Immunosuppression of recurrent pericardial graft versus host disease

Transcription

1 Immunosuppression of recurrent pericardial graft versus host disease Andrew Morley-Smith, Martin R Cowie and Ali Vazir Royal Brompton Hospital, London, UK

2 I have no conflicts of interest

3 Background 44 year old information technology consultant Fit and active keen cyclist Prior to 2007 no medical problems Non-smoker No family history of cardiac illness

4 Background Philadelphia-positive acute lymphoblastic leukaemia Diagnosed March 2007 UKALL XII regime primary refractory Imatinib & Ida-FLAG morphological remission only July 2007: allogeneic HSCT Full intensity myeloablation including total body irradiation Matched unrelated donor haematopoietic stem cells Good initial recovery

5 Complications Skin graft versus host disease (GVHD)

6 Complications Graft versus host disease (GVHD) Common complication of HSCT Donor immune cells attack non-self host cells Graft versus leukaemia Graft versus host Acute: skin, liver, GI tract Chronic: diverse, often affecting membranes Treat with immunosuppression

7 Complications Skin graft versus host disease (GVHD) Initial treatment with prednisolone then ciclosporin Stabilised with intermittent phototherapy Left pleural effusion Initially thought due to imatinib Recurred as the immunosuppression was withdrawn Conservative management Remains in complete remission

8 Presentation in July 2011 Gradual onset of dyspnoea over several months such that now breathless on minimal effort No orthopnoea, palpitations or syncope BP 150/80, P70 Elevated JVP to angle of jaw Normal heart sounds, no murmurs Signs of left pleural effusion Abdominal and ankle swelling

9 Investigations ECG: sinus rhythm, atrial ectopy, widespread T wave inversion Chest radiograph Echocardiogram Cardiac MR

10

11 Septal Ea wave 13 cm/sec

12 Mitral inflow varying with respiration End expiration End inspiration

13 Septal bounce

14 Dilated, non-collapsing IVC 22 mm

15 IVC 25 mm (arrows) Pleural effusion

16 Inversion recovery late Gd sequence Epicardial fat No significant enhancement: minor inferior RV/LV insertion point fibrosis only Pericardium (4mm)

17 Assessment Features of constrictive pericarditis Previous response to immunosuppression Differential diagnosis: Pleural-pericarditis due to chronic GVHD Radiotherapy-induced Other

18 Progress Prednisolone (once daily) Bumetanide (once daily) Eplerenone (once daily) 2011 July 60mg 2mg 25mg Rapid, marked symptomatic improvement Four flights of stairs Back to cycling long distances

19 Progress Prednisolone (once daily) Bumetanide (once daily) Eplerenone (once daily) 2011 July 60mg 2mg 25mg But developed steroid induced diabetes

20 Progress Prednisolone (once daily) Ciclosporin (twice daily) Bumetanide (once daily) Eplerenone (once daily) 2011 July Sept 60mg 30mg - 60mg 2mg 2mg 25mg 25mg But developed steroid induced diabetes Commenced ciclosporin Steroid dose reduced

21 Progress 2011 July Sept Oct 2012 Jan Feb Apr June July Prednisolone (once daily) Ciclosporin (twice daily) Bumetanide (once daily) Eplerenone (once daily) 60mg 30mg 15mg 15mg 12.5mg 12.5mg 12.5mg 12.5mg - 60mg 70mg 70mg 70mg 70mg 70mg 70mg 2mg 2mg 1mg 1mg 2mg 2mg 2mg 1mg 25mg 25mg 25mg 25mg 25mg 25mg 25mg 25mg

22 Reassessment Constrictive pericarditis due to cgvhd Improvement and clinical stability in NYHA class 1, but remains on immunosuppression Goal to wean off steroids Consideration of pericardectomy Other immunosuppression difficult

23 Left and right heart catheterisation

24 LV 163/14/ /mmhg RV 37/24/

25 LV 163/14/ /mmhg RV 37/24/

26 Physiological comparison

27 Less constriction: septal Ea wave Before After 13 cm/sec 7.8 cm/sec

28 IVC now collapses with sniffing Before After

29 Persistent mitral inflow variance Before After END EXP END INSP

30 Re-assessment Constrictive pericarditis due to cgvhd Improvement and clinical stability in NYHA class 1, but remains on immunosuppression Less marked but persistent signs of pericardial constriction No clear indication for pericardectomy Ongoing aim to wean the steroid

31 Discussion

32 Cardiac GVHD GVHD rarely affects the heart Manifestations include pericardial effusion, coronary artery disease and conduction disturbances Two reported cases of constrictive pericarditis

33 GVHD & constrictive pericarditis Insidious onset and mimics other pathology Unusual to have medical treatment option Early initiation of steroids and transition to steroid-sparing therapy Monitoring of physiology Role for pericardectomy

34 Conclusions Case of constrictive pericarditis due to cgvhd cgvhd is common complication of HSCT but rarely affects the pericardium It represents a form of pericardial constriction which is amenable to immunosuppressive therapy Careful evaluation is necessary to establish indications for pericardectomy

35 Immunosuppression of recurrent pericardial graft versus host disease Andrew Morley-Smith, Martin R Cowie and Ali Vazir Royal Brompton Hospital, London, UK

36 Further imaging

37 Septal bounce slowed

38 Septal flattening with inspiration

39 Coronaries

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41 Regadenoson 400mcg given intravenously with exercise

42 Immunosuppression of recurrent pericardial graft versus host disease Andrew Morley-Smith, Martin R Cowie and Ali Vazir Royal Brompton Hospital, London, UK