Kosuke Obama

L-Asparaginase-Based Induction Therapy for Advanced Extranodal NK/T-Cell Lymphoma

We describe treatment of a patient with advanced extranodal NK/T-cell lymphoma, nasal type, with multiple subcutaneous lesions and hemophagocytic syndrome. Considering the projected poor outcome of conventional treatments, we designed an L-asparaginase-based induction therapy. L-asparaginase (4000 units/day, day 1 to day 7) combined with vincristine (1 mg, day 1) and prednisolone (100 mg/day, day 1 to day 5) was administered by intravenous infusion every 3 weeks. Within a week after treatment was started, excellent response was observed. Because of an allergic reaction to L-asparaginase, 6 courses of CHOP (adriamycin, cyclophosphamide, vincristine and prednisolone) therapy were administered as consolidation after 4 courses of L-asparaginase. The lymphoma was controlled with complete remission lasting longer than 2 years without additional treatment. These results and related reports may contribute to greater therapeutic efficacy against at least some cases of extranodal NK/T-cell lymphoma and other related diseases. Further evaluations based on clinical study are expected to clarify these results.Int J Hematol. 2003;78:248-250.

Killer cell immunoglobulin-like receptor/3DL2 expression in adult T-cell leukaemia

a major advantage over the ristocetin-induced platelet aggregation mixing studies and the cryoprecipitate challenge. Most importantly, the referral of DNA samples to regional reference centres is far more feasible compared with fresh whole blood samples required for phenotypic testing. We have more experience with the genetic approach. Our methodology involves DNA extraction from whole blood, polymerase chain reaction amplification of the entire coding sequence of GPIBA followed by direct sequencing. While we agree that the interpretation of direct DNA sequencing is not without errors, we believe the likelihood of error is negligible when molecular cloning of the amplified material is performed. We are interested in performing molecular testing of additional type 2B VWD/PT-VWD patients. We believe that the question of this differential diagnosis merits a larger scale international study to heighten awareness of the diagnostic question, is PT-VWD truly rare or under diagnosed among type 2B VWD cases? We have recently received funds to initiate this survey and encourage the international haemostasis community to participate in this project. We hope that this study will add significantly to the clinical/molecular awareness of PT-VWD and will address a long recognised problem of the discrimination between the non-identical twins.

Adult T-cell leukemia predominantly involving exocrine glands.

Abstract:  Objectives: We describe a rare case of adult T‐cell leukemia (ATL) presenting with dry mouth and swelling of bilateral parotid and submandibular glands. The unusual involvement of these exocrine glands by malignant cells prompted us to conduct a detail characterization of these infiltrating and circulating leukemic T cells, which may provide insight to the pathogenesis of exocrine involvement in ATL. Methods: Immunophenotyping of peripheral ATL cells and microscopic examinations of various organs prepared by autopsy were performed. Analysis of the repertoire of T‐cell receptor (TCR) of parotid gland‐infiltrating ATL cells using molecular and immunohistochemical examinations were also performed. Results: Microscopic examinations of various organs prepared by autopsy revealed the predominant and specific exocrine gland infiltration of ATL cells. Reverse transcription‐polymerase chain reaction (RT‐PCR) followed by both TCR spectratyping and complementary determining region (CDR)‐3 sequencing analysis of TCR Vβ of parotid gland‐infiltrating T cells revealed a relatively restricted but not single usage of TCR Vβ. Immunohistochemical analyses of parotid gland specimens detected only a small number of TCR Vαβ‐positive cells in parotid gland‐infiltrating ATL cells. Conclusions: The predominant infiltration of ATL cells in exocrine glands implied that these T cells recognized exocrine gland‐specific antigen. However, the absence of both TCR Vβ mRNA transcripts and TCR Vαβ protein expression in most ATL cells suggested that antigen recognition via TCR may not have played a major role in adhesion and subsequent infiltration into the exocrine glands in this patient. These results provide important background information to further elucidate the pathogenesis of exocrine gland‐specific inflammation.

The correlation between erythropoiesis and thrombopoiesis as an index for pre-operative autologous blood donation.

We have previously reported that the platelet count and an increase in platelet number reflect individual erythropoietic capacity in pre-operative autologous blood donation (PABD). We have examined the correlation between erythropoiesis and thrombopoiesis by quantitative in vitro determination of thrombopoietin (TPO), erythropoietin (EPO), and interleukin-6 (IL-6) in patients with PABD. A sequential increase in platelet count with donation could not be explained by an increase in TPO. TPO showed a tendency to be inversely related to the pre-donation platelet count, and to be related to the pre-donation hemoglobin level. There was an inverse relationship between the TPO and EPO levels. As seen with these results, a high erythropoietic state induces restraint of thrombopoiesis, and a low erythropoietic state induces an increase in thrombopoiesis. These effects modulate EPO and TPO via negative feedback. These results provide some practical important information for performing autologous blood donation. Further studies are needed to elucidate the details of these correlations.

The platelet level indicates the erythropoietic capacity for preoperative autologous blood donation

UNLABELLED The erythropoietic capacity for preoperative autologous blood donation (ECPABD) shows marked inter individual variability. This study was performed to evaluate factors useful to predict individual ECPABD from data available before the first donation. The subjects consisted of 74 adult patients who received autologous blood donation, with a mean of 61 +/- 12.8 yr (SD). We classified the patients into four groups using our criteria for evaluating the ECPABD and investigated the relationships among age, disease, pre-platelet count, and the rate of platelet increase. RESULTS (1) Advanced age and the status of disease were not distinctly correlated with low ECPABD. (2) Patients with a high pre-platelet levels had a low ECPABD regardless of the haemoglobin. (3) Patients in which the platelet count increased in accordance with the level of collection exhibited low pre-platelet counts and high ECPABD. CONCLUSION In patients with high pre-platelet levels, we reduced the amount collected, considered early use of recombinant human erythropoietin and reevaluated the application of autologous blood donation.

Reduced-intensity hematopoietic stem cell transplantation for a patient with myelodysplastic syndrome and chronic obstructive pulmonary disease.

Allogeneic hematopoietic stem cell transplantation (SCT) following high-dose chemotherapy and total body irradiation (TBI) has improved the prognosis of advanced hematological diseases. In order to assess a patient’s suitability for SCT, a thorough pretransplantation survey is performed. However, patient eligibility has expanded because of the progress of supportive care, so it is difficult to define SCT eligibility limitations due to organ dysfunction. Moreover, recent progress in reduced-intensity stem cell transplantation (RIST) has facilitated the use of SCT in older patients and patients with various underlying diseases [1,2]. This article describes the case of a 65-year-old man with myelodysplastic syndrome (MDS), refractory anemia, and chronic obstructive pulmonary disease (COPD) (emphysema) who underwent SCT. The patient had a history of smoking for more than 40 years and had suffered from Burger’s disease since the age of 40 years. He occasionally complained of lower limb pain and was treated with prostaglandin. In 1998, he presented with anemia, and MDS (refractory anemia) was diagnosed. Two years prior to this report he required frequent red cell transfusions, the frequency of which gradually increased. In June 2004, he was admitted to our hospital for allogeneic hematopoietic SCT. Laboratory examinations confirmed bicytopenia: hemoglobin concentration, 5.7 g/dL; red blood cell count, 2010 109/L; white blood cell count, 3.3 109/L; platelet count, 183 109/L. The bone marrow survey demonstrated normocellular bone marrow with mild dysplasia and a small amount of blasts (<5%). The karyotype analysis showed 3 populations; 4 of 20 analyzed cells were 46XY, del(7)(q20); 3 of 20 analyzed cells were 46XY, +13; the remaining cells were 46XY. Prior to SCT the patient had received a total of 46 transfusions of 2 units of red cells. The pretransplantation Reduced-Intensity Hematopoietic Stem Cell Transplantation for a Patient with Myelodysplastic Syndrome and Chronic Obstructive Pulmonary Disease