Characteristics of central nervous system invasion in acute lymphoblastic leukemia: five-year experience in two centers in Mexico City
DOI:
https://doi.org/10.35509/01239015.860Keywords:
Precursor cell lymphoblastic leukemia-lymphoma, recurrence, central nervous system, injections, spinalAbstract
Introduction: Central nervous system (CNS) invasion or infiltration can occur at diagnosis and during follow-up. Factors such as hyperleukocytosis, T phenotype, t(1;19), or traumatic punctures increase the risk. The results with intrathecal treatment are variable and require a combination with systemic chemotherapy or radiotherapy. The association with bone marrow invasion worsens the prognosis.
Objectives: This study describes the characteristics of cases with acute lymphoblastic leukemia (ALL) and CNS infiltration in patients treated at two reference centers in Mexico.
Methods: Retrospective, observational study in adult patients with ALL and CNS infiltration at diagnosis or during follow-up, detected by cytomorphology or flow cytometry.
Results: The study included 30 patients; 73.3% were men. The mean age was 29 years (17 to 57 years); 86.70% (n=26) corresponded to patients at high risk of relapse, mostly with phenotype B (93.3%). The diagnosis was made by cytomorphology in 70% and flow cytometry in 26.70%. The main symptom was headache (56.70%), and 10% had some peripheral neuropathy. The median time to relapse was 417 days; 66.70% (n=20) achieved a favorable response to intensive intrathecal chemotherapy twice a week, and 33.30% (n=10) received a combination with other strategies. CNS infiltration in less than 400 days was associated with a worse prognosis.
Conclusion: CNS infiltration is an expected complication that requires rapid resolution to prevent bone marrow relapse.
Author Biographies
Christian Omar Ramos-Peñafiel, Departamento de Hematología, Hospital General de México “Dr. Eduardo Liceaga”, Ciudad de México, México.
1. Departamento de Hematología, Hospital General de México “Dr. Eduardo Liceaga”, Ciudad de México, México.
Daniela Pérez-Sámano, Departamento de Hematología, Hospital General de México “Dr. Eduardo Liceaga”, Ciudad de México, México.
1. Departamento de Hematología, Hospital General de México “Dr. Eduardo Liceaga”, Ciudad de México, México.
Irma Olarte-Carrillo, Laboratorio de Biología Molecular, Hospital General de México “Dr. Eduardo Liceaga”, Ciudad de México, México.
2. Laboratorio de Biología Molecular, Hospital General de México “Dr. Eduardo Liceaga”, Ciudad de México, México.
Adán Germán Gallardo-Rodríguez, Departamento de Investigación en Hematología, Hospital General de México “Dr. Eduardo Liceaga”, Ciudad de México, México
3. Departamento de Investigación en Hematología, Hospital General de México “Dr. Eduardo Liceaga”, Ciudad de México, México.
Rafael Cerón-Maldonado, Laboratorio de Biología Molecular, Hospital General de México “Dr. Eduardo Liceaga”, Ciudad de México, México.
2. Laboratorio de Biología Molecular, Hospital General de México “Dr. Eduardo Liceaga”, Ciudad de México, México.
Adolfo Martínez-Tovar, Laboratorio de Biología Molecular, Hospital General de México “Dr. Eduardo Liceaga”, Ciudad de México, México.
2. Laboratorio de Biología Molecular, Hospital General de México “Dr. Eduardo Liceaga”, Ciudad de México, México.
References
Jabbour E, O’Brien S, Konopleva M, Kantarjian H. New insights into the pathophysiology and therapy of adult acute lymphoblastic leukemia. Cancer. 2015;121:2517-28. https://doi.org/10.1002/cncr.29383
Aldoss I, Stein AS. Advances in adult acute lymphoblastic leukemia therapy. Leuk. Lymphoma. 2018;59:1033-50. https://doi.org/10.1080/10428194.2017.1354372
Del Príncipe MI, Maurillo L, Buccisano F, Sconocchia G, Cefalo M, De Santis G, et al. Central nervous system involvement in adult acute lymphoblastic leukemia: diagnostic tools, prophylaxis and therapy. Mediterr J Hematol Infect Dis. 2014;6:e2014075. https://doi.org/10.4084/mjhid.2014.075
Zhou F, Wen Y, Jin R, Chen H. New attempts for central nervous infiltration of pediatric acute lymphoblastic leukemia. Cancer Metastasis Rev. 2019;38:657-71. https://doi.org/10.1007/s10555-019-09827-z
Lenk L, Alsadeq A, Schewe DM. Involvement of the central nervous system in acute lymphoblastic leukemia: opinions on molecular mechanisms and clinical implications based on recent data. Cancer Metastasis Rev. 2020;39:173-87. https://doi.org/10.1007/s10555-020-09848-z
Levinsen M, Taskinen M, Abrahamsson J, Forestier E, Frandsen TL, Harila-Saari A, et al. Clinical features and early treatment response of central nervous system involvement in childhood acute lymphoblastic leukemia. Pediatr Blood Cancer. 2014;61:1416-21. https://doi.org/10.1002/pbc.24981
Liu J, Wang Y, Sun X, Liu S, Yu Z, Ji N, et al. Lesions of the central nervous system in leukemia: Pathological and magnetic resonance imaging features at presentation in 14 patients. Oncol Lett. 2017;14:8162-70. https://doi.org/10.3892/ol.2017.7192
Jabbour E, Thomas D, Cortés J, Kantarjian HM, O’Brien S. Central nervous system prophylaxis in adults with acute lymphoblastic leukemia. Cancer. 2010;116:2290-300. https://doi.org/10.1002/cncr.25008
Ceppi F, Weitzman S, Woessmann W, Davies K, Lassaletta A, Reismüller B, et al. Safety and efficacy of intrathecal rituximab in children with B cell lymphoid CD20+ malignancies: An international retrospective study. Am J Hematol. 2016;91:486-910 https://doi.org/10.1002/ajh.24329
Jaime-Pérez JC, Rodríguez-Romo LN, González-Llano O, Chapa-Rodríguez A, Gómez-Almaguer D. Effectiveness of intrathecal rituximab in patients with acute lymphoblastic leukaemia relapsed to the CNS and resistant to conventional therapy. Br J Haematol. 2009;144:794-5. https://doi.org/10.1111/j.1365-2141.2008.07497.x
Dass J, Dayama A, Mishra PC, Mahapatra M, Seth T, Tyagi S, et al. Higher rate of central nervous system involvement by flow cytometry than morphology in acute lymphoblastic leukemia. Int J Lab Hematol. 2017;39:546-51. https://doi.org/10.1111/ijlh.12694
Popov A, Henze G, Verzhbitskaya T, Roumiantseva J, Lagoyko S, Khlebnikova O, et al. Absolute count of leukemic blasts in cerebrospinal fluid as detected by flow cytometry is a relevant prognostic factor in children with acute lymphoblastic leukemia. J Cancer Res Clin Oncol. 2019;145:1331-9. https://doi.org/10.1007/s00432-019-02886-3
Larson RA. Managing CNS disease in adults with acute lymphoblastic leukemia. Leuk Lymphoma. 2018;59:3-13. https://doi.org/10.1080/10428194.2017.1326597
de Queiroz Mendonca C, Freire MV, Viana SS, Silva Tavares MKG, Almeida Silva WM, Cipolotti R. Ocular manifestations in acute lymphoblastic leukemia: A five-year cohort study of pediatric patients. Leuk Res. 2019;76:24-8. https://doi.org/10.1016/j.leukres.2018.11.017
Yi DH, Rashid S, Cibas ES, Arrigg PG, Dana MR. Acute unilateral leukemic hypopyon in an adult with relapsing acute lymphoblastic leukemia. Am J Ophthalmol. 2005;139:719-21. https://doi.org/10.1016/j.ajo.2004.09.074
Gorshein E, Kalathil S, Gharibo M. Prolonged survival of acute lymphoblastic leukemia with intrathecal treatments for isolated central nervous system relapse. Case Rep Hematol. 2018;2018:8765285. https://doi.org/10.1155/2018/8765285
Cheah CY, Herbert KE, O’Rourke K, Kennedy GA, George A, Fedele PL, et al. A multicentre retrospective comparison of central nervous system prophylaxis strategies among patients with high-risk diffuse large B-cell lymphoma. Br J Cancer. 2014;111:1072-9. https://doi.org/10.1038/bjc.2014.405
Walker GV, Shihadeh F, Kantarjian H, Allen P, Rondon G, Kebriaei P, et al. Comprehensive craniospinal radiation for controlling central nervous system leukemia. Int J Radiat Oncol. 2014;90:1119-25. https://doi.org/10.1016/j.ijrobp.2014.08.004
Salzer WL, Burke MJ, Devidas M, Dai Y, Hardy KK, Kairalla JA, et al. Impact of intrathecal triple therapy versus intrathecal methotrexate on disease-free survival for high-risk B-lymphoblastic leukemia: Childrens Oncology Group Study AALL1131. J Clin Oncol. 2020;38:2628-38. https://doi.org/10.1200/JCO.19.02892
Partap S, Murphy PA, Vogel H, Barnes PD, Edwards MSB, Fisher PG. Liposomal cytarabine for central nervous system embryonal tumors in children and young adults. J Neurooncol. 2011;103:561-6. https://doi.org/10.1007/s11060-010-0419-y
Canova F, Marino D, Trentin C, Soldà C, Ghiotto C, Aversa SML. Intrathecal chemotherapy in lymphomatous meningitis. Crit Rev Oncol Hematol. 2011;79:127-34. https://doi.org/10.1016/j.critrevonc.2010.07.005
Olmos-Jiménez R, Espuny-Miró A, Cárceles-Rodríguez C, Sacramento Díaz-Carrasco M. Practical aspects of the use of intrathecal chemotherapy Aspectos prácticos de la utilización de quimioterapia intratecal. Farm Hosp. 2017;41:105-29. https://doi.org/10.7399/fh.2017.41.1.10616
Sun H, Dai H, Shaik N, Elmquist WF. Drug efflux transporters in the CNS. Adv Drug Deliv Rev. 2003;55:83-105. https://doi.org/10.1016/S0169-409X(02)00172-2
Jonart LM, Ebadi M, Basile P, Johnson K, Makori J, Gordon PM. Disrupting the leukemia niche in the central nervous system attenuates leukemia chemoresistance. Haematologica. 2020;105:2130-40. https://doi.org/10.3324/haematol.2019.230334
Vicario N, Zappalà A, Calabrese G, Gulino R, Parenti C, Gulisano M, et al. Connexins in the central nervous system: Physiological traits and neuroprotective targets. Front Physiol. 2017;8:1060. https://doi.org/10.3389/fphys.2017.01060
Torrisi F, Alberghina C, Lo Furno D, Zappalà A, Valable S, Li Volti G, et al. Connexin 43 and sonic hedgehog pathway interplay in glioblastoma cell proliferation and migration. Biology (Basel). 2021;10:767. https://doi.org/10.3390/biology10080767
Alsadeq A, Lenk L, Vadakumchery A, Cousins A, Vokuhl C, Khadour A, et al. IL7R is associated with CNS infiltration and relapse in pediatric B-cell precursor acute lymphoblastic leukemia. Blood. 2018;132:1614-7. https://doi.org/10.1182/blood-2018-04-844209
Hunger SP, Raetz EA. How I treat relapsed acute lymphoblastic leukemia in the pediatric population. Blood. 2020;136:1803-12. https://doi.org/10.1182/blood.2019004043
Fielding AK, Richards SM, Chopra R, Lazarus HM, Litzow MR, Buck G, et al. Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12/ECOG 2993 study. Blood. 2007;109:944-50. https://doi.org/10.1182/blood-2006-05-018192
Kozak MM, Yoo CH, Gutkin PM, von Eyben R, Agarwal R, Donaldson SS, et al. Central nervous system relapse after stem cell transplantation in adolescents and young adults with acute lymphoblastic leukemia: a single-institution experience. J Adolesc Young Adult Oncol. 2020;9:166-71. https://doi.org/10.1089/jayao.2019.0121
Shigematsu A, Kako S, Mitsuhashi K, Iwato K, Uchida N, Kanda Y, et al. Allogeneic stem cell transplantation for adult patients with acute lymphoblastic leukemia who had central nervous system involvement: a study from the Adult ALL Working Group of the Japan Society for Hematopoietic Cell Transplantation. Int J Hematol. 2017;105:805-11. https://doi.org/10.1007/s12185-017-2197-1
How to Cite
Downloads
Downloads
Published
Issue
Section
License
Copyright (c) 2023 Revista Colombiana de Cancerología
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Todos los derechos reservados.
| Article metrics | |
|---|---|
| Abstract views | |
| Galley vies | |
| PDF Views | |
| HTML views | |
| Other views | |
