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- Höglund, M., et al.
(author)
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Dose-dependent mobilisation of haematopoietic progenitor cells in healthy volunteers receiving glycosylated rHuG-CSF
- 1996
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In: Bone Marrow Transplantation. - 0268-3369 .- 1476-5365. ; 18:1, s. 19-27
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Journal article (peer-reviewed)abstract
- In an attempt to optimise the dose of G-CSF for mobilisation of PBPC in allogeneic donors, four groups of six healthy male volunteers received lenograstim (glycosylated rHuG-CSF) at a dose of 3, 5, 7.5 or 10 micrograms/kg/day, respectively, for 6 days (days 1-6). All subjects underwent a 10 I leukapheresis. Lenograstim was well tolerated. Maximal mobilisation was observed on days 5 or 6, with a clear dose-response for all progenitor cell types (CD34+, CFU-GM, BFU-E, CFU-mix). The peak numbers of CD34+ cells/microlitre (mean, s.e.m.) were 30 +/- 5, 49 +/- 8, 44 +/- 5 and 122 +/- 30 in the 3, 5, 7.5 and 10 micrograms/kg groups, respectively. A good correlation was observed between the number of CD34+ cells in blood and leukapheresis product (LP), respectively. Increasing the dose of lenograstim did not increase the number of T cells in the LP. A comparison of LP and steady state BM CD34+ cells in paired samples from each individual, showed a higher proportion of primitive immunophenotypes (CDw90+, HLA-DR-, CD45RA-, CD33-) among LP CD34+ cells. We conclude that increased doses of G-CSF improve the mobilisation of PBPC, and that G-CSF favours mobilisation of primitive CD34+ cell subsets. Lenograstim 10 micrograms/kg/day for 6 days should provide a sufficiently effective mobilisation of PBPC in most healthy PBPC donors.
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- Höglund, M., et al.
(author)
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Mobilization of CD34+ cells by glycosylated and nonglycosylated G-CSF in healthy volunteers : a comparative study
- 1997
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In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 59:3, s. 177-183
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Journal article (peer-reviewed)abstract
- In vitro studies indicate that lenograstim (glycosylated G-CSF) is more potent than filgrastim (nonglycosylated G-CSF) on a weight for weight basis. However, such a difference has not yet been shown in vivo. The primary objective of this trial was to compare the efficacy of equivalent doses (microgram) of lenograstim and filgrastim in mobilizing CD34+ cells. Thirty-two healthy male volunteers, median age 27 yr (19-44 yr), were randomized to receive either lenograstim 10 micrograms/kg followed by filgrastim 10 micrograms/kg or vice versa with a washout period of a minimum 4 wk. Both drugs were administered as s.c. injections once daily for 5 d (d 1-5). CD34+ cells were mobilized with a similar kinetics, peaking at median d 6 (5-6) for both drugs. A significant difference in favour of lenograstim was shown for peak number of CD34+ cells/microliter blood (104 +/- 38 vs. 82 +/- 35, mean +/- 1 SD, p < 0.0001, paired t-test, n = 30) and number of CFU-GM/microliter blood at d 6 (14.6 +/- 8.4 vs. 10.2 +/- 4.6, p < 0.0001), respectively. There was no difference in the d 6 number of CD3+ cells. Both drugs were generally well tolerated and did not differ with respect to number of adverse events. In conclusion, lenograstim 10 micrograms/kg/d mobilizes PBPC more efficiently than the identical dose of filgrastim, indicating a difference in in vivo potency between the two G-CSFs.
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- Baccarani, Michele, et al.
(author)
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Chronic myeloid leukemia : an update of concepts and management recommendations of European LeukemiaNet
- 2009
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In: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 27:35, s. 6041-6051
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Research review (peer-reviewed)abstract
- PURPOSE: To review and update the European LeukemiaNet (ELN) recommendations for the management of chronic myeloid leukemia with imatinib and second-generation tyrosine kinase inhibitors (TKIs), including monitoring, response definition, and first- and second-line therapy. METHODS: These recommendations are based on a critical and comprehensive review of the relevant papers up to February 2009 and the results of four consensus conferences held by the panel of experts appointed by ELN in 2008. RESULTS: Cytogenetic monitoring was required at 3, 6, 12, and 18 months. Molecular monitoring was required every 3 months. On the basis of the degree and the timing of hematologic, cytogenetic, and molecular results, the response to first-line imatinib was defined as optimal, suboptimal, or failure, and the response to second-generation TKIs was defined as suboptimal or failure. CONCLUSION: Initial treatment was confirmed as imatinib 400 mg daily. Imatinib should be continued indefinitely in optimal responders. Suboptimal responders may continue on imatinb, at the same or higher dose, or may be eligible for investigational therapy with second-generation TKIs. In instances of imatinib failure, second-generation TKIs are recommended, followed by allogeneic hematopoietic stem-cell transplantation only in instances of failure and, sometimes, suboptimal response, depending on transplantation risk.
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- Baccarani, Michele, et al.
(author)
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Comparison of imatinib 400 mg and 800 mg daily in the front-line treatment of high-risk, Philadelphia-positive chronic myeloid leukemia : a European LeukemiaNet Study
- 2009
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 113:19, s. 4497-4504
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Journal article (peer-reviewed)abstract
- Imatinib mesylate (IM), 400 mg daily, is the standard treatment of Philadelphia-positive (Ph(+)) chronic myeloid leukemia (CML). Preclinical data and results of single-arm studies raised the suggestion that better results could be achieved with a higher dose. To investigate whether the systematic use of a higher dose of IM could lead to better results, 216 patients with Ph(+) CML at high risk (HR) according to the Sokal index were randomly assigned to receive IM 800 mg or 400 mg daily, as front-line therapy, for at least 1 year. The CCgR rate at 1 year was 64% and 58% for the high-dose arm and for the standard-dose arm, respectively (P = .435). No differences were detectable in the CgR at 3 and 6 months, in the molecular response rate at any time, as well as in the rate of other events. Twenty-four (94%) of 25 patients who could tolerate the full 800-mg dose achieved a CCgR, and only 4 (23%) of 17 patients who could tolerate less than 350 mg achieved a CCgR. This study does not support the extensive use of high-dose IM (800 mg daily) front-line in all CML HR patients. This trial was registered at www.clinicaltrials.gov as #NCT00514488.
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