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This single‐arm confirmatory study (JCOG1305) aimed to evaluate the utility of interim positron emission tomography (iPET)‐guided therapy for newly diagnosed advanced‐stage classic Hodgkin lymphoma (cHL). Patients aged 16–60 years with cHL received two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and then underwent an iPET scan (PET2), which was centrally reviewed using a five‐point Deauville scale. PET2‐negative patients continued an additional four cycles of ABVD, whereas PET2‐positive patients switched to six cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP). The co‐primary endpoints were 2‐year progression‐free survival (PFS) among all eligible and PET2‐positive patients. Ninety‐three patients were enrolled between January 2016 and December 2019. One patient was ineligible because of a diagnostic error. The median age of the 92 eligible patients was 35 (interquartile range, 28–48) years. Forty (43%) patients had stage III disease, and 43 (47%) had stage IV disease. The remaining nine (10%) patients had stage IIB disease with risk factors. Nineteen PET2‐positive (21%) patients received eBEACOPP, 18 completed six cycles of eBEACOPP, 73 PET2‐negative (79%) patients continued ABVD, and 70 completed an additional four cycles of ABVD. With a median follow‐up period of 41.1 months, the 2‐year PFS of 92 eligible patients and 19 PET2‐positive patients were 84.8% (80% confidence interval [CI], 79.2–88.9) and 84.2% (80% CI, 69.7–92.1), respectively. Both primary endpoints were met at the prespecified threshold. This study demonstrates that iPET‐guided therapy is a useful treatment option for younger patients with newly diagnosed advanced‐stage cHL. Registration number: jRCTs031180218. [ABSTRACT FROM AUTHOR]

In recent years, the significance of detecting minimal/measurable residual disease (MRD) in chronic lymphocytic leukemia (CLL) has increased due to the availability of highly effective therapeutic agents. Flow cytometry provides notable cost-effectiveness and immediacy, with an expected sensitivity level of approximately 10−4. The critical aspect of MRD detection via flow cytometry lies in accurately defining the region containing tumor cells. However, a subset of CLL, known as CLL with atypical immunophenotype, exhibits a distinct cell surface marker expression pattern that can make MRD detection challenging, because these markers often resemble those of normal B cells. To enhance the sensitivity of MRD detection in such atypical cases of CLL, we have capitalized on the observation that cell surface immunoglobulin (sIg) light chains tend to be expressed at a higher level in this subtype. For every four two-dimensional plots of cell surface markers, we used a plot to evaluate the expression of sIg kappa/lambda light chains and identified regions where the kappa/lambda ratio of sIg light chains deviated from a designated threshold within the putative CLL cell region. Using this method, we could detect atypical CLL cells at a level of 10−4. We propose this method as an effective MRD assay. [ABSTRACT FROM AUTHOR]

Brentuximab vedotin (BV), CD30 specific antibody drug conjugate, has been used to treat anaplastic large cell lymphoma (ALCL) and classic Hodgkin lymphoma (CHL); it is also used in the treatment of other CD30-positive peripheral T-cell lymphomas. We aimed to investigate the incidence and clinicopathological characteristics of patients with ALCL or CHL with loss of or decrease in CD30 expression after BV-containing therapy. Twelve and nine patients with refractory/relapsed CHL and ALCL, respectively, were analyzed after receiving BV-containing therapy. In four ALCL patients (44%), CD30 expression was lost/decreased in re-biopsy materials, including one with complete loss and three with a reduction of less than 20%. All 12 CHL patients showed consistent CD30 expression levels after BV treatment. Compared with five ALCL patients with consistent CD30 expression, four ALCL patients with a loss of/decrease in CD30 expression received a higher cumulative dose of BV (P = 0.014) and revealed a lower intensity of CD30 expression in initial biopsy materials (P = 0.017). The subtypes of ALCL (ALK positive, ALK negative, and primary cutaneous) were not related to the loss of/decrease in CD30 expression. In conclusion, 44% of ALCL patients, regardless of histological subtypes, showed a loss of/decrease in CD30 expression after receiving BV-containing therapy, but this phenomenon was not observed in CHL patients. A higher cumulative dose of BV and a lower amount of CD30 antigen in tumor cells in the initial biopsy materials might be predictors of a loss of/decrease in CD30 expression in ALCL patients. [ABSTRACT FROM AUTHOR]

Depression is a leading cause of disease worldwide. The association between gut microbiota and depression has barely been investigated in the Japanese population. We analyzed Iwaki health check-up data collected from 2017 to 2019 and constructed generalized linear mixed models. The independent variable was the relative abundance of each of the 37 gut microbiota genera that were reported to be associated with depression. The dependent variable was the presence of depression assessed by the Center for Epidemiologic Studies Depression Scale. Potential confounders, including grip strength, gender, height, weight, smoking, and drinking habits, were adjusted in the regression models. Nine genera's regression coefficients (Alistipes, Blautia, Coprococcus, Dorea, Faecalibacterium, Holdemania, Lactobacillus, Mitsuokella, and Oscillibacter) showed statistical significance after multiple comparisons adjustment. Among these nine gut bacteria genera, Alistipes, Blautia, Coprococcus, Dorea, Faecalibacterium, and Oscillibacter were reported to be associated with butyrate production in the intestine. Our results indicate that gut microbiotas may influence the depression condition of the host via the butyrate-producing process. [ABSTRACT FROM AUTHOR]

Tirabrutinib is a Bruton's tyrosine kinase inhibitor for treating B-cell malignancies. We report the final results of a Phase I study of tirabrutinib in 17 Japanese patients with B-cell malignancies. Patients were administered tirabrutinib at a dose of 160 mg, 320 mg, or 480 mg once daily, or 300 mg twice daily (N = 3, 3, 4, and 7, respectively). Three patients continued tirabrutinib until study completion (November 30, 2020). Adverse events (AEs) occurred in all 17 patients, with Grade 3–4 AEs in 8 (47.1%), serious AEs in 7 (41.2%), drug-related AEs in 16 (94.1%), and Grade 3–4 drug-related AEs in 6 (35.3%). Drug-related AEs reported in 3 or more patients were rash, vomiting, neutropenia, arthralgia, and malaise. One additional serious AE (benign neoplasm of the lung, unrelated to tirabrutinib) occurred after the previous data cutoff (January 4, 2018). Tirabrutinib administration and response assessment were continued for over 4 years in 4 patients. The overall response rate was 76.5% (13/17 patients). The median (range) time to response and duration of response were 0.9 (0.9–5.9) months and 2.59 (0.08–5.45) years, respectively. These findings demonstrate the long-term safety and efficacy of tirabrutinib in Japanese patients with B-cell malignancies. Clinical trial registration: JapicCTI-142682 (http://www.clinicaltrials.jp/). [ABSTRACT FROM AUTHOR]

The phase II study of tirabrutinib monotherapy at a daily dose of 480 mg under fasting conditions for treatment‐naïve and relapsed/refractory Waldenström's macroglobulinemia (ONO‐4059‐05 study) demonstrated a promising efficacy and tolerable safety profile. We conducted an unplanned analysis with a median follow‐up of 24.8 months to update the efficacy and safety results and to report patient‐reported quality of life. Of 27 enrolled patients, 22 patients continued receiving the study drug. The major response assessed by an independent review committee was observed in 25 patients (93%), including one and five patients who newly achieved complete response and very good partial response, respectively, after the primary analysis. The progression‐free and overall survival rates at 24 months were 92.6% and 100%, respectively. Serum IgM levels in all patients except one declined and were maintained at low levels, although transient increases occurred after temporal interruption of the study drug. The disease‐related symptoms including recurrent fever and hyperviscosity mostly disappeared. Health‐related quality of life, assessed by cancer‐specific questionnaires, was mostly maintained. Grade 3–4 neutropenia, lymphopenia, and leukopenia were newly recognized in three, two, and one patient, respectively. Grade 3 treatment‐related hypertriglyceridemia was also recognized. Nine patients experienced grade 1–2 bleeding events (33%), one patient experienced grade 2 treatment‐related atrial fibrillation, and one patient experienced grade 1 treatment‐related hypertension. Treatment‐related skin adverse events were observed in 14 patients (52%). Taken together, tirabrutinib has durable efficacy with an acceptable safety profile for treatment‐naïve and refractory/relapsed Waldenström's macroglobulinemia. [ABSTRACT FROM AUTHOR]

Watchful waiting (WW) is one of the standard approaches for newly diagnosed follicular lymphoma (FL) patients with low‐tumor burden. However, the impact of WW in FL patients at the first progression, remains unclear. We reviewed 206 FL patients who experienced the first progression after responding to the initial treatment at our institution between 1998 and 2017. Patients were classified into either the WW cohort (132 patients) or the immediate treatment cohort (74 patients). Overall, the median follow‐up from the first progression was 79.8 months (range, 2.1–227.0 months). In the WW cohort, the estimated median time to next treatment (TNT) was 19.7 months (95% confidence interval [CI], 13.4–30.2), and 76.5% (95% CI, 68.0–84.1) of the patients subsequently underwent the second‐line treatment at 5 years. There was a significant difference in the median time to treatment failure in the WW cohort (72.8 months; 95% CI, 64.6–94.0) compared to the immediate treatment cohort (23.3 months; 95% CI, 13.4–38.8) (HR, 2.13; 95% CI, 1.48–3.06), whereas overall survival and the cumulative incidence of histological transformation were not significantly different between two cohorts. In a multivariate analysis, rituximab refractory status, progression of disease within 24 months from the induction of first‐line therapy, and a high Follicular Lymphoma International Prognostic Index score at diagnosis were significantly associated with shorter TNT. Interestingly, 15 patients (11%) of the WW cohort experienced spontaneous tumor regression during WW, and their TNT (median, 82.1 months, 95% CI, 11.7‐NA) was longer than that of the remaining patients in the WW cohort (median, 16.5 months, 95% CI, 13.0–25.4), with a significant difference (p = 0.01). The results of the present study suggested that WW could be a safe and reasonable option even at the first progression for the selected FL patients, without a negative impact on clinical outcomes. [ABSTRACT FROM AUTHOR]

The prognosis of patients with aggressive adult T cell leukemia-lymphoma (ATLL) is dismal even with intensive chemotherapy. Allogeneic hematopoietic stem cell transplantation (HSCT) is a promising option for patients with aggressive ATLL, but the posttransplant outcome remains unsatisfactory. Hence, to further improve clinical outcomes, novel therapeutic approaches are needed. The clinical significance of immune checkpoint protein expression has not been well-established in aggressive ATLL. This study aims to identify the association between the expression profile of immune checkpoint proteins on ATLL cells and clinical outcomes. This retrospective study cohort included 65 patients with aggressive ATLL diagnosed between 2001 and 2015 at the National Cancer Center Hospital, Tokyo, Japan. Formalin-fixed paraffin-embedded tissue was used to immunohistochemically determine the expression of immune checkpoint proteins and assess the impact of expression profile on the probability of overall survival from diagnosis or HSCT. The current analysis shows that cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), and programmed death-ligand 1 (PD-L1) expressions were adverse prognostic factors in patients with aggressive ATLL. Experiments that assess the efficacy of immune checkpoint inhibitors are warranted to alleviate the adverse impacts associated with negative immune checkpoints. [ABSTRACT FROM AUTHOR]

Introduction: Excisional biopsy (EB) is considered the gold standard for lymphoma diagnosis. Although recent advances in interventional radiology enable sampling with core-needle biopsy (CNB), only few studies evaluated the utility of CNB compared to that of EB. Methods: We analyzed patients with lymphoma who had a diagnostic biopsy at the National Cancer Center Hospital during 2002–2017. We investigated the clinical and pathological characteristics of CNB in 2017. Results: The proportion of CNB utility in total biopsy procedures had increased from 11 to 48% during the 15 years. In 2017, CNB was opted more frequently than EB for a biopsy of superficial, abdominal, or anterior mediastinal lesions. Only one out of 72 patients who had CNB required re-biopsy with EB because of insufficiency. The incidence of complications was comparable between CNB and EB: 2 (4%) cases of minor bleeding with CNB and 1 (8%) case of minor bleeding with EB. The median time from the first visit to biopsy was significantly shorter with CNB (5.5 days) than with EB (15 days). Conclusion: There is an increasing trend in the utility of CNB. CNB is a less invasive method with shorter time to biopsy and can be considered an alternative to EB. [ABSTRACT FROM AUTHOR]

The diagnosis of histological transformation of follicular lymphoma can be challenging and ambiguous. We investigated the distribution of the Ki‐67 labeling index of histological transformation of follicular lymphoma and determined its cutoff value to predict poor outcomes. The diagnostic criteria for histological transformation were a diffuse pattern of proliferation and a proportion of large lymphoma cells ≥20%. Of the 1121 patients with follicular lymphoma, 171 (15%) showed histological transformation to diffuse large B‐cell lymphoma. Of these, 76 patients, whose biopsies were obtained from the sites with the highest maximum standardized uptake values, according to the positron emission tomography findings, were included. The Ki‐67 index ranged from 16.8% to 98.4% (median, 60.6%). In patients with histological transformation, the most significant differences were found in progression‐free survival (p = 0.087, 58% vs. 87% at 2 years) and overall survival (p = 0.024, 53% vs. 85% at 5 years) when a 70% cutoff was used. Additionally, overall survival was significantly shorter in patients with histological transformation with maximum standardized uptake values of ≥20 (p < 0.0001) and absence of a follicular lymphoma component (p = 0.004). A Ki‐67 index of ≥70% was a significant adverse factor for overall survival in patients with histological transformation of follicular lymphoma and may predict poor outcomes. [ABSTRACT FROM AUTHOR]

Background: Approximately 15% of patients with diffuse large B‐cell lymphoma (DLBCL) experience refractory or early relapsed disease after initial rituximab‐containing chemoimmunotherapy is regarded as a primary refractory disease. Although the standard treatment for relapsed DLBCL is high‐dose chemotherapy and autologous stem cell transplantation (HDC‐ASCT), the efficacy of this approach for primary refractory DLBCL is not well understood. We aimed to investigate the clinicopathological characteristics and outcomes of patients with primary refractory DLBCL. Methods: Sixty‐nine consecutive patients with primary refractory DLBCL who were treated at our institution were categorized as partial responders (partial response to rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone [R‐CHOP] or relapse within 6 months of R‐CHOP) (n = 41) or primary progressors (no response to R‐CHOP) (n = 28). Survival curves were constructed using the Kaplan–Meier method and compared using the log‐rank test. Results: At initial diagnosis, 70% of patients had Ann Arbor stage III/IV disease, 56% had non‐germinal center B‐cell‐like type DLBCL, and 42% had double‐expressor lymphoma (MYC and BCL2 expression). The 3‐year overall survival rate was significantly poorer in the primary progressors group than in the partial responders' group (15% vs. 48%, p < 0.001). Four of 17 patients treated with HDC‐ASCT were primary progressors; only one patient survived without relapse. Although double‐expressor lymphoma status did not significantly impact overall survival among all patients (p = 0.794), it was identified as an independent poor prognostic factor in HDC‐ASCT‐treated patients (p = 0.002). Conclusions: We identified a subgroup of patients with primary refractory DLBCL who may not benefit from current treatment strategies. Further treatment development is needed to improve the outcomes of these patients. [ABSTRACT FROM AUTHOR]

Objectives: In this study, we aimed to determine the clinicopathological factors influencing the treatment‐free period in patients with follicular lymphoma (FL) using a watch‐and‐wait (WW) strategy. Methods: We retrospectively assessed histopathological parameters of 82 patients with FL. Results: The median time from diagnosis to WW discontinuation was 62 months (range, 3‐138), and median follow‐up was 86 months (range, 3‐183). Intermediate or high‐risk Follicular Lymphoma International Prognostic Index score (P =.012), non‐duodenal‐type (P =.011), higher numbers of interfollicular CD4+ (P =.038) and intrafollicular FOXP3+ cells (P =.024) in the tumor microenvironment, and Ki‐67 index ≥10% (P =.031) were significant adverse factors for WW discontinuation in univariate analyses. Conclusion: Patients with adverse factors for WW discontinuation should be carefully observed during follow‐up. [ABSTRACT FROM AUTHOR]

Background: Tazemetostat is a selective and orally available inhibitor of enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and epigenetic regulator of cellular differentiation programs. We carried out a phase I study of tazemetostat in Japanese patients with relapsed or refractory B‐cell non‐Hodgkin‐type lymphoma (B‐NHL) to evaluate its tolerability, safety, pharmacokinetics, and preliminary antitumor activity. Methods: Tazemetostat was given orally at a single dose of 800 mg on the first day and 800 mg twice daily (BID: total 1600 mg/d) on following days in a 28‐day/cycle manner. Tazemetostat dose‐limiting toxicity (DLT) was evaluated up to the end of the first treatment cycle. Archival tumor tissues were analyzed for hotspot EZH2 mutations. Results: As of 15 January 2018, seven patients (four follicular lymphoma [FL] and three diffuse large B‐cell lymphoma [DLBCL]) were enrolled. The median age was 73 (range, 59‐85) years, and the median number of prior chemotherapy regimens was three (range, one to five). No DLT was observed (one patient was not evaluable due to early disease progression). The common treatment‐related adverse events (AEs) were thrombocytopenia and dysgeusia (three patients each; 42.9%). No treatment‐related serious AEs were observed. The objective response rate was 57% (4/7 patients), including responses in three of four patients with FL and one of three patients with DLBCL. An EZH2 mutation was detected in one patient with FL responding to treatment. Conclusions: Tazemetostat at 800 mg BID showed an acceptable safety profile and promising antitumor activity in Japanese patients with relapsed or refractory B‐NHL. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the outcomes of local radiotherapy (LRT) in patients with histologic transformation (HT) following rituximab‐containing chemotherapy. Methods: We retrospectively analysed 92 patients with biopsy‐confirmed HT undergoing rituximab‐containing chemotherapy at our institution between 2003 and 2015. Results: Of the 36 patients with limited‐stage disease at diagnosis of HT, 29 (78%) received LRT. The estimated 5‐year progression‐free survival (PFS) rate was significantly better in patients who underwent LRT than in those who did not (93% and 42%, respectively; P < 0.05). Multivariate analyses employing age, sex, performance status, LRT and treatment response demonstrated that LRT was an independent prognostic factor for PFS (hazard ratio [HR]: 11.8; 95% confidence interval [CI]: 1.28‐108.1; P < 0.05). Of the 32 patients who underwent LRT for HT lesion treatment, 31 (97%) did not show disease progression within radiation fields; among them, 27 patients (84%) survived without disease progression during the follow‐up period. One patient developed hypothyroidism due to LRT; the others had no acute or late‐onset complications of LRT. Conclusions: Our data support the recommendation of LRT for HT lesion treatment following rituximab‐containing chemotherapy in select patients with localised HT, as a rational treatment approach with potentially limited toxicity. [ABSTRACT FROM AUTHOR]

Although histologic analysis is the gold standard for diagnosing follicular lymphoma (FL) transformation, many patients are diagnosed with transformation by clinical factors as biopsy specimens often cannot be obtained. Despite the frequency of clinical diagnosis, no clinical assessment tool has yet been established for FL transformation in the rituximab era. We derived and validated a transformation scoring system (TSS) based on retrospective analyses of 126 patients with biopsy‐proven FL and histologic transformation (HT) at two hospitals of the National Cancer Center of Japan. In the derivation set (76 patients), the detailed analyses of the clinical characteristics at disease progression showed that lactate dehydrogenase (LDH) elevation, focal lymph nodal (LN) enlargement, hemoglobin <12 g/dl, and poor performance status (PS) (2‐4) were associated with HT. The weights of these variables were decided based on the regression coefficients. Next, we constructed a TSS encompassing the above four factors: LDH, (> upper limit of normal [ULN], ≤ULN ×2) (1 point), (≥ULN ×2) (2 points); focal LN enlargement, (≥3 cm, <7 cm) (1 point), (≥7 cm) (2 points); hemoglobin <12 g/dl (1 point); poor PS (2 points). We identified a high positive predictive value (PPV) (96.4%) and negative predictive value (NPV) (85.4%) for diagnosing HT when a cutoff score of 2 was selected for our TSS. In an external validation set (50 patients), the probability of HT was high with scores ≥2 (PPV, 93.3%; NPV, 82.9%). We developed a TSS that offers a simple, yet, valuable tool, for diagnosing HT, especially in patients who cannot undergo biopsy. [ABSTRACT FROM AUTHOR]

CD20− change after rituximab-containing therapy is considered one of the main reasons of rituximab resistance of B-cell non-Hodgkin lymphomas (B-NHLs). However, the clinicopathological characteristics of B-NHL with CD20− change are not entirely understood. In this study, 252 B-NHL patients who were CD20+ at initial diagnosis, whose diseases relapsed or were refractory after rituximab-containing therapy, and who were re-biopsied between 2000 and 2018, were included. The median number of rituximab administration was 11 (range, 1–48). Completely negative (cCD20−) and partially negative (pCD20−) change of CD20 was observed in 49 (20%) and 16 (6%) cases, respectively. Among cCD20− and pCD20− cases, 74% and 62% of the cases changed to CD20− at the second relapse or later, respectively. Overall survival was significantly shorter in cCD20− follicular lymphoma (FL) cases than in CD20+ FL cases. Seven histopathological patterns, such as CD20− change without histological change, histological transformation (HT) to CD20− diffuse large B-cell lymphoma, and proliferation of plasmablastic/plasmacytoid tumor cells, were associated with CD20− change. HT occurred more frequently in FLs with CD20− change than in FLs continuously expressing CD20 (P < 0.0001), regardless of the timing of HT. Nine out of 25 cases (36%) showed regain or heterogeneous regain of CD20 expression. In conclusion, 20% and 6% of the 252 B-NHL cases show cCD20− and pCD20− changes with 7 histological patterns after rituximab-containing therapy. Because changes in morphology and CD20 expression after rituximab-containing therapy vary, and recovery of CD20 expression is not rare, careful follow-up and re-biopsy in B-NHL patients are recommended. [ABSTRACT FROM AUTHOR]

Tirabrutinib is a second‐generation Bruton's tyrosine kinase inhibitor with greater selectivity than ibrutinib. Here, we conducted a multicenter, phase II study of tirabrutinib in patients with treatment‐naïve (Cohort A) or with relapsed/refractory (Cohort B) Waldenström's macroglobulinemia (WM). Patients were treated with tirabrutinib 480 mg once daily. The primary endpoint was major response rate (MRR; ≥ partial response). Secondary endpoints included overall response rate (ORR; ≥ minor response), time to major response (TTMR), progression‐free survival (PFS), overall survival (OS), and safety. In total, 27 patients (18 in Cohort A; 9 in Cohort B) were enrolled. The median age was 71 y, and the median serum immunoglobulin M level was 3600 mg/dL. Among the patients, 96.2% had the MYD88L265P mutation. MRR and ORR were 88.9% and 96.3%, respectively (Cohort A: MRR, 88.9%; ORR, 94.4%; Cohort B: MRR, 88.9%; ORR, 100%). Median TTMR was 1.87 mo. PFS and OS were not reached with a median follow‐up of 6.5 and 8.3 mo for Cohorts A and B, respectively. The most common adverse events (AEs) were rash (44.4%), neutropenia (25.9%), and leukopenia (22.2%), with most AEs classified as grade 1 or 2. Grade ≥ 3 AEs included neutropenia (11.1%), lymphopenia (11.1%), and leukopenia (7.4%). No grade 5 AEs were noted. All bleeding events were grade 1; none were associated with drug‐related atrial fibrillation or hypertension. Although the follow‐up duration was relatively short, the study met the primary endpoint. Therefore, tirabrutinib monotherapy is considered to be highly effective for both untreated and relapsed/refractory WM with a manageable safety profile. (JapicCTI‐173646). [ABSTRACT FROM AUTHOR]

Aims: The Lugano classification is a novel staging system for lymphomas established in 2014. In this staging system, 18F‐fluorodeoxyglucose‐positron emission tomography/computed tomography (FDG‐PET/CT) was formally incorporated into standard staging for FDG‐avid lymphomas, including Hodgkin lymphoma (HL). We retrospectively analyzed patients with HL who were newly diagnosed and treated at our institution to evaluate the utility of the Lugano classification compared to the Ann Arbor classification in Japanese patients with this type of lymphoma. Methods: Patients newly diagnosed with HL between 2005 and 2011 were identified through our departmental database. Data from neck‐chest‐abdomen‐pelvis CT scans, BM examinations, and FDG‐PET/CT that were routinely performed for staging at our clinical practice were retrieved and analyzed. Results: Fifty‐four patients with a median age of 35.5 years (range: 15‐78 years) were investigated in this retrospective study. The Lugano stage matched the Ann Arbor stage in 46 patients (85%). Six patients (11%) were upstaged while two (4%) were downstaged per the Lugano classification. Four patients (7%) were converted from early stage to advanced stage, but none was converted in the reverse. Among 11 patients (20%) with PET‐positive bone/bone marrow lesions, only one (2%) exhibited biopsy‐proven bone marrow involvement of HL cells. Conclusion: Our data revealed a high concordance rate between the Lugano and Ann Arbor staging system in Japanese patients with HL. Because of its low diagnostic value, routine bone marrow examination might be unnecessary for staging when FDG‐PET/CT is used as a substitute. [ABSTRACT FROM AUTHOR]

This is the first case report of alectinib as a bridge to allo‐SCT in a patient with ALK‐positive ALCL refractory to both conventional chemotherapies and BV. This report offers a ray of hope for a condition with poor prognosis. [ABSTRACT FROM AUTHOR]

We analyzed the clinicopathologic characteristics of 136 intestinal diffuse large B-cell lymphomas (DLBCLs) among 126 patients. The DLBCL sites were categorized as: duodenum (n = 23), ileocecal region (n = 63), other small intestine (n = 29), rectum (n = 7), and other large intestine (n = 14). Patients with DLBCLs of the ileocecal region or other small intestine frequently underwent surgery for ileus or perforations (P < 0.001), were predominantly male (P = 0.042), and had a higher incidence of limited-stage disease (P = 0.001), lower International Prognostic Index (P = 0.015), and lower incidence of lactate dehydrogenase elevation (P = 0.007) than those with DLBCLs of other regions. Half of the intestinal DLBCLs exhibited the germinal center B-cell phenotype. A low-grade B-cell lymphoma background was found in 21% of the cases; the prevalence was significantly lower in the ileocecal region (13%, P = 0.025), suggesting a higher incidence of de novo DLBCLs. Intestinal follicular lymphoma (FL) and mucosa-associated lymphoid tissue (MALT) lymphoma backgrounds were observed in 10% and 0% of the cases, respectively. Five percent (5/107) of intestinal DLBCL cases were Epstein-Barr virus-encoded RNA-1 positive. The clinicopathologic characteristics of the DLBCLs differed by region. Histologic transformation of intestinal FL was observed in around 10% of the intestinal DLBCL cases. [ABSTRACT FROM AUTHOR]

Epstein‐Barr virus (EBV) infection is associated with pathogenesis of various cancers, including extranodal natural killer/T‐cell lymphoma, nasal type (ENKL). ENKL tumor cells are positive for EBV‐encoded RNA1 (EBER1), which is the most useful marker to identify ENKL tumor cells in histopathology. Currently, EBER1 in situ hybridization (ISH) is recommended to evaluate bone marrow (BM) involvement of ENKL. However, the actual burden of EBER1‐positive cells in normal BM specimens remains unclear. In the present study, we performed EBER1 ISH on 111 BM specimens, which were obtained during an initial staging procedure in patients with EBV‐negative cancers and were also negative for BM involvement. One or more EBER1‐positive cells per whole specimen were observed in 38 specimens (34%). The number of EBER1‐positive cells was distributed as follows: single positive cell, n = 17; two positive cells, n = 13; three positive cells, n = 3; and four positive cells, n = 5. These findings suggest that four or fewer EBER1‐positive cells can be observed in BM specimens of patients with non‐EBV‐related cancers. The clinical implications of a small number of EBER1‐positive cells in BM specimens of patients with ENKL should be evaluated in further studies. [ABSTRACT FROM AUTHOR]

Translocation (11;18)(q21;q21) is found in mucosa-associated lymphoid tissue (MALT) lymphoma, resulting in API2/MALT1 gene fusion. It is known that t(11;18)-positive MALT lymphoma shows a tendency to disseminate and be resistant to Helicobacter pylori eradication by antibiotics. However, the prognostic features including recurrence and histological transformation (HT) remain unknown. We conducted a single-institute retrospective analysis of 464 patients with newly diagnosed MALT lymphoma, evaluating the impact of t(11;18) on clinical outcomes. One hundred and six patients were screened for the translocation by fluorescence in situ hybridization and/or reverse transcriptase-polymerase chain reaction. Of these patients, 26 patients (25%) were diagnosed as MALT lymphoma with t(11;18). The patients had a significantly shortened progression-free survival (PFS at 10 years; 26% v 57%; P = 0.004) compared to those without t(11;18). However, this did not translate into overall survival or incidence of HT. We confirmed previous reports stating that t(11;18)-positive MALT lymphoma showed disseminated disease and refractoriness to H. pylori eradication therapy. Patients with t(11;18) had more frequent monoclonal gammopathy, especially of IgM subtype (31% v 8%; P = 0.008), some of which developed class switch. These findings characterize the features of t(11;18)-positive MALT lymphoma, suggesting that it comprises a distinct clinical entity of MALT lymphoma. [ABSTRACT FROM AUTHOR]

We evaluated the safety, efficacy, pharmacokinetics, pharmacodynamics and predictive biomarkers of tirabrutinib, a second‐generation, enhanced‐selectivity Bruton's tyrosine kinase inhibitor in Japanese patients with relapsed/refractory B‐cell non−Hodgkin lymphoma (B‐cell NHL) and chronic lymphocytic leukemia (CLL). This was an open‐label, multicenter, phase I study. Seventeen patients (male N = 8) with a median age of 70 years were enrolled in 4 dose cohorts (160 mg once daily [N = 3], 320 mg once daily [N = 3], 480 mg once daily [N = 4] and 300 mg twice daily [N = 7]); 4 patients had continued tirabrutinib administration as of 4 January 2018. The maximum tolerated dose was not reached. Pneumonitis (N = 1) was the dose‐limiting toxicity for 300 mg twice daily. Common adverse events (AEs) were rash (35.3%) and vomiting (29.4%). Eight patients (47.1%) developed grade ≥3 AEs: neutropenia (23.5%), anemia (11.8%) and leukopenia (11.8%) were frequent. The overall response rate (≥PR) was 76.5% (13/17 patients), including 4 DLBCL patients with no CD79A/B or MYD88 mutations, and 1 CLL patient with a TP53 mutation, providing promising data for future developments. Of 16 patients with measurable lesions during the screening period, 12 showed ≥50% reductions in tumor diameter. In many patients, the tumor size decreased soon after beginning treatment. The maximum serum concentration for tirabrutinib was 611, 1220, 1280 and 886 ng/mL on Day 1 and 484, 971 1940, and 961 ng/mL on Day 28 for Cohorts 1‐4, respectively. Tirabrutinib pharmacokinetics were linear, with little accumulation following multiple doses. Tirabrutinib was well tolerated and showed promising efficacy for B‐cell NHL/CLL. [ABSTRACT FROM AUTHOR]

We present a case of atypical extraosseous plasmacytoma (EP) with a plasmablastic morphology and CD3+ CD56+ Epstein-Barr virus-encoded RNA-1 (EBER1)+ phenotypes of the nasal cavity. A 51-year-old male attended a local hospital with a tumor located in his left nasal cavity that was histologically diagnosed as extranodal NK/T cell lymphoma, nasal type. We reviewed the specimens and re-biopsied the tumor, and confirmed that the tumor was positive for CD3, CD56, and EBER1; however, the tumor showed a plasmablastic morphology without necrosis and angiocentricity, and was positive for CD138, but negative for CD20 and PAX5. Given a plasmablastic morphology and EBER1 positivity, but a relatively low Ki67 index (30%), we diagnosed the case as atypical EP. The CHOP regimen was administered and complete remission achieved. This case indicated that EP should be considered as a differential diagnosis even when a tumor shows large cell morphology and is positive for CD3, CD56, and EBER1. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: We aimed at investigating the relationship between classical Hodgkin lymphoma (cHL), primary mediastinal large B‐cell lymphoma (PMBL), and gray zone lymphoma (GZL) with intermediate characteristics between cHL and PMBL, from the perspective of the aberration in programed cell death 1 and the programed death ligands (PDLs) network. Methods: We explored the expression levels of PDLs and chromosomal anomalies in 67 cases: 34 cases with cHL, 20 with PMBL, and 13 with GZL, using immunohistochemical analyses and Fluorescence In Situ Hybridization (FISH). Results: Twenty‐one cHL (62%), 3 PMBL (15%), and 6 GZL (46%) cases showed staining to PD‐L1 antibodies in more than 70% of tumor cells. Two cHL (6%), 10 PMBL (50%), and 3 GZL (23%) cases were not stained by PD‐L1 antibodies. Patients over 40 years old manifest more frequent expression of PD‐L1 in cHL. Proportion of tumors stained by PD‐L2 antibody was increased in PMBL. FISH analyses with a PD‐L1/PD‐L2 probe detected 5 amplification, 1 gain, and 7 polysomy cases in cHL, 1 amplification and 1 polysomy case in GZL, and amplification in 1 PMBL case. Conclusion: We identified increased staining of PD‐L1 in cHL and that of PD‐L2 in PMBL. GZL had a pattern similar to that of cHL. [ABSTRACT FROM AUTHOR]

The current therapy for high-risk myelodysplastic syndrome (MDS) involves repeated cycles of the DNA demethylating agent 5-azacitidine (5-Aza), but combination treatments have been proposed to improve patient outcomes. We performed a phase Ib study to investigate the safety and tolerability of 5-Aza (75 mg/m2) combined with the histone deacetylase inhibitor panobinostat (PAN) in adult Japanese patients with MDS or chronic myelomonocytic leukemia (CMML). Eleven patients were enrolled; five received 20 mg PAN + 5-Aza and six received 30 mg PAN + 5-Aza. All patients in the 20 mg PAN cohort had MDS, while two in the 30 mg PAN cohort had MDS and three had CMML. All patients experienced ≥1 adverse event (AE) related to the study treatment, and five discontinued the study treatment because of AEs. One patient in each group exhibited dose-limiting toxicities: lung infection (PAN 20 mg + 5-Aza) and cellulitis (PAN 30 mg + 5-Aza). PAN exposure increased with ascending doses, and combination therapy did not affect PAN plasma trough concentrations. In summary, 20 or 30 mg PAN combined with 5-Aza was safe and tolerable in adult Japanese patients with CMML or MDS. Study registration ClinicalTrials.gov Identifier: NCT01613976. [ABSTRACT FROM AUTHOR]

We analyzed the distribution of tumors and lymphomas of the anterior mediastinum diagnosed between 1997 and 2016 at the National Cancer Center Hospital, Japan. The median age of 283 patients with anterior mediastinal tumors was 48 (range 6-84) years, and 143 (51%) were male. The incidence of tumors was as follows: thymoma, 34%; thymic carcinoma, 16%; primary mediastinal large B-cell lymphoma (PMBL), 13%; germ cell tumors, 10%; classical Hodgkin lymphoma (CHL), 9%; thymic cyst, 7%; metastatic tumors, 3%; T lymphoblastic leukemia/lymphoma (T-LBL), 2%; other lymphomas, 3%; and others, 3%. Of the newly diagnosed lymphomas in 60 patients, PMBL (46%) was the most frequent, followed by CHL (32%), T-LBL (12%), mucosa-associated lymphoid tissue lymphoma (3%), and other lymphomas (7%). These findings suggest a recent increase in PMBL in Japan. The frequency and subtype of lymphoma differ with age and sex. In female patients ≤40 years old, 58% of the anterior mediastinal tumors were PMBL (39%) or CHL (19%). Germ cell tumors were the most frequent in male patients ≤40 years old, followed by CHL (21%), PMBL (17%), and T-LBL (10%). This distribution may serve as a reference for routine histologic diagnosis of lymphomas in the anterior mediastinum in Japan. [ABSTRACT FROM AUTHOR]

The hedgehog signaling pathway regulates multiple morphogenetic processes during embryogenesis. Aberrant activation of the hedgehog pathway signal transduction in adult tissues is associated with the pathogenesis of hematologic malignancies and solid tumors. We report findings from an open-label, multicenter phase I trial of the selective, small-molecule hedgehog signaling inhibitor glasdegib ( PF-04449913) in Japanese patients with select advanced hematologic malignancies. Glasdegib was administered as once-daily oral doses (25, 50 and 100 mg) in 28-day cycles after a lead-in dose on Day −5. The primary objectives were to determine first-cycle dose-limiting toxicities, safety, vital signs and laboratory test abnormalities. Secondary objectives included evaluation of pharmacokinetics, pharmacodynamics and preliminary evidence of clinical activity of glasdegib. No dose-limiting toxicities were noted in the 13 patients in the present study. All patients experienced at least one treatment-emergent, all-causality adverse event. The most frequent treatment-related adverse events (observed in ≥3 patients) were dysgeusia ( n = 9), muscle spasms ( n = 5), alopecia, decreased appetite ( n = 4 each), and increased blood creatinine phosphokinase, constipation and diarrhea ( n = 3 each). Two deaths occurred during the study and were deemed not to be treatment-related due to disease progression. Glasdegib demonstrated dose-proportional pharmacokinetics, marked downregulation of the glioma-associated transcriptional regulator GLI1 expression in normal skin, and evidence of preliminary clinical activity, although data are limited. Glasdegib was safe and well tolerated across the dose levels tested. It is confirmed that the 100-mg dose is safe and tolerable in Japanese patients, and this dose level will be examined in the future clinical trial. [ABSTRACT FROM AUTHOR]

We report the case of a patient with relapsed classical Hodgkin lymphoma who developed fulminant type I diabetes mellitus as a severe adverse event of treatment with the anti-programmed cell death-1 (PD-1) antibody, nivolumab. On the first day of the sixth cycle, the blood glucose level was markedly elevated (375 mg/dL). Although neither ketoacidosis nor ketonuria was detected, the markedly acute onset of the hyperglycemia was consistent with the typical clinical course of fulminant type I diabetes mellitus, and this diagnosis was supported by clinical data. All autoantibodies associated with type I diabetes mellitus were negative. The endogenous insulin secretion ceased completely within 2 weeks. After the blood glucose level was brought under control, nivolumab was resumed and continued without other major adverse events. Human leukocyte antigen (HLA) analysis revealed that the patient carried the HLA-B*4002 haplotype, a susceptibility allele for this type of diabetes mellitus. This case suggests that fulminant type I diabetes mellitus may be triggered by nivolumab in patients with a genetic background associated with the condition, warranting careful future consideration of this particular adverse event. [ABSTRACT FROM AUTHOR]

Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)/CHOP-like chemotherapy has been mostly applied to patients with untreated peripheral T cell lymphoma (PTCL). Because the long-term outcome of patients with PTCL, especially those achieving complete response (CR), has not been fully elucidated, we retrospectively analyzed 78 consecutive patients initially treated with CHOP/CHOP-like chemotherapy, without high-dose chemotherapy followed by autologous stem cell transplantation (HDC/auto-SCT). Median overall and progression-free survivals in all 78 patients were 44 and 17 months, respectively, with a median follow-up of 62 months. In the 53 patients achieving CR, the median relapse-free survival (RFS) was 21 months, and 2-, 3-, and 5-year RFSs were 46, 45, and 36%, respectively. Although our results showed an unfavorable outcome for PTCL as a whole, those who achieved CR following CHOP/CHOP-like chemotherapy did not always have a poor outcome without the consolidation of HDC/auto-SCT; in particular, 45% of the 65 years or younger patients were alive without disease at 5 years. [ABSTRACT FROM AUTHOR]

We analyzed the effects of the initial approach to patients with follicular lymphoma (FL) on outcomes in order to investigate whether the watch and wait (WW) strategy is still an acceptable approach in the rituximab era. We retrospectively analyzed 348 patients who were initially diagnosed with FL between 2000 and 2012. We compared the clinical outcomes of the WW cohort and immediate treatment cohort. Among 348 patients (median age of 57 years, range: 19-85), 101 were initially managed with WW and 247 were immediately treated. The median follow-up duration was 75 months (range: 7-169). The estimated median time to treatment failure (TTF) in the treatment following WW cohort and immediate treatment cohort were 92 months (95 % CI, 60.1-NA) and 77 months (95 % CI, 65.1-107.6), respectively, which were not significantly different (P = 0.272) . In a multivariate analysis, clinical stage was identified as a predictive factor of TTF (HR 1.19, 95 % CI, 1.03-1.38, P < 0.05). Neither overall survival rate nor cumulative risk of transformation between the WW cohort and immediate treatment cohort was significant. The results of the present study suggested that the WW strategy is still an acceptable approach for selected FL patients in the rituximab era. [ABSTRACT FROM AUTHOR]

Although MM remains incurable, treatment strategies have been improved by developing new agents and the overall survival of MM patients has significantly increased in the last decades [[1]]. In our patient, CLd therapy was effective for MM with I IgH-FGFR3 i rearrangement and VGPR was maintained for 2 years. [Extracted from the article]

This study analysed incidence, patient outcome, immunophenotype and prognostic factors of histological transformation ( HT) from extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue ( MALT lymphoma) to diffuse large B-cell lymphoma ( DLBCL) in 467 patients (median age, 61 years). The primary sites of MALT lymphoma were the stomach (43%), ocular adnexa (25%), lung (8%), systemic (8%) and other tissues (16%). HT occurred in 8% of MALT lymphomas. Risk of HT by 15 years was 5%: 4% in limited-stage diseases ( n = 385) and 16% in advanced-stage diseases ( n = 56) ( P = 0·02). The median time to HT was 48 months (range, 4-139). Five-year progression-free survival ( PFS) and overall survival ( OS) rates after HT were 80% and 94%, respectively. Immunohistochemical results of DLBCL were as follows: germinal centre B-cell ( GCB)/non- GCB, 37%/63%; CD10, 9%; BCL6, 59%; MUM1, 38%; MYC, 42%; BCL2, 35%; Ki67 ≥ 90%, 23%; and CD5, 3%. The majority (75%, 9/12) of GCB-type DLBCLs exhibited CD10−, BCL6+ and MUM1− immunophenotypes; the remainder had CD10+ immunophenotypes. Multivariate analysis revealed that only advanced stage at HT was a significant adverse factor for PFS ( P = 0·037). Thus, overall risk of HT was low and prognosis after HT was favourable; however, in advanced-stage cases, risk of HT was relatively high and prognosis was unfavourable. [ABSTRACT FROM AUTHOR]

Brentuximab vedotin (BV) is an antibody-drug conjugate that targets CD30. It is highly effective for relapsed/refractory classical Hodgkin lymphoma (CHL), and has become a promising treatment option for these patients; however, approximately 25 % of patients are refractory to BV. Until now, the clinicopathologic features of CHL refractory to BV have not been well understood. Here, we report a patient with relapsed CHL with an unfavorable outcome, whose disease was primary refractory to BV and was histologically diagnosed as a transformation from mixed cellularity CHL to CD30-positive diffuse large B-cell lymphoma (DLBCL). The transformation to DLBCL showing high tumor density and high proliferative activity (Ki67 index >90 %) was possibly related to the primary refractory to BV and an aggressive clinical course, although the lymphoma was diffusely and strongly positive for CD30. [ABSTRACT FROM AUTHOR]

Hodgkin lymphoma (HL) is a rare subtype of malignant lymphoma in Japan, and there are few reports of HL in Japan in recent years. We retrospectively analyzed the clinical features of 139 patients with HL who were diagnosed and treated at our institution between 1997 and 2011. The median age at diagnosis was 34 years with 83 male. Of these patients, 83 (60 %) were early stage and 56 (40 %) were advanced-stage. Seventy-three patients (88 %) with early stage disease received ABVd followed by irradiation. All of the 56 advanced-stage patients received chemotherapy, mainly ABVd. The 5-year progression-free survival (PFS) rates and overall survival rates were 90 and 94 % in patients with early stage disease, and 71 and 90 % in those with advanced-stage disease. The PFS of patients with advanced-stage disease was significantly lower than those with early stage (p = 0.014). In conclusion, the outcomes of Japanese patients with HL in recent years were not improved as compared with the results of previous reports. We confirmed that patients with advanced-stage disease have lower PFS than those with early stage disease. Prospective studies are needed to establish novel treatment strategies to improve the outcome of HL patients, especially those with advanced disease. [ABSTRACT FROM AUTHOR]

B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (iBL/DLBCL), is a rare, but an aggressive subtype. In iBL/DLBCL, clinicopathological prognostic factors, including MYC and BCL2 translocations (double hit translocation, DHT) and the expression of both MYC and BCL2 (double hit score 2, DHS2), have not been studied thoroughly. We retrospectively analyzed the prognostic impact of clinicopathological factors, including MYC split, IGH/BCL2 fusion, MYC and BCL2 expressions, in 24 iBL/DLBCL patients (median age: 47 years). Fifteen patients (62 %) underwent intensive chemotherapy, and nine patients (38 %) underwent rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). The 5-year progression-free (PFS) and overall survival (OS) rates of intensive chemotherapy and R-CHOP were 57 and 72 %, respectively. PFS was significantly shorter in patients with high IPI score (P < .0001), stage IV (P = .001), aged ≥60 years (P = .042), IGH/BCL2 fusion (P = .029), DHS2 (P = .015), and DHT (P = .03). OS was significantly shorter in patients with high IPI score (P < .0001) and aged ≥60 years (P = .008). In iBL/DLBCL, IGH/BCL2 fusion, DHS2, and DHT were pathological prognostic factors for poor PFS, while IPI remained as more predictive for PFS and OS. [ABSTRACT FROM AUTHOR]

Unlabelled: In this phase I dose-escalation study we evaluated the safety, tolerability, pharmacokinetics, and antitumor activity of ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase (BTK, in Japanese patients with relapsed/refractory B cell malignancies (RRBCM). Fifteen patients aged 42-78 years were enrolled to one of three cohorts. Cohort 1 (n = 3) consisted of two phases, a single-dose (140 and 280 mg) phase and a multiple-dose (420 mg) phase of ibrutinib; cohort 2 (n = 6) included multiple doses of ibrutinib 560 mg; and cohort 3 (n = 6) included only patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) dosed at ibrutinib 420 mg. One patient (CLL/SLL cohort) experienced grade 3 pneumonia and sepsis, which were considered dose-limiting toxicities. No deaths were reported. The most common (≥ 20% patients) adverse events were neutropenia, anemia, nasopharyngitis, increased bilirubin, and rash. Dose-dependent increase in maximum plasma concentration and area under the concentration from 0 to the last quantifiable time was observed, while time to reach maximum plasma concentration and elimination half-life was similar between doses. The overall response rate was 73.3% (11/15) for all cohorts combined. Overall, ibrutinib (420 and 560 mg) was tolerable with acceptable safety profiles and effective for Japanese patients with RRBCM including CLL/SLL.Clinical Trial Registration: NCT01704963. [ABSTRACT FROM AUTHOR]

Detection of immunoglobulin light chain restriction (LCR) by flow cytometry (FCM) is a useful tool for B-cell non-Hodgkin lymphoma (B-NHL) diagnosis. Here, we identified B-NHLs without LCR by FCM and investigated the pathological causes for lack of LCR. A total of 89/471 cases (19%) of B-NHL were LCR-negative. The incidence of lack of LCR was 30% both in diffuse large B-cell lymphoma (DLBCL) and marginal zone lymphoma (MZL), and was 6% in follicular lymphoma (FL). In DLBCL cases, low expression of surface membrane light chain (33%), low proportion of lymphoma cells (11%), CD45 negativity (9%), and destruction or sampling error were suggested as reasons for lack of LCR. In MZL cases, the low proportion of lymphoma cells owing to admixture of many reactive germinal centres, and non-detection of plasmacytoid lymphoma cells by CD45 gating might be the reasons. Based on pathological subtypes, the frequency and reasons for lack of LCR by FCM varied. [ABSTRACT FROM AUTHOR]

We carried out a multicenter dose-escalation phase I study of oral OPB-51602, a signal transducer and activator of transcription 3 phosphorylation inhibitor, in patients with relapsed or refractory hematological malignancies to evaluate the safety, maximum tolerated dose ( MTD), pharmacokinetics, and preliminary antitumor activity. Twenty patients were treated with OPB-51602 at doses of 1, 2, 3, 4, and 6 mg in the '3 + 3' dose escalation design. The most common treatment-related adverse events included nausea (55%), peripheral sensory neuropathy (45%), and diarrhea (40%). The most frequently observed grade 3 or 4 drug-related adverse events were neutropenia (20%), leukopenia (15%), lymphopenia (10%), and thrombocytopenia (10%). The MTD was 6 mg, with dose-limiting toxicities of grade 3 lactic acidosis and increased blood lactic acid levels observed in one of three patients and grade 1-2 peripheral neuropathy in three of three patients. The recommended dose was determined to be 4 mg. OPB-51602 was rapidly absorbed, and exposure tended to increase in a dose-dependent manner. Accumulation of OPB-51602 was seen with 4 weeks of multiple treatments. No clear therapeutic response was observed. Durable stable disease was observed in two patients with acute myeloid leukemia and one with myeloma. In conclusion, the MTD of OPB-51602 was 6 mg. OPB-51602 was safe and well tolerated in a dose range of 1-4 mg. However, long-term administration at higher doses was difficult with the daily dosing schedule, and no response was seen. Therefore, further clinical development of OPB-51602 for hematological malignancies with a daily dosing schedule was terminated. [ABSTRACT FROM AUTHOR]

This study aimed to indicate patient outcomes and pathological characteristics of follicular lymphoma (FL) with peripheral blood (PB) involvement. Of 533 patients with FL, 56 (11%) had PB involvement. Of the patients treated with rituximab, 39 patients with PB involvement had significantly shorter progression-free survival than 107 patients with stage IV disease without PB involvement ( p = 0.021), but the overall survival was not different ( p = 0.804). The histopathology of the primary sites was usually nodal (95%) low-grade (86%) FL with IGH/BCL2 fusion (75%). Flow cytometric and immunohistochemical analyses revealed that the incidence of CD10 positivity was lower in the bone marrow (55% and 58%) and PB (41% and not available) than in the primary site (86% and 93%) ( p = 0.004 and p = 0.0001, respectively). Therefore, even if small lymphoma cells in the bone marrow and PB are negative for CD10, FL cannot be ruled out. [ABSTRACT FROM AUTHOR]

The article discusses research on incidental detection of malignant lymphoma in a cancer surveillance programme in Japan. Topics discussed include use of usefulness of [18F] fluoro-deoxyglucose (FDG) positron emission tomography/computerized tomography (PET/CT) in monitoring cancer, demonstration of superiority of PET/CT over conventional scintigraphy for diagnosing malignant lymphoma (ML), and diagnosis of mucosa-associated lymphoid tissue (MALT) lymphoma of the gastrointestinal tract.