Morris on Crit Care Haem Malignancies
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Ed Morris is an Englshman currently hailing from Townsville, Australia who is a superb haematologist. He gave this talk on haem malignancies with specific regards to the critical care aspects at last years bedside critical care conference.
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Morris on Crit Care Haem Malignancies
- 1. Critical Care 2012 - Ed Morris, Consultant Haematologist Haematology Townsville Cancer Centre Daydream Island, 27-09-12
- 2. Case: Mr CS April 2004: • 50 yrs, previously fit and well prison guard • Presented to GP with back pain and lethargy
- 3. Case: Mr CS
- 4. Case: Mr CS
- 5. Case: Mr CS
- 6. Case: Mr CS
- 8. Multiple myeloma • Clonal plasma cell malignancy • CRAB • Hyper-Calcaemia • Renal failure • Anaemia • Bone disease • Incurable
- 10. Multiple myeloma
- 11. • HDT: High Dose Therapy • ASCT: Autologous Stem Cell Transplant
- 12. Case: Mr CS • VAD induction chemotherapy • Vincristine, Adriamycin and Dexamethasone • 96 hour continuous infusion via Portacath • Good response • Autologous peripheral blood stem cell transplant • High dose Melphalan conditioning (200mg/m2)
- 13. Prognosis • International Staging System (ISS) Stag Albumi B2M e n 1 >35 <3.5 2 <35 3.5- 5.5 3 <35 >5.5
- 14. Prognosis • International Staging System (ISS) Stag Albumi B2M e n 1 >35 <3.5 2 <35 3.5- 5.5 3 <35 >5.5
- 15. Prognosis Greipp P R et al. JCO 2005;23:3412-3420
- 16. 2005-2006 2005 2006 - Floyd Landis 2006 – Oscar Pereiro
- 17. Case: Mr CS September 2006 (~2 years post-transplant) • Increasing serum paraprotein • Falling Hb • BM Bx: 43% plasma cells • Progressive disease
- 18. Relapsed incurable malignancy Re-treat or palliative care? • Already survived predicted median OS • ? further Rx options
- 19. Relapsed incurable malignancy Re-treat or palliative care? • Already survived predicted median OS • ? further Rx options BUT • 52 yrs old • Normal performance status and good QOL
- 21. Case: Mr CS • Oral CTD x4 • Cyclophosphamide, Thalidomide and Dexamethasone • Good response • 2nd autologous peripheral blood stem cell transplant • High dose Melphalan conditioning (200mg/m2)
- 22. Case: Mr CS • D+8 post-transplant • Unwell • Temp 39oc • Multiple cultures negative • Started Tazocin + Vancomycin
- 23. Case: Mr CS • D+10 post-transplant • Very unwell • Temp 39oc • P135 regular, BP 80/55 • Respiratory compromise • RR 24, O2 Sat 88% on 10L • Ambisome added + ICU consult
- 24. Case: Mr CS • Would ICU admission be appropriate?
- 25. Case: Mr CS • Would ICU admission be appropriate? Yes No Normal functional Relapsed incurable status pre-transplant malignancy Good response to Has used all currently salvage chemo available Rx Transient BM “failure” Predicted PFS < before Renal, etc OK APACHE III score 122
- 26. TTH ICU Data 2003-2011 Anni Paasilahti 2012 (Senior Registrar ICU, TTH)
- 27. APACHE III score 122 Anni Paasilahti 2012 (Senior Registrar ICU, TTH)
- 28. Case: Mr CS • Admitted ICU • CPAP, IV antibiotics, Vasopressor support • Excellent response • Discharged ICU after 48hrs
- 29. Case: Mr CS • Rapid improvement back on ward • Blood counts recovered • Discharged hospital D+26 post-transplant • Commenced Thalidomide maintenance D+70
- 30. 2007-2009 2008 – Carlos Sastre 2009 – Alberto Contador 2007 – Alberto Contador
- 31. Case: Mr CS March 2009 (5 yrs post-diagnosis) • Increasing serum paraprotein • Falling Hb • BM Bx: 31% plasma cells • Progressive disease
- 32. Relapsed incurable malignancy Re-treat or palliative care? • Already survived >>> predicted median OS • ? further Rx options BUT • 55 yrs old • Normal performance status and good QOL • 2+ yrs since we last considered palliation
- 33. NEJM 2008; 359; 906-17
- 34. NEJM 2008; 359; 906-17
- 35. Case: Mr CS • CyBorD • Cyclophosphamide, Bortezomib (Velcade), Dexamethasone • SE: peripheral neuropathy • Velcade maintenance
- 36. Case: Mr CS • August 2012 • 8 yrs post-diagnosis • Well • Good QOL • Myeloma in remission
- 37. Case: Mr CS • Is he cured? • No, but he may still live a number of years • Does he have further treatment options? • Lenalidomide • Lenalidomide + Velcade combinations • Pomalidomide • Carfilzomib, etc etc
- 38. Infusional VAD Autologous Stem cell transplant years Salvage attempts DEATH Myeloma 1998: Life expectancy 2-3
- 39. Thalidomide-based Rx Autologous Stem cell transplant years Maintenance Thalidomide Valcade-based Rx 2nd Autologous Stem cell transplant Maintenance Velcade Lenalidomide-based Rx Maintenance Lenalidomide Myeloma 2012: Life expectancy 10+
- 41. Monoclonal antibodies – flow cytometry Anti-CD20 CD20 Fluorochrome CD5 Anti-CD5 Different fluorochrome
- 42. Monoclonal antibodies – flow cytometry Gp 1 CD3 Neg PE NK1.1 .001 R2 CD20 R3 R4 100 101 102 103 104 CD5 CD3 FITC
- 43. Monoclonal antibodies – therapeutic agents • Rituximab (Mabthera)
- 44. Mrs TS • 59 yr old female • Diagnosed Follicular Lymphoma March 2008 • R-CHOP x6 • Good response
- 45. Haematologica 2007; 92; 826-831
- 46. Mrs TS • 59 yr old female • Diagnosed Follicular Lymphoma March 2008 • R-CHOP x6 • Good response • Mabthera every 2 months (planned for 2 years)
- 47. Mrs TS • Relapsed FL August 2011 • Salvage R-ICE – good response • Standard practice: consolidation with high dose chemo (BEAM) + autologous stem cell transplant
- 48. Cancer 2012; in press
- 49. Mrs TS • Consolidation Z-BEAM + autologous stem cell transplant
- 50. Mr JS • 68 yr old male • Diagnosed Hodgkin’s Lymphoma July 2009 • ABVD x6 • Good response • Relapsed August 2010 • ESHAP salvage • BEAM + autologous stem cell transplant
- 51. Mr JS • 2nd relapsed July 2012 • ICE salvage • Poorly tolerated • Disease progression during chemo • Options? • Palliative care • Experimental Rx
- 52. Brentuximab vedotin Reed-sternberg cell CD15+, CD30+, CD20- CD30+ Reed-Sternberg Cell
- 54. End-stage Hodgkin’s (relapse post transplant)
- 55. Mrs AB • 43 yr old female • Diagnosed Ph+ ALL April 2009 • Rx: BFM-based intensive chemo followed by allogeneic stem cell transplant • Relapsed January 2011 • Prognosis extremely poor • Options???
- 56. BiTE Antibodies
- 57. Mrs AB • Travelled to Germany: Phase 2 study of Blinatumomab • 6 months later: • In complete remission…
- 58. Infusional VAD Autologous Stem cell transplant years Salvage attempts DEATH Myeloma 1998: Life expectancy 2-3
- 59. Thalidomide-based Rx Autologous Stem cell transplant years Maintenance Thalidomide Valcade-based Rx 2nd Autologous Stem cell transplant Maintenance Velcade Lenalidomide-based Rx Maintenance Lenalidomide Myeloma 2012: Life expectancy 10+
- 60. Questions? Isabella Morris Age 4yrs