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- Koskenvesa, Perttu, et al.
(author)
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Imatinib and pegylated IFN-alpha 2b discontinuation in first-line chronic myeloid leukemia patients following a major molecular response
- 2014
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In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 92:5, s. 413-420
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Journal article (peer-reviewed)abstract
- Objectives Previous studies indicate that 40-50% of patients with chronic myeloid leukemia in prolonged complete molecular remission may discontinue imatinib therapy without imminent relapse. The combination of pegylated interferon-alpha (Peg-IFN-alpha 2b) and imatinib may increase the rate of successful discontinuation. Methods In this pilot study, we prospectively stopped imatinib from patients (n=12) who had achieved major molecular response (MMR) after >= 12months of treatment with either imatinib or imatinib+Peg-IFN-alpha 2b. Molecular monitoring was carried out monthly for BCR-ABL1. In addition, analyses of lymphocyte immunophenotype, function, and plasma cytokines were performed. Results In the monotherapy group, 5/6 patients lost MMR within 4months. One patient remains to date in MR4.0 61months after discontinuation. In the combination therapy group, 2/6 patients relapsed within 4months while still receiving Peg-IFN-alpha 2b. Four of six patients were able to discontinue both treatments, but three of these patients relapsed after 3months. One patient is still in sustained MR4.0 at 58months off all treatment. All relapsed patients re-responded to imatinib. The two successfully discontinued patients had either an increased number of NK-cells or functionally active T-cells. Conclusions A higher frequency of relapsed patients in our study in comparison with other studies may be due to the shorter duration of imatinib treatment prior to discontinuation. However, in selected patients with an active immune system, even a short duration of TKI therapy (<2yr) may allow for therapy discontinuation but this needs to be confirmed in larger prospective studies.
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| 2. |
- Kreutzman, Anna, et al.
(author)
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Killer-cell immunoglobulin-like receptor gene profile predicts good molecular response to dasatinib therapy in chronic myeloid leukemia
- 2012
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In: Experimental Hematology. - : Elsevier BV. - 1873-2399 .- 0301-472X. ; 40:11, s. 906-913
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Journal article (peer-reviewed)abstract
- Tyrosine kinase inhibitors have greatly improved the prognosis of chronic myeloid leukemia (CML). In addition to direct kinase inhibition, their effects can also be mediated through immune modulation, such as expansion of cytotoxic T and natural-killer cells observed during dasatinib therapy. As natural-killer cell and partially CD8(+) T-cell function are regulated by killer immunoglobulin-like receptors (KIRs), we studied whether the KIR gene profile is associated with clinical therapy response in dasatinib-treated CML patients (n = 191). In first-line patients, the absence of the inhibitory KIR2DL5A (p = 0.0489), 2DL5B (p = 0.030), and 2DL5all (p = 0.0272) genes were associated with improved molecular response at the 12-month time point. In addition, the same trend was seen with two activating KIR genes, 2DS1 (p = 0.061) and 2DS2 (p = 0.071). Furthermore, when patients were clustered into two groups by their KIR gene profile, the BCR-ABL1 transcript levels differed significantly between the groups (p = 0.047), showing that patients who lacked several KIR genes had better response. The comparison of first-line and second-line patients did not show any significant differences in either KIR or human leukocyte antigen genotypes. Our results show that immunogenetic factors, such as the KIR gene profile, can play a role in tyrosine kinase inhibitor therapy response. Additional studies are warranted to elucidate the functional significance of KIR genes associated with treatment outcomes. (C) 2012 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.
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| 4. |
- Sandart, Amelie, et al.
(author)
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Pattern and Prevalence of Liver Involvement in Pediatric Acute Lymphoblastic and Myeloid Leukemia at Diagnosis
- 2021
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In: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - 0277-2116 .- 1536-4801. ; 73:5, s. 630-635
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Journal article (peer-reviewed)abstract
- Objectives: The prevalence and significance of liver involvement at diagnosis was studied in pediatric acute lymphoblastic (ALL) and myeloid leukemia (AML).Methods: A population based cohort of 122 pre B-ALL, 22 T-ALL and 45 AML patients was formed from the Nordic Society of Pediatric Hematology and Oncology leukemia registries (years 2005-2017). Hepatomegaly, elevated alanine aminotransferase, high INR, hypoalbuminemia and conjugated hyperbilirubinemia at diagnosis were used as markers for liver involvement. Minimal residual disease (MRD), time to relapse and overall survival (OS) were correlated with liver involvements.Results: The pattern of liver involvement was significantly different between leukemia subtypes (P = 0.025). The proportion of patients without liver abnormalities was 50.0% in AML and 44.8% in pre B-ALL and 23.5% in T-ALL patients. Hepatomegaly characterized lymphatic leukemia being present in 41.8% and 58.8% of pre B- and T-ALL patients. Liver dysfunction was most common in AML (29.5%) and least frequent in pre B-ALL (7.4%,) (P = 0.001). Conjugated hyperbilirubinemia was present in less than 5% of patients. Hepatomegaly correlated positively with age in pre B-ALL (P = 0.036) and white blood cell count (WBC) in AML (P = 0.010). Hepatic dysfunction was related with high WBC in pre B-ALL (P = 0.037) and AML (P = 0.001). Liver involvement in patients with ALL was not associated with toxicity or outcome. Patients with AML without liver involvement demonstrated superior OS.Conclusions: Liver involvement is frequent at diagnosis in pediatric leukemia and its prevalence is related with leukemia subtype, age and WBC. In AML, but not in ALL, it associates with suboptimal prognosis.
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