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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
Author(s) -
Coutinho L. H.,
Brereton M. L.,
Santos A. M. W.,
Ryder W. D. J.,
Chang J.,
Harrison C. J.,
Liu Yin J. A.,
Dexter T. M.,
Testa N. G.
Publication year - 1996
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1996.d01-1733.x
Subject(s) - haematopoiesis , bone marrow , clonogenic assay , medicine , myeloid , transplantation , immunology , in vivo , stem cell , gastroenterology , biology , microbiology and biotechnology , genetics
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)‐α ( n = 12). In this study IFN‐α therapy resulted in a significantly higher incidence of patients with detectable Ph − clonogenic cells in the marrow ( P = 0.01) and with ≥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 high‐dose 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 leukaemic burden.