Anna Takahashi

Bearing 19q13 aberration predicts poor prognosis in non-germinal centre type of CD5+ DLBCL

Patients with CD5 positive (CD5) diffuse large B cell lymphoma (DLBCL) are frequently resistant to chemotherapy and have a poor prognosis (Yamaguchi et al, 2002; Ennishi et al, 2008; Johnson et al, 2009). In some literature, the clinical features of CD5DLBCL resemble activated B cell-like (ABC) DLBCL and the gene profiling analysis has demonstrated some similar gene expression patterns (Tagawa et al, 2005; Suguro et al, 2006). However, the data was heterogeneous and no common gene aberration has been detected. In this study, we retrospectively investigated 350 DLBCL cases treated at our hospital between 2000 and 2015, sub-classifying them as germinal centre B cell-like (GCB) and non-GCB (NGC) type by immunohistochemical staining with CD10, BCL6 and MUM1 (Hans et al, 2004; Hwang et al, 2013), and then comparing the prognoses. This protocol was approved by our Institutional Review Board and Genomic Review Board. Patients with central nervous system disease at diagnosis were excluded. Patients with stage I disease were given three cycles of R-CHOP therapy (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) followed by involved-field radiotherapy, and patients with stage II disease or higher received six cycles of R-CHOP therapy. In the enrolled DLBCL patients, 41 (11 7%) were CD5 and 309 (88 3%) were CD5 (Table SI). There was no significant difference in sex, stage and International Prognostic Index (IPI) score between these two groups. In the CD5 group, the cell of origin was NGC type in 30 cases (73 2%); the ratio of NGC type in the CD5 group was higher than that in the CD5 group (P = 0 023) (Table SI). With regard to outcome, there was no statistically significant difference in the complete remission (CR) rate between the CD5 and CD5 groups (73 1% and 87 7%, respectively, P = 0 4757; Table SII). However, there were significant differences in CD5 status for cases with progressive disease (PD: CD5, 24 4% vs. CD5 , 6 8%, P = 0 0013) or relapse (CD5, 14 2% vs. CD5 , 11 8%, P = 0 0031) (Table SII). Furthermore, when these groups were subdivided into GCB or NGC type, the GCB type showed no significant differences between the CD5 and CD5 groups regarding CR, PD or relapse rate (Table SII). For the NGC type, CR cases showed no significant differences between CD5 and CD5 status (70 0% and 87 5%, respectively, P = 0 4747, P = 0 0859). However, PD was significantly increased in the CD5 group compared to CD5 group (26 7% and 6 3%, respectively, P = 0 0042).

O1-15-1Azacytidine is effective in the therapy related myelodysplastic syndrome

The comprehensive genomic analysis by Next generation sequencing can make us find many oncodriver gene mutations. And at the same time, we can find many gene structural mutations outside of oncodriver gene mutations. Most of such gene mutations are not identified about the pathologic significance, so that they are called variants of uncertain significant (VUS) gene mutations. And evaluations of their function are important for patient treatment. Recently, we had experienced an adult pancreatoblastoma case. Using commercially available the cancer panel, OncoDeep, we found a missense mutation in APC gene, which has not been reported in the UMD-APC mutations database. Immunohistochemically analysis revealed nuclear accumulation of the b-catenin protein. Because CTNNB1 was not mutated in this case, these results indicated that the missense mutation of APC lost its function and caused Wnt signal activation. To identify the structure mutation of APC gene in germ line, we have done target sequence of DNA extracted from oral mucosa. We found heterozygous of APC gene. It was assumed that loss of heterozygosis of APC gene causes Wnt signal activation in pancreatoblastoma cells in this case. The patient harboring pathological APC gene mutations in germ line generally develop colon polyposis, but this patient did not have the past history of colon polyposis. To make clear the APC mutation we found in this case causes functional loss, we have done functional assay with cell line model. The results indicated the APC gene mutation in this case causes partial loss of suppression of Wnt signal activation. This is a very important case report in NGS era in which we found many VUS gene mutations. We will present detail analyzed data together with clinical course.

Study of patient risk factors for febrile neutropenia in non-Hodgkin lymphoma receiving R-CHOP regimen: STOP FN single institution analysis in Japan.

e21605Background: Cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (R-CHOP) is standard therapy for patients (pts) with CD20 positive non-Hodgkin lymphomas (CD20+NHLs). America...