Chronic myeloid leukaemia

2020 ◽  
pp. 5213-5227
Author(s):  
Mhairi Copland ◽  
Tessa L. Holyoake
Keyword(s):  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Peripheral Blood ◽  
Fusion Gene ◽  
Signs And Symptoms ◽  
Blood Film ◽  
Second Line ◽  
First Line ◽  
Conventional Cytogenetics ◽  
Third Line

Chronic myeloid leukaemia (CML) has a worldwide incidence of 1 to 2 per 100 000 of the population. Most cases are caused by translocation of the distal end of chromosome 9 on to chromosome 22 which leads to the creation of a fusion protein expressed from the fusion gene formed by juxtaposition of parts of the BCR and ABL1 genes. The resulting oncoprotein is a constitutive tyrosine kinase and appears to operate as an initiator for the development of the leukaemia. Clinical features—many patients are asymptomatic at diagnosis, which is made following a routine blood test. Others present with signs and symptoms including fatigue, sweats, fever, weight loss, haemorrhagic manifestations, and abdominal discomfort (due to splenomegaly). Diagnosis—this is typically made by the examination of a peripheral blood film and the demonstration of the Ph chromosome by conventional cytogenetics in a bone marrow aspirate or peripheral blood sample. Polymerase chain reaction analysis of peripheral blood confirms the presence of a BCR-ABL1 transcript and characterizes the BCR-ABL1 junction. Treatment—the original TKI, imatinib, has had a very significant impact on the first-line management of patients with CML. It induces durable complete cytogenetic responses in the majority of patients and prolongs overall survival substantially. Second- and third-generation TKIs show enhanced potency against BCR-ABL1 activity and are licensed within Europe for first-line (dasatinib, nilotinib) or second-line or subsequent (dasatinib, nilotinib, bosutinib, ponatinib) use in CML. Patients with suboptimal responses to first-line treatment can be offered a different second-line TKI; or a third-line TKI, such as ponatinib; or allogeneic stem cell transplantation—for patients less than 65 years of age and with a suitable donor.

Responses to Dasatinib as a Second- and Third-Line Tyrosine Kinase Inhibitor in Chronic Phase Chronic Myeloid Leukaemia Patients

2019 ◽  
Vol 142 (2) ◽  
pp. 79-86 ◽  
Author(s):  
Jiaqi Tan ◽  
Mengxing Xue ◽  
Jinlan Pan ◽  
Jiannong Cen ◽  
Xiaomei Qi ◽  
...  
Keyword(s):  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Chronic Phase ◽  
Molecular Response ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line ◽  
Dasatinib Treatment

We retrospectively evaluated the efficacy and safety of dasatinib among 48 Chinese patients with chronic phase chronic myeloid leukaemia. The proportions of patients achieving the optimal molecular responses at 3, 6, and 12 months, a major molecular response (MMR) rate and a complete cytogenetic response (CCyR) rate were 87.0, 87.0, 72.2, 45.8, and 72.7% for patients with dasatinib as second-line therapy, and 34.8, 34.8, 33.3, 20.8, and 46.2% as third-line therapy, respectively. A BCR-ABL1 transcript level on the International Scale (BCR-ABL1IS) of ≤10% at the initiation of ­dasatinib treatment was found to be associated with a higher probability of achieving MMR. Among patients with a ­BCR-ABL1IS higher than 10% at initiation of dasatinib treatment, dasatinib showed better performance as a second-line therapy than as a third-line therapy. The patients who achieved an optimal molecular response at 3 months had a superior cumulative incidence of MMR and CCyR compared with patients who failed to achieve such a response. Dasatinib induced considerable responses as a second-line treatment, especially in patients with a BCR-ABL1IS ≤10% at initiation of treatment, whereas the efficacy was limited in patients receiving third-line therapy with a BCR-ABL1IS >10% at the initiation of treatment.

BCR-ABL Fusion Gene and BCR-ABL Transcript - Correlation with Response to Therapy in Chronic Myeloid Leukaemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4868-4868
Author(s):  
C. Geraldes ◽  
A.C. Gonçalves ◽  
P. Santos ◽  
P. Tavares ◽  
A. Teixeira
Keyword(s):  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Peripheral Blood ◽  
Fusion Gene ◽  
Blast Crisis ◽  
Response To Therapy ◽  
Molecular Response ◽  
Total Rna ◽  
Therapeutic Decisions ◽  
Genomic Marker

Abstract INTRODUCTION: The quantification of BCR-ABL transcript (RNA) has been consistently associated with the evolution of Chronic Myeloid Leukaemia (CML), frequently determining therapeutic decisions. We did not find in the literature any attempt of measuring tumour burden directly by its genomic marker (DNA). AIMS: To correlate the quantification of BCR-ABL fusion gene with the quantification of BCR-ABL transcript, in the evaluation of response to therapy in patients (pts) with CML. METHODS: Between October/2002 and July/2005, we analysed 393 samples of peripheral blood of 33 pts, M/F:17/16, median age 52 (27–76) years, with chronic phase CML (2 pts developed blast crisis), median time since diagnosis 60,5 (19–170) months, under Imatinib or alpha Interferon (INF) + Cytarabin (Ara-C) therapy. Pts total RNA and genomic DNA were extracted from peripheral blood samples and total RNA was reverse transcribed into cDNA. Real-time PCR absolute quantification with TaqMan® probes was used to measure the fusion transcript’s levels and Sybr Green I® dye was used to measure the fusion gene levels. Imatinib was initiated in pts with cytogenetic responses (CyR) inferior to 90%, after more than 1 year of INF+Ara-C therapy. Criteria used in the evaluation of response: molecular response (MR) - reduction of transcript ≥ 3 logs, major MR (MMR) - reduction ≥ 4 logs, complete MR (CMR) - absence of transcript in 2 consecutive analyses. RESULTS: From 33 studied pts, 26 were under Imatinib therapy, after a median of 21 (2–38) months, 6 pts maintain therapy with INF+Ara-C and 1 pt died (lower respiratory tract infection), in therapy with INF+Ara-C. The evaluation of therapy demonstrated MR in 18 pts (55%), 5 of which with IFN+Ara-C. From these 18 pts, 7 achieved CMR and 6 MMR. In the 15 pts without MR, 8 presented reduction of transcript of 1 to 2 logs and 7 pts maintained stable levels of transcript. Two pts developed blast crisis, after 4 and 20 months of therapy with Imatinib, the latter 12 months after MMR. We observed a higher incidence of transcripts b3a2 (23 pts) compared with b2a2 (11 pts), but we did not find any correlation between the type of transcript and response to therapy. In all pts BCR-ABL fusion gene was present, including in those pts in CMR. We did not observe any correlation between the quantification of BCR-ABL fusion gene and the quantification of BCR-ABL transcript. CONCLUSIONS: The present data demonstrates that MR can be achieved in pts with CML by INF+Ara-C therapy. If INF+Ara-C fails to induce CyR, MR can be obtained with Imatinib. In the 33 CML presented pts, the evaluation of response to therapy showed that 55% pts obtained MR. No correlation between the quantification of BCR-ABL fusion gene and the quantification of BCR-ABL transcript was observed. These preliminary results suggest that the absence of BCR-ABL transcripts does not exclude the presence of BCR-ABL fusion gene. However more studies with larger series of pts are needed to confirm these results.

Determining the efficiency of the Imatinib mesylate and monitoring of relapse and emergence of IM resistance in Algerian adult patients with Chronic Myeloid Leukaemia

2019 ◽  
Vol 8 (3) ◽  
pp. 103-108
Author(s):  
Amel Sebaa ◽  
Mustapha Diaf ◽  
Sakina Cherif Touil
Keyword(s):  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Imatinib Mesylate ◽  
Second Generation ◽  
Adult Patients ◽  
Second Line ◽  
Second Line Therapy ◽  
Molecular Responses ◽  
Line Therapy ◽  
Significant Difference

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Prognostic factors of chronic myeloid leukaemia

2020 ◽  
pp. 63-78
Author(s):  
Michele Baccarani ◽  
Fausto Castagnetti ◽  
Gabriele Gugliotta ◽  
Francesca Palandri ◽  
Simona Soverini ◽  
...  
Keyword(s):  
Chronic Myeloid Leukaemia ◽  
Risk Stratification ◽  
Tyrosine Kinase ◽  
Myeloid Leukaemia ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
First Line ◽  
Abl Tyrosine Kinase ◽  
Baseline Characteristics ◽  
Kinase Domain Mutations

Two decades following the successful introduction of the ABL tyrosine kinase inhibitors in clinics for the treatment of patients with chronic myeloid leukaemia (CML), the principal objective of treatment in chronic phase (CP) is survival, preferably without life-long therapy. In tandem, the methodology and tools for assessing the prognosis of the newly diagnosed patient with CML in CP has evolved substantially. Prior to the era of tyrosine kinase inhibitors (TKIs), risk assessment depended more on the response to treatment than on baseline characteristics. The Sokal score, introduced in 1984, was the first one dividing patients into three risk categories based on a mathematical formula taking into account the patient’s age, and baseline characteristics like blast cell count, spleen size, and platelet count. This, and the several other subsequent risk stratification methods developed during the chemotherapy and interferon-alpha era, have remained useful in the first-line TKI treatment, and identifies a variable proportion of high-risk patients with lower response rates and worse outcomes. In second line, the most important risk factors are the absence of haematologic or cytogenetic response on first line, the presence of hematologic toxicity the development of additional cytogenetic abnormities (ACA), and the development of BCR-ABL1 kinase domain mutations. In this chapter, we address the prognosis of CML and the various methods for risk stratification.

P19 Mycophenolate mofetil in paediatric uveitis: an early experience

Rheumatology ◽  
2019 ◽  
Vol 58 (Supplement_4) ◽  
Author(s):  
Amany Tadrous ◽  
Kishore Warrier ◽  
Archana Pradeep ◽  
Nikki Camina ◽  
Satyapal Rangaraj
Keyword(s):  
Mycophenolate Mofetil ◽  
Conflicts Of Interest ◽  
Cystoid Macular Oedema ◽  
Favourable Result ◽  
Topical Steroids ◽  
Second Line ◽  
First Line ◽  
Small Cohort ◽  
Third Line ◽  
Paediatric Uveitis

Abstract Background Juvenile idiopathic arthritis (JIA) is the commonest cause of uveitis in children. Uveitis is a significant cause of visual impairment in children with potential complications such as band keratopathy, cataract, posterior synechiae, glaucoma, cystoid macular oedema and a retinal problems. Following the initial treatment with topical and systemic corticosteroids, a wide variety of immunosuppressant agents have been used in the treatment of non-infective uveitis including methotrexate (MTX) and biologic therapy, most of which are administered parenterally. Mycophenolate Mofetil (MMF) is an oral immunosuppressant that inhibits the proliferation of T and B lymphocytes, which has been tried in children with uveitis with mixed results. We started using MMF in children seen in our paediatric uveitis clinic initially as a third line agent when the inflammation is not well controlled despite therapeutic doses of MTX and Adalimumab, as the NHS England Clinical Commissioning Policy does not recommend the use of Infliximab in uveitis not associated with JIA. Buoyed by some favourable result, we have since then used MMF as second line and even first line agent in children with uveitis. Methods Retrospective analysis of the clinical profile of children with uveitis on MMF at a tertiary paediatric rheumatology centre with focus on response to treatment. Results Of the 8 patients who received MMF, six (75%) were girls. Half of them (4/8) had idiopathic uveitis and the rest, associated with JIA. 2/8 patients had MMF as third line agent on top of MTX and Adalimumab, while five of them had it as second line agent on top of Adalimumab due to either MTX intolerance or needle phobia. One patient was started on MMF as first line agent following topical steroids. 6 (75%) of the patients responded/stayed in remission following the addition of/switch to MMF. Conclusion MMF has shown initial promise in the treatment of uveitis in children with uveitis in this small cohort, in line with some existing evidence. It was initially used in patients who were not keen on injections/intolerant to MTX or had failed all existing options. This is a small cohort of patients and we would welcome more research in this area. Conflicts of Interest The authors declare no conflicts of interest.

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