| 61. |
- Ellin, Fredrik, et al.
(författare)
-
Central nervous system relapse in peripheral T-cell lymphomas: A Swedish lymphoma registry study.
- 2015
-
Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 126:1, s. 36-41
-
Tidskriftsartikel (refereegranskat)abstract
- Central Nervous System (CNS) relapse in non-Hodgkin lymphomas (NHL) carries a very poor prognosis. Risk factors and outcome have been studied in aggressive B-cell lymphomas but very little is known about the risk in peripheral T-cell lymphoma (PTCL). We aimed at analyzing risk factors for CNS involvement at first relapse or progression, and the outcome of these patients, in a large population-based cohort of PTCL patients. Twenty-eight out of 625 patients (4.5%) developed CNS disease over time. In multivariable analysis disease characteristics at diagnosis independently associated with an increased risk of later CNS involvement were involvement of >1 extranodal site (Hazard Ratio [HR] 2.60, 95% Confidence Interval [95% CI] 1.07-6.29, p=0.035), skin (HR 3.51, 95% CI 1.26-9.74, p=0.016) and gastrointestinal involvement (HR 3.06, 95% CI 1.30-7.18, p=0.010). The outcome of relapsed/refractory patients was very poor and CNS involvement was not associated with a significantly worse outcome compared to relapsed/refractory patients without CNS involvement in multivariable analysis (HR 1.6, 95% CI 0.96-2.6, p=0.074). The results from the present study indicate that CNS relapse in PTCL occurs at a frequency similar to what is seen in aggressive B-cell lymphomas, but the poor outcomes in relapse are largely driven by systemic rather than CNS disease.
|
|
| 62. |
|
|
| 63. |
- Ellin, Fredrik, et al.
(författare)
-
Impact of comorbidity on survival in peripheral T-cell lymphomas : A Swedish Lymphoma Registry study
- 2018
-
Ingår i: Hematological Oncology. - : Wiley. - 0278-0232. ; 36:1, s. 159-165
-
Tidskriftsartikel (refereegranskat)abstract
- Comorbidity impacts survival in B-cell lymphoma patients, but the influence in peripheral T-cell lymphomas (PTCLs) has been little studied. To investigate the impact of comorbidity on outcome in PTCL, we identified adult patients with newly diagnosed PTCL from 2000 to 2009 in the Swedish Lymphoma Registry. Data on comorbidity at diagnosis were retrospectively collected according to the Charlson Comorbidity Index (CCI). Comorbid conditions were present in 263 out of 694 (38%) patients. A CCI score of ≥2 was associated with inferior overall survival (OS) (hazard ratio [HR] 1.63, P < .001) and progression-free survival (HR 1.54, P < .001) in multivariate analysis. In patients undergoing front-line autologous stem cell transplantation (auto SCT), CCI >0 was associated with inferior OS (HR 2.40, P = .013). Chemotherapy regimens were classified as curative or low-intensity treatments. Among patients aged ≥75 years (n = 214), low-intensity and curative treatment groups had similar OS (HR 0.8, P = .6), also when adjusted for CCI. In summary, our results demonstrate CCI to be independently associated with survival in PTCLs. Even limited comorbidity impacted survival after front-line auto SCT, which needs to be considered in treatment decisions. Intensive anthracycline-based chemotherapy in elderly PTCL patients might be of limited benefit.
|
|
| 64. |
- Ellin, Fredrik, et al.
(författare)
-
Real world data on prognostic factors and treatment in peripheral T-cell lymphomas: a study from the Swedish Lymphoma Registry.
- 2014
-
Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 124:10, s. 1570-1577
-
Tidskriftsartikel (refereegranskat)abstract
- Peripheral T-cell Lymphomas (PTCLs) are rare lymphomas with mostly poor outcome with current treatment. Addition of etoposide to CHOP and up-front consolidation with autologous stem cell transplantation (autoSCT) have shown promising results, but have never been tested in randomized trials. As a complement to retrospective analyses of clinical trials, we aimed at analyzing prognostic factors and outcome in an unselected, population-based cohort. Through the Swedish Lymphoma Registry we identified 755 PTCL patients diagnosed during a 10-year period. In addition to International Prognostic Index (IPI) factors, male gender was associated with an adverse overall survival (OS) (HR 1.28, p=0.011) and progression-free survival (PFS) (HR 1.26, p=0.014). In an intention-to-treat analysis in 252 nodal PTCL and EATL patients (excluding ALK-positive ALCL), up-front autoSCT was associated with a superior OS (HR 0.58, p=0.004) and PFS (HR 0.56, p=0.002) compared to patients treated without autoSCT. Addition of etoposide to CHOP resulted in superior PFS in patients up to 60 years (HR 0.49, p=0.008). This study is the largest population-based PTCL cohort reported so far and provides important information on outcome in PTCL outside the setting of clinical trials.
|
|
| 65. |
- Ellin, Fredrik, et al.
(författare)
-
Treatment outcome in T-cell lymphoblastic lymphoma in adults : a population-based study from the Swedish Lymphoma Registry
- 2014
-
Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 53:7, s. 927-934
-
Tidskriftsartikel (refereegranskat)abstract
- Background. T-cell lymphoblastic lymphoma (T-LBL) is a rare neoplasm of precursor lymphoblast origin, for which there is no standard treatment for adults. Results of current treatment strategies in selected populations do exist but are largely unreported for unselected series. Here, we aimed to investigate treatment outcome in a population-based cohort. Material and methods. Patients were identified through the Swedish Lymphoma Registry and data was retrospectively collected for all adult (>= 18 years) Swedish T-LBL patients diagnosed during 2000-2009. Results. A total of 39 patients with median age 40 years (range 18-78) were identified with females being significantly older than males (median age 66 vs. 37, p = 0.027). The five-year overall survival for all patients was 42%. Female gender was associated with shorter survival also when adjusted for treatment strategy and age [hazard ratio (HR) 4.29; p = 0.002]. Thirty patients received intensive chemotherapy, otherwise used for treatment of acute lymphoblastic leukemia (ALL), which resulted in an overall response rate of 97% and a five-year progression-free survival (PFS) of 49%. In this group only CNS involvement at diagnosis predicted shorter PFS (HR 13.3; p = 0.03). Among patients treated with hyper-CVAD the addition of mediastinal irradiation resulted in prolonged time to progression compared to patients receiving only chemotherapy (p = 0.047). The major reason for treatment failure was relapse and in this series 18-fluoro-deoxyglucose positron emission tomography (PET) did not predict this risk. Conclusion. This population-based study indicates that all fit T-LBL patients should be considered for intensive treatment. Our results also suggest a beneficial effect of mediastinal irradiation in combination with hyper-CVAD treatment. Relapsing patients have a dismal outcome irrespective of salvage treatment.
|
|
| 66. |
- Engleson, Jens, et al.
(författare)
-
Midline carcinoma with t(15;19) and BRD4-NUT fusion oncogene in a 30-year-old female with response to docetaxel and radiotherapy
- 2006
-
Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Poorly differentiated midline carcinoma with a translocation between chromosomes 15 and 19, i.e. t(15; 19), has been recognized as a distinct clinical entity for over a decade. This tumor affects young individuals, shows a rapidly fatal clinical course despite intensive therapy. The t( 15; 19) results in the fusion oncogene BRD4-NUT. Information concerning treatment of this rare disorder is scarce. Case presentation: A 30-year-old woman was admitted with a rapidly progressing tumor in the mediastinum, cervical lymph nodes, vertebral column and the epidural space. Pathological, cytogenetic, FISH and PCR analysis revealed a glycogenated carcinoma rarely expressing cytokeratins and showing t( 15; 19) and BRD4-NUT gene rearrangement. The patient was initially treated with a Ewing sarcoma chemotherapy regimen, but had rapid progression after two cycles. She then received docetaxel and radiotherapy, which resulted in almost complete disappearance of the tumor. Conclusion: Docetaxel may be considered for initial chemotherapy in young patients presenting with a midline carcinoma with bone marrow involvement and cytogenetic and molecular genetic finding of a t( 15; 19)/BRD4-NUT-rearrangement. We herein describe, in detail, the laboratory methods by which the BRD4-NUT-rearrangement can be detected.
|
|
| 67. |
- Eskelund, Christian Winther, et al.
(författare)
-
Clonal hematopoiesis evolves from pretreatment clones and stabilizes after end of chemotherapy in patients with MCL
- 2020
-
Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 135:22, s. 2000-2004
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Eskelund et al examined clonal hematopoiesis (CH) in a cohort of patients with mantle cell lymphoma (MCL) treated with first-line chemotherapy and autologous stem cell transplantation. In young, good-risk MCL patients, CH after first-line therapy arises almost entirely from preexisting clones, stabilizes after a period of expansion posttransplantation, and does not negatively impact survival.
|
|
| 68. |
- Eskelund, Christian Winther, et al.
(författare)
-
Detailed Long-Term Follow-Up of Patients Who Relapsed After the Nordic Mantle Cell Lymphoma Trials : MCL2 and MCL3
- 2021
-
Ingår i: HemaSphere. - : Wolters Kluwer. - 2572-9241. ; 5:1
-
Tidskriftsartikel (refereegranskat)abstract
- Mantle cell lymphoma (MCL) is an incurable disease with a highly variable clinical course. The prognosis after relapse is generally poor, and no standard of care exists. We investigated the postrelapse outcomes of 149 patients who were initially treated in the Nordic Lymphoma Group trials, MCL2 or MCL3, both representing intensive cytarabine-containing frontline regimens including autologous stem cell transplant. Patients with progression of disease before 24 months (POD24, n = 51, 34%) displayed a median overall survival of 6.6 months compared with 46 months for patients with later POD (n = 98, 66%; P < 0.001). MCL international prognostic index, cell proliferation marker, blastoid morphology, and TP53 mutations showed independent prognostic value irrespective of POD24, and in a combined, exploratory risk score, patients with 0, 1, 2-3, or 4-5 high-risk markers, respectively, displayed a 5-year overall survival of 62%, 39%, 31%, and 0%. By a comparison of median progression-free survival of the different salvage therapies in the relapse setting, bendamustine-rituximab was superior to all other combination chemotherapy regimens; however, it was also associated with longer responses to last line of therapy. Collectively, we confirm the prognostic impact of POD24 and highlight the relevance of other biomarkers, and we emphasize the importance of novel therapies for patients with high-risk features at first POD.
|
|
| 69. |
|
|
| 70. |
- Eskelund, Christian W., et al.
(författare)
-
TP53 mutations identify younger mantle cell lymphoma patients who do not benefit from intensive chemoimmunotherapy
- 2017
-
Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 130:17, s. 1903-1910
-
Tidskriftsartikel (refereegranskat)abstract
- Despite recent advances in lymphoma treatment, mantle cell lymphoma (MCL) remains incurable, and we are still unable to identify patients who will not benefit from the current standard of care. Here, we explore the prognostic value of recurrent genetic aberrations in diagnostic bone marrow (BM) specimens from 183 younger patients with MCL from the Nordic MCL2 and MCL3 trials, which represent current standard-of-care regimens. In the univariate model, mutations of TP53 (11%) and NOTCH1 (4%), and deletions of TP53 (16%) andCDKN2A(20%),weresignificantly associatedwithinferioroutcomes(togetherwithMIPI, MIPI-c, blastoidmorphology, and Ki67 > 30%); however, inmultivariate analyses, only TP53 mutations (HR, 6.2; P <.0001) retained prognostic impact for overall survival (OS), whereas TP53 mutations (HR, 6.9; P <.0001) andMIPI-c high-risk (HR, 2.6; P5.003) had independent prognostic impact on time to relapse. TP53-mutated cases had a dismal outcome, with a median OS of 1.8 years, and 50% relapsed at 1.0 years, compared to a median OS of 12.7 years for TP53-unmutated cases (P <.0001). TP53 mutations were significantly associated with Ki67 > 30%, blastoid morphology, MIPI high-risk, and inferior responses to both induction- and high-dose chemotherapy. In conclusion, we show that TP53mutations identify a phenotypically distinct and highly aggressive form of MCL with poor or no response to regimens including cytarabine, rituximab, and autologous stem-cell transplant (ASCT). We suggest patients with MCL should be stratified according to TP53 status, and that patients with TP53 mutations should be considered for experimental frontline trials exploring novel agents.
|
|
