Marrow fibrosis and its relevance during imatinib treatment of chronic myeloid leukemia.
In chronic myeloid leukemia (CML), imatinib may reverse bone marrow fibrosis (MF). Whether the unfavorable prognosis of MF is also reversed and whether imatinib guarantees against evolution of MF are unclear as yet. Fifty-nine patients with Ph+ CML treated with > or = 400 mg imatinib/day were examined for MF in 6- to 12-month intervals. Imatinib effectively reversed initial MF (P<0.0005). However, during a follow-up period of up to 4.8 years, small foci with abnormal fiber increase (FFI) emerged in 8 of 30 pretreated and 6 of 29 non-pretreated patients. Patients with FFI showed a significantly lower probability of achieving a complete cytogenetic or major molecular response (36 versus 81%; P<0.007). During the further follow up, 57% of patients with FFI but none of the other patients suffered from full-blown MF (P=0.00005). None of the patients with FFI or MF showed a Janus kinase-2 mutation (V617F). Evolutions of FFI and MF were independent significant predictors of imatinib failure (P=0.0031), accelerated phase and death of patients (P=0.0001; multivariate analyses). Imatinib effectively reverses initial MF in CML, but neither eliminates its unfavorable prognosis nor guarantees completely against new evolution of MF.
Buesche
G
G
Institut für Pathologie, Medizinische Hochschule, Hannover, Germany. guntram.buesche@arcor.de
Ganser
A
A
Schlegelberger
B
B
von Neuhoff
N
N
Gadzicki
D
D
Hecker
H
H
Bock
O
O
Frye
B
B
Kreipe
H
H
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000032:analysis; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D018450:Disease Progression; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000032:analysis; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000627:therapeutic use; D053614:Janus Kinase 2 / Q000235:genetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D055728:Primary Myelofibrosis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D012008:Recurrence; D012074:Remission Induction; D016879:Salvage Therapy