title: Methylprednisolone in advanced chronic lymphocytic leukaemia: rationale for, and effectiveness of treatment suggested by DiSC assay.
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.
authors.affiliation: Bath Cancer Research Unit, Royal United Hospital, UK.
authors.forename: A G
authors.initials: AG
authors.lastname: Bosanquet
authors.forename: S R
authors.initials: SR
authors.lastname: McCann
authors.forename: G M
authors.initials: GM
authors.lastname: Crotty
authors.forename: M J
authors.initials: MJ
authors.lastname: Mills
authors.forename: D
authors.initials: D
authors.lastname: Catovsky
mesh_terms: D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects; D002699:Chlorambucil / Q000494:pharmacology / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008775:Methylprednisolone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D010166:Palliative Care; D010865:Pilot Projects; D011239:Prednisolone / Q000008:administration & dosage; D011241:Prednisone / Q000494:pharmacology; D012074:Remission Induction; D013194:Staining and Labeling; D016019:Survival Analysis; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D014748:Vinca Alkaloids / Q000008:administration & dosage / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
chemical_list: D000903:Antibiotics, Antineoplastic; D014748:Vinca Alkaloids; D002699:Chlorambucil; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan; D007069:Ifosfamide; D011241:Prednisone; D008775:Methylprednisolone