Reduced incidence of interstitial pneumonitis after allogeneic hematopoietic stem cell transplantation using a modified technique of total body irradiation

Abstract

Allogeneic hematopoietic stem cell transplantation is a curative-intent treatment for patients with high-risk hematologic diseases. However, interstitial pneumonitis (IP) and other toxicities remain major concerns after total body irradiation (TBI). We have proposed using linear accelerators with rice-bag compensators for intensity modulation (IM-TBI), as an alternative to the traditional cobalt-60 teletherapy with lung-shielding technique (Co-TBI). Patients who received a TBI-based myeloablative conditioning regimen between 1995 and 2014 were recruited consecutively. Before March 2007, TBI was delivered using Co-TBI (n = 181); afterward, TBI was administered using IM-TBI (n = 126). Forty-four patients developed IP; of these cases, 19 were idiopathic. The IP-related mortality rate was 50% in the total IP cohort and 63% in the idiopathic subgroup. The 1-year cumulative incidences of IP and idiopathic IP were 16.5% and 7.4%, respectively; both rates were significantly higher in the Co-TBI group than in the IM-TBI group. Multivariate analysis revealed that Co-TBI was an independent prognostic factor for both total and idiopathic IP. In the acute myeloid leukemia subgroup, patients with different TBI techniques had similar outcomes for both overall and relapse-free survival. In conclusion, IM-TBI is an easy and effective TBI technique that could substantially reduce the complication rate of IP without compromising treatment efficacy.

Adverse Effects of Total Body Irradiation: A Two-Decade, Single Institution Analysis

“…Several studies in the literature have addressed the issue of pulmonary toxicity in TBI. 7,8,[13][14][15][16][17][18][19][20][21][22] Rates of pneumonitis vary considerably throughout the literature. The considerable variation is likely due to the multifactorial nature of pulmonary toxicity related to stem cell transplantation as there are several variables related to patient characteristics, chemotherapy regimen, and radiation delivery.…”

Total body irradiation induced mouse small intestine senescence as a late effect

“…According to the guideline from the International Lymphoma Radiation Oncology Group (ILROG), the most common total body irradiation (TBI) schedules used before HSCT include the following plans: (i) twice-daily 2-Gy fractions given over 3 days (total dose 12 Gy); (ii) twice-daily 1.5-Gy fractions over 4–4.5 days (total dose 12–13.5 Gy); (iii) three-times-daily 1.2-Gy fractions over 4 days (total dose 12–13.2 Gy); and (iv) once-daily 3-Gy fractions for 4 days (total dose 12 Gy) [3]. As a result of TBI, acute injuries such as radiation pneumonitis [4] and oral mucositis [5] often occur 1–6 months after HSCT, but late injuries, including cataract [6] and gonad injury [7] can happen a long time after HSCT. It is well known that TBI can induce radiation enteritis several days after patients have been exposed to TBI [8, 9]; however, the late effects of TBI on small intestinal injury are rarely reported.…”

Total Body Irradiation for Hematopoietic Stem Cell Transplantation: What Can We Agree on?

“…Linear accelerators simplify and reduce the duration of TBI delivery [ 42 ]. Furthermore, interstitial pulmonary syndromes, an early and devastating complication of TBI, appear to have been reduced with the adoption of linear accelerators, although it is uncertain if this is due to the increased flexibility of radiation delivery permitted by linear accelerators compared to the limited options available with the cobalt machines [ 43 ]. Newer machines, such as those that use helical tomography, are being studied and deliver radiation throughout the body but can further concentrate the beam on the diseased tissue while greatly sparing the normal sensitive tissues, which may further minimize serious complications from TBI [ 35 ].…”

“…This proved to be very convenient for the patient and the most practical method given the equipment available and the techniques initially being used. However, lung toxicity, specifically fatal radiation pneumonitis, was a major concern [ 42 , 43 , 44 ]. Radiobiology modelling suggests that reduced dose-per-fraction minimizes normal tissue toxicity [ 45 , 46 ].…”