| 1. |
- Millot, F, et al.
(författare)
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Imatinib mesylate is effective in children with chronic myelogenous leukemia in late chronic and advanced phase and in relapse after stem cell transplantation
- 2006
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 20:2, s. 187-192
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Tidskriftsartikel (refereegranskat)abstract
- A multicentric phase 2 study was conducted to determine the efficiency and the tolerance of imatinib mesylate in children with chronic myelogenous leukemia (CML) in advanced phase of the disease, in relapse after stem cell transplantation, or in case of failure to an interferon a-based regimen. In all, 30 children from eight European countries were enrolled. In 18 children assessable for hematologic response, imatinib mesylate induced complete hematologic response in eight (80%) of the 10 patients included in chronic phase and in six (75%) of eight enrolled in advanced phase of the disease with acceptable toxicity. In 27 patients assessable for cytogenetic response, imatinib mesylate induced disappearance of Philadelphia chromosome-positive bone marrow cells in 12 (60%) of 20 children included in chronic phase and in two (29%) of seven included in advanced phase. A reduction of the bcr-abl/abl ratio to less than 10(-4) was achieved in 11 (50%) of the children included in chronic phase. Estimated 12-month overall survival rate was 95% ( 95% CI, 87-100%) for the patients included in chronic phase and 75% ( 95% CI, 45-100%) for those enrolled in advanced phase. Imatinib mesylate is well tolerated and molecular remission can be achieved in children with CML.
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| 2. |
- Feldman, E. J., et al.
(författare)
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On the use of lonafarnib in myelodysplastic syndrome and chronic myelomonocytic leukemia
- 2008
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 22:9, s. 1707-1711
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Tidskriftsartikel (refereegranskat)abstract
- Lonafarnib is an orally bio-available farnesyltransferase inhibitor that prevents farnesylation of specific target proteins including Ras. In a multicenter study, 67 patients with advanced myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) were treated with a continuous oral dose of 200-300 mg of lonafarnib and were evaluated for hematologic, pathologic and pharmacodynamic response. The median age of patients was 70 years (range 44-86). There were 32 patients with MDS (RAEB-20 and RAEB-t-12) and 35 with CMML. Overall 16 (24%) of the patients responded with two patients achieving a complete remission and one a partial response. Responses were seen in 6/32 and 10/35 patients with MDS and CMML, respectively. Of the 19 patients who were platelet transfusion-dependent prior to treatment, 5 (26%) became transfusion-free for a median duration of 185 days. A decrease in the farnesylation of the HDJ-2 protein measured in patient-derived cells was observed in the majority of patients during treatment with lonafarnib, but no clear correlation between changes in farnesylation and clinical effect could be made. Gastrointestinal toxicity was significant with 19% of patients discontinuing therapy due to diarrhea, nausea and/or anorexia. Lonafarnib has demonstrable activity in patients with advanced MDS and CMML.
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| 3. |
- Hochhaus, A, et al.
(författare)
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Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia.
- 2009
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 23:6, s. 1054-61
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Tidskriftsartikel (refereegranskat)abstract
- Imatinib mesylate is considered standard of care for first-line treatment of chronic phase chronic myeloid leukemia (CML-CP). In the phase III, randomized, open-label International Randomized Study of Interferon vs STI571 (IRIS) trial, previously untreated CML-CP patients were randomized to imatinib (n=553) or interferon-alpha (IFN) plus cytarabine (n=553). This 6-year update focuses on patients randomized to receive imatinib as first-line therapy for newly diagnosed CML-CP. During the sixth year of study treatment, there were no reports of disease progression to accelerated phase (AP) or blast crisis (BC). The toxicity profile was unchanged. The cumulative best complete cytogenetic response (CCyR) rate was 82%; 63% of all patients randomized to receive imatinib and still on study treatment showed CCyR at last assessment. The estimated event-free survival at 6 years was 83%, and the estimated rate of freedom from progression to AP and BC was 93%. The estimated overall survival was 88% -- or 95% when only CML-related deaths were considered. This 6-year update of IRIS underscores the efficacy and safety of imatinib as first-line therapy for patients with CML.
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| 4. |
- Mustjoki, S., et al.
(författare)
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Clonal expansion of T/NK-cells during tyrosine kinase inhibitor dasatinib therapy
- 2009
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 23:8, s. 1398-1405
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Tidskriftsartikel (refereegranskat)abstract
- Dasatinib, a broad-spectrum tyrosine kinase inhibitor (TKI), predominantly targets BCR-ABL and SRC oncoproteins and also inhibits off-target kinases, which may result in unexpected drug responses. We identified 22 patients with marked lymphoproliferation in blood while on dasatinib therapy. Clonality and immunophenotype were analyzed and related clinical information was collected. An abrupt lymphocytosis (peak count range 4-20 x 10(9)/l) with large granular lymphocyte (LGL) morphology was observed after a median of 3 months from the start of therapy and it persisted throughout the therapy. Fifteen patients had a cytotoxic T-cell and seven patients had an NK-cell phenotype. All T-cell expansions were clonal. Adverse effects, such as colitis and pleuritis, were common (18 of 22 patients) and were preceded by LGL lymphocytosis. Accumulation of identical cytotoxic T cells was also detected in pleural effusion and colon biopsy samples. Responses to dasatinib were good and included complete, unexpectedly long-lasting remissions in patients with advanced leukemia. In a phase II clinical study on 46 Philadelphia chromosome-positive acute lymphoblastic leukemia, patients with lymphocytosis had superior survival compared with patients without lymphocytosis. By inhibiting immunoregulatory kinases, dasatinib may induce a reversible state of aberrant immune reactivity associated with good clinical responses and a distinct adverse effect profile. Leukemia (2009) 23, 1398-1405; doi:10.1038/leu.2009.46; published online 19 March 2009
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