7 Management of 1000 patients with low- and intermediate-1 risk myelodysplastic syndromes in the European LeukemiaNet MDS Registry

Swart, Louise de; Smith, Alexandra; Fenaux, Pierre; Symeonidis, Argiris; Hellström‐Lindberg, Eva; Sanz, Guillermo; Čermák, Jaroslav; Georgescu, Otilia; Germing, Ulrich; MacKenzie, Mary J.; Beyne‐Rauzy, Odile; Malcovati, Luca; Stauder, Reinhard; Droste, Jackie; Bowen, D.; Witte, T. de

doi:10.1016/s0145-2126(11)70009-1

Cited by 10 publications

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“…As has been clearly demonstrated in PML–RARA + APL, in order to reliably predict relapse it is important to adopt a sequential MRD monitoring approach (reviewed Grimwade and Tallman, 2011). This was applied in the patient with STAT5b–RARA + APL, showing a failure to achieve CRm following intensive frontline therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Molecular diagnostics to establish the nature of the fusion partner are therefore important for appropriate management, but in addition the application of sensitive minimal residual disease (MRD) assays to track treatment response has been found to be clinically useful in patients with PML–RARα+ disease, with previous studies showing that achievement of molecular remission (CRm) as determined by qualitative or quantitative polymerase chain reaction (PCR) assays (with a sensitivity of 10–4) is a prerequisite for long-term remission and disease cure (reviewed Sanz et al, 2009; Grimwade and Tallman, 2011). These assays when applied at the post-consolidation timepoint are not sufficiently sensitive to identify all patients destined to relapse (Grimwade et al, 1996; Burnett et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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Development of Real-Time Quantitative Polymerase Chain Reaction Assays to Track Treatment Response in Retinoid Resistant Acute Promyelocytic Leukemia

Jovanović¹,

Rennie²,

Culligan³

et al. 2011

Front. Oncol.

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Molecular detection of minimal residual disease (MRD) has become established to assess remission status and guide therapy in patients with ProMyelocytic Leukemia–RARA+ acute promyelocytic leukemia (APL). However, there are few data on tracking disease response in patients with rarer retinoid resistant subtypes of APL, characterized by PLZF–RARA and STAT5b–RARA. Despite their rarity (<1% of APL) we identified 6 cases (PLZF–RARA, n = 5; STAT5b–RARA, n = 1), established the respective breakpoint junction regions and designed reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) assays to detect leukemic transcripts. The relative level of fusion gene expression in diagnostic samples was comparable to that observed in t(15;17) – associated APL, affording assay sensitivities of ∼1 in 104−105. Serial samples were available from two PLZF–RARA APL patients. One showed persistent polymerase chain reaction positivity, predicting subsequent relapse, and remains in CR2, ∼11 years post-autograft. The other, achieved molecular remission (CRm) with combination chemotherapy, remaining in CR1 at 6 years. The STAT5b–RARA patient failed to achieve CRm following frontline combination chemotherapy and ultimately proceeded to allogeneic transplant on the basis of a steadily rising fusion transcript level. These data highlight the potential of RT-qPCR detection of MRD to facilitate development of more individualized approaches to the management of rarer molecularly defined subsets of acute leukemia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development of Real-Time Quantitative Polymerase Chain Reaction Assays to Track Treatment Response in Retinoid Resistant Acute Promyelocytic Leukemia

Jovanović¹,

Rennie²,

Culligan³

et al. 2011

Front. Oncol.

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“…The majority of these patients will subsequently become transfusion dependent with time. Transfusion requirements vary from patient to patient, but, with the passage of time, once a patient becomes transfusion dependent, the intervals between transfusions reduce and the amount of blood they require increases (de Swart et al , ). As a unit of packed red cells contains approximately 200 mg of iron (Porter, ) and normal body loss is only small (1–2 mg per day), regular transfusion of red cells will inevitably lead to the accumulation of iron as there is no physiological mechanism for the excretion of excess iron.…”

Section: Part I: Debating the Evidencementioning

confidence: 99%

“…Analysis of the first 800 patients registered between 2008 and 2010 showed differences in OS between transfusion‐independent and transfusion‐dependent patients; 97% vs. 85% respectively ( P < 0·0001, HR 5·1) and leukaemia‐free survival (HR 4·1). In multivariate analysis, transfusion‐dependency, ferritin levels and IPSS score predicted survival (de Swart et al , ). Sanz et al () retrospectively reviewed 2994 de novo MDS patients.…”

Section: Part I: Debating the Evidencementioning

confidence: 99%

Iron chelation therapy in low risk myelodysplastic syndrome

Killick

2017

Br J Haematol

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Anaemia is the commonest cytopenia seen in patients with myelodysplastic syndrome (MDS), and the majority of patients will require transfusion support at some point. Blood transfusions are rich in iron, which leads to the accumulation of body iron over time. It is accepted that this ultimately causes end organ damage and may impact on both morbidity and mortality. In addition, recent data has increased our interest in the subject with regard to the potential impact on stem cell transplant outcome and an anti-leukaemic effect of iron chelation therapy. There is still debate over which patients should receive iron chelation therapy, but the emergence of new diagnostic and prognostic markers in MDS may help decision making in the clinic setting.

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“…That transfusional iron overload portends inferior survival in patients with congenital and acquired anemias is well documented . Iron chelation therapy (ICT) in conditions such as beta thalassemia major (BTM) is a mainstay of care, and patient survival is directly related to chelation efficacy.…”

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confidence: 99%

Hematologic improvement with iron chelation therapy in acquired anemias

Leitch

2016

European J of Haematology

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7 Management of 1000 patients with low- and intermediate-1 risk myelodysplastic syndromes in the European LeukemiaNet MDS Registry

Cited by 10 publications

References 0 publications

Development of Real-Time Quantitative Polymerase Chain Reaction Assays to Track Treatment Response in Retinoid Resistant Acute Promyelocytic Leukemia

Development of Real-Time Quantitative Polymerase Chain Reaction Assays to Track Treatment Response in Retinoid Resistant Acute Promyelocytic Leukemia

Iron chelation therapy in low risk myelodysplastic syndrome

Hematologic improvement with iron chelation therapy in acquired anemias

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