Kazuhiro Takei

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.

The value of oral cytarabine ocfosfate and etoposide in the treatment of refractory and elderly AML patients

Twenty-one acute myeloid leukemia (AML) patients were enrolled and received oral induction therapy with cytarabine ocfosfate (SPAC) and etoposide (EP). The median age was 69 years (range: 33–86). There were 11 patients with de novo AML and 10 AML cases that had evolved from myelodysplastic syndromes. Seventeen patients had abnormal karyotypes including eight complex abnormalities, various complications, and 7 of 21 had a poor performance status (PS) with Eastern Cooperative Oncology Group (ECOG) scores of 3–4. All patients completed induction therapy without severe adverse events. Seven achieved complete remission (CR), and two achieved partial remission (PR). Uni- and multivariate analyses demonstrated a positive and significant correlation between the results of therapy (CR ± PR) and overall survival. The plasma concentrations of cytosine arabinoside (ara-C) in some cases were higher than those previously reported, indicating the accumulation of ara-C with increasing numbers of days of SPAC administration. We conclude that this therapy is well tolerated and useful for refractory and elderly AML patients.

Effect of L -Asparaginase Combined with Vincristine and Prednisolone on Acute Myeloblastic Leukemia (M0) Associated with Non-Hodgkin Lymphoma

A 66-year-old Japanese woman was referred to us because of severe anemia and fever and presented at our hospital. She was eventually diagnosed as having acute myeloblastic leukemia (AML; M0) with non-Hodgkin lymphoma (NHL). We investigated the therapeutic efficacy of L-asparaginase (L-Asp), vincristine and prednisolone for both her AML and NHL. Asparagine synthetase (AS) activity in her AML blast cells was undetectable. A lymph node biopsy specimen revealed NHL of the marginal zone B cell type. Complete remission (CR) of AML and NHL was achieved. CR of the AML lasted for 18 months without further consolidation therapy. We conclude that L-Asp can be an effective drug for the treatment of AML in which blasts are negative for AS.

Feasibility and eligibility of retreatment with rabbit anti-T lymphocyte globulin for aplastic anemia previously treated with horse anti-thymocyte globulin

Horse anti-thymocyte globulin (h-ATG) and rabbit anti-T lymphocyte globulin (r-ATG) are widely used for patients with acquired aplastic anemia (AA). Although these globulins have improved clinical outcomes, one-third of the cases with AA are refractory to the first course of ATG, and another third relapse after an initial successful treatment [1]. The efficacy of an additional course of h-ATG was investigated by Tichelli [2] and they reported a 63% response rate (27 out of 43 patients responded). Currently, r-ATG can be used as substitute for h-ATG for patients who have failed the first course of h-ATG. In Japan, Iki et al. [3] reported the efficacy of retreatment with h-ATG for 21 cases of AA that failed the first course of ATG as 61.9%, however, there are hardly any studies that are done on retreatment with r-ATG because the product became commercially available in April 2001 and so far the first choice ATG for AA has been h-ATG. Here, we report our clinical experience of r-ATG treatment for AA, which had previously been treated with h-ATG. During the period from January 2001 to January 2005, we performed immunosuppressive therapy with r-ATG on a total of 9 transfusion-dependent AA patients, who had failed the previous treatment with horse ATG (four relapsed after successful treatment with h-ATG, and five did not respond). The severity of disease was evaluated at the start of r-ATG therapy. Severe AA was defined as satisfying at least two of the followings: (1) absolute neutrophil count \0.5 9 10/l; (2) absolute reticulocyte count \60 9 10/l; (3) platelet count \20 9 10/l [4, 5]. All cases were given r-ATG (Zetbulin , Nippon Zoki Pharmaceutical Co., Ltd., Osaka, Japan) at a dose of 5 mg/kg per day for 5 consecutive days according to the manufacture’s instruction. Oral prednisone at 1 mg/kg per day or intravenous methylprednisone at 2 mg/kg per day were administered from day 1 to 10 for prophylaxis of serum sickness and then tapered within a few weeks. According to physicians’ decision, patients no. 1 and 2 received concomitant cyclosporine A (CsA) at the start and 3 months after the treatment and patients no. 5, 6, 7, and 8 received granulocyte colony stimulating factor (G-CSF). Hematological response was evaluated 6 months after treatment according to the definition published by Camitta [6]. The patients’ characteristics and the results of our investigation are summarized in Table 1. All patients completed a 5-day course of r-ATG without any anaphylactoid reactions or related severe adverse reactions. Although one patient had moderate serum sickness, additional corticosteroid administration resulted in prompt recovery. No severe infections (bacterial, fungal or pneumocystis pneumonia) were observed during the 6-month observation period. Four out of nine patients (44%) who were previously treated with h-ATG obtained a satisfactory response after treatment with r-ATG. The response rate of patients who had relapsed after successful h-ATG treatment was high (three out of four; 75%). On the other hand, the response rate of patients who were refractory to pre-treatment with h-ATG was poor (one out of five; 20%). These results resemble the data of Scheinberg et al. [7] that has recently been reported. In their investigation the response rate to retreatment with r-ATG/CsA for patients who had once responded h-ATG/CsA was 66% and for those who had failed to h-ATG was 30%. K. Miura (&) Y. Hatta S. Kobayashi Y. Iriyama K. Takei J. Takeuchi Department of Hematology and Rheumatology, Division of Medicine, Nihon University School of Medicine, 30-1 Oyaguchikamicho, Itabashi Ward, Tokyo, Japan e-mail: javis@med.nihon-u.ac.jp