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

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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

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DEATH

Myeloma 2012: Life expectancy 10+ years

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Questions?

Isabella Morris Age 4yrs