High-dose cytarabine and recombinant human granulocyte colony-stimulating factor for the treatment of resistant acute myelogenous leukemia.
Few salvage treatments are successful for patients with relapsed acute myelogenous leukemia after a short first remission, multiple relapses, or for patients with disease refractory to initial induction chemotherapy. To improve the results of salvage therapy we studied the efficacy and toxicity of a combination of G-CSF (5 mu tg/kg IV q day) used as a priming agent followed by continued exposure to G-CSF and high-dose cyatarabine (2 gm/m(2) IV q 12 hours x 12 doses) in fifteen adult patients with relapsed or refractory acute myelogenous leukemia. Nine of fourteen (64%; 95% confidence interval 35 to 87%) achieved complete remission, four failed to enter remission and one died of multiorgan system failure after progressive leukemia cutis despite chemotherapy-induced bone marrow aplasia. Median disease-free survival is 148 days and median survival from study entry for responding patient is 174 days. Three patients who achieved complete remission subsequently relapsed with a median time to relapse of 147 days. Median time to granulocyte >0.5 x 10(9)/L was 22 days (19 to 34 days) and the median time to platelet recovery >20 x 10(9)/L was 30 days (23 to 214 days). Although gastrointestinal toxicity was common, no patient developed severe cardiac, hepatic, pulmonary, or neurologic complications. An elevation in the percent of bone marrow blasts in S-phase after 48 hours of treatment with G-CSF was identified in 7 of 12 evaluable patients. These results demonstrate that the combination of G-CSF and high-dose cytarabine may be used as an effective salvage treatment for patients with resistant acute myelogenous leukemia.
Schiller
G
G
Department of Medicine, UCLA School of Medicine, Los Angeles, California, USA.
Emmanoulides
C
C
Iastrebner
M C
MC
Lee
M
M
Naeim
F
F
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D000069585:Filgrastim; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D012074:Remission Induction; D016879:Salvage Therapy; D015996:Survival Rate; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D007155:Immunologic Factors; D011994:Recombinant Proteins; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim