Quantitation of Mafosfamide-Resistant Pre-Colony-Forming Units in Allogeneic Bone Marrow Transplantation: Relationship With Rate of Engraftment and Evidence for Long-Lasting Reduction in Stem Cell Numbers

• Published in: Blood Vol. 87; no. 9; pp. 3963 - 3969
• Main Authors: Kirkland, Mark A., Spencer, Andrew, Davidson, R.John, McDonald, Christine, Goldman, John M.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.05.1996; The Americain Society of Hematology
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antineoplastic Agents - pharmacology; Biological and medical sciences; Bone Marrow Transplantation; Bone marrow, stem cells transplantation. Graft versus host reaction; Cell Count; Colony-Forming Units Assay; Cyclophosphamide - analogs & derivatives; Cyclophosphamide - pharmacology; Drug Resistance; Graft Rejection - pathology; Graft Survival; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - metabolism; Hematopoietic Stem Cells - pathology; Humans; Medical sciences; Predictive Value of Tests; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation, Homologous; Human; Resistance; Evaluation; Investigation method; Stem cell; Bone marrow; Engraftment; Graft; In vitro; Allogeneic system; Colony forming cell
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V87.9.3963.bloodjournal8793963

Current assays of human committed-stem cells are of limited value in predicting the rate of engraftment or in assessing the integrity of the stem cell pool after allogeneic bone marrow (BM) transplantation (BMT). We have used a limiting dilution assay of mafosfamide-resistant progenitors (pre-colony-forming units [CFU]), which are ancestral to committed progenitors such as CFU-granulocyte-macrophage (GM) to analyze the kinetics of myeloid engraftment after BMT and to assess the size of the stem cell pool at intervals up to 66 months thereafter. In 24 patients transplanted for chronic myeloid leukemia in chronic phase (eight with matched unrelated donors and 16 with sibling donors), the rate of neutrophil engraftment correlated strongly with the number of pre-CFU transfused per kilogram recipient body weight (r = .7, P < .005) but not with CFU-GM per kilogram or nucleated cells per kilogram. In 25 patients studied 6 to 66 months after allogeneic BMT, the mean number of pre-CFU in the marrow was 3.1/105 mononuclear cells (MNC) (median, 3.47; range, 0.4 to 23.3), compared with 24.7/105 MNC (median, 27.3; range, 4.2 to 180) in 25 normal subjects. CFU-GM were also reduced in these patients, but with considerable overlap into the normal range (mean ± SD: 54 ± 45.6 per 105 MNC; normal, 129 ± 61.6). Low pre-CFU but not low CFU-GM levels were associated with reduced peripheral blood white blood cell counts in post-BMT patients. Pre-CFU and CFU-GM levels were not related to the interval posttransplant and remained low for up to 66 months. We conclude that the pre-CFU assay measures a population of stem/progenitor cells that are important in the kinetics of engraftment after allogeneic BMT. Our data suggest that pre-CFU levels may remain low for some years after BMT in humans.