Death after hematopoietic stem cell transplantation: changes over calendar year time, infections and associated factors

Jan Styczyński, Gloria Tridello, Linda Koster, Simona Iacobelli, Anja van Biezen, Steffie van der Werf, Małgorzata Mikulska, Lidia Gil, Catherine Cordonnier, Per Ljungman, Diana Averbuch, Simone Cesaro, Rafael de la Camara, Helen Baldomero, Peter Bader, Grzegorz Basak, Chiara Bonini, Rafael Duarte, Carlo Dufour, Jurgen Kuball, Arjan Lankester, Silvia Montoto, Arnon Nagler, John A Snowden, Nicolaus Kröger, Mohamad Mohty, Alois Gratwohl, Infectious Diseases Working Party EBMT, Jan Styczyński, Gloria Tridello, Linda Koster, Simona Iacobelli, Anja van Biezen, Steffie van der Werf, Małgorzata Mikulska, Lidia Gil, Catherine Cordonnier, Per Ljungman, Diana Averbuch, Simone Cesaro, Rafael de la Camara, Helen Baldomero, Peter Bader, Grzegorz Basak, Chiara Bonini, Rafael Duarte, Carlo Dufour, Jurgen Kuball, Arjan Lankester, Silvia Montoto, Arnon Nagler, John A Snowden, Nicolaus Kröger, Mohamad Mohty, Alois Gratwohl, Infectious Diseases Working Party EBMT

Abstract

Information on incidence, and factors associated with mortality is a prerequisite to improve outcome after hematopoietic stem cell transplantation (HSCT). Therefore, 55'668 deaths in 114'491 patients with HSCT (83.7% allogeneic) for leukemia were investigated in a landmark analysis for causes of death at day 30 (very early), day 100 (early), at 1 year (intermediate) and at 5 years (late). Mortality from all causes decreased from cohort 1 (1980-2001) to cohort 2 (2002-2015) in all post-transplant phases after autologous HSCT. After allogeneic HSCT, mortality from infections, GVHD, and toxicity decreased up to 1 year, increased at 5 years; deaths from relapse increased in all post-transplant phases. Infections of unknown origin were the main cause of infectious deaths. Lethal bacterial and fungal infections decreased from cohort 1 to cohort 2, not unknown or mixed infections. Infectious deaths were associated with patient-, disease-, donor type, stem cell source, center, and country- related factors. Their impact varied over the post-transplant phases. Transplant centres have successfully managed to reduce death after HSCT in the early and intermediate post-transplant phases, and have identified risk factors. Late post-transplant care could be improved by focus on groups at risk and better identification of infections of "unknown origin".

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Cumulative incidences of mortality after HSCT over four post-transplant phases and from cohort 1 to cohort 2. The stacked curves for the four post-transplant phases for the two cohorts combined in landmark analysis are presented: a 30-day mortality; b 100-day mortality (for patients alive at day 30); c 1-year mortality (for patients alive at day 100); d 5-year mortality (for patients alive at 1 year)
Fig. 2
Fig. 2
Main causes of death and of infectious deaths after HSCT. Main cause of death (in %)by post-transplant phase and by cohorts 1 and 2 (1 = cohort 1980–2001; 2 = cohort 2002–2015): a all patients; b allo-HSCT patients; c auto-HSCT patients. Cumulative incidences of mortality for the respective cause of death during the 4 post-transplant time periods, day 0 to day 30, day 30 to day 100, day 100 to 1 year, and 1 year to 5 years (see methods section for details), are shown
Fig. 3
Fig. 3
Main causes of death and of infectious deaths after HSCT. Causes of infectious deaths by post-transplant phase. Changes over time of causes of infectious deaths (in %) after HSCT for leukemia by post-transplant phase (1 = cohort 1980–2001; 2 = cohort 2002–2015): a all patients; b allo-HSCT patients; c auto-HSCT patients. Cumulative incidences of mortality for the respective cause of death during the 4 post-transplant time periods, day 0 to day 30, day 30 to day 100, day 100 to 1 year, and 1 year to 5 years (see methods section for details), are shown

References

    1. Gratwohl A, Brand R, Frassoni F, Rocha V, Niederwieser D, Reusser P, et al. Cause of death after allogeneic haematopoietic stem cell transplantation (HSCT) in early leukaemias: an EBMT analysis of lethal infectious complications and changes over calendar time. Bone Marrow Transpl. 2005;36:757–69. doi: 10.1038/sj.bmt.1705140.
    1. Gooley TA, Chien JW, Pergam SA, Hingorani S, Sorror ML, Boeckh M, et al. Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med. 2010;363:2091–101. doi: 10.1056/NEJMoa1004383.
    1. Gratwohl A, Pasquini MC, Aljurf M, Atsuta Y, Baldomero H, Foeken L, et al. One million haemopoietic stem-cell transplants: a retrospective observational study. Lancet Haematol. 2015;2:e91–100. doi: 10.1016/S2352-3026(15)00028-9.
    1. Passweg JR, Baldomero H, Bader P, Bonini C, Duarte RF, Dufour C, et al. Use of haploidentical stem cell transplantation continues to increase: the 2015 European Society for Blood and Marrow Transplant activity survey report. Bone Marrow Transpl. 2017;52:811–7. doi: 10.1038/bmt.2017.34.
    1. Sureda A, Bader P, Cesaro S, Dreger P, Duarte RF, Dufour C, et al. Indications for allo- and auto-SCT for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2015. Bone Marrow Transpl. 2015;50:1037–56. doi: 10.1038/bmt.2015.6.
    1. Gratwohl A, Baldomero H, Passweg J, Urbano-Ispizua A. Increasing use of reduced intensity conditioning transplants: report of the 2001 EBMT activity survey. Bone Marrow Transpl. 2002;30:813–31. doi: 10.1038/sj.bmt.1703819.
    1. Finke J, Schmoor C, Bethge WA, Ottinger HD, Stelljes M, Zander AR, et al. Prognostic factors affecting outcome after allogeneic transplantation for hematological malignancies from unrelated donors: results from a randomized trial. Biol Blood Marrow Transpl. 2012;18:1716–26. doi: 10.1016/j.bbmt.2012.06.001.
    1. Kolb HJ, Mittermuller J, Clemm C, Holler E, Ledderose G, Brehm G, et al. Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood. 1990;76:2462–5. doi: 10.1182/blood.V76.12.2462.2462.
    1. Averbuch D, Cordonnier C, Livermore DM, Mikulska M, Orasch C, Viscoli C, et al. Targeted therapy against multi-resistant bacteria in leukemic and hematopoietic stem cell transplant recipients: guidelines of the 4th European Conference on Infections in Leukemia (ECIL-4, 2011) Haematologica. 2013;98:1836–47. doi: 10.3324/haematol.2013.091330.
    1. Averbuch D, Orasch C, Cordonnier C, Livermore DM, Mikulska M, Viscoli C, et al. European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia. Haematologica. 2013;98:1826–35. doi: 10.3324/haematol.2013.091025.
    1. Tissot F, Agrawal S, Pagano L, Petrikkos G, Groll AH, Skiada A, et al. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica. 2017;102:433–44. doi: 10.3324/haematol.2016.152900.
    1. Winston DJ, Young JA, Pullarkat V, Papanicolaou GA, Vij R, Vance E, et al. Maribavir prophylaxis for prevention of cytomegalovirus infection in allogeneic stem cell transplant recipients: a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study. Blood. 2008;111:5403–10. doi: 10.1182/blood-2007-11-121558.
    1. Marty FM, Winston DJ, Rowley SD, Vance E, Papanicolaou GA, Mullane KM, et al. CMX001 to prevent cytomegalovirus disease in hematopoietic-cell transplantation. N Engl J Med. 2013;369:1227–36. doi: 10.1056/NEJMoa1303688.
    1. Marty FM, Ljungman P, Chemaly RF, Maertens J, Dadwal SS, Duarte RF, et al. Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation. N Engl J Med. 2017;377:2433–44. doi: 10.1056/NEJMoa1706640.
    1. Hahn T, Sucheston-Campbell LE, Preus L, Zhu X, Hansen JA, Martin PJ, et al. Establishment of definitions and review process for consistent adjudication of cause-specific mortality after allogeneic unrelated-donor hematopoietic cell transplantation. Biol Blood Marrow Transpl. 2015;21:1679–86. doi: 10.1016/j.bbmt.2015.05.019.
    1. Gratwohl A, Sureda A, Cornelissen J, Apperley J, Dreger P, Duarte R, et al. Alloreactivity: the Janus-face of hematopoietic stem cell transplantation. Leukemia. 2017;31:1752–9. doi: 10.1038/leu.2017.79.
    1. Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974;18:295–304. doi: 10.1097/00007890-197410000-00001.
    1. Gratwohl A, Sureda A, Baldomero H, Gratwohl M, Dreger P, Kröger N, et al. Economics and outcome after hematopoietic stemcell transplantation: a retrospective cohort study. EBioMedicine. 2015;2:2101–9. doi: 10.1016/j.ebiom.2015.11.021.
    1. Iacobelli S. Suggestions on the use of statistical methodologies in studies of the European Group for Blood and Marrow Transplantation. Bone Marrow Transpl. 2013;48(Suppl 1):S1–37. doi: 10.1038/bmt.2012.282.
    1. Klein JP, Moeschberger ML. Survival analysis: techniques for censored and truncated data. New York: Springer-Verlag; 2003.
    1. Meyers JD, Bowden RA, Counts GW. Infectious complications of marrow transplant: risk factors for infection. Prog Clin Biol Res. 1989;309:357–66.
    1. Gratwohl A, Brand R, McGrath E, van Biezen A, Sureda A, Ljungman P, et al. Use of the quality management system “JACIE” and outcome after hematopoietic stem cell transplantation. Haematologica. 2014;99:908–15. doi: 10.3324/haematol.2013.096461.
    1. Ljungman P, de la Camara R, Cordonnier C, Einsele H, Engelhard D, Reusser P, et al. Management of CMV, HHV-6, HHV-7 and Kaposi-sarcoma herpesvirus (HHV-8) infections in patients with hematological malignancies and after SCT. Bone Marrow Transpl. 2008;42:227–40. doi: 10.1038/bmt.2008.162.
    1. Styczynski J, van der Velden W, Fox CP, Engelhard D, de la Camara R, Cordonnier C, et al. Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines. Haematologica. 2016;101:803–11. doi: 10.3324/haematol.2016.144428.
    1. Tichelli André, Rovó Alicia, Gratwohl Alois. Late Pulmonary, Cardiovascular, and Renal Complications after Hematopoietic Stem Cell Transplantation and Recommended Screening Practices. Hematology. 2008;2008(1):125–133. doi: 10.1182/asheducation-2008.1.125.
    1. World Health Organization. WHO guiding principles on human cell, tissue and organ transplantation. Transplantation. 2010;90: 229–33.
    1. Snowden JA, McGrath E, Duarte RF, Saccardi R, Orchard K, Worel N, et al. JACIE accreditation for blood and marrow transplantation: past, present and future directions of an international model for healthcare quality improvement. Bone Marrow Transpl. 2017;52:1367–71. doi: 10.1038/bmt.2017.54.
    1. Hamblin A, Greenfield DM, Gilleece M, Salooja N, Kenyon M, Morris E, et al. Provision of long-term monitoring and late effects services following adult allogeneic haematopoietic stem cell transplant: a survey of UK NHS-based programmes. Bone Marrow Transpl. 2017;52:889–94. doi: 10.1038/bmt.2017.67.
    1. Miller PDE, de Silva TI, Skinner R, Gilleece M, Peniket A, Hamblin A, et al. Routine vaccination practice after adult and paediatric allogeneic haematopoietic stem cell transplant: a survey of UK NHS programmes. Bone Marrow Transpl. 2017;52:1082. doi: 10.1038/bmt.2017.87.

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