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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

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

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.

Previous reports of the influence of UGT1A1 gene polymorphisms on the pharmacokinetics of irinotecan metabolism have not assessed Asian patients treated with FOLFIRI plus bevacizumab for advanced and recurrent colorectal cancer. Twenty-one Japanese colorectal cancer patients received intravenous FOLFIRI (bolus irinotecan, folinic acid, and fluorouracil followed by 46-hour fluorouracil infusion) followed by bevacizumab (5 mg/kg) in Cycle 1. In Cycle 2, patients received bevacizumab followed by FOLFIRI. The regimen was in 2-week cycles. The area under-the-curves ratio (AUC0-last) (Cycle 2/Cycle 1) was determined from plasma concentrations of irinotecan and metabolites (SN-38, SN-38G). Safety, efficacy, and drug-drug interactions were analyzed. Median observation period was 7.8 months; median number of cycles 15. Drug-drug interactions were evaluated in eight patients without irinotecan dose reduction. Mean AUC0-last ratios (with/without bevacizumab) of irinotecan, SN-38, and SN-38G were 0.959, 0.927, and 0.931 respectively. Response rate was 65%; median progression-free survival 16.4 months. Response occurred in four patients with, and nine without, UGT1A1 polymorphism. No significant differences occurred between efficacy, safety, or polymorphism status. This cohort showed no differences in safety or efficacy compared to previous reports. Bevacizumab did not affect the pharmacokinetics of irinotecan and its metabolites, irrespective of UGT1A1 polymorphism status.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) was first described by Isaacson and Wright in 1983 [1]. MALT lymphoma, an extranodal lymphoma composed of morp...

Objectives The tumor microenvironment, including tumor-infiltrating lymphocytes and myeloid-derived cells, is an important factor in the pathogenesis and clinical behavior of malignant lymphoma. However, the prognostic significance of peripheral lymphocytes and monocytes in lymphoma remains unclear. Methods We evaluated the prognostic impact of the absolute lymphocyte count (ALC), absolute monocyte count (AMC), and lymphocyte/monocyte ratio (LMR) in 359 diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Results The median follow-up time of the surviving patients was 58 months. Low ALC and an elevated AMC were both associated with poor survival rates. Receiver operating characteristic curve analysis showed that LMR was the best predictor of survival, with 4.0 as the cutoff point. Patients with LMR ≤4.0 were more likely to have an aggressive tumor, and this was associated with poor treatment responses. Patients with LMR ≤4.0 at diagnosis had significantly poorer overall survival (OS) and progression-free survival (PFS) than those with LMR >4.0. Multivariate analysis, which included prognostic factors of the International Prognostic Index, showed LMR ≤4.0 to be an independent predictor for the OS (hazard ratio [HR], 2.507; 95% confidence interval [CI], 1.255–5.007; P = 0.009) and PFS (HR, 2.063; 95% CI, 1.249–3.408; P = 0.005). Conclusions The LMR at diagnosis, as a simple index which reflects host systemic immunity, predicts clinical outcomes in DLBCL patients treated with R-CHOP.

Background Although 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. Patients and Methods We 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 [n = 14 (64%)] or high [n = 8 (32%)] risk) underwent upfront HDT/ASCT between January 2004 and December 2008, achieving either a complete response (CR; n = 15 (68%)) or a partial response (PR; n = 7 (32%)). Results The 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 [n = 9 (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%, P = .002). Conclusion These 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.

Programmed cell death-1 (PD-1) is involved in one of the inhibitory pathways of the B7-cluster of differentiation (CD) 28 family; this pathway is known to be involved in the attenuation of T-cell responses and promotion of T-cell tolerance. PD-1 is known to negatively regulate T-cell receptor-mediated proliferation and cytokine production, lead to alternation in the tumor microenvironment. Although several studies have shown that high levels of PD-1-positive cells in follicular lymphoma (FL) patients influence their prognosis, those studies included patients treated without rituximab, and the prognostic impact of PD-1 positivity in the rituximab era (R-era) has not yet been elucidated. We retrospectively studied 82 patients with FL uniformly treated with standard R-CHOP therapy at six institutions between 2001 and 2009 (median follow-up for survivors: 55 months). We also collected and examined biopsy specimens for diagnosis with respect to PD-1 positivity. The PD-1 positivity was significantly higher in male patients and patients with high beta-2 microglobulin (B2M ≥ 3.0) (P = 0.03 and 0.003, respectively). Three-year progression free survival (PFS) and overall survival (OS) were 60% and 86%, respectively. By univariate analysis, elevated LDH (P = 0.07) worsened PFS. Male gender (P = 0.03), high FLIPI score (P = 0.05), and high B2M levels (P = 0.08) worsened OS. Multivariate analysis detected no significant prognostic factors, including PD-1 positivity. However, in male subgroup, high levels of PD-1-positive cells were found to be a prognostic factor for PFS. Addition of rituximab might have altered the prognostic impact of PD-1-positive cells.

Abstract 1630 Background: In almost all cases, follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are CD20 positive. Since the introduction of rituximab (R), the outcome of the patients with FL or DLBCL has improved perceptively. Since 2001 and 2003, the Yokohama City University Hematology Group in Japan has uniformly treated FL and DLBCL patients, respectively, with 6 cycles of standard (21 days) R-CHOP therapy with curative intent, except in the case of stage 1 FL. Here, we report our experience. Patients and Methods: Five hundred and twenty-six untreated consecutive patients (158, FL; 368, DLBCL) between 2001 and 2009 were the subjects of this study. All the patients were scheduled to undergo primary therapy with 6 cycles of full-dose R-CHOP in our 7 hospitals. Patients who had partial remission (PR) after the 4 initial cycles were administered a total of 8 R-CHOP cycles. Patients who did not achieve PR after the 4 initial R-CHOP cycles or those with disease progression at any given time received salvage therapy, and that time point was designated as the point at which the disease had started progressing. Patients who required more than 20% dose reduction were excluded from the study. Those with special forms of DLBCL, such as intravascular lymphoma, primary mediastinal large B-cell lymphoma, and T-cell-rich B-cell lymphoma, were also excluded. Additional local irradiation was performed in patients with PR or complete remission (CR) if deemed necessary by the attending physician. No patients received maintenance therapy with R. DLBCL patients who achieved CR but were initially at risk of central nervous system (CNS) involvement received methotrexate (15 mg) and hydrocortisone (25 mg) 4 times intrrathecally for CNS prophylaxis. Central pathological reviews were not performed; only the individual institutional diagnoses were used. Results: In the cases of FL, the pathological grading was grade 1 for 65 patients, grade 2 for 61 patients, grade 3a for 20 patients, and grade 3b for 12 patients. There were 81 men and 77 women, and the median age at diagnosis was 57 years (range, 25–76). In accordance with the International Prognostic Index (IPI), 60 patients were at low risk (L); 60, at low-intermediate risk (LI); 26, at high-intermediate risk (HI); and 12, at high risk (H). According to the Follicular Lymphoma IPI, 43 patients were classified as L; 49, as being at intermediate risk; and 59, as H. For 7 patients, the risk was undetermined. Ten patients received additional local irradiation in PR/CR at the end of the R-CHOP therapy. None received CNS prophylaxis. Twelve deaths were observed among the FL patients, 10 of which were due to the lymphoma. In the DLBCL group, there were 209 men and 159 women, and the median age at diagnosis was 64 years (range, 18–80). According to the IPI, 158 patients were classified as L; 93, as LI; 57, as HI; and 60, as H. Thirty-seven patients received additional local irradiation in PR/CR at the end of the R-CHOP therapy. CNS prophylaxis was performed in 42 patients who had an initial CNS risk and achieved CR. In the observaton period, there were 58 deaths among the DLBCL patients, 50 of which were due to the lymphoma. The median observation period for the living patients with FL and DLBCL was 45 months and 43 months, respectively. For the FL group, the CR, 5-year progression-free survival (PFS), and 5-year overall survival (OS) rates were 86%, 50%, and 92%, respectively. Between patients with grade 1–2 FL, and grade 3 FL, the PFS (P = 0.16) and OS (P = 0.17) were not significantly different. This was found to also be true when the PFS (P = 0.19) and OS (P = 0.32) of grade 1–3a and grade 3b FL patients were compared. For the DLBCL group, the CR, 5year PFS, and 5-year OS rates were 89%, 72%, and 80%, respectively. The PFS rate was significantly higher in the DLBCL group compared to the FL group (Fig 1(A), P = 0.001), but the OS was significantly greater in the FL group (Fig 1(B), P = 0.006). Conclusion: Standard R-CHOP therapy is effective for patients with FL and DLBCL, with the 5-year OS rate exceeding 80% for both. However, in the FL group, the PFS did not show a plateau, suggesting the incurability of this lymphoma with R-CHOP therapy. The good OS indicated the effectiveness of salvage therapy for FL patients. Since the OS and PFS in patients with grade 3 FL were similar to those in patients with grade 1–2 FL, all grades of FL should probably be categorized simply as “FL” with regard to R-CHOP therapy. Disclosures: No relevant conflicts of interest to declare.

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 and60 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 and1). The SIL index is a simple and objective prognostic indicator in DLBCL.

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.

Background Lymphoid neoplasm with 18q21.3/BCL2 and 8q24/MYC translocation to immunoglobulin (IG) genes as dual-hit lymphoma/leukemia is very rare and known to have a poor clinical outcome.Design and Methods To clarify the clinicopathological characteristics of this malignancy, we analyzed 27 cases of cytogenetically proven dual-hit lymphoma/leukemia.Results Dual-hit lymphoma/leukemia was diagnosed at presentation in 22 cases and at relapse or disease progression in 5 cases. At the time of diagnosis of dual-hit lymphoma/leukemia, extranodal involvement was found in 25 cases (93%) and central nervous system involvement occurred in 15 cases (56%). The median survival and 1-year survival rate of the 27 cases were only 6 months and 22%, respectively, after diagnosis of the dual-hit lymphoma/leukemia. Seven cases of triple-hit lymphoma/leukemia (dual-hit lymphoma/leukemia with 3q27/BCL6 translocation) were included; the median survival of these patients was only 4 months from the diagnosis of the dual-hit lymphoma/leukemia. The duration of survival of the patients with a triple-hit malignancy was shorter than that of the other 20 cases of dual-hit lymphoma/leukemia (p=0.02). The translocation partner of MYC subdivided the dual-hit cases into two groups; 14 cases of IGH and 13 cases of IGK/L. The MIB-1 index was investigated in 14 cases with aggressive B-cell lymphoma, and was higher in the group with MYC-IGH translocation (n=7) than in the MYC-IGK/L group (n=7) (p=0.02). Overall survival was not different between the MYC-IGH translocation group (n=14) and the MYC-IGK or MYC-IGL translocation group (n=13).Conclusions Dual-hit lymphoma/leukemia is a rare but distinct mature B-cell neoplasm with an extremely poor prognosis characterized by frequent extranodal involvement and central nervous system progression with either of the translocation partners of MYC.

Background: The existence of immunoglobulin light chain restriction (LCR) strongly indicates B cell monoclonality. Although LCR-deficient B cell malignancies are often observed, their details are barely known. Methods: We retrospectively analyzed LCR-negative diffuse large B cell lymphoma (DLBCL) to elucidate their clinical features. Consecutive DLBCL patients (n = 119), whose histological diagnostic specimens were analyzed by flow cytometry (FCM), were divided into 2 groups: LCR-positive and LCR-negative DLBCL. Cases wherein FCM did not capture tumor cells were excluded. Results: There were 91 LCR-positive (76%) and 28 LCR-negative (24%) DLBCL. The 2 groups did not differ with regard to background, including the International Prognostic Index (IPI), each factor of IPI, gender, bulky mass and B-symptoms. FCM analysis showed that CD10-positive cases were less frequent in the LCR-negative DLBCL group than in the LCR-positive DLBCL group. CD5-positive cases were absent in the LCR-negative DLBCL group. Chromosomal analysis showed that the frequency of BCL2, BCL6 and MYC translocations did not differ between the groups. There was no survival difference in the groups. Conclusion: LCR-negative DLBCL accounts for about one fourth of all DLBCL and their prognosis is similar to that of LCR-positive DLBCL. CD10-negative status might characterize LCR-negative DLBCL.

We sought to determine the frequency of primary extranodal lymphoma (ENL) and its characteristics in Kanagawa, a human T-cell leukemia virus type 1 (HTLV-1) nonendemic area in Japan. Subjects were 847 newly diagnosed patients with malignant lymphoma at the Yokohama City University Hospital and 8 affiliated hospitals mainly located in Kanagawa prefecture from 1999 to 2005. We compared the clinicopathological characteristics of primary ENL with primary nodal lymphoma (NL). Histological specimens were evaluated according to the World Health Organization classifications. A total of 395 (46.6%) and 452 (53.4%) patients had primary ENL and primary NL, respectively. The frequency of primary ENL increased with age. Primary extranodal sites included the gastrointestinal tract (30.4%), Waldeyer's ring (17.8%), orbits (7.0%), soft tissue and subcutaneous tissue (5.2%), bone (4.6%), skin (4.3%), thyroid gland (4.3%), testis and prostate (3.3%), bone marrow (3.3%), nasal and paranasal cavities (2.6%), salivary glands (2.3%), lung and pleura (2.0%), breast (1.8%), central nervous system (1.0%), uterus and ovary (0.5%), and others (9.8%). Among the 395 cases of primary ENL, diffuse large B-cell lymphoma (61.2%) was most frequently diagnosed, followed by extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (13.3%) and follicular lymphoma (5.6%). The frequency of primary ENL is approximately 50% of the total lymphoma cases in Kanagawa, an HTLV-1 nonendemic area in Japan. This frequency appears to be higher than that in Western countries.

We analysed the long-term outcome of the L86 protocol using L-asparaginase (L-asp), vincristine (VCR) and prednisolone (PSL), collectively known as LVP or L97 protocol using LVP along with pirarubicin hydrochloride (THP-ADR) for 97 patients with acute lymphoblastic leukemia (ALL) diagnosed between 1986 and 2002. No significant differences were seen in the two protocols regarding the complete remission (CR) rate or survival. Seventy-five of the 97 patients (77%) achieved a CR. The overall survival (OS) and disease-free survival (DFS) rates were 32.1% and 30.4% at 10 years, respectively. By univariate analysis, we identified seven adverse factors for DFS which included the L2 subtype by French-American-British classification, hepatosplenomegaly, a white blood cell count of more than 30 x 10(9)/L, a blast cell count of more than 10 x 10(9)/L in the peripheral blood, hemoglobin concentration greater than 10 g/dL, a serum lactate dehydrogenase value greater than twice the upper limit of normal and the presence of the Philadelphia chromosome (Ph). According to multivariate analysis, only the presence of Ph was a significant unfavourable factor for DFS and OS. In the 30 patients under 35 years of age without Ph, the OS in the 20 patients treated with L86 and in the 10 patients treated with L97 were 48 and 86%, respectively (P = 0.011). These results indicate that intensified chemotherapy, such as the L97 protocol that includes an anthracycline, might be beneficial for younger patients who are Ph-negative.

BACKGROUND Peripheral T-cell lymphomas (PTCLs) are a biologically heterogeneous subgroup of lymphomas with poor prognosis. In this study, the authors analyzed the clinical behaviors of PTCLs and diffuse large B-cell lymphoma (DLBCL). METHODS The authors compared the characteristics and outcomes of 59 patients with PTCLs, including 33 angioimmunoblastic T-cell lymphomas and 26 unspecified peripheral T-cell lymphomas, with the characteristics and outcomes of 193 patients with DLBCLs who were treated in the era before rituximab. RESULTS Based on the clinical characteristics, elevated lactate dehydrogenase (LDH), poor PS, advanced stage, higher International Prognostic Index score, and B symptoms were more common in patients with PTCLs, and bulky mass was more common in patients with DLBCL. The rates of complete response (CR) or an unconfirmed CR (CRu) were higher in patients with DLBCL (72%) than in patients with PTCLs (56%; P = .03). The 5-year overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) rates were 31%, 26%, and 47%, respectively, in patients with PTCLs and 59%, 55%, and 73%, respectively, in patients with DLBCL (P = .001, P < .001, and P = .003, respectively). Although multivariate analysis identified several risk factors that were significant in PTCLs, but not in DLBCLs, for the CR/CRu, OS, PFS, and DFS rates, the immunophenotype was not identified as a risk factor. CONCLUSIONS The poor response and survival of patients who had PTCLs, compared with patients who had DLBCL, was caused by numerous initial risk factors. T-cell phenotype itself did not appear to have a significant impact on either response or survival. Cancer 2007 © 2007 American Cancer Society.

We monitored the behavior of residual myeloma plasma cells in patients with multiple myeloma after high-dose therapy and autologous or allogeneic transplantation using 3 methods of a flow cytometric technique using 4-color staining, immunofixation, and polymerase chain reaction approaches. We analyzed 17 cases by a relatively simple flow cytometric technique using CD38/CD45/CD19/CD56. Detectable myeloma plasma cells were found in 5 patients at diagnosis and 9 patients after treatment. Of 14 cases, 9 (64%) had CD19–CD56+ myeloma plasma cells, and 5 (36%) of 14 had CD19–CD56– myeloma plasma cells. When 37 bone marrow samples that had less than 5% myeloma plasma cells were assessed, myeloma plasma cells were detected in all 20 immunofixation-positive cases and 3 of 17 immunofixation-negative cases ( P = .002). All 4 polymerase chain reaction–negative samples characterized as immunofixation-negative contained no detectable myeloma plasma cells. Flow cytometry can provide effective information to detect low levels of myeloma plasma cells.

This review summarizes current knowledge of secondary central nervous system lymphoma (SCNSL) in adults. We define SCNSL as CNS involvement not obvious at the initiation of treatment for systemic lymphoma. Recently, polymerase chain reaction and flow cytometry assays of cerebrospinal fluid have become available for the correct diagnosis of SCNSL. We reviewed reports of patients treated without CNS prophylaxis to evaluate the incidence of SCNSL. Elevated serum lactate dehydrogenase levels, the involvement of more than one extranodal site, an advanced stage, a high age-adjusted International Prognostic Index score at presentation, and special anatomic sites of involvement such as the testis are important risk factors for SCNSL. Histologic evidence of aggressiveness is generally an indicator of risk for SCNSL. In addition to conventional treatment, stem cell transplantation, intrathecal administration of rituximab, and liposomal cytarabine have come into clinical use for the treatment of established SCNSL. Prevention of isolated CNS recurrence is thought to be the main target of CNS prophylaxis. The value of CNS prophylaxis according to histologic subtype, status of systemic lymphoma, and other risk factors is summarized. Although prophylaxis is fundamental for treating highly aggressive non-Hodgkin's lymphoma (NHL), it is beginning to be appreciated for the treatment of aggressive NHL. CNS involvement is almost always fatal; however, a CNS-active strategy could complement other approaches that have led to recent improvements in the prognosis for lymphoma.

Here we describe 2 patients with acute leukemia in whom human herpesvirus-6 (HHV-6) encephalitis developed after cord blood transplantation. In patients 1 and 2, generalized seizure and coma developed on day 62 and day 15, respectively, after cord blood transplantation, which failed to engraft in patient 1. Magnetic resonance imaging (MRI) of patient 1's brain showed low-intensity signals at the gyri of the bilateral lateral lobes on T1-weighted images and high-intensity signals on T2-weighted images. MRI of patient 2's brain showed high-intensity signals in bilateral white matter on T2-weighted images and on fluid-attenuated inversion recovery (FLAIR) images. Cerebrospinal fluid examination revealed an increased protein level with pleocytosis in patient 1 and a normal protein level without pleocytosis in patient 2. Polymerase chain reaction analysis detected HHV-6 DNA in the cerebrospinal fluid of both patients. Patient 1 recovered after administration of gancyclovir for 3 weeks. However, she again suffered from encephalitis after discontinuation of gancyclovir, and died of sepsis. Patient 2 died from an anoxic brain caused by generalized seizure. When neurological symptoms and signs appear in hematopoietic stem cell transplantation recipients, we should consider HHV-6 encephalitis and promptly and empirically treat them with gancyclovir or foscarnet.

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.

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).

The levels of serum beta-2 microglobulin (β2MG) are determined mainly from lymphoid tissue. To examine its prognostic value in Hodgkin lymphoma (HL), we conducted a retrospective analysis. We analyzed 67 patients with HL diagnosed and treated at seven institutes of the Yokohama City University Hematology Group between 1998 and 2011. The patients included 40 males and 27 females with a median age of 41 years (range 16–81 years). The HL subtypes were nodular sclerosis classical HL in 37 patients, mixed cellular classical HL in 23, lymphocyte-rich classical HL in 6, and nodular lymphocyte-predominant HL in 1. The 4-year overall survival (OS) rate of all 67 patients was 89 %. Patients with β2MG levels ≥2.5 mg/L (n = 18) showed inferior progression-free survival (PFS; 4-year PFS rate, 42 %) and inferior OS (4-year OS rate, 60 %) compared to patients who had β2MG levels

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.

A 60 year-old woman with primary esophageal T-cell lymphoma in clinical stage I(E)B is presented. Immunohistologic examination showed tumor cells to be positive for anti-LCA, anti-UCHL-1, anti-MT-1, anti-CD3 antibodies, and negative for anti-L26 antibody. Disappearance of dysphagia and improvement in esophageal findings were noted after 65 Gy of irradiation, and biopsy specimens from the esophagus revealed no malignancy. Primary esophageal lymphoma is extremely rare, and this T-cell lymphoma is only the fourth case reported in the literature.

We describe a 55-year-old Japanese man with acute minimally differentiated myeloid leukemia (M0) with an inversion in the long arm of chromosome 3, i.e., inv(3)(q21q26). Patients with this chromosomal abnormality usually show normal or elevated platelet counts. However, our case had a low platelet count with megakaryocytic dysplasia at diagnosis. Furthermore, the 3q21q26 aberration is generally detected in patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome. To the best of our knowledge, it has also been reported in two cases of AML-M0 with 3q21q26 and this is the third case of AML-M0 with 3q21q26. Thus it is suggested that there is some relationship between this type of karyotype abnormality and leukemogenesis and/or thrombopoiesis.

Between January 1990 and May 1994, 59 previously untreated adult patients with acute myeloblastic leukemia (AML) were treated with a combination of behenoyl-cytosine-arabinoside (BHAC), daunorubicin (DNR), 6-mercaptopurine (6-MP) and prednisolone (PSL). Forty one patients (69.5%) achieved complete remission (CR). The Kaplan-Meier analysis revealed an actuarial probability for remaining in remission of 36% in patients who achieved remission and a survival of 29% in all patients at 5 years. A favorable factor relative to achieving CR was performance status (P=0.04). In addition the presence of 300 cells/microl or less of residual leukemic cell counts in the bone marrow at the end point of induction therapy tended to favor remission (P=0.06) using the multivariate analysis with a multiple logistic regression model. In addition the residual leukemic cells counts of less than 300/microl in the bone marrow at the end point of induction therapy was the most significant factor for durable remission (P=0.05) by the Cox's proportional hazard model. We concluded that residual leukemic cells counts in the bone marrow at the end point of intensive induction therapy is a valuable prognostic factor for adults receiving response-oriented individualized induction therapy for AML.

The MIB-1 labeling index, which is based on Ki67 immunostaining, is widely used to evaluate the proliferation of tumor cells in lymphoma. However, its clinical significance has not been fully assessed. We retrospectively evaluated the prognostic impact of the MIB-1 labeling index at the time of diagnosis, in 98 patients with follicular lymphoma (FL) grade 1-3b who were treated uniformly with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy. The 5-year progression-free survival (PFS) for an MIB-1 labeling index of ≥10% (n = 60) and

Previous reports of the influence of UGT1A1 gene polymorphisms on the pharmacokinetics of irinotecan metabolism have not assessed Asian patients treated with FOLFIRI plus bevacizumab for advanced and recurrent colorectal cancer. Twenty-one Japanese colorectal cancer patients received intravenous FOLFIRI (bolus irinotecan, folinic acid, and fluorouracil followed by 46-hour fluorouracil infusion) followed by bevacizumab (5 mg/kg) in Cycle 1. In Cycle 2, patients received bevacizumab followed by FOLFIRI. The regimen was in 2-week cycles. The area under-the-curves ratio (AUC0-last) (Cycle 2/Cycle 1) was determined from plasma concentrations of irinotecan and metabolites (SN-38, SN-38G). Safety, efficacy, and drug-drug interactions were analyzed. Median observation period was 7.8 months; median number of cycles 15. Drug-drug interactions were evaluated in eight patients without irinotecan dose reduction. Mean AUC0-last ratios (with/without bevacizumab) of irinotecan, SN-38, and SN-38G were 0.959, 0.927, and 0.931 respectively. Response rate was 65%; median progression-free survival 16.4 months. Response occurred in four patients with, and nine without, UGT1A1 polymorphism. No significant differences occurred between efficacy, safety, or polymorphism status. This cohort showed no differences in safety or efficacy compared to previous reports. Bevacizumab did not affect the pharmacokinetics of irinotecan and its metabolites, irrespective of UGT1A1 polymorphism status.

High-dose chemotherapy with autologous stem cell transplant is commonly used for diffuse large B-cell lymphoma that recurs after successful salvage chemotherapy. However, in patients in whom the disease recurs again, the prognosis is poor. A 40-year-old woman who underwent allogeneic stem cell transplant 4 years after autologous stem cell transplant developed recurrent diffuse large B-cell lymphoma 3 years after the initial autologous stem cell transplant. She then underwent reduced-intensity hematopoietic stem cell transplant from a human leukocyte antigen-matched, unrelated donor who was not the previous autologous stem cell transplant donor. She achieved a long survival (328 days after the reduced-intensity hematopoietic stem cell transplant and 1844 days after the first allogeneic transplant). A second allogenic transplant may provide survival benefits in a proportion of patients with malignant lymphoma recurring after allogeneic transplant, although careful consideration is required because of the high risk of treatment-related mortality with second allogenic transplant.

We studied immunophenotypic analysis of hematogones by flow cytometry. A total of 102 specimens from 93 patients with acute leukemia (52 specimens), myelodysplastic syndromes (4), or malignant lymphoma (46) were analyzed between April and August, 2011. Hematogones were detected in 55 specimens and highly identified in patients with acute myeloid leukemia in remission and B cell lymphoma. Stage 1 (CD34(+)CD20(-)) and stage 2/3 (CD34(-)CD20(+)) were detected in 9.9% and 52.7%, respectively. In addition, the intermediate type (CD34(+)CD20(+)) was identified in 37.4%. All specimens of stage 3 in bright CD45 expression were positive for CD5 and included CD5(+)CD23(-)CD11c(-), 11.1%, CD5(+)CD23(+)CD11c(-), 85.2%, and CD5(+)CD23(+)CD11c(+), 3.7%. These findings suggest that hematogones with unreported immunophenotypes may exist and the appearance of hematogones in hematologic malignancies may be relatively frequent.

A total of 32 previously untreated patients aged 65 years or older with non-Hodgkin's lymphoma (NHL) were treated with VEPA (vincristine, cyclophosphamide, prednisolone and doxorubicin) or ML-Y1 (doxorubicin, cyclophosphamide, vincristine, methotrexate, bleomycin, procarbazizin and prednisolone). The median age of the patients was 70 years (range 65-77), 19 males and 13 females. The outcome of 16 patients with VEPA and 16 patients with ML-Y1 was retrospectively evaluated. There were no significant differences in response or survival between VEPA and ML-Y1, complete remission rates were 37.5% vs. 31.3% and duration of 50% survival were 20 months and 13 months, respectively. Major side effects of both regimens were myelosuppression, hair loss, nausea, vomiting and peripheral neuropathy. There was no increased toxicity in ML-Y1 but this regimen seemed like VEPA, to be insufficient for NHL in elderly patients. A new intensive regimen should be designed to treat NHL in the elderly patients.

Bevacizumab (BV) is widely used for patients with metastatic colorectal cancer. We investigated the efficacy and safety of chemotherapy combined with BV for metastatic colorectal cancer. From July 2007 to October 2008, 59 patients were treated by chemotherapy with BV in our hospital. Of the 47 patients who received BV in first-line therapy, 3 cases (6%) with complete response (CR), 25 cases(53%) with partial response (PR), and 17 cases (36%) with stable disease (SD) were observed. The overall response rate and tumor control rate were 60% and 96%, respectively. The median progression-free survival (PFS) was 11. 9 months, and median overall survival (OS) was 23. 6 months. There were 12 patients treated first with BV in second-line therapy. Of the 12 patients, 1 case (8%) with CR, 3 cases (25%) with PR, and 4 (33%) with SD were observed. The overall response rate and tumor control rate were 33% and 67%, respectively. The median PFS was 6.0 months and median OS was not reached. With regard to the grade 3 to 4 adverse events by NCI-CTCAE ver3.0, neutropenia was observed in more than half of the patients (56%), but a few of patients had gastrointestinal toxicities, peripheral neuropathy and infections in non-hematologic toxicities. BV-associated adverse events were hypertension, proteinuria, venous thrombosis, wound healing complication, gastrointestinal perforation and bleeding, each of which were few and not serious. Six of the patients experienced PD after first-line therapy treated with BV continuously in second-line therapy. Four of six were surviving without disease progression at the last follow-up, which suggests the effectiveness of continuation of BV. Our study showed the efficacy and safety of BV for metastatic colorectal cancer.

Mantle cell lymphoma (MCL) is a rare subtype of B-celllymphoma characterized by amplification of cyclin D1.The effect of chemotherapies, such as CHOP (cyclophos-phamide, doxorubicin, vincristine, and prednisone), is oftentransient, and most patients die at median 3–5 years fromdiagnosis [1]. Before the rituximab era, a number of smallstudies evaluated the efficacy of high-dose chemotherapy(HDC) supported with autologous stem cell transplantation(ASCT), but did not find an evident contribution to survivalbenefit [2, 3]. Consequently, no single standard treatmentfor MCL has been established to date [4]. We thereforeconducted a nation-wide multicenter retrospective analysisof newly diagnosed patients with MCL in order to inves-tigate the efficacy and clinical outcome of each initialtreatments and HDC/ASCT in the rituximab era.Clinical data of 64 newly diagnosed MCL cases treated in12 institutions participating in the Lymphoma TreatmentStudyGroupinJapanbetween2001and2008werecollectedand analyzed by the end of April 2009. The data includedpatient characteristics [age, sex, performance status definedby European Cooperative Oncology Group (ECOG PS),clinical stage according to the Ann Arbor staging system,complete blood count, and serum lactate dehydrogenaselevel], as well as details of treatment and clinical outcome.Positivity of cyclin D1 and/or chromosomal abnormalityt(11;14)(q13;q32) in the biopsy specimen were required forthe diagnosis of MCL following the World Health Organi-zation classification system. This study was approved by theinstitutional review board in Nihon University ItabashiHospital, where the analysis was performed.Table 1 shows the clinical characteristics of all patientsand risk factors that might influence overall survival,including MCL international prognostic index (MIPI) [5].The median age of patients and median observation periodwere 64 years (range 47–80 years) and 34 months (range2–91 months), respectively. Most of patients were treatedwith rituximab-combined CHOP (R-CHOP)-based che-motherapy for a median 6 (range 2–8) cycles or R-Hyper-CVAD/MA regimen (rituximab, hyperfractionatedcyclophosphamide, vincristine, doxorubicin, and dexameth-asone alternating with high-dose methotrexate and cytara-bine), as initial treatment. As a result, 5-year overallsurvival (OS) and progression-free survival (PFS) for allpatients were 62 and 34%, respectively (Fig. 1a). Thecomplete response rate of the R-CHOP group was lowerthan that of the R-Hyper-CVAD/MA group (49 vs. 80%,P = 0.031), but there was no significant difference in OSor PFS (Fig. 1b, c). Sixteen patients (25%) received vari-ous combinations of HDC followed by ASCT. Amongthese patients, nine underwent HDC/ASCT in their firstcomplete remission, six were in a refractory phase of thedisease, and one was in a second remission. The clinicaloutcome of this group was quite encouraging, withouttreatment-related mortality or secondary malignancy dur-ing the observation period (93% of 5 year OS) (Fig. 1d).In this study, the majority of patients were treated withR-CHOP-based chemotherapy. After rituximab becameclinically available for treating B-cell lymphomas, theclinical outcome of MCL appeared to be improved.

Fifty-eight newly diagnosed patients with Hodgkin lymphoma were treated with ABVD chemotherapy at Yokohama City University Hematology group from October 1996 to June 2005. The median age of patients age was 41 years old and ranged from 15 to 75. Thirty-eight patients were in the early stage and 20 patients were in the advanced stage. Patients in the early stage received 3 cycles of ABVD chemotherapy and involved-field radiation therapy, while those in the advanced stage received 6 cycles of ABVD chemotherapy. The overall response rate in patients was 100% (CR 87%, PR 13%) in the early stage and 95% in the advanced stage. With a median follow-up of 44 months, the 3-year progression-free survival and overall survival were 89% and 95% in the early stage, and 70% and 81% in the advanced stage, respectively. The results of this study were similar to those previously reported in Western countries.

Background: Malignant lymphoma with central nervous system (CNS) involvement has an extremely poor prognosis. We retrospectively studied the risk factors for CNS involvement in patients with diffuse large B-cell lymphoma (DLBCL) treated by cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab (R) -CHOP chemotherapy. Patients and methods: We studied 375 consecutive patients who were newly diagnosed with DLBCL between 1996 and 2006. Patients with primary CNS involvement and patients who received CNS prophylaxis were excluded. All the patients received CHOP (n = 172) or R-CHOP (n = 203) chemotherapy. The following variables were assessed for their potential to predict CNS involvement: gender, age, serum lactate dehydrogenase (LDH) level, performance status, clinical stage, number of extranodal involvements, International Prognostic Index (IPI), bone marrow involvement, presence of a bulky mass, presence of B symptom, and treatment. Results: CNS involvement was observed in 13 cases (3.5%). In univariate analysis, LDH more than normal range, LDH more than twice as normal range, high IPI, bone marrow involvement, and systemic relapse were the predictors for CNS involvement. In multivariate analysis, no risk factors were detected for CNS involvement. The use of rituximab did not have an impact on CNS involvement. Conclusions: The incidence of CNS involvement dose not decrease in rituximab-era.

Sequential high-dose chemotherapy with in vivo rituximab-purged stem cell autografting was designed for previously untreated mantle cell lymphoma (MCL). The response rate, disease-free survival (DFS), overall survival (OS) and toxicity were investigated in this trial. Between November 2001 and August 2008, five patients younger than 65 years of age with MCL at diagnosis were enrolled in this study. Initial chemotherapy consisted of 3 cycles of CHOP regimen followed by four courses of high-dose chemotherapy. During the in vivo purging phase, the patient was administered high-dose cyclophosphamide and cytarabine, and then each administration was followed by two infusions of rituximab. Molecular monitoring of minimal residual disease was performed by assessing DNA samples from bone marrow and autografted cells using PCR amplification of the bcl-1/IgH rearrangement. The complete response rate was 100%, and the 3-year OS and DFS were 100% and 100%, respectively. PCR analysis of autografted cells from four evaluable patients, 75% lymphoma-negative harvests were achieved following in vivo purging. One patient relapsed 3.2 years after treatment. The principal toxicity in the study was hematologic but there were no treatment-related deaths. Intensive high-dose sequential chemotherapy with in vivo purged stem cell support can achieve long-term disease-free survival for MCL.

Ten previously untreated elderly patients with hypocellular acute leukemia received a low dose of cytosine arabinoside (Ara-C), 10 mg/m2 injected subcutaneously every 12 hours for 14-28 days. Six patients achieved a complete remission (CR) for periods ranging for 6-23 months (median 8.5 months) and the others had a partial remission (PR). Relapse has occurred in three patients to date. The median survival ranged from 10-24 months (median 14.5 months). Only two of the six patients, in whom bone marrow biopsy was performed at CR, had a normal cellularity. This change, however, did not appear to be a significant prognostic factor in those patients. In seven patients who achieved a CR or PR low-dose Ara-C was administrated as maintenance therapy at the same low dose for 10 days each month. Treatment was well tolerated in all patients despite for myelosuppression. There were no drug-related deaths. These observations suggest that low-dose Ara-C is effective in treating elderly patients with hypocellular acute leukemia.

1982年にmyelodysplastic syndrome (MDS)の概念が提唱されて以来,種々の報告がなされ,現在ではclonal diseaseとして考えられている.本症例は, 75歳女性,既往歴,家族歴とも特に問題なく,また,特殊薬剤の使用もなかった. 20年来のRA経過中にMDSを合併した症例であり,過去にMDSとRAの合併は我々の検索した限りでは4例しか報告されておらず,稀な症例といえる.また, RAの死亡原因には,悪性腫瘍,白血病,悪性リンパ腫等も少なくないとされている,しかし,その発生機序は未だ不明である.RAの免疫学的異常が,どの様にMDS(リンパ球系も含めたclonal disease)の発生機序に関与しているかを解明するためにも,今後症例を積み重ね検討することが望まれる.

Fourteen patients who received allogeneic hematopoietic stem cell transplantation (HSCT) from a serologically HLA one mismatched related donor (MMRD) between November 1987 and July 2003, were compared with HSCT from matched sibling donor (MSD) (n=142) or matched unrelated donor (MUD) (n=78). Cumulative incidence of acute graft-versus-host disease (GVHD) in patients with MMRD was significantly higher than in those with MSD, but was not different from that in those with MUD. There was no difference in the incidence of extensive type chronic GVHD in HSCT according to donor type. Overall survival (OS) at 5-years in patients with MMRD, MSD and MUD was 42.8%, 55.6% and 44.3%, respectively. The presence of acute GVHD and disease status at HSCT were identified as risk factors for overall survival by multivariate analysis. Acute GVHD was a risk factor for prognosis in patients with MSD and MUD, but not in those with MMRD. It was confirmed that the therapeutic results could be obtained in HSCT from MMRD as well as MUD.

The prognosis of diffuse large B-cell lymphoma (DLBCL) has improved markedly in recent years of rituximab era. The prognosis of de novo CD5-positive DLBCL is reported to be poor, but the effect of rituximab on this type of lymphoma remains unclear. To investigate the effect of rituximab on CD5-positive DLBCL, we collected DLBCL patients and analysed prognostic factors. A total of 157 patients with DLBCL who were immunophenotyped with flow-cytometry (FCM) and treated with chemotherapy were subjected to analysis. Those treated with radiotherapy alone or with supportive therapy only were not included. Patients diagnosed in 2003 or later were treated with rituximab combined chemotherapy. There were 95 males and 62 females. Their age ranged from 20 to 91 years old, and the median was 65 years. Nineteen patients were diagnosed as having de novo CD5-positive DLBCL. Rituximab was given alongside chemotherapy in 85 patients. Of these, 11 were positive for CD5 and 74 were negative. The addition of rituximab improved the overall survival (OS) of DLBCL patients (2-year OS: 82% vs. 70%, p = 0.01). For CD5-negative DLBCL, patients treated with rituximab showed 2-year OS of 84%, which was significantly better than those treated without rituximab (70%, p = 0.008). However, for CD5-positive DLBCL, the prognosis was not statistically different between the patients treated with and without rituximab (59% vs. 50%, p = 0.72). Although rituximab improved the prognosis of DLBCL, such improvement was restricted to the CD5-negative group. Further investigation is required to improve the prognosis of patients with CD5-positive DLBCL.

We studied the clinico-pathologic features and treatment outcome of patients with peripheral T-cell lymphoma (PTCL). This study included 215 patients with T/natural killer (NK)-cell lymphoma, including 59 with PTCL-unspecified (PTCL-U), 42 with angioimmunoblastic T-cell lymphoma (AILT) and 20 with anaplastic large-cell lymphoma (ALCL). Most of the analyses were performed on patients with AILD, ALCL and PTCL-U. The patients with AILT and PTCL-U tended to be older than those with ALCL. Stage III/IV disease was seen in 90.5% of the AILT cases, 55% of the ALCL cases and 67.8% of the PTCL-U cases. In addition, 61.9% of the AILT cases had an international prognostic index (IPI) of H-I or H risk. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 72.2 and 76.1% among the ALCL cases, 40.7 and 42.2% among the PTCL-U cases and 31.2 and 49.3% among the AILT cases, respectively. Among the patients with PTCL-U, the 5-year PFS and OS rates in group low (L), low-intermediate (L-I), high-intermediate (H-I) or high (H) risk group of IPI were: 47.6 and 56.1%, 55.6 and 53.8%, 42.4 and 40.1% and 9.1 and 9.1%, respectively. The 5-year PFS and OS rates in group 1, 2, 3 or 4 by prognostic index of PTCL-U (PIT) were: 88.9 and 85.7%, 57.1 and 54.9%, 33.5 and 28.8% or 13.3 and 13.3%, respectively. The 5-year PFS and OS rates among patients who received CHOP therapy, CyclOBEAP [cyclophosphamide (CPA), vincristine (VCR), bleomycine, etoposide, doxorubicin (DXR), prednisone (PDN)] therapy or autologous stem cell transplantation were: 22 and 25.7%, 59 and 61.7% or 33.3 and 60%, respectively. Multivariate analysis revealed that the PIT score was associated with OS and PFS. These results indicate that the presence of bone marrow (BM) involvement is an independent prognostic factor which may predict both OS and PFS. PTCL-U is a heterogeneous disease with regard to histological type and pathological state. Because PTCL-U is generally not responsive to CHOP therapy, new treatment strategies need to be developed. Copyright © 2008 John Wiley & Sons, Ltd.

Background: Rituximab (R) plus CHOP (R-CHOP) is the standard of care for patients with diffuse large B-cell lymphoma (DLBCL). The International Prognostic Index (IPI) and revised IPI were reported as prognostic indicators for DLBCL in 1993 and 2007, respectively. Although they are widely accepted, the performance status (PS) factor is sometimes ambiguous or subjective. Therefore, we developed a new prognostic index, the SIL, that includes only three objective prognostic factors: the clinical stage (S), a soluble interleukin-2 receptor level >2,500 U/mL (I), and an elevated lactate dehydrogenase level (L) (Cancer Sci. 2012). This study was conducted to confirm the value of the SIL index in a larger cohort and in each risk stratification of patients and to validate the SIL index in an independent patient cohort. Methods: Between 2003 and 2012, we registered and treated 781 consecutive patients with DLBCL, excluding those with mediastinal large B-cell lymphoma, intravascular large B-cell lymphoma, and primary effusion lymphoma. All the included patients were scheduled to undergo primary therapy with six cycles of full-dose R-CHOP. Patients in whom the initial therapy dose was reduced by >20% were excluded. Finally, 572 of 781 patients were retrospectively analyzed. Patients with partial remission (PR) after the initial four cycles underwent eight R-CHOP cycles in total, whereas those who did not achieve PR after the initial four R-CHOP cycles or those who exhibited disease progression at any given time received salvage therapy. If deemed necessary by the attending physician, additional local irradiation was performed in patients with PR or complete remission.Furthermore, we verified the value of the SIL index in an independent cohort of 89 DLBCL patients. Results: The median age at diagnosis was 63 years (range, 18-89 years). The median number of therapy cycles was 6 (range, 1-8), and 90% of patients received >6 cycles. Sixty-one patients (11%) received radiation therapy as primary treatment, which was often used to treat sites of residual masses at the end of chemotherapy. The median observation time for survivors was 55 months (range, 1-131 months). For 572 patients, the 5-year progression-free survival (PFS) and 5-year overall survival (OS) rates were 70% and 81%, respectively. The 5-year PFS rate was significantly different as 86%, 73%, 63%, and 41% for 0, 1, 2, and 3 of SIL index, respectively (Fig 1; P < 0.0001). The 5-year OS rate was also significantly different as 92%, 87%, 78%, and 52% for 0, 1, 2, and 3 of SIL index, respectively (P < 0.0001). According to the SIL index, 367 (64%) and 205 patients (36%) were classified as having standard (SIL index: 0 or 1) and high (SIL index: 2 or 3) risks, respectively. In patients with a low/low-intermediate risk on the IPI, 84% were categorized as having standard risk according to the SIL index, whereas in patients with a high-intermediate/high risk on the IPI, 82% were categorized as having high risk according to the SIL index. Five-year PFS rates in the standard and high risk groups according to the SIL index were 79% and 53%, respectively (Fig 2; P < 0.0001). Five-year OS rates in the standard risk and high risk groups were 90% and 66%, respectively (P < 0.0001). Cox regression analysis of the SIL index, age (>60 years), PS (2-4), sites of extranodal involvement (>1), and sex showed that the SIL index (P 60 years), the SIL index was a good prognostic indicator for PFS and OS in both groups. When they were divided by the number of extranodal involvement sites (0-1 and >1), and sex, the SIL index was still a good prognostic indicator for PFS and OS in both groups. Lastly, when they were divided by the PS (0-1 and 2-4), the SIL index was effective in the good PS group. However, in the poor PS group, the SIL index showed a statistically significant difference in the OS, but not in the PFS. In the validation cohort analysis, 5-year PFS rates in the standard and high risk groups were 81% and 49%, respectively (Fig 3; P = 0.001). Five-year OS rates in the standard risk and high risk groups were 87% and 59%, respectively (P = 0.003). Conclusion: The SIL index is a simple and objective prognostic indicator for DLBCL patients treated with R-CHOP. Disclosures Fujita: Chugai Pharmaceutical CO.,LTD.: Honoraria.

We report a patient who relapsed in a patella and knee joint after allogeneic bone marrow transplantation (BMT) for Ph chromosome-positive acute lymphoblastic leukemia. The patient complained of pain and swelling of knee joint 14 months post-BMT. Fluid from the knee joint included leukemic cells consistent with the immunophenotype of blasts prior to BMT and also revealed the bcr/abl transcript by reverse-transcriptase polymerase chain reaction. Magnetic resonance imaging demonstrated an abnormal signal in the patella. Radiotherapy to the localized extramedullary lesion was successful and no bone marrow relapse has been detected cytologically and cytogenetically to date. This case suggests that the physician should be aware of unusual relapse sites of leukemia post-BMT.

Recently, the cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) regimen plus rituximab (R-CHOP) have been used widely to treat patients with follicular lymphoma. We investigated a fixed scheme of combination chemotherapy protocol including CHOP, granulocyte colony stimulating factor (G-CSF) and rituximab (CHOP-GR) for patients with advanced-stage grade 1 or grade 2 follicular lymphoma in a phase II clinical trial, assessing enhancement of antibody-dependent cellular cytotoxicity of rituximab by G-CSF. Twenty-one untreated patients received two courses of CHOP chemotherapy followed by four courses of CHOP-GR, including G-CSF (s.c.) on days 11 - 14 and rituximab on day 15. Overall response rate was 76% (16 of 21 patients). Two patients, one with no response and subsequent allogeneic hematopoietic stem cell transplantation and one with progressive disease, died of lymphoma. One patient refused to continue therapy, whereas two were rediagnosed and no longer met histologic criteria; these three patients were classified as nonresponders. After a median observation time of 23 months, the 19 histologically assessable patients showed a 2-year progression-free survival rate of 82%, whereas 2-year overall survival was 95%. Fifteen patients (79%) continued in remission during this median follow-up period. Of seven patients with initial bulky mass, five responded to therapy. The most frequent adverse events were leukocytopenia (100%) and neutropenia (100%), followed in turn by alopetia (94%) and nausea/vomiting (79%). Of 11 patients examined for bcl-2 translocation in peripheral blood or marrow by polymerase chain reaction (PCR), four were positive, whereas three of the four had complete remissions and converted to PCR negativity after therapy. According to short-term observation, CHOP-GR is a safe and effective therapy for patients with advanced-stage follicular lymphoma.