Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia

Boglarka Gyurkocza, Rainer Storb, Barry E. Storer, Thomas R. Chauncey, Thoralf Lange, Judith A. Shizuru, Amelia A. Langston, Michael A. Pulsipher, Christopher N. Bredeson, Richard Maziarz, Benedetto Bruno, Finn B. Petersen, Michael B. Maris, Edward Agura, Andrew Yeager, Wolfgang Bethge, Firoozeh Sahebi, Frederick R. Appelbaum, David G. Maloney, Brenda M. Sandmaier

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Abstract

Purpose: Allogeneic hematopoietic cell transplantation (HCT) after high-dose conditioning regimens imposes prohibitively high risks of morbidity and mortality for patients with high-risk acute myeloid leukemia (AML) who are older or have comorbid conditions. Here, we examined outcomes after nonmyeloablative allogeneic HCT in such patients. Patients and Methods: Two hundred seventy-four patients (median age, 60 years) with de novo or secondary AML underwent allogeneic HCT from related (n = 118) or unrelated donors (n = 156) after conditioning with 2 Gy of total-body irradiation (TBI) with or without fludarabine. A calcineurin inhibitor and mycophenolate mofetil were used for postgrafting immunosuppression. Results: With a median follow-up of 38 months in surviving patients, the estimated overall survival at 5 years was 33%. The estimated 5-year relapse/progression and nonrelapse mortality rates were 42% and 26%, respectively. The cumulative incidences of grades 2, 3, and 4 acute graft-versushost disease (GVHD) were 38%, 9%, and 5%, respectively. The cumulative incidence of chronic GVHD at 5 years was 44%. Patients in first and second complete remission had better survival rates than patients with more advanced disease (37% and 34% v 18%, respectively). Patients with HLA-matched related or unrelated donors had similar survivals. Unfavorable cytogenetic risk status was associated with increased relapse and subsequent mortality. Chronic GVHD was associated with lower relapse risk. Conclusion: Allogeneic HCT from related or unrelated donors after conditioning with low-dose TBI and fludarabine, relying almost exclusively on graft-versus-leukemia effects, can result in long-term remissions in older or medically infirm patients with AML.

Original languageEnglish (US)
Pages (from-to)2859-2867
Number of pages9
JournalJournal of Clinical Oncology
Volume28
Issue number17
DOIs
StatePublished - Jun 10 2010
Externally publishedYes

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Cell Transplantation
Acute Myeloid Leukemia
Unrelated Donors
Transplants
Whole-Body Irradiation
Recurrence
Mortality
Mycophenolic Acid
Survival
Incidence
Cytogenetics
Immunosuppression
Leukemia
Survival Rate
Morbidity

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Gyurkocza, B., Storb, R., Storer, B. E., Chauncey, T. R., Lange, T., Shizuru, J. A., ... Sandmaier, B. M. (2010). Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. Journal of Clinical Oncology, 28(17), 2859-2867. https://doi.org/10.1200/JCO.2009.27.1460

Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. / Gyurkocza, Boglarka; Storb, Rainer; Storer, Barry E.; Chauncey, Thomas R.; Lange, Thoralf; Shizuru, Judith A.; Langston, Amelia A.; Pulsipher, Michael A.; Bredeson, Christopher N.; Maziarz, Richard; Bruno, Benedetto; Petersen, Finn B.; Maris, Michael B.; Agura, Edward; Yeager, Andrew; Bethge, Wolfgang; Sahebi, Firoozeh; Appelbaum, Frederick R.; Maloney, David G.; Sandmaier, Brenda M.

In: Journal of Clinical Oncology, Vol. 28, No. 17, 10.06.2010, p. 2859-2867.

Research output: Contribution to journalArticle

Gyurkocza, B, Storb, R, Storer, BE, Chauncey, TR, Lange, T, Shizuru, JA, Langston, AA, Pulsipher, MA, Bredeson, CN, Maziarz, R, Bruno, B, Petersen, FB, Maris, MB, Agura, E, Yeager, A, Bethge, W, Sahebi, F, Appelbaum, FR, Maloney, DG & Sandmaier, BM 2010, 'Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia', Journal of Clinical Oncology, vol. 28, no. 17, pp. 2859-2867. https://doi.org/10.1200/JCO.2009.27.1460
Gyurkocza, Boglarka ; Storb, Rainer ; Storer, Barry E. ; Chauncey, Thomas R. ; Lange, Thoralf ; Shizuru, Judith A. ; Langston, Amelia A. ; Pulsipher, Michael A. ; Bredeson, Christopher N. ; Maziarz, Richard ; Bruno, Benedetto ; Petersen, Finn B. ; Maris, Michael B. ; Agura, Edward ; Yeager, Andrew ; Bethge, Wolfgang ; Sahebi, Firoozeh ; Appelbaum, Frederick R. ; Maloney, David G. ; Sandmaier, Brenda M. / Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. In: Journal of Clinical Oncology. 2010 ; Vol. 28, No. 17. pp. 2859-2867.
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AU - Storb, Rainer

AU - Storer, Barry E.

AU - Chauncey, Thomas R.

AU - Lange, Thoralf

AU - Shizuru, Judith A.

AU - Langston, Amelia A.

AU - Pulsipher, Michael A.

AU - Bredeson, Christopher N.

AU - Maziarz, Richard

AU - Bruno, Benedetto

AU - Petersen, Finn B.

AU - Maris, Michael B.

AU - Agura, Edward

AU - Yeager, Andrew

AU - Bethge, Wolfgang

AU - Sahebi, Firoozeh

AU - Appelbaum, Frederick R.

AU - Maloney, David G.

AU - Sandmaier, Brenda M.

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N2 - Purpose: Allogeneic hematopoietic cell transplantation (HCT) after high-dose conditioning regimens imposes prohibitively high risks of morbidity and mortality for patients with high-risk acute myeloid leukemia (AML) who are older or have comorbid conditions. Here, we examined outcomes after nonmyeloablative allogeneic HCT in such patients. Patients and Methods: Two hundred seventy-four patients (median age, 60 years) with de novo or secondary AML underwent allogeneic HCT from related (n = 118) or unrelated donors (n = 156) after conditioning with 2 Gy of total-body irradiation (TBI) with or without fludarabine. A calcineurin inhibitor and mycophenolate mofetil were used for postgrafting immunosuppression. Results: With a median follow-up of 38 months in surviving patients, the estimated overall survival at 5 years was 33%. The estimated 5-year relapse/progression and nonrelapse mortality rates were 42% and 26%, respectively. The cumulative incidences of grades 2, 3, and 4 acute graft-versushost disease (GVHD) were 38%, 9%, and 5%, respectively. The cumulative incidence of chronic GVHD at 5 years was 44%. Patients in first and second complete remission had better survival rates than patients with more advanced disease (37% and 34% v 18%, respectively). Patients with HLA-matched related or unrelated donors had similar survivals. Unfavorable cytogenetic risk status was associated with increased relapse and subsequent mortality. Chronic GVHD was associated with lower relapse risk. Conclusion: Allogeneic HCT from related or unrelated donors after conditioning with low-dose TBI and fludarabine, relying almost exclusively on graft-versus-leukemia effects, can result in long-term remissions in older or medically infirm patients with AML.

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