Yoshimi Ishii

Absolute monocyte count in follicular lymphoma patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.

Elevated absolute monocyte counts (AMCs) have been reported to indicate poor prognosis for patients with lymphoproliferative disease, including those with follicular lymphoma (FL) receiving various treatments. We evaluated the prognostic impact of AMC in 150 consecutive FL patients who received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Progression-free survival (PFS) did not differ significantly according to the AMC level. Univariate and multivariate analyses did not indicate a prognostic significance of AMC for PFS. Thus, the AMC is not a prognostic factor for FL patients treated with R-CHOP. However, immunochemotherapy might influence the prognostic impact of AMC.

Clinical features of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue

We newly diagnosed 131 patients with extranodal marginal zone lymphoma of mucosa‐associated lymphoid tissue lymphoma between 1998 and 2010. We retrospectively studied 124 patients for whom complete clinical data were available at presentation and who had minimally undergone tumour staging by physical examination, computed tomography (CT), bone marrow aspiration, and biopsy. A slight female predominance (men, 58; women, 66) was observed in the study population; the median age was 67u2009years. The primary locations at presentation were the stomach (38%), orbita (20%), lung (12%), intestinal tract (8%), thyroid gland (6%), others (14%), and unknown (2%). Seventy per cent of patients had localized disease. Of the 124 patients, 14 (11%) had lymph node involvement, and 5 (4%) had bone marrow involvement. Five (4%) patients had both lung and gastric involvement. The 5‐year overall survival rate for the 124 patients was 96.1%. The overall vital prognosis was excellent. Moreover, gastro‐intestinal fiberscopic examination is essential, especially in cases with lung involvement at presentation. Copyright

Human leukocyte antigen-DR expression on flow cytometry and tumor-associated macrophages in diffuse large B-cell lymphoma treated by rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone therapy: retrospective cohort study

Abstract Loss of human leukocyte antigen (HLA)-DR expression may be related to a poor prognosis of diffuse large B-cell lymphoma (DLBCL), and tumor-associated macrophages (TAMs) may influence tumor progression. We retrospectively reviewed 36 patients with newly diagnosed DLBCL who received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) therapy at Kanagawa Cancer Center in Japan from 2004 to 2010. HLA-DR expression by lymphoma cells was evaluated using flow cytometry, and TAMs in lymphoma tissue were detected by immunohistochemistry for CD68 as a marker of macrophages and CD163 as a marker of M2 TAMs. Three-year overall survival was, respectively, 100% versus 69.6% in the HLA-DR “bright” and “not bright” groups (p = 0.012). Patients from the HLA-DR “not bright” group with strong CD163 expression had a much worse prognosis than other patients. The HLA-DR status shown by flow cytometry can be used to predict the prognosis of patients with DLBCL receiving R-CHOP therapy and prognostic accuracy can be increased by also assessing TAMs.

Clinicopathological analysis of mediastinal large B-cell lymphoma and classical Hodgkin lymphoma of the mediastinum

Abstract Primary mediastinal (thymic) large B-cell lymphoma (PMLBCL) and nodular sclerosing classical Hodgkin lymphoma (NSCHL) are the major histological types of lymphoma affecting the mediastinum. We reviewed 27 patients with PMLBCL and 14 patients with NSCHL. A poor performance status, high serum lactate dehydrogenase level and strong positivity for PAX5 were all significantly more common in patients with PMLBCL than in those with NSCHL. Severe fibrosis was frequent in NSCHL, but not in PMLBCL. PDL1 was expressed by 11/25 PMLBCLs (44.0%) vs. 1/9 NSCHLs (11.1%). Expression of BCL6 was significantly more frequent in PDL1-positive PMLBCL than in PDL1-negative PMLBCL, but there were no clinical differences between these two groups. Two patients with PMLBCL with a poor prognosis had CD20(−), CD79a(+), CD15(−), and CD30(−), possibly representing a subtype of mediastinal gray zone lymphoma.

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

Abstract 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 [50u2009mg/m2 pirarubicin, 750u2009mg/m2 cyclophosphamide, 1.4u2009mg/m2 vincristine (2.0u2009mg maximum) on day 1, and 100u2009mg/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 (nu2009=u20095), or angioimmunoblastic T‐cell lymphoma (nu2009=u200912). 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 62u2009years. The median follow‐up time in surviving patients was 30u2009months. 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). Copyright

Serum ferritin level is prognostic of patient outcome in extranodal NK/T cell lymphoma, nasal type.

The objective of the current study was to assess the prognostic factors in patients with extranodal natural killer (NK)/T cell lymphoma, nasal type (ENKL). We retrospectively analyzed 35 patients who were diagnosed with ENKL between 1998 and 2011. The median patient age was 63xa0years, and the male/female ratio was 22:13; twenty patients had localized ENKL, and 26 had a good Eastern Cooperative Oncology Group performance status (score 0 or 1). B symptoms were present in 17 patients. Twenty-five patients presented with nasal or paranasal lesions, or both. With a median follow-up duration among patients still alive at their last follow-up of 47xa0months (range 8–93xa0months), the 3-year overall survival (OS) rate was 44.5xa0%. Multivariate analysis revealed that advanced disease stage (Pxa0=xa00.002), the presence of extranasal disease (Pxa0=xa00.013), and serum ferritin levels greater than 300xa0ng/ml (Pxa0<xa00.001) were significant and independent (negative) prognostic factors. High serum ferritin levels were associated with the presence of B symptoms, elevated lactate dehydrogenase levels, and high soluble interleukin-2 receptor levels, but not with clinical stage. Patients with high ferritin levels had a remarkably low remission rate (23xa0%) and a short OS time (median: 4xa0months). Serum ferritin level at the time of diagnosis of ENKL was a useful prognostic factor.

Upfront Autologous Stem Cell Transplantation for Untreated High-Risk Diffuse Large B-Cell Lymphoma in Patients Up to 60 Years of Age

BACKGROUNDnAlthough rituximab added to CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) is the standard chemotherapy for untreated DLBCL, its therapeutic effect is limited in younger patients with high-intermediate risk or high-risk disease according to the age-adjusted international prognostic index. In fact, the efficacy and safety of HDT plus rituximab followed by ASCT for such patients remain unclear.nnnPATIENTS AND METHODSnWe retrospectively investigated the safety and effectiveness of HDT/ASCT in patients with untreated DLBCL. Twenty-two patients, aged 60 years and younger, with untreated DLBCL (classified as high-intermediate [nxa0=xa014 (64%)] or high [nxa0=xa08 (32%)] risk) underwent upfront HDT/ASCT between January 2004 and December 2008, achieving either a complete response (CR; nxa0= 15 (68%)) or a partial response (PR; nxa0= 7 (32%)).nnnRESULTSnThe 5-year overall survival rate was 81.0% and the progression-free survival rate was 73.0%, with no significant difference between risk groups based on the international prognostic index. The most common nonhematologic toxicity was febrile neutropenia [nxa0=xa09 (41%)]. The cause of all 3 fatalities was exacerbation of the underlying disease, and no treatment-related mortality was observed. No variables with a significant influence on overall survival were identified, but a correlation of the treatment response before transplanation with progression-free survival was suggested (CR vs. PR: 92% vs. 30%, Pxa0= .002).nnnCONCLUSIONnThese results suggest that adding rituximab to upfront HDT/ASCT is feasible and can improve the outcome in untreated patients with poor-prognosis DLBCL. In the future, upfront HDT/ASCT should be more extensively evaluated in clinical trials.

Serum ferritin level is a prognostic marker in patients with peripheral T-cell lymphoma

The prognostic value of serum ferritin level in patients with peripheral T‐cell lymphoma (PTCL) remains unknown.

The rate of reduction in the maximum standardized uptake value from the initial to the post-R-CHOP therapy in positron emission tomography scan predicts disease progression in diffuse large B cell lymphoma patients

Abstract[18F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is useful for primary staging and evaluation of treatment outcome in diffuse large B cell lymphoma (DLBCL) patients. The reduction in the maximum standardized uptake value (ΔSUVmax) from the initial to the interim 18F-FDG PET scan has been reported to predict survival in DLBCL patients. We retrospectively evaluated ΔSUVmax obtained by PET or PET-computed tomography before and after initial therapy in 31 newly diagnosed DLBCL patients who were treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) therapy. Receiver observation characteristic curve analysis was used to evaluate the optimal cutoff value for the ΔSUVmax for disease progression. The 3-year progression-free survival rate of patients with ΔSUVmax ≥83 and <83xa0% was found to be 91 and 25xa0%, respectively (Pxa0<xa00.001). The 4-year overall survival rate of patients with ΔSUVmax ≥83 and <83xa0% was found to be 100 and 83xa0%, respectively (Pxa0=xa00.046). The ΔSUVmax observed before and after R-CHOP therapy could be useful in the prediction of disease progression and survival in newly diagnosed DLBCL patients.