Bone Marrow Transplantation
3/12/10
SP Notes
PY Mindmaps
OH – Chapter 92
- used in a wide range of malignant and non-malignant disorders
- can be autologous or allogeneic
- autologous = donor and recipient are the same person (avoids GVHD).
- allogenic = genetically different but from the same species (GVHD and doesn’t need to be
stored, but a limited amount of GVHD may have an anti-tumour effect).
- don’t take an entirely nihilistic approach to these patients if marrow recovery is imminent.
- however, prolonged ventilation and/or dialysis in these patients results in a poor prognosis.
- haempoietic stem cells are obtained from either marrow aspiration or from peripheral blood
by apheresis using a blood cell separator following stimulation of the marrow with
haemopoietic growth factors +/- chemotherapy.
PRINICIPLES
- tumour must be responsive to chemotherapy +/- radiotherapy
- the limitation of chemotherapeutic agents used must related to bone marrow toxicity and
not other organs
- must have a source of un- or minimally contaminated haemopoietic stem cells (autologous
or allogenic)
- appropriate haemopoietic supportive therapy must be available during the marrow aplastic
period
- high quality clinical and laboratory must be available for the collection and preservation of
haemopoietic stem cells.
- strong MDT commitment
- well-documented clinical protocols and effective implementation
GENERAL OVEVIEW OF COMPLICATIONS
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NEUROLOGICAL COMPLICATIONS
- > with allogenic transplantation
- risk factors: high dose chemotherapy, immunosuppression, GVHD, thrombocytopaenia
CVA
- median day of presentation = 28
- usually haemorrhage (intracerebral, SAH) from thrombocytopaenia
- other causes: infarction from infection or thrombosis, non-bacterial endocarditis and
embolism
- high mortality (70%)
- standard management
CNS Infections
- aspergillosis (main cause), CMV, HSV, Toxoplasma, Candida, Cryptococcus, bacterial
meningitis
- prognosis is extremely poor
Metabolic Encephalopathy
- > in allogenic transplantation
- altered mental status, seizures, Wernicke encephalopathy (altered mental status, ataxia,
opthalmoplegia)
- causes: hypoxaemia, electrolyte abnormalities, metabolic acidosis, sepsis, hepatic failure,
medications (sedatives and analgesics), thiamine deficiency
- supportive care
Jeremy Fernando (2010)
Treatment related neurological complications
- OKT3: aseptic meningitis (can decrease risk with corticosteroids)
- cranial radiation
- imipenem: seizures
- corticosteroids: myopathy, psychosis
- cyclosporine A: encephalopathy, leukoencephalopathy, generalised cerebellar dysfunction,
hemiparesis, quadriplegia, seizures.
Graft vs Host Disease
- acute GVHD: encephalopathy associated with other organ dysfunction
- chronic GVHD: polyneuropathy, polymyositis, MG
- treatment: intensification of immunosuppressive therapy
CARDIAC COMPLICATIONS
Pulmonary oedema
- commonest cardiac indication for ICU admission
- risk factors: low EF, fluid overload, ARF, veno-occlussive disease, severe sepsis, anaemia
and high dose chemotherapy
Pericardial tamponade
- rare
- usually related to: cyclophosphamide toxicity, viral syndrome, chronic GVHD, renal failure,
bacterial infection (rarely)
Endocarditis
- rare (1.3%)
- clinical features are subtle: left sided murmurs, indwelling CVC’s, disruption of skin and
mucosal barriers by high dose chemotherapy and GVHD
- organisms: Staph aureus, Strep viridans, fungal, aseptic
Arrhythmias
-
electrolyte abnormalities
hypoxaemia
sepsis
MOF
PULMONARY COMPLICATIONS
- many reasons
- bilateral pulmonary infiltrate differential =
(1) Pneumonia
Viral – CMV, HSV, VSV
Bacterial – see Pneumonia in the Immunocompromised Document
Fungal – Pneumocystis, Aspergillus, Candida
Protozoa – Toxoplasma
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(2) Engraftment syndrome
(3) Bronchiolitis obliterans +/- organizing pneumonia (BOOP)
(4) Diffuse alveolar haemorrhage
(5) Idiopathic pneumonia syndrome
- organisms causing infection are temporally distributed:
-> early (< 30 days): bacteria, candida, aspergillus, HSV, RSV
-> mid (30-100 days): CMV, PCP, adenovirus, HZV, aspergillus
-> late (> 100 days): CMV
GASTROINTESTINAL COMPLICATIONS
GVHD of Intestine
- clinical features: abdominal pain, N+V, diarrhoea, bleeding, may have peritonism, often
associated with hepatitis and a skin rash (acute GVHD)
- CT: bowel wall oedema
- treatment: intensification of immunosuppressive therapy
Intestinal Pseudo-obstruction
- supportive and minimizing aggravating factors
Veno-occlusive Disease of Liver
- common
- may be mild -> rapidly fatal (in 40%)
- pathogenesis: thrombosis of the small central hepatic venules due to endothelial cell
damage by high dose chemotherapy
- clinical features: during first 21 days following transplant, weight gain, tender liver, jaundice
- investigations: transaminitis, hyperbilirubinaemia, Doppler U/S showing reversal or
diminished portal flow.
- management: supportive, fluid restriction, diuresis, paracentesis, avoid infections and
hepatotoxic medications, oral ursodeoxycholic acid (lowers biliriubin) possibly thrombolytics
GI Bleeding
- diffuse mucosal bleeding of the small intestine, mucosal ulcers and necrosis
- causes: chemotherapy induced, GVHD, adenovirus, CMV
- management: supportive, endoscopy (rarely required), surgery
Enteritis
- mild to self limiting -> severe dehydration, hypotension and ARF
- causes: GVHD, bacterial infection (clostridia), viral infections (rotavirus, adenovirus, CMV,
HSV, HZV)
- treatment: supportive, octreotide (decrease secretory hormones), rotavirus (oral
immunoglobulins)
Intestinal Perforation
Jeremy Fernando (2010)
- causes: CMV ulcers, corticosteroids, GVHD
- treatment: standard care
Pancreatitis
- rare
- causes: medications (cotrimoxazole, corticosteroids, cyclosporine A), infections (CMV and
adenovirus), GVHD, biliary sludge
- treatment: standard
Other Liver Disease
- viral hepatitis: adenovirus, HSV, HZV, CMV, Hep B and C
- acute GVHD: rarely producers fulminant liver failure
- fungal infection: liver involvement of Candida and Aspergillus
RENAL COMPLICATIONS
- if develops the need for dialysis -> mortality 90%
Tumour Lysis Syndrome
- rare as tumour burden is reduced prior to transplantation
- clinical features: hyperuricaemia, hyperkalaemia, hyperphosphataemia, hypocalcaemia,
renal failure
- treatment: IVF, allopurinol, rasburicase, phosphate binders, dialysis
Infusion of Stem Cells
- haemolysis -> haemoglobinuria -> proximal ATN -> ARF
- treatment: hydration, alkalinsation
Haemorrhagic Cystitis
- risk factors: cyclophosphamide, busulfan, irradiation, viral infections
- prevention: IVF, diuresis, irrigation of the bladder, mesna
Veno-occlusive Renal Disease
- clinical features: day 10-21 post transplant, hepatorenal syndrome
- risk factors: mismatched graft, age > 25 years, pre-existing renal failure, sepsis,
amphotericin B
Drug Nephrotoxicity
-
cyclosporine A: intensive renal arteriolar vasoconstriction
nitrourea
methotrexate
cyclophosphamide
amphotericin B
acyclovir
foscanet
aminoglycosides
tacrolimus
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INFECTIOUS COMPLICATIONS
Viral
-
CMV: pneumonitis is the most lethal -> ganciclovir/foscarnet, Ig’s
RSV: URTI->LRTI -> nasal wash/BAL, aerosolized ribavirin, Ig’s
HSV-6: pneumonitis, marrow suppression, encephalitis -> ganciclovir/foscarnet
HZV: pneumonia, hepatitis, skin rash, encephalitis, DIC -> high dose acyclovir
Bacterial
- risk factors: neutropenia, mucositis, skin breakdown, GI problems, IV catheters
- organisms: gram negatives (Pseudomonas, Klebsiella), gram positives (MRSA, Strep
viridans, enterococci)
Fungal
- invasive pulmonary aspergillus: lungs to haematogenous dissemination -> CXR: halo sign
and air crescent sign, sputum, BAL, voriconazole/caspofungin
- candida: fluconazole or caspofungin (evidence of endophthalmitis or resistant organisms)
- PCP: rare now c/o co-trimoxazole prophylaxis -> requires a BAL
SUMMARY
Acute (< 30 days) – neutropenia
-
acute tumour lysis
infection: bacterial, fungal and viral
respiratory: engraftment, haemorrhage
cardiovascular: CHF, arrhythmias, tamponade
gastrointestinal: GIH, enteritis, veno-occlusive disease of liver
nervous: CVA, encephalopathy
other: haemorrhagic cystitis
Early (30-100 days) – acute GVHD
-
graft failure
pneumonitis
BOOP
infection: bacterial, viral, fungi
Late (>100 days) – chronic GVHD
-
myopathy
neuropathy
HUS
infection: CMV
infertility
second malignancy
cataracts
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PROGNOSIS
- critical illness during engraftment period (< 30 days post BMT) -> mortality 33%
- acute GVHD (moderate to severe) -> mortality 90%
- more than two organ systems and need for mechanical ventilation/RRT are associated with
very poor outcome.
Jeremy Fernando (2010)