Fulminant blast crisis with de novo 11q23 rearrangement in a Philadelphia-positive CML patient undergoing treatment with dasatinib

2019 ◽  
Vol 105 (6) ◽  
pp. NP8-NP11 ◽  
Author(s):  
Snjezana Janjetovic ◽  
Anne Marie Asemissen ◽  
Frank Dicker ◽  
Mascha Binder ◽  
Judith Dierlamm ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
De Novo ◽  
Blast Crisis ◽  
Philadelphia Chromosome ◽  
Trisomy 8 ◽  
Extra Copy ◽  
First Line Therapy ◽  
Cytogenetic Analyses ◽  
Cytogenetic Evolution

Background: Progression of chronic myeloid leukemia (CML) is frequently accompanied by cytogenetic evolution, with an extra copy of the Philadelphia chromosome, trisomy 8 and 19, and isochromosome (17p) commonly detected. Translocations involving 11q23 chromosomal region have been rarely reported in CML. The few reported patients with blast crisis (BC) of CML carrying an 11q rearrangement have insufficient responses to tyrosine kinase inhibitors (TKIs) and possess a poor prognosis. Case report: We report the case of a 30-year-old man with CML who had a fulminant myeloid BC 4 months after initiation of first-line therapy with the TKI dasatinib, despite showing an optimal response at the 3-month timepoint. Despite cytoreductive therapy with hydroxyurea and 3rd-generation TKI ponatinib, the patient died within 10 days after the diagnosis of BC. Cytogenetic analyses revealed additional genetic aberrations including trisomy 8 and t(9;11)(p21;q23) involving the mixed lineage leukemia ( MLL) gene. Conclusion: The presence of 11q23 rearrangements in the relapse clone in BC of CML most likely accounts for the adverse clinical outcome. Thus, in the case of rapid and unexpected BC, the presence of 11q rearrangements should be tested together with other additional chromosomal alterations, and immediate addition of chemotherapy to the TKIs should be evaluated.

Imatinib (IM) Treatment In Chronic Myeloid Leukemia (CML). Clinical Practice Limitations

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4454-4454
Author(s):  
Alicia Inés Enrico ◽  
Georgina Bendek ◽  
Maria Virginia Prates ◽  
Virginia Guerrero ◽  
Juan Jose Napal ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Blast Crisis ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Trisomy 8 ◽  
History Of ◽  
One Year

Abstract Abstract 4454 Introduction: CML represents 15% all of oncohematologic diseases in adults. IM changed the history of the disease. At one year of treatment, the emblematic IRIS study showed Major Cytogenetic Responses (MCyR) of approximately 87% and Complete Cytogenetic Responses (CCyR) of around 76%, with PFS to accelerated phase or blast crisis of 97.7% and 91.5%, respectively. Objective: To assess treatment characteristics and responses in a group of patients treated with IM in clinical practice. Materials and Method: 113 medical records of patients with CML diagnosed between 1998–2011 from two institutions in the Argentine Republic were retrospectively analyzed. Result: Mean population age was 46 years old (r 18–73) 65 male, 48 female. 97% in chronic phase, the rest in accelerated phase. 31% presented comorbidities at diagnosis. Cytogenetic abnormalities at diagnosis, in addition to the classic t(9:22), included: trisomy 8 and double Philadelphia chromosome in 4 tests. Only 7 patients had qualitative BCR/ABL determined at diagnosis. 25% had received interferon, patients received IM 400 mg and only 2% received 300 or 600 mg doses. 2.6% of patients did not achieve CHR. Cytogenetic responses assessed at any time of treatment were: Major: 12%, Minor 20%, Complete 51%, None 3%, 14% were not assessed. With a mean follow-up time of 46 months, the overall survival was 75%. 10% of patients progressed to BC/AP, 11 % of patients died due to disease-related causes or comorbidities. Conclusions: With a mean follow-up time of 46 months for chronic phase CML, treatment with IM achieved complete cytogenetic responses in 51% of patients, and progression occurred in 10% of patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Coexistence of Recurrent Chromosomal Abnormalities and the Philadelphia Chromosome in Acute and Chronic Myeloid Leukemias: Report of Five Cases and Review of Literature

2020 ◽  
Author(s):  
Jinying Gong ◽  
Zhenhao Zhang ◽  
Wei Zhang ◽  
Huijun Wang ◽  
Xiaofang Feng ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chromosomal Abnormalities ◽  
Philadelphia Chromosome ◽  
Chromosomal Translocation ◽  
Myelogenous Leukemia ◽  
Trisomy 8 ◽  
Extra Copy ◽  
Genetic Abnormalities ◽  
Acute Myeloid

Abstract Progression of chronic myelogenous leukemia (CML) is frequently accompanied by cytogenetic evolution. Additional genetic abnormalities are seen in 10-20 % of CML cases at the time of diagnosis, and in 60–80 % of cases of advanced disease. Unbalanced chromosomal changes such as an extra copy of the Philadelphia chromosome (Ph), trisomy 8, and i(17)(q10) are common. Balanced chromosomal translocations, such as t(3;3), t(8;21), t(15;17), and inv(16) are typically found in acute myeloid leukemia, but rarely occur in CML. Translocations involving 11q23, t(8;21), and inv(16) are relatively common genetic abnormalities in acute leukemia, but are extremely rare in CML. In the literature to date, there are at least 76 Ph+ cases with t(3;21), 47 Ph+ cases with inv(16), 16 Ph+ cases with t(8;21), and 9 Ph+ cases with t(9;11). But most of what has been published is now over thirty years old, without the benefit of modern immunophenotyping to confirm diagnosis, and before the introduction of treatment regimes such as TKI. In this study, we explored the rare concomitant occurrence of coexistence current chromosomal translocation and t(9;22) in CML or acute myeloid leukemia (AML).

Incidence and outcomes of chronic myeloid leukemia (CML) patients (pts) treated with second-generation tyrosine kinase inhibitors (TKI) who develop other chromosomal abnormalities (OCA).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7090-7090
Author(s):  
Naveen Pemmaraju ◽  
Hagop M. Kantarjian ◽  
Elias Jabbour ◽  
Alfonso Quintas-Cardama ◽  
Gautam Borthakur ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Chromosomal Abnormalities ◽  
Philadelphia Chromosome ◽  
Initial Therapy ◽  
Adverse Impact ◽  
Trisomy 8 ◽  
Hematologic Disorders ◽  
2Nd Generation

7090 Background: Development of OCA has been reported among pts receiving imatinib as initial therapy for CML. Little is known about OCA development in CML pts treated with frontline 2nd generation TKI (dasatinib, nilotinib). Methods: OCA is defined as cytogenetic abnormality in non-Philadelphia chromosome positive clones as pts respond to TKI. Among pts treated with frontline dasatinib (n=99) or nilotinib (n=117), on parallel prospective single-arm phase II protocols at MDACC, 30 OCA ptswere identified, chronic (n=25) or accelerated phase (AP) (n=5). Results: 11 (11%) pts treated with dasatinib and 19 (16%) with nilotinib developed OCA; median follow-up 30 mo (range 0-71). Difference in OCA incidence with dasatinib and nilotinib was not statistically significant. At start of therapy, median age (years) of OCA pts was 53 (41-71) with dasatinib and 52 (37-82) with nilotinib, compared to those pts without OCA: 48 (18-83) with dasatinib and 49 (17-87) with nilotinib. Most common OCA was abnormality of chromosome 7 with 6 occurrences in 5 pts (1 pt with both inv(7) and +7) (inversion (n=1), 2 different translocations (n=2), deletions (n=2), and additions (n=1)). No pts developed trisomy 8 (historically most common OCA in imatinib-treated pts). Median time to first OCA: 9 mo (range 3-58) for all pts (12 mo (range 3-58) for dasatinib group and 9 mo (3-48) for nilotinib group). OCA disappeared spontaneously in 25 pts during follow-up. Outcomes for OCA versus non-OCA group (Table). For AP pts: 3/6 (50%) in dasatinib group and 2/17 (12%) in nilotinib group developed OCA. None of the OCA pts has developed AML or MDS. Conclusions: OCA is observed in 10-15% of pts receiving initial therapy with 2nd generation TKI. At median follow-up of 30 mo, occurrence of OCA confers no adverse impact on outcomes when compared to non-OCA pts treated with 2nd generation TKI and has not resulted in other hematologic disorders. [Table: see text]

scholarly journals Chromosomal Aberrations in Chronic Myeloid Leukemia: Response to Conventional TKIs and Risk of Blastic Transformation

2021 ◽  
Vol 6 (1) ◽  
pp. 35-39
Author(s):  
Shafaq Maqsood ◽  
Fatima Ali ◽  
Abdul Hameed ◽  
Neelam Siddiqui
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Chromosomal Abnormalities ◽  
Fusion Gene ◽  
Philadelphia Chromosome ◽  
Trisomy 8 ◽  
Additional Chromosomal Abnormalities

Background and Purpose: Chronic Myeloid Leukemia (CML) is a common hematological malignancy. The characteristic molecular abnormality is the presence of Philadelphia chromosome or BCR-ABL fusion gene which is the result of 9:22 translocation. Tyrosine kinase inhibitors (TKIs) form the main stay of treatment in CML with excellent responses. The purpose of this study was to determine the impact of additional chromosomal abnormalities on outcomes in CML.Methods: This is a retrospective chart review of all patients who were diagnosed with CML in chronic phase (CP) with additional chromosomal abnormalities (ACAs) over a period of 5 years from 2010 to 2015 at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan. Results: A total of 283 patients were diagnosed with CML from January 2010 to January 2015. 31 patients out of these were found to have additional chromosomal abnormalities at the time of diagnosis in addition to BCR-ABL fusion gene or Philadelphia chromosome detection. Out of these 31 patients, 23 (74.2%) were males whereas 8 (25.8%) were females. 13 (41.9%) were in the age group of 31 to 50 years whereas the other two groups that is 18 to 30 years and 51 to 70 years had 9 patients each. After approval from the government which usually takes a standard 2-3 weeks’ time, these patients were started on tyrosine kinase inhibitors which was Imatinib in 30 (96.8%) and Nilotinib in 1 (3.2%) patient. Conventional cytogenetic analysis performed for each patient at the time of diagnosis revealed that 11 (35.5%) of patients had variant Philadelphia chromosome followed by 7 patients (22.6%) with trisomy 8. 5 patients (16.1%) had multiple chromosomal abnormalities including trisomy 8, deletion 1 and isochrome 17q. 2 patents each had isochrome 17q, inversion 3 and deletion 9 abnormalities. 1 patient had deletion 7 whereas 1 had variant Philadelphia chromosome with other chromosomal abnormalities. Conclusion: It was evident that frequently occurring ACAs In our CML population were Variant Philadelphia chromosome and trisomy 8.

Effect of Dasatinib on Genes Related to Mitotic Catastrophe Pathway in Chronic Myeloid Leukemia Cells

2020 ◽  
Vol 20 ◽  
Author(s):  
Sezgi Kipcak ◽  
Buket Ozel ◽  
Cigir B. Avci ◽  
Leila S. Takanlou ◽  
Maryam S. Takanlou ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Fusion Gene ◽  
Philadelphia Chromosome ◽  
K562 Cells ◽  
Mitotic Catastrophe ◽  
Control Group ◽  
Cancer Therapies ◽  
Apoptosis Pathways

Background: Chronic myeloid leukemia (CML), is characterized by a reciprocal translocation t(9;22) and forms the BCR/ABL1 fusion gene, which is called the Philadelphia chromosome. The therapeutic targets for CML patients which are mediated with BCR/ABL1 oncogenic are tyrosine kinase inhibitors such as imatinib, dasatinib, and nilotinib. The latter two of which have been approved for the treatment of imatinib-resistant or intolerance CML patients. Mitotic catastrophe (MC) is one of the non-apoptotic mechanisms which frequently initiated in types of cancer cells in response to anti-cancer therapies; pharmacological inhibitors of G2 checkpoint members or genetic suppression of PLK1, PLK2, ATR, ATM, CHK1, and CHK2 can trigger DNA-damage-stimulated mitotic catastrophe. PLK1, AURKA/B anomalously expressed in CML cells, that phosphorylation and activation of PLK1 occur by AURKB at centromeres and kinetochores. Objective: The purpose of this study was to investigate the effect of dasatinib on the expression of genes in MC and apoptosis pathways in K562 cells. Methods: Total RNA was isolated from K-562 cells treated with the IC50 value of dasatinib and untreated cells as a control group. The expression of MC and apoptosis-related genes were analyzed by the qRT-PCR system. Results: The array-data demonstrated that dasatinib-treated K562 cells significantly caused the decrease of several genes (AURKA, AURKB, PLK, CHEK1, MYC, XPC, BCL2, and XRCC2). Conclusion: The evidence supply a basis to support clinical researches for the suppression of oncogenes such as PLKs with AURKs in the treatment of types of cancer especially chronic myeloid leukemia.

Human leukocyte antigen-DR negative de novo acute myeloid leukemia with Philadelphia chromosome

2008 ◽  
Vol 88 (5) ◽  
pp. 602-605
Author(s):  
Tohru Inaba ◽  
Hiroshi Nishimura ◽  
Junko Saito ◽  
Yoko Yamane ◽  
Takuya Nakatani ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Human Leukocyte Antigen ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Philadelphia Chromosome ◽  
Human Leukocyte ◽  
Leukocyte Antigen ◽  
Acute Myeloid

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 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.

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