Outcome of patients with acute myelogenous leukemia after second salvage therapy.
BACKGROUND
Although the prognosis is poor for patients with acute myelogenous leukemia (AML) who have disease recurrence after frontline therapy, this is a general reflection of first salvage therapies. The outcome of patients undergoing second salvage therapy in relation to complete response (CR) rates and survival has not been documented. The authors analyzed the outcome of patients with AML undergoing second salvage therapy, and identified prognostic factors associated with response and survival.


METHODS
The records of 594 patients with AML undergoing second salvage therapy from 1980 until 2004 were reviewed. The patient median age was 50 years. Salvage therapy included allogeneic stem cell transplantation (SCT) in 74 patients, standard-dose cytosine arabinoside (ara-C) combinations in 30 patients, high-dose ara-C combinations in 171 patients, non-ara-C combinations in 73 patients, and Phase I-II single agents in 246 patients.


RESULTS
Overall, 76 patients (13%) achieved CR. The median CR duration was 7 months. The median survival was 1.5 months, and the 1-year survival rate was 8%. A multivariate analysis of prognostic factors for CR identified the following 6 independent adverse factors: first CR duration < 6 months; second CR duration < 6 months; salvage therapy not including allogeneic SCT; non-inversion 16 AML; platelet counts < 50 x 10(9)/L, and leukocytosis > 50 x 10(9)/L. Patients were divided into low-risk (1-2 adverse factors; 8%), intermediate 1 (3 factors; 20%), intermediate 2 (4 factors; 38%), and high-risk groups (5-6 factors; 33%) with respective CR rates of 54%, 26%, 8%, and 0%. The respective 1-year survival rates were 36%, 21%, 6%, and 1%. A multivariate analysis for survival identified the following 7 independent adverse factors: first CR duration < 12 months; second CR duration < 6 months; bilirubin level > or = 1 mg/dL; albumin level < 3 g/dL; age > 60 years; bone marrow blasts > or = 50%; and year of therapy before 1991. Patients were divided into low-risk (0-2 adverse factors; 39%), intermediate (3 factors; 27%), and high-risk groups (> or = 4 factors; 34%) with estimated 1-year survival rates of 22%, 6%, and 0%, respectively. The respective CR rates were 26%, 8%, and 2%.


CONCLUSIONS
The current analysis established the outcome and prognostic factors associated with second salvage therapy in AML. It also proposed risk models and groups that could be used for comparison of results of present and future investigational strategies.
Giles
Francis
F
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, PO Box 301402, Houston, TX 77230-1402, USA. fgiles@mdanderson.org
O'Brien
Susan
S
Cortes
Jorge
J
Verstovsek
Srdan
S
Bueso-Ramos
Carlos
C
Shan
Jianqin
J
Pierce
Sherry
S
Garcia-Manero
Guillermo
G
Keating
Michael
M
Kantarjian
Hagop
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012074:Remission Induction; D016879:Salvage Therapy; D033581:Stem Cell Transplantation; D015996:Survival Rate; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D003561:Cytarabine