Session Item

Describe the efficacy and safety of total lymphoid irradiation (TLI) in a cohort of lung transplant patients with chronic lung allograft dysfunction (CLAD), both bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS) phenotype. 

Eligible patients were aged 18 years or old; diagnosed with CLAD and underwent to TLI in our center between June 1^st, 2011 and July 31^st, 2018. CLAD diagnosis and phenotyping were established according to the existing ISHLT Consensus. TLI effects on lung function were assessed for the whole cohort, according to the speed of FEV₁ decline. Patients were followed until redo-transplantation, death or end of study in December 31^st, 2019. Clinical, demographic, and follow-up data were registered. Spirometric follow-up was available in all patients the year before and after TLI. Toxicities were registered according to common terminology criteria for adverse events (CTCAE) version 5.0.

TLI was administered in twice a week session of 0.8 Gy, with a targeted total dose of 8 Gy at the clinical target volume, which involves the low cervical, supraclavicular, infraclavicular, axillary, mediastinal, hilar, paraaortic, iliac, inguinal, and femoral lymph nodes, the spleen and the thymus area with a 3D margin of 1cm. All the patients were treated with 6 and 18 MV photons on Clinac 2100CD linear accelerator with a 3D conformal technique, through 3 isocenters with AP-PA fields in each of them.

Results are expressed as frequencies and percentages for qualitative variables and as median (interquartile range) for quantitative variables. Mixed-model regression analysis was used to evaluate changes in FEV₁ during the year before and after TLI. A significant difference in all p-values was considered <0.05.

A total of 40 LT patients diagnosed with CLAD were treated with TLI in our center. Median time from the diagnosis of CLAD to TLI onset was 4.8 (1.2-48) months. Median follow-up after TLI was 18.1 (1.2 – 97.8) months.

TLI treatment led to an attenuation of the FEV₁ decline rate in the whole group. A regression analysis of mixed models is carried out (figure 1). A FEV₁ intercept was 1200 mL/month. We observe that for the entire group prior to TLI there is a significant drop for the entire group of -78.42 ml per month [95% CI -98.16; -58.68 mL/month (p=0.000)]. After the TLI, this drop stabilizes with a monthly gain of 1.6 ml per month during the first year post TLI [95% CI -10.42; 13.72 mL/month (p=0.7889)].

Hematological and gastrointestinal toxicities are described in Table 1. After TLI, severe lymphopenia (toxicity grade 3-4) was present in 22 (57%) patients. In the first 30 days after TLI, 5 (14%) patients had lower respiratory tract infection and one (3%) with an acute diverticulitis (Hinchey Ib). None of them required hospital admission.

We found TLI is a safe and effective procedure in stabilizing FEV₁-decline in both BOS and RAS phenotypes, which should be considered early after CLAD diagnosis.