scholarly journals Complex cytogenetic abnormalities in chronic myeloid leukemia resulting in early progression to blast crisis: a case report

2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Haider Ali Malakzai ◽  
Soma Rahmani ◽  
Ahmed Maseh Haidary ◽  
Sarah Noor ◽  
Maryam Ahmad ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Patient Management ◽  
Kinase Inhibitor ◽  
Blast Crisis ◽  
Marker Chromosome ◽  
Initial Response ◽  
Response To Therapy ◽  
Cytogenetic Abnormalities ◽  
Cytogenetic Monitoring

Abstract Introduction BCR-ABL1, resulting from t(9;22), is the oncogenic driver of chronic myeloid leukemia and the therapeutic target of the disease. Molecular studies have been the gold standard modality for patient assessment since the advent of tyrosine kinase inhibitor therapy. In spite of that, there are cytogenetic abnormalities that can render the disease unresponsive to conventional therapy, thus making cytogenetics an important component of patient management guidelines. Case presentation We present a case of a Tajik, Afghan patient with chronic myeloid leukemia with del(6)(q23.3q27), t(9;22)(q34;q11.2), monosomy 11, monosomy 12, and marker chromosome who, despite having typical clinical and hematological disease with initial response to therapy, progressed to blast crisis very early and thus required special interventions. Conclusion Cytogenetic monitoring is an important pillar in the management of patients with chronic myeloid leukemia that cannot be ignored. It should therefore be a part of patient management not only during diagnosis but also during management. We present an unusual cytogenetic abnormality in a patient with chronic myeloid leukemia that resulted in early disease progression.

scholarly journals Chronic Myeloid Leukemia with e19a2BCR-ABL1Transcripts and Marked Thrombocytosis: The Role of Molecular Monitoring

2012 ◽  
Vol 2012 ◽  
pp. 1-3 ◽  
Author(s):  
Stephen E. Langabeer ◽  
Sarah L. McCarron ◽  
Johanna Kelly ◽  
Janusz Krawczyk ◽  
Suzanne McPherson ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Patient Management ◽  
Kinase Inhibitor ◽  
Favourable Outcome ◽  
Molecular Monitoring ◽  
Real Time Quantitative Pcr ◽  
Treatment Interruptions ◽  
Dose Reductions

While most patients with chronic myeloid leukemia (CML) express either e13a2 or e14a2BCR-ABL1transcripts, a significant minority expresses variant transcripts, of which e19a2 is the most common. Although considered to have a relatively favourable outcome, reported responses to tyrosine kinase inhibitor (TKI) therapy are variable with molecular monitoring in CML patients with e19a2BCR-ABL1transcripts rarely reported. A case of e19a2BCR-ABL1CML with marked thrombocytosis is described in which the value of molecular monitoring is emphasised during treatment interruptions, dose reductions, and changes. This case serves to demonstrate the requirement for prospective real-time quantitative PCR (RQ-PCR) assays for patients with variantBCR-ABL1transcript types and standardisation of such assays to enable modern patient management.

scholarly journals Clonal evolution of AML1-ETO coexisting with BCR-ABL and additional chromosome abnormalities in a blastic transformation of chronic myeloid leukemia

2020 ◽  
Vol 48 (5) ◽  
pp. 030006052091923 ◽  
Author(s):  
Cheng-Cheng Ma ◽  
Ye Chai ◽  
Hui ling Chen ◽  
Xin Wang ◽  
Ying Gao ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Copy Number ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Chromosomal Abnormalities ◽  
Blast Crisis ◽  
Clonal Evolution ◽  
Molecular Genetic ◽  
Chronic Phase ◽  
Interesting Case

Blast crisis develops in a minority of patients with chronic myeloid leukemia even in the era of tyrosine kinase inhibitor (TKI) therapy. Reports suggest that we know little about the mechanism of BCR-ABL and AML1-ETO co-expression in blast crisis of chronic myeloid leukemia, and that other chromosomal abnormalities also coexist. Here, we document an unusual and interesting case of a 51-year-old female diagnosed in the chronic phase of chronic myeloid leukemia. After undergoing TKI treatment for 3 months, her bone marrow aspirates in the chronic phase had transformed to blast crisis. Molecular genetic testing indicated she was positive for p210 form of BCR-ABL (copy number decreased from 108.91% to 56.96%) and AML1-ETO fusion (copy number, 5.65%) genes and had additional chromosomal abnormalities of t(8; 21)(q22; q22)/t(9; 22)(q34; q11), t(2; 5)(p24; q13) and an additional +8 chromosome.

Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis

Blood ◽  
2006 ◽  
Vol 109 (8) ◽  
pp. 3207-3213 ◽  
Author(s):  
Jorge Cortes ◽  
Philippe Rousselot ◽  
Dong-Wook Kim ◽  
Ellen Ritchie ◽  
Nelson Hamerschlak ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Blast Crisis ◽  
Phase 1 ◽  
Src Family Kinases ◽  
Highly Active ◽  
Imatinib Resistant ◽  
Number Of Patients

AbstractThe prognosis for patients with chronic myeloid leukemia (CML) in myeloid blast crisis (MBC) or lymphoid blast crisis (LBC) remains poor. Although imatinib can induce responses in a subset of these patients, resistance to the drug develops rapidly. Dasatinib is a novel, oral, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases. After promising phase 1 results, we report the results of phase 2 clinical trials of dasatinib in patients with imatinib-resistant or -intolerant blast crisis CML (MBC, n = 74; LBC, n = 42). At the 8-month follow-up, dasatinib induced major hematologic responses (MaHRs) in 34% and 31% of MBC- and LBC-CML patients and major cytogenetic responses (MCyRs) in 31% and 50% of these patients, respectively. Most (86%) of these MCyRs were complete cytogenetic responses (CCyRs). Responses were rapid and durable: 88% and 46%, respectively, of MBC- and LBC-CML patients achieving MaHR had not experienced disease progression at the 8-month follow-up. Response rates were similar in patients with and without BCR-ABL mutations known to confer resistance to imatinib. Dasatinib was well tolerated. Nonhematologic adverse events were mild to moderate. Cytopenias were common and could be managed by dose modification. Dasatinib is highly active and produces hematologic and cytogenetic responses in a significant number of patients with imatinib-resistant or -intolerant MBC- and LBC-CML. These trials were registered at www.clinicaltrials.gov as #CA180006 and #CA180015.

scholarly journals Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS)

Blood ◽  
2010 ◽  
Vol 116 (19) ◽  
pp. 3758-3765 ◽  
Author(s):  
Timothy P. Hughes ◽  
Andreas Hochhaus ◽  
Susan Branford ◽  
Martin C. Müller ◽  
Jaspal S. Kaeda ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Blast Crisis ◽  
Randomized Study ◽  
Prognostic Significance ◽  
Cytogenetic Response ◽  
Response To Therapy ◽  
Molecular Response ◽  
Complete Cytogenetic Response

AbstractThis study examines the prognostic significance of early molecular response using an expanded dataset in chronic myeloid leukemia patients enrolled in the International Randomized Study of Interferon and STI571 (IRIS). Serial molecular studies demonstrate decreases in BCR-ABL transcripts over time. Analyses of event-free survival (EFS) and time to progression to accelerated phase/blast crisis (AP/BC) at 7 years were based on molecular responses using the international scale (IS) at 6-, 12-, and 18-month landmarks. Patients with BCR-ABL transcripts > 10% at 6 months and > 1% at 12 months had inferior EFS and higher rate of progression to AP/BC compared with all other molecular response groups. Conversely, patients who achieved major molecular response [MMR: BCR-ABL (IS) ≤ 0.1%] by 18 months enjoyed remarkably durable responses, with no progression to AP/BC and 95% EFS at 7 years. The probability of loss of complete cytogenetic response by 7 years was only 3% for patients in MMR at 18 months versus 26% for patients with complete cytogenetic response but not MMR (P < .001). This study shows a strong association between the degree to which BCR-ABL transcript numbers are reduced by therapy and long-term clinical outcome, supporting the use of time-dependent molecular measures to determine optimal response to therapy. This study is registered at www.clinicaltrials.gov as NCT00006343.

scholarly journals Pediatric Chronic Myeloid Leukemia with Megakaryocytic Blast Crisis as Initial Presentation: Case Report and Review of Literature

2021 ◽  
Vol 5 (4) ◽  
pp. 171-174
Author(s):  
Tuba Iqbal ◽  
◽  
Amber Younus ◽  
Uzma Zaidi ◽  
Jawad Hassan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
De Novo ◽  
Pediatric Population ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Transcript Level ◽  
Young Female

Abstract: Background: Pediatric Chronic Myeloid Leukemia (CML) is a rare entity accounting for 2-3% of pediatric malignancies. CML rarely presents as Blast Crisis (BC) at the time of diagnosis, and megakaryocytic blast crisis is even rarer. Case Presentation: We herein, report a case of a young female, 10-year-old who presented with anemia, leukocytosis and massive splenomegaly. Clinical features, peripheral film and bone marrow findings were consistent with CML in megakaryocytic blast crisis. Bone marrow cytogenetic analysis revealed karyotype of 46, XX, t(9:22)(q34;q11.2) in 20 metaphases and BCR-ABL P210 by PCR was detected with transcript level of 83%, which further confirmed our diagnosis. Conclusion: De novo presentation of chronic myeloid leukemia with megakaryocytic blast crisis is rarely observed in pediatric population with very few cases published till now. We are presenting this case because of its rarity, likelihood of misdiagnosis as AML (M7) and poor prognosis, if not treated precisely. Keywords: Chronic Myeloid Leukemia (CML), Acute Myeloid Leukemia (AML), Blast Crisis (BC), Acute Megakaryocytic Leukemia (AMKL), Chronic Phase (CP), Accelerated Phase (AP), Tyrosine Kinase Inhibitor (TKI).

scholarly journals Why is it critical to achieve a deep molecular response in chronic myeloid leukemia?

Haematologica ◽  
2020 ◽  
Vol 105 (12) ◽  
pp. 2730-2737
Author(s):  
Susan Branford
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Outcome Measurement ◽  
Quantitative Polymerase Chain Reaction ◽  
Response To Therapy ◽  
Molecular Response ◽  
Deep Molecular Response ◽  
Treatment Free Remission ◽  
Tki Discontinuation

The primary goal of tyrosine kinase inhibitor (TKI) therapy for patients with chronic myeloid leukemia is survival, which is achieved by the vast majority of patients. The initial response to therapy provides a sensitive measure of future clinical outcome. Measurement of BCR-ABL1 transcript levels using real-time quantitative polymerase chain reaction standardized to the international reporting scale is now the principal recommended monitoring strategy. The method is used to assess early milestone responses and provides a guide for therapeutic intervention. When patients successfully traverse the critical first 12 months of TKI therapy, most will head towards another milestone response, deep molecular response (DMR, BCR-ABL1 ≤0.01%). DMR is essential for patients aiming to achieve treatment-free remission and a prerequisite for a trial of TKI discontinuation. The success of discontinuation trials has led to new treatment strategies in order for more patients to reach this milestone response. DMR has been incorporated into endpoints of clinical trials and is considered by some expert groups as the optimal treatment response. But is DMR a stable response and does it provide the ultimate protection against TKI resistance and death? Do we need to increase the sensitivity of detection of BCR-ABL1 to better identify the patients who would likely remain in treatment-free remission after TKI discontinuation? Is it necessary to switch current TKI therapy to a more potent inhibitor if the goal is to achieve DMR? These are issues that I will explore in this review.

scholarly journals Monitoring after successful therapy for chronic myeloid leukemia

Hematology ◽  
2012 ◽  
Vol 2012 (1) ◽  
pp. 105-110 ◽  
Author(s):  
Susan Branford
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Response To Therapy ◽  
Inhibitor Therapy ◽  
Response Monitoring ◽  
Late Relapse ◽  
Molecular Response ◽  
Molecular Monitoring ◽  
Adherence Assessment

Abstract Monitoring response to therapy for patients with chronic myeloid leukemia using an effective strategy is fundamental for achieving optimal patient outcomes. It will allow the initiation of timely therapeutic intervention for patients with a suboptimal response or kinase inhibitor therapy failure. Evidence is mounting that reaching molecular targets early in therapy is as important as the initial hematologic and cytogenetic response for the identification of patients who may have a poorer outcome. When the molecular target of a major molecular response is achieved at 18 months, patients reach a safe haven where loss of response is rare. However, this benefit is dependent on continuous drug adherence in most patients. As some patients reach their second decade of successful imatinib therapy, how long will frequent response monitoring be necessary? Assuming that very late relapse will be extremely rare for responding patients remaining on kinase inhibitor therapy, there are reasons for maintaining a regular molecular monitoring frequency, including monitoring adherence assessment and confirming sustained undetectable BCR-ABL1 for those considering a discontinuation trial and for late molecular recurrence in patients who maintain response after treatment discontinuation.

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