Masayuki Kobayashi

Platelet size deviation width, platelet large cell ratio, and mean platelet volume have sufficient sensitivity and specificity in the diagnosis of immune thrombocytopenia

We investigated the significance of the platelet indices, mean platelet volume (MPV), platelet size deviation width (PDW), and platelet‐large cell ratio (P‐LCR), in the diagnosis of thrombocytopenia by comparing these levels in 40 patients with hypo‐productive thrombocytopenia (aplastic anaemia; AA) and 39 patients with hyper‐destructive thrombocytopenia (immune thrombo‐cytopenia; ITP). The sensitivity and specificity of platelet indices to make a diagnosis of ITP were also compared. All platelet indices were significantly higher in ITP than in AA, and platelet indices showed sufficient sensitivity and specificity. The area under the curve (AUC) of the receiver operating characteristics curve of platelet indices was large enough to enable the diagnosis of ITP. P‐LCR and PDW had the largest AUCs, which indicated that these values were very reliable for immune thrombocytopenia. Our results suggest that these indices provide clinical information about the underlying conditions of thrombocytopenia. More attention should be paid to these indices in the diagnosis of thrombocytopenia.

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, 822.3u2003±u2003185.0 v 205.4u2003±u200325.5u2003μg/kg (Pu2003<u20030.05) and 187.5u2003±u200352.5 v 72.0u2003±u200324.6u2003d (Pu2003<u20030.002), 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 (Pu2003=u20030.00). 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.

Functional results of low median and ulnar nerve repair with intraneural fascicular dissection and electrical fascicular orientation

Twenty-eight low median nerve injuries and 23 low ulnar nerve injuries were repaired using intraneural fascicular dissection and electrical fascicular orientation. Eleven freshly lacerated nerves were seen within 48 hours after injury; 40 nerve lacerations were chronic. Fascicular orientation between sensory and motor fascicles at the proximal nerve end could be accurately differentiated in 47 nerves (92%) independent of whether it was acute or chronic. At the distal nerve end in fresh lacerations, the motor fascicles could be determined conclusively by muscle contraction with sequential electrical stimulation of the fascicles. In chronic nerve lacerations, the distal fascicles could be estimated anatomically after internal neurolysis. After fascicular orientation, nerves were repaired with end-to-end group fascicular suture or interfascicular sural nerve grafting. Twenty-four nerves repaired with end-to-end suture and 13 nerves repaired with nerve grafting were monitored more than 25 months. Satisfactory sensory results (i.e., S3+ or S4 functions) were obtained in 29 nerves (78%) and M4 or M5 motor functions were achieved in 29 nerves (78%). There were no patients who needed additional tendon transfers to reconstruct thumb opposition or to correct claw finger deformity. These results suggest that low median or ulnar nerve lacerations, whether acute or chronic, partial or complete, may be successfully repaired with the aid of electrical fascicular orientation with or without intraneural fascicular dissection.

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.

Combination Chemotherapy with G-CSF, M-CSF and EPO: Successful Treatment for Acute Myelogenous Leukemia without Blood Transfusion at Lower Medical Costs

A 55-year-old Jehova’s Witness was treated for acute myelogenous leukemia (AML) by intensive chemotherapy with enocitabine, 6-mercaptopurine and daunorubicin. G-CSF, M-CSF and EPO were subsequently administered. Even though no blood transfusion was given for religious reasons, complete remission was achieved without serious infection and hemorrhage. The total cost for induction chemotherapy was less expensive than is the case for elderly AML patients. This case indicates that the administration of cytokines might reduce the incidence of infection and the necessity for blood products, which would result in favorable cost effectiveness for the treatment of elderly patients with AML.

Immunosuppressive therapy with antithymocyte globulin and cyclosporine for prolonged marrow failure after hemophagocytic syndrome

We describe a patient with typical hemophagocytic syndrome (HPS) in whom pancytopenia was refractory to steroid pulse therapy. He was successfully treated with immunosuppressive therapy using antithymocyte globulin (ATG) and cyclosporine (CyA), which is known to be effective for aplastic anemia (AA). Activation of histiocytes occurs in HPS as a response to several cytokines produced by activated T lymphocytes, while apoptosis of hematopoietic stem cells in AA is caused by T lymphocyte-derived cytokines. The response of this patient indicated that both diseases may have some similar immune-mediated conditions involving the activation of T lymphocytes and that intensive immunosuppressive therapy with ATG and CyA might be a useful strategy for steroid-resistant HPS.

CD2+ tetraploid acute promyelocytic leukemia variant with double (15;17) translocations

We report a patient with a variant form of CD2+ acute promyelocytic leukemia (APL) who had double translocations (15;17) in a single leukemic cell. The patient presented with severe neutropenia, thrombocytopenia, and disseminated intravascular coagulation. The bone marrow showed marked hyperplasia with large leukemic cells that had bizarre nuclear configuration and basophilic, hypogranular cytoplasm. Leukemic cells were positive for CD2, 13, 33, 34, and 56 and negative for HLA-DR.The karyotype of the abnormal clone was characterized as 92,XXYY, t(15;17)(q22;q21)x2. No other additional abnormal clone was found, and the patient’s condition was diagnosed as tetraploid APL variant. Fluorescence in situ hybridization assay revealed 2 promyelocytic leukemia and retinoic acid receptor α (PML/RARA) fusion signals, and reverse transcription-polymerase chain reaction assay revealed short-form PML/RARA fusion transcript. Tetraploidy in APL is a very rare abnormality. Double translocations were an additional abnormality in this case, and this patient’s karyotype might have had some influence on morphological characteristics, expression of CD2, and poor clinical outcome.

Secondary polycythemia as a paraneoplastic syndrome of testicular seminoma

A 45-year-old man was referred to our hospital because of polycythemia. A physical examination revealed a large tumor in his scrotum enlarged to the size of 13×10xa0cm. A laboratory examination revealed severe erythrocytosis with a red blood cell count of 6,820×109/L, a hemoglobin concentration of 21.2xa0g/dL, and a hematocrit of 59.8%. The total red cell volume was increased. A right radical orchidectomy was done with minimum bleeding, and he was diagnosed as having pure seminoma. After the operation, polycythemia improved spontaneously. Polycythemia is a rare complication of seminoma and only two cases have been reported previously. The precise mechanism of polycythemia in our patient could not be clearly evaluated, but clinical course did indicate a close relationship between two distinct disorders.

Intensified Daunorubicin in Induction Therapy and Autologous Peripheral Blood Stem Cell Transplantation in Postremission Therapy (Double-7 Protocol) for Adult Acute Myeloid Leukemia

To investigate whether an intensified dose of daunorubicin (DNR) in induction therapy and autologous peripheral blood stem cell transplantation (PBSCT) in the postremission period are effective treatments, we used a Double-7 protocol to treat adult patients with de novo acute myeloid leukemia (excluding M0 and M3). Induction therapy consisted of 40 mg/m2 of DNR intravenous drip infusion for 7 days and 200 mg/m2 of ara-C by continuous infusion for 7 days (7 + 7 DC regimen). Patients who achieved complete remission (CR) were given high-dose chemotherapy with autologous PBSCT in postremission therapy. Of the 22 assessable patients, 16 attained CR (73%). Disease-free survival (DFS) and overall survival (OS) at 3 years were 61.2% and 48.1%, respectively. Nine of the CR patients underwent PBSCT without therapy-related mortality. Patients in a favorable cytogenetic group (n = 7) attained 100% CR and long-term survival (71.4% DFS and 85.7% OS at 3 years). Thus, intensified DNR administration of 280 mg/m2 (40 mg/m2 per day for 7 days) in induction therapy for adult patients younger than 60 years of age might be optimal or at least comparable with the new anthracyclines such as idarubicin. In addition, autologous PBSCT in postremission therapy might improve DFS and OS, at least for patients in a favorable cytogenetic group, such as those with a t(8;21) abnormality.Int J Hematol. 2002; 76: 436-445.