Common noninfectious comorbidities to consider in adults with IEIs that confer worse outcome for HSCT
| System . | Complications commonly seen in adults with IEI . | Investigations recommended . | Influence on transplant planning . |
|---|---|---|---|
| Pulmonary | Structural lung disease including: • Bronchiectasis • Fibrosis • Pneumatocele | Lung function: spirometry and gas transfer. High resolution chest CT. Bronchoscopy and BAL if suspect active undiagnosed infection. | FVC and FEV1 < 60% predicted: acceptable if not oxygen-dependent and possibility for stabilization post-HSCT. Ensure optimal management of bronchiectasis and/or ILD before HSCT. Sputum surveillance to inform peritransplant antimicrobial prophylaxis and treatment. |
| Inflammatory lung disease including: • Granulomatous interstitial lung disease • Cryptogenic organizing pneumonia | Lung function: gas transfer is a good marker of extent of ILD. High resolution CT chest. Bronchoscopy and BAL if suspect active undiagnosed infection. | DLCO < 50% predicted: acceptable if not oxygen-dependent and possibility for stabilization post-HSCT. ILD anticipated to improve with immunosuppression conferred by conditioning. Associated structural change, such as fibrosis, may be a barrier to HSCT (see above). Occasionally thoracic surgery indicated before HSCT (eg, resection of infected cavity/lobe). | |
| Renal | Chronic renal impairment including: • Autoimmune renal disease • Vasculitis • Drug induced injury | Urea, creatinine, electrolytes and estimated GFR. Renal biopsy (occasionally indicated when renal diagnosis unclear). | GFR < 30 mL/kg/min poses a significant barrier to HSCT because of reduced drug tolerance and increased risk of sepsis associated acute kidney injury (AKI). For patients with GFR < 30 mL/kg/min and no other severe end organ damage, peritransplant hemofiltration can be considered, but requires highly specialist care and complicates drug dosing especially for chemotherapy. |
| Hepatic | Chronic liver disease including: • Nodular regenerative hyperplasia • Fibrosis/cirrhosis • Portal hypertension ± ascites | Liver function testing to include transaminases, alkaline phosphatase, bilirubin, albumin, INR, Hepatitis B and C DNA/RNA* Liver ultrasound. Fibroscan measuring liver stiffness. Liver biopsy. Portal venous pressure measurements. If portal hypertension, upper endoscopy for esophageal varices. | Severe chronic liver disease is an absolute barrier to HSCT including: • Liver synthetic failure • Decompensated portal hypertension with ascites • Severe portal hypertension with large splenomegaly • Cirrhosis Decision making requires involvement of an experienced hepatology team. Prior liver transplant or surgical TIPPS procedure (for portal hypertension) can be considered but there is little data for these procedures in adults with IEI to date, making this high risk. |
| Active inflammation • Autoimmune hepatitis | As above Also tissue specific autoantibodies. | Control of active inflammation using immunosuppression advised prior to HSCT. Decision making requires involvement of an experienced hepatology team and prior liver transplant may be required for refractory inflammation leading to liver failure. | |
| Gastrointestinal | Chronic diarrhea Malabsorption and poor nutrition | Stool samples for microscopy and culture/polymerase chain reaction to exclude bacterial and parasitic pathogens including disease specific considerations: eg, cryptosporidium in CD40L deficiency. Polymerase chain reaction for viruses, including norovirus. Vitamin levels. | Infectious disease or microbiology input indicated for chronic or relapsing infections. Eradication pre-HSCT may not be feasible but peri- and post-HSCT prophylaxis may be required. Nutrition should be optimized if possible, prior to HSCT, including use of parenteral nutrition if required. |
| Active inflammation/colitis • Inflammatory bowel disease • Granulomatous inflammation | Fecal calprotectin Upper and lower endoscopy with biopsies if pathogens excluded and diagnosis unclear. | Conditions with active inflammation typically improve with immunosuppression conferred by conditioning. | |
| Spleen | Splenomegaly for example • As a feature of the specific IEI • With autoimmune cytopenias • Secondary to liver disease and portal hypertension (see above) | Ultrasound or computed tomography scans of abdomen to ascertain size. Liver investigations if liver disease suspected (see above) | Large splenomegaly increases risk of engraftment failure and is associated with poor count recovery. If secondary to liver disease, follow advice for liver complications (see above) If related to immune dysregulation of the underlying IEI, consider whether size can be reduced prior to HSCT eg with immunosuppression such as sirolimus or rituximab or with control of autoimmune cytopenias. Splenectomy not advised due to risk of post-HSCT infections, in particular pneumococcal sepsis. Embolization also not advised due to risk of abscess formation, unless urgent need to reduce spleen size for control of severe refractory autoimmune cytopenia. |
| Prior splenectomy | None | Ensure pneumococcal antibiotic prophylaxis post HSCT, typically lifelong. Ensure pneumococcal vaccination post-HSCT with confirmation of protective antibody response. |
| System . | Complications commonly seen in adults with IEI . | Investigations recommended . | Influence on transplant planning . |
|---|---|---|---|
| Pulmonary | Structural lung disease including: • Bronchiectasis • Fibrosis • Pneumatocele | Lung function: spirometry and gas transfer. High resolution chest CT. Bronchoscopy and BAL if suspect active undiagnosed infection. | FVC and FEV1 < 60% predicted: acceptable if not oxygen-dependent and possibility for stabilization post-HSCT. Ensure optimal management of bronchiectasis and/or ILD before HSCT. Sputum surveillance to inform peritransplant antimicrobial prophylaxis and treatment. |
| Inflammatory lung disease including: • Granulomatous interstitial lung disease • Cryptogenic organizing pneumonia | Lung function: gas transfer is a good marker of extent of ILD. High resolution CT chest. Bronchoscopy and BAL if suspect active undiagnosed infection. | DLCO < 50% predicted: acceptable if not oxygen-dependent and possibility for stabilization post-HSCT. ILD anticipated to improve with immunosuppression conferred by conditioning. Associated structural change, such as fibrosis, may be a barrier to HSCT (see above). Occasionally thoracic surgery indicated before HSCT (eg, resection of infected cavity/lobe). | |
| Renal | Chronic renal impairment including: • Autoimmune renal disease • Vasculitis • Drug induced injury | Urea, creatinine, electrolytes and estimated GFR. Renal biopsy (occasionally indicated when renal diagnosis unclear). | GFR < 30 mL/kg/min poses a significant barrier to HSCT because of reduced drug tolerance and increased risk of sepsis associated acute kidney injury (AKI). For patients with GFR < 30 mL/kg/min and no other severe end organ damage, peritransplant hemofiltration can be considered, but requires highly specialist care and complicates drug dosing especially for chemotherapy. |
| Hepatic | Chronic liver disease including: • Nodular regenerative hyperplasia • Fibrosis/cirrhosis • Portal hypertension ± ascites | Liver function testing to include transaminases, alkaline phosphatase, bilirubin, albumin, INR, Hepatitis B and C DNA/RNA* Liver ultrasound. Fibroscan measuring liver stiffness. Liver biopsy. Portal venous pressure measurements. If portal hypertension, upper endoscopy for esophageal varices. | Severe chronic liver disease is an absolute barrier to HSCT including: • Liver synthetic failure • Decompensated portal hypertension with ascites • Severe portal hypertension with large splenomegaly • Cirrhosis Decision making requires involvement of an experienced hepatology team. Prior liver transplant or surgical TIPPS procedure (for portal hypertension) can be considered but there is little data for these procedures in adults with IEI to date, making this high risk. |
| Active inflammation • Autoimmune hepatitis | As above Also tissue specific autoantibodies. | Control of active inflammation using immunosuppression advised prior to HSCT. Decision making requires involvement of an experienced hepatology team and prior liver transplant may be required for refractory inflammation leading to liver failure. | |
| Gastrointestinal | Chronic diarrhea Malabsorption and poor nutrition | Stool samples for microscopy and culture/polymerase chain reaction to exclude bacterial and parasitic pathogens including disease specific considerations: eg, cryptosporidium in CD40L deficiency. Polymerase chain reaction for viruses, including norovirus. Vitamin levels. | Infectious disease or microbiology input indicated for chronic or relapsing infections. Eradication pre-HSCT may not be feasible but peri- and post-HSCT prophylaxis may be required. Nutrition should be optimized if possible, prior to HSCT, including use of parenteral nutrition if required. |
| Active inflammation/colitis • Inflammatory bowel disease • Granulomatous inflammation | Fecal calprotectin Upper and lower endoscopy with biopsies if pathogens excluded and diagnosis unclear. | Conditions with active inflammation typically improve with immunosuppression conferred by conditioning. | |
| Spleen | Splenomegaly for example • As a feature of the specific IEI • With autoimmune cytopenias • Secondary to liver disease and portal hypertension (see above) | Ultrasound or computed tomography scans of abdomen to ascertain size. Liver investigations if liver disease suspected (see above) | Large splenomegaly increases risk of engraftment failure and is associated with poor count recovery. If secondary to liver disease, follow advice for liver complications (see above) If related to immune dysregulation of the underlying IEI, consider whether size can be reduced prior to HSCT eg with immunosuppression such as sirolimus or rituximab or with control of autoimmune cytopenias. Splenectomy not advised due to risk of post-HSCT infections, in particular pneumococcal sepsis. Embolization also not advised due to risk of abscess formation, unless urgent need to reduce spleen size for control of severe refractory autoimmune cytopenia. |
| Prior splenectomy | None | Ensure pneumococcal antibiotic prophylaxis post HSCT, typically lifelong. Ensure pneumococcal vaccination post-HSCT with confirmation of protective antibody response. |
BAL, broncho-alveolar lavage; CT, computerised tomography; DLCO, diffusion capacity of lung for carbon monoxide; FVC, forced vital capacity; GFR, glomerular filtration rate; ILD, intersitial lung disease; INR, international normalised ratio; TIPPS, transjugular intrahepatic portosystemic shunt.
Serology is unreliable in IEIs because antibody production is commonly impaired or patients are on immunoglobulin replacement therapy. Autoantibodies are usually unhelpful for the same reasons.