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Evaluation of cytogenetic conversion to Ph- haemopoiesis in long-term bone marrow culture for patients with chronic myeloid leukaemia on conventional hydroxyurea therapy, on pulse high-dose hydroxyurea and on interferon-alpha

Lookup NU author(s): Professor Christine Harrison FRCPath FMedSci


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Long-term bone marrow culture (LTBMC) has been used successfully in autologous transplantation in chronic myeloid leukaemia (CML). However, variation between patients in the recovery of Ph- cells in culture limits the application of this procedure to a minority. Treatment that effectively reduces in vivo tumour burden prior to initiation of LTBMC may improve the selection of Ph- cells in culture. To test this hypothesis we evaluated the frequency and degree of cytogenetic conversion to Ph- haemopoiesis in LTBMC from four independent groups of CML patients: Untreated (n = 19); conventional dosage of hydroxyurea (HU) (n = 10); pulse high-dose HU (P-HU) (n = 22) and interferon (IFN)-alpha (n = 12). In this study IFN-alpha therapy resulted in a significantly higher incidence of patients with detectable Ph- clonogenic cells in the marrow (P = 0.01) and with > or = 50% Ph- haemopoiesis in LTBMC as compared to newly diagnosed patients (P = 0.05). Also, sequential culture studies undertaken in 14 CML patients at diagnosis and following the start of pulse highdose HU therapy showed that in eight patients the average proportion of Ph- metaphases detected in LTBMC substantially increased from 1.7% (range 0-7) at diagnosis to levels of 71% (range 14-100) after treatment. Therefore we conclude that the use of IFN or pulse high-dose HU in early stage disease appears to create an opportunity to harvest the marrow for long-term culture (LTC) purging with reduced leukaaemic burden.

Publication metadata

Author(s): Coutinho LH, Brereton ML, Santos AM, Ryder WD, Chang J, Harrison CJ, Yin JA, Dexter TM, Testa NG

Publication type: Article

Publication status: Published

Journal: British Journal of Haematology

Year: 1996

Volume: 93

Issue: 4

Pages: 869-877

Print publication date: 01/06/1996

ISSN (print): 0007-1048

ISSN (electronic): 1365-2141

Publisher: Wiley-Blackwell Publishing Ltd.


DOI: 10.1046/j.1365-2141.1996.d01-1733.x

Notes: Journal Article Research Support, Non-U.S. Gov't England


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