title: Transplantation of allogeneic CD34+-selected cells followed by early T-cell add-backs: favorable results in acute and chronic myeloid leukemia.
abstract: BACKGROUND
  The aim of this study was to investigate preservation of anti-leukemic activity and protection from opportunistic infections after transplantation of allogeneic + cells in patients with hematologic malignancies and bad prognosis. Methods 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 x 10(6) CD3+ cells/kg) were given while patients were on immunosuppressive therapy.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hematology, Oncology and Clinical Immunology Heinrich Heine University Düsseldorf Germany.
authors.forename: G
authors.initials: G
authors.lastname: Kobbe
authors.forename: R
authors.initials: R
authors.lastname: Fenk
authors.forename: F
authors.initials: F
authors.lastname: Neumann
authors.forename: A
authors.initials: A
authors.lastname: Bernhardt
authors.forename: U
authors.initials: U
authors.lastname: Steidl
authors.forename: M
authors.initials: M
authors.lastname: Kondakci
authors.forename: T
authors.initials: T
authors.lastname: Graef
authors.forename: M
authors.initials: M
authors.lastname: Aivado
authors.forename: M
authors.initials: M
authors.lastname: Vaupel
authors.forename: A-N
authors.initials: AN
authors.lastname: Huenerlituerkoglu
authors.forename: R
authors.initials: R
authors.lastname: Kronenwett
authors.forename: H
authors.initials: H
authors.lastname: Pape
authors.forename: B
authors.initials: B
authors.lastname: Hildebrand
authors.forename: U
authors.initials: U
authors.lastname: Germing
authors.forename: R
authors.initials: R
authors.lastname: Haas
mesh_terms: D000328:Adult; D018952:Antigens, CD34 / Q000276:immunology*; D006086:Graft vs Host Disease; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000628:therapy*; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000628:therapy*; D008875:Middle Aged; D018365:Neoplasm, Residual; D011379:Prognosis; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation*; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D018952:Antigens, CD34