Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies: Improved outcomes over two decades

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 h...

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Bibliographic Details
Published in:Haematologica (Roma) Vol. 106; no. 6; pp. 1599 - 1607
Main Authors: Cooper, Jason P, Storer, Barry E, Granot, Noa, Gyurkocza, Boglark, Sorror, Mohamed L, Chauncey, Thomas R, Shizuru, Judith, Franke, Georg-Nikolaus, Maris, Michael B, Boyer, Michael, Bruno, Benedetto, Sahebi, Firoozeh, Langston, Amelia A, Hari, Parameswaran, Agura, Edward D, Lykke Petersen, Søren, Maziarz, Richard T, Bethge, Wolfgang, Asch, Julie, Gutman, Jonathan A, Olesen, Gitte, Yeager, Andrew M, Hübel, Kai, Hogan, William J, Maloney, David G, Mielcarek, Marco, Martin, Paul J, Flowers, Mary E D, Georges, George E, Woolfrey, Ann E, Deeg, Joachim H, Scott, Bart L, McDonald, George B, Storb, Rainer, Sandmaier, Brenda M
Format: Journal Article
Language:English
Published: Italy Fondazione Ferrata Storti 01-06-2021
Ferrata Storti Foundation
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Summary: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.
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Disclosures
JPC, BES, NG, GMcD, RS and BMS contributed to the conception and design; RS and BMS secured financial support; RS and BMS provided administrative support; BG, MLS, TRC, JS, G-NF, MBM, MB, BB, FS, AAL, PH, EDA, SLP, RTM, WB, JA, JAG, GO, AMY, KH, WJH, DGM, MM, PJM, MEDF, GEG, AEW, HJD, BLS, GBMcD, RS and BMS provided study materials or patients; JPC, BG, MLS, TRC, JS, G-NF, MBM, MB, BB, FS, AAL, PH, EDA, SLP, RTM, WB, JA, JAG, GO, AMY, KH, WJH, DGM, MM, PJM, MEDF, GEG, AEW, HJD, BLS, GBMcD, RS and BMS collected and assembled data; JPC, BES, NG, GMcD, RS and BMS analyzed and interpreted data; all authors contributed to the writing and final apporval of the manuscript.
Contributions
No conflicts of interest to disclose.
ISSN:0390-6078
1592-8721
1592-8721
DOI:10.3324/haematol.2020.248187