Similar Survival Rates, Less Toxicity Reported With Reduced-Intensity vs Myeloablative Total-Body Irradiation Before Transplant in Acute Leukemia
Used as a conditioning regimen for allogeneic transplantation in patients with acute leukemia, reduced-intensity total-body irradiation yielded similar overall and relapse-free survival rates to those seen with myeloablative total-body irradiation but with shorter hospital stays and fewer intensive care unit admissions, according to the results of a retrospective study presented in the International Journal of Radiation Oncology • Biology • Physics. Mikell et al suggested that their favorable results with this less toxic treatment approach may offer a strong basis for extending its use in the future to younger, more fit patients.
Total-body irradiation remains a key component in the conditioning regimen for hematopoietic stem cell transplantation, which is often used in patients with acute leukemia whose disease is refractory to primary therapy. However, for many patients unable to tolerate myeloablative total-body irradiation, reduced-intensity total-body irradiation has emerged as an alternative. In fact, the reduced doses of radiation may help to suppress the immune system and deplete enough host hematopoietic elements to permit donor stem cell engraftment in those whose Karnofsky performance status and comorbidities might prevent them from being eligible candidates for allogeneic transplantation.
Study Details
To find out how reduced-intensity total-body irradiation measured up against standard myeloablative total-body irradiation in patients with acute leukemia before allogeneic transplantation, Mikell and colleagues at Winship Cancer Institute of Emory University, Atlanta, conducted a study using a prospectively acquired database of hematopoietic stem cell transplantation patients treated at their institution.
Of a patient population of 226 patients with acute leukemia who underwent total-body irradiation before transplantation, full radiation therapy data were available for analysis for 180 patients. The detailed information focused on the transplantation procedure, disease status, Karnofsky performance status, response rates, toxicity, survival time, and time to disease progression. Patients’ length of hospital stay after transplantation and intensive care unit admissions within 30 days of transplantation were also assessed.
A closer look at the study population revealed that approximately half of them had acute lymphoblastic leukemia, and the other half had acute myelogenous leukemia. A total of 135 patients received myeloablative total-body irradiation, and 45 patients received reduced-intensity total-body irradiation. Standard myeloablative therapy was defined as 12 Gy delivered twice a day (with at least 6 hours in between), and reduced-intensity therapy was defined as 2 Gy delivered in single fractions.
The investigators noted a few differences and similarities between the patients in both treatment groups. For instance, those who received reduced-intensity total-body irradiation were generally older than those who received myeloablative therapy (median age of 57 years vs 35 years, P < .001).
In addition, patients who underwent reduced-intensity therapy had lower mean CD34 counts in their grafts than did those who underwent myeloablative total-body irradiation (8.28 vs 12.48, respectively; P = .021). As for Karnofsky performance status and gender, they were similar across both conditioning regimen groups.
Favorable Results With Reduced-Intensity Treatment
The study data showed similar overall survival, relapse-free survival, and relapse rates for patients in both treatment groups. The median overall survival for all patients was 13.7 months, and the median relapse-free survival for all patients was 10.2 months.
When the investigators controlled for age, gender, Karnofsky performance status, disease status, and diagnosis, they found no significant differences in overall survival (hazard ratio [HR] = 1.23, 95% confidence interval [CI] = 0.76?2.02, P = .402) or relapse-free survival (HR = 1.18, 95% CI = 0.73?1.91, P = .499) between patients who underwent reduced-intensity total-body irradiation and those who underwent myeloablative total-body irradiation. Furthermore, nonrelapse survival rates also were similar between the two groups (P = .186).
However, differences were demonstrated in terms of toxicity between the groups. For example, the median length of hospital stay for those who received reduced-intensity therapy was 16 days, compared with 23 days (P < .001) for those who received myeloablative therapy. On univariate analysis, reduced-intensity total-body irradiation was associated with a shorter length of hospital stay after transplantation than was myeloablative total-body irradiation (95% CI = ?13.11 to ?4.39, P < .0001).
As for admissions to the intensive care unit, 2.2% of those in the reduced-intensity group were admitted to the intensive care unit within 30 days of transplantation, compared with 12.7% of those in the myeloablative group (P = .043).
Future Clinical Implications
Along with the similar survival outcomes between the two groups, shorter hospital stays and fewer admissions to the intensive care unit with the reduced-intensity treatment reflected its improved toxicity profile, according to the investigators. Although Mikell and colleagues admitted that these outcomes are indirect measures of toxicity, the authors stated that these outcomes are readily defined and clinically relevant endpoints.
“Our findings provide a strong basis for protocols designed to extend the use of reduced-intensity total-body irradiation to younger, more fit patients, potentially obviating the need for more toxic myeloablative therapy,” concluded the investigators.
John L. Mikell, MD, of the Department of Radiation Oncology, Emory University School of Medicine, Atlanta, is the corresponding author of the article in the International Journal of Radiation Oncology • Biology • Physics. The study authors reported no potential conflicts of interest.
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