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

Buesche, Guntram; Hehlmann, R; Hecker, Hartmut; Heimpel, Hermann; Heinze, B; Schmeil, A.; Pfirrmann, Markus; Gómez, Germán A.; Tobler, Andreas; Herrmann, Heinz; Kappler, Martin; Hasford, Joerg; Buhr, T.; Kreipe, Hans; Georgii, A.

doi:10.1038/sj.leu.2403172

Cited by 59 publications

(68 citation statements)

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“…Worse bone marrow fibrosis at the time of diagnosis, 3 and worsening bone marrow fibrosis while the patient is receiving therapy, 8,9 are markers of CML disease progression and poor prognosis. Bone marrow fibroblasts have been shown to be polyclonal (therefore not derived from the cytogenetically abnormal CML clones).…”

Section: Discussionmentioning

confidence: 99%

“…Progressive myelofibrosis contributes to significant morbidity and mortality in 10 -30% of patients, and to a worse outcome. 3,8,9 Because the process is potentially reversible, any therapy that consistently reduces fibrosis in CML may improve prognosis in a substantial proportion of patients. We previously demonstrated that IFN-␣ therapy reduced bone marrow fibrosis in 26% of patients and stabilized fibrosis in 54% of patients after a median follow up of 25 months of therapy.…”

Section: Discussionmentioning

confidence: 99%

“…7 Bone marrow fibrosis occurring prior to treatment and serially has been shown to be associated independently with adverse prognosis. 8,9 Its resolution with imatinib therapy may improve the prognosis of CML patients, in parallel with other positive effects (e.g., the suppression of Ph-positive cells). This is the subject of the current analysis.…”

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confidence: 99%

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Imatinib mesylate therapy reduces bone marrow fibrosis in patients with chronic myelogenous leukemia

Bueso‐Ramos

Cortes

Talpaz

et al. 2004

Cancer

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BACKGROUNDReticulin‐stained bone marrow fibrosis is associated with a poor prognosis in patients with chronic myelogenous leukemia (CML). Resolution of fibrosis with therapy may improve patient outcome.METHODSThe effect of imatinib therapy on bone marrow fibrosis was evaluated in 40 patients with chronic‐phase CML who were treated after interferon‐α failure.RESULTSThirty‐one patients (78%) had severe (Grade 3 or 4) reticulin fibrosis prior to therapy. After imatinib therapy was administered for 3 to > 24 months, fibrosis was reduced by at least 2 grades in 19 of the 31 patients (61%) and by at least 1 grade in 34 patients (85%). There was no correlation noted between reduction of fibrosis and cytogenetic response. However, a reduction in fibrosis was found to correlate with a reduction in bone marrow megakaryocytosis (P = 0.002).CONCLUSIONSTreatment with imatinib mesylate appears to reduce CML‐associated bone marrow fibrosis in most patients who are treated during the chronic phase of disease. This effect may be independent of the degree of suppression of Philadelphia chromosome‐positive cells, and may improve prognosis in patients with CML. Cancer 2004. © 2004 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Imatinib mesylate therapy reduces bone marrow fibrosis in patients with chronic myelogenous leukemia

Bueso‐Ramos

Cortes

Talpaz

et al. 2004

Cancer

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“…Moreover, increased angiogenesis and fibrosis in the bone marrow (BM) and other hematopoietic tissues have been associated with progression in CML 21, 22, 23, 24, 25, 26…”

Section: Introductionmentioning

confidence: 99%

The underestimated role of basophils in Ph⁺ chronic myeloid leukaemia

Valent

Horny

Arock

2018

Eur J Clin Investigation

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Chronic myeloid leukaemia (CML) is a hematopoietic neoplasm defined by the chromosome translocation t(9;22) and the related oncogene, BCR‐ABL1. In most patients, leukaemic cells can be kept under control using BCR‐ABL1‐targeting drugs. However, many patients relapse which remains a clinical challenge. In particular, patients with advanced (accelerated or blast phase) CML have a poor prognosis. So far, little is known about molecular and cellular interactions and features that contribute to disease progression and drug resistance in CML. One key prognostic factor at diagnosis is marked basophilia. However, although basophils are well‐known multifunctional effector cells, their impact in CML remains uncertain. In this article, we discuss the potential role of basophils as active contributors to disease evolution and progression in CML. In particular, basophils serve as a unique source of inflammatory, angiogenic and fibrogenic molecules, such as vascular endothelial growth factor or hepatocyte growth factor. In addition, basophils provide vasoactive substances, like histamine as well as the cytokine‐degrading enzyme dipeptidyl‐peptidase IV which may promote stem cell mobilization and the extramedullary spread of stem and progenitor cells. Finally, basophils may produce autocrine growth factors for myeloid cells. Understanding the role of basophils in CML evolution and progression may support the development of more effective treatment concepts.

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“…3,[7][8][9] Recently, an independent poor prognostic significance has been detected on basis of a prospective controlled trial. 10 CML responds well to therapy with interferon-a [11][12][13][14][15][16] or a tyrosine kinase inhibitor [17][18][19][20] and can be cured by stem cell allografting. However, whereas reversal of MF was reported during tyrosine kinase inhibition or after allografting, [18][19][20][21] the few retrospective results on the effect of interferon-a on MF in CML are controversial ranging from retardation or reversal [22][23][24][25] to progression of fibrosis during therapy with this cytokine.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2004

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

Cited by 59 publications

References 37 publications

Imatinib mesylate therapy reduces bone marrow fibrosis in patients with chronic myelogenous leukemia

Imatinib mesylate therapy reduces bone marrow fibrosis in patients with chronic myelogenous leukemia

The underestimated role of basophils in Ph⁺ chronic myeloid leukaemia

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

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

Cited by 59 publications

References 37 publications

Imatinib mesylate therapy reduces bone marrow fibrosis in patients with chronic myelogenous leukemia

Imatinib mesylate therapy reduces bone marrow fibrosis in patients with chronic myelogenous leukemia

The underestimated role of basophils in Ph+ chronic myeloid leukaemia

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

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The underestimated role of basophils in Ph⁺ chronic myeloid leukaemia