Critical role of flow cytometry in evaluating peripheral blood hematopoietic stem cell grafts

In the late 1950s, Thomas et al. (1) successfully trans-planted bone marrow cells into supralethally irradiatedrecipients, and until the 1990s, the majority of autologousand allogeneic hematopoietic stem/progenitor cell trans-plants were performed utilizing bone marrow as a sourceof stem cells. In the mid-1980s, reports demonstrated thefeasibility of obtaining clinically useful numbers of periph-eral blood stem/progenitor cells (HPSC) from cancer pa-tients recovering from chemotherapy (2). By the early1990s, the availability of a number of hematopoietic cyto-kines used either singly or in combination and/or withchemotherapy facilitated the harvesting of peripheralblood stem cells (PBSC) (3). This development, coupledwith clear data that time to hematopoietic reconstitutionis significantly shorter with PBSC compared to bone mar-row, has led to the widespread use of PBSC for autologousand, increasingly, allogeneic transplantation (reviewed in4). More recently, cord blood has provided a source ofHPSC, with an estimate of over 2,500 transplants per-formed worldwide since the first one in 1988 (5). Tradi-tionally, the absolute mononuclear count in relation topatient body weight was used to predict the engraftmentpotential of bone marrow and, more recently, cord blood.However, due to the variable HPSC content of peripheralblood, this number is unreliable. Initially, colony-formingcell (CFC) assays were used as a surrogate for PBSC, butthis test has the limitation of requiring 10–14 days toperform, making it unsuitable for planning apheresisschedules. In addition, CFC assays are subjective and lackstandardization in both methodology and reagents.