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. 1. Critical Care 2012 - Ed Morris, Consultant Haematologist Haematology Townsville Cancer Centre Daydream Island, 27-09-12
  2. 2. Case: Mr CSApril 2004: • 50 yrs, previously fit and well prison guard • Presented to GP with back pain and lethargy
  3. 3. Case: Mr CS
  4. 4. Case: Mr CS
  5. 5. Case: Mr CS
  6. 6. Case: Mr CS
  7. 7. Bone Marrow Biopsy
  8. 8. Multiple myeloma• Clonal plasma cell malignancy• CRAB • Hyper-Calcaemia • Renal failure • Anaemia • Bone disease• Incurable
  9. 9. Multiple myeloma
  10. 10. Multiple myeloma
  11. 11. • HDT: High Dose Therapy• ASCT: Autologous Stem Cell Transplant
  12. 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. 13. Prognosis• International Staging System (ISS)Stag Albumi B2Me n1 >35 <3.52 <35 3.5- 5.53 <35 >5.5
  14. 14. Prognosis• International Staging System (ISS)Stag Albumi B2Me n1 >35 <3.52 <35 3.5- 5.53 <35 >5.5
  15. 15. Prognosis Greipp P R et al. JCO 2005;23:3412-3420
  16. 16. 2005-20062005 2006 - Floyd Landis 2006 – Oscar Pereiro
  17. 17. Case: Mr CSSeptember 2006 (~2 years post-transplant) • Increasing serum paraprotein • Falling Hb • BM Bx: 43% plasma cells • Progressive disease
  18. 18. Relapsed incurable malignancyRe-treat or palliative care? • Already survived predicted median OS • ? further Rx options
  19. 19. Relapsed incurable malignancyRe-treat or palliative care? • Already survived predicted median OS • ? further Rx options BUT • 52 yrs old • Normal performance status and good QOL
  20. 20. 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)
  21. 21. Case: Mr CS• D+8 post-transplant • Unwell • Temp 39oc • Multiple cultures negative • Started Tazocin + Vancomycin
  22. 22. 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
  23. 23. Case: Mr CS • Would ICU admission be appropriate?
  24. 24. 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
  25. 25. TTH ICU Data 2003-2011 Anni Paasilahti 2012 (Senior Registrar ICU, TTH)
  26. 26. APACHE III score 122 Anni Paasilahti 2012 (Senior Registrar ICU, TTH)
  27. 27. Case: Mr CS • Admitted ICU • CPAP, IV antibiotics, Vasopressor support • Excellent response • Discharged ICU after 48hrs
  28. 28. Case: Mr CS • Rapid improvement back on ward • Blood counts recovered • Discharged hospital D+26 post-transplant • Commenced Thalidomide maintenance D+70
  29. 29. 2007-2009 2008 – Carlos Sastre 2009 – Alberto Contador2007 – Alberto Contador
  30. 30. Case: Mr CSMarch 2009 (5 yrs post-diagnosis) • Increasing serum paraprotein • Falling Hb • BM Bx: 31% plasma cells • Progressive disease
  31. 31. Relapsed incurable malignancyRe-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
  32. 32. NEJM 2008; 359; 906-17
  33. 33. NEJM 2008; 359; 906-17
  34. 34. Case: Mr CS• CyBorD • Cyclophosphamide, Bortezomib (Velcade), Dexamethasone • SE: peripheral neuropathy• Velcade maintenance
  35. 35. Case: Mr CS• August 2012 • 8 yrs post-diagnosis • Well • Good QOL • Myeloma in remission
  36. 36. 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
  37. 37. Infusional VAD Autologous Stem cell transplant years Salvage attemptsDEATH Myeloma 1998: Life expectancy 2-3
  38. 38. Thalidomide-based RxAutologous Stem cell transplant yearsMaintenance ThalidomideValcade-based Rx2nd Autologous Stem cell transplantMaintenance VelcadeLenalidomide-based RxMaintenance Lenalidomide Myeloma 2012: Life expectancy 10+
  39. 39. Monoclonal antibodies
  40. 40. Monoclonal antibodies – flowcytometry Anti-CD20 CD20 Fluorochrome CD5 Anti-CD5 Different fluorochrome
  41. 41. Monoclonal antibodies – flowcytometry Gp 1 CD3 Neg PE NK1.1 .001 R2 CD20 R3 R4 100 101 102 103 104 CD5 CD3 FITC
  42. 42. Monoclonal antibodies – therapeuticagents• Rituximab (Mabthera)
  43. 43. Mrs TS• 59 yr old female• Diagnosed Follicular Lymphoma March 2008 • R-CHOP x6 • Good response
  44. 44. Haematologica 2007; 92; 826-831
  45. 45. Mrs TS• 59 yr old female• Diagnosed Follicular Lymphoma March 2008 • R-CHOP x6 • Good response • Mabthera every 2 months (planned for 2 years)
  46. 46. Mrs TS• Relapsed FL August 2011 • Salvage R-ICE – good response • Standard practice: consolidation with high dose chemo (BEAM) + autologous stem cell transplant
  47. 47. Cancer 2012; in press
  48. 48. Mrs TS • Consolidation Z-BEAM + autologous stem cell transplant
  49. 49. 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
  50. 50. Mr JS• 2nd relapsed July 2012 • ICE salvage • Poorly tolerated • Disease progression during chemo• Options? • Palliative care • Experimental Rx
  51. 51. Brentuximab vedotinReed-sternberg cell CD15+, CD30+,CD20- CD30+ Reed-Sternberg Cell
  52. 52. End-stage Hodgkin’s (relapse posttransplant)
  53. 53. 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???
  54. 54. BiTE Antibodies
  55. 55. Mrs AB• Travelled to Germany: Phase 2 study of Blinatumomab• 6 months later: • In complete remission…
  56. 56. Infusional VAD Autologous Stem cell transplant years Salvage attemptsDEATH Myeloma 1998: Life expectancy 2-3
  57. 57. Thalidomide-based RxAutologous Stem cell transplant yearsMaintenance ThalidomideValcade-based Rx2nd Autologous Stem cell transplantMaintenance VelcadeLenalidomide-based RxMaintenance Lenalidomide Myeloma 2012: Life expectancy 10+
  58. 58. Questions? Isabella Morris Age 4yrs

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