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, Joachim H Deeg, Bart L Scott, George B McDonald, Rainer Storb, Brenda M Sandmaier, 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, Joachim H Deeg, Bart L Scott, George B McDonald, Rainer Storb, Brenda M Sandmaier

Abstract

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.

Figures

Figure 1.
Figure 1.
Adjusted cumulative incidence rates of major clinical endpoints by era of transplant. (A) Overall survival, (B) progression-free survival (PFS), (C) nonrelapse mortality (NRM), and (D) relapse. Era of transplant: 1997–2003 (black line), 2004–2009 (blue line), and 2010–2017 (red line).
Figure 2.
Figure 2.
Adjusted cumulative incidence rates of acute and chronic graft-versus-host disease by era of transplant. (A) Grades 2–4 acute graft-versus-host disease (GVHD), (B) grades 3–4 acute GvHD, and (C) chronic GvHD. Era of transplant: 1997–2003 (black line), 2004–2009 (blue line), and 2010–2017 (red line).

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