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 ◽  
Vol 110 (5) ◽  
pp. 1698-1698 ◽  
Author(s):  
Marc C. Chamberlain ◽  
Michael J. Glantz
Keyword(s):  
Acute Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Liposomal Cytarabine ◽  
High Dose Methotrexate ◽  
Neurologic Complications ◽  
Dose Methotrexate

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 ◽  
Vol 109 (8) ◽  
pp. 3214-3218 ◽  
Author(s):  
Elias Jabbour ◽  
Susan O'Brien ◽  
Hagop Kantarjian ◽  
Guillermo Garcia-Manero ◽  
Alessandra Ferrajoli ◽  
...  
Keyword(s):  
Acute Lymphocytic Leukemia ◽  
Cauda Equina ◽  
Neoplastic Meningitis ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Liposomal Cytarabine ◽  
High Dose Methotrexate ◽  
Cns Prophylaxis ◽  
Dose Methotrexate

Abstract Central nervous system (CNS) prophylaxis has led to a significant improvement in the outcome of patients with acute lymphocytic leukemia (ALL). Liposomal cytarabine (Enzon Pharmaceuticals, Piscataway, NJ; Skye Pharma, San Diego, CA), an intrathecal (IT) preparation of cytarabine with a prolonged half-life, has been shown to be safe and effective in the treatment of neoplastic meningitis. Liposomal cytarabine was given for CNS prophylaxis to 31 patients with newly diagnosed ALL. All patients were treated concurrently with hyper-CVAD chemotherapy (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) including high-dose methotrexate (MTX) and cytarabine on alternating courses. Liposomal cytarabine 50 mg was given intrathecally on days 2 and 15 of hyper-CVAD and day 10 of high-dose MTX and cytarabine courses until completion of either 3, 6, or 10 IT treatments, depending on risk for CNS disease. Five patients (16%) experienced serious unexpected neurotoxicity, including seizures, papilledema, cauda equina syndrome (n = 2), and encephalitis after a median of 4 IT administrations of liposomal cytarabine. Toxicities usually manifested after the MTX and cytarabine courses. One patient died with progressive encephalitis. After a median follow-up of 7 months, no isolated CNS relapses have been observed. Liposomal cytarabine given via intrathecal route concomitantly with systemic chemotherapy that crosses the blood-brain barrier such as high-dose MTX and cytarabine can result in significant neurotoxicity.

scholarly journals Efficacy of high-dose methotrexate in childhood acute lymphocytic leukemia: analysis by contemporary risk classifications

Blood ◽  
1988 ◽  
Vol 71 (4) ◽  
pp. 866-869 ◽  
Author(s):  
M Abromowitch ◽  
J Ochs ◽  
CH Pui ◽  
D Fairclough ◽  
SB Murphy ◽  
...  
Keyword(s):  
Acute Lymphocytic Leukemia ◽  
Leukemic Cell ◽  
Risk Groups ◽  
Cranial Irradiation ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Average Risk ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Table Analysis

Abstract High-dose methotrexate (HDMTX) added to a basic regimen of chemotherapy proved superior to cranial irradiation and sequentially administered drug pairs (RTSC) in prolonging complete remissions in children with “standard-risk” acute lymphocytic leukemia. To extend this result to more contemporary risk groups, we reclassified the patients according to methods of the Pediatric Oncology Group (POG), the Childrens Cancer Study Group (CCG), the Rome workshop, and St Jude Total Therapy Study XI. By life table analysis, 70% to 78% of patients with a favorable prognosis would remain in continuous complete remission (CCR) at 4 years if treated with HDMTX. Uniformly lower CCR rates could be expected with RTSC, especially in St Jude better-risk patients. HDMTX also would show greater efficacy than RTSC in the CCG average-risk and POG poor-risk groups, but the results appear inferior to those being achieved with intensified regimens for high-risk leukemia. Although both therapies would provide adequate CNS prophylaxis in favorable-risk groups, RTSC would offer greater protection in patients classified as being in a worse-risk group by St Jude criteria. We conclude that HDMTX- based therapy, as described in this report, would be most effective in patients with a presenting leukocyte count of less than 25 x 10(9)/L, of the white race, aged 2 to 10 years, and having leukemic cell hyperdiploidy without translocations.

Clinical Pharmacodynamics of High-Dose Methotrexate in Acute Lymphocytic Leukemia

1986 ◽  
Vol 314 (8) ◽  
pp. 471-477 ◽  
Author(s):  
William E. Evans ◽  
William R. Crom ◽  
Minnie Abromowitch ◽  
Richard Dodge ◽  
A. Thomas Look ◽  
...  
Keyword(s):  
Acute Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate

scholarly journals Efficacy of high-dose methotrexate in childhood acute lymphocytic leukemia: analysis by contemporary risk classifications

Blood ◽  
1988 ◽  
Vol 71 (4) ◽  
pp. 866-869
Author(s):  
M Abromowitch ◽  
J Ochs ◽  
CH Pui ◽  
D Fairclough ◽  
SB Murphy ◽  
...  
Keyword(s):  
Acute Lymphocytic Leukemia ◽  
Leukemic Cell ◽  
Risk Groups ◽  
Cranial Irradiation ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Average Risk ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Table Analysis

High-dose methotrexate (HDMTX) added to a basic regimen of chemotherapy proved superior to cranial irradiation and sequentially administered drug pairs (RTSC) in prolonging complete remissions in children with “standard-risk” acute lymphocytic leukemia. To extend this result to more contemporary risk groups, we reclassified the patients according to methods of the Pediatric Oncology Group (POG), the Childrens Cancer Study Group (CCG), the Rome workshop, and St Jude Total Therapy Study XI. By life table analysis, 70% to 78% of patients with a favorable prognosis would remain in continuous complete remission (CCR) at 4 years if treated with HDMTX. Uniformly lower CCR rates could be expected with RTSC, especially in St Jude better-risk patients. HDMTX also would show greater efficacy than RTSC in the CCG average-risk and POG poor-risk groups, but the results appear inferior to those being achieved with intensified regimens for high-risk leukemia. Although both therapies would provide adequate CNS prophylaxis in favorable-risk groups, RTSC would offer greater protection in patients classified as being in a worse-risk group by St Jude criteria. We conclude that HDMTX- based therapy, as described in this report, would be most effective in patients with a presenting leukocyte count of less than 25 x 10(9)/L, of the white race, aged 2 to 10 years, and having leukemic cell hyperdiploidy without translocations.

Effect of hydration on methotrexate plasma concentrations in children with acute lymphocytic leukemia.

1988 ◽  
Vol 6 (5) ◽  
pp. 797-801 ◽  
Author(s):  
M L Christensen ◽  
G K Rivera ◽  
W R Crom ◽  
M L Hancock ◽  
W E Evans
Keyword(s):  
Acute Lymphocytic Leukemia ◽  
Renal Toxicity ◽  
Plasma Concentrations ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Severe Toxicity ◽  
High Dose Methotrexate ◽  
Kidney Tubules ◽  
Dose Methotrexate ◽  
The Mean

Hydration and urinary alkalinization are used with high-dose methotrexate (HDMTX) to minimize renal toxicity resulting from methotrexate (MTX) precipitation in the kidney tubules. The effect of two hydration and alkalinization schedules on MTX plasma concentrations were evaluated in 100 children with acute lymphocytic leukemia (ALL) following two courses of MTX, 2 g/m2. The mean 21- and 44-hour MTX plasma concentrations were significantly lower in the group receiving the greater hydration and alkalinization schedule: 0.79 (0.90 SD) v 1.39 (1.99 SD) mumol/L for 21-hour MTX plasma concentrations, P = .01; and 0.18 (0.38 SD) v 0.25 (0.50 SD) mumol/L for 44-hour MTX plasma concentrations, P = .01. Although the overall incidence of toxic events was similar in both groups, the incidence of severe toxicity was reduced in the group that received the greater hydration and alkalinization, 6% v 16%. This study demonstrated that the amount of hydration and alkalinization can affect MTX plasma concentrations. Optimizing the hydration and alkalinization schedule is important for minimizing the incidence of severe toxicity associated with HDMTX.

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