Susan M Hiniker1, Rajni Agarwal2, Leslie A Modlin1, Christine C Gray3, Jeremy P Harris1, Lynn Million1, Eileen F Kiamanesh4, Sarah S Donaldson5. 1. Department of Radiation Oncology, Stanford University, Stanford, California. 2. Section of Stem Cell Transplantation, Department of Pediatrics, Stanford University, Stanford, California. 3. Division of Child and Adolescent Psychiatry, Department of Psychiatry, Stanford University, Stanford, California. 4. Cancer Clinical Trials Office, Stanford Cancer Institute, Stanford University, Stanford, California. 5. Department of Radiation Oncology, Stanford University, Stanford, California. Electronic address: sarah2@stanford.edu.
Abstract
PURPOSE: To evaluate survival and neurocognitive outcomes in pediatric acute lymphoblastic leukemia (ALL) patients with central nervous system (CNS) involvement treated according to an institutional protocol with stem cell transplantation (SCT) and a component of craniospinal irradiation (CSI) in addition to total-body irradiation (TBI) as preparative regimen. METHODS AND MATERIALS: Forty-one pediatric ALL patients underwent SCT with TBI and received additional cranial irradiation or CSI because of CNS leukemic involvement. Prospective neurocognitive testing was performed before and after SCT in a subset of patients. Cox regression models were used to determine associations of patient and disease characteristics and treatment methods with outcomes. RESULTS: All patients received a cranial radiation boost; median total cranial dose was 24 Gy. Eighteen patients (44%) received a spinal boost; median total spinal dose for these patients was 18 Gy. Five-year disease-free survival (DFS) for all patients was 67%. Those receiving CSI had a trend toward superior DFS compared with those receiving a cranial boost alone (hazard ratio 3.23, P=.14). Patients with isolated CNS disease before SCT had a trend toward superior DFS (hazard ratio 3.64, P=.11, 5-year DFS 74%) compared with those with combined CNS and bone marrow disease (5-year DFS 59%). Neurocognitive testing revealed a mean post-SCT overall intelligence quotient of 103.7 at 4.4 years. Relative deficiencies in processing speed and/or working memory were noted in 6 of 16 tested patients (38%). Pre- and post-SCT neurocognitive testing revealed no significant change in intelligence quotient (mean increase +4.7 points). At a mean of 12.5 years after transplant, 11 of 13 long-term survivors (85%) had completed at least some coursework at a 2- or 4-year college. CONCLUSION: The addition of CSI to TBI before SCT in pediatric ALL with CNS involvement is effective and well-tolerated. Craniospinal irradiation plus TBI is worthy of further protocol investigation in children with CNS leukemia.
PURPOSE: To evaluate survival and neurocognitive outcomes in pediatric acute lymphoblastic leukemia (ALL) patients with central nervous system (CNS) involvement treated according to an institutional protocol with stem cell transplantation (SCT) and a component of craniospinal irradiation (CSI) in addition to total-body irradiation (TBI) as preparative regimen. METHODS AND MATERIALS: Forty-one pediatric ALL patients underwent SCT with TBI and received additional cranial irradiation or CSI because of CNS leukemic involvement. Prospective neurocognitive testing was performed before and after SCT in a subset of patients. Cox regression models were used to determine associations of patient and disease characteristics and treatment methods with outcomes. RESULTS: All patients received a cranial radiation boost; median total cranial dose was 24 Gy. Eighteen patients (44%) received a spinal boost; median total spinal dose for these patients was 18 Gy. Five-year disease-free survival (DFS) for all patients was 67%. Those receiving CSI had a trend toward superior DFS compared with those receiving a cranial boost alone (hazard ratio 3.23, P=.14). Patients with isolated CNS disease before SCT had a trend toward superior DFS (hazard ratio 3.64, P=.11, 5-year DFS 74%) compared with those with combined CNS and bone marrow disease (5-year DFS 59%). Neurocognitive testing revealed a mean post-SCT overall intelligence quotient of 103.7 at 4.4 years. Relative deficiencies in processing speed and/or working memory were noted in 6 of 16 tested patients (38%). Pre- and post-SCT neurocognitive testing revealed no significant change in intelligence quotient (mean increase +4.7 points). At a mean of 12.5 years after transplant, 11 of 13 long-term survivors (85%) had completed at least some coursework at a 2- or 4-year college. CONCLUSION: The addition of CSI to TBI before SCT in pediatric ALL with CNS involvement is effective and well-tolerated. Craniospinal irradiation plus TBI is worthy of further protocol investigation in children with CNS leukemia.
Authors: William Su; Marcher Thompson; Ren-Dih Sheu; Amir Steinberg; Luis Isola; Richard Stock; Richard L Bakst Journal: Pract Radiat Oncol Date: 2016-06-23
Authors: Debra Lynch Kelly; David Buchbinder; Rafael F Duarte; Jeffrey J Auletta; Neel Bhatt; Michael Byrne; Zachariah DeFilipp; Melissa Gabriel; Anuj Mahindra; Maxim Norkin; Helene Schoemans; Ami J Shah; Ibrahim Ahmed; Yoshiko Atsuta; Grzegorz W Basak; Sara Beattie; Sita Bhella; Christopher Bredeson; Nancy Bunin; Jignesh Dalal; Andrew Daly; James Gajewski; Robert Peter Gale; John Galvin; Mehdi Hamadani; Robert J Hayashi; Kehinde Adekola; Jason Law; Catherine J Lee; Jane Liesveld; Adriana K Malone; Arnon Nagler; Seema Naik; Taiga Nishihori; Susan K Parsons; Angela Scherwath; Hannah-Lise Schofield; Robert Soiffer; Jeff Szer; Ida Twist; Anne Warwick; Baldeep M Wirk; Jean Yi; Minoo Battiwalla; Mary E Flowers; Bipin Savani; Bronwen E Shaw Journal: Biol Blood Marrow Transplant Date: 2017-09-20 Impact factor: 5.742
Authors: David Buchbinder; Debra Lynch Kelly; Rafael F Duarte; Jeffery J Auletta; Neel Bhatt; Michael Byrne; Zachariah DeFilipp; Melissa Gabriel; Anuj Mahindra; Maxim Norkin; Helene Schoemans; Ami J Shah; Ibrahim Ahmed; Yoshiko Atsuta; Grzegorz W Basak; Sara Beattie; Sita Bhella; Christopher Bredeson; Nancy Bunin; Jignesh Dalal; Andrew Daly; James Gajewski; Robert Peter Gale; John Galvin; Mehdi Hamadani; Robert J Hayashi; Kehinde Adekola; Jason Law; Catherine J Lee; Jane Liesveld; Adriana K Malone; Arnon Nagler; Seema Naik; Taiga Nishihori; Susan K Parsons; Angela Scherwath; Hannah-Lise Schofield; Robert Soiffer; Jeff Szer; Ida Twist; Anne B Warwick; Baldeep M Wirk; Jean Yi; Minoo Battiwalla; Mary D E Flowers; Bipin Savani; Bronwen E Shaw Journal: Bone Marrow Transplant Date: 2018-01-17 Impact factor: 5.483