Ken Kaito

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, 822.3 ± 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.

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.

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.

Persistent Remission after Immunosuppressive Therapy of Hairy Cell Leukemia Mimicking Aplastic Anemia : Two Case Reports

Some patients with hairy cell leukemia (HCL) manifest pancytopenia and bone marrow hypoplasia without an apparent increase in atypical cells, so their disease resembles severe aplastic anemia at onset.We treated 2 HCL patients, who were initially diagnosed with aplastic anemia, with antithymocyte globulin (ATG) in combination with cyclosporine or antilymphocyte globulin (ALG). Both patients obtained partial remission in response to the immunosuppressive therapy and did not need transfusion treatment for more than 3 years. Sustained improvement of hematopoiesis in such B-cell malignancies after ATG/ ALG therapy suggests that the mechanisms underlying successful immunosuppressive therapy for aplastic anemia may involve B-cell suppression, inhibiting hematopoietic stem cells.

Serum Soluble Interleukin-2 Receptor in Eosinophilia

The relationship between soluble interleukin-2 receptor (sIL-2R) levels and clinical characteristics was evaluated in patients with eosinophilia. Thirty-eight out of 60 patients showed sIL-2R levels of more than 800 U/ml. In these patients, sIL-2R was closely related to the eosinophil count, but not the IgE level. Their underlying diseases were heterogeneous, including neoplasms and collagen diseases. In patients with lower sIL-2R levels, there was no relationship to the eosinophil count, but sIL-2R was correlated with the IgE level. These findings indicate that patients with eosinophilia and higher sIL-2R levels tend to have underlying diseases other than allergy, and might be more severely ill than patients with lower sIL-2R levels. sIL-2R may be a good marker for evaluating patients with eosinophilia, as an indicator of the probable etiology and severity of their diseases.

Carcinoembryonic antigen—producing multiple myeloma detected by a transcription—reverse transcription concerted reaction system

Multiple myeloma is a disease involving the clonal evolution of plasma cells that produce monoclonal immunoglobulin; however, other products, such as ammonia and amylase, reportedly are secreted by neoplastic plasma cells. We describe a patient with immunoglobulin A (IgA) myeloma who showed a high serum level of carcinoembryonic antigen (CEA) that correlated well with disease status and IgA level. We detected CEA-specific messenger RNA in plasma cells by means of a recently introduced rapid and quantitative RNA-amplification system, the transcription-reverse transcription concerted reaction system. This report is the first of a patient with a diagnosis of CEA-producing multiple myeloma.