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J.P. Cooper et al.
Table 4. Summary of changes in clinical practice that affected non-relapse mortality over time. Increased use of topically-active GI glucocorticoids for patient with GI acute GvHD
Decreased use of systemic glucocorticoids for patients with acute GvHD
Addition of sirolimus to CI and MMF for GvHD prophylaxis
Increased use of ursodiol to prevent cholestasis and hyperbilirubinemia
Increased use of fluoroquinolones as antibacterial prophylaxis in neutropenic patients Increased use of mold-active triazoles as antifungal prophylaxis
Increased use of empiric antifungal therapy for patients with pulmonary nodules
Increasing use of pre-emptive antiviral therapy for CMV viremia
NRM: non-relapse mortality; GI: gastrointestinal; GvHD: graft-versus-host disease; CI: calcineurin inhibitor; MMF: mycophenolate mofetil; CMV: cytomegalovirus.
era. While those outcomes which did not show statistical improvements in the most recent era had hazard ratios that trended toward improvement, it is likely that the con- tinual improvement in OS and PFS had different predom- inant components at different times: improvements in NRM, relapse-related mortality, and organ toxicity con- tributing earlier (between 1997–2003 and 2004–2009) and improvement in the rate of relapse contributing later (between 2004–2009 and 2010 –2017).
The present findings are similar to those of prior analy- ses which predominantly included patients who received high-intensity conditioning.35,46,47 It is notable, however, that in these prior studies the increased use of lower-inten- sity conditioning regimens and granulocyte colony-stimu- lating factor-mobilized peripheral blood stem cell (PBSC) grafts were cited as prominent reasons for the improved outcomes – particularly reductions in NRM. The homoge- neous nature of the current patient population, with all patients receiving lower-intensity conditioning regimens and HLA-matched PBSC grafts, allowed us to more inde- pendently appraise the influence of changes in supportive care that are critical for successful outcomes after HCT.
In conclusion, we show that improvements in support- ive care after HCT with non-myeloablative conditioning for patients with advanced hematologic malignancies dur- ing the past two decades have yielded higher rates of over- all survival and PFS and lower risks of NRM, grades 2–4 acute GvHD, and chronic GvHD. During this period, the age of patients and burden of comorbidity at the time of HCT has increased, and use of unrelated donors has also increased, thereby making allogeneic HCT more widely available for patients with otherwise incurable hemato- logic malignancies. These results should encourage the referral of elderly and medically infirm younger patients with hematologic malignancies for evaluation at a trans- plant center.
Disclosures
No conflicts of interest to disclose.
Contributions
JPC, BES, NG, GMcD, RS and BMS contributed to the con- ception 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 inter- preted data; all authors contributed to the writing and final apporval of the manuscript.
Acknowledgments
The authors are grateful to the research nurses and data coor- dinators who implemented the study protocols; to the many physi- cians, nurses, physician assistants, nurse practitioners, pharma- cists, and support staff who cared for our patients; and to the patients who allowed us to care for them and participated in our research. We are deeply indebted to Helen S. Crawford for assis- tance in preparing the manuscript, tables, and figures. The con- tent is solely the responsibility of the authors and does not repre- sent the official views of the institutions who provided funding support.
Funding
Research reported in this publication was supported by P01 HL36444, P01 HL122173, and T32 HL007093 from the NHLBI; P01 CA078902 and P30 CA015704 from the NCI and NIH; and grants from the Laura Landro Solomon Endowment Fund and Gabrielle’s Angels Foundation.
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