Patterns and Outcomes of Relapse Treated With Radiotherapy Following Total Marrow and Lymphoid Irradiation in High-Risk and/or Relapsed/Refractory Acute Leukemia

Abstract

Total Marrow and Lymphoid Irradiation (TMLI) is a promising component of the preparative regimen for hematopoietic cell transplantation in patients with high-risk and/or relapsed/refractory acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL), which has poor 5-yr OS at ∼15%. Extramedullary (EM) relapse rates in patients treated with this regimen has been reported to be ∼13%. This study evaluates patterns and outcomes of radiotherapy (RT) used to treat patients with EM relapse previously treated with TMLI.An IRB-approved analysis of 5 prospective TMLI trials was interrogated (IRB 04199, 05013, 05021, 14012, and 14106). Pre-transplant conditioning consisted of TMLI and etoposide (VP-16)/cyclophosphamide, fludarabine/melphalan, or bulsulfan/VP-16. TMLI targeted bones and major lymphoid tissues using image-guided tomotherapy, with total dose ranging from 12 to 20Gy delivered twice daily. EM recurrences were treated at the discretion of the hematologist and radiation oncologist using RT ± chemotherapy. Descriptive statistics and survival analysis were then performed on this cohort.In total, 254 patients with AML or ALL were treated with TMLI at our institution between 2006 and 2018. 21 of these patients were identified as receiving at least one subsequent course of radiation. A total of 67 relapse sites (median = 2 sites/patient, range = 1-16) were treated (6 lymph node, 34 soft tissue, 23 bone, and 4 CNS). At time of transplant, median age was 31 yrs (21-61 years). The median follow-up from date of transplant of these patients was 32.2 mo (3.9-154.1 mo). Of the 21 patients, 17 had active disease (MRD+ and/or bone marrow+) at transplant and 6 had prior history of EM disease. 12 patients had EM relapse only without BM relapse, while 5 had prior BM relapse and 4 had simultaneous EM and BM relapse. 12 recurrences were treated with systemic therapy prior to RT. The median mean TMLI dose to these sites was 12.0 Gy (4.0-20.8 Gy). 1-yr and 5-yr estimates of OS were 80.9% (95% CI = 56.9-92.4%) and 35.6% (95% CI = 13.8-58.3%), respectively. 1 and 2-yr OS following salvage RT to the first site of EM recurrence was 45.4% (95% CI = 23.1-65.3%) and 38.9% (95% CI = 17.7-59.8%), respectively. The median salvage RT dose was 24 Gy (6-30 Gy). Following RT, 86.6% of the sites had durable local control.To our knowledge, this is the largest analysis to date of patients treated with TMLI. Relapse incidence was as frequent in regions receiving ≥12 Gy as those receiving < 12 Gy, suggesting TMLI is not associated with an increased EM relapse risk. These patients did not have significantly different OS compared to historical controls. RT is an effective modality to treat EM relapse in patients with acute leukemia who were previously treated with TMLI.