Delayed recovery after autologous peripheral hematopoietic cell transplantation: potential effect of a high number of total nucleated cells in the graft

Authors

  • Hélène Trébéden-Negre,

    1. From the Department of Biotherapy, Unité de Recherche Clinique, and the Department of Hematology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris; the Department of Hematology, AP-HP, Hôpital Necker, Paris; AP-HP, Transfusion Medicine Unit, Hôpital Cochin, Paris; and the Department of Hematology, AP-HP, Hôtel-Dieu, Paris, France.
    Search for more papers by this author
  • Michelle Rosenzwajg,

    1. From the Department of Biotherapy, Unité de Recherche Clinique, and the Department of Hematology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris; the Department of Hematology, AP-HP, Hôpital Necker, Paris; AP-HP, Transfusion Medicine Unit, Hôpital Cochin, Paris; and the Department of Hematology, AP-HP, Hôtel-Dieu, Paris, France.
    Search for more papers by this author
  • Marie-Laure Tanguy,

    1. From the Department of Biotherapy, Unité de Recherche Clinique, and the Department of Hematology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris; the Department of Hematology, AP-HP, Hôpital Necker, Paris; AP-HP, Transfusion Medicine Unit, Hôpital Cochin, Paris; and the Department of Hematology, AP-HP, Hôtel-Dieu, Paris, France.
    Search for more papers by this author
  • François Lefrere,

    1. From the Department of Biotherapy, Unité de Recherche Clinique, and the Department of Hematology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris; the Department of Hematology, AP-HP, Hôpital Necker, Paris; AP-HP, Transfusion Medicine Unit, Hôpital Cochin, Paris; and the Department of Hematology, AP-HP, Hôtel-Dieu, Paris, France.
    Search for more papers by this author
  • Nabih Azar,

    1. From the Department of Biotherapy, Unité de Recherche Clinique, and the Department of Hematology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris; the Department of Hematology, AP-HP, Hôpital Necker, Paris; AP-HP, Transfusion Medicine Unit, Hôpital Cochin, Paris; and the Department of Hematology, AP-HP, Hôtel-Dieu, Paris, France.
    Search for more papers by this author
  • Farhad Heshmati,

    1. From the Department of Biotherapy, Unité de Recherche Clinique, and the Department of Hematology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris; the Department of Hematology, AP-HP, Hôpital Necker, Paris; AP-HP, Transfusion Medicine Unit, Hôpital Cochin, Paris; and the Department of Hematology, AP-HP, Hôtel-Dieu, Paris, France.
    Search for more papers by this author
  • Ramdane Belhocine,

    1. From the Department of Biotherapy, Unité de Recherche Clinique, and the Department of Hematology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris; the Department of Hematology, AP-HP, Hôpital Necker, Paris; AP-HP, Transfusion Medicine Unit, Hôpital Cochin, Paris; and the Department of Hematology, AP-HP, Hôtel-Dieu, Paris, France.
    Search for more papers by this author
  • Jean-Paul Vernant,

    1. From the Department of Biotherapy, Unité de Recherche Clinique, and the Department of Hematology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris; the Department of Hematology, AP-HP, Hôpital Necker, Paris; AP-HP, Transfusion Medicine Unit, Hôpital Cochin, Paris; and the Department of Hematology, AP-HP, Hôtel-Dieu, Paris, France.
    Search for more papers by this author
  • David Klatzmann,

    1. From the Department of Biotherapy, Unité de Recherche Clinique, and the Department of Hematology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris; the Department of Hematology, AP-HP, Hôpital Necker, Paris; AP-HP, Transfusion Medicine Unit, Hôpital Cochin, Paris; and the Department of Hematology, AP-HP, Hôtel-Dieu, Paris, France.
    Search for more papers by this author
  • Françoise Norol

    1. From the Department of Biotherapy, Unité de Recherche Clinique, and the Department of Hematology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris; the Department of Hematology, AP-HP, Hôpital Necker, Paris; AP-HP, Transfusion Medicine Unit, Hôpital Cochin, Paris; and the Department of Hematology, AP-HP, Hôtel-Dieu, Paris, France.
    Search for more papers by this author

H. Trébéden-Negre, Service de Biothérapies, Groupe Hospitalier Pitié Salpêtrière, 47-83 Boulevard de l'Hôpital, 75013 Paris, France; e-mail: helene.trebeden-negre@psl.aphp.fr.

Abstract

BACKGROUND: Some patients demonstrate delayed recoveries after autologous hematopoietic stem cell transplantation despite infusion of an adequate number of CD34+ cells/kg and clinically stable status. Factors considered being possible predictors of this outcome in this context were explored.

STUDY DESIGN AND METHODS: A total of 246 patients were evaluated in terms of engraftment. Delayed recovery was defined by white blood cell recovery time exceeding mean + 1 SEM. Clinical factors and graft characteristics were examined. Comparisons between patients with normal or delayed engraftment were made. Proinflammatory cytokines and proteolytic enzyme quantification and CXCR4+ and CD44+ cell enumeration were performed on peripheral hematopoietic stem cells (PHSC) product samples of patients with delayed engraftment and patients with usual engraftment time.

RESULTS: Sixteen patients, who received at least 3 × 106 CD34+ cells/kg without known clinical factors likely to affect engraftment, demonstrated a delayed recovery time of over 20 days. Some graft variables were found to be significantly increased in these patients by univariate analysis. One variable was the total number of nucleated cells cryopreserved and infused. Among the nucleated cells, the absolute number of granulocytes before and after cryopreservation also differed significantly between the two groups. A multivariate analysis showed that the main predictive factor for delayed recovery was the number of nucleated cells in the graft (p = 0.0044). The influence of contaminating cells might be related to the release of elastase, matrix metalloproteinase-9, interleukin (IL)-1β, and IL-6 involved in stem cell homing.

CONCLUSION: Therefore, the numeration of total nucleated cells and granulocytes should be considered as a possible quality control variable of PHSCs submitted for cryopreservation.

Ancillary