The Impact of Low-Dose Cranial Boost on the Long-Term Outcomes of Adult Patients with High-Risk Acute Lymphoblastic Leukemia Undergoing Total Body Irradiation and Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Purpose: Total body irradiation (TBI) is an integral part of the conditioning regimen for patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic, hematopoietic, cell transplantation (allo-HCT). There are conflicting data in the literature regarding the utility of a cranial irradiation boost in high-risk adult ALL without evidence of preexisting central nervous system (CNS) involvement. This study investigates the posttransplant clinical outcomes of patients with high-risk adult ALL undergoing TBI conditioning for allo-HCT with or without a whole-brain boost, without overt CNS involvement at the time of diagnosis. Methods and materials: A retrospective cohort study was conducted using a medical record analysis. We identified 58 patients who were treated between January 1998 and December 2016, and met our preset inclusion criteria of adults (age >18 years old) who carried a pathologically confirmed diagnosis of CNS-negative, high-risk ALL, who underwent hematopoietic stem cell transplantation with TBI conditioning. A multivariate analysis of correlation between patient outcomes and collected categorical variables was assessed with stepwise Cox logistic regression. Survival analyses were assessed using the Kaplan-Meier technique with a log-rank test. Results: With a median follow-up time of 5.3 years, there was a statistically significant improvement in actuarial 7-year CNS relapse-free survival (100% vs 76.4%; P Z .043) in favor of patients undergoing a cranial boost. There was no statistically significant improvement in 7-year progression-free survival (78.3% vs 62.5%; P Z .076) or overall survival (49.4% vs 43.5%; Practical Radiation Oncology (2019) 9, e283-e289 www.practicalradonc.org P Z .921) with versus without a cranial boost. On multivariate analysis, the presence of a cranial boost was the only identified variable with an independent relationship to CNS relapse-free survival. Conclusions: Adult patients with high-risk, CNS-negative ALL were found to have a statistically significant improvement in CNS relapse-free survival and a trend toward improved progressionfree survival with the inclusion of a cranial boost with TBI pretransplant conditioning. Our data indicate that further investigation into the use of cranial boost in this patient population is warranted. Ó

A narrative review of central nervous system involvement in acute leukemias

“…The OS rates at 10 years did not differ significantly. The annual rates of non-CNS relapses were 17% lower in the methotrexate group (P=0.02), while the CNS and isolated CNS rates were both non significantly lower in this group (244)(245)(246)(247)(248)(249).…”

Central Nervous System Relapse After Stem Cell Transplantation in Adolescents and Young Adults with Acute Lymphoblastic Leukemia: A Single-Institution Experience

“…20 As such, a lower radiation dose CB may be recommended in cases where such preventive therapies are administered in conjunction with other effective systemic treatments or for those patients at significant risk of CNS leukemia. The studies by Famoso and Su et al 11,12 reported a CB of a low dose, 6 Gy in three fractions, resulting in a total dose of 18 Gy to the entire brain, a lower total dose than that traditionally used for whole brain ALL treatment. Su et al, noted one incident of late cataract formation attributed to radiotherapy, but no neurocognitive toxicity.…”

“…Famoso et al showed a significant improvement in 7-year CNS relapse-free survival (100% vs. 76.4%) in high-risk adult ALL patients undergoing TBI conditioning for SCT who received a CB. 11 Su et al evaluated 55 adults with high-risk ALL treated with or without a CB and found an overall CNS failure rate of 2.8% in the CB group and 10.5% in the non-CB group. 12 A recent study by Gao et al demonstrated the efficacy of a pretransplant CB as part of TBI in reducing the risk of CNS relapse.…”

Optimizing Management of the Central Nervous System in Patients with Acute Lymphoblastic Leukemia Undergoing Allogeneic Stem Cell Transplantation

“…A retrospective study from the University of Arizona evaluated 58 patients with high-risk ALL, none of whom had CNS disease at diagnosis, who underwent an allogeneic HSCT using a uniform myeloablative TBI-based conditioning regimen (12 Gy/6 fractions). 11 All patients received prophylactic IT chemotherapy in addition to systemic therapy. A low-dose (6 Gy) cranial boost was associated with improved CNS-relapse free survival at 7 years (100% vs 76%, P = .04), but this did not translate to improved PFS or OS, likely because most patients (4/6) who relapsed in the CNS had a simultaneous marrow failure.…”

“…However, there remains some uncertainty whether additional RT to the CNS axis is beneficial in patients without known CNS involvement, and there is wide practice variation regarding RT recommendations in patients with known CNS disease, including field size (CrI vs CSI) and dose. 10 , 11 , 12 …”