Transplantation of allogeneic CD34+-selected cells followed by early T-cell add-backs: favorable results in acute and chronic myeloid leukemia.
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.
Kobbe
G
G
Department of Hematology, Oncology and Clinical Immunology Heinrich Heine University Düsseldorf Germany.
Fenk
R
R
Neumann
F
F
Bernhardt
A
A
Steidl
U
U
Kondakci
M
M
Graef
T
T
Aivado
M
M
Vaupel
M
M
Huenerlituerkoglu
A-N
AN
Kronenwett
R
R
Pape
H
H
Hildebrand
B
B
Germing
U
U
Haas
R
R
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
D018952:Antigens, CD34