Noriyuki Morikawa

Bcl-2, Bcl-6, and the International Prognostic Index are prognostic indicators in patients with diffuse large B-cell lymphoma treated with rituximab-containing chemotherapy.

This study aimed to clarify the clinicopathological prognostic parameters of de novo diffuse large B‐cell lymphoma (DLBCL) in the rituximab era. We examined the correlation of 22 clinicopathological parameters with progression‐free survival (PFS), overall survival (OS), and primary refractory disease in 285 DLBCL patients treated with rituximab‐containing chemotherapy. Complete response rate was 87%, overall response rate was 91%, 5‐year PFS rate was 72%, and 5‐year OS rate was 91%. By log–rank test, higher International Prognostic Index (IPI) (P < 0.0001), Bcl‐2 positivity (P = 0.0013), Bcl‐6 negativity (P = 0.0112), and no irradiation (P = 0.0371) were significantly correlated with shorter PFS; higher IPI (P = 0.0107), starry sky pattern (P = 0.0466), and no irradiation (P = 0.0264) correlated with shorter OS. In multivariate analyses, higher IPI (P = 0.0006), Bcl‐2 positivity (P = 0.0015), and Bcl‐6 negativity (P = 0.04) were significantly correlated with shorter PFS; higher IPI (P = 0.0045) correlated with shorter OS. Bcl‐2 (P = 0.0029), Bcl‐6 (P = 0.002), and IPI (P < 0.0001) were significantly correlated with primary refractory disease. In conclusion, Bcl‐2 positivity, Bcl‐6 negativity, and higher IPI were indicators of shorter PFS and OS plus primary refractory disease in patients with DLBCL in the rituximab era.

Follow-up data of 10 patients with B-cell non-Hodgkin lymphoma with a CD20-negative phenotypic change after rituximab-containing therapy.

Recently, a CD20-negative phenotypic change in CD20-positive B-cell non-Hodgkin lymphoma (B-NHL) after rituximab therapy was described. We report the follow-up data of 10 B-NHL patients showing this change after rituximab therapy. Ten patients (4 men and 6 women; median age, 57 y) with B-NHL who were initially CD20 positive and became CD20 negative after rituximab therapy were analyzed. Clinicopathologic features, including clinical course, CD20 expression, and histopathology, were examined. CD20 expression in lymphoma cells was evaluated using immunohistochemistry and/or flow cytometry. Histopathologically, diagnosis at initial presentation was follicular lymphoma (FL) in 7 patients; diffuse large B-cell lymphoma in 1; and chronic lymphocytic leukemia in 2. Six patients (60%, 3 FL, 1 diffuse large B-cell lymphoma, and 2 chronic lymphocytic leukemia patients) showed continuous CD20 negativity until 24 months after the phenotypic change. Three patients (30%) with FL regained CD20 expression within 1 to 7 months after detection of the CD20 change. Two patients (20%) with FL, including 1 who regained CD20 expression, showed heterogenous CD20 expression with a CD20-negative low-grade component and a CD20-positive large cell component. The overall response rate to therapy before the CD20-negative change was 70%. We reported the follow-up data of 10 B-NHL patients with a CD20-negative phenotypic change associated with rituximab-containing therapy. The most common histologic phenotypes were continuous CD20 negativity, recovery of CD20 expression within 7 months, and heterogenous CD20 expression. As the changes in morphology and CD20 expression after rituximab therapy vary widely, careful follow-up and rebiopsy are recommended.

Incidental detection of malignant lymphoma in subjects in a cancer surveillance programme

Cancer surveillance programmes have recently been introduced in Japan. The usefulness of [F] fluoro-deoxyglucose (FDG) positron emission tomography/computerized tomography (PET/CT) has been established for the diagnosis/treatment monitoring of various types of cancer. The superiority of PET/CT over conventional scintigraphy for diagnosing malignant lymphoma (ML) has been demonstrated; PET/CT has also been used to evaluate treatment responses in ML (Moog et al, 1997, 1998). However, the diagnostic value of this modality for each histopathological type continues to be debated; in particular, its value for diagnosing low-grade lymphoma is controversial (Karam et al, 2006). We analysed the data for 10 659 individuals who participated in a cancer surveillance programme that included PET/ CT at the Research Centre for Cancer Prevention, National Cancer Centre, Japan, from 2004 to 2011. The subjects were healthy individuals over the age of 40 years with no history of cancer who had elected to participate in this programme. Written informed consent was obtained from all participants. The median age of participants was 59 years and the oldest was 89 years old. For four consecutive years after the screening, all participants were surveyed annually about their health by questionnaires that included questions about development of cancer. The participants could opt for repeated screening. The screening included blood tests, urinalysis, sputum cytology, abdominal ultrasonography, thoracic CT, upper gastrointestinal endoscopy and either colonoscopy or colon X-ray examination. Cervical cytology, mammography, breast ultrasonography and pelvic magnetic resonance imaging (MRI) were also performed on women. PET/CT was performed optionally. Blood tests included a complete blood count, biochemical tests, hepatitis virus screening and serum concentrations of the tumour markers carcinoembryonic antigen, cancer antigen (CA)19-9, prostate-specific antigen in men and CA125 in women. Histopathological subtype, examination(s) that contributed to making the diagnosis, survival and the cause of death were collected for the subjects who had been diagnosed with ML. ML was detected in the initial screening of 18 participants, representing a prevalence of 0 16%, which is higher than the estimated incidence (0 012%) in the general Japanese population (Matsuda et al, 2012). ML was diagnosed in subsequent optional screening in another seven subjects who had not been found to have ML in their initial screening (Fig 1). The questionnaire survey identified that diffuse large B cell lymphoma (DLBCL) had been found in another two cases at other institutions. This cancer screening programme detected 25 cases of ML including 12 marginal zone lymphoma, five follicular lymphoma (FL), four DLBCL, two small lymphocytic

High non-relapse mortality and low relapse incidence in gender-mismatched allogeneic hematopoietic stem cell transplantation from a parous female donor with a male child

Abstract To clarify the influence of exposure to a male fetus during a female donor’s (FD) pregnancy in allogeneic hematopoietic stem cell transplantation (HSCT), we retrospectively examined 292 HSCT patients. The 5-year non-relapse mortality (NRM) was 33.5% among 31 male recipients who had HSCT from FD with a male child (MC), 23.0% among 40 male recipients who had HSCT from FD without MC and 19.6% among 221 other recipients. The 5-year relapse incidence (RI) was 22.6%, 42.0%, and 43.1% for the respective group. In multivariate analysis, male recipients who had HSCT from FD with MC had an increased risk of NRM (hazard ratio [HR] 1.92, 95% CI 1.08–3.42, p = .03), a reduced risk of RI (HR 0.42, 95% CI 0.18–0.96, p = .04), resulting in no significant difference regarding overall survival. Male child of FD is suggested to influence NRM and RI in gender-mismatched HSCT.