Skip to main content
Top

Open Access 13-06-2024 | Acute Lymphoblastic Leukemia

Glucocorticoid Therapy in Acute Lymphoblastic Leukemia: Navigating Short-Term and Long-Term Effects and Optimal Regimen Selection

Authors: Hoda Pourhassan, Lindsey Murphy, Ibrahim Aldoss

Published in: Current Hematologic Malignancy Reports

Login to get access

Abstract

Purpose of Review

Glucocorticoids are a mainstay in acute lymphoblastic leukemia treatment and lack of early response is predictive for overall disease prognosis. Given the vital position of glucocorticoids and well known long and short-term side effects associated with differing glucocorticoids, we aim to highlight the wide breadth of historical and more contemporary data to describe the current landscape of glucocorticoid use in this arena.

Recent Findings

Emerging studies aim to overcome issues such as steroid resistance and to optimize the antileukemic effects of glucocorticoids while aiming to mitigate the risks and side effects associated with their exposure.

Summary

Glucocorticoids have and likely always will be a fundamental component of acute lymphoblastic leukemia treatment and understanding how to navigate short- and long-term effects and how to optimize regimens is at the heart of continued treatment success.
Literature
1.
go back to reference Nguyen K, et al. Factors influencing survival after relapse from acute lymphoblastic leukemia: a Children’s Oncology Group study. Leukemia. 2008;22:2142–50.PubMedPubMedCentralCrossRef Nguyen K, et al. Factors influencing survival after relapse from acute lymphoblastic leukemia: a Children’s Oncology Group study. Leukemia. 2008;22:2142–50.PubMedPubMedCentralCrossRef
2.
go back to reference Dördelmann M, et al. Prednisone response is the strongest predictor of treatment outcome in infant acute lymphoblastic leukemia. Blood. 1999;94(1209–1217):47. Dördelmann M, et al. Prednisone response is the strongest predictor of treatment outcome in infant acute lymphoblastic leukemia. Blood. 1999;94(1209–1217):47.
5.
go back to reference Kaspers GJ, Veerman AJ, Popp-Snijders C, et al. Comparison of the antileukemic activity in vitro of dexamethasone and prednisolone in childhood acute lymphoblastic leukemia. Med Pediatr Oncol. 1996;27:114–21.PubMedCrossRef Kaspers GJ, Veerman AJ, Popp-Snijders C, et al. Comparison of the antileukemic activity in vitro of dexamethasone and prednisolone in childhood acute lymphoblastic leukemia. Med Pediatr Oncol. 1996;27:114–21.PubMedCrossRef
6.
go back to reference Balis FM, Lester CM, Chrousos GP, Heideman RL, Poplack DG. Differences in cerebrospinal fluid penetration of corticosteroids: possible relationship to the prevention of meningeal leukemia. J Clin Oncol. 1987;5(2):202–7.PubMedCrossRef Balis FM, Lester CM, Chrousos GP, Heideman RL, Poplack DG. Differences in cerebrospinal fluid penetration of corticosteroids: possible relationship to the prevention of meningeal leukemia. J Clin Oncol. 1987;5(2):202–7.PubMedCrossRef
7.
go back to reference Jones B, Freeman AI, Shuster JJ, et al. Lower incidence of meningeal leukemia when prednisone is replaced by dexamethasone in the treatment of acute lymphocytic leukemia. Med Pediatr Oncol. 1991;19(4):269–75.PubMedCrossRef Jones B, Freeman AI, Shuster JJ, et al. Lower incidence of meningeal leukemia when prednisone is replaced by dexamethasone in the treatment of acute lymphocytic leukemia. Med Pediatr Oncol. 1991;19(4):269–75.PubMedCrossRef
8.
go back to reference Veerman AJ, Hählen K, Kamps WA, et al. High cure rate with a moderately intensive treatment regimen in non-high-risk childhood acute lymphoblastic leukemia. Results of protocol ALL VI from the Dutch Childhood Leukemia Study Group. J Clin Oncol. 1996;14(3):911–8.PubMedCrossRef Veerman AJ, Hählen K, Kamps WA, et al. High cure rate with a moderately intensive treatment regimen in non-high-risk childhood acute lymphoblastic leukemia. Results of protocol ALL VI from the Dutch Childhood Leukemia Study Group. J Clin Oncol. 1996;14(3):911–8.PubMedCrossRef
9.
go back to reference Quddus FF, Leventhal BG, Boyett JM, Pullen DJ, Crist WM, Borowitz MJ. Glucocorticoid receptors in immunological subtypes of childhood acute lymphocytic leukemia cells: a Pediatric Oncology Group Study. Cancer Res. 1985;45:6482–6.PubMed Quddus FF, Leventhal BG, Boyett JM, Pullen DJ, Crist WM, Borowitz MJ. Glucocorticoid receptors in immunological subtypes of childhood acute lymphocytic leukemia cells: a Pediatric Oncology Group Study. Cancer Res. 1985;45:6482–6.PubMed
10.
go back to reference Tissing WJ, Meijerink JP, den Boer ML, Pieters R. Molecular determinants of glucocorticoid sensitivity and resistance in acute lymphoblastic leukemia. Leukemia. 2003;17:17–25.PubMedCrossRef Tissing WJ, Meijerink JP, den Boer ML, Pieters R. Molecular determinants of glucocorticoid sensitivity and resistance in acute lymphoblastic leukemia. Leukemia. 2003;17:17–25.PubMedCrossRef
11••.
go back to reference . Bostrom BC, Sensel MR, Sather HN, et al. Dexamethasone versus prednisone and daily oral versus weekly intravenous mercaptopurine for patients with standard-risk acute lymphoblastic leukemia: a report from the Children's Cancer Group. Blood. 2003;101:3809–17. Landmark paper highlighting higher EFS and less CNS relapse with dexamethasone.PubMedCrossRef . Bostrom BC, Sensel MR, Sather HN, et al. Dexamethasone versus prednisone and daily oral versus weekly intravenous mercaptopurine for patients with standard-risk acute lymphoblastic leukemia: a report from the Children's Cancer Group. Blood. 2003;101:3809–17. Landmark paper highlighting higher EFS and less CNS relapse with dexamethasone.PubMedCrossRef
12••.
go back to reference . Mitchell CD, Richards SM, Kinsey SE, Lilleyman J, Vora A, Eden TO. Benefit of dexamethasone compared with prednisolone for childhood acute lymphoblastic leukaemia: results of the UK Medical Research Council ALL97 randomized trial. Br J Haematol. 2005;129:734–45. Landmark paper highlighting superiority of dexamethasone over prednisone resulting in early closure of randomization.PubMedCrossRef . Mitchell CD, Richards SM, Kinsey SE, Lilleyman J, Vora A, Eden TO. Benefit of dexamethasone compared with prednisolone for childhood acute lymphoblastic leukaemia: results of the UK Medical Research Council ALL97 randomized trial. Br J Haematol. 2005;129:734–45. Landmark paper highlighting superiority of dexamethasone over prednisone resulting in early closure of randomization.PubMedCrossRef
13••.
go back to reference . Vrooman LM, Neuberg DS, Stevenson KE, Supko JG, Sallan SE, Silverman LB. Dexamethasone and individualized asparaginase dosing are each associated with superior event-free survival in childhood acute lymphoblastic leukemia: results from DFCI-ALL Consortium Protocol 00-01. Blood (ASH Annual Meeting Abstracts). 2009;114:321. Landmark paper demonstrating that higher EFS is even observed when dexamethasone is used only after induction therapy and can abrogate the adversity of high-risk disease. . Vrooman LM, Neuberg DS, Stevenson KE, Supko JG, Sallan SE, Silverman LB. Dexamethasone and individualized asparaginase dosing are each associated with superior event-free survival in childhood acute lymphoblastic leukemia: results from DFCI-ALL Consortium Protocol 00-01. Blood (ASH Annual Meeting Abstracts). 2009;114:321. Landmark paper demonstrating that higher EFS is even observed when dexamethasone is used only after induction therapy and can abrogate the adversity of high-risk disease.
14••.
go back to reference . Schrappe M, Zimmermann M, Moricke A, et al. Dexamethasone in induction can eliminate one third of all relapses in childhood acute lymphoblastic leukemia (ALL): results of an international randomized trial in 3655 Patients (Trial AIEOP-BFM ALL 2000). Blood (ASH Annual Meeting Abstracts). 2008;112:7. Landmark study of higher dose prednisone vs dexamethasone during induction demonstrating overall reduced relapse risk and improved outcomes with dexamethasone though offset but risk of life-threatening infection, specifically patients aged 10 or older. . Schrappe M, Zimmermann M, Moricke A, et al. Dexamethasone in induction can eliminate one third of all relapses in childhood acute lymphoblastic leukemia (ALL): results of an international randomized trial in 3655 Patients (Trial AIEOP-BFM ALL 2000). Blood (ASH Annual Meeting Abstracts). 2008;112:7. Landmark study of higher dose prednisone vs dexamethasone during induction demonstrating overall reduced relapse risk and improved outcomes with dexamethasone though offset but risk of life-threatening infection, specifically patients aged 10 or older.
15.
go back to reference Conter V, Bartram CR, Valsecchi MG, et al. Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study. Blood. 2010;115(16):3206–14.PubMedCrossRef Conter V, Bartram CR, Valsecchi MG, et al. Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study. Blood. 2010;115(16):3206–14.PubMedCrossRef
16.
go back to reference Schrappe M, Valsecchi MG, Bartram CR, et al. Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL: results of the AIEOP-BFM-ALL 2000 study. Blood. 2011;118(8):2077–84.PubMedCrossRef Schrappe M, Valsecchi MG, Bartram CR, et al. Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL: results of the AIEOP-BFM-ALL 2000 study. Blood. 2011;118(8):2077–84.PubMedCrossRef
17.
go back to reference Möricke A, Zimmermann M, Stanulla M, Biondi A, et al. Dexamethasone vs prednisone in induction treatment of pediatric ALL: results of the randomized trial AIEOP-BFM ALL 2000. Blood. 2016;127(17):2101–12.PubMedCrossRef Möricke A, Zimmermann M, Stanulla M, Biondi A, et al. Dexamethasone vs prednisone in induction treatment of pediatric ALL: results of the randomized trial AIEOP-BFM ALL 2000. Blood. 2016;127(17):2101–12.PubMedCrossRef
18.
go back to reference Reiter A, Schrappe M, Parwaresch R, Henze G, Müller-Weihrich S, Sauter S, et al. Non-Hodgkin's lymphomas of childhood and adolescence: results of a treatment stratified for biologic subtypes and stage–a report of the Berlin-Frankfurt-Münster Group. J Clin Oncol. 1995;13:359–72.PubMedCrossRef Reiter A, Schrappe M, Parwaresch R, Henze G, Müller-Weihrich S, Sauter S, et al. Non-Hodgkin's lymphomas of childhood and adolescence: results of a treatment stratified for biologic subtypes and stage–a report of the Berlin-Frankfurt-Münster Group. J Clin Oncol. 1995;13:359–72.PubMedCrossRef
19.
go back to reference Beesley AH, Palmer ML, Ford J, Weller RE, Cummings AJ, Freitas JR, et al. Authenticity and drug resistance in a panel of acute lymphoblastic leukaemia cell lines. Br J Cancer. 2006;95:1537–44.PubMedPubMedCentralCrossRef Beesley AH, Palmer ML, Ford J, Weller RE, Cummings AJ, Freitas JR, et al. Authenticity and drug resistance in a panel of acute lymphoblastic leukaemia cell lines. Br J Cancer. 2006;95:1537–44.PubMedPubMedCentralCrossRef
20.
go back to reference Beesley AH, Weller RE, Senanayake S, Welch M, Kees UR. Receptor mutation is not a common mechanism of naturally occurring glucocorticoid resistance in leukaemia cell lines. Leuk Res. 2009;33:321–5.PubMedCrossRef Beesley AH, Weller RE, Senanayake S, Welch M, Kees UR. Receptor mutation is not a common mechanism of naturally occurring glucocorticoid resistance in leukaemia cell lines. Leuk Res. 2009;33:321–5.PubMedCrossRef
22.
go back to reference Borin C, Pieters T, Serafin V, Ntziachristos P. Emerging Epigenetic and Posttranslational Mechanisms Controlling Resistance to Glucocorticoids in Acute Lymphoblastic Leukemia. HemaSphere. 2023;7(7):e916.PubMedPubMedCentralCrossRef Borin C, Pieters T, Serafin V, Ntziachristos P. Emerging Epigenetic and Posttranslational Mechanisms Controlling Resistance to Glucocorticoids in Acute Lymphoblastic Leukemia. HemaSphere. 2023;7(7):e916.PubMedPubMedCentralCrossRef
23.
go back to reference Gao J, Liu WJ. Prognostic Value of the Response to Prednisone for Children with Acute Lymphoblastic Leukemia: A Meta-Analysis. Eur Rev Med Pharmacol Sci. 2018;22:7858–66.PubMed Gao J, Liu WJ. Prognostic Value of the Response to Prednisone for Children with Acute Lymphoblastic Leukemia: A Meta-Analysis. Eur Rev Med Pharmacol Sci. 2018;22:7858–66.PubMed
24.
go back to reference Van der Zwet JCG, Smits W, Buijs-Gladdines JGCAM, Pieters R, Meijerink JPP. Recurrent NR3C1 Aberrations at First Diagnosis Relate to Steroid Resistance in Pediatric T-Cell Acute Lymphoblastic Leukemia Patients. HemaSphere. 2020;5:e513.PubMedPubMedCentralCrossRef Van der Zwet JCG, Smits W, Buijs-Gladdines JGCAM, Pieters R, Meijerink JPP. Recurrent NR3C1 Aberrations at First Diagnosis Relate to Steroid Resistance in Pediatric T-Cell Acute Lymphoblastic Leukemia Patients. HemaSphere. 2020;5:e513.PubMedPubMedCentralCrossRef
25.
go back to reference Caratti G, Matthews L, Poolman T, Kershaw S, Baxter M, Ray D. Glucocorticoid Receptor Function in Health and Disease. Clin. Endocrinol. 2015;83:441–448. 26.CrossRef Caratti G, Matthews L, Poolman T, Kershaw S, Baxter M, Ray D. Glucocorticoid Receptor Function in Health and Disease. Clin. Endocrinol. 2015;83:441–448. 26.CrossRef
26.
go back to reference Nick ZLU, Cidlowski JA. The Origin and Functions of Multiple Human Glucocorticoid Receptor Isoforms. Ann N Y Acad Sci. 2004;1024:102–23.CrossRef Nick ZLU, Cidlowski JA. The Origin and Functions of Multiple Human Glucocorticoid Receptor Isoforms. Ann N Y Acad Sci. 2004;1024:102–23.CrossRef
27.
go back to reference Lu NZ, Cidlowski JA. Translational Regulatory Mechanisms Generate N-Terminal Glucocorticoid Receptor Isoforms with Unique Transcriptional Target Genes. Mol Cell. 2005;18:331–42.PubMedCrossRef Lu NZ, Cidlowski JA. Translational Regulatory Mechanisms Generate N-Terminal Glucocorticoid Receptor Isoforms with Unique Transcriptional Target Genes. Mol Cell. 2005;18:331–42.PubMedCrossRef
28.
go back to reference Cain DW, Cidlowski JA. Specificity and Sensitivity of Glucocorticoid Signaling in Health and Disease. Best Pract Res Clin Endocrinol Metab. 2015;29:545–56.PubMedPubMedCentralCrossRef Cain DW, Cidlowski JA. Specificity and Sensitivity of Glucocorticoid Signaling in Health and Disease. Best Pract Res Clin Endocrinol Metab. 2015;29:545–56.PubMedPubMedCentralCrossRef
29.
go back to reference Beger C, Gerdes K, Lauten M, Tissing WJE, Fernandez-Munoz I, Schrappe M, Welte K. Expression and Structural Analysis of Glucocorticoid Receptor Isoform Gamma in Human Leukaemia Cells Using an Isoform-Specific Real-Time Polymerase Chain Reaction Approach. Br J Haematol. 2003;122:245–52.PubMedCrossRef Beger C, Gerdes K, Lauten M, Tissing WJE, Fernandez-Munoz I, Schrappe M, Welte K. Expression and Structural Analysis of Glucocorticoid Receptor Isoform Gamma in Human Leukaemia Cells Using an Isoform-Specific Real-Time Polymerase Chain Reaction Approach. Br J Haematol. 2003;122:245–52.PubMedCrossRef
30.
go back to reference Jing D, Bhadri VA, Beck D, Thoms JAI, Yakob NA, Wong JWH, Knezevic K, Pimanda JE, Lock RB. Opposing Regulation of BIM and BCL2 Controls Glucocorticoid-Induced Apoptosis of Pediatric Acute Lymphoblastic Leukemia Cells. Blood. 2015;125:273–83.PubMedCrossRef Jing D, Bhadri VA, Beck D, Thoms JAI, Yakob NA, Wong JWH, Knezevic K, Pimanda JE, Lock RB. Opposing Regulation of BIM and BCL2 Controls Glucocorticoid-Induced Apoptosis of Pediatric Acute Lymphoblastic Leukemia Cells. Blood. 2015;125:273–83.PubMedCrossRef
31.
go back to reference Malyukova A, Brown S, Papa R, O’Brien R, Giles J, Trahair TN, Dalla PL, Sutton R, Liu T, Haber M, et al. FBXW7 Regulates Glucocorticoid Response in T-Cell Acute Lymphoblastic Leukaemia by Targeting the Glucocorticoid Receptor for Degradation. Leukemia. 2013;27:1053–62.PubMedCrossRef Malyukova A, Brown S, Papa R, O’Brien R, Giles J, Trahair TN, Dalla PL, Sutton R, Liu T, Haber M, et al. FBXW7 Regulates Glucocorticoid Response in T-Cell Acute Lymphoblastic Leukaemia by Targeting the Glucocorticoid Receptor for Degradation. Leukemia. 2013;27:1053–62.PubMedCrossRef
32.
go back to reference Marke R, Havinga J, Cloos J, Demkes M, Poelmans G, Yuniati L, van Ingen Schenau D, Sonneveld E, Waanders E, Pieters R, et al. Tumor Suppressor IKZF1 Mediates Glucocorticoid Resistance in B-Cell Precursor Acute Lymphoblastic Leukemia. Leukemia. 2015;30:1599–603.PubMedCrossRef Marke R, Havinga J, Cloos J, Demkes M, Poelmans G, Yuniati L, van Ingen Schenau D, Sonneveld E, Waanders E, Pieters R, et al. Tumor Suppressor IKZF1 Mediates Glucocorticoid Resistance in B-Cell Precursor Acute Lymphoblastic Leukemia. Leukemia. 2015;30:1599–603.PubMedCrossRef
34.
go back to reference Li Y, Buijs-Gladdines JGCAM, Canté-Barrett K, Stubbs AP, Vroegindeweij EM, Smits WK, van Marion R, Dinjens WNM, Horstmann M, Kuiper RP, et al. IL-7 Receptor Mutations and Steroid Resistance in Pediatric T Cell Acute Lymphoblastic Leukemia: A Genome Sequencing Study. PLoS Med. 2016;13:e1002200.PubMedPubMedCentralCrossRef Li Y, Buijs-Gladdines JGCAM, Canté-Barrett K, Stubbs AP, Vroegindeweij EM, Smits WK, van Marion R, Dinjens WNM, Horstmann M, Kuiper RP, et al. IL-7 Receptor Mutations and Steroid Resistance in Pediatric T Cell Acute Lymphoblastic Leukemia: A Genome Sequencing Study. PLoS Med. 2016;13:e1002200.PubMedPubMedCentralCrossRef
35.
go back to reference Delgado-Martin C, Meyer LK, Huang BJ, Shimano KA, Zinter MS, Nguyen JV, Smith GA, Taunton J, Winter SS, Roderick JR, et al. JAK/STAT Pathway Inhibition Overcomes IL7-Induced Glucocorticoid Resistance in a Subset of Human T-Cell Acute Lymphoblastic Leukemias. Leukemia. 2017;31:2568–76.PubMedPubMedCentralCrossRef Delgado-Martin C, Meyer LK, Huang BJ, Shimano KA, Zinter MS, Nguyen JV, Smith GA, Taunton J, Winter SS, Roderick JR, et al. JAK/STAT Pathway Inhibition Overcomes IL7-Induced Glucocorticoid Resistance in a Subset of Human T-Cell Acute Lymphoblastic Leukemias. Leukemia. 2017;31:2568–76.PubMedPubMedCentralCrossRef
36.
go back to reference Piovan E, Yu J, Tosello V, Herranz D, Ambesi-Impiombato A, DaSilva AC, Sanchez-Martin M, Perez-Garcia A, Rigo I, Castillo M, et al. Direct Reversal of Glucocorticoid Resistance by AKT Inhibition in Acute Lymphoblastic Leukemia. Cancer Cell. 2013;24:766–76.PubMedCrossRef Piovan E, Yu J, Tosello V, Herranz D, Ambesi-Impiombato A, DaSilva AC, Sanchez-Martin M, Perez-Garcia A, Rigo I, Castillo M, et al. Direct Reversal of Glucocorticoid Resistance by AKT Inhibition in Acute Lymphoblastic Leukemia. Cancer Cell. 2013;24:766–76.PubMedCrossRef
37.
go back to reference Meyer LK, Huang BJ, Delgado-Martin C, Roy RP, Hechmer A, Wandler AM, Vincent TL, Fortina P, Olshen AB, Wood BL, et al. Glucocorticoids Paradoxically Facilitate Steroid Resistance in T Cell Acute Lymphoblastic Leukemias and Thymocytes. J Clin Investig. 2020;130:863–76.PubMedPubMedCentralCrossRef Meyer LK, Huang BJ, Delgado-Martin C, Roy RP, Hechmer A, Wandler AM, Vincent TL, Fortina P, Olshen AB, Wood BL, et al. Glucocorticoids Paradoxically Facilitate Steroid Resistance in T Cell Acute Lymphoblastic Leukemias and Thymocytes. J Clin Investig. 2020;130:863–76.PubMedPubMedCentralCrossRef
38.
go back to reference Kośmider K, Karska K, Kozakiewicz A, Lejman M, Zawitkowska J. Overcoming Steroid Resistance in Pediatric Acute Lymphoblastic Leukemia-The State-of-the-Art Knowledge and Future Prospects. Int J Mol Sci. 2022;23(7):3795.PubMedPubMedCentralCrossRef Kośmider K, Karska K, Kozakiewicz A, Lejman M, Zawitkowska J. Overcoming Steroid Resistance in Pediatric Acute Lymphoblastic Leukemia-The State-of-the-Art Knowledge and Future Prospects. Int J Mol Sci. 2022;23(7):3795.PubMedPubMedCentralCrossRef
42.
go back to reference Paugh SW, Bonten EJ, Savic D, Ramsey LB, Thierfelder WE, Gurung P, Malireddi RKS, Actis M, Mayasundari A, Min J, et al. NALP3 Inflammasome Upregulation and CASP1 Cleavage of the Glucocorticoid Receptor Cause Glucocorticoid Resistance in Leukemia Cells. Nat Genet. 2015;47:607–14.PubMedPubMedCentralCrossRef Paugh SW, Bonten EJ, Savic D, Ramsey LB, Thierfelder WE, Gurung P, Malireddi RKS, Actis M, Mayasundari A, Min J, et al. NALP3 Inflammasome Upregulation and CASP1 Cleavage of the Glucocorticoid Receptor Cause Glucocorticoid Resistance in Leukemia Cells. Nat Genet. 2015;47:607–14.PubMedPubMedCentralCrossRef
43.
go back to reference Burke MJ, Ziegler DS, Bautista Sirvent FJ, Attarbaschi A, Gore L, Locatelli F, O’Brien MM, Pauly M, Obreja M, Morris CL, et al. Phase 1b Study of Carfilzomib in Combination with Induction Chemotherapy in Children with Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL). Blood. 2019;134:3873. https://doi.org/10.1182/blood-2019-127350.CrossRef Burke MJ, Ziegler DS, Bautista Sirvent FJ, Attarbaschi A, Gore L, Locatelli F, O’Brien MM, Pauly M, Obreja M, Morris CL, et al. Phase 1b Study of Carfilzomib in Combination with Induction Chemotherapy in Children with Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL). Blood. 2019;134:3873. https://​doi.​org/​10.​1182/​blood-2019-127350.CrossRef
44.
go back to reference Jonas BA, Fisch SC, Rosenberg AS, Hoeg RT, Tuscano JM, Abedi M. Phase I Study of Escalating Doses of Carfilzomib with HyperCVAD in Patients with Newly Diagnosed Acute Lymphoblastic Leukemia. Am J Hematol. 2021;96:E114–7.PubMedCrossRef Jonas BA, Fisch SC, Rosenberg AS, Hoeg RT, Tuscano JM, Abedi M. Phase I Study of Escalating Doses of Carfilzomib with HyperCVAD in Patients with Newly Diagnosed Acute Lymphoblastic Leukemia. Am J Hematol. 2021;96:E114–7.PubMedCrossRef
45.
46.
go back to reference Kaspers GJ, Veerman AJ, Pieters R, et al. In vitro cellular drug resistance and prognosis in newly diagnosed childhood acute lymphoblastic leukemia. Blood. 1997;90:2723–9.PubMedCrossRef Kaspers GJ, Veerman AJ, Pieters R, et al. In vitro cellular drug resistance and prognosis in newly diagnosed childhood acute lymphoblastic leukemia. Blood. 1997;90:2723–9.PubMedCrossRef
47.
go back to reference Den Boer ML, Harms DO, Pieters R, et al. Patient stratification based on prednisolone-vincristine-asparaginase resistance profiles in children with acute lymphoblastic leukemia. J Clin Oncol. 2003;21:3262–8.CrossRef Den Boer ML, Harms DO, Pieters R, et al. Patient stratification based on prednisolone-vincristine-asparaginase resistance profiles in children with acute lymphoblastic leukemia. J Clin Oncol. 2003;21:3262–8.CrossRef
48.
go back to reference Hunger SP, Mullighan CG. Acute lymphoblastic leukemia in children. N Engl J Med. 2015;373:1541–52.PubMedCrossRef Hunger SP, Mullighan CG. Acute lymphoblastic leukemia in children. N Engl J Med. 2015;373:1541–52.PubMedCrossRef
50.
go back to reference Zweidler-McKay PA, Hogan MS, Jubran R, et al. Navigating your career path in pediatric hematology/oncology: On and off the beaten track. Pediatr Blood Cancer. 2016;63:1723–30.PubMedCrossRef Zweidler-McKay PA, Hogan MS, Jubran R, et al. Navigating your career path in pediatric hematology/oncology: On and off the beaten track. Pediatr Blood Cancer. 2016;63:1723–30.PubMedCrossRef
51.
go back to reference Delgado-Martin C, Meyer LK, Huang BJ, et al. JAK/STAT pathway inhibition overcomes IL7-induced glucocorticoid resistance in a subset of human T-cell acute lymphoblastic leukemias. Leukemia. 2017;31:2568–76.PubMedPubMedCentralCrossRef Delgado-Martin C, Meyer LK, Huang BJ, et al. JAK/STAT pathway inhibition overcomes IL7-induced glucocorticoid resistance in a subset of human T-cell acute lymphoblastic leukemias. Leukemia. 2017;31:2568–76.PubMedPubMedCentralCrossRef
52.
go back to reference Meyer LK, Delgado-Martin C, Sharp PP, et al. Inhibition of the Sec61 translocon overcomes cytokine-induced glucocorticoid resistance in T-cell acute lymphoblastic leukaemia. Br J Haematol. 2022;198:137–41.PubMedPubMedCentralCrossRef Meyer LK, Delgado-Martin C, Sharp PP, et al. Inhibition of the Sec61 translocon overcomes cytokine-induced glucocorticoid resistance in T-cell acute lymphoblastic leukaemia. Br J Haematol. 2022;198:137–41.PubMedPubMedCentralCrossRef
54.
go back to reference Velentza L, Zaman F, Sävendahl L. Bone health in glucocorticoid-treated childhood acute lymphoblastic leukemia. Crit Rev Oncol Hematol. 2021 Dec;168:103492.PubMedCrossRef Velentza L, Zaman F, Sävendahl L. Bone health in glucocorticoid-treated childhood acute lymphoblastic leukemia. Crit Rev Oncol Hematol. 2021 Dec;168:103492.PubMedCrossRef
56.
go back to reference te Winkel ML, Pieters R, Hop WC, Roos JC, Bokkerink JP, Leeuw JA, et al. Bone mineral density at diagnosis determines fracture rate in children with acute lymphoblastic leukemia treated according to the DCOG-ALL9 protocol. Bone. 2014;59:223–8.CrossRef te Winkel ML, Pieters R, Hop WC, Roos JC, Bokkerink JP, Leeuw JA, et al. Bone mineral density at diagnosis determines fracture rate in children with acute lymphoblastic leukemia treated according to the DCOG-ALL9 protocol. Bone. 2014;59:223–8.CrossRef
57.
go back to reference Rayar MS, Nayiager T, Webber CE, Barr RD, Athale UH. Predictors of bony morbidity in children with acute lymphoblastic leukemia. Pediatr Blood Cancer. 2012;59(1):77–82.PubMedCrossRef Rayar MS, Nayiager T, Webber CE, Barr RD, Athale UH. Predictors of bony morbidity in children with acute lymphoblastic leukemia. Pediatr Blood Cancer. 2012;59(1):77–82.PubMedCrossRef
58.
go back to reference Cummings EA, Ma J, Fernandez CV, Halton J, Alos N, Miettunen PM, et al. Incident vertebral fractures in children with leukemia during the four years following diagnosis. J Clin Endocrinol Metab. 2015;100(9):3408–17.PubMedCrossRef Cummings EA, Ma J, Fernandez CV, Halton J, Alos N, Miettunen PM, et al. Incident vertebral fractures in children with leukemia during the four years following diagnosis. J Clin Endocrinol Metab. 2015;100(9):3408–17.PubMedCrossRef
59.
go back to reference Mostoufi-Moab S, Brodsky J, Isaacoff EJ, Tsampalieros A, Ginsberg JP, Zemel B, et al. Longitudinal assessment of bone density and structure in childhood survivors of acute lymphoblastic leukemia without cranial radiation. J Clin Endocrinol Metab. 2012;97(10):3584–92.PubMedPubMedCentralCrossRef Mostoufi-Moab S, Brodsky J, Isaacoff EJ, Tsampalieros A, Ginsberg JP, Zemel B, et al. Longitudinal assessment of bone density and structure in childhood survivors of acute lymphoblastic leukemia without cranial radiation. J Clin Endocrinol Metab. 2012;97(10):3584–92.PubMedPubMedCentralCrossRef
60.
go back to reference Orgel E, Mueske NM, Wren TA, Gilsanz V, Butturini AM, Freyer DR, et al. Early injury to cortical and cancellous bone from induction chemotherapy for adolescents and young adults treated for acute lymphoblastic leukemia. Bone. 2016;85:131–7.PubMedPubMedCentralCrossRef Orgel E, Mueske NM, Wren TA, Gilsanz V, Butturini AM, Freyer DR, et al. Early injury to cortical and cancellous bone from induction chemotherapy for adolescents and young adults treated for acute lymphoblastic leukemia. Bone. 2016;85:131–7.PubMedPubMedCentralCrossRef
61.
go back to reference Jarfelt M, Fors H, Lannering B, Bjarnason R. Bone mineral density and bone turnover in young adult survivors of childhood acute lymphoblastic leukaemia. Eur J Endocrinol. 2006;154(2):303–9.PubMedCrossRef Jarfelt M, Fors H, Lannering B, Bjarnason R. Bone mineral density and bone turnover in young adult survivors of childhood acute lymphoblastic leukaemia. Eur J Endocrinol. 2006;154(2):303–9.PubMedCrossRef
62.
go back to reference van Atteveld JE, Pluijm SMF, Ness KK, Hudson MM, Chemaitilly W, Kaste SC, et al. Prediction of low and very low bone mineral density among adult survivors of childhood cancer. J Clin Oncol. 2019;37(25):2217–25.PubMedPubMedCentralCrossRef van Atteveld JE, Pluijm SMF, Ness KK, Hudson MM, Chemaitilly W, Kaste SC, et al. Prediction of low and very low bone mineral density among adult survivors of childhood cancer. J Clin Oncol. 2019;37(25):2217–25.PubMedPubMedCentralCrossRef
63.
go back to reference Inaba H, Cao X, Han AQ, Panetta JC, Ness KK, Metzger ML, et al. Bone mineral density in children with acute lymphoblastic leukemia. Cancer. 2018;124(5):1025–35.PubMedCrossRef Inaba H, Cao X, Han AQ, Panetta JC, Ness KK, Metzger ML, et al. Bone mineral density in children with acute lymphoblastic leukemia. Cancer. 2018;124(5):1025–35.PubMedCrossRef
64.
go back to reference Ward LM, Ma J, Lang B, Ho J, Alos N, Matzinger MA, et al. Bone morbidity and recovery in children with acute lymphoblastic leukemia: results of a six-year prospective cohort study. J Bone Miner Res. 2018;33(8):1435–43.PubMedCrossRef Ward LM, Ma J, Lang B, Ho J, Alos N, Matzinger MA, et al. Bone morbidity and recovery in children with acute lymphoblastic leukemia: results of a six-year prospective cohort study. J Bone Miner Res. 2018;33(8):1435–43.PubMedCrossRef
65.
go back to reference Elmantaser M, Stewart G, Young D, Duncan R, Gibson B, Ahmed SF. Skeletal morbidity in children receiving chemotherapy for acute lymphoblastic leukaemia. Arch Dis Child. 2010;95(10):805–9.PubMedCrossRef Elmantaser M, Stewart G, Young D, Duncan R, Gibson B, Ahmed SF. Skeletal morbidity in children receiving chemotherapy for acute lymphoblastic leukaemia. Arch Dis Child. 2010;95(10):805–9.PubMedCrossRef
66.
go back to reference Mattano LA, Sather HN, Trigg ME, Nachman JB. Osteonecrosis as a complication of treating acute lymphoblastic leukemia in children: a report from the Children’s Cancer Group. J Clin Oncol. 2000;18(18):3262–3272 70.PubMedCrossRef Mattano LA, Sather HN, Trigg ME, Nachman JB. Osteonecrosis as a complication of treating acute lymphoblastic leukemia in children: a report from the Children’s Cancer Group. J Clin Oncol. 2000;18(18):3262–3272 70.PubMedCrossRef
67.
go back to reference Strauss AJ, Su JT, Dalton VM, Gelber RD, Sallan SE, Silverman LB. Bony morbidity in children treated for acute lymphoblastic leukemia. J Clin Oncol. 2001;19(12):3066–72.PubMedCrossRef Strauss AJ, Su JT, Dalton VM, Gelber RD, Sallan SE, Silverman LB. Bony morbidity in children treated for acute lymphoblastic leukemia. J Clin Oncol. 2001;19(12):3066–72.PubMedCrossRef
68.
go back to reference Mattano LA, Devidas M, Nachman JB, et al. Children’s Oncology GroupEffect of alternate-week versus continuous dexamethasone scheduling on the risk of osteonecrosis in paediatric patients with acute lymphoblastic leukaemia: results from the CCG-1961 randomized cohort trial. Lancet Oncol. 2012;13(9):906–15.PubMedPubMedCentralCrossRef Mattano LA, Devidas M, Nachman JB, et al. Children’s Oncology GroupEffect of alternate-week versus continuous dexamethasone scheduling on the risk of osteonecrosis in paediatric patients with acute lymphoblastic leukaemia: results from the CCG-1961 randomized cohort trial. Lancet Oncol. 2012;13(9):906–15.PubMedPubMedCentralCrossRef
69.
go back to reference Hyakuna N, Shimomura Y, Watanabe A, et al. Japanese Childhood Cancer and Leukemia Study Group (JCCLSG)Assessment of corticosteroid-induced osteonecrosis in children undergoing chemotherapy for acute lymphoblastic leukemia: a report from the Japanese Childhood Cancer and Leukemia Study Group. J Pediatr Hematol/Oncol. 2014;36(1):22–9.PubMedCrossRef Hyakuna N, Shimomura Y, Watanabe A, et al. Japanese Childhood Cancer and Leukemia Study Group (JCCLSG)Assessment of corticosteroid-induced osteonecrosis in children undergoing chemotherapy for acute lymphoblastic leukemia: a report from the Japanese Childhood Cancer and Leukemia Study Group. J Pediatr Hematol/Oncol. 2014;36(1):22–9.PubMedCrossRef
70.
go back to reference Burger B, Beier R, Zimmermann M, Beck JD, Reiter A, Schrappe M. Osteonecrosis: a treatment related toxicity in childhood acute lymphoblastic leukemia (ALL)--experiences from trial ALL-BFM 95. Pediatr Blood Cancer. 2005;44:220–5.PubMedCrossRef Burger B, Beier R, Zimmermann M, Beck JD, Reiter A, Schrappe M. Osteonecrosis: a treatment related toxicity in childhood acute lymphoblastic leukemia (ALL)--experiences from trial ALL-BFM 95. Pediatr Blood Cancer. 2005;44:220–5.PubMedCrossRef
71.
go back to reference Kadan-Lottick NS, Dinu I, Wasilewski-Masker K, et al. Osteonecrosis in adult survivors of childhood cancer: a report from the childhood cancer survivor study. J Clin Oncol. 2008;26:3038–45.PubMedPubMedCentralCrossRef Kadan-Lottick NS, Dinu I, Wasilewski-Masker K, et al. Osteonecrosis in adult survivors of childhood cancer: a report from the childhood cancer survivor study. J Clin Oncol. 2008;26:3038–45.PubMedPubMedCentralCrossRef
72.
go back to reference Valtis YK, Stevenson KE, Place AE, Silverman LB, Vrooman LM, Gotti G, Brunner AM, Nauffal M, DeAngelo DJ, Luskin MR. Orthopedic toxicities among adolescents and young adults treated in DFCI ALL Consortium Trials. Blood Adv. 2022 Jan 11;6(1):72–81.PubMedCrossRef Valtis YK, Stevenson KE, Place AE, Silverman LB, Vrooman LM, Gotti G, Brunner AM, Nauffal M, DeAngelo DJ, Luskin MR. Orthopedic toxicities among adolescents and young adults treated in DFCI ALL Consortium Trials. Blood Adv. 2022 Jan 11;6(1):72–81.PubMedCrossRef
73.
go back to reference Patel B, Richards SM, Rowe JM, Goldstone AH, Fielding AK. High incidence of avascular necrosis in adolescents with acute lymphoblastic leukaemia: a UKALL XII analysis. Leukemia. 2008;22(2):308–12.PubMedCrossRef Patel B, Richards SM, Rowe JM, Goldstone AH, Fielding AK. High incidence of avascular necrosis in adolescents with acute lymphoblastic leukaemia: a UKALL XII analysis. Leukemia. 2008;22(2):308–12.PubMedCrossRef
74.
go back to reference Toft N, Birgens H, Abrahamsson J, et al. Toxicity profile and treatment delays in NOPHO ALL2008-comparing adults and children with Philadelphia chromosome-negative acute lymphoblastic leukemia. Eur J Haematol. 2016;96(2):160–9.PubMedCrossRef Toft N, Birgens H, Abrahamsson J, et al. Toxicity profile and treatment delays in NOPHO ALL2008-comparing adults and children with Philadelphia chromosome-negative acute lymphoblastic leukemia. Eur J Haematol. 2016;96(2):160–9.PubMedCrossRef
75.
go back to reference Yao S, Zhu Q, Cole PD, et al. Genetic ancestry and skeletal toxicities among childhood acute lymphoblastic leukemia patients in the DFCI 05-001 cohort. Blood Adv. 2021;5(2):451–8.PubMedPubMedCentralCrossRef Yao S, Zhu Q, Cole PD, et al. Genetic ancestry and skeletal toxicities among childhood acute lymphoblastic leukemia patients in the DFCI 05-001 cohort. Blood Adv. 2021;5(2):451–8.PubMedPubMedCentralCrossRef
76.
go back to reference Hurwitz CA, Silverman LB, Schorin MA, et al. Substituting dexamethasone for prednisone complicates remission induction in children with acute lymphoblastic leukemia. Cancer. 2000;88:1964–9.PubMedCrossRef Hurwitz CA, Silverman LB, Schorin MA, et al. Substituting dexamethasone for prednisone complicates remission induction in children with acute lymphoblastic leukemia. Cancer. 2000;88:1964–9.PubMedCrossRef
77.
go back to reference Gregoriou K, Craigie I, Gibson B, Mason A, Shaikh MG. Risk factors and management of corticosteroid-induced hyperglycaemia in paediatric acute lymphoblastic leukaemia. Pediatr Blood Cancer. 2020;67:e28085.PubMedCrossRef Gregoriou K, Craigie I, Gibson B, Mason A, Shaikh MG. Risk factors and management of corticosteroid-induced hyperglycaemia in paediatric acute lymphoblastic leukaemia. Pediatr Blood Cancer. 2020;67:e28085.PubMedCrossRef
78.
go back to reference Beaudry J, Riddell M. Effects of glucocorticoids and exercise on pancreatic β-cell function and diabetes development. Diabetes Metab Res Rev. 2012;28(7):560–73.PubMedCrossRef Beaudry J, Riddell M. Effects of glucocorticoids and exercise on pancreatic β-cell function and diabetes development. Diabetes Metab Res Rev. 2012;28(7):560–73.PubMedCrossRef
79.
go back to reference Lowas S, Malempati S, Marks D. Body mass index predicts insulin resistance in survivors of pediatric acute lymphoblastic leukemia. Pediatr Blood Cancer. 2009;53(1):58–63.PubMedPubMedCentralCrossRef Lowas S, Malempati S, Marks D. Body mass index predicts insulin resistance in survivors of pediatric acute lymphoblastic leukemia. Pediatr Blood Cancer. 2009;53(1):58–63.PubMedPubMedCentralCrossRef
80.
go back to reference Weiser M, Cabanillas M, Konopleva M, et al. Relation between the duration of remission and hyperglycemia during induction chemotherapy for acute lymphocytic leukemia with a hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone/methotrexate-cytarabine regimen. Cancer. 2004;100(6):1179–85.PubMedCrossRef Weiser M, Cabanillas M, Konopleva M, et al. Relation between the duration of remission and hyperglycemia during induction chemotherapy for acute lymphocytic leukemia with a hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone/methotrexate-cytarabine regimen. Cancer. 2004;100(6):1179–85.PubMedCrossRef
81.
go back to reference Lowas S, Marks D, Malempati S. Prevalence of transient hyperglycemia during induction chemotherapy for pediatric acute lymphoblastic leukemia. Pediatr Blood Cancer. 2009;52(7):814–8.PubMedCrossRef Lowas S, Marks D, Malempati S. Prevalence of transient hyperglycemia during induction chemotherapy for pediatric acute lymphoblastic leukemia. Pediatr Blood Cancer. 2009;52(7):814–8.PubMedCrossRef
82.
go back to reference Koltin D, Sung L, Naqvi A, Urbach S. Medication induced diabetes during induction in pediatric acute lymphoblastic leukemia: prevalence, risk factors and characteristics. Support Care Cancer. 2011;20(9):2009–15.PubMedCrossRef Koltin D, Sung L, Naqvi A, Urbach S. Medication induced diabetes during induction in pediatric acute lymphoblastic leukemia: prevalence, risk factors and characteristics. Support Care Cancer. 2011;20(9):2009–15.PubMedCrossRef
83.
go back to reference Gatzioura I, Papakonstantinou E, Dimitriadou M, et al. Glucose levels before the onset of asparaginase predicts transient hyperglycemia in children with acute lymphoblastic leukemia. Pediatr Blood Cancer. 2016;63(7):1181–4.PubMedCrossRef Gatzioura I, Papakonstantinou E, Dimitriadou M, et al. Glucose levels before the onset of asparaginase predicts transient hyperglycemia in children with acute lymphoblastic leukemia. Pediatr Blood Cancer. 2016;63(7):1181–4.PubMedCrossRef
84.
go back to reference Dare J, Moppett J, Shield J, Hunt L, Stevens M. The impact of hyperglycemia on risk of infection and early death during induction therapy for acute lymphoblastic leukemia (ALL). Pediatr Blood Cancer. 2013;60(12):E157–9.PubMedCrossRef Dare J, Moppett J, Shield J, Hunt L, Stevens M. The impact of hyperglycemia on risk of infection and early death during induction therapy for acute lymphoblastic leukemia (ALL). Pediatr Blood Cancer. 2013;60(12):E157–9.PubMedCrossRef
85.
go back to reference Roberson J, Raju S, Shelso J, Pui C, Howard S. Diabetic ketoacidosis during therapy for pediatric acute lymphoblastic leukemia. Pediatr Blood Cancer. 2008;50(6):1207–12.PubMedCrossRef Roberson J, Raju S, Shelso J, Pui C, Howard S. Diabetic ketoacidosis during therapy for pediatric acute lymphoblastic leukemia. Pediatr Blood Cancer. 2008;50(6):1207–12.PubMedCrossRef
86.
go back to reference Dropcho EJ, Soong SJ. Steroid-induced weakness in patients with primary brain tumors. Neurology. 1991;41:1235–9.PubMedCrossRef Dropcho EJ, Soong SJ. Steroid-induced weakness in patients with primary brain tumors. Neurology. 1991;41:1235–9.PubMedCrossRef
87.
go back to reference Wolkowitz OM. Prospective controlled studies of the behavioral and biological effects of exogenous corticosteroids. Psychoneuroendocrinology. 1994;19:233–55.PubMedCrossRef Wolkowitz OM. Prospective controlled studies of the behavioral and biological effects of exogenous corticosteroids. Psychoneuroendocrinology. 1994;19:233–55.PubMedCrossRef
88.
go back to reference Danilczuk Z, Ossowska G, Lupina T, Cieslik K, Zebrowska-Lupina I. Effect of NMDA receptor antagonists on behavioral impairment induced by chronic treatment with dexamethasone. Pharmacol Rep. 2005;57:47–54.PubMed Danilczuk Z, Ossowska G, Lupina T, Cieslik K, Zebrowska-Lupina I. Effect of NMDA receptor antagonists on behavioral impairment induced by chronic treatment with dexamethasone. Pharmacol Rep. 2005;57:47–54.PubMed
89.
go back to reference Waber DP, Carpentieri SC, Klar N, et al. Cognitive sequelae in children treated for acute lymphoblastic leukemia with dexamethasone or prednisone. J Pediatr Hematol Oncol. 2000;22:206–13.PubMedCrossRef Waber DP, Carpentieri SC, Klar N, et al. Cognitive sequelae in children treated for acute lymphoblastic leukemia with dexamethasone or prednisone. J Pediatr Hematol Oncol. 2000;22:206–13.PubMedCrossRef
90.
go back to reference Kadan-Lottick NS, Brouwers P, Breiger D, et al. A comparison of neurocognitive functioning in children previously randomized to dexamethasone or prednisone in the treatment of childhood acute lymphoblastic leukemia. Blood. 2009;114:1746.PubMedPubMedCentralCrossRef Kadan-Lottick NS, Brouwers P, Breiger D, et al. A comparison of neurocognitive functioning in children previously randomized to dexamethasone or prednisone in the treatment of childhood acute lymphoblastic leukemia. Blood. 2009;114:1746.PubMedPubMedCentralCrossRef
91.
go back to reference Rangel-Patiño J, Lee-Tsai YL, Urbalejo-Ceniceros VI, Luna-Perez MEM, et al. A modified CALGB 10403 in adolescents and young adults with acute lymphoblastic leukemia in Central America. Blood Adv. 2023;7(18):5202–9.PubMedPubMedCentralCrossRef Rangel-Patiño J, Lee-Tsai YL, Urbalejo-Ceniceros VI, Luna-Perez MEM, et al. A modified CALGB 10403 in adolescents and young adults with acute lymphoblastic leukemia in Central America. Blood Adv. 2023;7(18):5202–9.PubMedPubMedCentralCrossRef
92.
go back to reference Aumann S, Shaulov A, Haran A, Gross Even-Zohar N, Vainstein V, Nachmias B. The Emerging Role of Venetoclax-Based Treatments in Acute Lymphoblastic Leukemia. Int J Mol Sci. 2022;23(18):10957.PubMedPubMedCentralCrossRef Aumann S, Shaulov A, Haran A, Gross Even-Zohar N, Vainstein V, Nachmias B. The Emerging Role of Venetoclax-Based Treatments in Acute Lymphoblastic Leukemia. Int J Mol Sci. 2022;23(18):10957.PubMedPubMedCentralCrossRef
93.
go back to reference Peirs S, Matthijssens F, Goossens S, Van De Walle I, Ruggero K, De Bock CE, et al. ABT-199 mediated inhibition of BCL-2 as a novel therapeutic strategy in T-cell acute lymphoblastic leukemia. Blood. 2014;124:3738–47.PubMedCrossRef Peirs S, Matthijssens F, Goossens S, Van De Walle I, Ruggero K, De Bock CE, et al. ABT-199 mediated inhibition of BCL-2 as a novel therapeutic strategy in T-cell acute lymphoblastic leukemia. Blood. 2014;124:3738–47.PubMedCrossRef
94.
go back to reference Rahmat LT, Nguyen A, Abdulhaq H, Prakash S, Logan AC, Mannis GN. Venetoclax in combination with decitabine for relapsed T-cell acute lymphoblastic leukemia after allogeneic hematopoietic cell transplant. Case Rep Hematol. 2018;2018:6092646.PubMedPubMedCentral Rahmat LT, Nguyen A, Abdulhaq H, Prakash S, Logan AC, Mannis GN. Venetoclax in combination with decitabine for relapsed T-cell acute lymphoblastic leukemia after allogeneic hematopoietic cell transplant. Case Rep Hematol. 2018;2018:6092646.PubMedPubMedCentral
95.
go back to reference Farhadfar N, Li Y, May WS, Adams CB. Venetoclax and decitabine for treatment of relapsed T-cell acute lymphoblastic leukemia: A case report and review of literature. Hematol Oncol Stem Cell Ther. 2021;14:246–51.PubMedCrossRef Farhadfar N, Li Y, May WS, Adams CB. Venetoclax and decitabine for treatment of relapsed T-cell acute lymphoblastic leukemia: A case report and review of literature. Hematol Oncol Stem Cell Ther. 2021;14:246–51.PubMedCrossRef
96.
go back to reference Ni Chonghaile T, Roderick JE, Glenfield C, Ryan J, Sallan SE, Silverman LB, et al. Maturation stage of T-cell acute lymphoblastic leukemia determines BCL-2 versus BCL-XL dependence and sensitivity to ABT-199. Cancer Discov. 2014;4:1074–87.CrossRef Ni Chonghaile T, Roderick JE, Glenfield C, Ryan J, Sallan SE, Silverman LB, et al. Maturation stage of T-cell acute lymphoblastic leukemia determines BCL-2 versus BCL-XL dependence and sensitivity to ABT-199. Cancer Discov. 2014;4:1074–87.CrossRef
97.
go back to reference Hohtari H, Kankainen M, Adnan-Awad S, Yadav B, Potdar S, Ianevski A, et al. Targeting apoptosis pathways with BCL2 and MDM2 inhibitors in adult B-cell acute lymphoblastic leukemia. HemaSphere. 2022;6:e701.PubMedPubMedCentralCrossRef Hohtari H, Kankainen M, Adnan-Awad S, Yadav B, Potdar S, Ianevski A, et al. Targeting apoptosis pathways with BCL2 and MDM2 inhibitors in adult B-cell acute lymphoblastic leukemia. HemaSphere. 2022;6:e701.PubMedPubMedCentralCrossRef
98.
go back to reference Zhang Y, Qian JJ, Shen YJ, Hang SJ, Jin J, Zhu HH. The first report of complete remission following treatment with venetoclax plus prednisone in elderly patients with Philadelphia chromosome-negative acute lymphoblastic leukemia. Ann Hematol. 2022;101:1141–4.PubMedCrossRef Zhang Y, Qian JJ, Shen YJ, Hang SJ, Jin J, Zhu HH. The first report of complete remission following treatment with venetoclax plus prednisone in elderly patients with Philadelphia chromosome-negative acute lymphoblastic leukemia. Ann Hematol. 2022;101:1141–4.PubMedCrossRef
100.
go back to reference Wandler AM, Huang BJ, Craig JW, Hayes K, Yan H, Meyer LK, Scacchetti A, et al. Loss of Glucocorticoid Receptor Expression Mediates in Vivo Dexamethasone Resistance in T-Cell Acute Lymphoblastic Leukemia. Leukemia. 2020;34:2025–37.PubMedPubMedCentralCrossRef Wandler AM, Huang BJ, Craig JW, Hayes K, Yan H, Meyer LK, Scacchetti A, et al. Loss of Glucocorticoid Receptor Expression Mediates in Vivo Dexamethasone Resistance in T-Cell Acute Lymphoblastic Leukemia. Leukemia. 2020;34:2025–37.PubMedPubMedCentralCrossRef
101.
go back to reference Bressanin D, Evangelisti C, Ricci F, Tabellini G, Chiarini F, Tazzari PL, Melchionda F, Buontempo F, Pagliaro P, Pession A, et al. Harnessing the PI3K/Akt/MTOR Pathway in T-Cell Acute Lymphoblastic Leukemia: Eliminating Activity by Targeting at Different Levels. Oncotarget. 2012;3:811–23.PubMedPubMedCentralCrossRef Bressanin D, Evangelisti C, Ricci F, Tabellini G, Chiarini F, Tazzari PL, Melchionda F, Buontempo F, Pagliaro P, Pession A, et al. Harnessing the PI3K/Akt/MTOR Pathway in T-Cell Acute Lymphoblastic Leukemia: Eliminating Activity by Targeting at Different Levels. Oncotarget. 2012;3:811–23.PubMedPubMedCentralCrossRef
102.
go back to reference Ksionda O, Mues M, Wandler AM, Donker L, Tenhagen M, Jun J, Ducker GS, Matlawska-Wasowska K, Shannon K, Shokat KM, et al. Comprehensive Analysis of T Cell Leukemia Signals Reveals Heterogeneity in the PI3 Kinase-Akt Pathway and Limitations of PI3 Kinase Inhibitors as Monotherapy. PLoS ONE. 2018;13:e0193849.PubMedPubMedCentralCrossRef Ksionda O, Mues M, Wandler AM, Donker L, Tenhagen M, Jun J, Ducker GS, Matlawska-Wasowska K, Shannon K, Shokat KM, et al. Comprehensive Analysis of T Cell Leukemia Signals Reveals Heterogeneity in the PI3 Kinase-Akt Pathway and Limitations of PI3 Kinase Inhibitors as Monotherapy. PLoS ONE. 2018;13:e0193849.PubMedPubMedCentralCrossRef
103.
go back to reference Dail M, Wong J, Lawrence J, O’Connor D, Nakitandwe J, Chen SC, Xu J, Lee LB, Akagi K, Li Q, et al. Loss of Oncogenic Notch1 with Resistance to a PI3K Inhibitor in T-Cell Leukaemia. Nature. 2014;513:512–6.PubMedPubMedCentralCrossRef Dail M, Wong J, Lawrence J, O’Connor D, Nakitandwe J, Chen SC, Xu J, Lee LB, Akagi K, Li Q, et al. Loss of Oncogenic Notch1 with Resistance to a PI3K Inhibitor in T-Cell Leukaemia. Nature. 2014;513:512–6.PubMedPubMedCentralCrossRef
104.
go back to reference Pereira JKN, Machado-Neto JA, Lopes MR, Morini BC, Traina F, Costa FF, Saad STO, Favaro P. Molecular Effects of the Phosphatidylinositol-3-Kinase Inhibitor NVP-BKM120 on T and B-Cell Acute Lymphoblastic Leukaemia. Eur J Cancer. 2015;51:2076–85.PubMedCrossRef Pereira JKN, Machado-Neto JA, Lopes MR, Morini BC, Traina F, Costa FF, Saad STO, Favaro P. Molecular Effects of the Phosphatidylinositol-3-Kinase Inhibitor NVP-BKM120 on T and B-Cell Acute Lymphoblastic Leukaemia. Eur J Cancer. 2015;51:2076–85.PubMedCrossRef
105.
go back to reference Lonetti A, Antunes IL, Chiarini F, Orsini E, Buontempo F, Ricci F, Tazzari PL, Pagliaro P, Melchionda F, Pession A, et al. Activity of the Pan-Class I Phosphoinositide 3-Kinase Inhibitor NVP-BKM120 in T-Cell Acute Lymphoblastic Leukemia. Leukemia. 2014;28:1196–206.PubMedCrossRef Lonetti A, Antunes IL, Chiarini F, Orsini E, Buontempo F, Ricci F, Tazzari PL, Pagliaro P, Melchionda F, Pession A, et al. Activity of the Pan-Class I Phosphoinositide 3-Kinase Inhibitor NVP-BKM120 in T-Cell Acute Lymphoblastic Leukemia. Leukemia. 2014;28:1196–206.PubMedCrossRef
106.
go back to reference Delgado-Martin C, Meyer LK, Huang BJ, Shimano KA, Zinter MS, Nguyen JV, Smith GA, Taunton J, Winter SS, Roderick JR, et al. JAK/STAT Pathway Inhibition Overcomes IL7-Induced Glucocorticoid Resistance in a Subset of Human T-Cell Acute Lymphoblastic Leukemias. Leukemia. 2017;31:2568–76.PubMedPubMedCentralCrossRef Delgado-Martin C, Meyer LK, Huang BJ, Shimano KA, Zinter MS, Nguyen JV, Smith GA, Taunton J, Winter SS, Roderick JR, et al. JAK/STAT Pathway Inhibition Overcomes IL7-Induced Glucocorticoid Resistance in a Subset of Human T-Cell Acute Lymphoblastic Leukemias. Leukemia. 2017;31:2568–76.PubMedPubMedCentralCrossRef
107.
go back to reference Böhm JW, Sia KCS, Jones C, Evans K, Mariana A, Pang I, Failes T, Zhong L, Mayoh C, Landman R, et al. Combination Efficacy of Ruxolitinib with Standard-of-Care Drugs in CRLF2-Rearranged Ph-like Acute Lymphoblastic Leukemia. Leukemia. 2021;35:3101–12.CrossRef Böhm JW, Sia KCS, Jones C, Evans K, Mariana A, Pang I, Failes T, Zhong L, Mayoh C, Landman R, et al. Combination Efficacy of Ruxolitinib with Standard-of-Care Drugs in CRLF2-Rearranged Ph-like Acute Lymphoblastic Leukemia. Leukemia. 2021;35:3101–12.CrossRef
108.
go back to reference Van der Zwet JCG, Buijs-Gladdines JGCAM, Cordo V, Debets DO, Smits WK, Chen Z, Dylus J, Zaman GJR, Altelaar M, Oshima K, et al. MAPK-ERK Is a Central Pathway in T-Cell Acute Lymphoblastic Leukemia That Drives Steroid Resistance. Leukemia. 2021;35:3394–405.PubMedCrossRef Van der Zwet JCG, Buijs-Gladdines JGCAM, Cordo V, Debets DO, Smits WK, Chen Z, Dylus J, Zaman GJR, Altelaar M, Oshima K, et al. MAPK-ERK Is a Central Pathway in T-Cell Acute Lymphoblastic Leukemia That Drives Steroid Resistance. Leukemia. 2021;35:3394–405.PubMedCrossRef
109.
go back to reference Degryse S, de Bock CE, Demeyer S, Govaerts I, Bornschein S, Verbeke D, Jacobs K, Binos S, Skerrett-Byrne DA, Murray HC, et al. Mutant JAK3 Phosphoproteomic Profiling Predicts Synergism between JAK3 Inhibitors and MEK/BCL2 Inhibitors for the Treatment of T-Cell Acute Lymphoblastic Leukemia. Leukemia. 2018;32:788–800.PubMedCrossRef Degryse S, de Bock CE, Demeyer S, Govaerts I, Bornschein S, Verbeke D, Jacobs K, Binos S, Skerrett-Byrne DA, Murray HC, et al. Mutant JAK3 Phosphoproteomic Profiling Predicts Synergism between JAK3 Inhibitors and MEK/BCL2 Inhibitors for the Treatment of T-Cell Acute Lymphoblastic Leukemia. Leukemia. 2018;32:788–800.PubMedCrossRef
110.
go back to reference Irving J, Matheson E, Minto L, Blair H, Case M, Halsey C, Swidenbank I, Ponthan F, Kirschner-Schwabe R, Groeneveld-Krentz S, et al. Ras Pathway Mutations Are Prevalent in Relapsed Childhood Acute Lymphoblastic Leukemia and Confer Sensitivity to MEK Inhibition. Blood. 2014;124:3420–30.PubMedPubMedCentralCrossRef Irving J, Matheson E, Minto L, Blair H, Case M, Halsey C, Swidenbank I, Ponthan F, Kirschner-Schwabe R, Groeneveld-Krentz S, et al. Ras Pathway Mutations Are Prevalent in Relapsed Childhood Acute Lymphoblastic Leukemia and Confer Sensitivity to MEK Inhibition. Blood. 2014;124:3420–30.PubMedPubMedCentralCrossRef
111.
go back to reference Polak A, Kiliszek P, Sewastianik T, Szydłowski M, Jabłońska E, Białopiotrowicz E, Górniak P, Markowicz S, Nowak E, Grygorowicz MA, et al. MEK Inhibition Sensitizes Precursor B-Cell Acute Lymphoblastic Leukemia (B-ALL) Cells to Dexamethasone through Modulation of MTOR Activity and Stimulation of Autophagy. PLoS ONE. 2016;11:e0155893.PubMedPubMedCentralCrossRef Polak A, Kiliszek P, Sewastianik T, Szydłowski M, Jabłońska E, Białopiotrowicz E, Górniak P, Markowicz S, Nowak E, Grygorowicz MA, et al. MEK Inhibition Sensitizes Precursor B-Cell Acute Lymphoblastic Leukemia (B-ALL) Cells to Dexamethasone through Modulation of MTOR Activity and Stimulation of Autophagy. PLoS ONE. 2016;11:e0155893.PubMedPubMedCentralCrossRef
112.
go back to reference Kerstjens M, Driessen EMC, Willekes M, Pinhanços SS, Schneider P, Pieters R, Stam RW. MEK Inhibition Is a Promising Therapeutic Strategy for MLL-Rearranged Infant Acute Lymphoblastic Leukemia Patients Carrying RAS Mutations. Oncotarget. 2017;8:14835–46.PubMedCrossRef Kerstjens M, Driessen EMC, Willekes M, Pinhanços SS, Schneider P, Pieters R, Stam RW. MEK Inhibition Is a Promising Therapeutic Strategy for MLL-Rearranged Infant Acute Lymphoblastic Leukemia Patients Carrying RAS Mutations. Oncotarget. 2017;8:14835–46.PubMedCrossRef
113.
go back to reference Esbenshade AJ, Simmons JH, Koyama T, Lindell RB, Friedman DL. Obesity and insulin resistance in pediatric acute lymphoblastic leukemia worsens during maintenance therapy. Pediatr Blood Cancer. 2013 Aug;60(8):1287–91.PubMedCrossRef Esbenshade AJ, Simmons JH, Koyama T, Lindell RB, Friedman DL. Obesity and insulin resistance in pediatric acute lymphoblastic leukemia worsens during maintenance therapy. Pediatr Blood Cancer. 2013 Aug;60(8):1287–91.PubMedCrossRef
114.
go back to reference Garmey EG, Liu Q, Sklar CA, et al. Longitudinal changes in obesity and body mass index among adult survivors of childhood acute lymphoblastic leukemia: A report from the childhood cancer survivor study. J Clin Oncol. 2008;26:4639–45.PubMedPubMedCentralCrossRef Garmey EG, Liu Q, Sklar CA, et al. Longitudinal changes in obesity and body mass index among adult survivors of childhood acute lymphoblastic leukemia: A report from the childhood cancer survivor study. J Clin Oncol. 2008;26:4639–45.PubMedPubMedCentralCrossRef
115.
go back to reference Orgel E, Tucci J, Alhushki W, Malvar J, Sposto R, Fu CH, Freyer DR, Abdel-Azim H, Mittelman SD. Obesity is associated with residual leukemia following induction therapy for childhood B-precursor acute lymphoblastic leukemia. Blood. 2014;124(26):3932–8.PubMedCrossRef Orgel E, Tucci J, Alhushki W, Malvar J, Sposto R, Fu CH, Freyer DR, Abdel-Azim H, Mittelman SD. Obesity is associated with residual leukemia following induction therapy for childhood B-precursor acute lymphoblastic leukemia. Blood. 2014;124(26):3932–8.PubMedCrossRef
116.
go back to reference Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N. Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989–1002.PubMedCrossRef Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N. Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989–1002.PubMedCrossRef
117.
go back to reference Popoviciu MS, Păduraru L, Yahya G, Metwally K, Cavalu S. Emerging Role of GLP-1 Agonists in Obesity: A Comprehensive Review of Randomised Controlled Trials. Int J Mol Sci. 2023 Jun 21;24(13):10449.PubMedPubMedCentralCrossRef Popoviciu MS, Păduraru L, Yahya G, Metwally K, Cavalu S. Emerging Role of GLP-1 Agonists in Obesity: A Comprehensive Review of Randomised Controlled Trials. Int J Mol Sci. 2023 Jun 21;24(13):10449.PubMedPubMedCentralCrossRef
Metadata
Title
Glucocorticoid Therapy in Acute Lymphoblastic Leukemia: Navigating Short-Term and Long-Term Effects and Optimal Regimen Selection
Authors
Hoda Pourhassan
Lindsey Murphy
Ibrahim Aldoss
Publication date
13-06-2024
Publisher
Springer US
Published in
Current Hematologic Malignancy Reports
Print ISSN: 1558-8211
Electronic ISSN: 1558-822X
DOI
https://doi.org/10.1007/s11899-024-00735-w