title: Allogeneic transplantation of selected peripheral CD34+ cells with controlled CD3+ cells add-back in high-risk patients.
abstract: We evaluated the feasibility of allogeneic transplantation of CliniMACS-selected peripheral CD34+ cells from siblings (four patients: AML-M4, M2, CLL, MDS); nonoptimal related donors (two patients: AML-M4, CML); and unrelated donors (two patients: CML, ALL, both without engraftment after preceding URDBMT). All patients had high-risk of aGVHD and/or graft failure due to multiple transplantation risk factors. Conditioning treatment was myeloablative (n=7) or nonmyeloablative (n=1). Immunosuppression consisted of CsA (n=8), Mtx (n=5), ATG (n=4). Selected CD34+ cells were transplanted (average 3.91 x 10(6)/kg, range 1.29 to 7.27 x 10(6)/kg) together with 0.01 to 0.5 x 10(7) CD3+ cells/kg to assure proper engraftment. The remaining CD34-negative fraction was cryopreserved for further CD3+ cell add-back. Average recovery and purity of CD34+ cells following CliniMACS selection were 74% and 97%. No severe complications were observed in the first 100 days. Regeneration times were satisfactory in seven of eight patients (87.5%) with ANO > 0.5 g/L and Plt > 50 g/L reached on average on days +26 and +32 (range 15 to 29 and 15 to 67), respectively. In three patients (37.5%) T-lymphocytes were added-back one to three times (due to low numbers of initially transfused CD3+ cells in two patients, in one patient with PRCA caused by ABO incompatibility). One to four additional transplantations of nonselected peripheral cells were performed on days +28 to +270 in consequence of infections (CMV-two patients; parvovirus-one patient), poor regeneration and residual disease (one patient) and prolonged transfusion dependency (one patient). Severe aGVHD grade III or IV developed in three patients (37.5%) following the nonselected cells transplantation. Finally, five patients (62.5%) are alive and in remission (median follow-up 815 days). We conclude that allogeneic transplantation of selected peripheral CD34+ cells (CliniMACS) with controlled add-back of CD3+ cells is an effective, well, tolerated procedure in high-risk patients.
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Silesian Medical University, Katowice, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Markiewicz
authors.forename: J
authors.initials: J
authors.lastname: Hołowiecki
authors.forename: J
authors.initials: J
authors.lastname: Wojnar
authors.forename: M
authors.initials: M
authors.lastname: Krawczyk-Kuliś
authors.forename: K
authors.initials: K
authors.lastname: Jagoda
authors.forename: S
authors.initials: S
authors.lastname: Giebel
authors.forename: T
authors.initials: T
authors.lastname: Kruzel
mesh_terms: D015703:Antigens, CD / Q000097:blood; D018952:Antigens, CD34 / Q000097:blood; D017252:CD3 Complex / Q000097:blood; D005260:Female; D006801:Humans; D018189:Immunomagnetic Separation; D007165:Immunosuppression Therapy / Q000379:methods; D007938:Leukemia / Q000628:therapy*; D019520:Living Donors / Q000706:statistics & numerical data; D008297:Male; D035781:Siblings; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000166:cytology; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D017252:CD3 Complex