Myeloablative versus reduced-intensity hematopoietic cell transplantation for acute myeloid leukemia and myelodysplastic syndromes

Bart L. Scott, Marcelo C. Pasquini, Brent R. Logan, Juan Wu, Steven M. Devine, David L. Porter, Richard Maziarz, Erica D. Warlick, Hugo F. Fernandez, Edwin P. Alyea, Mehdi Hamadani, Asad Bashey, Sergio Giralt, Nancy L. Geller, Eric Leifer, Jennifer Le-Rademacher, Adam M. Mendizabal, Mary M. Horowitz, H. Joachim Deeg, Mitchell E. Horwitz

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Abstract

Purpose The optimal regimen intensity before allogeneic hematopoietic cell transplantation (HCT) is unknown. We hypothesized that lower treatment-related mortality (TRM) with reduced-intensity conditioning (RIC) would result in improved overall survival (OS) compared with myeloablative conditioning (MAC). To test this hypothesis, we performed a phase III randomized trial comparing MAC with RIC in patients with acute myeloid leukemia or myelodysplastic syndromes. Patients and Methods Patients age 18 to 65 years with HCT comorbidity index#4 and,5% marrow myeloblasts pre-HCT were randomly assigned to receive MAC (n = 135) or RIC (n = 137) followed by HCT from HLAmatched related or unrelated donors. The primary end point was OS 18 months post-random assignment based on an intent-to-treat analysis. Secondary end points included relapse-free survival (RFS) and TRM. Results Planned enrollment was 356 patients; accrual ceased at 272 because of high relapse incidence with RIC versus MAC (48.3%; 95% CI, 39.6% to 56.4% and 13.5%; 95% CI, 8.3% to 19.8%, respectively; P <.001). At 18 months, OS for patients in the RIC arm was 67.7% (95% CI, 59.1% to 74.9%) versus 77.5% (95% CI, 69.4% to 83.7%) for those in the MAC arm (difference, 9.8%; 95% CI, 20.8% to 20.3%; P = .07). TRM with RIC was 4.4% (95% CI, 1.8% to 8.9%) versus 15.8% (95% CI, 10.2% to 22.5%) with MAC (P = .002). RFS with RIC was 47.3% (95% CI, 38.7% to 55.4%) versus 67.8% (95% CI, 59.1% to 75%) with MAC (P <.01). Conclusion OS was higher with MAC, but this was not statistically significant. RIC resulted in lower TRM but higher relapse rates compared with MAC, with a statistically significant advantage in RFS with MAC. These data support the use of MAC as the standard of care for fit patients with acute myeloid leukemia or myelodysplastic syndromes.

Original languageEnglish (US)
Pages (from-to)1154-1161
Number of pages8
JournalJournal of Clinical Oncology
Volume35
Issue number11
DOIs
StatePublished - Apr 10 2017

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Myelodysplastic Syndromes
Cell Transplantation
Acute Myeloid Leukemia
Survival
Recurrence
Mortality
Granulocyte Precursor Cells
Unrelated Donors
Therapeutics
Standard of Care
Comorbidity
Bone Marrow
Incidence

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Scott, B. L., Pasquini, M. C., Logan, B. R., Wu, J., Devine, S. M., Porter, D. L., ... Horwitz, M. E. (2017). Myeloablative versus reduced-intensity hematopoietic cell transplantation for acute myeloid leukemia and myelodysplastic syndromes. Journal of Clinical Oncology, 35(11), 1154-1161. https://doi.org/10.1200/JCO.2016.70.7091

Myeloablative versus reduced-intensity hematopoietic cell transplantation for acute myeloid leukemia and myelodysplastic syndromes. / Scott, Bart L.; Pasquini, Marcelo C.; Logan, Brent R.; Wu, Juan; Devine, Steven M.; Porter, David L.; Maziarz, Richard; Warlick, Erica D.; Fernandez, Hugo F.; Alyea, Edwin P.; Hamadani, Mehdi; Bashey, Asad; Giralt, Sergio; Geller, Nancy L.; Leifer, Eric; Le-Rademacher, Jennifer; Mendizabal, Adam M.; Horowitz, Mary M.; Deeg, H. Joachim; Horwitz, Mitchell E.

In: Journal of Clinical Oncology, Vol. 35, No. 11, 10.04.2017, p. 1154-1161.

Research output: Contribution to journalArticle

Scott, BL, Pasquini, MC, Logan, BR, Wu, J, Devine, SM, Porter, DL, Maziarz, R, Warlick, ED, Fernandez, HF, Alyea, EP, Hamadani, M, Bashey, A, Giralt, S, Geller, NL, Leifer, E, Le-Rademacher, J, Mendizabal, AM, Horowitz, MM, Deeg, HJ & Horwitz, ME 2017, 'Myeloablative versus reduced-intensity hematopoietic cell transplantation for acute myeloid leukemia and myelodysplastic syndromes', Journal of Clinical Oncology, vol. 35, no. 11, pp. 1154-1161. https://doi.org/10.1200/JCO.2016.70.7091
Scott, Bart L. ; Pasquini, Marcelo C. ; Logan, Brent R. ; Wu, Juan ; Devine, Steven M. ; Porter, David L. ; Maziarz, Richard ; Warlick, Erica D. ; Fernandez, Hugo F. ; Alyea, Edwin P. ; Hamadani, Mehdi ; Bashey, Asad ; Giralt, Sergio ; Geller, Nancy L. ; Leifer, Eric ; Le-Rademacher, Jennifer ; Mendizabal, Adam M. ; Horowitz, Mary M. ; Deeg, H. Joachim ; Horwitz, Mitchell E. / Myeloablative versus reduced-intensity hematopoietic cell transplantation for acute myeloid leukemia and myelodysplastic syndromes. In: Journal of Clinical Oncology. 2017 ; Vol. 35, No. 11. pp. 1154-1161.
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abstract = "Purpose The optimal regimen intensity before allogeneic hematopoietic cell transplantation (HCT) is unknown. We hypothesized that lower treatment-related mortality (TRM) with reduced-intensity conditioning (RIC) would result in improved overall survival (OS) compared with myeloablative conditioning (MAC). To test this hypothesis, we performed a phase III randomized trial comparing MAC with RIC in patients with acute myeloid leukemia or myelodysplastic syndromes. Patients and Methods Patients age 18 to 65 years with HCT comorbidity index#4 and,5{\%} marrow myeloblasts pre-HCT were randomly assigned to receive MAC (n = 135) or RIC (n = 137) followed by HCT from HLAmatched related or unrelated donors. The primary end point was OS 18 months post-random assignment based on an intent-to-treat analysis. Secondary end points included relapse-free survival (RFS) and TRM. Results Planned enrollment was 356 patients; accrual ceased at 272 because of high relapse incidence with RIC versus MAC (48.3{\%}; 95{\%} CI, 39.6{\%} to 56.4{\%} and 13.5{\%}; 95{\%} CI, 8.3{\%} to 19.8{\%}, respectively; P <.001). At 18 months, OS for patients in the RIC arm was 67.7{\%} (95{\%} CI, 59.1{\%} to 74.9{\%}) versus 77.5{\%} (95{\%} CI, 69.4{\%} to 83.7{\%}) for those in the MAC arm (difference, 9.8{\%}; 95{\%} CI, 20.8{\%} to 20.3{\%}; P = .07). TRM with RIC was 4.4{\%} (95{\%} CI, 1.8{\%} to 8.9{\%}) versus 15.8{\%} (95{\%} CI, 10.2{\%} to 22.5{\%}) with MAC (P = .002). RFS with RIC was 47.3{\%} (95{\%} CI, 38.7{\%} to 55.4{\%}) versus 67.8{\%} (95{\%} CI, 59.1{\%} to 75{\%}) with MAC (P <.01). Conclusion OS was higher with MAC, but this was not statistically significant. RIC resulted in lower TRM but higher relapse rates compared with MAC, with a statistically significant advantage in RFS with MAC. These data support the use of MAC as the standard of care for fit patients with acute myeloid leukemia or myelodysplastic syndromes.",
author = "Scott, {Bart L.} and Pasquini, {Marcelo C.} and Logan, {Brent R.} and Juan Wu and Devine, {Steven M.} and Porter, {David L.} and Richard Maziarz and Warlick, {Erica D.} and Fernandez, {Hugo F.} and Alyea, {Edwin P.} and Mehdi Hamadani and Asad Bashey and Sergio Giralt and Geller, {Nancy L.} and Eric Leifer and Jennifer Le-Rademacher and Mendizabal, {Adam M.} and Horowitz, {Mary M.} and Deeg, {H. Joachim} and Horwitz, {Mitchell E.}",
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TY - JOUR

T1 - Myeloablative versus reduced-intensity hematopoietic cell transplantation for acute myeloid leukemia and myelodysplastic syndromes

AU - Scott, Bart L.

AU - Pasquini, Marcelo C.

AU - Logan, Brent R.

AU - Wu, Juan

AU - Devine, Steven M.

AU - Porter, David L.

AU - Maziarz, Richard

AU - Warlick, Erica D.

AU - Fernandez, Hugo F.

AU - Alyea, Edwin P.

AU - Hamadani, Mehdi

AU - Bashey, Asad

AU - Giralt, Sergio

AU - Geller, Nancy L.

AU - Leifer, Eric

AU - Le-Rademacher, Jennifer

AU - Mendizabal, Adam M.

AU - Horowitz, Mary M.

AU - Deeg, H. Joachim

AU - Horwitz, Mitchell E.

PY - 2017/4/10

Y1 - 2017/4/10

N2 - Purpose The optimal regimen intensity before allogeneic hematopoietic cell transplantation (HCT) is unknown. We hypothesized that lower treatment-related mortality (TRM) with reduced-intensity conditioning (RIC) would result in improved overall survival (OS) compared with myeloablative conditioning (MAC). To test this hypothesis, we performed a phase III randomized trial comparing MAC with RIC in patients with acute myeloid leukemia or myelodysplastic syndromes. Patients and Methods Patients age 18 to 65 years with HCT comorbidity index#4 and,5% marrow myeloblasts pre-HCT were randomly assigned to receive MAC (n = 135) or RIC (n = 137) followed by HCT from HLAmatched related or unrelated donors. The primary end point was OS 18 months post-random assignment based on an intent-to-treat analysis. Secondary end points included relapse-free survival (RFS) and TRM. Results Planned enrollment was 356 patients; accrual ceased at 272 because of high relapse incidence with RIC versus MAC (48.3%; 95% CI, 39.6% to 56.4% and 13.5%; 95% CI, 8.3% to 19.8%, respectively; P <.001). At 18 months, OS for patients in the RIC arm was 67.7% (95% CI, 59.1% to 74.9%) versus 77.5% (95% CI, 69.4% to 83.7%) for those in the MAC arm (difference, 9.8%; 95% CI, 20.8% to 20.3%; P = .07). TRM with RIC was 4.4% (95% CI, 1.8% to 8.9%) versus 15.8% (95% CI, 10.2% to 22.5%) with MAC (P = .002). RFS with RIC was 47.3% (95% CI, 38.7% to 55.4%) versus 67.8% (95% CI, 59.1% to 75%) with MAC (P <.01). Conclusion OS was higher with MAC, but this was not statistically significant. RIC resulted in lower TRM but higher relapse rates compared with MAC, with a statistically significant advantage in RFS with MAC. These data support the use of MAC as the standard of care for fit patients with acute myeloid leukemia or myelodysplastic syndromes.

AB - Purpose The optimal regimen intensity before allogeneic hematopoietic cell transplantation (HCT) is unknown. We hypothesized that lower treatment-related mortality (TRM) with reduced-intensity conditioning (RIC) would result in improved overall survival (OS) compared with myeloablative conditioning (MAC). To test this hypothesis, we performed a phase III randomized trial comparing MAC with RIC in patients with acute myeloid leukemia or myelodysplastic syndromes. Patients and Methods Patients age 18 to 65 years with HCT comorbidity index#4 and,5% marrow myeloblasts pre-HCT were randomly assigned to receive MAC (n = 135) or RIC (n = 137) followed by HCT from HLAmatched related or unrelated donors. The primary end point was OS 18 months post-random assignment based on an intent-to-treat analysis. Secondary end points included relapse-free survival (RFS) and TRM. Results Planned enrollment was 356 patients; accrual ceased at 272 because of high relapse incidence with RIC versus MAC (48.3%; 95% CI, 39.6% to 56.4% and 13.5%; 95% CI, 8.3% to 19.8%, respectively; P <.001). At 18 months, OS for patients in the RIC arm was 67.7% (95% CI, 59.1% to 74.9%) versus 77.5% (95% CI, 69.4% to 83.7%) for those in the MAC arm (difference, 9.8%; 95% CI, 20.8% to 20.3%; P = .07). TRM with RIC was 4.4% (95% CI, 1.8% to 8.9%) versus 15.8% (95% CI, 10.2% to 22.5%) with MAC (P = .002). RFS with RIC was 47.3% (95% CI, 38.7% to 55.4%) versus 67.8% (95% CI, 59.1% to 75%) with MAC (P <.01). Conclusion OS was higher with MAC, but this was not statistically significant. RIC resulted in lower TRM but higher relapse rates compared with MAC, with a statistically significant advantage in RFS with MAC. These data support the use of MAC as the standard of care for fit patients with acute myeloid leukemia or myelodysplastic syndromes.

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