Marrow fibrosis, indicator of therapy failure in chronic myeloid leukemia - prospective long-term results from a randomized-controlled trial

被引:46
作者
Buesche, G
Hehlmann, R
Hecker, H
Heimpel, H
Heinze, B
Schmeil, A
Pfirrmann, M
Gomez, G
Tobler, A
Herrmann, H
Kappler, M
Hasford, J
Buhr, T
Kreipe, HH
Georgii, A
机构
[1] Hannover Med Sch, Inst Pathol, D-30625 Hannover, Germany
[2] Univ Heidelberg, Klinikum Mannheim, Med Klin 3, D-6900 Heidelberg, Germany
[3] Hannover Med Sch, Inst Biometrie, Hannover, Germany
[4] Univ Ulm Klinikum, Abt Innere Med 3, Ulm, Germany
[5] Univ Ulm, Tumorzytogenet Lab, Abt Innere Med 3, D-89069 Ulm, Germany
[6] Univ Munich, Inst Med Informat Biometrie & Epidemiol, D-80539 Munich, Germany
[7] Univ Bern, Inselspital, Hamatol Zent Lab, CH-3012 Bern, Switzerland
关键词
chronic myeloid leukemia; bone marrow biopsies; marrow fibrosis; interferon-alpha; hydroxyurea; bone marrow; transplantation;
D O I
10.1038/sj.leu.2403172
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:2444 / 2453
页数:10
相关论文
共 41 条
[1]   UK MEDICAL-RESEARCH-COUNCIL RANDOMIZED, MULTICENTER TRIAL OF INTERFERON-ALPHA-N1 FOR CHRONIC MYELOID-LEUKEMIA - IMPROVED SURVIVAL IRRESPECTIVE OF CYTOGENETIC RESPONSE [J].
ALLAN, NC ;
RICHARDS, SM ;
SHEPHERD, PCA .
LANCET, 1995, 345 (8962) :1392-1397
[2]  
ARLIN ZA, 1990, LEUKEMIA, V4, P755
[3]   Treatment of chronic myelogenous leukemia with the tyrosine kinase inhibitor STI571 results in marked regression of bone marrow fibrosis [J].
Beham-Schmid, C ;
Apfelbeck, U ;
Sill, H ;
Tsybrovsky, O ;
Höfler, G ;
Haas, OA ;
Linkesch, W .
BLOOD, 2002, 99 (01) :381-383
[4]   Evaluating the volume ratio of bone marrow affected by fibrosis: A parameter crucial for the prognostic significance of marrow fibrosis in chronic myeloid leukemia [J].
Buesche, G ;
Georgii, A ;
Duensing, A ;
Schmeil, A ;
Schlue, J ;
Kreipe, HH .
HUMAN PATHOLOGY, 2003, 34 (04) :391-401
[5]   THE IMPACT OF MEGAKARYOCYTE PROLIFERATION FOR THE EVOLUTION OF MYELOFIBROSIS - HISTOLOGICAL FOLLOW-UP-STUDY IN 186 PATIENTS WITH CHRONIC MYELOID-LEUKEMIA [J].
BUHR, T ;
CHORITZ, H ;
GEORGII, A .
VIRCHOWS ARCHIV A-PATHOLOGICAL ANATOMY AND HISTOPATHOLOGY, 1992, 420 (06) :473-478
[6]  
CERVANTES F, 1989, ACTA HAEMATOL-BASEL, V82, P12
[7]  
DEKMEZIAN R, 1987, CANCER, V59, P1739, DOI 10.1002/1097-0142(19870515)59:10<1739::AID-CNCR2820591011>3.0.CO
[8]  
2-2
[9]  
Delannoy A, 1997, J NATL CANCER I, V89, P1616
[10]  
Domingues MA, 1998, HAEMATOLOGICA, V83, P1124