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.

Clinical symptoms

Pulmonary function testing (PFT)

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

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

Differential diagnosis

Grading of pulmonary GvHD

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:

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

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


About this Canterbury DHB document (81078):
Document Owner:	Not assigned (see Who's Who)
Last Reviewed:	December 2016
Next Review:	December 2018
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Note: Only the electronic version is controlled. Once printed, this is no longer a controlled document. Disclaimer The Haematology Department Protocols and Guidelines (the Red Book) are intended as a guide for registered health professionals to communicate guidelines and share best practices with supporting health professionals within New Zealand district health boards. They are not intended to be provided to or used as a reference for patients or non-registered health professionals. All health professionals must exercise their own clinical judgement and use pertinent clinical data when treating patients. The authors and editors of this publication have checked with sources believed to be reliable in their effort to provide information that is complete and in accord with the standards accepted at the time of publication. However, in view of the possibility of human error or changes in medical science, neither the authors, editors, publisher, nor any other party who has been involved in preparing or publishing this work warrants that the information contained in it is accurate or complete in every respect. They therefore have no liability (whether in tort (including negligence) or otherwise) for any loss or damage arising out of any reliance on this information. This publication has been compiled by the staff and contractors of Canterbury District Health Board (CDHB) and as such CDHB has copyright for this book. Amendments must be authorised in accordance with the documented process. No release of part of, or all of, this publication to any other party or organisation is permissible without the prior approval of the designated document owner.
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Obstructive	Restrictive
FEV₁<80% predicted	FEV₁or FVC <80% predicted
FEV₁/FVC <70%	FEV₁/FVC >70%

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

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


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


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