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. Bone Marrow Transplantation (2001) 27, 1221–1225.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Frassoni F, Barrett AJ, Granena A et al. Relapse after allogeneic bone marrow transplantation for acute leukemia: a survey by the EBMTR of 117 cases Br J Haematol 1988 70: 317–320
Mortimer J, Blinder M, Schulman S et al. Relapse of acute leukemia after marrow transplantation: natural history and results of subsequent therapy J Clin Oncol 1989 7: 50–57
Giralt S, Hester J, Huh Y et al. CD8-depleted donor lymphocyte infusion as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation Blood 1995 86: 4337–4343
Issa J-PJ, Baylin SB, Herman JG . DNA methylation changes in hematologic malignancies: biologic and clinical implications Leukemia 1997 11: (Suppl. 1) S7–S11
Pliml J, Sorm F . Synthesis of 2′-deoxy-D-ribofuranosyl-5-azacytosine Coll Czech Chem Commun 1964 29: 2576–2577
Sorm F, Vesely J . Effect of 5-aza-2′-deoxycytidine against leukemic and hemopoietic tissues in AKR mice Neoplasma 1968 15: 339–343
Pinto A, Zagonei V . 5-Aza-2′-deoxycytidine (Decitabine) and 5-azacytidine in the treatment of acute myeloid leukemia and myelodysplastic syndromes: past, present and future trends Leukemia 1993 7: 51–60
Santi DV, Garrett CE, Barr PJ . On the mechanism of inhibition of DNA-cytosine methyltransferase by cytidine analogs Cell 1983 83: 9–10
Momparler RL, Bouchard J, Samson J . Induction of differentiation and inhibition of DNA methylation in HL60 myeloid leukemic cells by 5-aza-2′-deoxycytidine Leukemia Res 1985 9: 1361–1366
Pinto A, Attadia V, Fusco A et al. 5-aza-2′-deoxycytidine induces terminal differentiation of leukemic blasts from patients with acute myeloid leukemia Blood 1984 64: 922–929
Pinto A, Maio M, Attadia V et al. Modulation of HLA-DR antigen expression in human myeloid leukemic cells by cytarabine and 5-aza-2′-deoxycytidine Lancet 1984 2: 867–868
Pinto A, Zagonel V, Attadia V et al. 5-aza-2′-deoxycytidine as a differentiation inducer in acute myeloid leukemias and myelodysplastic syndromes of the elderly Bone Marrow Transplant 1989 4: (Suppl. 2) 28–32
Giralt S, Davis M, O'Brien S et al. Studies of decitabine with allogeneic progenitor cell transplantation Leukemia 1997 11: (Suppl. 1) S32–S34
Rivard GE, Momparler RL, Demers J et al. Phase I study on 5-aza-2′-deoxycytidine in children with acute leukemia Leukemia Res 1981 5: 452–462
Momparler RL, Gyger M, Rivard GE . Clinical trial on 5-aza-2′-deoxycytidine in patients with acute leukemia Pharmacol Ther 1985 30: 277–286
Richel DJ, Colly LP, Kluin-Nelemans JC et al. The antileukemic activity of 5-aza-2′-deoxycytidine (Aza-dC) in patients with relapsed and resistant acute leukemia Br J Cancer 1991 64: 144–148
Bearman S, Appelbaum F, Buckner C et al. Regimen related toxicity in patients undergoing bone marrow transplantation J Clin Oncol 1988 6: 1562–1568
Gluksberg H, Storb R, Fefer A et al. Clinical manifestations of graft versus host disease in human recipients of marrow from HLA matched sibling donors Transplantation 1974 18: 295–304
Schulman HM, Sullivan KM, Weiden PL et al. Chronic graft-versus-host disease syndrome in man . A long term clinical pathologic study of 20 Seattle patients Am J Med 1980 69: 204–217
Kolb HJ, Schattenberg A, Goldman JM et al. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. European Group for Blood and Marrow Transplantation Working Party on Chronic Leukemia Blood 1995 86: 2041–2050
Sanders JE, Buckner CD, Clift RA et al. Second marrow transplants for patients with leukemia who relapse after allogeneic marrow transplantation Bone Marrow Transplant 1988 3: 11–21
Giles FJ, Cortes JF, Beran M et al. Phase I study of BCH4556 in patients with advanced leukemia Proc ASCO 1999 18: 28a (Abstr.)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ravandi, F., Kantarjian, H., Cohen, A. et al. 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 Transplant 27, 1221–1225 (2001). https://doi.org/10.1038/sj.bmt.1703028
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bmt.1703028
Keywords
This article is cited by
-
Immune responses to azacytidine in animal models of inflammatory disorders: a systematic review
Journal of Translational Medicine (2021)
-
Decitabine for relapsed acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation
Current Medical Science (2017)
-
Monosomal karyotype predicts poor survival after allogeneic stem cell transplantation in chromosome 7 abnormal myelodysplastic syndrome and secondary acute myeloid leukemia
Leukemia (2013)
-
Decitabine in patients with relapsed acute myeloid leukemia (AML) after allogeneic stem cell transplantation (allo-SCT)
Annals of Hematology (2013)
-
Epigenetic approaches in stem cell transplantation
Clinical Epigenetics (2011)