1 / 20

I’ve just been diagnosed with CML. Could you answer my questions?

I’ve just been diagnosed with CML. Could you answer my questions?. Sameer Tulpule Royal Hallamshire Hospital Sheffield. What now?. Leukemia. Can be cured. Fast Facts. Rare disease 1 to 1.5 new cases per 100,000 population per year Rare in young adults under 19 years

vickien
Download Presentation

I’ve just been diagnosed with CML. Could you answer my questions?

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. I’ve just been diagnosed with CML.Could you answer my questions? Sameer Tulpule Royal Hallamshire Hospital Sheffield

  2. What now? Leukemia Can be cured

  3. Fast Facts • Rare disease 1 to 1.5 new cases per 100,000 population per year • Rare in young adults under 19 years • Not inherited – cannot pass down to kids

  4. How did I get it? • In almost all cases there are no identifiable predisposing causes • Radiation is the only clearly established external factor predisposing to development of CML • Benzene is implicated only on an anecdotal basis

  5. What is CML Wang et al. Genes Chromosomes Cancer. 2001;32:97 Wang et al. Genes Chromosomes Cancer. 2001;32:97

  6. Diagnostic Considerations in Chronic Myeloid Leukemia Demonstrating the presence of the t(9;22) or its gene product is absolutely essential in diagnosing a patient with CML Karyotyping in CML 1) Allows for the diagnosis of CML 2) Requires a bone marrow aspirate for optimal metaphases

  7. Ch 9 Ch 22 FISH in CML Bcr- Ch 22 Abl – Ch 9 Bcr-Abl Fusion Red → Bcr probe Green → Abl Probe Yellow → fusion of Bcr and Abl

  8. Bcr-Abl cDNA Bcr Abl Diagnostic Considerations in Chronic Myeloid Leukemia Quantitative RT-PCR for Bcr-Abl in CML 1) Allows for the diagnosis of CML 2) Does not require a bone marrow aspirate for optimal results 3) Can quantify the amount of disease

  9. Disease Diagnosis and Monitoring in CML *Number of leukemic cells detectable per 100 cells. BM = bone marrow; FISH = fluorescence in situ hybridization; PB = peripheral blood;MRD = minimal residual disease; RT-PCR = reverse transcriptase polymerase chain reaction. Wang et al. Genes Chromosomes Cancer. 2001;32:97

  10. Substrate Effector Bcr-Abl ADP P P P P P P P P SIGNALING Normal Bcr-Abl Signaling* • The kinase domain activates a substrate protein, eg, PI3 kinase, by phosphorylation • This activated substrate initiates a signaling cascade culminating in cell proliferation and survival ATP ADP = adenosine diphosphate; ATP = adenosine triphosphate; P = phosphate. Savage and Antman. N Engl J Med. 2002;346:683 Scheijen and Griffin. Oncogene. 2002;21:3314.

  11. Bcr-Abl ATP P P P P Imatinib mesylate SIGNALING Imatinib Mesylate: Mechanism of Action* • Imatinib mesylate occupies the ATP binding pocket of the Abl kinase domain • This prevents substrate phosphorylation and signaling • A lack of signaling inhibits proliferation and survival Savage and Antman. N Engl J Med. 2002;346:683.

  12. 1 0 0 9 0 8 0 7 0 6 0 Estimated overall survival at 8 years was 85% (93%, considering onlyCML related deaths) % 5 0 , e v i l 4 0 A 3 0 2 0 S u r v i v a l : d e a t h s a s s o c i a t e d w i t h C M L 1 0 O v e r a l l S u r v i v a l 0 0 1 2 2 4 3 6 4 8 6 0 7 2 8 4 9 6 1 0 8 M o n t h s S i n c e R a n d o m i z a t i o n IRIS 8-Year UpdateOverall Survival (Intent-to-Treat) –Imatinib Arm % Alive

  13. IRIS Study: Most Frequently Reported AEs Imatinib is a Safe Drug.... • Only Serious Adverse Events (SAEs) were collected after 2005 • Grade 3/4 adverse events decreased in incidence after years 1-2 IRIS 8 year update

  14. How often do I need tests

  15. Definitions of Treatment Response * Cytogenetic response is based on analysis of at least 20 metaphases Deininger, 2005; National Comprehensive Cancer Network, 2007.

  16. Do I need repeated Bone marrows? • No • Usually only at diagnosis • Part of trial • If there is loss of response

  17. CML – Phases of Disease National Comprehensive Cancer Network, 2007; National Cancer Institute, 2007; Calabretta & Perrotti, 2004; Cortes et al.,2006.

  18. Summary • Rare disease • Potentially curable disease • Good long term survival • Imatinib has a good safety profile

More Related