Transplantation of allogeneic CD34+-selected cells followed by early T-cell add-backs: favorable results in acute and chronic myeloid leukemia

• Published in: Cytotherapy (Oxford, England) Vol. 6; no. 6; pp. 533 - 542
• Main Authors: Kobbe, G., Fenk, R., Neumann, F., Bernhardt, A., Steidl, U., Kondakci, M., Graef, T., Aivado, M., Vaupel, M., Huenerlituerkoglu, A.-N., Kronenwett, R., Pape, H., Hildebrand, B., Germing, U., Haas, R.
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.12.2004; Informa UK Ltd
• Subjects: Adult; Antigens, CD34 - immunology; CD34 selection; Graft vs Host Disease; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - immunology; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - therapy; Leukemia, Myeloid, Acute - immunology; Leukemia, Myeloid, Acute - therapy; Middle Aged; Neoplasm, Residual; Prognosis; Survival Rate; T-Lymphocytes - immunology; T-Lymphocytes - transplantation; Transplantation Chimera; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome; unrelated donor transplantation; CD34 selection; unrelated donor transplantation
• ISSN: 1465-3249; 1477-2566
• DOI: 10.1080/14653240410005375

The aim of this study was to investigate preservation of anti-leukemic activity and protection from opportunistic infections after transplantation of allogeneic CD34+ cells in patients with hematologic malignancies and bad prognosis. Thirty-three patients [median age 42 years, range 23–55 years, diagnosis AML/myelodysplastic syndrome (MDS) 14, ALL nine, CML seven and multiple myeloma (MM) three] received myeloablative conditioning followed by infusion of selected CD34+ cells from matched unrelated donors (31) or HLA-identical siblings (two). Early donor lymphocyte infusions (DLI; 0.5 and 1.0×106 CD3+ cells/kg) were given while patients were on immunosuppressive therapy. Ninety-seven per cent of patients engrafted and 24 of 29 patients surviving more than 30 days received at least one pre-emptive DLI. Three patients (10%) developed acute (a)GvHD (two grade I–II, one grade III–IV) spontaneously, and 16 patients (67%) developed aGvHD after DLI (12 grade I–II, four grade III–IV). Eight of 24 evaluable patients developed chronic (c)GvHD (33%, six limited, two extensive). After a median follow-up of 590 days (range 138–1610 days) 18 patients were alive (55%), 16 in complete remission (CR), one in hematologic and one in molecular relapse. Seven patients died after relapse (21%) and eight died from transplantation-related causes (24%). Patients with myeloid malignancies had a significantly better survival than patients with ALL or MM (74% ± 10 vs. 30% ± 13, P<0.05). Early pre-emptive low-dose DLI following transplantation of selected CD34+ cells from unrelated donors after myeloablative conditioning is feasible and effective without undue toxicity, especially in patients with myeloid malignancies.