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.
dc.contributor.author | Coutinho, Lucia H | |
dc.contributor.author | Brereton, M L | |
dc.contributor.author | Santos, A M | |
dc.contributor.author | Ryder, W David J | |
dc.contributor.author | Chang, James | |
dc.contributor.author | Harrison, Christine J | |
dc.contributor.author | Yin, J A | |
dc.contributor.author | Dexter, T Michael | |
dc.contributor.author | Testa, Nydia G | |
dc.date.accessioned | 2010-04-06T11:47:39Z | |
dc.date.available | 2010-04-06T11:47:39Z | |
dc.date.issued | 1996-06 | |
dc.identifier.citation | 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. 1996, 93 (4):869-77 Br. J. Haematol. | en |
dc.identifier.issn | 0007-1048 | |
dc.identifier.pmid | 8703819 | |
dc.identifier.doi | 10.1046/j.1365-2141.1996.d01-1733.x | |
dc.identifier.uri | http://hdl.handle.net/10541/95703 | |
dc.description.abstract | 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. | |
dc.language.iso | en | en |
dc.subject | Haematopoiesis | en |
dc.subject | Leukaemia | en |
dc.subject | Cultured Tumour Cells | en |
dc.subject.mesh | Adult | |
dc.subject.mesh | Aged | |
dc.subject.mesh | Aged, 80 and over | |
dc.subject.mesh | Bone Marrow | |
dc.subject.mesh | Female | |
dc.subject.mesh | Hematopoiesis | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Hydroxyurea | |
dc.subject.mesh | Interferon-alpha | |
dc.subject.mesh | Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative | |
dc.subject.mesh | Male | |
dc.subject.mesh | Middle Aged | |
dc.subject.mesh | Tumor Cells, Cultured | |
dc.title | 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. | en |
dc.type | Article | en |
dc.contributor.department | CRC Department of Experimental Haematology, Christie Hospital NHS Trust, Manchester. | en |
dc.identifier.journal | British Journal of Haematology | en |
html.description.abstract | 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. |