Decitabine with allogeneic peripheral blood stem cell transplantation in the therapy of leukemia relapse following a prior transplant

Results of a phase I study

F. Ravandi, H. Kantarjian, A. Cohen, M. Davis, S. O'Brien, P. Anderlini, B. Andersson, D. Claxton, M. Donato, J. Gajewski, I. Khouri, M. Korbling, N. Ueno, D. DeVos, R. Champlin, S. Giralt

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Relapse after allogeneic progenitor cell transplant is associated with a poor prognosis for patients with advanced leukemia, with few curative options available. Use of novel chemotherapeutic agents with limited toxicity is warranted. We investigated the role of decitabine, a pyrimidine analogue with significant anti-leukemic effect and limited toxicity, in this setting. Fourteen patients with advanced acute leukemia or transformed chronic myelogenous leukemia (CML) who had failed previous allogeneic transplant were treated. Decitabine at doses of 100 mg/m2 to 150 mg/m2 given every 12 h for 5 days was followed by infusion of stem cells from the original donor 2 to 5 days after the completion of chemotherapy. Dose of decitabine was escalated in cohorts of three patients based on the modified Fibonacci scheme. The primary study end-point was assessment of the toxicity of the regimen with secondary endpoints of response and survival. Eight patients responded with either a complete remission or partial hematological remission (absence of blasts in peripheral blood and bone marrow but with platelet count <100 × 109/l). Toxicity was limited with no grade 3 or 4 toxicity directly attributable to the treatment. The median survival for all patients was 190 days (range 11 to 1215+ days). Decitabine at doses of 100 mg/m2 to 150 mg/m2 given every 12 h for 5 days, followed by stem cell infusion from the original donor was well tolerated, and was associated with acceptable myelosuppression. Current response data should encourage further study of this drug, either alone or in combination with other agents, for treatment of relapsed acute leukemia after an allogeneic transplant.

Original languageEnglish (US)
Pages (from-to)1221-1225
Number of pages5
JournalBone Marrow Transplantation
Volume27
Issue number12
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

decitabine
Peripheral Blood Stem Cell Transplantation
Leukemia
Transplants
Recurrence
Stem Cells
Tissue Donors
Therapeutics
Survival
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Platelet Count
Bone Marrow
Drug Therapy

Keywords

  • Advanced leukemia
  • Allogeneic SCT
  • Decitabine

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Decitabine with allogeneic peripheral blood stem cell transplantation in the therapy of leukemia relapse following a prior transplant : Results of a phase I study. / Ravandi, F.; Kantarjian, H.; Cohen, A.; Davis, M.; O'Brien, S.; Anderlini, P.; Andersson, B.; Claxton, D.; Donato, M.; Gajewski, J.; Khouri, I.; Korbling, M.; Ueno, N.; DeVos, D.; Champlin, R.; Giralt, S.

In: Bone Marrow Transplantation, Vol. 27, No. 12, 2001, p. 1221-1225.

Research output: Contribution to journalArticle

Ravandi, F, Kantarjian, H, Cohen, A, Davis, M, O'Brien, S, Anderlini, P, Andersson, B, Claxton, D, Donato, M, Gajewski, J, Khouri, I, Korbling, M, Ueno, N, DeVos, D, Champlin, R & Giralt, S 2001, 'Decitabine with allogeneic peripheral blood stem cell transplantation in the therapy of leukemia relapse following a prior transplant: Results of a phase I study', Bone Marrow Transplantation, vol. 27, no. 12, pp. 1221-1225. https://doi.org/10.1038/sj.bmt.1703028
Ravandi, F. ; Kantarjian, H. ; Cohen, A. ; Davis, M. ; O'Brien, S. ; Anderlini, P. ; Andersson, B. ; Claxton, D. ; Donato, M. ; Gajewski, J. ; Khouri, I. ; Korbling, M. ; Ueno, N. ; DeVos, D. ; Champlin, R. ; Giralt, S. / Decitabine with allogeneic peripheral blood stem cell transplantation in the therapy of leukemia relapse following a prior transplant : Results of a phase I study. In: Bone Marrow Transplantation. 2001 ; Vol. 27, No. 12. pp. 1221-1225.
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abstract = "Relapse after allogeneic progenitor cell transplant is associated with a poor prognosis for patients with advanced leukemia, with few curative options available. Use of novel chemotherapeutic agents with limited toxicity is warranted. We investigated the role of decitabine, a pyrimidine analogue with significant anti-leukemic effect and limited toxicity, in this setting. Fourteen patients with advanced acute leukemia or transformed chronic myelogenous leukemia (CML) who had failed previous allogeneic transplant were treated. Decitabine at doses of 100 mg/m2 to 150 mg/m2 given every 12 h for 5 days was followed by infusion of stem cells from the original donor 2 to 5 days after the completion of chemotherapy. Dose of decitabine was escalated in cohorts of three patients based on the modified Fibonacci scheme. The primary study end-point was assessment of the toxicity of the regimen with secondary endpoints of response and survival. Eight patients responded with either a complete remission or partial hematological remission (absence of blasts in peripheral blood and bone marrow but with platelet count <100 × 109/l). Toxicity was limited with no grade 3 or 4 toxicity directly attributable to the treatment. The median survival for all patients was 190 days (range 11 to 1215+ days). Decitabine at doses of 100 mg/m2 to 150 mg/m2 given every 12 h for 5 days, followed by stem cell infusion from the original donor was well tolerated, and was associated with acceptable myelosuppression. Current response data should encourage further study of this drug, either alone or in combination with other agents, for treatment of relapsed acute leukemia after an allogeneic transplant.",
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AU - O'Brien, S.

AU - Anderlini, P.

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AU - Khouri, I.

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