Dose-dense induction with sequential high-dose cytarabine and mitoxantone (S-HAM) and pegfilgrastim results in a high efficacy and a short duration of critical neutropenia in de novo acute myeloid leukemia: a pilot study of the AMLCG.
Dose density during early induction has been demonstrated to be one of the prime determinants for treatment efficacy in acute myeloid leukemia (AML). The German AML Cooperative Group has therefore piloted a dose-dense induction regimen sequential high-dose AraC and mitoxantrone followed by pegfilgrastim (S-HAM) in which 2 induction cycles are applied over 11 to 12 days instead of 25 to 29 days as used in conventional double induction, thereby increasing dose density 2-fold. Of 172 de novo AML patients (excluding acute promyelocytic leukemia), 61% reached a complete remission, 22% a complete remission with incomplete peripheral recovery, 7% had persistent leukemia, 10% died (early death) resulting in an overall response rate of 83%. Kaplan-Meier estimated survival at 2 years was 61% for the whole group (patients with unfavorable karyotypes, 38%; patients with favorable karyotypes, 69%; patients with intermediate karyotypes, 75%) after S-HAM treatment. Importantly, the compression of the 2 induction cycles into the first 11 to 12 days of treatment was beneficial for normal hematopoiesis as demonstrated by a significantly shortened duration of critical neutropenia of 31 days compared with 46 days after conventionally timed double induction.
Braess
Jan
J
Department of Internal Medicine III, Laboratory for Leukemia Diagnostics, Klinikum Grosshadern der LMU, München, Germany. jan.braess@med.uni-muenchen.de
Spiekermann
Karsten
K
Staib
Peter
P
Grüneisen
Andreas
A
Wörmann
Bernhard
B
Ludwig
Wolf-Dieter
WD
Serve
Hubert
H
Reichle
Albrecht
A
Peceny
Rudolf
R
Oruzio
Daniel
D
Schmid
Christoph
C
Schiel
Xaver
X
Hentrich
Marcus
M
Sauerland
Christina
C
Unterhalt
Michael
M
Fiegl
Michael
M
Kern
Wolfgang
W
Buske
Christian
C
Bohlander
Stefan
S
Heinecke
Achim
A
Baurmann
Herrad
H
Beelen
Dietrich W
DW
Berdel
Wolfgang E
WE
Büchner
Thomas
T
Hiddemann
Wolfgang
W
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D003561:Cytarabine / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000009:adverse effects / Q000627:therapeutic use*; D009503:Neutropenia / Q000139:chemically induced*; D010865:Pilot Projects; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012955:Societies, Medical; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
D011994:Recombinant Proteins; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D008942:Mitoxantrone; D000069585:Filgrastim