Myeloablative conditioning with total body irradiation for AML: Balancing survival and pulmonary toxicity

Abstract

PurposeThe purpose of this study was to compare leukemia-free survival (LFS) and other clinical outcomes in patients with acute myelogenous leukemia who underwent a myeloablative allogeneic stem cell transplant with and without total body irradiation (TBI).Methods and materialsAdult patients with acute myelogenous leukemia undergoing myeloablative allogeneic stem cell transplant at Duke University Medical Center between 1995 and 2012 were included. The primary endpoint was LFS. Secondary outcomes included overall survival (OS), nonrelapse mortality, and the risk of pulmonary toxicity. Kaplan-Meier survival estimates and Cox proportional hazards multivariate analyses were performed.ResultsA total of 206 patients were evaluated: 90 received TBI-based conditioning regimens and 116 received chemotherapy alone. Median follow-up was 36 months. For all patients, 2-year LFS and OS were 36% (95% confidence interval [CI], 29-43) and 39% (95% CI, 32-46), respectively. After adjusting for known prognostic factors using a multivariate analysis, TBI was associated with improved LFS (hazard ratio: 0.63; 95% CI: 0.44-0.91) and OS (hazard ratio: 0.63; 95% CI, 0.43-0.91). There was no difference in nonrelapse mortality between cohorts, but pulmonary toxicity was significantly more common with TBI (2-year incidence 42% vs 12%, P < .001). High-grade pulmonary toxicity predominated with both conditioning strategies (70% and 93% of cases were grade 3-5 with TBI and chemotherapy alone, respectively).ConclusionsTBI-based regimens were associated with superior LFS and OS but at the cost of increased pulmonary toxicity.

Comparison of Different Conditioning Regimens in Allogeneic Hematopoietic Stem-Cell Transplantation Shows Superiority of Total Body Irradiation–Based Regimen for Younger Patients With Acute Leukemia: A Nationwide Study

“…1,21 Especially for AML, TBI-based conditioning has traditionally been associated with survival benefits, including lower rates of leukemia relapse, lower TRM, and higher disease-free survival, with comparable adverse events compared to chemotherapy-only conditioning. 6,22,23 This was challenged with the introduction of IV Bu, and in recent analyses of 1230 AML patients, the nonrelapse mortality was significantly less frequent and survival rates were higher in patients receiving IV Bu compared to the TBI group. 24 Another large retrospective multicenter study performed by the European Group for Blood and Marrow Transplantation (EBMT) in 2013 demonstrated that although a TBI-based regimens resulted in a significantly lower incidence of relapse and comparable survival outcomes compared to IV BuCy, it led to higher rates of GVHD in AML patients.…”

The safety and efficacy of a novel hypo-fractionated total marrow and lymphoid irradiation before allogeneic stem cell transplantation for lymphoma and acute leukemia

“…TBI provides therapy to sanctuary sites not easily reached by chemotherapy drugs and provides another mechanism of tumor cell kill against chemotherapy-resistant cell clones. The other is immunosuppression to decrease the risk of graft versus host disease (GVHD) and to enable sustained engraftment [3,4]. However, treatment-related morbidity and mortality can increase, negating any potential advantage for survival [5,6].…”

Gonadal-sparing total body irradiation with the use of helical tomotherapy for nonmalignant indications

“…Both traditional TBI approaches (opposed lateral and AP/PA) use extended source to skin dis-tances (SSDs), custom compensators, blocks, and beam spoilers to ensure adequate skin dose [1]. However, traditional linear accelerator-based delivery has several limitations, including dose-limiting toxicity [2,3]. For men, attempts to use a "clamshell" testicular shield may increase dose due to increased electron scatter [4].…”