TY - JOUR
T1 - Excessive spinal cord toxicity from intensive central nervous system ‐directed therapies
AU - Watterson, Jan
AU - Toogood, Ian
AU - Nieder, Michael
AU - Morse, Margaret
AU - Frierdich, Sharon
AU - Lee, Yisheng
AU - Moertel, Christopher L
AU - Priest, John R.
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 1994/12/1
Y1 - 1994/12/1
N2 - Background. Intrathecal chemotherapy, radiation therapy, and systemic chemotherapy are used for both prophylaxis and treatment of central nervous system (CNS) disease in hematologic malignancies. Twenty‐three cases of myelopathy that occurred in patients who received intensive CNS‐directed therapy were evaluated to identify the determinants of this severe CNS toxicity. Methods. Nine cases treated by the authors and 14 collected from the literature are discussed. Twelve had Burkitt's leukemia/lymphoma. Patient ages ranged from 3 to 30 years (median, 15 years). The dose intensity of CNS‐directed therapies, including intrathecal cytosine arabinoside (ara‐C), intrathecal methotrexate (MTX), systemic high dose (HD) MTX, systemic HD ara‐C, systemic thiotepa, and CNS radiation, was evaluated by the determination of single drug doses and cumulative total drug or irradiation doses over elapsed treatment durations. Results. Central nervous system treatment was prophylactic in 10 cases; active CNS disease was being treated in 13 cases. One patient received only intrathecal ara‐C before toxicity occurred; others received intrathecal ara‐C and varying combinations of intrathecal MTX, HD ara‐C, HD MTX, CNS radiation, and systemic thiotepa. Eight patients died of toxicity, of whom 6 had autopsy‐proven cord necrosis; 3 were ventilator‐dependent; 10 had persistent paraplegia or paraparesis; and 2 recovered completely. Conclusion. Both highly intensive, short CNS treatment sequences and lower intensity, long term cumulative treatments may result in this rare but severe myelopathy. The cause is multifactorial, with systemic chemotherapy, intrathecal chemotherapy, and radiation therapy contributing to toxicity. Multiple intrathecal ara‐C and/or MTX doses given at frequent (daily) intervals should be avoided. Concurrent intrathecal ara‐C and systemic HD ara‐C also appear to be especially toxic. Intrathecal hydrocortisone given with intrathecal ara‐C does not protect against myelopathy. Multiple, frequently spaced courses of CNS‐directed therapies must be avoided, especially in patients who have received prior CNS radiation.
AB - Background. Intrathecal chemotherapy, radiation therapy, and systemic chemotherapy are used for both prophylaxis and treatment of central nervous system (CNS) disease in hematologic malignancies. Twenty‐three cases of myelopathy that occurred in patients who received intensive CNS‐directed therapy were evaluated to identify the determinants of this severe CNS toxicity. Methods. Nine cases treated by the authors and 14 collected from the literature are discussed. Twelve had Burkitt's leukemia/lymphoma. Patient ages ranged from 3 to 30 years (median, 15 years). The dose intensity of CNS‐directed therapies, including intrathecal cytosine arabinoside (ara‐C), intrathecal methotrexate (MTX), systemic high dose (HD) MTX, systemic HD ara‐C, systemic thiotepa, and CNS radiation, was evaluated by the determination of single drug doses and cumulative total drug or irradiation doses over elapsed treatment durations. Results. Central nervous system treatment was prophylactic in 10 cases; active CNS disease was being treated in 13 cases. One patient received only intrathecal ara‐C before toxicity occurred; others received intrathecal ara‐C and varying combinations of intrathecal MTX, HD ara‐C, HD MTX, CNS radiation, and systemic thiotepa. Eight patients died of toxicity, of whom 6 had autopsy‐proven cord necrosis; 3 were ventilator‐dependent; 10 had persistent paraplegia or paraparesis; and 2 recovered completely. Conclusion. Both highly intensive, short CNS treatment sequences and lower intensity, long term cumulative treatments may result in this rare but severe myelopathy. The cause is multifactorial, with systemic chemotherapy, intrathecal chemotherapy, and radiation therapy contributing to toxicity. Multiple intrathecal ara‐C and/or MTX doses given at frequent (daily) intervals should be avoided. Concurrent intrathecal ara‐C and systemic HD ara‐C also appear to be especially toxic. Intrathecal hydrocortisone given with intrathecal ara‐C does not protect against myelopathy. Multiple, frequently spaced courses of CNS‐directed therapies must be avoided, especially in patients who have received prior CNS radiation.
KW - Burkitt's lymphoma
KW - cytosine arabinoside
KW - intrathecal chemotherapy
KW - paraparesis
KW - paraplegia
KW - spinal cord toxicity
KW - spinal radiation
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U2 - 10.1002/1097-0142(19941201)74:11<3034::AID-CNCR2820741122>3.0.CO;2-O
DO - 10.1002/1097-0142(19941201)74:11<3034::AID-CNCR2820741122>3.0.CO;2-O
M3 - Article
C2 - 7954266
AN - SCOPUS:0028054230
VL - 74
SP - 3034
EP - 3041
JO - Cancer
JF - Cancer
SN - 0008-543X
IS - 11
ER -