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Jin Takeuchi

Publications and source records attributed to Jin Takeuchi.

14 recordsLinked to original sources
PubMed2006

Clinical features and outcome of T-lineage acute lymphoblastic leukemia in adults: a low initial white blood cell count, as well as a high count predict decreased survival rates.

Although biological and clinical features differ between B-lineage acute lymphoblastic leukemia (ALL) and T-lineage ALL (T-ALL), there have been few reports that focused on the prognosis for T-ALL in adults, primarily due to its rarity. Here, we studied the long-term outcomes and prognostic factors specific for adult T-ALL by combining patient data from the three prospective trials conducted by the Japan Adult Leukemia Study Group (JALSG). Among 559 patients whose immunophenotypes could be evaluated, 87 (15.6%) were identified as T-ALL. Of them, 66 patients (75.8%) achieved complete remission, and relapse occurred in 41 patients. With a median follow-up for surviving patients of 7.5 years, the probability of overall survival was 35.0% at 5 years. Risk factor analysis revealed that serum albumin levels, initial white blood cell (WBC) counts, and age had independent values for predicting survival. For WBC, not only the high-count group (50 x 10(9)l(-1) or higher), but also the low-count group (less than 3 x 10(9)l(-1)) showed a significantly lower survival rates than the intermediate-count group (p=0.0055 and 0.0037, respectively). Although our findings need confirmation, these results will be helpful in the identification of prognostically distinct subgroups within adult T-ALL.

Adolescent↗
PubMed2006

Treatment of high-risk peripheral T-cell lymphomas other than anaplastic large-cell lymphoma with a dose-intensified CHOP regimen followed by high-dose chemotherapy. A single institution study.

We investigated the efficacy of a dose-intensified double-CHOP regimen followed by high-dose chemotherapy with or without peripheral blood stem cell transplantation (PBSCT) in 11 patients with four types of peripheral T-cell lymphoma (PTCL). Three of the 4 patients with unspecified PTCL (PTCLu) achieved complete response (CR); 1 patient relapsed and 1 died of secondary leukemia after consolidation therapy. All angioimmunoblastic T-cell lymphoma (AILT) and subcutaneous panniculitis-like T-cell lymphoma (SPTCL) patients achieved CR; 5 of 6 have remained disease free for more than 3 years. The patient with hepatosplenic lymphoma did not achieve CR even after PBSCT and underwent allogenic bone marrow transplantation (allo-BMT). Thus, our regimen appears to be effective for high-risk AILT and SPTCL. However, allo-BMT should be considered for high-risk of PTCLu and hepatosplenic T-cell lymphoma.

Adolescent↗
PubMed2006

Pioglitazone inhibits the growth of human leukemia cell lines and primary leukemia cells while sparing normal hematopoietic stem cells.

Peroxisome proliferator-activated receptors (PPARs) compose a subfamily of nuclear hormone receptors functioning as transcriptional regulators. Originally, the PPARgamma ligand known as thiazolidinedione (TZD) was used for the treatment of diabetic patients. However, recent studies have shown that TZD also has an antitumor effect that inhibits cell growth in several types of human malignant neoplasms, including leukemia cell lines. Since pioglitazone is the only TZD currently available in clinics in Japan and the role of TZD in normal human hematopoietic cells or primary leukemia cells has not been previously reported, we investigated the effect of pioglitazone on human normal hematopoietic progenitor cells, primary leukemia cells, and leukemia cell lines (HL60, K562, U937, HEL, CEM, Jurkat, and NALM1). Pioglitazone inhibited the proliferation of leukemia cells in a dose-dependent manner. The viable cell numbers of HL60, K562, and Jurkat leukemia cell lines were profoundly reduced when the cells were cocultured with pioglitazone. Colony formation in the leukemia cell lines as well as the primary leukemia cells was significantly inhibited to 20-71% and 1-25% of that in control cultures by the addition of 100 and 300 microM of pioglitazone, respectively. However, the CFU-E and CFU-GM colonies of cells obtained from healthy volunteers were not altered in the presence of 100 microM of pioglitazone. Pioglitazone (300 microM) induced slight decrease of CFU-E and CFU-GM. BFU-E was more sensitive to pioglitazone than CFU-E and CFU-GM. Pioglitazone-induced growth inhibition in HL60 cells was associated with cell cycle arrest at the G1 phase, as has been reported for another TZD, troglitazone. Similar levels of PPARgamma protein were observed in both leukemia and normal bone marrow cells by Western blotting, suggesting that the expression of PPARgamma protein was not associated with the inhibitory potency of pioglitazone. In conclusion, our results suggest that pioglitazone may offer a new therapeutic approach to aid in the treatment of leukemia.

Cell Line, Tumor↗
PubMed2005

High complete remission rate and promising outcome by combination of imatinib and chemotherapy for newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia: a phase II study by the Japan Adult Leukemia Study Group.

PURPOSE: A novel therapeutic approach is urgently needed for BCR-ABL-positive acute lymphoblastic leukemia (ALL). In this study, we assessed the efficacy and feasibility of chemotherapy combined with imatinib. PATIENTS AND METHODS: A phase II study of imatinib-combined chemotherapy was conducted for newly diagnosed BCR-ABL-positive ALL in adults. Eighty patients were entered into the trial between September 2002 and January 2005. RESULTS: Remission induction therapy resulted in complete remission (CR) in 77 patients (96.2%), resistant disease in one patient, and early death in two patients, as well as polymerase chain reaction negativity of bone marrow in 71.3%. The profile and incidence of severe toxicity were not different from those associated with our historic chemotherapy-alone regimen. Relapse occurred in 20 patients after median CR duration of 5.2 months. Allogeneic hematopoietic stem-cell transplantation (HSCT) was performed for 49 patients, 39 of whom underwent transplantation during their first CR. The 1-year event-free and overall survival (OS) rates were estimated to be 60.0%, and 76.1%, respectively, which were significantly better than those for our historic controls treated with chemotherapy alone (P < .0001 for both). Among the current trial patients, the probability for OS at 1 year was 73.3% for those who underwent allogeneic HSCT, and 84.8% for those who did not. CONCLUSION: Our results demonstrated that imatinib-combined regimen is effective and feasible for newly diagnosed BCR-ABL-positive ALL. Despite a relatively short period of observation, a major potential of this treatment is recognized. Longer follow-up is required to determine its overall effect on survival.

Adolescent↗
PubMed2005

Two patients with all-trans retinoic acid-resistant acute promyelocytic leukemia treated successfully with gemtuzumab ozogamicin as a single agent.

Acute promyelocytic leukemia (APL) cells express a considerable level of CD33, which is the target of gemtuzumab ozogamicin (GO), and a significantly lower level of P-glycoprotein (P-gp). Therefore, GO is predicted to be a successful treatment for APL. In this article, we report on the GO treatment of 2 patients with APL, who had fully relapsed after induction therapy with all-trans retinoic acid (ATRA) following chemotherapy. Both patients had relapsed 3 times and were resistant to reinduction therapy with ATRA. GO (9 mg/m2) was administered on days 1 and 15. After GO treatment, both patients achieved complete hematologic and molecular remission. GO may be another promising agent for the treatment of ATRA-resistant relapsed APL when given as salvage chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Combination of intensive chemotherapy and imatinib can rapidly induce high-quality complete remission for a majority of patients with newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia.

The outcome for adult patients with BCR-ABL-positive acute lymphoblastic leukemia (ALL) remains dismal and long-term survival can hardly be achieved except by allogeneic hematopoietic stem cell transplantation (HSCT). The Japan Adult Leukemia Study Group (JALSG) has recently started a phase 2 trial with intensive chemotherapy and imatinib for newly diagnosed BCR-AB-positive ALL patients, and we present here the interim results for the first 24 patients. All patients except one case of early death (96%) attained complete remission (CR) after a single course of remission induction therapy. Polymerase chain reaction (PCR) negativity was achieved in 28% of the patients on day 28, in 50% on day 63, and in up to 78% during the follow-up period. The toxicity profile was almost similar to that with chemotherapy alone. As a result, 15 patients (63%) could receive an allogeneic HSC transplant during their first CR. Although the number of patients is small and the observation period is too short, the combination therapy is very promising and produces high-quality CR for most newly diagnosed patients with BCR-ABL-positive ALL. This is especially useful because it provides the patients with a better chance to receive an allogeneic HSC transplant.

Adolescent↗
PubMed2004

[Multiple myeloma of the IgD-lambda type invading CNS].

A 52-year-old woman was admitted to the gynecological department of our hospital on July 29, 2002 because of a right lower abdominal mass. She has been suffering from pain in the right leg and inguinal area for a month before coming to the hospital. She was found to have pancytopenia and high serum levels of LDH and IgD. A bone marrow examination showed 63.8% of plasma cells and serum immunoelectrophoresis showed M-protein of the IgD-lambda type. She was diagnosed as having multiple myeloma and transferred to our department. VAD therapy was started from August 22. Although the plasma cells in the bone marrow almost disappeared, the right lower abdominal mass remained and a new mass appeared on the right frontal chest wall after two courses of the treatment. Combination chemotherapy with vincristine, ranimustine, melphalan, and dexamethasone (ROAD) was started on November 1. This was followed with thalidomide and radiation therapy of the right inguinal region was added. On December 16th, she suddenly experienced speech disturbance, nausea and the disturbance of consciousness. Examination of her cerebrospinal fluid showed 368/microl mononuclear cells with 93% plasma cells. The plasma cells disappeared after the 6th intrathecal injection with MTX and prednisolone and the chemotherapy was resumed. One month later, CNS relapse was apparent followed by generalized spread of the tumor mass, and she died on March 17, 2003.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Prognostic significance of CD7+CD56+ phenotype and chromosome 5 abnormalities for acute myeloid leukemia M0.

Myeloid/natural killer (NK) cell precursor acute leukemia is an entity of acute leukemia characterized by poor prognosis and a CD7+CD56+ myeloid antigen+ phenotype without light-microscopic myeloperoxidase reactivity. This disease shares several clinical characteristics with acute myeloid leukemia (AML) M0. To clarify the relationship between these 2 leukemias, we analyzed 105 cases of AML M0. Among them, 17 were CD7+ and CD56+, 77 were negative for either antigen, and 11 could not be determined. CD7+CD56+ AML M0 showed onset at significantly lower patient age (median 46 versus 63 years, P = .004). The disease localization and the hematological manifestations were significantly different: CD7+CD56+ AML showed more frequent extramedullary involvement, fewer circulating leukemic blasts, less anemia, and less thrombocytopenia than did AML M0. The cytogenetic aberrations were also unique, because no 5q abnormalities were found in CD7+CD56+ M0. The prognosis of CD7+CD56+ M0 was poor in patients younger than 46 years (P = .03). Multivariate analysis showed that the CD7+CD56+ phenotype was a significant prognostic factor for AML M0, as well as age, circulating blast percentage, and chromosome 5 abnormalities These findings suggest that AML M0 consists of heterogeneous subgroups to be managed separately, and CD7+CD56+ M0 constitutes a distinct subtype of AML M0.

Acute Disease↗
PubMed2003

Mutational analysis of IkappaBalpha in hematologic malignancies.

The activation of the NF-kappaB family of transcription factors plays a crucial role in oncogenesis. The IkappaB family has the ability to retain the NF-kappaB in an inactive complex in the cytoplasm. Recently, mutations of the IkappaBalpha gene were found in Hodgkin's lymphoma, which allows NF-kappaB proteins to translocate into the nucleus in an active form. In this report, we describe a mutational analysis of IkappaBalpha for primary tumor cells obtained from patients with a variety of hematologic malignancies (acute myelogenous leukemia, chronic myelogenous leukemia, myelodysplastic syndrome, hairy cell leukemia, adult T-cell leukemia, and mantle cell lymphoma) as well as 15 leukemia, lymphoma, and myeloma cell lines (HL60, U937, HEL, K562, NALM1, Jurkat, JM, MOLT4, Raji, KS1, OKM2T, OKM3T, F6T, Su9T01, and C2-2). RT-PCR, followed by direct sequencing, was performed and all samples expressed IkappaBalpha. One missense mutation was identified in a primary effusion lymphoma cell line, KS1. However, NF-kappaB (p65) protein was absent from the nucleus of KS1 immunohistochemically, suggesting that the mutation did not alter the function of IkappaBalpha in this case. Taken together, although it is not clear whether normal IkappaBalpha protein was expressed in hematologic malignancies, mutations of IkappaBalpha could be rare events in these diseases, except for Hodgkin's lymphoma. Alterations of other members of NF-kappaB/ IkappaB family proteins might act on the development of hematologic malignancies.

DNA Mutational Analysis↗
PubMed2002

Different clones of t(1;12)/t(12;12) involving the ETV6 gene in a case of acute myeloid leukemia.

We describe here a case of a 77-year-old Japanese man who developed acute myeloid leukemia (AML-M2). Chromosome analysis of the bone marrow blast cells showed 46,XY,del(7q) at onset, and after relapse, two clones, 46,XY,t(1;12) and 46,XY,del(7q),t(12;12), were present. Fluorescence in situ hybridization analysis confirmed that each clone with the 12p abnormality involved the ETV6 gene. These findings suggest that the ETV6 gene rearrangements in this case were apparently independent of contribution to leukemogenesis, because this cytogenetic aberration appeared as a secondary change. To our knowledge, this is the first report of two different clones with ETV6 gene rearrangements in the same patient.

Aged↗
PubMed2002

[Human herpesvirus-8 negative primary effusion lymphoma with complete clinical remission after removal of ascites].

A 58-year-old HIV-negative woman was admitted to our hospital with abdominal distension. She had a 5-year history of hypothyroidism and a 4-year history of diabetes mellitus. Physical examination revealed ascites. There was no lymphadenopathy or splenomegaly. Laboratory examination showed elevated levels of serum LDH and Al-p, polyclonal hypergammaglobulinemia, and was positive for anti-nuclear antibody, several autoantibodies and HCV-RNA. A computed tomographic scan of the abdomen and chest showed massive ascites, but there was no evidence of tumor masses or lymph node enlargement. Cytologic examination of the ascitic fluid revealed numerous abnormal lymphocytes which by flow cytometry demonstrated expression of CD5, CD19, CD20, and CD4. Cytogenetical analysis demonstrated a hyperdiploid karyotype, with numerical abnormalities. Southern blot analysis demonstrated rearranged monoclonal bands in JH and c-mycgenes. Polymerase chain reaction (PCR) analysis failed to detect the genomes of EBV and HHV-8 in the abnormal lymphocytes. A diagnosis of primary effusion lymphoma of B cell lineage was made. Following abdominal paracentesis, the patient remained in complete clinical remission for 7 months and died of an unrelated cause (cerebral bleeding). The present case demonstrated an HIV-, HHV-8-, and EBV-negative, and HCV-positive primary effusion lymphoma of B cell lineage, with a unique clinical course.

Ascites↗
PubMed2002

[Airway hyperreactivity in patients undergoing hematopoietic stem cell transplantation].

Airway hyperreactivity (AHR) was studied with an astograph for 34 sequential hematopoietic stem cell transplantation (HSCT) patients before and after HSCT. The percentage of Dmin positive patients was 25.0% before HSCT and 25.0-57.1% after HSCT, while all normal subjects were negative for Dmin. The mean Dmin of post HSCT patients was 22.7 u in days 501-1000 and 19.3 u after 1001 days, which was significantly lower than the 45.2 u of normal controls. The patients were divided into two groups according to the treatment before HSCT, strongly treated (S, acute leukemia and non-Hodgikin lymphoma) and weakly treated (W, chronic myelogenous leukemia and aplastic anemia) patients. The ratio of Dmin positive patients and mean Dmin in the W group after HSCT (38.9%, 27.8 u), and the S group before and after HSCT (55.6%, 20.5 u and 45.5%, 23.8 u, respectively), were significantly impaired compared with the findings in the normal controls (0%, 45.2 u). The mean sGrs/Grs count was higher in the W group before HSCT than in the other groups (W before and after HSCT, 0.58 and 0.19, respectively; S before and after HSCT, 0.21 and 0.22, respectively). Taken together, AHR was observed in HSCT patients, particularly for patients in the S group. These data indicate that high dose chemo-radiotherapy including conditioning regimen causes AHR. The mechanisms leading to AHR may be infection, inflammation, and remodeling of the airway.

Adolescent↗