Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies: Improved outcomes over two decades
Jason P. Cooper,
Barry E. Storer,
Noa Granot,
Boglark Gyurkocza,
Mohamed L. Sorror,
Thomas R. Chauncey,
Judith Shizuru,
Georg-Nikolaus Franke,
Michael B. Maris,
Michael Boyer,
Benedetto Bruno,
Firoozeh Sahebi,
Amelia A. Langston,
Parameswaran Hari,
Edward D. Agura,
Søren Lykke Petersen,
Richard T. Maziarz,
Wolfgang Bethge,
Julie Asch,
Jonathan A. Gutman,
Gitte Olesen,
Andrew M. Yeager,
Kai Hübel,
William J. Hogan,
David G. Maloney,
Marco Mielcarek,
Paul J. Martin,
Mary E.D. Flowers,
George E. Georges,
Ann E. Woolfrey,
H. Joachim Deeg,
Bart L. Scott,
George B. McDonald,
Rainer Storb,
Brenda M. Sandmaier
Affiliations
Jason P. Cooper
Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, WA, USA;
Barry E. Storer
Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, WA, USA;
Noa Granot
Fred Hutchinson Cancer Research Center, Seattle, WA, USA;
Boglark Gyurkocza
Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, WA, USA;
Mohamed L. Sorror
Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, WA, USA;
Thomas R. Chauncey
Fred Hucthinson Cancer Research Center, Univ of Washington, VA Puget Sound Health Care, Seattle, USA;
Judith Shizuru
Stanford University, Palo Alto, CA, USA;
Georg-Nikolaus Franke
University of Leipzig, Leipzig, Germany;
Michael B. Maris
Colorado Blood Cancer Institute at HealthONE Presbyterian/St. Luke Medical Center, Denver, USA;
Michael Boyer
University of Utah, Salt Lake City, UT, USA;
Benedetto Bruno
Azienda Ospedaliera S Giovanni Battista, University of Turin, Turin, Italy;
Firoozeh Sahebi
City of Hope/Kaiser Permanente Medical Group, Duarte, CA, USA;
Amelia A. Langston
Winship Cancer Institute at Emory University, Atlanta, GA, USA;
Parameswaran Hari
Medical College of Wisconsin, Milwaukee, WI, USA;
Edward D. Agura
Baylor University, Dallas, TX, USA;
Søren Lykke Petersen
University of Copenhagen Rigshospitalet, Copenhagen, Denmark;
Richard T. Maziarz
Oregon Health and Science University, Portland, OR, USA;
Wolfgang Bethge
Medical Center University of Tübingen, Tübingen, Germany;
Julie Asch
LDS Hospital, Salt Lake City, UT, USA;
Jonathan A. Gutman
University of Colorado, Denver, CO, USA;
Gitte Olesen
Aarhus University, Aarhus, Denmark;
Andrew M. Yeager
University of Arizona Cancer Center, Tucson, AZ, USA;
Kai Hübel
University Hospital of Cologne, Cologne, Germany;
William J. Hogan
Mayo Clinic, Rochester, MN, USA
David G. Maloney
Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, WA, USA;
Marco Mielcarek
Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, WA, USA;
Paul J. Martin
Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, WA, USA;
Mary E.D. Flowers
Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, WA, USA;
George E. Georges
Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, WA, USA;
Ann E. Woolfrey
Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, WA, USA;
H. Joachim Deeg
Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, WA, USA;
Bart L. Scott
Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, WA, USA;
George B. McDonald
Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, WA, USA;
Rainer Storb
Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, WA, USA;
Brenda M. Sandmaier
Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, WA, USA;
We have used a non-myeloablative conditioning regimen for allogeneic hematopoietic cell transplantation for the past twenty years. During that period, changes in clinical practice have been aimed at reducing morbidity and mortality from infections, organ toxicity, and graft-versus-host disease. We hypothesized that improvements in clinical practice led to better transplantation outcomes over time. From 1997-2017, 1,720 patients with hematologic malignancies received low-dose total body irradiation +/- fludarabine or clofarabine before transplantation from HLA-matched sibling or unrelated donors, followed by mycophenolate mofetil and a calcineurin inhibitor ± sirolimus. We compared outcomes in three cohorts by year of transplantation: 1997 +/- 2003 (n=562), 2004 +/- 2009 (n=594), and 2010 +/- 2017 (n=564). The proportion of patients ≥60 years old increased from 27% in 1997 +/- 2003 to 56% in 2010–2017, and with scores from the Hematopoietic Cell Transplantation Comborbidity Index of ≥3 increased from 25% in 1997 +/- 2003 to 45% in 2010 +/- 2017. Use of unrelated donors increased from 34% in 1997 +/- 2003 to 65% in 2010–2017. When outcomes from 2004 +/- 2009 and 2010–2017 were compared to 1997 +/- 2003, improvements were noted in overall survival (P=.0001 for 2004–2009 and P <.0001 for 2010–2017), profression-free survival (P=.002 for 2004–2009 and P <.0001 for 2010 +/- 2017), non-relapse mortality (P<.0001 for 2004 +/- 2009 and P <.0001 for 2010 +/- 2017), and in rates of grades 2 +/- 4 acute and chronic graft-vs.-host disease. For patients with hematologic malignancies who underwent transplantation with non-myeloablative conditioning, outcomes have improved during the past two decades. Trials reported are registered under ClinicalTrials.gov identifiers: NCT00003145, NCT00003196, NCT00003954, NCT00005799, NCT00005801, NCT00005803, NCT00006251, NCT00014235, NCT00027820, NCT00031655, NCT00036738, NCT00045435, NCT00052546, NCT00060424, NCT00075478, NCT00078858, NCT00089011, NCT00104858, NCT00105001, NCT00110058, NCT00397813, NCT00793572, NCT01231412, NCT01252667, NCT01527045.
