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Takeaki Takenaka,
Kuniaki Itoh,
Takayo Suzuki,
Atae Utsunomiya,
Shin Matsuda,
Takaaki Chou,
Toshiaki Sai,
Masayuki Sano,
Susumu Konda,
Tatsuji Ohno, [......],
Takashi Yamada,
Fumi Mizorogi, Haruhisa Nagoshi,
Masao Tomonaga,
Tomomitsu Hotta,
Kohichi Kawano,
Keitaro Tsushita,
Masami Hirano,
Masanori Shimoyama,
Lymphoma Study Group of the Japan Clinical Oncology Group
[show abstract]
[hide abstract]
ABSTRACT: To investigate whether combination chemotherapy with vincristine, cyclophosphamide, prednisolone, and melphalan (COP/ MP)
with the addition of ranimustine (MCNU) (MCNU-COP/MP) is superior to the slightly modified COP/MP (mCOP/MP) regimen in multiple
myeloma (MM), a multicenter randomized study was performed. Two hundred ten patients with newly diagnosed, overt MM not treated
with chemotherapy were enrolled from 32 institutions of the Lymphoma Study Group of the Japan Clinical Oncology Group and
were randomized to receive either MCNU-COP/MP or mCOP/MP. The response rate (RR) to mCOP/MP was 43.7% (95% confidence interval
[CI], 33.9%–53.8%] and to MCNU-COP/MP was 56.1 % (95% CI, 46.1 %–65.7%) (P = .097). The progression-free survival (PFS) was
significantly longer for patients treated with MCNU-COP/MP than for patients treated with mCOP/MP (median, 23.0 months [95%
CI, 18.9–25.8] versus 15.8 months [95% CI, 14.1–19.4]) (P = .014). However, no significant difference in overall survival
rate (OS) was observed between the groups (median, 49.9 months [95% CI, 40.4-59.1] versus 44.0 months [95% CI, 32.8–59.8])
( P = .75). Grades 3 and 4 hematological toxicities were more frequently observed with MCNU-COP/MP than with mCOP/MP, but
the incidence of grades 3 and 4 nonhematological toxicities was low in both groups. In conclusion, MCNU-COP/MP in comparison
with mCOP/MP improved RR and PFS in overt MM; however, this outcome did not contribute to prolonging OS, indicating that addition
of MCNU to mCOP/MP has no benefit on survival.
Key wordsRanimustine-MP-Combination chemotherapy-Randomized study-Multiple myeloma
International Journal of Hematology 04/2012; 79(2):165-173. · 1.27 Impact Factor
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Kunihiro Tsukasaki,
Atae Utsunomiya,
Haruhiko Fukuda,
Taro Shibata,
Takuya Fukushima,
Yoshifusa Takatsuka,
Shuichi Ikeda,
Masato Masuda, Haruhisa Nagoshi,
Ryuzo Ueda,
Kazuo Tamura,
Masayuki Sano,
Saburo Momita,
Kazunari Yamaguchi,
Fumio Kawano,
Shuichi Hanada,
Kensei Tobinai,
Masanori Shimoyama,
Tomomitsu Hotta,
Masao Tomonaga
[show abstract]
[hide abstract]
ABSTRACT: Our previous phase II trial for treating human T-lymphotropic virus type I-associated adult T-cell leukemia-lymphoma (ATLL) with vincristine, cyclophosphamide, doxorubicin, and prednisone (VCAP), doxorubicin, ranimustine, and prednisone (AMP), and vindesine, etoposide, carboplatin, and prednisone (VECP) showed promising results. To test the superiority of VCAP-AMP-VECP over biweekly cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), we conducted a randomized controlled trial exclusively for ATLL.
Previously untreated patients with aggressive ATLL were assigned to receive either six courses of VCAP-AMP-VECP every 4 weeks or eight courses of biweekly CHOP. Both treatments were supported with granulocyte colony-stimulating factor and intrathecal prophylaxis.
A total of 118 patients were enrolled. The complete response (CR) rate was higher in the VCAP-AMP-VECP arm than in biweekly CHOP arm (40% v 25%, respectively; P = .020). Progression-free survival rate at 1 year was 28% in the VCAP-AMP-VECP arm compared with 16% in the CHOP arm (P = .100, two-sided P = .200). Overall survival (OS) at 3 years was 24% in the VCAP-AMP-VECP arm and 13% in the CHOP arm (P = .085, two-sided P = .169). For VCAP-AMP-VECP versus biweekly CHOP, grade 4 neutropenia, grade 4 thrombocytopenia, and grade 3 or 4 infection rates were 98% v 83%, 74% v 17%, and 32% v 15%, respectively. There were three toxic deaths in the VCAP-AMP-VECP arm.
The longer OS at 3 years and higher CR rate with VCAP-AMP-VECP compared with biweekly CHOP suggest that VCAP-AMP-VECP might be a more effective regimen at the expense of higher toxicities, providing the basis for future investigations in the treatment of ATLL.
Journal of Clinical Oncology 01/2008; 25(34):5458-64. · 18.37 Impact Factor
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Koichiro Yuji,
Shigesaburo Miyakoshi,
Daisuke Kato,
Yuji Miura,
Tomohiro Myojo,
Naoko Murashige,
Yukiko Kishi,
Kazuhiro Kobayashi,
Eiji Kusumi,
Hiroto Narimatsu, [......],
Atsushi Wake,
Junichi Ueyama,
Akiko Yoneyama,
Ko Miyamoto, Haruhisa Nagoshi,
Michio Matsuzaki,
Shinichi Morinaga,
Yoshitomo Muto,
Yoichi Takeue,
Shuichi Taniguchi
[show abstract]
[hide abstract]
ABSTRACT: We report the results of reduced-intensity unrelated cord blood transplantation (RI-UCBT) in patients with advanced malignant lymphoma. Twenty patients (median age, 46.5 years; range, 27-66 years) underwent RI-UCBT with a preparative regimen consisting of fludarabine 125 mg/m2 , melphalan 80 mg/m 2 , and 4 Gy of total body irradiation. The median infused total cell dose was 2.75 x 10(7)/kg (range, 2.3-3.4 x 10(7)/kg). Graft-versus-host disease (GVHD) prophylaxis was composed of cyclosporine or tacrolimus alone. Fifteen patients achieved primary neutrophil engraftment after a median of 20 days. Eight patients developed grade II to IV acute GVHD, and 2 developed chronic GVHD. Of the 16 patients with evaluable disease, 10 achieved a complete response. Primary disease recurred in 1 patient, and transplant-related mortality within 100 days occurred in 8 of 20 patients. The estimated 1-year probability of progression-free survival was 50%. These data suggest that RI-UCBT is a feasible option for patients with refractory lymphoma who lack an HLA-matched donor.
Biology of Blood and Marrow Transplantation 05/2005; 11(4):314-8. · 3.87 Impact Factor
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Takeaki Takenaka,
Kuniaki Itoh,
Takayo Suzuki,
Atae Utsunomiya,
Shin Matsuda,
Takaaki Chou,
Toshiaki Sai,
Masayuki Sano,
Susumu Konda,
Tatsuji Ohno, [......],
Kijoh Deura,
Takashi Yamada,
Fumi Mizorogi, Haruhisa Nagoshi,
Masao Tomonaga,
Tomomitsu Hotta,
Kohichi Kawano,
Keitaro Tsushita,
Masami Hirano,
Masanori Shimoyama
[show abstract]
[hide abstract]
ABSTRACT: To investigate whether combination chemotherapy with vincristine, cyclophosphamide, prednisolone, and melphalan (COP/ MP) with the addition of ranimustine (MCNU) (MCNU-COP/MP) is superior to the slightly modified COP/MP (mCOP/MP) regimen in multiple myeloma (MM), a multicenter randomized study was performed. Two hundred ten patients with newly diagnosed, overt MM not treated with chemotherapy were enrolled from 32 institutions of the Lymphoma Study Group of the Japan Clinical Oncology Group and were randomized to receive either MCNU-COP/MP or mCOP/MP. The response rate (RR) to mCOP/MP was 43.7% (95% confidence interval [CI], 33.9%-53.8%] and to MCNU-COP/MP was 56.1% (95% CI, 46.1%-65.7%) (P = .097). The progression-free survival (PFS) was significantly longer for patients treated with MCNU-COP/MP than for patients treated with mCOP/MP (median, 23.0 months [95% CI, 18.9-25.8] versus 15.8 months [95% CI, 14.1-19.4]) (P = .014). However, no significant difference in overall survival rate (OS) was observed between the groups (median, 49.9 months [95% CI, 40.4-59.1] versus 44.0 months [95%, CI, 32.8-59.8]) (P = .75). Grades 3 and 4 hematological toxicities were more frequently observed with MCNU-COP/MP than with mCOP/MP, but the incidence of grades 3 and 4 nonhematological toxicities was low in both groups. In conclusion, MCNU-COP/MP in comparison with mCOP/MP improved RR and PFS in overt MM; however, this outcome did not contribute to prolonging OS, indicating that addition of MCNU to mCOP/MP has no benefit on survival.
International Journal of Hematology 03/2004; 79(2):165-73. · 1.27 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Intracellular transcobalamins (TCs) in 17 cultured cells established from hematological malignancies were measured to solve the cellular origin of TCs. The cultured cell lines used in this study are as follows: myeloid cell lines K-562, HL-60, NALM-1; T-cell lines P12/lchikawa, MOLT-4B, CCRF-CEM, RPMI-8402, MT-1; B-cell lines P3HR-1, Daudi, BALL-1; nonT, nonB cell lines NALM-16, KOPN-1, Reh, P30/Ohkubo, NALL-1; and, as control cells, P13/Koyama derived from normal B-cells, normal human lymphocytes and granulocytes. The homogenized cytoplasmic fraction was incubated with 57Co B 12 and subjected to DE 52 cellulose column chromatography and polyacryla mide gel electrophoresis (PAGE) to separate TC 11 from R-binders. In myeloid cell lines established from blastic crises of chronic myeloid leukemia, K-562 had the highest TC 11 /R-binders ratio, while NALM-1 had the lowest, suggesting that the myeloid and lymphoid crises of chronic myeloid leukemia may have different TC 11 /R-binders ratio. T and B cell lines showed no difference in intracellular TC levels. NonT, nonB cell lines had the lowest level of intracellular TC.
