COMPARISON BETWEEN BONE-MARROW AND G-CSF-MOBILIZED PERIPHERAL-BLOOD ALLOGRAFTS UNDERGOING CLINICAL-SCALE CD34(+) CELL SELECTION

Allogeneic transplantation of selected CD34(+) cells, rather than conv entional transplantation of bone marrow (BM) harvest or peripheral blo od (PB) leukapheresis products, has the advantage of reducing volume, facilitating storage and decreasing the amount of dimethylsulfoxide (D MSO) and cell lysis products, as well as reducing the number of T-lymp hocytes responsible for graft-versus-host disease (GVHD). Using biotin -avidin immunoaffinity columns (Ceprate(TM) SC system, CellPro; Bothel l, WA), CD34(+) cells were selected from each of 20 allografts (12 G-C SF-mobilized PB and 8 BM) collected from 14 HLA-identical normal healt hy donors for transplantation. After the clinical-scale selection, the median concentration of CD34(+) cells was 44.6% (range, 13% to 91%) i n BM and 50.4% (range, 15% to 77%) in PB. Whereas 75% of the PB allogr afts had a CD34(+) cell yield of more than 65%, only 37.5% of the BM a llografts achieved such a yield, p < 0.01. The number of T-lymphocytes in the selected CD34(+) cell allografts was reduced by two to three l ogs from a median of 4.2 x 10(9) to 7.8 x 10(5) CD3(+) cells. The enri chment in CD34(+) cells was 240-fold (range, 24- to 382-fold) in PB ve rsus only 34-fold (range, 14- to 108-fold) in BM. Also, the enrichment in clonogenic cells was significantly more in PB (median value of 38. 6-fold) than in BM (median value of 19.2-fold) and more in allografts from younger (< 50 years old) rather than older (greater than or equal to 50 years old) adult donors. A correlation was found between the pe rcentage of CD34 or CD3(+) cells before and after selection (r = 0.58 or r = 0.60, respectively, p < 0.05). Selective enrichment of the colo ny forming units-granulocyte-macrophage (CFU-GM) was found in all 20 a llografts. The progenitor cell recovery after freezing and thawing was similar in BM and PB allografts, with a mean of about 60% for the CFU -GM and BFU-E. In the same six donors, the CD34(+) cell yield was sign ificantly more in the PB after mobilization (median 78.5%, range (50% to 90%) than in the BM before mobilization (median 41.54, range 25% to 87%), p < 0.01. Ten patients with hematologic malignancies have been allotransplanted with 14 of the 20 selected CD34(+) cells either combi ned BM + PB (n = 4) or single (n = 6) grafts. Seven patients did not d evelop acute GVHD, and only two patients developed greater than or equ al to grade II GVHD, one of whom developed only grade II GVHD that res olved after brief treatment with corticosteriods. Only one patient sho wed chronic GVHD (skin and liver). The low incidence and severity of G VHD seen in the present study (only 30%) could be due to the two- to t hree-log reduction of T-lymphocytes in the selected CD34(+) cell allot ransplants. All 10 patients had stable hematological recovery, and sev en had full donor hematopoiesis. In conclusion, G-CSF-mobilized PB leu kapheresis products undergoing selection of CD34(+) cells have a great er yield and enrichment of progenitor cells than EM harvests collected from HLA-identical normal healthy donors for allogeneic transplantati on. The low incidence and severity of both acute and chronic GVHD (30% ) seen in the present study are very encouraging.