scholarly journals Chronic Myeloid Leukemia and Cesarean Section: The Anesthesiologist’s Point of View

2018 ◽  
Vol 2018 ◽  
pp. 1-3
Author(s):  
Houssam Rebahi ◽  
Mourad Ait Sliman ◽  
Ahmed-Rhassane El Adib
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Cesarean Section ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Hematologic Malignancy ◽  
Blast Crisis ◽  
Myeloproliferative Neoplasm ◽  
Point Of View ◽  
Poor Outcomes ◽  
Challenging Situation

Background. Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm related to chromosomal reciprocal translocation t(9;22). Tyrosine kinase inhibitors (TKIs) such as imatinib have drastically revolutionized the course and the prognosis of this hematologic malignancy. As we know, the association pregnancy-CML is an infrequent situation. Also the use of TKI in pregnant women is unsafe with a lack of alternatives and effective therapeutic options. Thus its cessation during gestation puts those patients at high risk of developing blast crisis characterized by poor outcomes.Case Report. A 37-year-old pregnant woman, gravida 2, para 2, with a previous cesarean section in 2011, presented to the obstetric unit. Her medical past revealed that she is a newly diagnosed patient with CML managed by TKI during her preconception period. Due to the perilous use of TKI during her pregnancy, a switch to interferon-αadministration was adopted. But after the completion of 36 weeks of gestation, disease progression (relapse with blast crisis), attested by biological worsening, a white blood cell count = 245000/mm3with 32% blasts in the peripheral blood, urged the medical team to opt for cesarean delivery. She underwent general endotracheal anesthesia without any perioperative incidents and gave birth to a healthy newborn. Ten days later, the patient was started on TKI.Discussion. Although data on this specific and challenging situation are limited, this case highlights the difficulties encountered by the anesthesiologists when choosing the accurate anesthetic strategy and how important it is to weigh the risks and benefits inherent to each technique. Above all, taking into consideration the possible central nervous system (CNS) contamination by circulating blast cells when performing spinal or epidural approach is primordial. This potential adverse event (CNS blast crisis) is extremely scarce but it is responsible for high rates of morbidity and mortality.

scholarly journals Ramadan Fasting in a Patient with Chronic Myeloid Leukemia Receiving Nilotinib as Upfront

2020 ◽  
Vol 13 (2) ◽  
pp. 664-667
Author(s):  
Husam N. Al-Dubai ◽  
Mohammed A. Yassin ◽  
Mohammed A. Abdulla ◽  
Mahmood S. Aldapt ◽  
Rola S. Ghassoub
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Unmet Needs ◽  
Blast Crisis ◽  
Myeloproliferative Neoplasm ◽  
Intermittent Fasting ◽  
Molecular Response ◽  
Major Molecular Response ◽  
Ramadan Fasting

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm classically described as triphasic disease: chronic, accelerated, and blast crisis. There are many unmet needs and unanswered questions about CML. Intermittent fasting in patients with CML on tyrosine kinase inhibitors is among these unmet needs. Here we report the effect of intermittent fasting on response to nilotinib as upfront in a 49-year-old female Muslim who fasted during Ramadan and took her medication once instead of twice daily and remained in major molecular response.

Educational Session: Managing Chronic Myeloid Leukemia as a Chronic Disease

Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 128-135 ◽  
Author(s):  
Andreas Hochhaus
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Blast Crisis ◽  
Treatment Options ◽  
Age Groups ◽  
Continuous Treatment ◽  
Symptomatic Therapy ◽  
Therapeutic Success

Abstract Elucidation of the pathogenesis of chronic myeloid leukemia (CML) and the introduction of tyrosine kinase inhibitors (TKIs) has transformed this disease from being invariably fatal to being the type of leukemia with the best prognosis. Median survival associated with CML is estimated at > 20 years. Nevertheless, blast crisis occurs at an incidence of 1%-2% per year, and once this has occurred, treatment options are limited and survival is short. Due to the overall therapeutic success, the prevalence of CML is gradually increasing. The optimal management of this disease includes access to modern therapies and standardized surveillance methods for all patients, which will certainly create challenges. Furthermore, all available TKIs show mild but frequent side effects that may require symptomatic therapy. Adherence to therapy is the key prerequisite for efficacy of the drugs and for long-term success. Comprehensive information on the nature of the disease and the need for the continuous treatment using the appropriate dosages and timely information on efficacy data are key factors for optimal compliance. Standardized laboratory methods are required to provide optimal surveillance according to current recommendations. CML occurs in all age groups. Despite a median age of 55-60 years, particular challenges are the management of the disease in children, young women with the wish to get pregnant, and older patients. The main challenges in the long-term management of CML patients are discussed in this review.

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

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.

scholarly journals An integrative model of pathway convergence in genetically heterogeneous blast crisis chronic myeloid leukemia

Blood ◽  
2020 ◽  
Vol 135 (26) ◽  
pp. 2337-2353 ◽  
Author(s):  
Tun Kiat Ko ◽  
Asif Javed ◽  
Kian Leong Lee ◽  
Thushangi N. Pathiraja ◽  
Xingliang Liu ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tumor Suppressor ◽  
Myeloid Leukemia ◽  
High Throughput Sequencing ◽  
Kinase Inhibitors ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Integrative Model ◽  
Dna Hypermethylation ◽  
Molecular Alterations

Abstract Targeted therapies against the BCR-ABL1 kinase have revolutionized treatment of chronic phase (CP) chronic myeloid leukemia (CML). In contrast, management of blast crisis (BC) CML remains challenging because BC cells acquire complex molecular alterations that confer stemness features to progenitor populations and resistance to BCR-ABL1 tyrosine kinase inhibitors. Comprehensive models of BC transformation have proved elusive because of the rarity and genetic heterogeneity of BC, but are important for developing biomarkers predicting BC progression and effective therapies. To better understand BC, we performed an integrated multiomics analysis of 74 CP and BC samples using whole-genome and exome sequencing, transcriptome and methylome profiling, and chromatin immunoprecipitation followed by high-throughput sequencing. Employing pathway-based analysis, we found the BC genome was significantly enriched for mutations affecting components of the polycomb repressive complex (PRC) pathway. While transcriptomically, BC progenitors were enriched and depleted for PRC1- and PRC2-related gene sets respectively. By integrating our data sets, we determined that BC progenitors undergo PRC-driven epigenetic reprogramming toward a convergent transcriptomic state. Specifically, PRC2 directs BC DNA hypermethylation, which in turn silences key genes involved in myeloid differentiation and tumor suppressor function via so-called epigenetic switching, whereas PRC1 represses an overlapping and distinct set of genes, including novel BC tumor suppressors. On the basis of these observations, we developed an integrated model of BC that facilitated the identification of combinatorial therapies capable of reversing BC reprogramming (decitabine+PRC1 inhibitors), novel PRC-silenced tumor suppressor genes (NR4A2), and gene expression signatures predictive of disease progression and drug resistance in CP.

scholarly journals Molecular biology of bcr-abl1–positive chronic myeloid leukemia

Blood ◽  
2009 ◽  
Vol 113 (8) ◽  
pp. 1619-1630 ◽  
Author(s):  
Alfonso Quintás-Cardama ◽  
Jorge Cortes
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Current Knowledge ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Oncogenic Signaling ◽  
Stem Cell Quiescence ◽  
Oncogenic Signaling Pathways

Abstract Chronic myeloid leukemia (CML) has been regarded as the paradigmatic example of a malignancy defined by a unique molecular event, the BCR-ABL1 oncogene. Decades of research zeroing in on the role of BCR-ABL1 kinase in the pathogenesis of CML have culminated in the development of highly efficacious therapeutics that, like imatinib mesylate, target the oncogenic kinase activity of BCR-ABL1. In recent years, most research efforts in CML have been devoted to developing novel tyrosine kinase inhibitors (TKIs) as well as to elucidating the mechanisms of resistance to imatinib and other TKIs. Nonetheless, primordial aspects of the pathogenesis of CML, such as the mechanisms responsible for the transition from chronic phase to blast crisis, the causes of genomic instability and faulty DNA repair, the phenomenon of stem cell quiescence, the role of tumor suppressors in TKI resistance and CML progression, or the cross-talk between BCR-ABL1 and other oncogenic signaling pathways, still remain poorly understood. Herein, we synthesize the most relevant and current knowledge on such areas of the pathogenesis of CML.

Abstract 2134: Rational design of selective MNK 1 and 2 kinase inhibitors for the treatment of blast crisis chronic myeloid leukemia patients

2016 ◽  
Author(s):  
Kassoum Nacro ◽  
Haiyan Yang ◽  
Melvyn Wai Tuck Ho ◽  
Yoon Sheng Yeap ◽  
Lohitha Rao Chennamaneni ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Rational Design ◽  
Kinase Inhibitors ◽  
Blast Crisis

scholarly journals Ponatinib as a Valid Alternative Strategy in Patients with Blast Crisis-Chronic Myeloid Leukemia Not Eligible for Allogeneic Stem Cells Transplantation and/or Conventional Chemotherapy: Report of a Case

2017 ◽  
Vol 2017 ◽  
pp. 1-5
Author(s):  
Cristina Bucelli ◽  
Daniele Cattaneo ◽  
Valeria Ferla ◽  
Manuela Zappa ◽  
Caterina de Benedittis ◽  
...  
Keyword(s):  
Stem Cells ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Blast Crisis ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
T315i Mutation ◽  
Stem Cells Transplantation ◽  
One Year

Currently, imatinib and dasatinib are the only tyrosine-kinase inhibitors approved in the US and Europe for the treatment of blast crisis of chronic myeloid leukemia (BC-CML) at diagnosis, while ponatinib is the only inhibitor used in patients bearing T315I mutation. Here we report the case of a 61-year-old man diagnosed with B-cell lymphoid BC-CML, initially treated with imatinib 800 mg day and then with dasatinib 140 mg day because of intolerance. A complete cytogenetic response (CCyR) was achieved at three months; however, three months later a relapse was observed, and the T315I mutation was detected. Ponatinib 45 mg once daily was then started together with a short course of chemotherapy. Bone marrow evaluation after six months of therapy showed the regaining of CCyR, together with the achievement of a deep molecular response. However, one year from ponatinib start the patient experienced a new disease relapse; he was effectively treated with ponatinib and chemotherapy once again, but in the meanwhile an ischemic stroke was detected. This case report confirms the high efficacy of ponatinib monotherapy in BC-CML patients, representing a valid option for non-allogeneic stem cells transplantation eligible cases and the only one available for those carrying the T315I mutation.

scholarly journals Vitamin E TPGS 1000 Induces Apoptosis in the K562 Cell Line: Implications for Chronic Myeloid Leukemia

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Jazmin Calvo-Alvarez ◽  
Marlene Jimenez-Del-Rio ◽  
Carlos Velez-Pardo
Keyword(s):  
Chronic Myeloid Leukemia ◽  
K562 Cell ◽  
Myeloid Leukemia ◽  
Caspase 3 ◽  
Kinase Inhibitors ◽  
Hematologic Malignancy ◽  
Chromatin Condensation ◽  
K562 Cells ◽  
Signaling Mechanism ◽  
Factor C

Chronic myeloid leukemia (CML) is a hematologic malignancy derived from the myeloid lineage molecularly characterized by t(9;22)(q34;q11) resulting in BCR-ABL1 gene fusion, which is known as Philadelphia (Ph) chromosome. Although tyrosine kinase inhibitors (TKIs) have restored and maintained the quality of life of patients with CML, an important minority of patients become resistant to first-and-second-generation TKIs and require an alternative treatment. The K562 cell (Ph+, p53-/-) line was treated with Vit E TPGS 1000 (20–80 μM) only or with other products of interest (e.g., antioxidant N-acetylcysteine (NAC), specific JNK and caspase-3 inhibitor SP600125, and NSCSI, respectively) for 24 h at 37°C. Cells were analyzed by fluorescence microscopy (FM), flow cytometry (FC), and Western blotting (WB) techniques. We show that TPGS induces apoptosis in K562 cells through H2O2 signaling mechanism comprising the activation of a minimal molecular cascade: the kinase JNK>the transcription factor c-JUN>the activation of BCL-only BH3 proapoptotic protein PUMA>loss of mitochondrial membrane potential (ΔΨm)>activation of caspase-3>chromatin condensation>fragmentation of DNA. Additionally, TPGS oxidizes the stress sensor protein DJ-1-Cys106-SH into DJ-1-Cys106-SO3 and arrested the cell cycle in the S phase. Remarkably, NAC, SP600125, and NSCSI blocked TPGS-induced OS and apoptosis in K562. Since TPGS is safe in mice and humans, it is especially promising for preclinical and clinical CML leukemia research. Our findings support the view that oxidation therapy offers an important opportunity to eliminate CML.

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