The central nervous system leukemia: a clinical and pathological study

Lana-Peixoto, Maria Inês Vilhena; Lana-Peixoto, Marco Aurélio

doi:10.1590/S0004-282X1985000100001

Abstracts

Post-mortem clinical and pathological study of 18 cases of central nervous system leukemia showed that this complication occurred mostly in chronic myelogenous leukemia (38.8%). No diagnostic criteria was found. The great majority of signs and symptoms were related to either d sturbances of the mental status or cranial nerves dysfunction. Cerebrospinal fluid may be found normal. CNS involvement may occur at any time during the course of systemic leukemia, when the disease is under apparently good therapeutic control as well as during relapse. Pathological findings in order of decre sing frequency were: parenchymal hemorrhage (61%); subarachnoid hemorrhage (55%); meningeal infiltrates (44%); leukostasis (28%); edema and herniation (28%); parenchymal infiltrates (22%); ischemic infarcts (17%); progressive multifocal leucoencephalopathy (10%); calcifications (5%); meningitis (5%). Total survival time ranged from 8 to 1980 days a median of 300 days. Survival time after CNS involvement ranged from 1 to 180 days with a median of 21 days.

Estudo postmortem abrangendo os aspectos clínicos e patológicos de 18 casos de leucemia do sistema nervoso central mostrou que esta complicação ocorreu com mais frequência na leucemia mielógena crônica (38,8%). Não houve um quadro clínico típico, mas na grande maioria dos casos os sinais e sintomas estavam relacionados ou a alterações do estado mental ou à disfunção de nervos cranianos. O líquor pode ser normal. Os achados patológicos em ordem decrescente de frequência foram: hemorragia intraparenquimatosa (61%); hemorragia subaracnóidea (55%); infiltrados meníngeos (44%); leucostase (28%); edema e herniação (28%); infiltrado n parênquima (22%); infarto isquêmico (17%); leucoencefalopatia progressiva multifocal (10%); calcificações (5%); meningite (5%). O tempo total de sobrevida variou de 8 a 1.980 dias, com uma mediana de 300 dias. O tempo de sobrevida após acometimento do sistema nervoso central variou de 1 a 180 dias com uma mediana de 21 dias. O acometimento do sistema nervoso central pod ocorrer em qualquer época durante o curso de leucemia sistêmica, mesmo quando a doença está aparentemente sob bom controle terapêutico, mas é mais comum durante os seus relapsos.

The central nervous system leukemia: a clinical and pathological study

Leucemia do sistema nervoso central: estudo clinico e patológico

Maria Inês Vilhena Lana-Peixoto; Marco Aurélio Lana-Peixoto

Assistant Professor. Department of Neurology, Federal University of Minas Gerais Medical School

SUMMARY

Post-mortem clinical and pathological study of 18 cases of central nervous system leukemia showed that this complication occurred mostly in chronic myelogenous leukemia (38.8%). No diagnostic criteria was found. The great majority of signs and symptoms were related to either d sturbances of the mental status or cranial nerves dysfunction. Cerebrospinal fluid may be found normal. CNS involvement may occur at any time during the course of systemic leukemia, when the disease is under apparently good therapeutic control as well as during relapse. Pathological findings in order of decre sing frequency were: parenchymal hemorrhage (61%); subarachnoid hemorrhage (55%); meningeal infiltrates (44%); leukostasis (28%); edema and herniation (28%); parenchymal infiltrates (22%); ischemic infarcts (17%); progressive multifocal leucoencephalopathy (10%); calcifications (5%); meningitis (5%). Total survival time ranged from 8 to 1980 days a median of 300 days. Survival time after CNS involvement ranged from 1 to 180 days with a median of 21 days.

RESUMO

Estudo postmortem abrangendo os aspectos clínicos e patológicos de 18 casos de leucemia do sistema nervoso central mostrou que esta complicação ocorreu com mais frequência na leucemia mielógena crônica (38,8%). Não houve um quadro clínico típico, mas na grande maioria dos casos os sinais e sintomas estavam relacionados ou a alterações do estado mental ou à disfunção de nervos cranianos. O líquor pode ser normal. Os achados patológicos em ordem decrescente de frequência foram: hemorragia intraparenquimatosa (61%); hemorragia subaracnóidea (55%); infiltrados meníngeos (44%); leucostase (28%); edema e herniação (28%); infiltrado n parênquima (22%); infarto isquêmico (17%); leucoencefalopatia progressiva multifocal (10%); calcificações (5%); meningite (5%). O tempo total de sobrevida variou de 8 a 1.980 dias, com uma mediana de 300 dias. O tempo de sobrevida após acometimento do sistema nervoso central variou de 1 a 180 dias com uma mediana de 21 dias. O acometimento do sistema nervoso central pod ocorrer em qualquer época durante o curso de leucemia sistêmica, mesmo quando a doença está aparentemente sob bom controle terapêutico, mas é mais comum durante os seus relapsos.

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Departamento de Neurologia, Faculdade de Medicina da UFMG - Avenida Alfredo Balena, 180 - 30.000, Belo Horizonte, M.G. - Brasil.

1. AUR, R.J.A.; SIMONE, J.; HUSTU, H.O.; WALTERS. T.; BARELLA, L.; PRATT, C. & PINKEL, D. - Central nervous system therapy, and combination chemotherapy of childhood lymphocytic leukemia. Blood 37:272, 1971.
2. CROSLEY, C.J.; RORKE, L.B.; EVANS, A. & NIGRO, M. - Central nervous system lesions in childhood leukemia. Neurology (Minneapolis) 28:678, 1978.
3. DEARTH, J.C.; FOUNTAIN, K.S.; SMITHSON, W.A.; BURGET, E.O. & GILCHRIST, G.S. - Extreme leukocytosis (blast crisis) in childhood. Mayo Clin. Proc. 53:207, 1978.
4. EVANS, A.E.; GILBERT, E.S. & SANDSTRA, R. - The increasing incidence of central nervous system leukemia in children. Cancer 26:404, 1970.
5. FITZPATRICK, H.; LIEBERMAN, N. & SINKS, L.F. - Staging of acute leukemia and the relationship to CNS involvement Cancer 33:1376, 1974.
6. FLAMENT-DURANT, J.; KETELBANT-BALASSE, P.; MAURUS, R.; REGNIER, R. & SPEHL, M. - Intracerebral calcification appearing during the course of acute lymphocytic leukemia treated with methotrexate and X-rays. Cancer 35:319, 1975.
7. FREIREICH, E.J.; THOMAS, L.B.; FREI, E.; FRITZ, R.D. & FORKNER, C.E. - A distinctive type of intracerebral hemorrhage associated with blastic crisis in patients with leukemia. Cancer 13:146, 1980.
8. FRITZ, R.D.; FORKNER, C.E., Jr; FREIREICH, E.H.; FREI, E. & THOMAS, L.B.B. - The association of fatal intracranial hemorrhage and «blastic crisis» in patients with acute leukemia. New Engl. J. Med. 261:59, 1959.
9. GARWICZ, S.; ARONSON, A.S., ELMQVIST, D. & LANDBERG, T. - Postirradiation syndrome and EEG findings in children with acute lymph blastic leukemia. Acta pediatr. scand. 64:399, 1975.
10. GILBERT, E.F. & RICE, E.C. - Neurologic manifestation of leukemia. Pediatrics 19:801, 1957.
11. GONDOR, B. & KING, E.B. - Cerebrospinal fluid cytology: diagnostic accuracy and comparison of different techniques. Acta cytol. 20:542, 1976.
12. GREYDANUS, D.; BURGERT, E.O. & GILCHRIST, G.S. - Hypothalamic syndrome in children with acute lymphocytic leukemia. Mayo Clin. Proc. 53:217, 1978.
13. HARDISTY, R.M. & NORMAN, P.M. - Meningeal leukemia. Arch. Dis. Childh. 42:441, 1967.
14. HOAGLAND, H.C. - Acute leukemia and its complications. Mayo Clin. Proc. 53: 260, 1978.
15. HYMAN, C.B.; BOGLE, J.M.; BRUBAKER, C.A.; WILLIAMS, K. & HAMMOND, D. - Central nervous system involvement by leukemia in children. I. Relationship to systemic leukemia and description of clinical and laboratory manifestations. J. Hematol. 25:1, 1965.
16. LOWENTHAL, R.M.; BUSKARD, N.A.; GOLDMAN, J.M.; SPIERS, A.S.D.; BERGIER, N.; GRAUBNER, M. & GAI/TON, D.A.G. - Intensive leukapharesis as initial therapy for chronic granulocytic leukemia. Blood 46: 835, 1975.
17. McKEE, C. & COLLINS, R.D. - Intravascular leukocyte trombi and aggregates as a cause of morbidity and mortality in leukemia. Medicine 53:463, 1974.
18. MELLOR, D. - Encephalitis and encephalopathy in childhood leukemia. Develop. Med. Child. Neurol. 18:90, 1976.
19. MILLER, R.W. - Etiology of childhood leukemia. Ped. Clin. N. Amer. 13:267, 1966.
20. MOORE, E.W.; THOMAS, L.B.; SHAW, R.K. & FREIREICH, E.J. - The central nervous system in acute leukemia. Arch. int. Med. 105:142, 1960.
21. MUELLER, S., BELL, W. & SEIBERT, J. - Cerebral calcifications associated with intrathecal methotrexate therapy in acute lymphocytic leukemia. J. Ped. 88:650, 1976.
22. PHAIR, J.P.; ANDERSON, R.E. & NAMIKI, H. - The central nervous system in childhood leukemia. Ann. int. Med. 61:863, 1964.
23. PIERCE, M.I. - Neurologic complications in acute leukemia in children. Ped. Clin. N. Amer. 9:425, 1962.
24. PRICE, R.A. & JOHNSON, W.W. - The central nervous system in childhood leukemia. I. The arachnoid. Cancer 31:520, 1973.
25. SHAW, R.K.; MOORE, E.W.; FREIREICH, E.J. & THOMAS, L.B. - Meningeal leukemia. Neurology (Minneapolis) 10:823, 1960.
26. STEFFEY, J.M. - The central nervous system manifestations of leukemia. J. Ped. 60:183, 1962.
27. SULLIVAN, M.P. - Intracranial complications of leukemia in children. Pediatr. 5:751, 1957.
28. SULLIVAN, M.P.; BATTY, E.C.; HYMAN, C.B.; MURPHY, L.M.; PIERCE, M..i. & SEVERO, N.C. - A comparison of the effettiveness of standard dose of 6-mercaptopurine, combination 6-mercaptopurine and DON, and high loading, 6-mercaptopurine therapies. Cancer Chemotherapy Reports 18:83, 1962.
29. WELLS, C.E. & SILVER, R.T. - The neurologic manifestations of the acute leukemias: a clinical study. Ann. int. Med. 46:439, 1957.
30. WEST, R.J.; GRAHAM-POLE, J.; HARDISTY, R.M. & PIKE, M.C. - Factors in pathogenesis of central nervous system leukemia. Brit. med. J. 3:311, 1972.
31. WOLK, R.W.; MASSE, S.R.; CONKLIN, R. & FREIREICH, E.J. - The. incidence of central nervous system leukemia in adults wich acute leukemia. Cancer 33: 863, 1974.
32. ZU RHEIN, G. & CHAN, S. - Particles resembling papovaviruses in human cerebral demyelinating disease. Acta neuropath. 8:57, 1967.

Publication Dates

Publication in this collection
15 Aug 2012
Date of issue
Mar 1985

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. AUR, R.J.A.; SIMONE, J.; HUSTU, H.O.; WALTERS. T.; BARELLA, L.; PRATT, C. & PINKEL, D. - Central nervous system therapy, and combination chemotherapy of childhood lymphocytic leukemia. Blood 37:272, 1971.

[2] 2. CROSLEY, C.J.; RORKE, L.B.; EVANS, A. & NIGRO, M. - Central nervous system lesions in childhood leukemia. Neurology (Minneapolis) 28:678, 1978.

[3] 3. DEARTH, J.C.; FOUNTAIN, K.S.; SMITHSON, W.A.; BURGET, E.O. & GILCHRIST, G.S. - Extreme leukocytosis (blast crisis) in childhood. Mayo Clin. Proc. 53:207, 1978.

[4] 4. EVANS, A.E.; GILBERT, E.S. & SANDSTRA, R. - The increasing incidence of central nervous system leukemia in children. Cancer 26:404, 1970.

[5] 5. FITZPATRICK, H.; LIEBERMAN, N. & SINKS, L.F. - Staging of acute leukemia and the relationship to CNS involvement Cancer 33:1376, 1974.

[6] 6. FLAMENT-DURANT, J.; KETELBANT-BALASSE, P.; MAURUS, R.; REGNIER, R. & SPEHL, M. - Intracerebral calcification appearing during the course of acute lymphocytic leukemia treated with methotrexate and X-rays. Cancer 35:319, 1975.

[7] 7. FREIREICH, E.J.; THOMAS, L.B.; FREI, E.; FRITZ, R.D. & FORKNER, C.E. - A distinctive type of intracerebral hemorrhage associated with blastic crisis in patients with leukemia. Cancer 13:146, 1980.

[8] 8. FRITZ, R.D.; FORKNER, C.E., Jr; FREIREICH, E.H.; FREI, E. & THOMAS, L.B.B. - The association of fatal intracranial hemorrhage and «blastic crisis» in patients with acute leukemia. New Engl. J. Med. 261:59, 1959.

[9] 9. GARWICZ, S.; ARONSON, A.S., ELMQVIST, D. & LANDBERG, T. - Postirradiation syndrome and EEG findings in children with acute lymph blastic leukemia. Acta pediatr. scand. 64:399, 1975.

[10] 10. GILBERT, E.F. & RICE, E.C. - Neurologic manifestation of leukemia. Pediatrics 19:801, 1957.

[11] 11. GONDOR, B. & KING, E.B. - Cerebrospinal fluid cytology: diagnostic accuracy and comparison of different techniques. Acta cytol. 20:542, 1976.

[12] 12. GREYDANUS, D.; BURGERT, E.O. & GILCHRIST, G.S. - Hypothalamic syndrome in children with acute lymphocytic leukemia. Mayo Clin. Proc. 53:217, 1978.

[13] 13. HARDISTY, R.M. & NORMAN, P.M. - Meningeal leukemia. Arch. Dis. Childh. 42:441, 1967.

[14] 14. HOAGLAND, H.C. - Acute leukemia and its complications. Mayo Clin. Proc. 53: 260, 1978.

[15] 15. HYMAN, C.B.; BOGLE, J.M.; BRUBAKER, C.A.; WILLIAMS, K. & HAMMOND, D. - Central nervous system involvement by leukemia in children. I. Relationship to systemic leukemia and description of clinical and laboratory manifestations. J. Hematol. 25:1, 1965.

[16] 16. LOWENTHAL, R.M.; BUSKARD, N.A.; GOLDMAN, J.M.; SPIERS, A.S.D.; BERGIER, N.; GRAUBNER, M. & GAI/TON, D.A.G. - Intensive leukapharesis as initial therapy for chronic granulocytic leukemia. Blood 46: 835, 1975.

[17] 17. McKEE, C. & COLLINS, R.D. - Intravascular leukocyte trombi and aggregates as a cause of morbidity and mortality in leukemia. Medicine 53:463, 1974.

[18] 18. MELLOR, D. - Encephalitis and encephalopathy in childhood leukemia. Develop. Med. Child. Neurol. 18:90, 1976.

[19] 19. MILLER, R.W. - Etiology of childhood leukemia. Ped. Clin. N. Amer. 13:267, 1966.

[20] 20. MOORE, E.W.; THOMAS, L.B.; SHAW, R.K. & FREIREICH, E.J. - The central nervous system in acute leukemia. Arch. int. Med. 105:142, 1960.

[21] 21. MUELLER, S., BELL, W. & SEIBERT, J. - Cerebral calcifications associated with intrathecal methotrexate therapy in acute lymphocytic leukemia. J. Ped. 88:650, 1976.

[22] 22. PHAIR, J.P.; ANDERSON, R.E. & NAMIKI, H. - The central nervous system in childhood leukemia. Ann. int. Med. 61:863, 1964.

[23] 23. PIERCE, M.I. - Neurologic complications in acute leukemia in children. Ped. Clin. N. Amer. 9:425, 1962.

[24] 24. PRICE, R.A. & JOHNSON, W.W. - The central nervous system in childhood leukemia. I. The arachnoid. Cancer 31:520, 1973.

[25] 25. SHAW, R.K.; MOORE, E.W.; FREIREICH, E.J. & THOMAS, L.B. - Meningeal leukemia. Neurology (Minneapolis) 10:823, 1960.

[26] 26. STEFFEY, J.M. - The central nervous system manifestations of leukemia. J. Ped. 60:183, 1962.

[27] 27. SULLIVAN, M.P. - Intracranial complications of leukemia in children. Pediatr. 5:751, 1957.

[28] 28. SULLIVAN, M.P.; BATTY, E.C.; HYMAN, C.B.; MURPHY, L.M.; PIERCE, M..i. & SEVERO, N.C. - A comparison of the effettiveness of standard dose of 6-mercaptopurine, combination 6-mercaptopurine and DON, and high loading, 6-mercaptopurine therapies. Cancer Chemotherapy Reports 18:83, 1962.

[29] 29. WELLS, C.E. & SILVER, R.T. - The neurologic manifestations of the acute leukemias: a clinical study. Ann. int. Med. 46:439, 1957.

[30] 30. WEST, R.J.; GRAHAM-POLE, J.; HARDISTY, R.M. & PIKE, M.C. - Factors in pathogenesis of central nervous system leukemia. Brit. med. J. 3:311, 1972.

[31] 31. WOLK, R.W.; MASSE, S.R.; CONKLIN, R. & FREIREICH, E.J. - The. incidence of central nervous system leukemia in adults wich acute leukemia. Cancer 33: 863, 1974.

[32] 32. ZU RHEIN, G. & CHAN, S. - Particles resembling papovaviruses in human cerebral demyelinating disease. Acta neuropath. 8:57, 1967.