Abstract
The effect of methylprednisolone on fresh cells from patients with chronic lymphocytic leukaemia (CLL) has been studied using the differential staining cytotoxicity (DiSC) assay resulting in LC90s of < or = 0.2 to 2,000 micrograms/ml. Cells from previously treated patients were, on average, significantly more sensitive to methylprednisolone than those from untreated patients (mean LC90 = 5.7 micrograms/ml, n = 61 vs 31.0 micrograms/ml, n = 17, respectively; p < 0.05). Twelve patients with advanced disease were given high-dose methylprednisolone (1 g/m2/day i.v. x 5 days). In 7 cases, > or = 3 courses were given; 3 patients did not respond (2 achieved palliation) and 4 (57%) achieved a good partial response. These latter 4 patients were all clinically resistant to chlorambucil and anthracyclines and 2 were resistant to fludarabine. In 5 cases, 1 or 2 courses were given but no patients responded. The 8 nonresponders survived a median of 3.5 months whilst the responders have survived a median of 28.5+ months (3 of 4 still alive). This work suggests a rationale for why CLL patients resistant to standard chemotherapy may benefit from high-dose methylprednisolone therapy. Due to cost and toxicity associated with therapy, the decision to treat would be best made on the basis of a DiSC assay result. This pilot study requires confirmation with a well-designed controlled clinical trial.
Publication types
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Case Reports
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Clinical Trial
MeSH terms
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Adult
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Antibiotics, Antineoplastic / administration & dosage
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Antibiotics, Antineoplastic / pharmacology
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Cell Survival / drug effects
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Chlorambucil / pharmacology
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Chlorambucil / therapeutic use
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Cyclophosphamide / pharmacology
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Doxorubicin / pharmacology
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Drug Resistance
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Drug Screening Assays, Antitumor
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Fatal Outcome
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Female
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Humans
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Ifosfamide / administration & dosage
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Ifosfamide / pharmacology
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Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
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Leukemia, Lymphocytic, Chronic, B-Cell / mortality
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Leukemia, Lymphocytic, Chronic, B-Cell / pathology
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Male
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Melphalan / administration & dosage
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Methylprednisolone / administration & dosage
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Methylprednisolone / pharmacology
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Methylprednisolone / therapeutic use*
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Middle Aged
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Neoplastic Stem Cells / drug effects*
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Palliative Care
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Pilot Projects
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Prednisolone / administration & dosage
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Prednisone / pharmacology
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Remission Induction
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Staining and Labeling
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Survival Analysis
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Treatment Outcome
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Tumor Cells, Cultured
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Vidarabine / administration & dosage
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Vidarabine / analogs & derivatives
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Vidarabine / pharmacology
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Vinca Alkaloids / administration & dosage
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Vinca Alkaloids / pharmacology
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Vincristine / pharmacology
Substances
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Antibiotics, Antineoplastic
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Vinca Alkaloids
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Chlorambucil
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Vincristine
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Doxorubicin
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Cyclophosphamide
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Prednisolone
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Vidarabine
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fludarabine
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Melphalan
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Ifosfamide
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Prednisone
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Methylprednisolone