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Published in: Current Neurology and Neuroscience Reports 2/2017

01-02-2017 | Neurology of Systemic Diseases (J Biller, Section Editor)

Neurological Complications of the Leukemias Across the Ages

Authors: Stephanie Berg, Sucha Nand

Published in: Current Neurology and Neuroscience Reports | Issue 2/2017

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Abstract

Purpose of Review

Acute and chronic leukemias are heterogeneous diseases and can affect any part of the body upon initial discovery. Understanding the sequela of systemic involvement is key for proper diagnosis and treatment.

Recent Findings

Over the decades, new research has emerged regarding neurological complications of the myeloid or lymphoid leukemias. Central nervous system involvement usually confers a poor prognosis and requires emergent treatment. Standard of care still involves systemic therapy, intrathecal administration of chemotherapeutic agents, and cranial radiation. Treatment-related side effects can occur and need to be recognized by any practitioner involved with patient care.

Summary

It is imperative to understand neurologic complications from leukemia to prevent delays and initiate necessary treatment to maintain neurologic and cognitive function.
Literature
2.
go back to reference Pui CH, Howard SC. Current management and challenges of malignant disease in the CNS in paediatric leukemia. Lancet Oncol. 2008;9:257068.CrossRef Pui CH, Howard SC. Current management and challenges of malignant disease in the CNS in paediatric leukemia. Lancet Oncol. 2008;9:257068.CrossRef
3.
go back to reference Morra E et al. The role of systemic high-dose cytarabine in the treatment of central nervous system leukemia. Cancer. 1993;72(2):439–45.CrossRefPubMed Morra E et al. The role of systemic high-dose cytarabine in the treatment of central nervous system leukemia. Cancer. 1993;72(2):439–45.CrossRefPubMed
4.
go back to reference Aoki J, Ishiyama K, Taniguchi S, Fukuda T, Takami A, et al. Outcome of allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia patients with central nervous system involvement. Biol Blood Marrow Transplant. 2014;20(12):2029–33.CrossRefPubMed Aoki J, Ishiyama K, Taniguchi S, Fukuda T, Takami A, et al. Outcome of allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia patients with central nervous system involvement. Biol Blood Marrow Transplant. 2014;20(12):2029–33.CrossRefPubMed
5.
go back to reference Bar M, Tong W, Othus M, Loeb KR, Estey EH. Central nervous system involvement in acute myeloid leukemia patients undergoing hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2015;21(3):546–51.CrossRefPubMed Bar M, Tong W, Othus M, Loeb KR, Estey EH. Central nervous system involvement in acute myeloid leukemia patients undergoing hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2015;21(3):546–51.CrossRefPubMed
6.
go back to reference Walker GV, Shihadeh F, Kantarjian H, et al. Comprehensive craniospinal radiation for controlling central nervous system leukemia. Int J Radiat Oncol Biol Phys. 2014;90(5):1119–25.CrossRefPubMedPubMedCentral Walker GV, Shihadeh F, Kantarjian H, et al. Comprehensive craniospinal radiation for controlling central nervous system leukemia. Int J Radiat Oncol Biol Phys. 2014;90(5):1119–25.CrossRefPubMedPubMedCentral
7.
go back to reference Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–405.CrossRefPubMed Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–405.CrossRefPubMed
8.
go back to reference • Shihadeh F, Reed V, Faderl S, Medeiros LJ, Mazloom A, Hadziahmetovic M, et al. Cytogenetic profile of patients with acute myeloid leukemia and central nervous system disease. Cancer. 2012;118(1):112. Shihadeh et al. provided a thorough review of important cytogenetic profiles characteristic of AML patients diagnosed with CNS disease. Cytogenetics play a vital role in determining prognosis for all patients diagnosed with AML.CrossRefPubMed • Shihadeh F, Reed V, Faderl S, Medeiros LJ, Mazloom A, Hadziahmetovic M, et al. Cytogenetic profile of patients with acute myeloid leukemia and central nervous system disease. Cancer. 2012;118(1):112. Shihadeh et al. provided a thorough review of important cytogenetic profiles characteristic of AML patients diagnosed with CNS disease. Cytogenetics play a vital role in determining prognosis for all patients diagnosed with AML.CrossRefPubMed
9.
go back to reference Ferro A et al. Cranial irradiation in adults diagnosed with acute myelogenous leukemia presenting with hyperleukocytosis and neurologic dysfunction. Leuk Lymphoma. 2014;55(1):105–9.CrossRefPubMed Ferro A et al. Cranial irradiation in adults diagnosed with acute myelogenous leukemia presenting with hyperleukocytosis and neurologic dysfunction. Leuk Lymphoma. 2014;55(1):105–9.CrossRefPubMed
10.
go back to reference •• Rollig C, Ehninger G. How I treat hyperleukocytosis in acute myeloid leukemia. Blood. 2015;125(21):3246–52. This was a good review regarding hyperleukocytosis in AML patients with important treatment options and pathophysiology. CrossRefPubMed •• Rollig C, Ehninger G. How I treat hyperleukocytosis in acute myeloid leukemia. Blood. 2015;125(21):3246–52. This was a good review regarding hyperleukocytosis in AML patients with important treatment options and pathophysiology. CrossRefPubMed
11.
go back to reference Porcu P et al. Therapeutic leukapheresis in hyperleucocytic leukemias: lack of correlation between degree of cytoreduction and early mortality rate. Br J Haematol. 1997;98(2):433–6.CrossRefPubMed Porcu P et al. Therapeutic leukapheresis in hyperleucocytic leukemias: lack of correlation between degree of cytoreduction and early mortality rate. Br J Haematol. 1997;98(2):433–6.CrossRefPubMed
12.
go back to reference Pastore F, Pastore A, Whittmann G, Hiddlemann W, Spiekermann K. The role of therapeutic leukaphresis in hyperleukocytotic AML. PLoS ONE. 2014;9(4):e95062.CrossRefPubMedPubMedCentral Pastore F, Pastore A, Whittmann G, Hiddlemann W, Spiekermann K. The role of therapeutic leukaphresis in hyperleukocytotic AML. PLoS ONE. 2014;9(4):e95062.CrossRefPubMedPubMedCentral
13.
go back to reference Saito T, Koyama T, Nagata K, et al. Anticoagulant effects of retinoic acids on leukemia cells. Blood. 1996;87:657–65.PubMed Saito T, Koyama T, Nagata K, et al. Anticoagulant effects of retinoic acids on leukemia cells. Blood. 1996;87:657–65.PubMed
14.
go back to reference Lawrence JB, Yomtovian RA, Hammons T, Masarik SR, Chongkolwatana V, Creger RJ, et al. Lowering the prophylactic platelet transfusion threshold: a prospective analysis. Leuk Lymphoma. 2001;41(1–2):67–76.CrossRefPubMed Lawrence JB, Yomtovian RA, Hammons T, Masarik SR, Chongkolwatana V, Creger RJ, et al. Lowering the prophylactic platelet transfusion threshold: a prospective analysis. Leuk Lymphoma. 2001;41(1–2):67–76.CrossRefPubMed
15.
go back to reference Avni B, Koren-Michowitz M. Myeloid sarcoma: current approach and therapeutic options. Adv Hematol. 2011;2:309–16.CrossRef Avni B, Koren-Michowitz M. Myeloid sarcoma: current approach and therapeutic options. Adv Hematol. 2011;2:309–16.CrossRef
16.
go back to reference Nayak L, Pentsova E, Batchelor TT, Primary CNS. Lymphoma and neurologic complications of hematologic malignancies. Continuum. 2015;21(2):355–72.PubMed Nayak L, Pentsova E, Batchelor TT, Primary CNS. Lymphoma and neurologic complications of hematologic malignancies. Continuum. 2015;21(2):355–72.PubMed
17.
go back to reference Cervantes GM, Cayci Z. Intracranial CNS manifestations of myeloid sarcoma in patients with acute myeloid leukemia: review of the literature and three case reports from the authors institution. J Clin Med. 2015;4(5):1102–12.CrossRefPubMedPubMedCentral Cervantes GM, Cayci Z. Intracranial CNS manifestations of myeloid sarcoma in patients with acute myeloid leukemia: review of the literature and three case reports from the authors institution. J Clin Med. 2015;4(5):1102–12.CrossRefPubMedPubMedCentral
18.
go back to reference Bakst R, Wolden S, Yahalorn J. Radiation therapy for chloroma. Int J Radiat Oncol Biol Phys. 2012;82(5):1816–22.CrossRefPubMed Bakst R, Wolden S, Yahalorn J. Radiation therapy for chloroma. Int J Radiat Oncol Biol Phys. 2012;82(5):1816–22.CrossRefPubMed
19.
go back to reference Thomas X, Boiron JM, Huguet F, Dombert H, Bradstock K, Vet N, et al. Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol. 2004;22:4075–86.CrossRefPubMed Thomas X, Boiron JM, Huguet F, Dombert H, Bradstock K, Vet N, et al. Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol. 2004;22:4075–86.CrossRefPubMed
20.
go back to reference • Del Principe ML, Maurillo L, Buccisano F, et al. Central nervous system involvement in adult acute lymphoblastic leukemia: diagnostic tools, prophylaxis, and therapy. Mediterr J Hematol Infect Dis. 2014;6(1):e2014075. Del Principe et al. reviewed many cases from European data regarding ALL and CNS involvement citing important diagnostic tests with corresponding literature citations. CrossRefPubMedPubMedCentral • Del Principe ML, Maurillo L, Buccisano F, et al. Central nervous system involvement in adult acute lymphoblastic leukemia: diagnostic tools, prophylaxis, and therapy. Mediterr J Hematol Infect Dis. 2014;6(1):e2014075. Del Principe et al. reviewed many cases from European data regarding ALL and CNS involvement citing important diagnostic tests with corresponding literature citations. CrossRefPubMedPubMedCentral
21.
go back to reference Thomas X, Le QH. Central nervous system involvement in adult acute lymphoblastic leukemia. Hematology. 2008;13:293–302.CrossRefPubMed Thomas X, Le QH. Central nervous system involvement in adult acute lymphoblastic leukemia. Hematology. 2008;13:293–302.CrossRefPubMed
22.
go back to reference Lazarus HM et al. Central Nervous system involvement in adult acute lymphoblastic leukemia at diagnosis: results from the international ALL trial MRC UKALL XII/ECOG E 2993. Blood. 2006;108(2):465–72.CrossRefPubMedPubMedCentral Lazarus HM et al. Central Nervous system involvement in adult acute lymphoblastic leukemia at diagnosis: results from the international ALL trial MRC UKALL XII/ECOG E 2993. Blood. 2006;108(2):465–72.CrossRefPubMedPubMedCentral
23.
go back to reference Surapaneni UR, Cortes JE, Thomas D, et al. Central nervous system relapse in adults with acute lymphoblastic leukemia. Cancer. 2002;94(3):773–9.CrossRefPubMed Surapaneni UR, Cortes JE, Thomas D, et al. Central nervous system relapse in adults with acute lymphoblastic leukemia. Cancer. 2002;94(3):773–9.CrossRefPubMed
24.
go back to reference Wellwood J, Taylor K. Central nervous system prophylaxis in haematological malignancies. Intern Med J. 2001;32:252–8.CrossRef Wellwood J, Taylor K. Central nervous system prophylaxis in haematological malignancies. Intern Med J. 2001;32:252–8.CrossRef
25.
go back to reference Altintas A, Cil TT, Kilinc I, Kaplan MA, Ayyildiz O. Central nervous system blastic crisis in chronic myeloid leukemia on imatinib mesylate therapy: a case report. J Neurooncol. 2007;84(1):103–5.CrossRefPubMed Altintas A, Cil TT, Kilinc I, Kaplan MA, Ayyildiz O. Central nervous system blastic crisis in chronic myeloid leukemia on imatinib mesylate therapy: a case report. J Neurooncol. 2007;84(1):103–5.CrossRefPubMed
26.
go back to reference Sancho JM, Ribera JM, Oriol A, et al. Central nervous system recurrence in adult patients with acute lymphoblastic leukemia. Cancer. 2006;106:2540–6.CrossRefPubMed Sancho JM, Ribera JM, Oriol A, et al. Central nervous system recurrence in adult patients with acute lymphoblastic leukemia. Cancer. 2006;106:2540–6.CrossRefPubMed
28.
go back to reference Reman O, Pigneux A, Huguet F, Vey N, Thomas X, et al. Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis and/or at first relapse: results from the GET-LALA group. Leuk Res. 2008;32:1741–50.CrossRefPubMed Reman O, Pigneux A, Huguet F, Vey N, Thomas X, et al. Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis and/or at first relapse: results from the GET-LALA group. Leuk Res. 2008;32:1741–50.CrossRefPubMed
29.
go back to reference Cortes J, O’Brien SM, Pierce S, Keating MJ, Freireich EJ, Kantarjian HM. The value of high-dose systemic chemotherapy and intrathecal therapy for central nervous system prophylaxis in different risk groups of adult acute lymphoblastic leukemia. Blood. 1995;86(6):2091–7.PubMed Cortes J, O’Brien SM, Pierce S, Keating MJ, Freireich EJ, Kantarjian HM. The value of high-dose systemic chemotherapy and intrathecal therapy for central nervous system prophylaxis in different risk groups of adult acute lymphoblastic leukemia. Blood. 1995;86(6):2091–7.PubMed
30.
go back to reference Pui C-H, Mahmoud HH, River GK, et al: Early intensification of intrathecal chemotherapy virtually eliminates central nervous system relapse in children with acute lymphoblastic leukemia. Blood. 1998;92: 411–15. Pui C-H, Mahmoud HH, River GK, et al: Early intensification of intrathecal chemotherapy virtually eliminates central nervous system relapse in children with acute lymphoblastic leukemia. Blood. 1998;92: 411–15.
31.
go back to reference Kantarjian HM, Obrien S, Smith TL, et al. Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J Clin Oncol. 2000;18:547–61.CrossRefPubMed Kantarjian HM, Obrien S, Smith TL, et al. Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J Clin Oncol. 2000;18:547–61.CrossRefPubMed
32.
go back to reference Kantarjian H, Thomas D, O’Brien S, et al. Long-term follow up results of Hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. Cancer. 2004;101:2788–801.CrossRefPubMed Kantarjian H, Thomas D, O’Brien S, et al. Long-term follow up results of Hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. Cancer. 2004;101:2788–801.CrossRefPubMed
33.
go back to reference Jabbour E, O’Brien S, Kantarjian H, Manero GG, Ferrajoli A, Ravandi F, et al. Neurologic complications associated with intrathecal liposomal cytarabine given prophylactically in combination with high-dose methotrexate and cytarabine to patients with acute lymphocytic leukemia. Blood. 2007;109(8):3214–8.CrossRefPubMed Jabbour E, O’Brien S, Kantarjian H, Manero GG, Ferrajoli A, Ravandi F, et al. Neurologic complications associated with intrathecal liposomal cytarabine given prophylactically in combination with high-dose methotrexate and cytarabine to patients with acute lymphocytic leukemia. Blood. 2007;109(8):3214–8.CrossRefPubMed
34.
go back to reference Demopoulos A, DeAngelis LM. Neurologic complications of leukemia. Curr Opin Neurol. 2002;15:691–9.CrossRefPubMed Demopoulos A, DeAngelis LM. Neurologic complications of leukemia. Curr Opin Neurol. 2002;15:691–9.CrossRefPubMed
35.
go back to reference LeClerc JM, Billett AL, Gelber RD, et al. Treatment of childhood acute lymphoblastic leukemia: results of Dana-Farber ALL Consortium Protocol 87-01. J Clin Oncol. 2002;20:237–46.CrossRefPubMed LeClerc JM, Billett AL, Gelber RD, et al. Treatment of childhood acute lymphoblastic leukemia: results of Dana-Farber ALL Consortium Protocol 87-01. J Clin Oncol. 2002;20:237–46.CrossRefPubMed
36.
go back to reference Chamberlin MC. Neurotoxicity of intra-CSF liposomal cytarabine (DepoCyt) administered for treatment of leptomeningeal metastases: a retrospective case series. J Neurooncol. 2012;109(1):143–8. doi:10.1007/s11060-012-0880-x.CrossRef Chamberlin MC. Neurotoxicity of intra-CSF liposomal cytarabine (DepoCyt) administered for treatment of leptomeningeal metastases: a retrospective case series. J Neurooncol. 2012;109(1):143–8. doi:10.​1007/​s11060-012-0880-x.CrossRef
37.
go back to reference Khan et al. Neurologic morbidity and quality of life in survivors of childhood acute lymphoblastic leukemia: a prospective cross-sectional study. J Cancer Surviv. 2014;8(4):688–96.CrossRefPubMedPubMedCentral Khan et al. Neurologic morbidity and quality of life in survivors of childhood acute lymphoblastic leukemia: a prospective cross-sectional study. J Cancer Surviv. 2014;8(4):688–96.CrossRefPubMedPubMedCentral
40.
go back to reference Moazzam AA, Drappatz J, Kim TY, Kesari S. Chronic lymphocytic leukemia with central nervous system involvement: report of two cases with a comprehensive literature review. J Neurooncol. 2012;106:185–200.CrossRefPubMed Moazzam AA, Drappatz J, Kim TY, Kesari S. Chronic lymphocytic leukemia with central nervous system involvement: report of two cases with a comprehensive literature review. J Neurooncol. 2012;106:185–200.CrossRefPubMed
41.
go back to reference Hanse MC, Van Veer MB, van Lom K, Van den Bent MJ. Incidence of central nervous system involvement in chronic lymphocytic leukemia and outcome to treatment. J Neurol. 2008;255(6):828–30.CrossRefPubMed Hanse MC, Van Veer MB, van Lom K, Van den Bent MJ. Incidence of central nervous system involvement in chronic lymphocytic leukemia and outcome to treatment. J Neurol. 2008;255(6):828–30.CrossRefPubMed
42.
go back to reference Soni A, Paluri R, Deal T, Peker D. Extramedullary involvement by chronic myelogeneous leukemia in five patients with unusual clinicopathologic features: a review of the effectiveness of tyrosine kinase inhibitors. Clin Med Res. 2016;8(6):480–5.CrossRef Soni A, Paluri R, Deal T, Peker D. Extramedullary involvement by chronic myelogeneous leukemia in five patients with unusual clinicopathologic features: a review of the effectiveness of tyrosine kinase inhibitors. Clin Med Res. 2016;8(6):480–5.CrossRef
43.
go back to reference Pileri SA, Ascani S, Cox MC, Campidelli C, Bacci F, Piccioli M, et al. Myeloid sarcoma: clinico-pathologic, phenotypic and cytogenetic analysis of 92 adult patients. Leukemia. 2007;21(2):340–50.CrossRefPubMed Pileri SA, Ascani S, Cox MC, Campidelli C, Bacci F, Piccioli M, et al. Myeloid sarcoma: clinico-pathologic, phenotypic and cytogenetic analysis of 92 adult patients. Leukemia. 2007;21(2):340–50.CrossRefPubMed
44.
go back to reference Grace RF, Dahlberg SE, Neuberg D, Sallan ES, Connors JM, Neufeld EJ, et al. The frequency and management of asparaginase-related thrombosis in paediatric and adult patients with acute lymphoblastic leukaemia on Dana-Farber Cancer Institute consortium protocols. Br J Hematol. 2011;152:452–9.CrossRef Grace RF, Dahlberg SE, Neuberg D, Sallan ES, Connors JM, Neufeld EJ, et al. The frequency and management of asparaginase-related thrombosis in paediatric and adult patients with acute lymphoblastic leukaemia on Dana-Farber Cancer Institute consortium protocols. Br J Hematol. 2011;152:452–9.CrossRef
45.
go back to reference Ranta S, Tuckuviene R, Mäkipernaa A, Albertsen BK, Frisk T, Tedgård U, et al. Cerebral sinus venous thromboses in children with acute lymphoblastic leukaemia—a multicentre study from the Nordic Society of Paediatric Haematology and Oncology. Br J Haematol. 2015;168(4):547–52. doi:10.1111/bjh.13162.CrossRefPubMed Ranta S, Tuckuviene R, Mäkipernaa A, Albertsen BK, Frisk T, Tedgård U, et al. Cerebral sinus venous thromboses in children with acute lymphoblastic leukaemia—a multicentre study from the Nordic Society of Paediatric Haematology and Oncology. Br J Haematol. 2015;168(4):547–52. doi:10.​1111/​bjh.​13162.CrossRefPubMed
46.
go back to reference Vavricka SR, Walter RB, Irani S, Halter J, Schanz U. Safety of lumbar puncture for adults with acute leukemia and restrictive prophylactic platelet transfusion. Ann Hematol. 2003;82:570–3.CrossRefPubMed Vavricka SR, Walter RB, Irani S, Halter J, Schanz U. Safety of lumbar puncture for adults with acute leukemia and restrictive prophylactic platelet transfusion. Ann Hematol. 2003;82:570–3.CrossRefPubMed
47.
go back to reference Williams AM, Zent CS, Janelsins MC. What is known and unknown about chemotherapy-related cognitive impairment in patients with haematological malignancies and areas of needed research. Br J Haematol. 2016;174:835–46.CrossRefPubMed Williams AM, Zent CS, Janelsins MC. What is known and unknown about chemotherapy-related cognitive impairment in patients with haematological malignancies and areas of needed research. Br J Haematol. 2016;174:835–46.CrossRefPubMed
48.
go back to reference Dutta V. Chemotherapy, neurotoxicity, and cognitive changes in breast cancer. J Cancer Res Ther. 2011;7:264–9.CrossRefPubMed Dutta V. Chemotherapy, neurotoxicity, and cognitive changes in breast cancer. J Cancer Res Ther. 2011;7:264–9.CrossRefPubMed
49.
go back to reference Janelsin MC, Kesler SR, Ahles TA, et al. Prevalence, mechanisms, and management of cancer-related cognitive impairment. Int Rev Psychiatry. 2014;26:102–13.CrossRef Janelsin MC, Kesler SR, Ahles TA, et al. Prevalence, mechanisms, and management of cancer-related cognitive impairment. Int Rev Psychiatry. 2014;26:102–13.CrossRef
50.
go back to reference Gaynon PS, Angiolillo AL, Carroll WL, et al. Long-term results of the children’s cancer group studies for childhood ALL 1983–2002: a Children’s Oncology Group Report. Leukemia. 2010;24:285–97.CrossRefPubMed Gaynon PS, Angiolillo AL, Carroll WL, et al. Long-term results of the children’s cancer group studies for childhood ALL 1983–2002: a Children’s Oncology Group Report. Leukemia. 2010;24:285–97.CrossRefPubMed
Metadata
Title
Neurological Complications of the Leukemias Across the Ages
Authors
Stephanie Berg
Sucha Nand
Publication date
01-02-2017
Publisher
Springer US
Published in
Current Neurology and Neuroscience Reports / Issue 2/2017
Print ISSN: 1528-4042
Electronic ISSN: 1534-6293
DOI
https://doi.org/10.1007/s11910-017-0726-1

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