| 1. |
- Thörn, Ingrid, et al.
(författare)
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Applicability of IG/TCR gene rearrangements as targets for minimal residual disease assessment in a population-based cohort of Swedish childhood acute lymphoblastic leukaemia diagnosed 2002-2006.
- 2010
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Ingår i: European journal of haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 84:2, s. 117-27
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Tidskriftsartikel (refereegranskat)abstract
- Minimal residual disease (MRD) detection during the early treatment phase has become an important stratification parameter in many childhood acute lymphoblastic leukaemia (ALL) treatment protocols. Here, we aimed to address the applicability of rearranged antigen-receptor genes as potential MRD markers using real-time quantitative polymerase chain reaction (RQ-PCR) in a Swedish population-based cohort. From 334 childhood ALL cases diagnosed during 2002-2006, we analysed 279 diagnostic samples (84%) by screening for rearranged immunoglobulin (IG) and T-cell receptor (TCR) genes. Allele-specific oligonucleotides were designed, and the sensitivity and quantitative level was determined for each target. Overall, clonal IG/TCR rearrangements were detected in 97% (236/244) of B-cell precursor ALL (BCP ALL) and 94% (33/35) of T-ALL. A sensitive RQ-PCR analysis (< or = 10(-4)) was obtained in 89% (216/244) of BCP ALL and in 74% (26/35) of T-ALL, whereas two sensitive targets were only available in 47% (115/244) of BCP ALL and 29% (10/35) of T-ALL cases. With the stratification threshold of > or = 10(-3), which is applied in the current Nordic treatment protocol (NOPHO-ALL 2008) for the identification of high-risk patients, 93% of BCP ALL and 86% of T-ALL reached this quantitative range by at least one target gene. Taken together, this national retrospective study demonstrates that an IG/TCR target for MRD monitoring can be identified in the majority of childhood ALL cases, whereas identification of a second sensitive target gene needs to be improved.
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| 2. |
- Blimark, Cecilie, et al.
(författare)
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Melphalan 100mg/m(2) with stem cell support as first relapse treatment is safe and effective for myeloma patients with long remission after autologous stem cell transplantation.
- 2011
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Ingår i: European journal of haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 87:2, s. 117-22
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Today, a number of therapeutic options are available as the patient with myeloma relapses from initial treatment with high-dose melphalan and autologous stem cell transplantation (ASCT). For patients who experience a durable response to primary ASCT, retreatment with high-dose melphalan is recommended by many current guidelines. Yet, toxicity is an important aspect in the choice of relapse treatment, and a second ASCT in this setting could be associated with enhanced toxicity. As the goal for the treatment for relapsed myeloma should be disease control while maintaining quality of life, lower doses of melphalan might be preferable. Methods and Objectives: In this retrospective study, we account for the outcome of 66 patients with myeloma in first systemic relapse after ASCT, who were treated with intermediate-dose melphalan, 100mg/m(2) , and stem cell support (MEL 100). The aim was to evaluate this treatment in relation to prior response duration after initial ASCT and with respect to response rate, toxicity and survival. Results: The overall response rate was 62%. There was limited, mostly haematological, toxicity, and no treatment-related mortality was observed. The median progression-free survival (PFS) was 8.5months, and the median overall survival was 24months. Patients with time to progression of 34months or more (n=17; ≥75th percentile) after initial ASCT had a median PFS of 12.5months after MEL 100. Conclusion: For patients with a long-lasting response after ASCT, MEL 100 could be a therapeutic option with low toxicity and with efficacy comparable to newer immunomodulatory drugs.
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| 3. |
- Hjorth, Martin, et al.
(författare)
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Thalidomide and dexamethasone vs. bortezomib and dexamethasone for melphalan refractory myeloma: a randomized study.
- 2012
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Ingår i: European journal of haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 88:6, s. 485-496
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: Thalidomide and bortezomib have been frequently used for second-line therapy in patients with myeloma relapsing after or refractory to initial melphalan-based treatment, but no randomized trials have been published comparing these two treatment alternatives. Methods: Thalidomide- and bortezomib-naïve patients with melphalan refractory myeloma were randomly assigned to low-dose thalidomide + dexamethasone (Thal-Dex) or bortezomib + dexamethasone (Bort-Dex). At progression on either therapy, the patients were offered crossover to the alternative drug combination. An estimated 300 patients would be needed for the trial to detect a 50% difference in median PFS between the treatment arms. Results: After inclusion of 131 patients, the trial was prematurely closed because of low accrual. Sixty-seven patients were randomized to Thal-Dex and 64 to Bort-Dex. Progression-free survival was similar (median, 9.0 months for Thal-Dex and 7.2 for Bort-Dex). Response rate was similar (55% for Thal-Dex and 63% for Bort-Dex), but time to response was shorter (P < 0.05) and the VGPR rate higher (P < 0.01) for Bort-Dex. Time-to-other treatment after crossover was similar (median, 13.2 months for Thal-Dex and 11.2 months for Bort-Dex), as was overall survival (22.8 months for Thal-Dex and 19.0 for Bort-Dex). Venous thromboembolism was seen in seven patients and cerebrovascular events in four patients in the Thal-Dex group. Severe neuropathy, reactivation of herpes virus infections, and mental depression were more frequently observed in the Bort-Dex group. In the quality-of-life analysis, no difference was noted for physical function, pain, and global quality of life. Fatigue and sleep disturbances were significantly more prevalent in the Bort-Dex group. Conclusions: Thalidomide (50–100 mg daily) in combination with dexamethasone seems to have an efficacy comparable with that of bortezomib and dexamethasone in melphalan refractory myeloma. However, the statistical strength of the results in this study is limited by the low number of included patients.
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| 4. |
- Jin, Tao, 1973, et al.
(författare)
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Staphylokinase reduces plasmin formation by endogenous plasminogen activators.
- 2008
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Ingår i: European journal of haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 81:1, s. 8-17
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Tidskriftsartikel (refereegranskat)abstract
- Hyperfibrinolysis is a consequence of imbalance between fibrinolytic activators and their inhibitors. Increased levels of circulating plasminogen (Plg) activators such as tissue- or urokinase-type plasminogen activators (tPA or uPA respectively) are the most common causes of hyperfibrinolysis, occasionally causing major hemorrhages. We found that staphylokinase (SAK), a well-known Plg activator of bacterial origin, inhibits Plg activation mediated by endogenous tPA and uPA. Furthermore, mixture of SAK with tPA led to a significantly reduced Plg-dependent fibrinolysis. This inhibitory effect was exerted through direct action of SAK on Plg rather than indirectly on tPA or uPA. Inhibition of Plg activation by SAK is readily abrogated by interaction of SAK with human neutrophil peptides (HNPs). Finally, we show that NH2-terminal residues of SAK are important for the inhibitory effect of SAK on tPA- and uPA-mediated Plg activation. In conclusion, SAK reduces tPA/uPA-mediated Plg activation by means of SAK.Plg complex formation, consequently downregulating tPA/uPA-induced fibrinolysis.
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| 5. |
- Askman, Sandra, et al.
(författare)
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Decreased neutrophil function in newly diagnosed multiple myeloma patients is restored with lenalidomide therapy
- 2024
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Ingår i: EUROPEAN JOURNAL OF HAEMATOLOGY. - 0902-4441 .- 1600-0609. ; 113:1, s. 72-81
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesBacterial infections are common and a major cause of morbidity and mortality in multiple myeloma (MM). We have investigated the function of polymorphonuclear leukocyte (PMN), the immune system's first line of defense against bacteria, in peripheral blood (PB) and bone marrow (BM) samples from patients with newly diagnosed MM (NDMM), smoldering MM (SMM), monoclonal gammopathy of undetermined significance (MGUS) and healthy controls.MethodsPhagocytosis and oxidative burst in PMN cells from patients and healthy donors were investigated using PhagoTest and PhagoBurst assay.ResultsPMN from NDMM, SMM, and MGUS patients had reduced phagocytosis and oxidative burst ability compared with healthy controls. The dysfunction was most prominent in BM samples from MM, SMM, and MGUS patients. Importantly the reduced phagocytosis in MM patients was restored in patients on lenalidomide therapy. Consistently the ability of Escherichia coli stimulated oxidative burst in BM was reduced for the MM, SMM, and MGUS cohort in contrast to the healthy controls and the patients on lenalidomide treatment.ConclusionOur results show that MM patients have neutrophil dysfunction that could contribute to susceptibility for bacterial infections and that lenalidomide therapy was associated with restored PMN function.
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| 6. |
- Blimark, Cecilie, et al.
(författare)
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Outcome data from >10 000 multiple myeloma patients in the Danish and Swedish national registries
- 2022
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 108:2, s. 99-108
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Tidskriftsartikel (refereegranskat)abstract
- Objective We describe real-world evidence (RWE) from the nationwide Swedish and Danish registries that provide important information on incidence and outcome in multiple myeloma (MM). Method First line treatment data on more than 10.000 MM patients from Denmark and Sweden between 2005-2018 are presented. Key results from research conducted within the Swedish and Danish myeloma registries are summarized, describing subgroups of patients with comorbidity, myeloma complications, and early relapse. Results We show that national guidelines, generated on results from randomized clinical trials (RCTs) are rapidly implemented and improve overall survival (OS). We find that both the incidence of MM and the median age at diagnosis is higher in national registries compared to results from referral centres, indicating a more complete coverage. This highlights the need of validation of prognostic scoring systems and indices in e.g., SMM and high-risk MM in a real- world-population. We show that these subgroups are unlikely to be captured in RCTs with narrow inclusion and exclusion criteria, that they have worse survival, and are in need of new treatment approaches. Conclusion National registries that include all MM patients are an important source of knowledge on epidemiology, treatment and outcome with implications for the planning of MM care. Despite the introduction of new and better treatments, rapidly implemented in our countries, our registries uncover subgroups of patients that still have inferior outcome. Our RWE can help to identify important research questions to be studied in further clinical trials also in patients currently not included in RCTs.
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| 7. |
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| 8. |
- Langabeer, Stephen E, et al.
(författare)
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Molecular diagnostics of myeloproliferative neoplasms (MPN).
- 2015
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Ingår i: European journal of haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 95:4, s. 270-279
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Forskningsöversikt (refereegranskat)abstract
- Since the discovery of the JAK2 V617F mutation in the majority of the myeloproliferative neoplasms (MPN) of polycythemia vera, essential thrombocythemia and primary myelofibrosis ten years ago, further MPN-specific mutational events, notably in JAK2 exon 12, MPL exon 10 and CALR exon 9 have been identified. These discoveries have been rapidly incorporated into evolving molecular diagnostic algorithms. While many of these mutations appear to have prognostic implications, establishing MPN diagnosis is of immediate clinical importance with selection, implementation and the continual evaluation of the appropriate laboratory methodology to achieve this diagnosis similarly vital. The advantages and limitations of these approaches in identifying and quantitating the common MPN-associated mutations is considered herein with particular regard to their clinical utility. The evolution of molecular diagnostic applications and platforms has occurred in parallel with the discovery of MPN-associated mutations and it therefore appears likely that emerging technologies such as next-generation sequencing and digital PCR will in the future, play an increasing role in the molecular diagnosis of MPN. This article is protected by copyright. All rights reserved.
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| 9. |
- Lindgren, Marie, 1971, et al.
(författare)
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Survival and risk of vascular complications in myelofibrosis—A population-based study from the Swedish MPN group
- 2022
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 109:4, s. 336-342
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To gain knowledge of underlying risk factors for vascular complications and their impact on life expectancy in myelofibrosis. Methods: From a cohort of 392 myelofibrosis patients registered in the Swedish MPN registry 58 patients with vascular complications during follow-up were identified. Patients with vascular complications were compared with both 1:1 matched controls and the entire myelofibrosis cohort to explore potential risk factors for vascular complications and their impact on survival. Results: Incidence of vascular complications was 2.8 events per 100 patient-years and the majority of complications were thrombotic. Patients with complications were significantly older and had lower hemoglobin when compared to the entire cohort. In the case–control analysis, no significant risk factor differences were observed. The major cause of death was vascular complications and median survival was significantly impaired in patients with vascular complications (48 months) compared to controls (92 months). Inferior survival in patients with vascular complications was found to be dependent on IPSS risk category in a Cox regression model. Conclusion: Vascular complications have a considerable impact on survival in MF. At diagnosis, risk assessment by IPSS does not only predict survival but is also associated with the risk of vascular complications.
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| 10. |
- Lund, Johan, et al.
(författare)
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Addition of thalidomide to melphalan and prednisone treatment prolongs survival in multiple myeloma - a retrospective population based study of 1162 patients.
- 2014
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Ingår i: European journal of haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 92:1, s. 19-25
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Tidskriftsartikel (refereegranskat)abstract
- The combination of melphalan and prednisone (MP) has been the standard treatment of multiple myeloma (MM). Since the introduction of novel agents, the clinical outcome in MM has improved. Several prospective studies with thalidomide combined with MP (MPT) compared to MP have been performed, most of them showing that MPT gives a better response rate and median overall survival (OS). Among 1843 MM patients admitted to 15 Swedish centres, we selected all patients treated with MP and MPT in 1(st) , 2(nd) , 3(rd) or 4(th) line of therapy, in total 888 patients treated with MP and 274 with MPT. Patients were evaluated for response rate, OS and TTNT. Multivariate Cox model analysis was made to adjust for different criteria at time for MM-diagnosis. The median OS from beginning of 1(st) line of treatment was 2.2/4.2 years after MP/MPT respectively, and in 2(nd) , 3(rd) and 4(th) line of treatment 1.8/2.9, 1.4/1.6 and 1.1/1.9 years (P<0.0001, 0.003, 0.74 and 0.235). The relative risk for death in the MPT group vs. the MP group was 0.61 (95% CI: 0.45-0.84) in 1(st) and 0.55 (0.38-0.83), p<0.01) in 2(nd) line. Treatment with MPT gave a significantly better overall survival rate after both 1(st) and 2(nd) line of therapy compared to treatment with MP only. This article is protected by copyright. All rights reserved.
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