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 Cytomegalovirus-induced Hemorrhagic Colitis in a Patient with Chronic Myeloid Leukemia (Chronic Phase) on Dasatinib as an Upfront Therapy

2015 ◽  
Vol 8 ◽  
pp. CCRep.S25327 ◽  
Author(s):  
Mohamed A. Yassin ◽  
Abdulqadir J. Nashwan ◽  
Ashraf T Soliman ◽  
Anil Yousif ◽  
Afra Moustafa ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Fluid Retention ◽  
Hemorrhagic Colitis ◽  
Newly Diagnosed ◽  
First Case ◽  
Upfront Therapy

Dasatinib is a kinase inhibitor indicated for the treatment of newly diagnosed adults with Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia (CML) in chronic phase 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 1 The most common adverse reactions (≥15%) in patients with newly diagnosed chronic-phase (CP) CML include myelosuppression, fluid retention, and diarrhea, whereas in patients with resistance or intolerance to prior imatinib therapy, side effects include myelosuppression, fluid retention, diarrhea, headache, dyspnea, skin rash, fatigue, nausea, and hemorrhage. We report a 39-year-old Ethiopian female patient who received dasatinib as upfront therapy for the treatment of CP-CML who experienced chronic diarrhea for two months, which progressed to hemorrhagic colitis due to cytomegalovirus (CMV) infection of the colon. To our knowledge, this is the first case of CMV colitis in a patient receiving dasatinib as upfront therapy.

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.

Bosutinib (BOS) for chronic phase (CP) chronic myeloid leukemia (CML) after imatinib (IMA) failure: ≥8-y update of a phase I/II study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 7549-7549
Author(s):  
Tim H. Brümmendorf ◽  
Jorge E. Cortes ◽  
Yeow Tee Goh ◽  
Musa Yilmaz ◽  
Rebecca B. Klisovic ◽  
...  
Keyword(s):  
Phase I ◽  
Kinase Inhibitor ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Dose Intensity ◽  
Term Treatment ◽  
Prior Therapy ◽  
Long Term Treatment ◽  
New Treatment

7549 Background: BOS is approved for newly diagnosed CP CML and CML resistant/intolerant to prior therapy. In a phase I/II study, BOS showed durable efficacy and manageable toxicity in patients (pts) with CP CML after IMA failure. We report an ≥8-y update of this phase I/II and ongoing extension study. Methods: Pts with CP CML resistant/intolerant to IMA (CP2L) or IMA + dasatinib and/or nilotinib (CP3L) or with accelerated/blast phase (AP/BP) CML or Philadelphia chromosome+ acute lymphoblastic leukemia with prior tyrosine kinase inhibitor (TKI) therapy (ADV) received BOS starting at 500 mg/d. Results: 54/284 (19%) CP2L pts were still on BOS after ≥9 y and 8/119 (7%) CP3L and 5/167 (3%) ADV pts after ≥8 y; 61 CP2L pts discontinued BOS since y 5 and 21 CP3L and 12 ADV pts since y 4. Overall, the most common reason for discontinuation was disease progression/lack of efficacy in CP2L (27%), CP3L (42%) and ADV (50%) pts; last dose before discontinuation was ≥500 mg/d in 59 (21%), 28 (24%) and 46 (28%) pts, respectively. In CP2L pts, median (range) of follow-up was 54 (1–155) mo, treatment duration 26 (<1–155) mo and dose intensity 438 (87–599) mg/d; responses were durable (Table) and overall survival (OS) at 9 y was 74% vs 84% at 5 y. OS at 8 y was 69% in CP3L, 54% in AP CML and 23% in BP CML pts vs 78%, 59% and 23% at 4 y. 55 CP2L, 29 CP3L and 98 ADV pts died on study (10, 3 and 2 since the 4/5-y reports); 15, 5 and 3 had on-treatment transformations to AP/BP. Most common new treatment-emergent adverse events since y 5 in CP2L pts were pleural effusion (n=13), arthralgia (n=12) and increased blood creatinine (n=11). Conclusions: After ≥8 y, BOS continued to show durable efficacy and no new safety signals in pts with CP CML on long-term treatment, providing further support for BOS use after prior TKIs. Clinical trial information: NCT00261846 and NCT01903733 . [Table: see text]

Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome–positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance

Blood ◽  
2007 ◽  
Vol 110 (10) ◽  
pp. 3540-3546 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Francis Giles ◽  
Norbert Gattermann ◽  
Kapil Bhalla ◽  
Giuliana Alimena ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Kinase Inhibitor ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Myelogenous Leukemia ◽  
Imatinib Resistance ◽  
Abl Tyrosine Kinase ◽  
Abl Tyrosine Kinase Inhibitor ◽  
Philadelphia Chromosome Positive

Abstract Nilotinib, an orally bioavailable, selective Bcr-Abl tyrosine kinase inhibitor, is 30-fold more potent than imatinib in pre-clinical models, and overcomes most imatinib resistant BCR-ABL mutations. In this phase 2 open-label study, 400 mg nilotinib was administered orally twice daily to 280 patients with Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia in chronic phase (CML-CP) after imatinib failure or intolerance. Patients had at least 6 months of follow-up and were evaluated for hematologic and cytogenetic responses, as well as for safety and overall survival. At 6 months, the rate of major cytogenetic response (Ph ≤ 35%) was 48%: complete (Ph = 0%) in 31%, and partial (Ph = 1%-35%) in 16%. The estimated survival at 12 months was 95%. Nilotinib was effective in patients harboring BCR-ABL mutations associated with imatinib resistance (except T315I), and also in patients with a resistance mechanism independent of BCR-ABL mutations. Adverse events were mostly mild to moderate, and there was minimal cross-intolerance with imatinib. Grades 3 to 4 neutropenia and thrombocytopenia were observed in 29% of patients; pleural or pericardial effusions were observed in 1% (none were severe). In summary, nilotinib is highly active and safe in patients with CML-CP after imatinib failure or intolerance. This clinical trial is registered at http://clinicaltrials.gov as ID no. NCT00109707.

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 Success and Challenges in the Management of Chronic Myeloid Leukemia

2019 ◽  
Vol 55 (03) ◽  
pp. 135-137
Author(s):  
Anil Kumar Tripathi
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Myeloproliferative Neoplasms ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Therapeutic Modalities ◽  
Drug Of Choice ◽  
Normal Life Span

AbstractChronic myeloid leukemia (CML) is one of the most common myeloproliferative neoplasms characterized by the presence of Philadelphia chromosome, that is, t(9:22), a reciprocal translocation between long arms of chromosomes 9 and 22. In its natural course CML has three phases, that is, chronic phase, accelerated phase, and blast crises phase. Peripheral blood shows marked leukocytosis and left shift. Diagnosis is confirmed by demonstration of specific molecular abnormality by polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH) method or cytogenetics. The drug of choice is tyrosine kinase inhibitor (TKI); imatinib. Other TKIs are dasatinib and nilotinib. Most patients respond and have almost normal life span. However, challenges remain. At present the drug is prescribed for lifelong. Recent studies have shown that the drug may be stopped in certain groups of which around 50% remain in long term remission (operational cure). However, around 20% did not respond and showed resistance. Research is in progress to find out the mechanism of resistance and newer therapeutic modalities or agents.

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.

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