Initial treatment for patients with CML.
For adult patients who present with chronic myeloid leukemia (CML) in chronic phase it is now generally agreed that initial treatment should start with the tyrosine kinase inhibitor (TKI) imatinib at 400 mg daily. Five years after starting imatinib about 60% of these patients will be in complete cytogenetic response (CCyR), still taking imatinib; an appreciable proportion of these will have achieved a major molecular response, defined as a 3-log reduction in the level of BCR-ABL1 transcripts in their blood. The patients in CCyR seem to have a very low risk of relapse to chronic phase or of progression to advanced phase. Other patients may be resistant to imatinib or may experience significant side effects that require change of therapy. The best method of monitoring responding patients is to enumerate Philadelphia chromosome-positive marrow metaphases at 3-month intervals until CCyR and to perform RQ-PCR for BCR-ABL1 transcripts at 3-month intervals after starting imatinib. The recommendations for defining "failure" and "sub-optimal response" proposed by the European LeukemiaNet in 2006 have proved to be a major contribution to assessing responses in individual patients and are now being updated. Patients who fail imatinib may respond to second-generation TKIs, but allogeneic stem cell transplantation still plays an important role for eligible patients who fare badly with TKIs. Patients who present in advanced phases of CML should be treated initially with TKI alone or with TKI in conjunction with cytotoxic drugs, but their overall prognosis is likely to be much inferior to that of those presenting in early chronic phase.
Goldman
John M
JM
Department of Hematology, Imperial College London, Hammersmith Hospital, London, United Kingdom. jgoldman@imperial.ac.uk
D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000097:blood; D054697:Cytostatic Agents / Q000627:therapeutic use; D016903:Drug Monitoring; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000097:blood; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000188:drug therapy*; D015465:Leukemia, Myeloid, Accelerated Phase / Q000097:blood / Q000188:drug therapy / Q000601:surgery; D015466:Leukemia, Myeloid, Chronic-Phase / Q000097:blood / Q000188:drug therapy; D008297:Male; D018579:Patient Selection; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017410:Practice Guidelines as Topic; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000188:drug therapy; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D014184:Transplantation, Homologous
D000970:Antineoplastic Agents; D001549:Benzamides; D014408:Biomarkers, Tumor; D054697:Cytostatic Agents; D016898:Interferon-alpha; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl