Treatment intensity significantly influencing fibrosis in bone marrow independently of the cytogenetic response: meta-analysis of the long-term results from two prospective controlled trials on chronic myeloid leukemia

Buesche, Guntram; Freund, Mathias; Hehlmann, Rüdiger; Georgii, A.; Ganser, Arnold; Hecker, Hartmut; Heimpel, Hermann; Fonatsch, Christa; Heinze, B; Pfirrmann, Markus; Holgado, Susana; Schmeil, A.; Tobler, Andreas; Hasford, Joerg; Buhr, T.; Kreipe, Hans

doi:10.1038/sj.leu.2403451

Cited by 8 publications

(6 citation statements)

References 38 publications

(55 reference statements)

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“…These data support previous observations during therapy with IFN or CHT. 10,22 First data from the pilot phase of the German CML Study IV show similar results. 44 Thus, although imatinib therapy reverses initial MF, it does not appear to reverse its unfavorable prognosis.…”

Section: Discussionsupporting

confidence: 65%

“…5,6 The antifibrotic efficacy of imatinib does not furthermore appear to be influenced by failure of a previous therapy with IFN and CHT, which may indicate a superior antifibrotic efficacy of imatinib. Nevertheless, a direct comparison with the antifibrotic effect of a combination therapy with high-dose IFN-a and low-dose cytosine arabinoside 22 does not exist as yet.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, we started a pilot study (1) to evaluate whether imatinib reliably prevents evolution of MF in CML, (2) to estimate the possible prognostic significance of MF and its change during imatinib therapy and (3) if MF should emerge or relapse during imatinib therapy, to evaluate whether the evolution of MF can be predicted. Since MF may evolve during long-term therapy with interferon-a (IFN) and chemotherapy (CHT) 10,22 and since the prognostic significance of MF may be influenced by pretreatment with IFN, 20,21 a possible impact of pretreatment with IFN or CHT was taken into consideration.…”

Section: Introductionmentioning

confidence: 99%

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Marrow fibrosis and its relevance during imatinib treatment of chronic myeloid leukemia

et al. 2007

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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 þ CML treated with X400 mg imatinib/day were examined for MF in 6-to 12-month intervals. Imatinib effectively reversed initial MF (Po0.0005). 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%; Po0.007). During the further follow up, 57% of patients with FFI but none of the other patients suffered from full-blown MF (P ¼ 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 ¼ 0.0031), accelerated phase and death of patients (P ¼ 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.

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Marrow fibrosis and its relevance during imatinib treatment of chronic myeloid leukemia

et al. 2007

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“…Attaining CR is the main goal of treatment, since this is directly related to patient survival. In addition, individuals who do not respond are called refractory and this event is associated to disease progression and worse prognosis (Guimarães et al, 2006;Buesche et al, 2004;Sattler, Griffin, 2003;Goldman, Mello, 2003;Druker, Talpaz, Resta, 2002). The results obtained showed that 77.27% of patients presented less than 35% of chromosome Ph 1 positive cells in the cytogenetic tests during the monitoring period.…”

Section: Discussionmentioning

confidence: 64%

Assessment of fibrosis and vascularization of bone marrow stroma of chronic myeloid Leukemia patients treated with imatinib mesylate and their relationship with the cytogenetic response

Jesus

I-Ching

Neiva

et al. 2011

Braz. J. Pharm. Sci.

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Chronic Myeloid Leukemia (CML) is a myeloproliferative disease characterized by the presence of the Philadelphia chromosome (translocation between chromosomes 9 and 22), resulting in the formation of the hybrid BCR-ABL protein. Currently, the treatment of CML patients is performed with imatinib mesylate (IM), which promotes the elimination of leukemic cells by inhibiting the kinase activity of BCR-ABL. This study evaluated the effectiveness of IM by monitoring 22 CML patients in a chronic phase treated at the CEPON/SC with IM for a minimum follow-up period of two years. Cytogenetic Response (CR) and bone marrow biopsies (BMB) were evaluated before and after IM treatment. BMB were evaluated by detection of reticulin degree and vascularization. The results were correlated to the CR. Mean time to achieve CR was 9 months and was attained by 77.27% of the patients. The results from the initial BMB analysis showed that 59.09% presented reticulin of between 2+ and 4+ whereas after treatment, only 27.17% presented this degree. With regard to vascularization of the initial sample, 90.91% were graded between II and IV, whereas after treatment, 40.91% had this degree. The results suggest a positive correlation of degree of reticulin and vascularization with CR.Uniterms: Chronic myeloid leukemia/treatment. Imatinib mesylate/effectiveness/leukemia treatment. Bone marrow/biopsies. Fibrosis. Vascularization.A Leucemia Mielóide Crônica (LMC) é uma doença mieloproliferativa caracterizada pela presença do cromossomo Filadélfia (translocação entre os cromossomos 9 e 22), que resulta na formação da proteína híbrida BCR-ABL. Atualmente o tratamento de pacientes com LMC é realizado com mesilato de imatinibe (MI), o qual promove a eliminação das células leucêmicas pela inibição da atividade quinase de BCR-ABL. O presente estudo avaliou a eficácia do MI por meio do acompanhamento de pacientes portadores de LMC em fase crônica, atendidos no CEPON/SC tratados com MI pelo tempo mínimo de dois anos. Foram avaliadas a Resposta Citogenética (RC) e as biópsias de medula óssea (BMO) antes e após o tratamento com MI. As BMO foram avaliadas quanto ao grau de reticulina e vascularização. Os resultados correlacionaram-se com a RC cujo tempo médio para obtenção da RC foi de 9 meses, sendo atingida por 77.27% dos pacientes. Na primeira BMO, 59.09% dos pacientes apresentaram grau de reticulina entre 2+ e 4+ e após o tratamento, apenas 27.17% apresentaram esta graduação. Quanto à vascularização da primeira amostra, 90.91% foram graduadas entre II e IV e após o tratamento, 40.91% apresentaram esta graduação. Os resultados sugerem uma correlação diretamente proporcional entre os graus de reticulina e vascularização com a RC.

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“…Although this complication has been known for many years and appears to provide independent prognostic information as shown in prospective controlled trials, 8,10 there is a marked diversity in two important issues: (i) the methods used to prove and quantify marrow fibrosis (MF), 6,[8][9][10][11][12][13][14][15] and (ii) the technical processing of bone marrow biopsies (BMBs). The diversity of the methods has been previously analysed in detail, 9 whereas data as to the relevance of biopsy processing for the diagnosis and quantification of MF, such as fixation, decalcification, and embedding of a BMB, the degree of tissue shrinkage during biopsy processing, and the thickness of tissue section do not, as yet, exist, although the potential significance of these influences is known from biopsies taken from other organ systems.…”

Section: Introductionmentioning

confidence: 99%

Diagnosis and quantification of bone marrow fibrosis are significantly biased by the pre‐staining processing of bone marrow biopsies

Buesche

Georgii

2005

Histopathology

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Treatment intensity significantly influencing fibrosis in bone marrow independently of the cytogenetic response: meta-analysis of the long-term results from two prospective controlled trials on chronic myeloid leukemia

Cited by 8 publications

References 38 publications

Marrow fibrosis and its relevance during imatinib treatment of chronic myeloid leukemia

Marrow fibrosis and its relevance during imatinib treatment of chronic myeloid leukemia

Assessment of fibrosis and vascularization of bone marrow stroma of chronic myeloid Leukemia patients treated with imatinib mesylate and their relationship with the cytogenetic response

Diagnosis and quantification of bone marrow fibrosis are significantly biased by the pre‐staining processing of bone marrow biopsies

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