scholarly journals Dasatinib-induced diffuse alveolar hemorrhage

2021 ◽  
Vol 9 (41) ◽  
pp. 54-57
Author(s):  
Dhara Dave ◽  
John Kimbugwe ◽  
Randa Hazam ◽  
Saria Tasnim ◽  
Manish Patel
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Diffuse Alveolar Hemorrhage ◽  
Alveolar Hemorrhage ◽  
Caucasian Woman ◽  
Abl Tyrosine Kinase ◽  
Hypoxic Respiratory Failure ◽  
Abl Tyrosine Kinase Inhibitor ◽  
Parenchymal Abnormalities

The BCR-ABL tyrosine kinase inhibitor dasatinib is a potent treatment for chronic myeloid leukemia (CML). However, it is associated with pulmonary toxicities. Commonly reported dasatinib related pulmonary toxicities include pleural effusion, lung parenchymal abnormalities, and pulmonary hypertension. Diffuse alveolar hemorrhage (DAH) during treatment with dasatinib is very rare. To the best of our knowledge there are only two cases reported. Here we report a 57-year-old Caucasian woman who developed acute hypoxic respiratory failure while on dasatinib for treatment of CML. She was diagnosed with DAH suspected to be secondary to dasatinib, after other common etiologies were ruled out. There was full recovery after stopping dasatinib and treatment with corticosteroids. Keywords: Dasatinib, pulmonary toxicity, diffuse alveolar hemorrhage, chronic myeloid leukemia

scholarly journals Dasatinib-Induced Colitis with Rectal Sparing in a Patient with Chronic Myeloid Leukemia (Chronic Phase) on Dasatinib as an Upfront Therapy: Case Report

2021 ◽  
Vol 14 (3) ◽  
pp. 1441-1446
Author(s):  
Zakaria Maat ◽  
Kamran Mushtaq ◽  
Mohamed A. Yassin
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Prior Therapy ◽  
Abl Tyrosine Kinase ◽  
Upfront Therapy ◽  
Abl Tyrosine Kinase Inhibitor

Dasatinib is a BCR-ABL tyrosine kinase inhibitor which was approved in 2006 for the treatment of adults diagnosed with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP) and accelerated (myeloid or lymphoid blast) phase and CML with resistance or intolerance to prior therapy including imatinib and in adults with Ph+ acute lymphoblastic leukemia. Common adverse reactions (>15%) in patients diagnosed with CP-CML include myelosuppression, fluid retention, and diarrhea. We report a 34-year-old Filipino female patient who received dasatinib as upfront therapy for the treatment of CP-CML who experienced chronic diarrhea for 2 months, which progressed to colitis.

scholarly journals CHRONIC MYELOID LEUKEMIA IN PATIENT WITH THE KLINEFELTER SYNDROME

2016 ◽  
Vol 38 (3) ◽  
pp. 195-197 ◽  
Author(s):  
S V Andreieva ◽  
K V Korets ◽  
O A Kyselova ◽  
O E Ruzhinska ◽  
I M Serbin
Keyword(s):  
Targeted Therapy ◽  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Chromosomal Abnormality ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Klinefelter Syndrome ◽  
Abl Tyrosine Kinase ◽  
Abl Tyrosine Kinase Inhibitor

Aim: Genetic inborn along with acquired diseases arise due to the lesions in genome of multipotent hematopoietic stem cells. The aim was to study an influence of constitutional anomaly, Klinefelter syndrome, and additional structural rearrangements on the BCR-ABL tyrosine kinase inhibitor targeted therapy efficacy. Material and Methods: We describe a 32-year-old male patient with chronic myeloid leukemia (CML) who was detected to have sex chromosomal abnormality during evaluation for Philadelphia chromosome. Results: At diagnosis of CML, two clones were detected by standard cytogenetic investigation of bone marrow cells: 1) clone with translocation t(9;22)(q34;q11), with two sex X chromosomes and absence sex chromosome Y; 2) clone with t(9;22) and unbalanced t(Y;20)(q11;q13). Analysis of blast transformed lymphocytes from peripheral blood showed karyotype 47,XXY. Monitoring of targeted therapy with second generation inhibitor of BCR-ABL tyrosine kinase indicated a cytogenetic remission and absence of BCR-ABL1 fusion signals after 11 months. Conclusions: Absence of translocation t(9;22)(q34;q11) in blast transformed T-lymphocytes at diagnosis of CML evidences that this translocation may appear not only at the level of multipotent haemopoietic cell progenitors but also may have oligo lineage myeloid origin. Presence of additional structural chromosomal abnormality in the clone with t(9;22)(q34;q11) does not affect the efficacy of therapy with the use of second generation BCR-ABL tyrosine kinase inhibitor.

scholarly journals Is going for cure in chronic myeloid leukemia possible and justifiable?

Hematology ◽  
2012 ◽  
Vol 2012 (1) ◽  
pp. 122-128 ◽  
Author(s):  
François-Xavier Mahon
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Clinical Results ◽  
Major Question ◽  
Abl Tyrosine Kinase ◽  
Show Evidence ◽  
Abl Tyrosine Kinase Inhibitor

Abstract After more than a decade of treatment of chronic myeloid leukemia (CML) patients with the BCR-ABL tyrosine kinase inhibitor imatinib, and despite the impressive clinical results of this targeted therapeutic, many questions remain unresolved. One major question is how to cure CML, and the next step for the future will be to address this key issue. CML is a good model of cancer. The fact that the majority of CML patients who respond very well but discontinue tyrosine kinase inhibitors later show evidence of molecular recurrence focuses attention on the need for further research on leukemic stem cells. The challenge now is to understand why, after stopping treatment, the leukemia recurs in some patients but not in others. If we win this battle, this progress will certainly benefit the treatment and management of other leukemias and solid tumors and will validate this new topic.

scholarly journals Axl Blockade by BGB324 Inhibits BCR-ABL Tyrosine Kinase Inhibitor–Sensitive and -Resistant Chronic Myeloid Leukemia

2016 ◽  
Vol 23 (9) ◽  
pp. 2289-2300 ◽  
Author(s):  
Isabel Ben-Batalla ◽  
Robert Erdmann ◽  
Heather Jørgensen ◽  
Rebecca Mitchell ◽  
Thomas Ernst ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Abl Tyrosine Kinase ◽  
Abl Tyrosine Kinase Inhibitor

scholarly journals Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure

Blood ◽  
2012 ◽  
Vol 119 (15) ◽  
pp. 3403-3412 ◽  
Author(s):  
H. Jean Khoury ◽  
Jorge E. Cortes ◽  
Hagop M. Kantarjian ◽  
Carlo Gambacorti-Passerini ◽  
Michele Baccarani ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Adverse Events ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Phase 1 ◽  
Chronic Phase ◽  
Progression Free Survival ◽  
Cytogenetic Response ◽  
Abl Tyrosine Kinase ◽  
Kaplan Meier

Bosutinib, a dual Src/Abl tyrosine kinase inhibitor (TKI), has shown potent activity against chronic myeloid leukemia (CML). This phase 1/2 study evaluated the efficacy and safety of once-daily bosutinib 500 mg in leukemia patients after resistance/intolerance to imatinib. The current analysis included 118 patients with chronic-phase CML who had been pretreated with imatinib followed by dasatinib and/or nilotinib, with a median follow-up of 28.5 months. In this subpopulation, major cytogenetic response was attained by 32% of patients; complete cytogenetic response was attained by 24%, including in one of 3 patients treated with 3 prior TKIs. Complete hematologic response was achieved/maintained in 73% of patients. On-treatment transformation to accelerated/blast phase occurred in 5 patients. At 2 years, Kaplan-Meier–estimated progression-free survival was 73% and estimated overall survival was 83%. Responses were seen across Bcr-Abl mutations, including those associated with dasatinib and nilotinib resistance, except T315I. Bosutinib had an acceptable safety profile; treatment-emergent adverse events were primarily manageable grade 1/2 gastrointestinal events and rash. Grade 3/4 nonhematologic adverse events (> 2% of patients) included diarrhea (8%) and rash (4%). Bosutinib may offer a new treatment option for patients with chronic-phase CML after treatment with multiple TKIs. This trial was registered at www.clinicaltrials.gov as NCT00261846.

scholarly journals Denaturing-HPLC-Based Assay for Detection of ABL Mutations in Chronic Myeloid Leukemia Patients Resistant to Imatinib

2004 ◽  
Vol 50 (7) ◽  
pp. 1205-1213 ◽  
Author(s):  
Simona Soverini ◽  
Giovanni Martinelli ◽  
Marilina Amabile ◽  
Angela Poerio ◽  
Michele Bianchini ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Large Scale ◽  
Kinase Inhibitor ◽  
Direct Sequencing ◽  
Point Mutations ◽  
Kinase Domain ◽  
Imatinib Treatment ◽  
Abl Tyrosine Kinase ◽  
Reverse Transcription Pcr

Abstract Background: Despite the efficacy of the BCR-ABL tyrosine kinase inhibitor Imatinib mesylate for the treatment of chronic myeloid leukemia (CML), resistance has been observed in a proportion of cases, especially those with advanced stages of the disease. Point mutations within the ABL kinase domain are emerging as the most frequent mechanism for reactivation of kinase activity within the leukemic clone. Methods: We developed a denaturing-HPLC (D-HPLC)-based assay for screening for ABL point mutations. For each sample, two partially overlapping fragments of 393 and 482 bp corresponding to the kinase domain were amplified by nested reverse transcription-PCR and analyzed under selected temperature and acetonitrile gradient conditions. Fifty-one bone marrow and/or peripheral blood specimens from 27 CML patients who showed cytogenetic resistance to Imatinib were screened in parallel by D-HPLC and by direct sequencing. Results: In 12 of 27 (44%) patients, D-HPLC showed an abnormal elution profile suggesting the presence of a nucleotide change. Direct sequencing confirmed the presence of a point mutation in all cases. Conversely, all samples scored as wild type by D-HPLC showed no evidence of mutations by direct sequencing. In two cases, novel amino acid substitutions at codons already known for being hot-spots of mutation were identified (F311I and E355D). Conclusions: The proposed D-HPLC-based assay is highly specific and at least as sensitive as sequencing; with respect to the latter, it provides a much faster and less expensive semiautomated system for mutational screening. It may therefore potentially be a valuable tool for regular, large-scale testing of patients undergoing Imatinib treatment.

Overcoming STI571 resistance with the farnesyl transferase inhibitor SCH66336

Blood ◽  
2002 ◽  
Vol 100 (3) ◽  
pp. 1068-1071 ◽  
Author(s):  
Russell R. Hoover ◽  
Francois-Xavier Mahon ◽  
Junia V. Melo ◽  
George Q. Daley
Keyword(s):  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Blood Samples ◽  
Farnesyl Transferase ◽  
Abl Tyrosine Kinase ◽  
Farnesyl Transferase Inhibitor ◽  
Enhanced Expression ◽  
Abl Tyrosine Kinase Inhibitor ◽  
Induced Apoptosis

Abstract The development of chronic myeloid leukemia (CML) is dependent on the deregulated tyrosine kinase of the oncoprotein BCR-ABL. STI571 (imatinib mesylate), an abl tyrosine kinase inhibitor, has proven remarkably effective for the treatment of CML. However, resistance to STI571 because of enhanced expression or mutation of theBCR-ABL gene has been detected in patients. In the current study we show that the farnesyl transferase inhibitor (FTI) SCH66336 (lonafarnib) inhibits the proliferation of STI571-resistant BCR-ABL–positive cell lines and hematopoietic colony formation from peripheral blood samples of STI571-resistant patients with CML. Moreover, SCH66336 enhances STI571-induced apoptosis in STI571-sensitive cells and, in patients with STI571 resistance from gene amplification, cooperates with STI571 to induce apoptosis. Our data provide a rationale for combination clinical trials of STI571 and SCH66336 in CML patients and suggest that combination therapy may be effective in patients with STI571 resistance.

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