Allogeneic transplantation of selected peripheral CD34 + cells with controlled CD3 + cells add-back in high-risk patients

• Published in: Transplantation proceedings Vol. 36; no. 10; pp. 3194 - 3199
• Main Authors: Markiewicz, M., Hołowiecki, J., Wojnar, J., Krawczyk-Kuliś, M., Jagoda, K., Giebel, S., Krużel, T.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.12.2004; Elsevier Science
• Subjects: Antigens, CD - blood; Antigens, CD34 - blood; Biological and medical sciences; CD3 Complex - blood; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunomagnetic Separation; Immunosuppression - methods; Leukemia - therapy; Living Donors - statistics & numerical data; Male; Medical sciences; Siblings; Stem Cell Transplantation - methods; Stem Cells - cytology; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Tissue, organ and graft immunology; Transplantation Conditioning - methods; Transplantation, Homologous; Human; Medicine; High risk; Treatment; Surgery; Homograft; Graft; Transplantation; Cell
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2004.09.052

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 × 10 6/kg, range 1.29 to 7.27 × 10 6/kg) together with 0.01 to 0.5 × 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.