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Intensive chemotherapy followed by autologous stem cell transplantation in primary central nervous system lymphomas (PCNSLs). Therapeutic outcomes in real life—experience of the French Network

Bone Marrow Transplantation volume 57, pages 966–974 (2022)Cite this article

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Abstract

We analysed the therapeutic outcomes of all consecutive patients with primary central nervous system lymphoma (PCNSL) registered in the prospective French database for PCNSL and treated with intensive chemotherapy (IC) followed by autologous stem cell transplantation (IC-ASCT) between 2011 and November 2019 (271 patients recruited, 266 analysed). In addition, treatment-related complications of thiotepa-based IC-ASCT were analysed from the source files of 85 patients from 3 centers. Patients had received IC-ASCT either in first-line treatment (n = 147) or at relapse (n = 119). The median age at IC-ASCT was 57 years (range: 22–74). IC consisted of thiotepa-BCNU (n = 64), thiotepa-busulfan (n = 24), BCNU-etoposide-cytarabine-melphalan (BEAM, n = 36) and thiotepa-busulfan-cyclophosphamide (n = 142). In multivariate analysis, BEAM and ASCT beyond the first relapse were adverse prognostic factors for relapse risk. The risk of treatment-related mortality was higher for ASCT performed beyond the first relapse and seemed higher for thiotepa-busulfan-cyclophosphamide. Thiotepa-BCNU tends to result in a higher relapse rate than thiotepa-busulfan-cyclophosphamide and thiotepa-busulfan. This study confirms the role of IC-ASCT in first-line treatment and at first-relapse PCNSL (5-year overall survival rates of 80 and 50%, respectively). The benefit/risk ratio of thiotepa-busulfan/thiotepa-busulfan-cyclophosphamide-ASCT could be improved by considering ASCT earlier in the course of the disease and dose adjustment of the IC.

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Fig. 1: Outcomes according to line of treatment at IC-ASCT and to the type of IC.
Fig. 2: Relapse rate according to IC type.
Fig. 3: Main complications during hospitalization for ASCT (n = 85).

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Data availability

All data generated or analysed during this study are included in this published article (and its supplementary information files).

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Acknowledgements

We thank the clinicians involved in the French National “Lymphome Oculo-Cérébral” LOC network, part of the network for rare cancers of the central nervous system, “RENOCLIP-LOC Network”, approved by the French National Institute of Cancer (INCa).

Author information

Author notes

  1. These authors contributed equally: Laurence Schenone, Caroline Houillier, Marie Laure Tanguy, Carole Soussain.

Authors and Affiliations

  1. Université de Lorraine, Department of Hematology, CHRU de Nancy, Hôpital de Brabois, Nancy, France

    Laurence Schenone

  2. Department of Neurology, APHP, Sorbonne Université, IHU, ICM, Groupe Hospitalier Pitié-Salpêtrière, Paris, France

    Caroline Houillier & Khê Hoang-Xuan

  3. Department of Biostatistics, Institut Gustave Roussy, Villejuif, Paris, France

    Marie Laure Tanguy

  4. Department of Hematology, APHP, Sorbonne Université, Hôpital Pitié-Salpêtrière, Paris, France

    Sylvain Choquet

  5. Department of Hematology, Institut Curie, Site Saint-Cloud, France

    Kossi Agbetiafa & Carole Soussain

  6. Department of Hematology, Centre Hospitalier Lyon Sud, Lyon, France

    Hervé Ghesquières

  7. Department of Hematology, CHU de Caen Normandie, Caen, France

    Gandhi Damaj

  8. Department of Hematology, Institut Bergonié, Bordeaux, France

    Anna Schmitt

  9. Department of hematology and cell therapy, University Hospital of Bordeaux, F-33000, Bordeaux, France

    Krimo Bouabdallah

  10. Department of Neurology Pôle NNORR, Hôpitaux Civils de Colmar, Colmar, France

    Guido Ahle

  11. Department of Hematology, CHU de Grenoble, Grenoble, France

    Remy Gressin

  12. Department of Hematology, Institut de Cancérologie Lucien Neuwirth, Saint-Priest-en-Jarez, France

    Jérôme Cornillon

  13. Department of Hematology, CHU Rennes, Rennes, France

    Roch Houot

  14. Department of Hematology, CHU Amiens, Amiens, France

    Jean-Pierre Marolleau

  15. Department of Hematology, Institut de Cancérologie Strasbourg Europe, Strasbourg, France

    Luc-Matthieu Fornecker

  16. Department of Neuro-oncology, AP-HM, CHU Timone, Marseille, France

    Olivier Chinot

  17. Department of Hematology, Centre Antoine Lacassagne, Nice, France

    Frédéric Peyrade

  18. Hôpital Privé de Provence, Pôle de cancérologie, Aix-en-Provence, France

    Reda Bouabdallah

  19. Department of Hematology, CHU Clermont-Ferrand, Clermont-Ferrand, France

    Cécile Moluçon-Chabrot

  20. Department of Hematology and Cellular Therapy, CHU de Tours, Tours, France

    Emmanuel Gyan

  21. Department of Hematology, CHRU de Besançon, Besançon, France

    Adrien Chauchet

  22. Department of Hematology, CHU Dijon Bourgogne, Dijon, France

    Olivier Casasnovas

  23. Department of Hematology, Institut Universitaire du Cancer de Toulouse, Toulouse, France

    Lucie Oberic

  24. Department of Hematology and cellular Therapy, CHU de Poitiers, Poitiers, France

    Vincent Delwail

  25. Department of Hematology, CHU Dupuytren Limoges, Limoges, France

    Julie Abraham

  26. Department of Hematology, CH Saint Jean, Perpignan, France

    Virginie Roland

  27. Department of Hematology, CHU Nimes Caremeau, Nimes, France

    Agathe Waultier-Rascalou

  28. Department of Hematology, CHU Paris Centre Site Cochin, Paris, France

    Lise Willems

  29. Institute of Hematology-transfusion, CHRU de Lille, Lille, France

    Franck Morschhauser

  30. Department of Oncology, Institut regional cancer Montpellier, Montpellier, France

    Michel Fabbro

  31. Department of Neurology, AP-HP, Hôpital Saint-Louis, Paris, France

    Renata Ursu

  32. Department of Hematology, AP-HP, Hôpital Saint-Louis, Paris, France

    Catherine Thieblemont

  33. Department of Hematology, Centre Henri Becquerel, Rouen, France

    Fabrice Jardin

  34. Department of Hematology, CHRU de Brest, Brest, France

    Adrian Tempescul

  35. Department of Ophthalmology, Institut Curie, Paris, France

    Denis Malaise

  36. Institut Curie, PSL University, Inserm U1288, Laboratoire d’Imagerie Translationnelle en Oncologie, Orsay, France

    Denis Malaise

  37. Department of Ophthalmology, APHP, Hôpital Pitié-Salpêtrière, Paris, France

    Valérie Touitou

  38. Department of Neuro-radiology, APHP, Hôpital Pitié-Salpêtrière, Paris, France

    Lucia Nichelli

  39. Department of biological Hematology, APHP, Hôpital Pitié-Salpêtrière, Paris, France

    Magali Le Garff-Tavernier

  40. Department of Hepato gastroenterology, APHP, Hôpital Beaujon, Paris, France

    Aurélie Plessier

  41. Department of functional explorations, APHP, Hôpital Necker, Paris, France

    Philippe Bourget

  42. Department of Hematology, CHRU de Nancy, Hôpital de Brabois, Nancy, France

    Caroline Bonmati

  43. Université de Lorraine, CNRS, Inria, IECL, F-54000, Nancy, France

    Sophie Wantz-Mézières

  44. Pharmacy department, CHR Metz-Thionville, Hôpital de Mercy, Metz, France

    Quentin Giordan

  45. Department of Hematology, CHR Metz-Thionville, Hôpital de Mercy, Metz, France

    Véronique Dorvaux

  46. Intensive care department, University Hospital Ambroise Paré, AP-HP, Boulogne-Billancourt, France

    Cyril Charron

  47. Department of Neurology, Hôpital Foch, Suresnes, France

    Waliyde Jabeur

  48. Department of Neurology, CHRU de Nancy, Hôpital Central, Nancy, France

    Luc Taillandier

  49. INSERM U932 Institut Curie, PSL Research University, Paris, France

    Carole Soussain

  50. CHU Pitié Salpêtrière, Paris, France

    Caroline Houillier, Sylvain Choquet, Khê Hoang-Xuan & Valérie Touitou

  51. Institut Curie, Saint Cloud, France

    Carole Soussain, Nathalie Cassoux & Denis Malaise

  52. Hôpital Saint-Louis, Paris, France

    Renata Ursu

  53. CHU Paris Centre Site Cochin, Paris, France

    Lise Willems

  54. CHU Lyon Sud, Lyon, France

    Hervé Ghesquières

  55. Institut Bergonié, Bordeaux, France

    Anna Schmitt

  56. CHU de la Timone, Marseille, France

    Olivier Chinot & Emeline Tabouret

  57. CHU de Nancy, Nancy, France

    Luc Taillandier & Marie Blonski

  58. CHU de Rennes, Rennes, France

    Roch Houot

  59. Hôpitaux Civils, Colmar, France

    Guido Ahle

  60. CHU de Caen, Caen, France

    Gandhi Damaj

  61. CHU de Clermont-Ferrand, Clermont-Ferrand, France

    Cécile Moluçon-Chabrot

  62. CHU de Poitiers, Poitiers, France

    Vincent Delwail

  63. Institut du Cancer de Montpellier Val d’Aurelle, Montpellier, France

    Michel Fabbro

  64. Centre Henri Becquerel, Rouen, France

    Fabrice Jardin

  65. CHU de Besançon, Besançon, France

    Adrien Chauchet

  66. CHRU de Lille, Lille, France

    Franck Morschhauser

  67. CHU de Dijon, Dijon, France

    Olivier Casasnovas

  68. CHU de Grenoble, Grenoble, France

    Rémy Gressin

  69. CHU de Strasbourg, Strasbourg, France

    Luc-Matthieu Fornecker

  70. CHU de Limoges, Limoges, France

    Julie Abraham

  71. CHU d’Amiens, Amiens, France

    Jean-Pierre Marolleau

  72. CHU de Brest, Brest, France

    Adrian Tempescul

  73. Institut de Cancérologie de l’Ouest, Saint Herblain, France

    Philippe Agapé

  74. Institut Universitaire du Cancer de Toulouse, Toulouse, France

    Lucie Oberic

  75. CHU Tours, Tours, France

    Emmanuel Gyan

  76. Centre Antoine Lacassagne, Nice, France

    Frédéric Peyrade

  77. CHU de Nantes, Nantes, France

    Thomas Gastinne

Authors
  1. Laurence Schenone
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  2. Caroline Houillier
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  3. Marie Laure Tanguy
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  4. Sylvain Choquet
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  5. Kossi Agbetiafa
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  6. Hervé Ghesquières
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  7. Gandhi Damaj
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  8. Anna Schmitt
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  9. Krimo Bouabdallah
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  10. Guido Ahle
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  11. Remy Gressin
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  12. Jérôme Cornillon
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  13. Roch Houot
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  14. Jean-Pierre Marolleau
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  15. Luc-Matthieu Fornecker
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  16. Olivier Chinot
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  17. Frédéric Peyrade
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  18. Reda Bouabdallah
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  19. Cécile Moluçon-Chabrot
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  20. Emmanuel Gyan
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  21. Adrien Chauchet
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  22. Olivier Casasnovas
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  23. Lucie Oberic
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  24. Vincent Delwail
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  25. Julie Abraham
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  26. Virginie Roland
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  27. Agathe Waultier-Rascalou
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  28. Lise Willems
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  29. Franck Morschhauser
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  30. Michel Fabbro
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  31. Renata Ursu
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  32. Catherine Thieblemont
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  33. Fabrice Jardin
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  34. Adrian Tempescul
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  35. Denis Malaise
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  36. Valérie Touitou
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  37. Lucia Nichelli
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  38. Magali Le Garff-Tavernier
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  39. Aurélie Plessier
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  40. Philippe Bourget
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  41. Caroline Bonmati
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  42. Sophie Wantz-Mézières
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  43. Quentin Giordan
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  44. Véronique Dorvaux
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  45. Cyril Charron
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  46. Waliyde Jabeur
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  47. Khê Hoang-Xuan
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  48. Luc Taillandier
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  49. Carole Soussain
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Consortia

on behalf of the French network for oculocerebral lymphoma (LOC network)

  • Caroline Houillier
  • , Sylvain Choquet
  • , Khê Hoang-Xuan
  • , Valérie Touitou
  • , Carole Soussain
  • , Nathalie Cassoux
  • , Denis Malaise
  • , Renata Ursu
  • , Lise Willems
  • , Hervé Ghesquières
  • , Anna Schmitt
  • , Olivier Chinot
  • , Emeline Tabouret
  • , Luc Taillandier
  • , Marie Blonski
  • , Roch Houot
  • , Guido Ahle
  • , Gandhi Damaj
  • , Cécile Moluçon-Chabrot
  • , Vincent Delwail
  • , Michel Fabbro
  • , Fabrice Jardin
  • , Adrien Chauchet
  • , Franck Morschhauser
  • , Olivier Casasnovas
  • , Rémy Gressin
  • , Luc-Matthieu Fornecker
  • , Julie Abraham
  • , Jean-Pierre Marolleau
  • , Adrian Tempescul
  • , Philippe Agapé
  • , Lucie Oberic
  • , Emmanuel Gyan
  • , Frédéric Peyrade
  •  & Thomas Gastinne

Contributions

LS: conceived and designed the work that led to the submission, acquired data, and played an important role in interpreting the results, drafted and revised the manuscript, approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. CS: conceived and designed the work that led to the submission, acquired data, and played an important role in interpreting the results, drafted and revised the manuscript, approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. CH: Retrieved data from the database, approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. MLT: performed the statistical analyses, revised the manuscript and approved the final version. LT: acquired data, approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. SC: acquired data, approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. KA: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. HG: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. GD: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. AS: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. KB: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. GA: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. RG: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. JC: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. RH: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. JPM: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. LMF: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. OC: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. FP: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. RB: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. CMC: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. EG: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. AC: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. OC: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. LO: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. VDE: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. JA: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. VR: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. AWR: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. LW: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. FM: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. MF: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. RU: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. CT: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. FJ: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. AT: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. DM: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. VT: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. LN: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. MLGT: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. AP: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. PB: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. CB: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. SWM: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. QG: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. VD: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. CC: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. WJ: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. KHX: acquired data and approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Carole Soussain.

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Schenone, L., Houillier, C., Tanguy, M.L. et al. Intensive chemotherapy followed by autologous stem cell transplantation in primary central nervous system lymphomas (PCNSLs). Therapeutic outcomes in real life—experience of the French Network. Bone Marrow Transplant 57, 966–974 (2022). https://doi.org/10.1038/s41409-022-01648-z

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