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Research ArticleBrain

Pretransplantation Conditioning Influence on the Occurrence of Cyclosporine or FK-506 Neurotoxicity in Allogeneic Bone Marrow Transplantation

Walter S. Bartynski, Zella R. Zeigler, Richard K. Shadduck and John Lister
American Journal of Neuroradiology February 2004, 25 (2) 261-269;
Walter S. Bartynski
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Zella R. Zeigler
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Richard K. Shadduck
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John Lister
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    Fig 1.

    Images in a 40-year-old woman with non-Hodgkin lymphoma who presented 27 days after allo-BMT with a seizure. Conditioning regimen was BEAM therapy. Blood pressure was 114/64 mm Hg and FK-506 level at the time of toxicity was 12.7 ìg/L (normal range, 5–20 ìg/l).

    A–D, FLAIR images demonstrate abnormal signal intensity in the cortex and subcortical white matter of the left inferior temporal-occipital junction (arrowhead in A), occipital poles (large arrows in A), parietal region (short arrows in B and C), and frontal lobes (long arrows in C and D) bilaterally, typical of cyclosporine or FK-506 neurotoxicity. The brain lesions in this patient are somewhat confluent and demarcate the junction between lateral cerebral hemispheric branches from the middle cerebral artery and medial hemispheric supply from the anterior and posterior cerebral arteries.

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    TABLE 1:

    Reasons for transplantation

    Clinical Problem Requiring TransplantationNo. of Patients
    Acute myelogenous leukemia82
    Chronic myelogenous leukemia81
    Non-Hodgkin lymphoma37
    Acute lymphocytic leukemia30
    Chronic lymphocytic leukemia1
    Multiple myeloma8
    Myelodysplastic syndrome29
    Aplastic anemia6
    Hodgkin disease4
    Myelofibrosis5
    Other*7
      Total290
    • * Included biphenotypic expression (features of both acute myelogenous leukemia and acute lymphocytic leukemia) in two patients, and Fanconi anemia, Waldenstrom macroglobulinemia, hairy cell leukemia, breast carcinoma, and hypereosinophilic syndrome in one patient each.

    • View popup
    TABLE 2:

    Major conditioning regimens

    RegimenNo. of Patients (n = 274)Neurotoxicity*Onset of Neurotoxicity*Average Survival after Neurotoxicity (days)
    EarlyMidLate
    Cy 2 days, busulfan 4 days975(5.1)31158
    Cy 2 days, busulfan 3 days, thiotepa 3 days51(20)1
    Cy 1 day, TBI 4 days30(0)
    Cy 2 days, TBI 4 days684(5.9)30151
    Cy 2 days, TBI 4 days, thiotepa 1 day393(7.7)325
    Cy 4 days, TBI 4 days517(13.7)†32249
    Cy 4 days, thiotepa 4 days, carboplatnium 4 days10(0)
    BEAM therapy101(10)1
    • * Data are number of patients. Numbers in parentheses are percentages.

    • † Statistically significant (P < .05) compared with the rate for Cy 2 days, busulfan 4 days.

    • View popup
    TABLE 3:

    Other conditioning regimens

    RegimenNo. of Patients (n = 16)
    Cy 2 days, TLI 1 day1
    Cy 4 days, TLI 4 days2
    Cy 4 days, TLI 1 day1
    Cy 4 days1
    Melphalan 1 day, TBI3
    Cy 2 days, etoposide 3 days, cisplatin 3 days1
    Thiotepa 1 day, melphalan 1 day, TBI 4 days1
    Cy 1 day, etoposide 1 day, TBI 4 days6
    • Note.—These regimens did not demonstrate neurotoxicity.

    • View popup
    TABLE 4:

    Clinical summary of patients undergoing allo-BMT

    Patient No./Age (y)/SexPreconditioning RegimenMTXHLA MatchNeurotoxicity (days)Survival after Neurotoxicity (days)CSP or FK-506 Level (μg/L)Presenting SymptomsImaging Time (hrs)*Blood pressure (mm Hg)BMT-TM GradeLDH Level (u/L)
    BaselineToxic
    1/25/FCy 4D, TBI 4D6/617ACSP 1367Seizure3130/81160/1442426
    2/36/FCy 2D, TBI 4D6/61418CSP 174Confusion28115/85167/1043→4†432→1980
    3/42/FCy 4D, TBI 4D6/678112CSP 439Confused, agitated, hallucinations8105/80150/1003†875
    4/43/FCy 4D, TBI 4D6/6238CSP 260Seizure1692/52210/1303†1055
    5/20/MCy 4D, TBI 4D5/6151112CSP 333Seizure3114/86130/1004→3†2880→546
    6/30/MCy 4D, TBI 4D4/65512CSP 556Seizure3124/88120/844†890
    7/49/MCy 4D, TBI 4D6/617ACSP 324Seizure4124/86150/952237
    8/30/MCy 4D, TBI 4D6/648050CSP 138HA20140/82164/1063†900
    9/19/MCy 2D, TBI 4DY6/623173CSP 508Seizure5112/70182/1303†415
    10/40/FCy 2D, TBI 4DY5/61510FK NPSeizure3140/90159/1104†2214
    11/46/FCy 2D, busulfan 4D6/6815CSP 209Seizure3110/70152/963→4†240→2680
    12/25/FCy 2D, busulfan 4D6/675102CSP 296Seizure11124/72150/100NP285
    13/28/MCy 2D, busulfan 4D6/627373CSP 1124Seizure1.5126/84115/8541515
    14/43/MCy 2D, busulfan 4D6/617623CSP 144Seizure3160/90170/1103→4†718
    15/41/MCy 2D, busulfan 4D6/65ACSP 377Seizure4120/70168/98NP143
    16/42/FCy 2D, TBI 4D, thiotepa 1DY6/627ACSP 1128Seizure5132/88140/953204
    17/26/FCy 2D, TBI 4D, thiotepa 1DY6/62664CSP 301Seizure3138/100140/100NP283
    18/38/FCy 2D, thiotopa 3D, busulfan 3DY6/6164CSP 302Vision loss, HA2150/88180/1003222
    19/25/MCy 2D, TBI 4D, thiotepa 1D4/62333FK 5.7Vision loss then seizure1125/70165/10031125
    20/17/FCy 2D, TBI 4DY6/617392CSP 330Seizure18110/60120/801→31179
    21/40/FBEAMY6/627115FK 2.7Seizure6108/60114/6422495
    • Note.—MTX indicates methotrexate; CSP, cyclosporine; LDH, lactate dehydrogenase; D, number of days of regimen; HA, ?; Y, yes; NP, not performed; A, alive survivor.

    • * Time after patient presentation with symptoms that imaging study was performed.

    • † Patient undergoing apheresis for BMT-TM.

    • View popup
    TABLE 5:

    Onset of neurotoxicity

    OnsetNo. (%) of Patients (n = 21)Average Time from Transplantation to Neurotoxicity (days)Average Survival after Neurotoxicity (days)
    Early14(67)19120
    Mid3(14)6975
    Late4(19)26962
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American Journal of Neuroradiology: 25 (2)
American Journal of Neuroradiology
Vol. 25, Issue 2
1 Feb 2004
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Pretransplantation Conditioning Influence on the Occurrence of Cyclosporine or FK-506 Neurotoxicity in Allogeneic Bone Marrow Transplantation
Walter S. Bartynski, Zella R. Zeigler, Richard K. Shadduck, John Lister
American Journal of Neuroradiology Feb 2004, 25 (2) 261-269;
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Cite this article
Walter S. Bartynski, Zella R. Zeigler, Richard K. Shadduck, John Lister
Pretransplantation Conditioning Influence on the Occurrence of Cyclosporine or FK-506 Neurotoxicity in Allogeneic Bone Marrow Transplantation
American Journal of Neuroradiology Feb 2004, 25 (2) 261-269;

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