morris on crit care haem malignancies
DESCRIPTION
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.TRANSCRIPT
Critical Care 2012 - Haematology
Daydream Island, 27-09-12
Ed Morris, Consultant HaematologistTownsville Cancer Centre
Case: Mr CS
April 2004:
• 50 yrs, previously fit and well prison guard
• Presented to GP with back pain and lethargy
Case: Mr CS
Case: Mr CS
Case: Mr CS
Case: Mr CS
Bone Marrow Biopsy
Multiple myeloma
• Clonal plasma cell malignancy
• CRAB
• Hyper-Calcaemia
• Renal failure
• Anaemia
• Bone disease
• Incurable
Multiple myeloma
Multiple myeloma
• HDT: High Dose Therapy
• ASCT: Autologous Stem Cell Transplant
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)
Prognosis
• International Staging System (ISS)
Stage Albumin
B2M
1 >35 <3.52 <35 3.5-
5.53 <35 >5.5
Prognosis
• International Staging System (ISS)
Stage Albumin
B2M
1 >35 <3.52 <35 3.5-
5.53 <35 >5.5
Prognosis
Greipp P R et al. JCO 2005;23:3412-3420
2005-2006
2006 - Floyd Landis
2005
2006 – Oscar Pereiro
Case: Mr CS
September 2006 (~2 years post-transplant)
• Increasing serum paraprotein
• Falling Hb
• BM Bx: 43% plasma cells
• Progressive disease
Relapsed incurable malignancy
Re-treat or palliative care?
• Already survived predicted median OS
• ? further Rx options
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
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)
Case: Mr CS
• D+8 post-transplant
• Unwell
• Temp 39oc
• Multiple cultures negative
• Started Tazocin + Vancomycin
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
Case: Mr CS
• Would ICU admission be appropriate?
Case: Mr CS
• Would ICU admission be appropriate?
Yes No
Normal functional status pre-transplant
Relapsed incurable malignancy
Good response to salvage chemo
Has used all currently available Rx
Transient BM “failure” Predicted PFS < before
Renal, etc OK APACHE III score 122
TTH ICU Data 2003-2011
Anni Paasilahti 2012 (Senior Registrar ICU, TTH)
APACHE III score 122
Anni Paasilahti 2012 (Senior Registrar ICU, TTH)
Case: Mr CS
• Admitted ICU
• CPAP, IV antibiotics, Vasopressor support
• Excellent response
• Discharged ICU after 48hrs
Case: Mr CS
• Rapid improvement back on ward
• Blood counts recovered
• Discharged hospital D+26 post-transplant
• Commenced Thalidomide maintenance D+70
2007-2009
2007 – Alberto Contador
2008 – Carlos Sastre 2009 – Alberto Contador
Case: Mr CS
March 2009 (5 yrs post-diagnosis)
• Increasing serum paraprotein
• Falling Hb
• BM Bx: 31% plasma cells
• Progressive disease
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
NEJM 2008; 359; 906-17
NEJM 2008; 359; 906-17
Case: Mr CS
• CyBorD
• Cyclophosphamide, Bortezomib (Velcade), Dexamethasone
• SE: peripheral neuropathy
• Velcade maintenance
Case: Mr CS
• August 2012
• 8 yrs post-diagnosis
• Well
• Good QOL
• Myeloma in remission
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
Myeloma 1998: Life expectancy 2-3 years
Infu
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DEATH
Myeloma 2012: Life expectancy 10+ years
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Monoclonal antibodies
Monoclonal antibodies – flow cytometry
CD20
Anti-CD20
Fluorochrome
CD5
Anti-CD5
Different fluorochrome
Monoclonal antibodies – flow cytometry
CD5
CD
20
100 101 102 103 104
CD3 FITC
Gp 1 CD3 Neg PE NK1.1 .001
100 101 102 103 104
CD3 FITC
Gp 1 CD3 Neg PE NK1.1 .001
R2
R3
R4
Monoclonal antibodies – therapeutic agents
• Rituximab (Mabthera)
Mrs TS
• 59 yr old female
• Diagnosed Follicular Lymphoma March 2008
• R-CHOP x6
• Good response
Haematologica 2007; 92; 826-831
Mrs TS
• 59 yr old female
• Diagnosed Follicular Lymphoma March 2008
• R-CHOP x6
• Good response
• Mabthera every 2 months (planned for 2 years)
Mrs TS
• Relapsed FL August 2011
• Salvage R-ICE – good response
• Standard practice: consolidation with high dose chemo (BEAM) + autologous stem cell transplant
Cancer 2012; in press
Mrs TS
• Consolidation Z-BEAM + autologous stem cell transplant
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
Mr JS
• 2nd relapsed July 2012
• ICE salvage
• Poorly tolerated
• Disease progression during chemo
• Options?
• Palliative care
• Experimental Rx
CD30+ Reed-Sternberg Cell
Reed-sternberg cell CD15+, CD30+, CD20-
Brentuximab vedotin
End-stage Hodgkin’s (relapse post transplant)
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???
BiTE Antibodies
Mrs AB
• Travelled to Germany: Phase 2 study of Blinatumomab
• 6 months later:
• In complete remission…
Myeloma 1998: Life expectancy 2-3 years
Infu
sion
al V
AD
Auto
logou
s Ste
m c
ell
transp
lan
t
Salv
age a
ttem
pts
DEATH
Myeloma 2012: Life expectancy 10+ years
Th
alid
om
ide-b
ase
d R
x
Auto
logou
s Ste
m c
ell
transp
lan
t
Main
tenan
ce T
halid
om
ide
Valc
ade-b
ase
d R
x
2n
d A
uto
logous
Ste
m c
ell
transp
lant
Main
tenan
ce V
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ade
Lenalid
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ase
d R
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Main
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Questions?
Isabella Morris Age 4yrs