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Survival and Neurocognitive Outcomes Following Cranial or Craniospinal Irradiation Plus Total Body Irradiation Prior to Transplantation in Children with CNS Leukemia

Track: Poster Abstracts
Wednesday, February 26, 2014, 6:45 PM-7:45 PM
Longhorn Hall E (Exhibit Level 1) (Gaylord Texan)
Susan M Hiniker, MD , Radiation Oncology, Stanford University, Stanford, CA
Rajni Agarwal, MD , Pediatric Stem Cell Transplantation, Stanford University, Palo Alto, CA
Leslie A Modlin , Radiation Oncology, Stanford University, Stanford, CA
Jeremy P Harris, MPhil , Radiation Oncology, Stanford University, Stanford, CA
Eileen F Kiamanesh , Stanford University, Stanford, CA
Lynn Million , Stanford University, Stanford, CA
Christine C Gray, PhD , Pediatric Psychiatry, Stanford University, Stanford, CA
Sarah S Donaldson, MD , Radiation Oncology, Stanford University, Stanford, CA
Purpose/Objective(s): Optimal management of pediatric acute lymphoblastic leukemia (ALL) patients with CNS involvement remains a challenge, with limited data to guide treatment. The goal of this study is to evaluate survival and neurocognitive outcomes among pediatric ALL patients with CNS involvement who underwent stem cell transplantation (SCT) and received cranial or craniospinal irradiation in addition to total body irradiation (TBI) as pre-transplant preparative regimen according to an institutional protocol. 

Materials/Methods:A retrospective analysis was performed of pediatric ALL patients with CNS involvement who underwent SCT at our institution between 1986 and 2011. The Kaplan-Meier method was used to compute estimates of disease-free survival (DFS). Cox regression models were used to determine associations of patient and disease characteristics and treatment methods.

Results:Forty-one pediatric ALL patients underwent SCT with TBI as a preparative regimen and received additional cranial or craniospinal irradiation due to CNS involvement. Median age at diagnosis was 5 years (range 1 to 21 years). Twenty-six patients were standard-risk by NCI criteria, and 14 were high-risk. Five patients underwent transplant in first complete remission (CR), 25 in CR 2, and 11 in CR 3 or greater. All patients received a cranial boost; median cranial dose was 24 Gy (range 18-35.4 Gy). Eighteen patients received a spinal boost; median spinal dose for these patients was 18 Gy (range 15-24.6 Gy). Survival analysis from date of SCT revealed a 1 year DFS of 78%, 2 year 67%, and 5 year 67%. Univariate Cox regression revealed no statistically significant associations; however, omission of a spinal boost was associated with inferior DFS (HR 3.23, p=0.14). A combined CNS and bone marrow relapse prior to transplant was associated with an inferior DFS (HR 3.64, p=0.11), as compared with an isolated CNS relapse. 17/41 patients had an isolated CNS relapse, and analysis of these patients revealed a 1 year DFS of 88%, 2 year 81%, and 5 year 74%. A battery of neurocognitive testing was performed in 16 patients and at a mean of 4.4 years after transplant, mean post-transplant overall IQ was 103.7 (range 84-143). Pre and post-transplant neurocognitive testing in a subset revealed a mean overall IQ change of +4.8 points (range -1 to +9).

Conclusions: We show that addition of craniospinal irradiation to TBI is feasible in the preparative regimen for SCT in children with CNS leukemia and is associated with favorable DFS at 5 years post transplant, particularly in those patients with isolated CNS relapse. The use of craniospinal as opposed to cranial irradiation may be important in maximizing disease control. Post-transplant neurocognitive testing reveals average intelligence. Pre and post-transplant testing shows no change in IQ scores, though numbers remain small. CSI plus TBI is worthy of further protocol investigation.

Disclosures:
Nothing To Disclose
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