Long-term survival in refractory acute myeloid leukemia after sequential treatment with chemotherapy and reduced-intensity conditioning for allogeneic stem cell transplantation.
A sequential regimen of chemotherapy, reduced-intensity conditioning (RIC) for allogeneic stem cell transplantation (SCT), and prophylactic donor lymphocyte transfusion (pDLT) was studied in 103 patients with refractory acute myeloid leukemia (AML). According to published criteria, refractoriness was defined by primary induction failure (PIF; n = 37), early (n = 53), refractory (n = 8), or second (n = 5) relapse. Chemotherapy consisted of fludarabine (4 x 30 mg/m(2)), cytarabine (4 x 2 g/m(2)), and amsacrine (4 x 100 mg/m(2)), followed 4 days later by RIC, comprising 4 Gy total body irradiation (TBI), cyclophosphamide, and antithymocyte globulin. Patients without graft-versus-host disease (GvHD) at day +120 received pDLT in escalating doses. Patients' median age was 51.8 years. Before conditioning, 99 patients had active disease, 3 were aplastic, 1 was in second complete remission (CR2). Forty-one patients had family donors, 62 had unrelated donors. With a 25-month median follow-up, overall survival (OS) at 1, 2, and 4 years was 54%, 40%, and 32%; the respective leukemia-free survival (LFS) was 47%, 37%, and 30%. Patients with PIF showed a 2-year OS of 62.5%. OS was 87% in 17 patients receiving pDLT. One-year cumulative incidence of leukemic death and non-relapse-mortality was 28.7% and 17.2%. In a multivariate analysis, more than 2 courses of prior chemotherapy were the strongest predictor for poor outcome (P = .007; HR = 3.01 [OS]; P = .002; HR = 3.25 [LFS]). These results indicate a high activity of the regimen in refractory AML.
Schmid
Christoph
C
Department of Internal Medicine III, José Carreras Unit for Hematopoietic Stem Cell Transplantation, Ludwig-Maximilians-University Hospital, Marchioninistr 15, 81379 Munich, Germany. christoph.schmid@2med.zk.augsburg-med.de
Schleuning
Michael
M
Schwerdtfeger
Rainer
R
Hertenstein
Bernd
B
Mischak-Weissinger
Eva
E
Bunjes
Donald
D
Harsdorf
Stephanie V
SV
Scheid
Christoph
C
Holtick
Udo
U
Greinix
Hildegard
H
Keil
Felix
F
Schneider
Barbara
B
Sandherr
Michael
M
Bug
Gesine
G
Tischer
Johanna
J
Ledderose
Georg
G
Hallek
Michael
M
Hiddemann
Wolfgang
W
Kolb
Hans-Jochem
HJ
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007951:Leukemia, Myeloid / Q000401:mortality / Q000628:therapy*; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D016879:Salvage Therapy / Q000379:methods*; D016019:Survival Analysis; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous