title: Marrow fibrosis, indicator of therapy failure in chronic myeloid leukemia - prospective long-term results from a randomized-controlled trial.
abstract: Marrow fibrosis (MF) has rarely been considered in therapy studies on chronic myeloid leukemia (CML), and there is a lack of long-term observations on the basis of sequential bone marrow biopsies (BMBs) taken prospectively during the course of disease. A total of 848 BMBs from 400 patients with Ph(+) CML recruited in the German randomized CML study I were examined for MF before and during therapy. In total, 110 patients had been randomized to receive interferon (IFN)-alpha, and 290 to receive chemotherapy (hydroxyurea (HU): 154, busulfan: 136). During IFN-alpha and HU medication, MF was reduced or did not increase for about 2 years. Evolving or progressive MF was an independent and early predictor of therapy failure about 2 years earlier than indicated by changes in the peripheral blood, spleen size, marrow blast count and cytogenetics (P<0.00005), resulting in a significant shortening of the survival times of patients independent of the type of therapy applied including allografting (multivariate analyses; P<0.00005). The analyzed long-term observations strongly indicate that MF is an independent poor prognostic complication of CML, allowing an early prediction of therapy failure. Consideration of the fiber content in marrow may therefore significantly improve the prediction of therapy efficacy and outcome of disease.
authors.affiliation: Institut für Pathologie, Medizinische Hochschule Hannover, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Buesche
authors.forename: R
authors.initials: R
authors.lastname: Hehlmann
authors.forename: H
authors.initials: H
authors.lastname: Hecker
authors.forename: H
authors.initials: H
authors.lastname: Heimpel
authors.forename: B
authors.initials: B
authors.lastname: Heinze
authors.forename: A
authors.initials: A
authors.lastname: Schmeil
authors.forename: M
authors.initials: M
authors.lastname: Pfirrmann
authors.forename: G
authors.initials: G
authors.lastname: Gomez
authors.forename: A
authors.initials: A
authors.lastname: Tobler
authors.forename: H
authors.initials: H
authors.lastname: Herrmann
authors.forename: M
authors.initials: M
authors.lastname: Kappler
authors.forename: J
authors.initials: J
authors.lastname: Hasford
authors.forename: T
authors.initials: T
authors.lastname: Buhr
authors.forename: H-H
authors.initials: HH
authors.lastname: Kreipe
authors.forename: A
authors.initials: A
authors.lastname: Georgii
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology*; D016026:Bone Marrow Transplantation; D002066:Busulfan / Q000008:administration & dosage; D002869:Chromosome Aberrations; D019008:Drug Resistance, Neoplasm; D005260:Female; D005355:Fibrosis; D005500:Follow-Up Studies; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage; D016898:Interferon-alpha / Q000008:administration & dosage*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D017211:Treatment Failure
chemical_list: D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D016898:Interferon-alpha; D002066:Busulfan; D006918:Hydroxyurea