Thymic recovery after allogeneic hematopoietic cell transplantation with non-myeloablative conditioning is limited to patients younger than 60 years of age

• Published in: Haematologica (Roma) 2011-02, Vol.96 (2), p.298-306
• Main Authors: CASTERMANS, Emilie, HANNON, Muriel, SANDMAIER, Brenda M, STORB, Rainer, BEGUIN, Yves, BARON, Frédéric, DUTRIEUX, Jacques, HUMBLET-BARON, Stephanie, SEIDEL, Laurence, CHEYNIER, Remi, WILLEMS, Evelyne, GOTHOT, André, VANBELLINGHEN, Jean-François, GEENEN, Vincent
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Child; Chronic Disease; Cyclophosphamide - administration & dosage; Female; Graft vs Host Disease - immunology; Graft vs Host Disease - prevention & control; Hematologic and hematopoietic diseases; Hematopoietic Stem Cell Transplantation; Humans; Life Sciences; Male; Medical sciences; Middle Aged; Original; Prognosis; Receptors, Antigen, T-Cell - metabolism; Survival Rate; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Thymus Gland - immunology; Thymus Gland - metabolism; Transplantation Conditioning; Transplantation, Homologous; Vidarabine - administration & dosage; Vidarabine - analogs & derivatives; Whole-Body Irradiation; Young Adult
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2010.029702

Long-term immune recovery in older patients given hematopoietic cell transplantation after non-myeloablative conditioning remains poorly understood. This prompted us to investigate long-term lymphocyte reconstitution and thymic function in 80 patients given allogeneic peripheral blood stem cells after non-myeloablative conditioning. Median age at transplant was 57 years (range 10-71). Conditioning regimen consisted of 2 Gy total body irradiation (TBI) with (n=46) or without (n=20) added fludarabine, 4 Gy TBI with fludarabine (n=6), or cyclophosphamide plus fludarabine (n=8). Stem cell sources were unmanipulated (n=56), CD8-depleted (n=19), or CD34-selected (n=5) peripheral blood stem cells. Immune recovery was assessed by signal-joint T-cell receptor excision circle quantification and flow cytometry. Signal-joint T-cell receptor excision circle levels increased from day 100 to one and two years after transplantation in patients under 50 years of age (n=23; P=0.02 and P=0.04, respectively), and in those aged 51-60 years (n=35; P=0.17 and P=0.06, respectively), but not in patients aged over 60 (n=22; P=0.3 and P=0.3, respectively). Similarly, CD4(+)CD45RA(+) (naïve) T-cell counts increased from day 100 to one and two years after transplantation in patients aged 50 years and under 50 (P=0.002 and P=0.02, respectively), and in those aged 51-60 (P=0.4 and P=0.001, respectively), but less so in patients aged over 60 (P=0.3 and P=0.06, respectively). In multivariate analyses, older patient age (P