Canterbury DHB

Context

Pulmonary GvHD

Bronchiolitis Obliterans (BO) is the manifestation of GvHD in the lungs and is found in 6% of all HCT recipients and 16% of patients with cGvHD.

Chronic GvHD and overlap syndrome should be diagnosed primarily using clinical criteria, supported by biopsy when possible. (1B)

Chronic GvHD should be graded as mild, moderate or severe according to NIH consensus criteria. (1A)

All patients with signs or symptoms suggestive of chronic GvHD in one organ should be assessed for involvement of other organs. (1A)

From Dignan, F. L., et al. (2012). "Diagnosis and management of chronic graft-versus-host disease." Br J Haematol 158(1): 46-61.

In This Section

Clinical symptoms

Diagnosis

Differential diagnosis

Grading of pulmonary GvHD

Lung function score

Prognosis

Management

Monitoring

Essential reading

Clinical symptoms

Ask about:

Pulmonary function testing (PFT)

Routine screening can detect pulmonary GvHD before it becomes symptomatic.

FEV1 and FVC are the simplest, cheapest, most sensitive and most reproducible measurements of GvHD.

Obstructive

Restrictive

FEV1 <80% predicted

FEV1 or FVC <80% predicted

FEV1/FVC <70%

FEV1/FVC >70%

DLCO is frequently measured but is not associated with outcomes. It has the lowest reproducibility and varies considerably from test to test. DLCO can decrease post HCT but improve over time.

Broncho-alveolar lavage (BAL)

BAL is highly recommended as the only manifestation of an infection may be a decline in FEV1 or FVC.

Diagnosis

Diagnostic

Distinctive

Common

  • BO diagnosed on lung biopsy or
  • BO diagnosed on CT and/or PFT and
  • BOOP
  • BO diagnosed on CT and/or PFT and at least 1 diagnostic feature in another system
  • Absence of infection in the respiratory tract

 

Differential diagnosis

Grading of pulmonary GvHD

Grade 1

Grade 2

Grade 3

  • SOB after climbing one flight of steps
  • SOB walking on flat ground
  • SOB at rest or requiring O2
  • FEV1 60-79% predicted
  • FEV1 40-59%
  • FEV1 <39%
  • LFS 3-5
  • LFS 6-9
  • LFS 10-12

Lung function score

The lung function score (LFS) is preferred by ASBMT GvHD working party. If DLCO is not available, grade using FEV1 score alone as in the table above. The LFS is a global assessment made after the diagnosis of BO. It is calculated as follows:

Score

FEV1

DLCO (adjusted for Hb but not alveolar volume)

1

>80%

>80%

2

70-79%

70-79%

3

60-69%

60-69%

4

50-59%

50-59%

5

40-49%

40-49%

6

<40%

<40%

LFS = FEV1 score + DLCO score

Prognosis

Although a few studies have failed to show any effect on outcome, most report a dismal outcome for patients with BO.

"Even modest progressive airflow obstruction, defined as an annualized decrease of at least 5% per year, has been associated with attributable mortality rates of 9% at 3 years, 12% at 5 years, and 18% at 10 years after transplantation. Among patients with chronic GvHD, attributable mortality rates were even higher: 22% at 3 years, 27% at 5 years, and 40% at 10 years."[from Palmer, J., et al. (2014). Biol Blood Marrow Transplant 20(3): 337-344].

Management

Therapy

Recommended

Consider

1st line

  • Prednisone 1 mg/kg/d +/- calcineurin inhibitor and
  • Inhaled steroids:
    • beclomethasone (Beclozone 100 inhaler™) 200 micrograms BD or
    • fluticasone (Flixotide Accuhaler 100™) 2 puffs BD and
  • azithromycin 250 mg three times per week (requires NPPA) and
  • monteleukast (Singulair™) 10 mg once daily (requires NPPA)
  • Referral to a pulmonologist
  • Supplemental oxygen if <87% on room air
  • Pulmonary rehabilitation programmes as for COPD
  • Spacer device for use with inhalers
  • Inhaled bronchodilator (Salbutamol 100 micrograms/puff, 2 puffs as required)
  • Vaccinations
  • IVIG if hypogammaglobulinemic

2nd line and beyond *

  • Imatinib
  • ECP
  • MMF
  • Pentostatin

 

General

  • All patients on immunosuppression for GvHD should
    • receive prophylaxis against viral, PCP and Strep pneumoniae infection
    • have appropriate CMV and EBV monitoring
    • receive a mould-active antifungal prophylactic agent, e.g. posaconazole or voriconazole
    • receive vaccination against Pneumococcus, influenza and Haemophilus
  • All patients on steroids should have
    • BP and glucose monitoring
    • Gastric protection

 

*There is no 2nd line agent specific for pulmonary GHVD which has clear advantages over others. ECP is less effective than in skin GvHD. MMF is myelosuppressive and may cause GI toxicity which mimics GvHD both clinically and histologically

Choice of agent beyond 1st line will depend on availability in NZ at the time. Some or all will require NPPA.

Monitoring

There is conflicting data on whether serial monitoring predicts outcome but it is generally recommended to serially monitor the pulmonary symptom score and spirometry. The optimal frequency of monitoring is not known but we recommend:

** High risk factors are MTX prophylaxis, busulfan conditioning, PB source and respiratory viral infection within 100 days, advanced disease, female-to-male, early GvHD, older age.

Essential reading

Carpenter, P. A. (2011). "How I conduct a comprehensive chronic graft-versus-host disease assessment." Blood 118(10): 2679-2687.

The video can be viewed online at http://www.fredhutch.org/en/labs/clinical/projects/gvhd.html

About this Canterbury DHB document (81078):

Document Owner:

Not assigned (see Who's Who)

Issue Date:

December 2016

Next Review:

December 2018

Keywords:

Note: Only the electronic version is controlled. Once printed, this is no longer a controlled document. Disclaimer

Topic Code: 81078