Vitreous hemorrhage: A rare ophthalmic adverse effect due to imatinib treatment

Introduction Imatinib is generally well tolerated by patients. The most common ophthalmic side effects are eyelid edema and periorbital edema. Other side effects which occur at rates of <1% include blepharitis, blurred vision, conjunctival hemorrhage, conjunctivitis, retinal hemorrhage, etc. An uncommon case is here reported of a 51-year-old male with chronic myeloid leukemia who developed vitreous hemorrhage due to imatinib after 9 months of treatment. Case report A 51-year-old male with leukocytosis detected in the blood test examination was referred to the Hematology Department. The bone marrow biopsy result was compatible with chronic myeloid leukemia. Imatinib treatment (400 mg/day) was started. In the ninth month of imatinib treatment, the patient complained of a sudden decrease in vision. Vitreous hemorrhage was detected in the left eye and the patient underwent surgery. Vitreous hemorrhage recurred 1 month after the operation. On the fourth day after the discontinuation of imatinib treatment, the patient's ophthalmic complaints improved significantly. The Naranjo algorithm was applied and a score of 9 was detected. The vitreous hemorrhage of the patient was attributed to imatinib, and so the treatment of the patient was switched to bosutinib. Discussion Imatinib is an oral signal inhibitor that targets tyrosine kinase for BCR/ABL, platelet-derived growth factor, stem cell factor, and c-kit (CD117). The conjunctiva and sclera have a large amount of c-kit positive mast cells which are inhibited by imatinib. The inhibition of c-kit positive mast cells by imatinib may be responsible for further exposure of the conjunctival mucosa to injuries.

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Decision letter for "A Phase 1 study to evaluate the feasibility and efficacy of the addition of ropeginterferon alpha 2b to imatinib treatment in patients with chronic phase chronic myeloid leukemia not achieving a deep molecular response (MR 4.5) – AGMT_CML 1"

10.1002/hon.2786/v2/decision1 ◽

2020 ◽

Keyword(s):

Chronic Myeloid Leukemia ◽

Myeloid Leukemia ◽

Phase 1 ◽

Chronic Phase ◽

Molecular Response ◽

Imatinib Treatment ◽

Phase 1 Study ◽

Deep Molecular Response

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Philadelphia-negative acute myeloid leukemia with new chromosomal abnormalities developing after first-line imatinib treatment for chronic phase chronic myeloid leukemia

American Journal of Hematology ◽

10.1002/ajh.21230 ◽

2008 ◽

Vol 83 (9) ◽

pp. 755-755 ◽

Cited By ~ 4

Author(s):

Carmen Fava ◽

Jorge Cortes

Keyword(s):

Acute Myeloid Leukemia ◽

Chronic Myeloid Leukemia ◽

Myeloid Leukemia ◽

Chromosomal Abnormalities ◽

Chronic Phase ◽

Imatinib Treatment ◽

First Line ◽

Acute Myeloid

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The Role of Monitoring the Bcr-Abl Transcript Levels in the Management of Patients with Chronic Myeloid Leukemia

Acta Medica Marisiensis ◽

10.2478/amma-2013-0015 ◽

2013 ◽

Vol 59 (2) ◽

pp. 71-74

Author(s):

Aliz-Beáta Tunyogi ◽

I Benedek ◽

Judit Beáta Köpeczi ◽

Erzsébet Benedek ◽

Enikő Kakucs ◽

...

Keyword(s):

Chronic Myeloid Leukemia ◽

Myeloid Leukemia ◽

Kinase Inhibitors ◽

Blast Crisis ◽

Chronic Gvhd ◽

Molecular Response ◽

Imatinib Treatment ◽

Molecular Monitoring ◽

Hematopoietic Stem ◽

Transcript Levels

Abstract Introduction: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder; the molecular hallmark of the disease is the BCR-ABL gene rearrangement, which usually occurs as the result of a reciprocal translocation between chromosomes 9 and 22. Tyrosine kinase inhibitors (TKI) were the first drugs that targeted the constitutively active BCR-ABL kinase and it have become the standard frontline therapy for CML. Monitoring the treatment of CML patients with detection of bcr-abl transcript levels with real time qualitative polymerase chain reaction (RQ-PCR) is essential in evaluating the therapeutic response. Material and method: At the Clinical Hematology and BMT Unit Tîrgu Mureș, between 2008-2011, we performed the molecular monitoring of bcr-abl transcript levels with RQ-PCR in 16 patients diagnosed with CML. Results: We have 11 patients on imatinib treatment who achieved major molecular response. One patient lost the complete molecular response after 5 years of treatment. Two patients in blast crisis underwent allogeneic hematopoietic stem cell transplantation from identical sibling donors. The first patient is in complete molecular remission after 4 years of the transplant with mild chronic GVHD. The other patient had an early relapse with treatment refractory disease and died from evolution of the disease. Three patients with advanced phases of the disease present increasing transcript levels. We performed the dose escalation, and for two of them the switch to the second generation of TKI. Conclusions: Regular molecular monitoring of individual patients with CML is clearly desirable. It allows for a reassessment of the therapeutic strategy in cases of rising levels of BCR-ABL as an early indication of loss of response.

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Kit ligand/mast cell growth factor-independent differentiation of mast cells in myelodysplasia and chronic myeloid leukemic blast crisis

Blood ◽

10.1182/blood.v84.12.4322.bloodjournal84124322 ◽

1994 ◽

Vol 84 (12) ◽

pp. 4322-4332 ◽

Cited By ~ 29

Author(s):

P Valent ◽

E Spanblochl ◽

HC Bankl ◽

WR Sperr ◽

C Marosi ◽

...

Keyword(s):

Mast Cell ◽

Growth Factor ◽

Mast Cells ◽

Chronic Myeloid Leukemia ◽

Myeloid Leukemia ◽

Blast Crisis ◽

Cell Lineage ◽

Kit Ligand ◽

Mast Cell Growth Factor

Autonomous, factor-independent growth and differentiation of malignant cells in preleukemic and leukemic disease states is a well-recognized phenomenon and is often associated with a poor prognosis. Mast cells are distinct hematopoietic cells and express a unique profile of antigens. Growth and differentiation of normal mast cells is dependent on mast cell growth factor (MGF), the ligand of the c-kit protooncogene product. In this study, we screened for mast cell-lineage involvement in 52 patients suffering from myeloid leukemias, myelodysplastic syndromes (MDS), systemic mastocytosis, or other diseases by probing for mast cell-related molecules (c-kit, tryptase, histamine, and MGF) and by analyzing kit ligand/MGF-independent growth of mast cells in long-term suspension culture. Of the 52 patients tested, 2 patients with refractory anemia with excess of blast cells in transformation and 1 patient suffering from chronic myeloid leukemia blast crisis (CML-BC) were diagnosed as mastocytic disease. These patients were characterized by complex chromosomal abnormalities, splenomegaly, high percentages of circulating metachromatic cells (5% to 25%), high levels of cellular tryptase (> 10 ng/10(5) peripheral blood mononuclear cells/mL) and a tryptase/histamine (ng:ng) ratio greater than 1. The metachromatic cells expressed the mast-cell-related surface antigen c-kit, but not basophil-related antigens (CD11b, CDw17). Furthermore, in these 3 patients, spontaneous, MGF-independent growth of mast cells along with spontaneous synthesis of tryptase was demonstrable in long-term culture. No autocrine production, paracrine production, or overproduction of MGF was found. The spontaneous growth of mast cells could neither be abbrogated by addition of monoclonal antibodies (MoAbs) to c-kit nor by MoAbs against MGF (< 5% inhibition), whereas factor (MGF)-dependent differentiation of mast cells in these patients could be abbrogated by MoAbs to c-kit or MoAbs to MGF (> 70% inhibition, P < .001). In addition, serum MGF levels in these patients were within the normal range and MGF could not be detected in cell-free culture supernatants. All 3 patients showed rapid progression of disease and had a survival time of less than 1 year. In conclusion, we describe a unique form of transformation in MDS and CML-BC characterized by mast cell lineage involvement and factor-independent differentiation of mast cells. This form of leukemic transformation has to be delineated from chronic myeloid leukemia with basophilia or basophil crisis, from primary mast cell leukemia, and from monocytic leukemias and myelodysplastic disorders associated with basophilia.

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The PERK-eIF2α phosphorylation arm is a pro-survival pathway of BCR-ABL signaling and confers resistance to imatinib treatment in chronic myeloid leukemia cells

Cell Cycle ◽

10.4161/cc.22387 ◽

2012 ◽

Vol 11 (21) ◽

pp. 4069-4078 ◽

Cited By ~ 35

Author(s):

Monika Kusio-Kobialka ◽

Paulina Podszywalow-Bartnicka ◽

Philippos Peidis ◽

Eliza Glodkowska-Mrowka ◽

Kamila Wolanin ◽

...

Keyword(s):

Chronic Myeloid Leukemia ◽

Myeloid Leukemia ◽

Leukemia Cells ◽

Imatinib Treatment ◽

Eif2α Phosphorylation ◽

Survival Pathway

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Chronic Myeloid Leukemia

Hematology ◽

10.1182/asheducation-2003.1.132 ◽

2003 ◽

Vol 2003 (1) ◽

pp. 132-152 ◽

Cited By ~ 65

Author(s):

Junia V. Melo ◽

Timothy P. Hughes ◽

Jane F. Apperley

Keyword(s):

Chronic Myeloid Leukemia ◽

Myeloid Leukemia ◽

Molecular Mechanisms ◽

Treatment Options ◽

Philadelphia Chromosome ◽

Current Treatment ◽

Patient Specific ◽

Imatinib Treatment ◽

Molecular Monitoring ◽

Cytogenetic Analyses

Abstract Chronic myeloid leukemia (CML) was the first human malignancy to be associated with a specific genetic lesion, the Philadelphia chromosome, harboring the BCR-ABL oncogene. Since then, it has become a paradigm for the discovery of molecular mechanisms and targeted therapeutic approaches in the field of hematologic neoplasias. The past 5 years or so have been particularly fruitful in the dissection of the signal transduction pathways abnormally activated in CML and in the translation of this knowledge to clinical practice. In this report, we discuss the biological basis for such translation and highlight the current and potential tools for the effective treatment of CML patients. The first part presents a review of the basic concepts on the biology of CML and their application to the design of targeted therapy. The mechanisms of action of the molecular-specific drugs currently used in clinical trials are discussed, with emphasis on the description of the most promising new compounds that are enhancing the potential for effective alternative or combination chemotherapy in CML. In the following section, we explain how molecular monitoring of response to imatinib mesylate in patients with CML can be used as a guide to clinical management. In particular, we discuss the relative value of regular quantitative RT/PCR and cytogenetic analyses, how responding patients should be monitored and managed, and how to investigate patients who are refractory or become resistant to imatinib treatment. In the last part of this report, a discussion on the possibility of managing CML with patient-specific strategies is presented. We review the current treatment options, highlight the factors impacting on decision making, discuss the range of possibilities for future therapeutic strategies and propose a systematic approach for individualizing treatment for patients in different disease categories.

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