Editorial

What does total body irradiation do in bone marrow transplants for leukemia?

In patients with right-sided breast cancer (BC) the liver might be partially irradiated during adjuvant radiotherapy (RT). Thus, we performed a prospective observational study to evaluate the dose delivered to the liver, and its potential biological impact.

We enrolled 34 patients with right-sided BC treated with adjuvant RT. The RT schedules were either the Canadian (42.5 Gy in 16 fx) or standard fractionated (50 Gy in 25 fx) regimen respectively with 9 (26.5%) and 25 (73.5%) patients each, ± a boost of 10–16 Gy. Each patient had a complete blood count and liver enzymes analysis, before starting and during the last week of treatment.

A significant decrease in white blood cells and thrombocytes counts was observed during RT. We observed a significant correlation between certain hepatic parameters and the volume of the irradiated liver and/or the mean liver dose. A significant correlation between the volume of the right lung and the liver mean dose was found (P = 0.008). In the bivariate analysis, a significant correlation between fatigue and the white blood cell count's evolution was observed (P < 0.025).

With the standard RT technique, incidental irradiation of the liver was documented in a large number of patients, and some significant hepatic parameters alterations were observed, without an apparent clinical impact, but this study cannot exclude them. The liver mean dose was correlated with the right lung volume suggesting that deep inspiration breath hold (DIBH) techniques may represent a way to decrease the liver dose. These findings need to be evaluated in further larger studies.

Chez les patientes atteintes d’un cancer du sein droit, le foie peut être partiellement irradié durant une radiothérapie adjuvante. Nous avons réalisé une étude prospective observationnelle évaluant la dose administrée au foie, et son impact biologique potentiel.

Nous avons inclus 34 patientes atteintes d’un cancer du sein droit et traités par irradiation adjuvante. Les fractionnements utilisés étaient soit le schéma canadien (42,5 Gy en 16 fractions) soit un schéma standard (50 Gy en 25 fractions), chez respectivement neuf (26,5 %) et 25 (73,5 %) patientes, avec ou non un complément d’irradiation de 10–16 Gy. Chaque patiente a bénéficié d’une formule sanguine simple et d’un dosage des enzymes hépatiques, avant de débuter la radiothérapie, puis lors de la dernière semaine de traitement.

Une diminution significative du nombre des leucocytes et des thrombocytes a été observée durant la radiothérapie ainsi qu’une corrélation significative entre l’altération de certains paramètres hépatiques et le volume hépatique irradié et/ou la dose moyenne délivrée au foie. Une corrélation significative entre le volume pulmonaire droit et la dose moyenne délivrée foie a été observée (p = 0,008). Une corrélation significative entre l’asthénie et l’évolution de la concentration des leucocytes a été observée (p < 0,025).

Avec des techniques de radiothérapie standard, nous avons documenté une irradiation hépatique partielle dans une grande proportion des patientes et nous avons observé des altérations significatives des paramètres hépatiques, sans traduction clinique apparente. Nous avons trouvé une corrélation significative entre la dose moyenne dans le foie et le volume pulmonaire droit, suggérant que la technique d’inspiration profonde bloquée pourrait représenter une solution pour diminuer la dose dans le foie. Ces résultats devraient être évalués avec des études plus larges.

Total body irradiation (TBI) has been widely utilized as part of the conditioning regimen for hematopoietic stem cell transplantation (HSCT), but is associated with significant toxicities. Targeted TBI using helical Tomotherapy allows precise and homogeneous tumor coverage and excellent sparing of organs at risk. The purpose of this study was to evaluate the clinical outcomes of a novel hypo-fractionation strategy for patients receiving total marrow and involved lymphoid irradiation (TMLI) as part of the conditioning regimen before HSCT.

61 patients (7 acute myelogenous leukemia (AML), 33 acute lymphoblastic leukemia (ALL), 18 non-Hodgkin’s lymphoma (NHL), 3 mixed acute leukemia (MAL)) received conditioning radiation treatment with TMLI (8 Gy to bone marrow, 10 Gy to involved field in 2 fractions per day) in conjunction with chemotherapy before transplantation.

The median age of 61 patients with TMLI was 24 (4–54) years. The prescribed dose covered the entire bone and involved target volume, and the dose of organs at risk (OAR) was reduced by 28%−78% of the prescription dose. Grade 1–2 nausea and vomiting occurred in 12 patients and grade 1–2 pain in 6 patients during radiotherapy. Fatigue occurred in 16 patients. 2 patients had diarrhea, enteritis, and 1 patient had fever. None of patient had grade 3–4 non-hematologic adverse reactions. Late (30 days after HSCT) grade 2 toxicities including reversible enteritis occurred in 3 patients. 5 patients developed infectious pneumonia. The 2 years progression-free survival (PFS) was 64.1% (95% CI: 0.16–0.22) and overall survival (OS) was 74.7% (95% CI: 0.19–0.24) for the 61 patients who had received their planned HSCT. The 2-year non-relapse mortality was significantly reduced to 5% in this patient cohort.

This study demonstrates that hypo-fractionated TMLI (8 Gy to bone marrow, 10 Gy to involved field in a single day) as a conditioning regimen for lymphoma and acute leukemia was feasible and the clinical outcomes were acceptable.

Hematopoietic stem cell transplantation (HSCT) is often indicated for patients with high-risk and relapsed or refractory hematologic cell malignancies. Historically the role of radiation therapy (RT) when combined with allogeneic HSCT was as a form of myeloablative conditioning with total-body irradiation (TBI). However, RT can also be used as a form of treatment intensification when combined with HSCT to improve local control in this patient population at sites of tumor bulk, multiple refractory disease, or in sanctuary areas that systemic therapy alone may not adequately address. In this chapter we review the potential role of external beam radiation therapy in the setting of allogeneic and autologous HSCT for patients with hematologic malignances.

We sought to determine whether the total body irradiation (TBI) schedule affected outcome in patients with acute leukemia in complete remission who received T cell–depleted allogeneic hematopoietic stem cell transplantation from HLA identical siblings.

The study recruited 55 patients (median age, 48 years; age range, 20-66 years; 30 men and 25 women; 34 with acute myeloid leukemia and 21 with acute lymphoid leukemia). Hyperfractionated TBI (HTBI) (1.2 Gy thrice daily for 4 days [for a total dose of 14.4 Gy] from day −12 to day −9) was administered to 29 patients. Single-dose TBI (STBI) (8 Gy, at a median dose rate of 10.7 cGy/min on day −9) was given to 26 patients.

All patients achieved primary, sustained engraftment with full donor-type chimerism. At 10 years, the overall cumulative incidence of transplant-related mortality was 11% (SE, ±0.1%). It was 7% (SE, ±0.2%) after HTBI and 15% (SE, ±0.5%) after STBI (P=.3). The overall cumulative incidence of relapse was 33% (SE, ±0.5). It was 13% (SE, ±0.5%) after HTBI and 46% (SE, ±1%) after STBI (P=.02). The overall probability of disease-free survival (DFS) was 59% (SE, ±7%). It was 67% (SE, ±0.84%) after HTBI and 37% (SE, ±1.4%) after STBI (P=.01). Multivariate analyses showed the TBI schedule was the only risk factor that significantly affected relapse and DFS (P=.01 and P=.03, respectively).

In patients with acute leukemia, HTBI is more efficacious than STBI in eradicating minimal residual disease after HLA-matched T cell–depleted hematopoietic stem cell transplantation, thus affecting DFS.