receptor levels > 5000 U/mL, anemia, a bulky mass and the presence of > 1 extranodal sites, B symptom at diagnosis were associated with a poor prognosis. CONCLUSION: Female genital lymphoma is very rare, and further study of more cases is warranted.

Chronic lymphocytic leukemia/small lymphocytic lymphoma with t (2;18) (p12;q21) accompanied by a cutaneous nodule with histological features of diffuse large B-cell lymphoma.

A 73-year-old woman presented a 3-year history of indolent enlargement of cutaneous tumor nodules. Peripheral blood flow cytometry revealed thrombocytopenia (platelets; 85,000/µl) and the presence of an abnormal, small B lymphocyte population (CD5+, CD10-, CD20+, CD22+, CD23dim, FMC7+, SmIgλ+, and SmIgκ-; 4,000/µl). Skin biopsy indicated infiltration of CD5+, CD10-, CD20+, BCL2+, BCL6+, and cyclin D1- atypical large B-cells, suggesting diffuse large B-cell lymphoma. Cytogenetic analysis of the peripheral blood revealed a complex karyotype [t (2;18) (p12;q21) and +12]. Fluorescence in situ hybridization detected the presence of BCL2 split signal and the absence of IGH/CCND1 fusion signal. Cervical lymph node biopsy indicated a pseudofollicular pattern. The sequence of immunoglobulin heavy chain variable region from the peripheral blood and the skin tumor contained the same mutated pattern, and therefore, confirmed clonality. Because the patient's clinical course and skin tumor were indolent, the possibility of Richter syndrome was discarded, and the final diagnosis was chronic lymphocytic leukemia/small lymphocytic lymphoma, Rai stage IV and Binet stage C. The patient achieved complete remission after 4 cycles of a fludarabine plus rituximab regimen, without disease progression since >1 year of treatment.

The SIL index is a simple and objective prognostic indicator in diffuse large B-cell lymphoma.

We previously developed a prognostic index, SIL, which includes advanced stage (S), soluble interleukin-2 receptor level (I), and elevated lactate dehydrogenase level (L) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, hydroxydaunomycin, oncovin, and prednisone (R-CHOP). This time we evaluated the index in a larger cohort and its utility in the risk stratification. The above three factors were independent risk of progression-free survival (PFS). Five-year PFS rates in the standard-risk (SIL index: 0 or 1, n = 367) and high-risk groups (SIL index: 2 or 3, n = 205) were 79% and 53%, respectively (p < 0.0001). When the patients were divided by age (≤60 years and >60 years), the SIL index was a good prognostic indicator for PFS in both groups as well as divided by the number of extranodal involvement site (0-1 and >1). The SIL index is a simple and objective prognostic indicator in DLBCL.

Beta-2 microglobulin is a strong prognostic factor in patients with DLBCL receiving R-CHOP therapy.

Useful prognostic markers for patients with diffuse large B cell lymphoma (DLBCL) have been reported. To identify which biomarker best predicts the prognosis of patients with DLBCL, we performed a retrospective study that included 319 DLBCL patients who had received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy between 2003 and 2012. We assessed the prognostic significance of six biomarkers [lactate dehydrogenase, soluble interleukin-2 receptor, thymidine kinase activity, beta-2 microglobulin (B2M), C-reactive protein, and ferritin] and representative clinical characteristics using progression-free survival (PFS) as the endpoint. The study group included 181 men and 138 women with a median age of 63 years (range, 22-89 years). In a multivariate analysis, the serum B2M level most strongly correlated with PFS (hazard ratio, 2.11; P=0.04). In a univariate analysis, patients with serum B2M levels >1.75µg/mL (n=210) had a worse 3-year PFS rate (71.2%) than those with B2M levels <1.75µg/mL (n=109; 90.0%). Therefore, serum B2M level at the time of diagnosis is a useful prognostic indicator in DLBCL patients receiving R-CHOP.

Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan.

Enteropathy-associated T-cell lymphoma (EATL) is a rare primary T-cell lymphoma of the digestive tract. EATL is classified as either Type I, which is frequently associated with and thought to arise from celiac disease and is primarily observed in Northern Europe, and Type II, which occurs de novo and is distributed all over the world with predominance in Asia. The pathogenesis of EATL in Asia is unknown. We aimed to clarify the histological and genomic profiles of EATL in Japan in a homogeneous series of 20 cases. The cases were characterized by immunohistochemistry, high-resolution oligonucleotide microarray, and fluorescence in situ hybridization (FISH) at five different loci: 1q21.3 (CKS1B), 6q16.3 (HACE1), 7p22.3 (MAFK), 9q33.3 (PPP6C), and 9q34.3 (ASS1, CARD9) using formalin-fixed paraffin-embedded sections. The histological appearance of EATL ranged from medium- to large-sized cells in 13 cases (65%), small- to medium-sized cells in five cases (25%), and medium-sized in two cases (10%). The immunophenotype was CD2(+) (60%), CD3ɛ(+) (100%), CD4(+) (10%), CD7(+) (95%), CD8(+) (80%), CD56(+) (85%), TIA-1(+) (100%), Granzyme B(+) (25%), T-cell receptor (TCR)ß(+) (10%), TCRγ(+) (35%), TCRγδ(+) (50%), and double negative for TCR (six cases, 30%). All cases were EBER(-). The genomic profile showed recurrent copy number gains of 1q32.3, 4p15.1, 5q34, 7q34, 8p11.23, 9q22.31, 9q33.2, 9q34.13, and 12p13.31, and losses of 7p14.1. FISH showed 15 patients (75%) with a gain of 9q34.3 with good correlation with array comparative genomic hybridization. EATL in Japan is characterized by non-monomorphic cells with a cytotoxic CD8(+) CD56(+) phenotype similar to EATL Type II. The genomic profile is comparable to EATL of Western countries, with more similarity to Type I (gain of 1q and 5q) rather than Type II (gain of 8q24, including MYC). The 9q34.3 gain was the most frequent change confirmed by FISH irrespective of the cell origin of αß-T-cells and γδ-T-cells.

Post-treatment PET-CT Findings may Predict the Prognosis of DLBCL with a Bulky Mass.

We retrospectively analyzed the prognosis of patients with diffuse large B cell lymphoma (DLBCL) and a bulky mass at diagnosis. We retrospectively analyzed clinical data for 29 consecutive DLBCL patients with an initial bulky mass receiving R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) therapy from 2004 to 2011. Bulky disease was defined as a measurable tumor mass >10 cm in diameter or a mediastinal mass >1/3 of the chest diameter. Patients with primary mediastinal large B-cell lymphoma were excluded. The median age was 65 years (20-78 years) and the maximum tumor diameter was 11.5 cm (10.0-17.0 cm). Complete response and partial response were achieved in 14 patients each, while 1 patient had progressive disease. The 3-year overall survival (OS) rate and progression-free survival (PFS) rate were 66 and 56 %, respectively. Findings on post-treatment positron emission tomography-computed tomography (PET-CT) were significantly associated with OS (34 % for patients with abnormal uptake vs. 75 % for those without, P = 0.014), and were also associated with PFS (36 vs. 83 %, respectively, P < 0.001). Nine patients with a single site of abnormal uptake on PET-CT underwent radiotherapy and 5 of them subsequently relapsed. An initial bulky mass does not indicate a poor prognosis of DLBCL. However, the post-treatment PET-CT findings may have predictive value in DLBCL patients with a bulky mass.

Monitoring of Hepatitis B Virus (HBV) DNA and Risk of HBV Reactivation in B-Cell Lymphoma: A Prospective Observational Study.

BACKGROUND: There is no standard management of reactivation of hepatitis B virus (HBV) infection in HBV-resolved patients without hepatitis B surface antigen (HBsAg), but with antibodies against hepatitis B core antigen and/or antibodies against HBsAg (anti-HBs). METHODS: We conducted a prospective observational study to evaluate the occurrence of HBV reactivation by serial monthly monitoring of HBV DNA and to establish preemptive therapy guided by this monitoring in B-cell non-Hodgkin lymphoma (B-NHL) treated with rituximab plus corticosteroid-containing chemotherapy (R-steroid-chemo). The primary endpoint was the incidence of HBV reactivation defined as quantifiable HBV DNA levels of ≥ 11 IU/mL. RESULTS: With a median HBV DNA follow-up of 562 days, HBV reactivation was observed in 21 of the 269 analyzed patients. The incidence of HBV reactivation at 1.5 years was 8.3% (95% confidence interval, 5.5-12.4). No hepatitis due to HBV reactivation was observed in patients who received antiviral treatment when HBV DNA levels were between 11 and 432 IU/mL. An anti-HBs titer of <10 mIU/mL and detectable HBV DNA remaining below the level of quantification at baseline were independent risk factors for HBV reactivation (hazard ratio, 20.6 and 56.2, respectively; P < .001). Even in 6 patients with a rapid increase of HBV due to mutations, the monthly HBV DNA monitoring was effective at preventing HBV-related hepatitis. CONCLUSIONS: Monthly monitoring of HBV DNA is useful for preventing HBV reactivation-related hepatitis among B-NHL patients with resolved HBV infection following R-steroid-chemo (UMIN000001299).

R-CHOP therapy alone for limited-stage follicular lymphoma.

Irradiation therapy alone is a standard strategy for limited-stage FL, leading to a 10-year progression-free survival (PFS) rate of 30-50%. However, we have been administering R-CHOP therapy alone to patients with limited-stage FL. A total of 35 patients with newly diagnosed FL received R-CHOP therapy with curative intent between 2002 and 2009. The median age of the 35 patients was 61 years; 7 patients had in CS 1 FL, and 28 patients, CS 2 FL. The median number of R-CHOP cycles was 6. On completion of the R-CHOP therapy, 33 patients achieved complete response and 1 showed partial response (PR). The patient showing PR after the completion of R-CHOP was administered additional irradiation. The remaining 1 patient was not evaluated because of discontinuation of hospital visit. In all the 35 patients, the 5-year PFS rate was 70%, and the 5-year overall survival rate was 92%. In the 15 patients with a PFS>5 years, only 1 patient showed disease progression. The outcome of R-CHOP therapy alone in patients with limited-stage FL was at least equivalent to the reported outcome of irradiation therapy alone. R-CHOP therapy could be an alternative to irradiation therapy in limited-stage FL patients.

Analysis of outcomes in patients with supra-diaphragmatic vs infra-diaphragmatic diffuse large B cell lymphoma treated with R-CHOP therapy.

The prognostic implications of infra-diaphragmatic (InD) versus supra-diaphragmatic (SpD) primary lesions in limited-stage diffuse large B-cell lymphoma (DLBCL) remains unknown. This retrospective study aimed to assess the prognostic impact of spD and InD lesions as well as presence of gastrointestinal (GI) involvements in adults with limited-stage DLBCL. We analyzed data from 178 patients with limited-stage DLBCL who were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone therapy at 7 institutions of the Yokohama City University Hematology Group between 2003 and 2009. The median age was 63 years (range, 18-80 years). The primary sites were SpD in 109 patients, and InD in 69. No statistical differences in progression-free survival (PFS) or overall survival (OS) were observed between patients with SpD lesions and those with InD lesions. However, when patients with SpD lesions, InD lesions with (n=35), and without (n=34) GI involvement were compared, the presence of GI lesions was associated with favorable PFS. The multivariate analysis revealed that SpD or InD localization had no independent effect on PFS or OS, whereas the presence of GI lesions was correlated with favorable PFS (P=0.024, HR 0.09).

Post-therapy ¹8F-fluorodeoxyglucose positron emission tomography for predicting outcome in patients with peripheral T cell lymphoma.

The International Harmonization Project on Lymphoma recommends (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) for the routine assessment of treatment efficacy in patients with FDG-avid lymphomas such as Hodgkin's and diffuse large B cell lymphomas. The utility of FDG-PET in predicting outcomes in patients with peripheral T cell lymphomas (PTCL) has not been fully elucidated. We retrospectively determined the predictive value of FDG-PET after first-line treatment (post-PET) for outcome in PTCL. Of the 36 patients enrolled, 16 were histologically diagnosed with PTCL not otherwise specified and 20 were diagnosed with angioimmunoblastic T cell lymphoma. All patients received curative-intent anthracycline-containing chemotherapy regimens. Post-PET images were visually evaluated by local nuclear medicine physicians. The median observation period for the surviving patients was 44 months. Positive and negative post-PET results were obtained in 31 % (11/36) and 69 % (25/36) of patients, respectively. The 3-year progression-free survival rates in the positive and negative post-PET result groups were 18 % and 62 %, respectively (P < 0.001). Nine of the 11 patients in the positive post-PET result group experienced progressive disease (PD) (positive predictive value, 82 %), whereas 16 of the 25 patients in the negative post-PET result group did not experience PD (negative predictive value, 64 %). The 3-year overall survival rates in the positive and negative post-PET result groups were 44 % and 84 %, respectively (P = 0.03). Our findings indicate that post-PET is predictive of outcome in patients with PTCL.

Intrathecal methotrexate prophylaxis and central nervous system relapse in patients with diffuse large B-cell lymphoma following rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone.

This study evaluated the efficacy of central nervous system (CNS) prophylaxis using intrathecal methotrexate (IT-MTX) in patients with diffuse large B-cell lymphoma (DLBCL). We retrospectively studied 322 patients who achieved first complete remission (CR) after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. The CNS prophylaxis consisted of four doses of IT-MTX (15 mg) with hydrocortisone (25 mg) administered after CR was achieved. Forty patients (12%) received CNS prophylaxis (group A) and 282 patients (88%) did not (group B). Three patients in group A (8%) and eight in group B (3%) experienced isolated CNS relapse during the first CR, although this difference was not statistically significant (p = 0.14). Ten of 11 CNS relapses occurred in the brain parenchyma with (n = 3) or without (n = 7) leptomeningeal involvement, and the remaining patient had exclusive leptomeningeal involvement. In patients with DLBCL attaining CR after R-CHOP, IT-MTX administration was insufficient to prevent CNS relapse.

Biweekly THP-COP therapy for newly diagnosed peripheral T-cell lymphoma patients.

Pirarubicin tetrahydropyranyl adriamycin (THP-ADR) is an analogue of doxorubicin. This agent exhibits activity against some doxorubicin-resistant cell lines. We performed a phase II study of biweekly THP-COP [50 mg/m(2) pirarubicin, 750 mg/m(2) cyclophosphamide, 1.4 mg/m(2) vincristine (2.0 mg maximum) on day 1, and 100 mg/body predonisolone on days 1-5] in patients with peripheral T-cell lymphoma (PTCL). Seventeen patients with newly diagnosed PTCL were enrolled. Histological diagnoses were of PTCL, not otherwise specified (n = 5), or angioimmunoblastic T-cell lymphoma (n = 12). All diagnostic specimens including those of the historical control group were centrally reviewed by hematological pathologists. All patients received six cycles of biweekly THP-COP. The patient group included 13 male and 4 female patients, with a median age of 62 years. The median follow-up time in surviving patients was 30 months. Overall response rate was 94% with 15 cases of complete remission (88%). The 3-year progression-free survival and overall survival rates were 57% and 75%, respectively. The most frequent adverse events associated with biweekly THP-COP were leukocytopenia (100%), neutropenia (100%), and lymphopenia (100%), followed by alopecia (92%) and anaemia (88%). All of these occurred only transiently, and the patients subsequently recovered. Biweekly THP-COP is a safe and promising therapy for patients with newly diagnosed PTCL. This study is registered in a public database (UMIN000010485).

Prognostic significance of pleural or pericardial effusion and the implication of optimal treatment in primary mediastinal large B-cell lymphoma: a multicenter retrospective study in Japan.

The prognosis of patients with primary mediastinal large B-cell lymphoma has improved over recent years. However, the optimal treatment strategy including the role of radiotherapy remains unknown. We retrospectively analyzed the clinical outcomes of 345 patients with newly diagnosed primary mediastinal large B-cell lymphoma in Japan. With a median follow up of 48 months, the overall survival at four years for patients treated with R-CHOP (n=187), CHOP (n=44), DA-EPOCH-R (n=9), 2(nd)- or 3(rd)-generation regimens, and chemotherapy followed by autologous stem cell transplantation were 90%, 67%, 100%, 91% and 92%, respectively. Focusing on patients treated with R-CHOP, a higher International Prognostic Index score and the presence of pleural or pericardial effusion were identified as adverse prognostic factors for overall survival in patients treated with R-CHOP without consolidative radiotherapy (IPI: hazard ratio 4.23, 95% confidence interval 1.48-12.13, P=0.007; effusion: hazard ratio 4.93, 95% confidence interval 1.37-17.69, P=0.015). Combined with the International Prognostic Index score and the presence of pleural or pericardial effusion for the stratification of patients treated with R-CHOP without radiotherapy, patients with lower International Prognostic Index score and the absence of effusion comprised approximately one-half of these patients and could be identified as curable patients (95% overall survival at 4 years). The DA-EPOCH-R regimen might overcome the effect of these adverse prognostic factors. Our simple indicators of International Prognostic Index score and the presence of pleural or pericardial effusion could stratify patients with primary mediastinal large B-cell lymphoma and help guide selection of treatment.