Nothing to disclose. Title of the presentation - Author

Transcription

1 Nothing to disclose Title of the presentation - Author 1

2 Complications after HSCT Alicia Rovó MD London 9/04/2013

3 Introduction Risk factors for transplant complication Type of complications Case discussion 3

4 The EBMT activity survey: Bone Marrow Transplant

5 Indications for HSCT in Europe in 2010 Allogeneic HSCT Autologous HSCT EBMT activity survey: Bone Marrow Transplant

6 Use of different donor types for allogeneic HSCT in Europe EBMT activity survey: Bone Marrow Transplant

7 Complications post HSCT Risk factors Pre-HSCT Conditioning related Related to GVHD and its management Patient (age, gender, comorbidities) Conditioning regimen Graft source Disease features Donor characteristics GVHD and immunosuppression 7

8 Sequence of onset of complications after HSCT Pulmonary Renal Cardiovascular Neoplasm Chronic GVHD Calcineurin inhibitors Cardiovascular risk factors TBI 8

9 Complications after transplantation toxicities of the high dose of chemo-radiotherapy (conditioning) organ damage infection bleeding early complications of vascular origin thrombosis GVHD and its therapy relapse 9

10 HSCT- Complications after MAC Timeline conditioning engraftment Cy-TBI 0 Mucositis Bleeding Infections GVHD HSCT Aplasia GVHD Prophylaxis 10

11 HSCT- Complications after RIC Timeline conditioning engraftment RIC 0 Infections GVHD GVHD Prophylaxis HSCT 11

12 HSCT- Timeline Early complications conditioning engraftment Cy-TBI 0 Mucositis Bleeding Infections GVHD HSCT Aplasia GVHD Prophylaxis usually occur within 5 to 10 days: Nausea and vomiting. Mouth sores Pain Diarrhea Hair loss 12

13 Infections Title of the presentation - Author 13

14 HSCT- Timeline Infections Risk conditioning engraftment Cy-TBI 0 Mucositis Bleeding Infections GVHD HSCT Aplasia GVHD Prophylaxis 14

15 HSCT- Timeline Infections Risk conditioning engraftment Cy-TBI 0 Mucositis Bleeding Infections GVHD HSCT Aplasia GVHD Prophylaxis 3 weeks 3 months Neutropenia Damaged barrier Central venous catheter Cellular and humoral immunity severely impaired Cellular and humoral immunity impaired Slowly recovery 15

16 Infection risk factors Pre-engraftment (first three weeks after HSCT) Mucositis and cutaneous damage Mechanisms: disrupt the natural barriers of the skin and mucous membranes Neutropenia Loss of phagocytic function Organ dysfunction Post-engraftment (three weeks to three months after HSCT) Mucositis and cutaneous damage Cellular immune dysfunction Immunomodulating viruses Hyposplenism For allogeneic HSCT recipients, GVHD and its therapy Late post-engraftment (after 3 months post HSCT) Main risk factor GVHD and its therapy. Muco-cutaneous damage (GVHD/) Immunodeficiency (low counting of lymphocyte subpopulations, hypogammaglobulinemia) Hyposplenism 16

17 Phases of opportunistic infections BBMT

18 Hemorrhagic cystitis Title of the presentation - Author 18

19 HSCT- Timeline Hemorrhagic cystitis conditioning engraftment Cy-TBI 0 Mucositis Bleeding Infections GVHD HSCT Aplasia GVHD Prophylaxis Early onset may be explained by toxicity of chemo-radiotherapy Cyclofosfamide, Ifosfamide, Busulfan, less common: Etopoxide or TBI Late onset multifactorial viral infections: human polyomavirus type BK or JC, less frequent: Adenovirus type 11 or MCV (exceptional) 19

20 Hemorrhagic cystitis Incidence: varies from <10% to more than 70%. Characterized by hemorrhagic inflammation of urinary tract mucosa. Symptoms: variable -asymptomatic microscopic hematuria -frank hematuria with clot formation -urinary tract obstruction Prophylaxis: Based on hyper hydration and Mesna administration. Treatment: 1. Forced hydration plus intensive platelet support 2. Bladder irrigation 3. Salvages approaches: selective embolization of bladder arteries, suprapubic catheter, cystoscopy with clot evacuation, fibrin glue, endoscopic laser coagulation Hassan. Pediatr Transpl

21 Early complications of vascular origin Title of the presentation - Author 21

22 Early complications of vascular origin 1- Veno-occlusive disease of the liver (VOD) 2- Capillary leak syndrome (CLD) 3- Engraftment syndrome (ES) 4- Diffuse alveolar hemorrhage (DAH) 5- Thrombotic microangiopathy (TMA) 6- Idiopathic pneumonia syndrome (IPS) 7- Multiple-organ dysfunction syndrome (MODS) 22

23 Common pathogenesis of early complications of vascular origin after HSCT engraftment 0 HSCT Modified from E. Carreras EBMT

24 Growth factors PBSCT High CD34 GVHD HSCT- Fast engraftment Timeline ES (72 hs) Fever Skin rash Lung infiltrates TBI CYA, Sirolimus HLA-missmatch Infections TMA Around d +60 MHA/ low Plt Fever Renal dysfunction conditioning engraftment Cy-TBI 0 MODS Mucositis Bleeding Infections DAH GVHD DAH d +30 Dyspnea, cough Tachypnea Hypoxemia Lung infiltrat Older age previous thoracic radiation, allogeneic HSCT TBI severe agvhd HSCT CLD 1+ to 15+d Fluid retention Weight gain Generalized edemas Cumulative chemotherapy pre-hsc G or GM-CSF Unrelated of HLA mismatched Aplasia IPS VOD 1+ to 40+d Jaundice Fluid retention Tender hepatomegaly Allogeneic Previous HSCT Mismatch Conditioning Liver disease Hepatotoxic drugs GVHD Prophylaxis IPS d +21 Fever, Cough, Tachypnea, Hypoxemia lung infiltration age (>40 y) MAC allogeneic HSCT TBI severe agvhd 24

25 GVHD Title of the presentation - Author 25

26 Distinguishing acute and chronic GHVD Acute GVHD 100 days Chronic GVHD 26

27 Distinguishing acute and chronic GHVD Category Time of symptoms Acute GVHD features Chronic GVHD features Acute GVHD Classic acute 100 days yes no Persistent, recurrent or late-onset acute > 100 days yes no Chronic GVHD Classic chronic No time limit no yes Overlap syndrome No time limit yes yes EBMT 2012 Apperley & Masszi 27

28 GVHD classification after the NIH consensus conference. Pavletic S Z, and Fowler D H Hematology 2012;2012: by American Society of Hematology

29 agvhd 29

30 Acute GVHD agvhd remains a major complication of HSCT incidence :10 80%, depending upon the risk factors Broad spectrum of clinical manifestations (mild to potentially fatal) Difficult differential diagnosis with other entities (VOD, infections, toxicity, etc Biopsy for histopathological diagnosis is recommended. BMT, 2008;41:

31 Initial treatment algorithm of agvhd Dignan BJH

32 Treatment algorithm for Grade III-IV GVHD Dignan BJH

33 Chronic GVHD Immunoregulatory disorder Features of autoimmunity and immunodeficiency. Main cause of late non-relapse morbi-mortality after HSCT Infections (immundeficiency due cgvhd and its therapy). Any organ can be the target of cgvhd. Mechanisms: Autoreactive T-lymphocytes play role B-lymphocyte Risk factors: Older age CMV seropositivity of recipient Splenectomy Prior acute GVHD 33

34 Cases Title of the presentation - Author 34

35 HSCT- Timeline ES conditioning Fever Engraftment EBV Death Cy-TBI 0 Mucositis HHV Encephalitis Candida sepsis Pulmonary Rhizomucor Probable Aspergillosis 42y Diag B-ALL BCR-ABL+ CNS infiltration Complex cytogenetic First Diag: Aplasia GVHD Prophylaxis HSCT CR Id sibl donor Acute Resp Decompens Cause of death: Cardiotoxicity GVHD GVHD Grade IV Skin Transplant related GVHD 35

36 HSCT- Timeline Parainfluenza 4 Pneumonia Riibavirin conditioning CyBu Fever 0 Engraftment LMWH Mucositis TVE Probable Aspergillosis 22y Diag AML FLT3-ITD First Diag: HSCT CR MRD+ Id sibl donor Aplasia GVHD Prophylaxis 1 Mt. CR Muco G2, skin G1 +60d Sorafenib Alive CR GVHD GVHD 3 Mt. CR 36

37 HSCT- Complications after RIC Timeline conditioning engraftment RIC 0 Mix chimerism Full donor type chimerism GVHD Prophylaxis 3 Mt. CR agvhd 6 Mt. CR HSCT AML CR DLI 69 y Diag AML Poor risk First Diag: Alive CR Full chimerism agvhd 37

38 Acknowledgement Hanneke Schep Data manager at University Hospital Basel 38