The Association of Gilbert's Syndrome with Hyperbilirubinaemia Occurring on Any of Imatinib, Dasatinib and Nilotinib in Patients with Chronic Myeloid Leukaemia (CML)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2795-2795 ◽  
Author(s):  
Jeeyune Bahk ◽  
Simone Claudiani ◽  
Richard M Szydlo ◽  
Sarmad Toma ◽  
Faisal Abdillah ◽  
...  
Keyword(s):  
Liver Function ◽  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Research Funding ◽  
Chronic Phase ◽  
Gilbert’S Syndrome ◽  
Gilbert's Syndrome ◽  
Number Of Patients ◽  
Increased Risk ◽  
Grade 3

Abstract Background: Individuals with Gilbert's syndrome present with mild, unconjugated hyperbilirubinaemia, resulting from impaired glucuronidation by reduced uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) expression. The A(TA)7TAA polymorphism responsible for the syndrome has been associated with nilotinib-induced hyperbilirubinaemia in patients with chronic myeloid leukaemia (CML). Our study extends UGT1A1 molecular analysis to a larger cohort of CML patients receiving other tyrosine kinase inhibitors (TKIs) and explores the relationship with other abnormalities of liver function. Methods: We interrogated our database of 832 patients treated with a TKI for CML at our center and identified 467 individuals who presented in first chronic phase, who had received only a TKI (prior interferon, combination experimental therapy, autologous and allogeneic transplant patients were all excluded) and for whom serial liver function results were available. We then performed PCR to identify variations in dinucleotide repeats in the UGT1A1 promoter region. Genotypes were assigned as follows: 6/6 (homozygous for (TA)6 allele; wild-type), 7/7 (homozygous for (TA)7allele) and 6/7 (heterozygous). Because individual patients may have received more than one TKI, we defined the period on treatment with each TKI as an 'episode' in order to be able to attribute abnormalities of liver function to a specific drug. Hyperbilirubinaemia was graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Both ALT and ALP were defined as increased if they were above the upper limit of normal. To date we have completed the analysis for 340 patients comprising a total of 568 episodes of TKI therapy (imatinib 313, dasatinib 125, nilotinib 130). Results: The UGT1A1 genotype analysis showed six variants. The majority of patients displayed one of 6/6 (149 patients), 6/7 (138 patients) or 7/7 (48 patients) genotypes. Small numbers of patients with the 5/6, 5/7 and 6/8 genotypes were excluded from further analysis. Hyperbilirubinaemia was seen in patients with all three genotypes, but was more frequent in patients on nilotinib (44%), compared to imatinib (14%) and dasatinib (8%). The incidence of hyperbilirubinaemia in individuals with the 6/6 genotype was 6%, 0% and 22% for imatinib, dasatinib and nilotinib respectively, and 10%, 6% and 56% for patients with the 6/7 genotype. The frequency of hyperbilirubinaemia in those with the 7/7 genotype was significantly higher compared to the occurrence of such events in any other genotype, irrespective of treatment. However, it occurred more often in patients on nilotinib (80%), followed by imatinib (61%) and dasatinib (44%). A significantly higher number of patients with the 7/7 genotype on nilotinib reported Grade 3 hyperbilirubinaemia (25%), with no grade 3 events on imatinib and only one on dasatinib. Hyperbilirubinaemia on any single drug did not predict for this event on any subsequent drug. Further analysis of liver function tests (LFTs) and bilirubin levels divided episodes into four groups: 1. Episodes with normal bilirubin and normal LFTs (n = 273), 2. Episodes with isolated raised LFTs but normal bilirubin (n = 179), 3. Episodes with isolated hyperbilirubinaemia (n = 27) but normal LFTs and 4. Episodes with raised bilirubin and raised LFTs (n = 84). Abnormal LFTs with or without hyperbilirubinaemia were most commonly seen on nilotinib (65%) compared to imatinib (40%) and dasatinib (46%), confirming previous reports of the frequencies of transaminitis on the various TKIs. Isolated hyperbilirubnaemia was uncommon (<6%) on any of the drugs, but was more frequent in the 7/7 than the 6/6 or 6/7 genotypes for imatinib or dasatinib. Interestingly it was not seen in patients with the 7/7 genotype on nilotinib, as 80% of the 7/7 patients with hyperblirubinaemia on nilotinib had other abnormalities of liver function. Conclusion. We confirmed the increased risk of hyperbilirubinaemia in individuals with the A(TA)7TAA polymorphism when treated with nilotinib. In contrast to other reports, we found that all patients with the 7/7 genotype are susceptible to increases in bilirubin when treated with any of imatinib, dasatinib or nilotinib. Hyperbilirubinaemia most commonly occurs alongside elevations in LFTs on nilotinib, indicating a nilotinib-induced hepatotoxicity that is compounded by the additional UGT1A1 inhibition. Disclosures Milojkovic: ARIAD Pharmaceuticals Inc.: Honoraria; Pfizer: Honoraria; BMS: Honoraria; Novartis: Honoraria. Apperley:Pfizer: Honoraria; Bristol Myers Squibb: Honoraria; Ariad: Honoraria; Novartis: Honoraria. Foroni:Bristol Myers Squibb: Research Funding; Novartis: Research Funding; Ariad: Research Funding.

Early Dose-Escalation in Chronic Myeloid Leukaemia Patients with Low Plasma Imatinib Levels Leads to Equivalent BCR-ABL Values and Drug Levels at 6 Months to Those with Optimal Drug Levels: First Analysis From the TIDEL II Trial of De-Novo Patients Treated with 600mg Imatinib.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1131-1131 ◽  
Author(s):  
Michael P Osborn ◽  
Deborah L White ◽  
Verity A Saunders ◽  
Bronwyn Cambareri ◽  
Susan Branford ◽  
...  
Keyword(s):  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Dose Escalation ◽  
Research Funding ◽  
Trough Level ◽  
Chronic Phase ◽  
Prognostic Impact ◽  
Drug Levels ◽  
Optimal Drug ◽  
Trough Levels

Abstract Abstract 1131 Poster Board I-153 Aim Low trough plasma imatinib levels have been associated with a poorer response to treatment in chronic myeloid leukaemia (CML) in chronic phase. We hypothesised that dose-escalation in patients with low day 22 trough levels could improve outcomes. In this interim analysis, we compared the BCR-ABL levels for patients who were dose escalated due to initial suboptimal imatinib levels to those with optimal imatinib levels. We also determined whether dose escalation leads to an increase in plasma imatinib levels. Method Imatinib trough and peak levels were measured in 74 chronic phase CML patients enrolled to the Australasian Leukaemia and Lymphoma Group TIDEL II study at day 8, day 22, and 3 and 6 months after commencing imatinib 600 mg. Patients with a day 22 imatinib trough level of <1000 ng/ml were dose escalated to 800 mg daily where tolerated. BCR-ABL levels were measured at 1, 2, 3 and 6 months using RQ-PCR and values were reported on the international reporting scale (IS). Results The median follow-up was 36 weeks, with 64 of 74 patients having 3 month data and 50 having 6 month data. At day 22, 11 (15%) patients had an imatinib trough level <1000 ng/ml, with 7 of these able to dose-escalate to 800 mg. The other 4 subjects with a low imatinib trough level were either unable to tolerate dose-escalation or were already on a dose <600 mg. At 3 and 6 months, the mean (±SD) imatinib trough level in those who had been dose escalated to 800 mg due to a day 22 trough level of <1000 ng/ml was no longer significantly different from those with a day 22 trough level of ≥1000 ng/ml (1710 ±392 vs 1760 ±949 ng/ml at 3 months, p=0.74; 1642 ±566 vs 1535 ±755 ng/ml at 6 months, p=0.75). At 2 months, the patients who were dose escalated had a significantly higher median BCR-ABL% IS level compared with those with optimal imatinib levels at day 22 (17.5% vs 6.4%, p=0.02). By 3 and 6 months this difference in BCR-ABL level had diminished and was no longer significantly different (7.3% vs 1.9% at 3 months, p=0.06; 2.1% vs 2.7% at 6 months, p=0.66). Conclusion This data suggests that selective dose-escalation based on Day 22 imatinib trough levels of <1000 ng/ml may result in subsequent plasma concentrations equivalent to patients with day 22 levels of >1000 ng/ml and equivalent BCR-ABL reductions. Whether this strategy can ameliorate the adverse prognostic impact of low plasma imatinib concentrations on standard dose will be the subject of ongoing study. Disclosures White: Novartis and Britol-Myers Squibb: Research Funding. Branford:Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding. Slader:Novartis Pharmaceuticals Australia: Employment, Equity Ownership. Hughes:Bristol Meyers Squibb: Advisor, Honoraria, Research Funding; Novartis: Advisor, Honoraria, Research Funding.

scholarly journals PF-114: A 4th Generation Tyrosine Kinase-Inhibitor for Chronic Phase Chronic Myeloid Leukaemia Including BCRABL1T315I

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1638-1638 ◽  
Author(s):  
Anna G. Turkina ◽  
Olga Vinogradova ◽  
Elza Lomaia ◽  
Evgeniya Shatokhina ◽  
Oleg A. Shukhov ◽  
...  
Keyword(s):  
Adverse Events ◽  
Chronic Myeloid Leukaemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Myeloid Leukaemia ◽  
Research Funding ◽  
Kinase Inhibitor ◽  
Molecular Response ◽  
Travel Grant ◽  
Grade 3

Background: PF-114 is a 4th-generation oral tyrosine kinase-inhibitor (TKI) active against wild-type and mutated BCR-ABL1 isoforms including BCR-ABL1T315I. We present data from a phase-1 study in patients with chronic or accelerated phase chronic myeloid leukaemia (CML) failing ≥2 TKIs or with BCR-ABL1T315I (NCT02885766) with ≥6 months therapy. Methods: 3+3 dose-escalation study to determine maximum tolerated dose (MTD) and dose-limiting toxicity (DLT). Secondary objectives included safety and efficacy based on haematological, cytogenetic, and molecular criteria. Adverse events (AEs) were graded using NCI-CTCAE v4.03. Results: 51 patients were enrolled. Daily doses were 50 mg (n=3), 100 mg (n=3), 200 mg (n=9), 300 mg (n=11), 400 mg (n=12), 500 mg (n=3), 600 mg (n=6), 750 mg (n=4) given continuously. Median age was 50 years (range, 29-82 years). Median CML duration pre-study was 10 years (range, 0.3-23 years). All patients had baseline ECOG performance scores 0-1. Twelve patients had BCR-ABL1T315I. Patients were heavily pre-treated: 25 received ≥3 prior TKIs; 5 patients with BCR-ABL1T315I received 1 prior TKI. Interim analysis was conducted at follow-up of ≥6 months (cut-off date January 16th 2019). Therapy was ongoing in 17 patients at doses 200 mg (n=4), 300 mg (n=9), 400 mg (n=3) and 600 mg (n=1) with median duration of exposure of 7,4 (range, 4,6-26), 9,2 (range, 7,4-26), 9,2 (range, 8,3-9,2) and 9,2 months. Other patients discontinued because of progression (n=18), adverse events (n=6), consent withdrawal (n=4), participation in another study (n=3) or other reasons (n=3). The MTD was 600 mg with the grade-3 psoriasis-like skin lesions the DLT, which occurred during the first 28 days of treatment. Reversible grade-3 skin toxicity occurred in 11 patients at doses ≥400 mg. There were no other drug-related non-hematologic grade-3 toxicities except 1 grade-3 toxic hepatitis at 400 mg and there were no detectable effects on ankle-brachial index or vascular occlusive events. The best safety/efficacy dose was 300 mg/d with 6 of 11 patients achieving a major cytogenetic response (MCyR) and 4 of them - a major molecular response (MMR). Higher doses were less effective probably because of toxicity-related therapy interruptions and discontinuations. Five of 12 patients with BCR-ABL1T315I responded, 3 of which achieved a complete hematologic response and 4 achieved MCyR. Conclusion: PF-114 was safe and effective in patients with CML failing ≥2 TKIs or with BCR-ABL1T315I. The most effective dose was 300 mg/d. Five of 12 patients with BCR-ABL1T315I responded. A pivotal study is beginning. Disclosures Turkina: Novartis: Consultancy, Speakers Bureau; Pfizer: Consultancy; Bristol Myers Squibb: Consultancy; fusion pharma: Consultancy; Novartis: Consultancy, Speakers Bureau. Vinogradova:Novartis: Consultancy; Fusion Pharma: Consultancy. Lomaia:Novartis: Other: Travel Grant;Lecture fee; Pfizer: Other: Travel Grant. Shukhov:Pfizer: Consultancy; Novartis: Consultancy. Chelysheva:Novartis: Consultancy, Honoraria; Fusion Pharma: Consultancy. Shikhbabaeva:Novartis: Consultancy; Fusion Pharma: Consultancy. Shuvaev:Fusion Pharma: Consultancy; Novartis: Consultancy; Pfize: Honoraria; BMS: Consultancy. Cortes:Pfizer: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Biopath Holdings: Consultancy, Honoraria; Immunogen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Astellas Pharma: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; BiolineRx: Consultancy; Sun Pharma: Research Funding; Merus: Consultancy, Honoraria, Research Funding; Forma Therapeutics: Consultancy, Honoraria, Research Funding. Baccarani:Novartis: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Takeda: Consultancy. Ottmann:Roche: Honoraria; Pfizer: Honoraria; Fusion Pharma: Honoraria; Takeda: Honoraria; Novartis: Honoraria; Celgene: Honoraria, Research Funding; Incyte: Honoraria, Research Funding; Amgen: Honoraria, Research Funding. Mikhailov:Fusion Pharma: Employment. Novikov:Fusion Pharma: Employment. Shulgina:Fusion Pharma: Employment. Chilov:Fusion Pharma: Consultancy.

Safety and Management of Toxicities in the BELA Trial of Bosutinib Versus Imatinib in Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1685-1685 ◽  
Author(s):  
Carlo Gambacorti-Passerini ◽  
Jorge E Cortes ◽  
Patricia Harris ◽  
Christine Powell ◽  
Athena Countouriotis ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Liver Function ◽  
Liver Function Test ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Chronic Phase ◽  
Primary Reason ◽  
Newly Diagnosed ◽  
Function Test ◽  
Grade 3

Abstract Abstract 1685 Bosutinib (BOS) is an orally active, dual competitive Src/Abl kinase inhibitor. The phase 3 BELA study compared the safety and activity of BOS 500 mg/d with imatinib (IM) 400 mg/d in patients (pts) with newly diagnosed chronic phase chronic myeloid leukemia (CP CML). This analysis summarizes the safety profile of each agent, addressing management of gastrointestinal toxicities and liver function test changes. The median age was 48 y (range, 19–91 y) in the BOS arm and 47 y (range, 18–89 y) in the IM arm. Median treatment durations were 19.3 mo for BOS and 19.5 mo for IM; 67% and 74% of pts are still receiving therapy. The primary reason for BOS discontinuation was adverse events (AEs; 23% BOS [15/55 without prior dose adjustment] vs 6% IM). The primary reason for IM discontinuation was disease progression (4% BOS vs 13% IM). Deaths occurred in 6 (2%) BOS pts versus 13 (5%) IM pts; the majority occurred after treatment discontinuation. Non–CML-related deaths (1 pt each) included mesenteric embolia/intestinal necrosis (BOS), cardiovascular disease (IM), fatal septicemia (IM), lung embolism (IM), and pneumonia (IM). BOS was associated with higher incidences versus IM of all grades of gastrointestinal toxicities (diarrhea [69% vs 22%], vomiting [32% vs 14%], and abdominal pain [13% vs 6%]) and pyrexia (18% vs 10%). In contrast, BOS was associated with lower incidences of edema (peripheral edema [4% vs 11%] and periorbital edema [1% vs 14%]) and musculoskeletal events (myalgia [5% vs 11%], muscle cramps [4% vs 22%], and bone pain [4% vs 10%]). Diarrhea (11% vs 1%, respectively) and vomiting (3% vs 0%) were the most common grade 3/4 AEs. Elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were reported as grade 3/4 AEs for 18% and 8% of pts on BOS, respectively, versus 2% and 2% of pts on IM. Diarrhea typically occurred during the initial month of treatment, with the median time to first event of 3 d (range, 1–589 d) on BOS (n = 172) and 26 d (range, 1–829 d) on IM (n = 56) and median duration of a diarrhea event of 3 d (range, 1–836 d) and 5 d (range, 1–771 d), respectively. Diarrhea was managed with antidiarrheal medication in 68% of BOS pts and 43% of IM pts; 22% and 9% of pts with diarrhea required temporary dose interruption, while 8% and 0% had a reduction of their dose. Of the pts who had a temporary dose interruption due to diarrhea, 34/38 pts on BOS and 5/5 pts on IM were rechallenged without recurrence of diarrhea or permanent discontinuation due to diarrhea. Grade 3/4 liver function test laboratory abnormalities were more common among pts receiving BOS versus IM, including elevation of ALT (23% vs 4%) and AST (12% vs 3%); the majority experienced grade 3 events. The median times to first ALT elevation were 28 d for BOS (n = 78) and 114 d for IM (n = 18); median times to first AST elevation were 28 d for BOS (n = 65) and 107 d for IM (n = 19). For BOS and IM, respectively, median durations for a grade 3/4 event to grade ≤1 severity were 21.0 versus 25.0 d for ALT elevation and 21.5 versus 25.0 d for AST elevation. Of the pts with ALT elevations, 35% versus 56% had a dose reduction and 56% versus 28% had a temporary dose interruption. Of the 40 pts who were rechallenged with BOS after dose interruption due to ALT elevation, 32 (80%) were successfully rechallenged without reoccurrence of their event or did not discontinue due to ALT elevation; all 4 pts who were rechallenged after IM interruption were successfully rechallenged. Of the pts with AST elevations, 17% versus 5% had a dose reduction and 43% versus 16% had a temporary dose interruption. All of the 26 pts who were rechallenged with BOS after dose interruption due to AST elevation were successfully rechallenged without reoccurrence of their event or discontinuation due to AST elevation; all 3 pts who were rechallenged after IM interruption were successfully rechallenged. No cases met the Hy's Law criteria. Ten pts discontinued BOS due to ALT elevation; no other discontinuations due to liver function test abnormalities were reported. In conclusion, BOS and IM were associated with acceptable but distinct safety profiles in pts with newly diagnosed CP CML. BOS was mainly associated with gastrointestinal AEs and transient liver function test elevations, both of which were managed with dose modifications and were not life threatening. Additional experience in managing the toxicities associated with BOS treatment may reduce the overall number of pts discontinuing BOS due to toxicity. Disclosures: Gambacorti-Passerini: Pfizer Inc: Honoraria, Research Funding; BMS: Research Funding; Novartis: Honoraria; Biodiversity: Honoraria. Cortes:Pfizer Inc: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Harris:Pfizer Inc: Employment. Powell:Pfizer Inc: Employment, Equity Ownership. Countouriotis:Pfizer Inc: Employment. Kantarjian:Novartis: Consultancy, Research Funding; BMS: Research Funding; Pfizer Inc: Research Funding; Ariad: Research Funding.

scholarly journals Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yotaro Ochi ◽  
Kenichi Yoshida ◽  
Ying-Jung Huang ◽  
Ming-Chung Kuo ◽  
Yasuhito Nannya ◽  
...  
Keyword(s):  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Kinase Inhibitors ◽  
Blast Crisis ◽  
Clonal Evolution ◽  
Chronic Phase ◽  
Genetic Alterations ◽  
Prognostic Impact ◽  
Genetic Abnormalities ◽  
Prior Use

AbstractBlast crisis (BC) predicts dismal outcomes in patients with chronic myeloid leukaemia (CML). Although additional genetic alterations play a central role in BC, the landscape and prognostic impact of these alterations remain elusive. Here, we comprehensively investigate genetic abnormalities in 136 BC and 148 chronic phase (CP) samples obtained from 216 CML patients using exome and targeted sequencing. One or more genetic abnormalities are found in 126 (92.6%) out of the 136 BC patients, including the RUNX1-ETS2 fusion and NBEAL2 mutations. The number of genetic alterations increase during the transition from CP to BC, which is markedly suppressed by tyrosine kinase inhibitors (TKIs). The lineage of the BC and prior use of TKIs correlate with distinct molecular profiles. Notably, genetic alterations, rather than clinical variables, contribute to a better prediction of BC prognosis. In conclusion, genetic abnormalities can help predict clinical outcomes and can guide clinical decisions in CML.

Low-dose dasatinib in older patients with chronic myeloid leukaemia in chronic phase (DAVLEC): a single-arm, multicentre, phase 2 trial

2021 ◽  
Vol 8 (12) ◽  
pp. e902-e911 ◽  
Author(s):  
Kazunori Murai ◽  
Hiroshi Ureshino ◽  
Takashi Kumagai ◽  
Hideo Tanaka ◽  
Kaichi Nishiwaki ◽  
...  
Keyword(s):  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Older Patients ◽  
Low Dose ◽  
Chronic Phase ◽  
Phase 2 ◽  
Multicentre Phase ◽  
Phase 2 Trial

scholarly journals Prognostic significance of cellular vascular endothelial growth factor (VEGF) expression in the course of chronic myeloid leukaemia

2009 ◽  
Vol 137 (7-8) ◽  
pp. 379-383 ◽  
Author(s):  
Ana Vidovic ◽  
Gradimir Jankovic ◽  
Dragica Tomin ◽  
Maja Perunicic-Jovanovic ◽  
Irena Djunic ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Prognostic Significance ◽  
Chronic Phase ◽  
Vascular Endothelial ◽  
Vegf Expression ◽  
Endothelial Growth Factor ◽  
The Impact

Introduction. Increased angiogenesis in bone marrow is one of the characteristics of chronic myeloid leukaemia (CML), a clonal myeloproliferative disorder that expresses a chimeric bcr/abl protein. Vascular endothelial growth factor (VEGF) is one of the most potent and a specific regulator of angiogenesis which principally targets endothelial cells and regulates several of their functions, including mitogenesis, permeability and migration. The impact of elevated VEGF expression on the course of chronic myeloid leukaemia is unknown. Objective. The aim of this study was the follow-up of VEGF expression during the course of CML. Methods. We studied VEGF expression of 85 CML patients (median age 50 years, range 16-75 years). At the commencement of the study, 29 patients were in chronic phase (CP), 25 in an accelerated phase (AP), and 31 in the blast crisis (BC). The temporal expression (percentage positivity per 1000 analysed cells) VEGF proteins over the course of CML were studied using the immunohistochemical technique utilizing relevant monoclonal antibodies. It was correlated with the laboratory (Hb, WBC and platelet counts, and the percentage of blasts) and clinical parameters (organomegaly, duration of CP, AP, and BC) of disease progression. Results. The expression of VEGF protein was most pronounced in AP (ANOVA, p=0.033). The level of VEGF expression correlated inversely with the degree of splenomegaly (Pearson, r=-0.400, p=0.011). High expression of VEGF correlated with a shorter overall survival (log rank, p=0.042). Conclusion. Immunohistochemically confirmed significance of the expression of VEGF in dependence of the CML stage could be of clinical importance in deciding on the timing therapy. These data suggest that VEGF plays a role in the biology of CML and that VEGF inhibitors should be investigated in CML.

scholarly journals Treatment-Free Remission in Chronic Myeloid Leukaemia: Can We Identify Prognostic Factors?

2021 ◽  
Author(s):  
Hilbeen Hisham Saifullah ◽  
Claire Marie Lucas
Keyword(s):  
Prognostic Factors ◽  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Kinase Inhibitors ◽  
Chronic Phase ◽  
Molecular Response ◽  
Predicting Success ◽  
Treatment Free Remission ◽  
Almost All ◽  
Tki Discontinuation

Following the development of tyrosine kinase inhibitors (TKI), the survival of patients with chronic myeloid leukaemia (CML) drastically improved. With the introduction of these agents, CML is now considered a chronic disease, for some patients. Taking into consideration the side effects, toxicity, and high cost, discontinuing TKIs became a goal for patients with chronic phase CML. Patients who achieved deep molecular response (DMR) and discontinued TKI, remained in treatment-free remission (TFR). Currently, the data from the published literature demonstrate that 40-60% of patients achieve TFR, with relapses occurring within the first six months. In addition, almost all patients who relapsed regained a molecular response upon re-treatment, indicating TKI discontinuation is safe. However, there is still a gap in the understanding the mechanisms behind TFR, and whether there are prognostic factors that can predict the best candidates who qualify for TKI discontinuation with a view to keeping them in TFR. Furthermore, the information about a second TFR attempt and the role of gradual de-escalation of TKI before complete cessation is limited. This review highlights the factors predicting success or failure of TFR. In addition, it ex-amines the feasibility of a second TFR attempt after the failure of the first one, and the current guidelines concerning TFR in clinical practice.

scholarly journals Rupture Spleen as Initial Presentation in A Patient of Chronic Myeloid Leukaemia: A Case Report

2016 ◽  
Vol 13 (2) ◽  
pp. 52-54
Author(s):  
Mohammad Ibrahim Khalil ◽  
Md. Nazmul Islam ◽  
Mafruha Akter ◽  
AZM Mostaque Hossain ◽  
Md. Amir Hossain
Keyword(s):  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Female Student ◽  
Care Center ◽  
Chronic Phase ◽  
Abdominal Distension ◽  
Emergency Laparotomy ◽  
Rare Presentation ◽  
Health Care Center ◽  
Common Presentation

A 22 years female student presented with sudden severe abdominal pain in left upper quadrant followed by abdominal distension. She attended in surgery unit of a tertiary health care center. On examination she was in shock and the abdomen was distended, tender. She was evaluated as  surgical acute abdomen and emergency laparotomy revealed rupture of spleen and splenectomy was done. Her CBC showed gross leucocytosis with predominance of neutrophils and significant number of myelocytes and the PBF showed the features of chronic phase of chronic myeloid leukaemia. BCR-ABL was positive from bone marrow that confirms the diagnosis. Splenomegaly is a common presentation of CML. However spontaneous rupture of spleen is a very rare presentation of CML. Journal of Science Foundation, 2015;13(2):52-54DOI: http://dx.doi.org/10.3329/jsf.v13i2.27935

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