Methylprednisolone in advanced chronic lymphocytic leukaemia: rationale for, and effectiveness of treatment suggested by DiSC assay.
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.
Bosanquet
A G
AG
Bath Cancer Research Unit, Royal United Hospital, UK.
McCann
S R
SR
Crotty
G M
GM
Mills
M J
MJ
Catovsky
D
D
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
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