Session Item

Myeloablative conditioning regimens using total body irradiation (TBI) have been associated with reductions in acute leukemia recurrence after allogeneic hematopoietic cell transplant (AHCT) but are accompanied by relevant pulmonary toxicity. In this study we investigate the effect of lung dose reduction and intensified pulmonary protection while keeping a 13.5 Gy prescribed dose on toxicity and survival.

All consecutive adult AHCT recipients who received a TBI-based conditioning due to acute leukemia between 1993 and 2021 were included. All patients were treated with 15 MV photons from LINAC in a semi-standing position, using individualized lung shields hanging in a methacrylate spoiler close to the patient in the beam’s path. From 2010 onwards, margins between the edge of the lung shadow and the edge of the bloc were reduced from 2 cm to 1cm laterally and from 2,5 cm to 1,5 cm craniocaudally. Moreover, lung dose was reduced from 9.5+/- 0,5 Gy to 8.5+/-0,5 Gy. Our aims were to analyse the incidence and risk factors of idiopathic pneumonia syndrome (IPS) and survival. Overall survival (from day 0 to death or last control) and disease-specific survival (considering events in which patients died due to the leukemia or any complication related to the treatment) were calculated using the Kaplan-Meier estimator and compared in two different periods (treatments performed before or after 2010) using the log-rank test.  

A total of 185 patients, 65 (35%) with ALL and 120 (65%) with AML were included. Median age was 38 years (18-59) and 83 were women (45%); 61% were in first complete remission. Median follow-up for survivors: 1,6 years (1-27). Nineteen patients had IPS (10,3%), and 7 of them died early after transplant. Most IPS cases were diagnosed before 2010 (15% vs 4,7%; p= 0,028) and all them received lung doses over 8.5 Gy. The 1y/5y-DSS were 61,4%/47,9% and 90,2%/81,4% before and after 2020, respectively (p=0,000) (Fig.1). Multivariate analyses showed that pre-transplant abnormalities in baseline chest X-Ray (p=0.001) and lung irradiation dose (p=0,005) were significantly associated with IPS development. In fact, the risk of pneumonitis increased four times for each Gy in the lungs. The 1y/5y-OS were 54%/37,7% before 2020 and 81%/69,5% after 2020 (p=0,000) (Fig2). Transplant period (before 2010), lung dose and development of pneumonitis were associated with lower OS (p=0,000).

Fig 1.  Disease specific survival (death due to leukemia or related to the treatment were computed as events) (In red, patients treated since 2010 an in blue, patients treated before 2010)

Fig 2. Overall survival (In red, patients treated since 2010 and in blue, patients treated before  2010)

Our results suggest that use of individualized lung shields with maximum protection and avoidance of lung doses over 8.5 Gy are associated with lower lung toxicity without reducing long term survival in high risk AL patients receiving 13.5 TBI-conditioning schedules.