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

Learn about the rare disease CML, diagnosis methods, treatment options like Imatinib, and long-term survival rates. Get answers to your questions on CML from Sameer Tulpule at Royal Hallamshire Hospital, Sheffield.

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

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  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

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