Augmenting Total Body Irradiation with a Cranial Boost before Stem Cell Transplantation Protects Against Post-Transplant Central Nervous System Relapse in Acute Lymphoblastic Leukemia

Gao, Robert W.; Dusenbery, Kathryn E.; Cao, Qing; Smith, Angela R.; Yuan, Jianling

doi:10.1016/j.bbmt.2017.11.013

Cited by 26 publications

(16 citation statements)

References 32 publications

(30 reference statements)

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“…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).…”

Section: Therapeutic Option For Cns Leukemiamentioning

confidence: 74%

A narrative review of central nervous system involvement in acute leukemias

Deak¹,

Gorcea-Andronic²,

Sas³

et al. 2021

Ann Transl Med

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Acute leukemias (both myeloid and lymphoblastic) are a group of diseases for which each year more successful therapies are implemented. However, in a subset of cases the overall survival (OS) is still exceptionally low due to the infiltration of leukemic cells in the central nervous system (CNS) and the subsequent formation of brain tumors. The CNS involvement is more common in acute lymphocytic leukemia (ALL), than in adult acute myeloid leukemia (AML), although the rates for the second case might be underestimated. The main reasons for CNS invasion are related to the expression of specific adhesion molecules (VLA-4, ICAM-1, VCAM, L-selectin, PECAM-1, CD18, LFA-1, CD58, CD44, CXCL12) by a subpopulation of leukemic cells, called "sticky cells" which have the ability to interact and adhere to endothelial cells. Moreover, the microenvironment becomes hypoxic and together with secretion of VEGF-A by ALL or AML cells the permeability of vasculature in the bone marrow increases, coupled with the disruption of blood brain barrier. There is a single subpopulation of leukemia cells, called leukemia stem cells (LSCs) that is able to resist in the new microenvironment due to its high adaptability. The LCSs enter into the arachnoid, migrate, and intensively proliferate in cerebrospinal fluid (CSF) and consequently infiltrate perivascular spaces and brain parenchyma. Moreover, the CNS is an immune privileged site that also protects leukemic cells from chemotherapy. CD56/NCAM is the most important surface molecule often overexpressed by leukemic stem cells that offers them the ability to infiltrate in the CNS. Although

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Section: Therapeutic Option For Cns Leukemiamentioning

confidence: 74%

A narrative review of central nervous system involvement in acute leukemias

Deak¹,

Gorcea-Andronic²,

Sas³

et al. 2021

Ann Transl Med

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“…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. 13 In their study, with a median patient age of 17.9 years, patients with prior CNS involvement and a pretransplantation CB had a 2year CNS relapse risk of 0%, while those with prior CNS involvement without a pretransplant CB had a 2-year CNS relapse risk of 21% ( p = 0.03). These three studies provide the rationale for our analysis.…”

Section: Discussionmentioning

confidence: 94%

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

Kozak

Yoo

Gutkin

et al. 2020

Journal of Adolescent and Young Adult Oncology

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Purpose: To evaluate outcomes and central nervous system (CNS) relapse in adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL), who underwent total body irradiation (TBI) before allogeneic hematopoietic stem cell transplantation (allo-SCT). Methods: A total of 136 AYA patients with ALL who received TBI before allo-SCT between 1998 and 2018 were reviewed. Twenty patients received cranial radiation in their initial treatment before conditioning for transplant and were excluded. Competing risk analysis was used to estimate the cumulative incidence of relapse. Kaplan-Meier and log-rank tests were used to calculate overall survival (OS) and to identify factors predictive of relapse. OS and time to relapse were calculated from date of allo-SCT. Results: One hundred sixteen patients were included in the analysis. Median age was 27 years and median follow-up time was 42 months. Twenty-six patients suffered a disease relapse and 49 died, 26 of posttransplantation complications. The median time to relapse was 7 months and the 5-year OS was 60%. Seven patients had a CNS relapse: 4 of 20 patients (25%) with pre-SCT CNS disease had a post-allo-SCT CNS relapse compared to 3 of 97 (3.1%) without pre-SCT CNS disease. Median time to CNS relapse was 7 months. Patients with post-SCT CNS relapse had median OS of 19 months. Conclusions: AYA patients with CNS disease who undergo an allo-SCT have a high rate of CNS relapse. The addition of additional CNS-directed therapy to transplant protocols warrants further investigation.

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“…Overt CNS involvement has been shown to be an independent predictor of benefit from the addition of a CNS boost. 22 Therefore, the authors evaluated their cohort after removing patients with prior CNS involvement. Much like the findings detailed in the current study, the researchers were able to demonstrate that a CNS boost improved 3-year CNS disease-free survival rates, and 100% of patients who received a boost remained diseasefree compared with 90% of patients who did not receive a boost.…”

Section: Discussionmentioning

confidence: 99%

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

Famoso

Grow

Laughlin

et al. 2019

Practical Radiation Oncology

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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

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Augmenting Total Body Irradiation with a Cranial Boost before Stem Cell Transplantation Protects Against Post-Transplant Central Nervous System Relapse in Acute Lymphoblastic Leukemia

Cited by 26 publications

References 32 publications

A narrative review of central nervous system involvement in acute leukemias

A narrative review of central nervous system involvement in acute leukemias

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

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

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