Subject(s)
Cancer Vaccines/administration & dosage , Fusion Proteins, bcr-abl/chemistry , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Adult , Aged , Amino Acid Sequence , CD4-Positive T-Lymphocytes/immunology , Cancer Vaccines/therapeutic use , Enzyme-Linked Immunosorbent Assay , Female , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/immunology , Male , Middle Aged , Molecular Sequence Data , Pilot ProjectsABSTRACT
Acute promyelocytic leukemia (APL) is a rare subtype of acute myeloid leukemia (AML) for which a number of targeted therapies have been developed. The "targets" have included both genotypic and phenotypic features of the disease. The application of monoclonal antibodies (MAbs) to this disease to date have been limited to a relatively small number of studies where this therapy has been used to supplement effective approaches to the disease. The preliminary results have been promising, and further development of this modality as an effective adjunct to existing treatment regimens will most certainly occur in the near future.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Leukemia, Promyelocytic, Acute/drug therapy , Aminoglycosides/therapeutic use , Animals , Antibodies, Monoclonal, Humanized , Antigens, CD/immunology , Antigens, Differentiation, Myelomonocytic/immunology , Gemtuzumab , HL-60 Cells , Humans , Mice , Sialic Acid Binding Ig-like Lectin 3 , Treatment OutcomeABSTRACT
Given the high treatment-related mortality in elderly patients with acute myelogenous leukemia (AML), we undertook a study using granulocyte colony-stimulating factor (G-CSF) following chemotherapy in an effort to ameliorate toxicity. Patients ( > 60 years) received induction with idarubicin 12 mg/m2/day x 3 and cytosine arabinoside (Ara-C) 200 mg/m2/day x 5. A second course of chemotherapy consisting of mitoxantrone 12mg/m2/day x 3, etoposide (VP-16) 150 mg/m2/day x 3 and Ara-C 200 mg/m2/day x 4 was given approximately 1 month after achieving a complete remission (CR) or immediately if patients failed the first induction. Twenty-four hours following completion of the chemotherapy, G-CSF (10 micrograms/kg/day continuous i.v. infusion) was started. A historical control group of 28 patients treated without G-CSF was used for comparison. Twenty-six patients were evaluable for response. Following induction, the recovery of neutrophils to greater than 500/microliters and 1000/microliters was more raped in the responders who received G-CSF compared to historical controls (median 13 vs 17 days, P = 0.008; 14 vs 19 days, P = 0.005). The toxic death rate of 8% in the study group was significantly lower than the 32% mortality observed in the historical controls (P = 0.04). There was no difference in supportive care requirements or infectious complications. The complete remission (CR) rate was 58% in the entire study group with 71% of de novo AML patients achieving CR. Disease-free survival and overall survival were comparable between the study and historical control groups. These results indicate that G-CSF benefits elderly patients after intensive chemotherapy for AML by decreasing the duration of neutropenia. The reduced neutropenic period may have contributed to the small number of early toxic deaths.