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Bone Marrow Transplantation
Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies: improved outcomes over two decades
Ferrata Storti Foundation
Haematologica 2021 Volume 106(6):1599-1607
Jason P. Cooper,1,2 Barry E. Storer,1,2 Noa Granot,1 Boglarka Gyurkocza,1,2o Mohamed L. Sorror,1,2 Thomas R. Chauncey,1,2,3 Judith Shizuru,4 Georg-Nikolaus Franke,5 Michael B. Maris,6 Michael Boyer,7
Benedetto Bruno,8 Firoozeh Sahebi,9 Amelia A. Langston,10
Parameswaran Hari,11 Edward D. Agura,12 Søren Lykke Petersen,13
Richard T. Maziarz,14 Wolfgang Bethge,15 Julie Asch,16 Jonathan A. Gutman,17 Gitte Olesen,18 Andrew M. Yeager,19 Kai Hübel,20 William J. Hogan,21
David G. Maloney,1,2 Marco Mielcarek,1,2 Paul J. Martin,1,2
Mary E. D. Flowers,1,2 George E. Georges,1,2 Ann E. Woolfrey,1,2
H. Joachim Deeg,1,2 Bart L. Scott,1,2 George B. McDonald,1,2 Rainer Storb1,2 and Brenda M. Sandmaier1,2
1Fred Hutchinson Cancer Research Center, Seattle, WA, USA; 2University of Washington, Seattle, WA, USA; 3Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA; 4Stanford University, Palo Alto, CA, USA; 5University of Leipzig, Leipzig, Germany; 6Colorado Blood Cancer Institute at HealthONE Presbyterian/St. Luke Medical Center, Denver, CO, USA; 7University of Utah, Salt Lake City, UT, USA; 8University of Turin, Turin, Italy; 9City of Hope/Kaiser Permanente Medical Group, Duarte, CA, USA; 10Winship Cancer Institute at Emory University, Atlanta, GA, USA; 11Medical College of Wisconsin, Milwaukee, WI, USA; 12Baylor University, Dallas, TX, USA; 13University of Copenhagen Rigshospitalet, Copenhagen, Denmark; 14Oregon Health and Science University, Portland, OR, USA; 15University of Tübingen, Tübingen, Germany; 16LDS Hospital, Salt Lake City, UT, USA; 17University of Colorado, Denver, CO, USA; 18Aarhus University, Aarhus, Denmark; 19University of Arizona Cancer Center, Tucson, AZ, USA; 20University Hospital of Cologne, Cologne, Germany and 21Mayo Clinic, Rochester, MN, USA
oCurrent address: Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
ABSTRACT
We have used a non-myeloablative conditioning regimen for allo- geneic hematopoietic cell transplantation for the past 20 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 Comorbidity 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, improve- ments were noted in overall survival (P=0.0001 for 2004–2009 and P≤0.0001 for 2010–2017), progression-free survival (P=0.002 for 2004–2009 and P<0.0001 for 2010–2017), non-relapse mortality (P<0.0001 for 2004– 2009 and P<0.0001 for 2010–2017), and in rates of grades 2–4 acute and chronic graft-versus-host disease. For patients with hematologic malignan- cies who underwent transplantation with non-myeloablative conditioning, outcomes have improved during the past two decades. Trials reported are registered under clinicaltrials gov. Identifiers: NCT00003145,
Correspondence:
JASON P. COOPER
jpcooper@fredhutch.org
Received: January 27, 2020. Accepted: May 27, 2020. Pre-published: June 4, 2020.
https://doi.org/10.3324/haematol.2020.248187
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