Katayama T

Long‐term administration of G‐CSF for aplastic anaemia is closely related to the early evolution of monosomy 7 MDS in adults

There is an increasing incidence of the evolution of myelodysplastic syndrome (MDS) from aplastic anaemia (AA) with immunosuppressive treatment. In paediatric patients G‐CSF is also reported to increase MDS evolution, but this process is not precisely understood in children or in adults. Therefore risk factors of MDS evolution in adults are evaluated here. Of 72 patients, five developed MDS. In 47 patients without cyclosporine (CyA) or antithymocyte globulin (ATG) therapy, only one developed MDS with trisomy 8, 242 months after diagnosis. But of 25 patients treated with either CyA or ATG, four developed monosomy 7 MDS within 3 years. Of these 25 patients, 18 were treated with G‐CSF and the four patients (22.2%) who developed MDS were found in this group. The cumulative dose and the duration of G‐CSF administration were significantly elevated in patients who developed MDS when compared with those who did not, 822.3 ± 185.0 v 205.4 ± 25.5 μg/kg (P < 0.05) and 187.5 ± 52.5 v 72.0 ± 24.6 d (P < 0.002), respectively. However these two values for CyA did not differ significantly. Statistically, treatment with CyA, G‐CSF and combined G‐CSF and CyA were significantly related to MDS evolution. The administration of G‐CSF for more than a year was the most important factor (P = 0.00). These results suggested that a close relationship exists between G‐CSF and subsequent monosomy 7 MDS from AA in adults who receive immunosuppressive therapy. Long‐term administration of G‐CSF should be prohibited in order to prevent MDS evolution.

Diffuse large B cell lymphoma expressing the natural killer cell marker CD56

The expression of the natural killer (NK) cell antigen, CD56, in hematological malignancies is rare. However, there are several reports that some hematological malignancies, such as T/NK cell lymphoma, multiple myeloma (MM) and acute myeloid leukemia (AML), express this molecule. In B cell non‐Hodgkin’s lymphomas (NHL), however, very limited number of cases have been reported to express CD56 molecule. Although one study has recently described that half of microvillous B cell lymphoma (MVL), an uncommon subset of large cell lymphoma, expressed CD56, there have been no reports about most common type of B‐NHL, diffuse large B cell lymphoma (DLBL) other than a mention of weak CD56 expression in one of 83 DLBL. We herein presented the first case of diffuse large B cell lymphoma expressing CD56 clearly. The immunophenotype determined by immunostaining and flow cytometric analysis was CD10+, CD19+, CD20+, CD45RO−, CD3− and CD56+. On immunohistochemical study, neither bcl‐2 nor TIA‐1 was positive for tumor cell. Monoclonal immunoglobulin heavy chain (IgH) gene rearrangement was detected, and the sequence analysis of the variable region of IgH (VH) suggested that this tumor was derived from antigen selected post germinal center B cell. Conventional combination chemotherapy (CHOP) was administered, and the patient has still been in complete remission for 10 months.

Primary Central Nervous System Lymphomas Express Vh Genes with Intermediate to High Somatic Mutations

Primary central nervous system lymphoma (PCNSL) is a rare disease, especially among non-AIDS patients. Although almost all PCNSLs belong to the diffuse large B-cell lymphoma (DLBL) category, its clinical course differs from that of other types of DLBL. To elucidate the histogenesis of PCNSL, we analyzed the source of the cells from its variable region (VH) sequences using the polymerase chain reaction (PCR) method to amplify the immunoglobulin heavy chain (IgH) gene of DNA extracted from paraffin sections. Fifteen patients with AIDS-unrelated PCNSL of DLBL type, (7 males and 8 females), were evaluated. Only one case showed positive evidence of EBV infection. The prognosis was very poor with a median survival of 9 months. Analysis of the VH sequences revealed that the VH4 family was used in 4 cases and the VH3 family in 2 cases. The homology with previously published germline sequences was random, ranging from 82.7–93.2%, showing intermediate to high somatic mutations. In 3 of 6 cases, the existence of intraclonal diversity was suspected. These findings suggest that PCNSLs are histogenetically derived from antigen selected B cells in the germinal center (GC) environment.

Hepatitis B virus variants in carriers with hematologic malignancies in whom fulminant hepatic failure develops after chemotherapy

Abstract Three patients who were carriers of hepatitis B virus (HBV) and had hematologic malignancies, experienced fulminant hepatic failure after withdrawal of chemotherapy. Before treatment, each patient had inactive HBV infection with undetectable viral DNA polymerase; two patients were negative for hepatitis B e antigen. After chemotherapy, DNA polymerase increased and HBV variants with mutations in the precore region prevailed in their sera. These results implicate precore mutants thriving after chemotherapy and restored immune responses of patients in the pathogenesis of severe hepatic failure.