Therapeutic potential of a reduced-intensity preparative regimen for allogeneic transplantation with cladribine, busulfan, and antithymocyte globulin against advanced/refractory acute leukemia/lymphoma

Takeshi Saito, Yoshinobu Kanda, Masahiro Kami, Kazunori Kato, Nahoko Shoji, Sachiyo Kanai, Toshihiro Ohnishi, Yoshifumi Kawano, Kunihisa Nakai, Toshie Ogasawara, Hiroshi Matsubara, Atsushi Makimoto, Ryuji Tanosaki, Kensei Tobinai, Hiro Wakasugi, Yoichi Takaue, Shin Mineishi

Research output: Contribution to journalArticle

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Abstract

Purpose: Cladribine (2-CdA) is a purine analogue that exhibits activity against a variety of hematological malignancies and has a potent immunosuppressive effect. We therefore performed a pilot study to evaluate the feasibility of a novel 2-CdA-based reduced-intensity stem cell transplantation (RIST) regimen. Experimental Design: A total of 16 scheduled patients with hematological malignancies were enrolled for comparison of their data with conventional stem cell transplantation (n = 19). The regimen for RIST consisted of 2-CdA (0.11 mg/kg/day for 6 days), busulfan (4 mg/kg/day for 2 days), and rabbit antithymocyte globulin (2.5 mg/kg/day for 4, 2, or 0 days). The underlying diseases included acute myelogenous leukemia (n = 6), chronic myelogenous leukemia (n = 2), myelodysplastic syndrome (n = 6), and non-Hodgkin's lymphoma (n = 2). Results: After RIST, four patients died before day 100 as a result of acute graft-versus-host disease (n = 1), bacteremia (n = 1), disseminated candidasis (n = 1) and congestive heart failure (n = 1). Another patient died of cerebral infarction on day 140. Thus, acute-phase regimen-related toxicities >grade III were observed in only one patient. Engraftment and complete donor chimerism were achieved by day 28 in 14 evaluable patients, and 6 of them (43%) experienced grade II-IV acute graft-versus-host disease. With a median follow-up of 328 days (range, 231-633 days), the actuarial 1-year overall and disease-free survival rates were 69% and 50%, respectively. Notably, among seven high-risk patients (five patients had been in complete remission two or more times and two not in complete remission with refractory disease at transplant), only two patients developed leukemia relapse after RIST. Although the recovery of CD4+ cells was significantly slower (P = 0.02) in RIST than in conventional stem cell transplantation, the incidence of clinically documented infections was not significantly different between the two groups. Conclusion: The results suggest that this novel regimen containing 2-CdA is well tolerated and induces early complete donor chimerism. The unexpected durable remission achieved in patients with advanced disease at transplant suggests the presence of an acceptable antileukemia/lymphoma effect, which would warrant a further clinical trial.

Original languageEnglish
Pages (from-to)1014-1020
Number of pages7
JournalClinical Cancer Research
Volume8
Issue number4
Publication statusPublished - 2002 Apr 1
Externally publishedYes

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Cladribine
Busulfan
Antilymphocyte Serum
Homologous Transplantation
Lymphoma
Stem Cell Transplantation
Leukemia
Chimerism
Therapeutics
Graft vs Host Disease
Hematologic Neoplasms
Tissue Donors
Transplants
Myelodysplastic Syndromes
Cerebral Infarction
Immunosuppressive Agents
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Bacteremia
Acute Myeloid Leukemia
Non-Hodgkin's Lymphoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Therapeutic potential of a reduced-intensity preparative regimen for allogeneic transplantation with cladribine, busulfan, and antithymocyte globulin against advanced/refractory acute leukemia/lymphoma. / Saito, Takeshi; Kanda, Yoshinobu; Kami, Masahiro; Kato, Kazunori; Shoji, Nahoko; Kanai, Sachiyo; Ohnishi, Toshihiro; Kawano, Yoshifumi; Nakai, Kunihisa; Ogasawara, Toshie; Matsubara, Hiroshi; Makimoto, Atsushi; Tanosaki, Ryuji; Tobinai, Kensei; Wakasugi, Hiro; Takaue, Yoichi; Mineishi, Shin.

In: Clinical Cancer Research, Vol. 8, No. 4, 01.04.2002, p. 1014-1020.

Research output: Contribution to journalArticle

Saito, T, Kanda, Y, Kami, M, Kato, K, Shoji, N, Kanai, S, Ohnishi, T, Kawano, Y, Nakai, K, Ogasawara, T, Matsubara, H, Makimoto, A, Tanosaki, R, Tobinai, K, Wakasugi, H, Takaue, Y & Mineishi, S 2002, 'Therapeutic potential of a reduced-intensity preparative regimen for allogeneic transplantation with cladribine, busulfan, and antithymocyte globulin against advanced/refractory acute leukemia/lymphoma', Clinical Cancer Research, vol. 8, no. 4, pp. 1014-1020.
Saito, Takeshi ; Kanda, Yoshinobu ; Kami, Masahiro ; Kato, Kazunori ; Shoji, Nahoko ; Kanai, Sachiyo ; Ohnishi, Toshihiro ; Kawano, Yoshifumi ; Nakai, Kunihisa ; Ogasawara, Toshie ; Matsubara, Hiroshi ; Makimoto, Atsushi ; Tanosaki, Ryuji ; Tobinai, Kensei ; Wakasugi, Hiro ; Takaue, Yoichi ; Mineishi, Shin. / Therapeutic potential of a reduced-intensity preparative regimen for allogeneic transplantation with cladribine, busulfan, and antithymocyte globulin against advanced/refractory acute leukemia/lymphoma. In: Clinical Cancer Research. 2002 ; Vol. 8, No. 4. pp. 1014-1020.
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abstract = "Purpose: Cladribine (2-CdA) is a purine analogue that exhibits activity against a variety of hematological malignancies and has a potent immunosuppressive effect. We therefore performed a pilot study to evaluate the feasibility of a novel 2-CdA-based reduced-intensity stem cell transplantation (RIST) regimen. Experimental Design: A total of 16 scheduled patients with hematological malignancies were enrolled for comparison of their data with conventional stem cell transplantation (n = 19). The regimen for RIST consisted of 2-CdA (0.11 mg/kg/day for 6 days), busulfan (4 mg/kg/day for 2 days), and rabbit antithymocyte globulin (2.5 mg/kg/day for 4, 2, or 0 days). The underlying diseases included acute myelogenous leukemia (n = 6), chronic myelogenous leukemia (n = 2), myelodysplastic syndrome (n = 6), and non-Hodgkin's lymphoma (n = 2). Results: After RIST, four patients died before day 100 as a result of acute graft-versus-host disease (n = 1), bacteremia (n = 1), disseminated candidasis (n = 1) and congestive heart failure (n = 1). Another patient died of cerebral infarction on day 140. Thus, acute-phase regimen-related toxicities >grade III were observed in only one patient. Engraftment and complete donor chimerism were achieved by day 28 in 14 evaluable patients, and 6 of them (43{\%}) experienced grade II-IV acute graft-versus-host disease. With a median follow-up of 328 days (range, 231-633 days), the actuarial 1-year overall and disease-free survival rates were 69{\%} and 50{\%}, respectively. Notably, among seven high-risk patients (five patients had been in complete remission two or more times and two not in complete remission with refractory disease at transplant), only two patients developed leukemia relapse after RIST. Although the recovery of CD4+ cells was significantly slower (P = 0.02) in RIST than in conventional stem cell transplantation, the incidence of clinically documented infections was not significantly different between the two groups. Conclusion: The results suggest that this novel regimen containing 2-CdA is well tolerated and induces early complete donor chimerism. The unexpected durable remission achieved in patients with advanced disease at transplant suggests the presence of an acceptable antileukemia/lymphoma effect, which would warrant a further clinical trial.",
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T1 - Therapeutic potential of a reduced-intensity preparative regimen for allogeneic transplantation with cladribine, busulfan, and antithymocyte globulin against advanced/refractory acute leukemia/lymphoma

AU - Saito, Takeshi

AU - Kanda, Yoshinobu

AU - Kami, Masahiro

AU - Kato, Kazunori

AU - Shoji, Nahoko

AU - Kanai, Sachiyo

AU - Ohnishi, Toshihiro

AU - Kawano, Yoshifumi

AU - Nakai, Kunihisa

AU - Ogasawara, Toshie

AU - Matsubara, Hiroshi

AU - Makimoto, Atsushi

AU - Tanosaki, Ryuji

AU - Tobinai, Kensei

AU - Wakasugi, Hiro

AU - Takaue, Yoichi

AU - Mineishi, Shin

PY - 2002/4/1

Y1 - 2002/4/1

N2 - Purpose: Cladribine (2-CdA) is a purine analogue that exhibits activity against a variety of hematological malignancies and has a potent immunosuppressive effect. We therefore performed a pilot study to evaluate the feasibility of a novel 2-CdA-based reduced-intensity stem cell transplantation (RIST) regimen. Experimental Design: A total of 16 scheduled patients with hematological malignancies were enrolled for comparison of their data with conventional stem cell transplantation (n = 19). The regimen for RIST consisted of 2-CdA (0.11 mg/kg/day for 6 days), busulfan (4 mg/kg/day for 2 days), and rabbit antithymocyte globulin (2.5 mg/kg/day for 4, 2, or 0 days). The underlying diseases included acute myelogenous leukemia (n = 6), chronic myelogenous leukemia (n = 2), myelodysplastic syndrome (n = 6), and non-Hodgkin's lymphoma (n = 2). Results: After RIST, four patients died before day 100 as a result of acute graft-versus-host disease (n = 1), bacteremia (n = 1), disseminated candidasis (n = 1) and congestive heart failure (n = 1). Another patient died of cerebral infarction on day 140. Thus, acute-phase regimen-related toxicities >grade III were observed in only one patient. Engraftment and complete donor chimerism were achieved by day 28 in 14 evaluable patients, and 6 of them (43%) experienced grade II-IV acute graft-versus-host disease. With a median follow-up of 328 days (range, 231-633 days), the actuarial 1-year overall and disease-free survival rates were 69% and 50%, respectively. Notably, among seven high-risk patients (five patients had been in complete remission two or more times and two not in complete remission with refractory disease at transplant), only two patients developed leukemia relapse after RIST. Although the recovery of CD4+ cells was significantly slower (P = 0.02) in RIST than in conventional stem cell transplantation, the incidence of clinically documented infections was not significantly different between the two groups. Conclusion: The results suggest that this novel regimen containing 2-CdA is well tolerated and induces early complete donor chimerism. The unexpected durable remission achieved in patients with advanced disease at transplant suggests the presence of an acceptable antileukemia/lymphoma effect, which would warrant a further clinical trial.

AB - Purpose: Cladribine (2-CdA) is a purine analogue that exhibits activity against a variety of hematological malignancies and has a potent immunosuppressive effect. We therefore performed a pilot study to evaluate the feasibility of a novel 2-CdA-based reduced-intensity stem cell transplantation (RIST) regimen. Experimental Design: A total of 16 scheduled patients with hematological malignancies were enrolled for comparison of their data with conventional stem cell transplantation (n = 19). The regimen for RIST consisted of 2-CdA (0.11 mg/kg/day for 6 days), busulfan (4 mg/kg/day for 2 days), and rabbit antithymocyte globulin (2.5 mg/kg/day for 4, 2, or 0 days). The underlying diseases included acute myelogenous leukemia (n = 6), chronic myelogenous leukemia (n = 2), myelodysplastic syndrome (n = 6), and non-Hodgkin's lymphoma (n = 2). Results: After RIST, four patients died before day 100 as a result of acute graft-versus-host disease (n = 1), bacteremia (n = 1), disseminated candidasis (n = 1) and congestive heart failure (n = 1). Another patient died of cerebral infarction on day 140. Thus, acute-phase regimen-related toxicities >grade III were observed in only one patient. Engraftment and complete donor chimerism were achieved by day 28 in 14 evaluable patients, and 6 of them (43%) experienced grade II-IV acute graft-versus-host disease. With a median follow-up of 328 days (range, 231-633 days), the actuarial 1-year overall and disease-free survival rates were 69% and 50%, respectively. Notably, among seven high-risk patients (five patients had been in complete remission two or more times and two not in complete remission with refractory disease at transplant), only two patients developed leukemia relapse after RIST. Although the recovery of CD4+ cells was significantly slower (P = 0.02) in RIST than in conventional stem cell transplantation, the incidence of clinically documented infections was not significantly different between the two groups. Conclusion: The results suggest that this novel regimen containing 2-CdA is well tolerated and induces early complete donor chimerism. The unexpected durable remission achieved in patients with advanced disease at transplant suggests the presence of an acceptable antileukemia/lymphoma effect, which would warrant a further clinical trial.

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