Reduced intensity conditioning and prophylactic DLI can cure patients with high-risk acute leukaemias if complete donor chimerism can be achieved.
23 patients with ALL (n=9) and AML (n=14) underwent nonmyeloablative stem cell transplantation (NST) from an HLA-identical donor after conditioning with fludarabine (180 mg/m(2)), busulfan (8 mg/kg) and anti-T-lymphocyte globulin (40 mg/kg). After NST, 20/23 patients engrafted. Ten out of 14 patients with uncontrolled disease reached complete remission. A multiplex-PCR using short tandem repeats was used for chimerism analysis and detected mixed chimerism (MC) in 14/22 evaluable patients (64%) after NST. Prophylactic donor lymphocyte infusions (DLI) were given to 11/14 patients with MC; MC converted to complete donor chimerism (CC) in 6/11 patients within 2-6 weeks. All patients with persistent MC with or without DLI relapsed during further follow-up. MC predicted impending relapse 4-52 weeks before clinical diagnosis. Ten of 23 patients (43%) are alive 2-34 months after stem cell transplantation. 12 of 23 patients (52%), have died from leukaemia after NST. One out of 23 patients has died from severe sepsis. In conclusion, NST leads to stable engraftment and complete remission in patients with advanced acute leukaemias. NST can cure a substantial proportion of these patients, but the relapse rate is still high. Repeated chimerism analysis is a useful tool to detect recipient cells, especially in patients without molecular markers of disease and can be used to monitor immunomodulatory therapies. MC is unstable in these patients and predicts impending relapse. Prophylactic DLI can convert MC to CC, which seemed to lower relapse risk.
Massenkeil
G
G
Department of Internal Medicine, University Hospital Charité, Campus Virchow-Klinikum, Germany.
Nagy
M
M
Lawang
M
M
Rosen
O
O
Genvresse
I
I
Geserick
G
G
Dörken
B
B
Arnold
R
R
D000328:Adult; D000368:Aged; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D020080:Tandem Repeat Sequences; D018183:Transplantation Chimera; D019172:Transplantation Conditioning