Infused total nucleated cell dose is a better predictor of transplant outcomes than CD34+ cell number in reduced-intensity mobilized peripheral blood allogeneic hematopoietic cell transplantation

• Published in: Haematologica (Roma) 2016-04, Vol.101 (4), p.499-505
• Main Authors: Martin, Paul S, Li, Shuli, Nikiforow, Sarah, Alyea, 3rd, Edwin P, Antin, Joseph H, Armand, Philippe, Cutler, Corey S, Ho, Vincent T, Kekre, Natasha, Koreth, John, Luckey, C John, Ritz, Jerome, Soiffer, Robert J
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Antigens, CD34 - analysis; Biomarkers - analysis; Cell Count; Cell Nucleus - immunology; Chronic Disease; Female; Gene Expression; Graft vs Host Disease - immunology; Graft vs Host Disease - mortality; Graft vs Host Disease - pathology; Graft vs Host Disease - prevention & control; Granulocyte Colony-Stimulating Factor - pharmacology; Hematologic Neoplasms - immunology; Hematologic Neoplasms - mortality; Hematologic Neoplasms - pathology; Hematologic Neoplasms - therapy; Hematopoietic Stem Cell Mobilization - methods; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - immunology; Humans; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; Male; Middle Aged; Peripheral Blood Stem Cell Transplantation - methods; Retrospective Studies; Survival Analysis; Transplantation Conditioning - methods; Transplantation, Homologous; Treatment Outcome
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2015.134841

Mobilized peripheral blood is the most common graft source for allogeneic hematopoietic stem cell transplantation following reduced-intensity conditioning. In assessing the effect of donor cell dose and graft composition on major transplant outcomes in the reduced-intensity setting, prior studies focused primarily on CD34(+)cell dose and reported conflicting results, especially in relation to survival end-points. While the impact of total nucleated cell dose has been less frequently evaluated, available studies suggest higher total nucleated cell dose is associated with improved survival outcomes in the reduced-intensity setting. In order to further explore the relationship between CD34(+)cell dose and total nucleated cell dose on reduced-intensity transplant outcomes, we analyzed the effect of donor graft dose and composition on outcomes of 705 patients with hematologic malignancies who underwent reduced-intensity peripheral blood stem cell transplantation at the Dana Farber Cancer Institute from 2000 to 2010. By multivariable analysis we found that higher total nucleated cell dose (top quartile; ≥10.8 × 10(10)cells) was associated with improved overall survival [HR 0.69 (0.54-0.88),P=0.0028] and progression-free survival [HR 0.68 (0.54-0.85),P=0.0006]. Higher total nucleated cell dose was independently associated with decreased relapse [HR 0.66 (0.51-0.85),P=0.0012] and increased incidence of chronic graft-versus-host disease [HR 1.4 (1.12-1.77),P=0.0032]. In contrast, higher doses of CD34(+)cells (top quartile; ≥10.9 × 10(6)/kg) had no significant effect on graft-versus-host disease or survival outcomes. These data suggest total nucleated cell dose is a more relevant prognostic variable for reduced-intensity transplant outcomes than the more commonly studied CD34(+)cell dose.