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Transplant Toxicities

Risk of sinusoidal obstruction syndrome in allogeneic stem cell transplantation after prior gemtuzumab ozogamicin treatment: a retrospective study from the Acute Leukemia Working Party of the EBMT

Bone Marrow Transplantation volume 52, pages 592–599 (2017)Cite this article

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Abstract

Gemtuzumab ozogamicin (GO) may increase the risk of sinusoidal obstruction syndrome (SOS) when used prior to allogeneic stem cell transplantation (HSCT). We assessed SOS incidence and outcomes after HSCT of 146 adults, with a median age of 50 years, previously receiving GO. SOS prophylaxis was used in 69 patients (heparin n=57, ursodeoxycholic acid n=8, defibrotide n=4). Cumulative incidence (CI) of SOS was 8% (n=11), with death in 3 patients. Median interval between last GO dose and HSCT was 130 days. Overall survival (OS) and SOS incidence did not differ for patients receiving GO ⩽3.5 months before HSCT and the others. CI of acute and chronic GVHD was 31% and 25%, respectively. Probability of OS and leukemia-free survival (LFS) at 5 years was 40% and 37%, respectively. Relapse incidence and non-relapse mortality were 42% and 21%, respectively. In multivariate analysis, active disease at HSCT was associated with relapse and worse LFS and OS (P<0.03). Liver abnormalities before HSCT correlated with worse OS (P<0.03). Use of low-dose GO prior to HSCT is associated with an acceptable SOS incidence. Prospective studies investigating the role and the utility of SOS prophylaxis are warranted.

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Acknowledgements

We thank Audrey Mailhol and Emmanuelle Polge for helping with data collection.

Author contributions

GB and MM designed the study. GB collected the data from the database of the ALWP of the EBMT (chaired by MM and AN). AC, RF, JEC, DB, MM, AR, NC, JMR, MS, JS, PAvdB, AB and GS were the principal investigators of the 11 highest recruiting centers of the study. ML, GB, MM and AN analyzed and interpreted the data. GB, MM and AN wrote or revised the manuscript, and all authors reviewed its final version.

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Author notes

  1. A Nagler and M Mohty: These authors contributed equally to this work.

Authors and Affiliations

  1. Hematology Department, Hôpital Saint Antoine, Service d'Hématologie et Thérapie Cellulaire, Paris, France

    G Battipaglia, M Labopin, A Ruggeri & M Mohty

  2. Hematology Department, Federico II University, Naples, Italy

    G Battipaglia

  3. Hospital Saint-Antoine, Paris University UPMC, Paris, France

    M Labopin & M Mohty

  4. Hematology Department, Azienda Ospedaliero Universitaria S Maria della Misericordia di Udine, Udine, Italy

    A Candoni & R Fanin

  5. Hematology Department, Institut Paoli-Calmettes, Marseille, France

    J El Cheikh & D Blaise

  6. Hematology Department 1G, Centre Hospitalier Lyon Sud, Pierre Benite, France

    M Michallet

  7. Hematology Department, Centre Becquerel, Rouen, France

    N Contentin

  8. Department of Hematology, ICO Badalona-Germans Trias i Pujol Hospital, Josep Carreras Leukemia Research Institute, Universitat Autonoma de Barcelona, Badalona, Spain

    J M Ribera

  9. Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany

    M Stadler

  10. Hematology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    J Sierra

  11. Hematology Department, Leiden University Medical Center, The Netherlands

    P A von dem Borne

  12. The Christie Clinic, Manchester, UK

    A Bloor

  13. Haematology Department, Hopital Saint-Louis, Paris, France

    G Socié

  14. Acute Leukemia Working Party of EBMT, Paris, France

    A Nagler & M Mohty

  15. Hematology Division, Chaim Sheba Medical Center, Tel Hashomer, Israel

    A Nagler

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  1. G Battipaglia
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  2. M Labopin
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  3. A Candoni
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  9. N Contentin
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  10. J M Ribera
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  15. G Socié
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  16. A Nagler
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  17. M Mohty
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Corresponding author

Correspondence to G Battipaglia.

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The authors declare no conflict of interest.

List of participating centers

List of participating centers

The following transplant centers (in alphabetical order of the country) contributed cases for the study: Department of Clinical Hematology, Universitair Ziekenhuis Brussel, Brussels, Belgium; Hématologie CHU Amiens, France, Institut Paoli Calmettes, Marseille, France; Hopital Saint Louis, Paris, France; Hopital Claude Huriez, Lille, France; Hopital A Michallon, Pole Cancérologie, Grenoble, France; Centre Hospitalier Lyon Sud, Pierre Benite, France; Hopital Saint Antoine, Paris, France; Centre Becquerel, Rouen, France; Hopital Saint Louis, Paris, France; Hannover Medical University, Hannover, Germany; Azienda Ospedaliero Universitaria S Maria della Misericordia di Udine, Italy; Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; ICO-Hospital Universitari Germans Trias i Pujol, Barcelona, Spain; Hospital Santa Creu i Sant Pau, Barcelona, Spain; Hospital Reina Sofia, Cordoba, Spain; The Christie Clinic, Manchester, United Kingdom.

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Battipaglia, G., Labopin, M., Candoni, A. et al. Risk of sinusoidal obstruction syndrome in allogeneic stem cell transplantation after prior gemtuzumab ozogamicin treatment: a retrospective study from the Acute Leukemia Working Party of the EBMT. Bone Marrow Transplant 52, 592–599 (2017). https://doi.org/10.1038/bmt.2016.302

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