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1. The CNS relapse in T-cell lymphoma index predicts CNS relapse in patients with T- and NK-cell lymphomas

Author

Bhansali, Rahul S., Ellin, Fredrik, Relander, Thomas, Cao, Miao, Li, Wenrui, Long, Qi, Ganesan, Nivetha, Stuver, Robert, Horwitz, Steven M., Wudhikarn, Kitsada, Hwang, Steven R., Bennani, N. Nora, Chavez, Julio, Sokol, Lubomir, Saeed, Hayder, Duan, Frank, Porcu, Pierluigi, Pullarkat, Priyanka, Mehta-Shah, Neha, Zain, Jasmine M., Ruiz, Miguel, Brammer, Jonathan E., Prakash, Rishab, Iyer, Swaminathan P., Olszewski, Adam J., Major, Ajay, Riedell, Peter A., Smith, Sonali M., Goldin, Caroline, Haverkos, Bradley, Hu, Bei, Zhuang, Tony Z., Allen, Pamela B., Toama, Wael, Janakiram, Murali, Brooks, Taylor R., Jagadeesh, Deepa, Hariharan, Nisha, Goodman, Aaron M., Hartman, Gabrielle, Ghione, Paola, Fayyaz, Fatima, Rhodes, Joanna M., Chong, Elise A., Gerson, James N., Landsburg, Daniel J., Nasta, Sunita D., Schuster, Stephen J., Svoboda, Jakub, Jerkeman, Mats, and Barta, Stefan K.

Published
2024
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2. Impact of comorbidity in elderly patients with peripheral T-cell lymphoma: an international retrospective analysis of 891 patients

Author

Mead, Monica, Cederleuf, Henrik, Björklund, Maja, Wang, Xiaoyan, Relander, Thomas, Jerkeman, Mats, Gaut, Daria, Larson, Sarah, and Ellin, Fredrik

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Oncology and Carcinogenesis, Cancer, Clinical Research, Lymphoma, Aging, Rare Diseases, Hematology, Aged, Cohort Studies, Comorbidity, Humans, Lymphoma, T-Cell, Peripheral, Retrospective Studies, Cardiovascular medicine and haematology
Abstract

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive neoplasms with poor outcomes, commonly affecting older patients with comorbidities. This study aims to describe outcomes of older patients with PTCL in a large international cohort. Patients aged ≥70 years with PTCL diagnosed from 1 January 2010 to 31 December 2015 in the Swedish Lymphoma Registry (SLR) and California Cancer Registry (CCR) were identified. Data on comorbidity were retrospectively collected according to the Charlson Comorbidity Index (CCI), and clinical outcomes were extracted. A total of 891 patients were included (SLR, n = 173; CCR, n = 718). Median age was 77 (SLR) and 78 (CCR) years. Included subtypes were as follows: angioimmunoblastic T-cell lymphoma, n = 226; anaplastic large-cell lymphoma, n = 122; enteropathy-associated T-cell lymphoma (EATL), n = 31; hepatosplenic TCL, n = 7; natural killer-/T-cell lymphoma, n = 62; PTCL not otherwise specified, n = 443. CCI data were available in 775 patients (87%), and CCI scores were divided into the groups CCI = 0 (39%), CCI = 1 (22%), and CCI > 1 (39%). Median age did not differ among the CCI groups (P = .72). Patients with a CCI > 1 had a worse median overall survival (4.4 months) compared with patients with CCI = 0 (11.9 months) and CCI = 1 (8.4 months; P < .001). Comorbidity and advancing age in as little as 5-year increments are important adverse factors in this group. Most patients died of lymphoma within a year from diagnosis, underscoring the importance of developing new treatments.

Published
2022

6. Idelalisib (PI3Kδ inhibitor) therapy for patients with relapsed/refractory chronic lymphocytic leukemia: A Swedish nation-wide real-world report on consecutively identified patients.

Author

Mattsson, Agnes, Sylvan, Sandra Eketorp, Axelsson, Per, Ellin, Fredrik, Kjellander, Christian, Larsson, Karin, Lauri, Birgitta, Lewerin, Catharina, Scharenberg, Christian, Tätting, Love, Johansson, Hemming, Österborg, Anders, and Hansson, Lotta

Subjects
CHRONIC lymphocytic leukemia, FLUDARABINE, CHRONIC leukemia, PATIENT experience, PROGRESSION-free survival, SALVAGE therapy
Abstract

Objectives: We examined the efficacy and toxicity of the PI3Kδ inhibitor idelalisib in combination with rituximab salvage therapy in consecutively identified Swedish patients with chronic lymphocytic leukemia (CLL). Methods and Results: Thirty-seven patients with relapsed/refractory disease were included. The median number of prior lines of therapy was 3 (range 1-11); the median age was 69 years (range 50-89); 22% had Cumulative Illness Rating Scale (CIRS) >6 and 51% had del(17p)/TP53 mutation. The overall response rate was 65% (all but one was partial response [PR]). The median duration of therapy was 9.8 months (range 0.9-44.8). The median progression-free survival was 16.4 months (95% CI: 10.4-26.3) and median overall survival had not been reached (75% remained alive at 24 months of follow-up). The most common reason for cessation of therapy was colitis (n = 8, of which seven patients experienced grade ≥3 colitis). The most common serious adverse event was grade ≥3 infection, which occurred in 24 patients (65%). Conclusions: Our real-world results suggest that idelalisib is an effective and relatively safe treatment for patients with advanced-stage CLL when no other therapies exist. Alternative dosing regimens and new PI3K inhibitors should be explored, particularly in patients who are double-refractory to inhibitors of BTK and Bcl-2. [ABSTRACT FROM AUTHOR]

Published
2023
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7. Nationwide Assessment of Patient Trajectories in Mantle Cell Lymphoma : The Swedish MCLcomplete Project

Author

Jerkeman, Mats, Ekberg, Sara, Glimelius, Ingrid, Albertsson-Lindblad, Alexandra, Entrop, Joshua P., Ellin, Fredrik, Sonnevi, Kristina, Lewerin, Catharina, Brandefors, Lena, Smedby, Karin E., Jerkeman, Mats, Ekberg, Sara, Glimelius, Ingrid, Albertsson-Lindblad, Alexandra, Entrop, Joshua P., Ellin, Fredrik, Sonnevi, Kristina, Lewerin, Catharina, Brandefors, Lena, and Smedby, Karin E.

Abstract

Mantle cell lymphoma (MCL) is a B-cell malignancy currently considered incurable. Although some patients obtain prolonged remission after first-line chemoimmunotherapy, many will need several treatment lines. Here, we present a nationwide assessment of treatment strategies, time to progression and survival in MCL. All patients diagnosed with MCL 2006-2018 were identified in the Swedish Lymphoma Register. Information on all lines of therapy was extracted from the medical records. Overall and progression-free survival (OS and PFS) were assessed through August 2021. In total, 1367 patients were included (median age, 71 years) and median follow-up was 6.8 years. Two hundred and one (15%) were managed initially with watch-and-wait, but 1235 (90%) eventually received treatment. The most frequently used first-line regimens were rituximab-bendamustine (BR) (n = 368; 30%) and Nordic MCL2 (n = 342; 28%). During follow-up, 630 patients (46%) experienced relapse/progression and 546 (40%) received second-line treatment. The most frequently used second-line regimen was BR (n = 185; 34%) but otherwise a wide variety of second-line treatments were used. Further, 382 and 228 patients experienced a second or third relapse/progression, respectively. Median PFS after first (PFS-1), second (PFS-2), third (PFS-3), and fourth (PFS-4) treatment lines was 29.4, 8.9, 4.3, and 2.7 months. Patients with early progression, defined as a PFS-1 <24 months, had an inferior median OS of 13 versus 37 months in patients with later relapse. For patients treated with frontline BR, however, time to relapse had no impact on later outcome. By use of nationwide population-based data, we provide important benchmarks for future studies of all treatment lines in MCL.

Published
2023
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8. Idelalisib (PI3K delta inhibitor) therapy for patients with relapsed/refractory chronic lymphocytic leukemia: A Swedish nation-wide real-world report on consecutively identified patients

Author

Mattsson, Agnes, Sylvan, Sandra Eketorp, Axelsson, Per, Ellin, Fredrik, Kjellander, Christian, Larsson, Karin, Lauri, Birgitta, Lewerin, Catharina, Scharenberg, Christian, Tätting, Love, Johansson, Hemming, Osterborg, Anders, Hansson, Lotta, Mattsson, Agnes, Sylvan, Sandra Eketorp, Axelsson, Per, Ellin, Fredrik, Kjellander, Christian, Larsson, Karin, Lauri, Birgitta, Lewerin, Catharina, Scharenberg, Christian, Tätting, Love, Johansson, Hemming, Osterborg, Anders, and Hansson, Lotta

Abstract

Objectives: We examined the efficacy and toxicity of the PI3K delta inhibitor idelalisib in combination with rituximab salvage therapy in consecutively identified Swedish patients with chronic lymphocytic leukemia (CLL). Methods and Results: Thirty-seven patients with relapsed/refractory disease were included. The median number of prior lines of therapy was 3 (range 1-11); the median age was 69 years (range 50-89); 22% had Cumulative Illness Rating Scale (CIRS) >6 and 51% had del(17p)/TP53 mutation. The overall response rate was 65% (all but one was partial response [PR]). The median duration of therapy was 9.8 months (range 0.9-44.8). The median progression-free survival was 16.4 months (95% CI: 10.4-26.3) and median overall survival had not been reached (75% remained alive at 24 months of follow-up). The most common reason for cessation of therapy was colitis (n = 8, of which seven patients experienced grade =3 colitis). The most common serious adverse event was grade =3 infection, which occurred in 24 patients (65%). Conclusions: Our real-world results suggest that idelalisib is an effective and relatively safe treatment for patients with advanced-stage CLL when no other therapies exist. Alternative dosing regimens and new PI3K inhibitors should be explored, particularly in patients who are double-refractory to inhibitors of BTK and Bcl-2., Funding Agencies|AFA Forsakring [130054]; Cancer Society in Stockholm; Felix Mindus Foundation; Gilead Sciences Nordic Fellowship Program; Insamlingsstiftelsen Cancer- och Allergifonden; Karolinska Institutet Foundations; King Gustaf V Jubilee Fund; Senior Clinical Research Position (SLL/KI) [K2894-2016]; Stockholm County Council (SLL/ALF) [20150070]; Swedish Cancer Society [150930, 160534]

Published
2023
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9. Outcome of limited-stage peripheral T-Cell lymphoma after CHOP(−like) therapy:A population based study of 239 patients from the Nordic lymphoma epidemiology group

Author

Ludvigsen Al-Mashhadi, Ahmed, Cederleuf, Henrik, Kuhr Jensen, Rasmus, Holm Nielsen, Torsten, Bjerregård Pedersen, Martin, Bech Mortensen, Thomas, Relander, Thomas, Jerkeman, Mats, Gang, Anne Ortved, Kristensen, Anne Louise, Roost Clausen, Michael, Brown, Peter de Nully, Tang Severinsen, Marianne, Jakobsen, Lasse Hjort, Ellin, Fredrik, El-Galaly, Tarec Christoffer, Ludvigsen Al-Mashhadi, Ahmed, Cederleuf, Henrik, Kuhr Jensen, Rasmus, Holm Nielsen, Torsten, Bjerregård Pedersen, Martin, Bech Mortensen, Thomas, Relander, Thomas, Jerkeman, Mats, Gang, Anne Ortved, Kristensen, Anne Louise, Roost Clausen, Michael, Brown, Peter de Nully, Tang Severinsen, Marianne, Jakobsen, Lasse Hjort, Ellin, Fredrik, and El-Galaly, Tarec Christoffer

Abstract

Peripheral T-Cell Lymphomas (PTCLs) are rare, aggressive lymphomas with poor outcomes, but limited-stage disease is infrequent and not well-described. This study reports outcomes and prognostic factors in limited-stage nodal PTCLs in a binational population-based setting. Patients were identified from the Danish and Swedish lymphoma registries. Adults diagnosed with limited-stage nodal PTCL (stage I-II) and treated with CHOP(−like) therapy ±radiotherapy between 2000 and 2014 were included. Medical records were reviewed by local investigators. A total of 239 patients with a median age of 62 years were included; 67% received 6–8 cycles of CHOP(−like) therapy and 22% received 3–4 cycles, of which 59% also received radiotherapy. Autologous stem cell transplant consolidation was administered to 16% of all patients. Median follow-up was 127 months with 5-years overall survival (OS) of 58% (95% CI: 53–65) and progression-free survival (PFS) of 53% (95% CI: 47–59). In multivariable analysis, age ≥ 60 years and B-symptoms were unfavorable and ALK+ anaplastic large cell T-Cell lymphoma was favorable for survival outcomes. There was no difference in treatment-specific outcome (3–4 cycles vs. 6–8 cycles of CHOP(−like) ± radiotherapy). Low-risk patients (age < 60 without B-symptoms) had a 5-year OS of 77% (95% CI 67–89%). In the present study of limited-stage nodal PTCL, survival after curative intent chemotherapy +/− radiotherapy was inferior to that of limited-stage diffuse large B-cell lymphoma, but a subgroup of young patients without B-symptoms had very good outcomes. Treatment outcomes after 3–4 cycles versus 6–8 cycles of CHOP(−like) therapy were comparable.

Published
2023

10. Outcome of limited‐stage peripheral T‐Cell lymphoma after CHOP (−like) therapy: A population based study of 239 patients from the Nordic lymphoma epidemiology group

Author

Ludvigsen Al‐Mashhadi, Ahmed, primary, Cederleuf, Henrik, additional, Kuhr Jensen, Rasmus, additional, Holm Nielsen, Torsten, additional, Bjerregård Pedersen, Martin, additional, Bech Mortensen, Thomas, additional, Relander, Thomas, additional, Jerkeman, Mats, additional, Ortved Gang, Anne, additional, Kristensen, Anne Louise, additional, Roost Clausen, Michael, additional, de Nully Brown, Peter, additional, Tang Severinsen, Marianne, additional, Jakobsen, Lasse Hjort, additional, Ellin, Fredrik, additional, and El‐Galaly, Tarec Christoffer, additional

Published
2023
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12. Long-Term Follow-up of Clinical Outcome Determinants and Correlative Biological Features from the Nordic NLG-T-01 Trial

Author

Relander, Thomas, primary, Pedersen, Martin Bjerregård, additional, Ellin, Fredrik, additional, Lauritzsen, Grete Fossum, additional, Jantunen, Esa, additional, Hagberg, Hans, additional, Holte, Harald, additional, Österborg, Anders, additional, Brown, Peter De Nully, additional, Kuittinen, Outi, additional, Erlanson, Martin, additional, Ostenstad, Bjorn, additional, Fagerli, Unn-Merete, additional, Delabie, Jan, additional, Sundström, Christer, additional, Sander, Birgitta, additional, Hamilton-Dutoit, Stephen, additional, Ehinger, Mats, additional, Liestol, Knut, additional, Toldbod, Helle, additional, Feldman, Andrew L., additional, and d'Amore, Francesco Annibale, additional

Published
2022
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13. CNS Relapse in T-Cell Lymphoma Index: A Risk Score to Predict Central Nervous System Relapse in Patients with T-Cell Lymphomas

Author

Bhansali, Rahul S., primary, Ellin, Fredrik, additional, Cao, Miao, additional, Relander, Thomas, additional, Li, Wenrui, additional, Long, Qi, additional, Ganesan, Nivetha, additional, Stuver, Robert, additional, Horwitz, Steven M., additional, Wudhikarn, Kitsada, additional, Hwang, Steven R, additional, Bennani, N. Nora, additional, Chavez, Julio C., additional, Sokol, Lubomir, additional, Saeed, Hayder, additional, Duan, Frank, additional, Porcu, Pierluigi, additional, Pullarkat, Priyanka, additional, Mehta-Shah, Neha, additional, Zain, Jasmine, additional, Ruiz, Miguel, additional, Brammer, Jonathan E, additional, Prakash, Rishab, additional, Iyer, Swami P., additional, Olszewski, Adam J., additional, Major, Ajay, additional, Smith, Sonali M., additional, Riedell, Peter A., additional, Goldin, Caroline, additional, Haverkos, Bradley M., additional, Hu, Bei, additional, Allen, Pamela B., additional, Toama, Wael, additional, Janakiram, Murali, additional, Brooks, Taylor, additional, Jagadeesh, Deepa, additional, Hariharan, Nisha, additional, Goodman, Aaron M, additional, Ghione, Paola, additional, Fayyaz, Fatima, additional, Rhodes, Joanna M., additional, Chong, Elise A., additional, Gerson, James N., additional, Landsburg, Daniel J., additional, Dwivedy Nasta, Sunita, additional, Schuster, Stephen J., additional, Svoboda, Jakub, additional, Jerkeman, Mats, additional, and Barta, Stefan K., additional

Published
2022
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15. Outcome of limited‐stage peripheral T‐Cell lymphoma after CHOP(−like) therapy: A population based study of 239 patients from the Nordic lymphoma epidemiology group.

Author

Ludvigsen Al‐Mashhadi, Ahmed, Cederleuf, Henrik, Kuhr Jensen, Rasmus, Holm Nielsen, Torsten, Bjerregård Pedersen, Martin, Bech Mortensen, Thomas, Relander, Thomas, Jerkeman, Mats, Ortved Gang, Anne, Kristensen, Anne Louise, Roost Clausen, Michael, de Nully Brown, Peter, Tang Severinsen, Marianne, Jakobsen, Lasse Hjort, Ellin, Fredrik, and El‐Galaly, Tarec Christoffer

Published
2023
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17. The Burkitt Lymphoma International Prognostic Index (BL-IPI)

Author

Olszewski, Adam J, Jakobsen, Lasse H., Collins, Graham P., Cwynarski, Kate, Bachanova, Veronika, Blum, Kristie A., Boughan, Kirsten M, Bower, Mark, Dalla Pria, Alessia, Danilov, Alexey, David, Kevin A., Diefenbach, Catherine, Ellin, Fredrik, Epperla, Narendranath, Farooq, Umar, Feldman, Tatyana A., Gerrie, Alina S., Jagadeesh, Deepa, Kamdar, Manali, Karmali, Reem, Kassam, Shireen, Kenkre, Vaishalee P., Khan, Nadia, Klein, Andreas, Lossos, Izidore S., Lunning, Matthew A., Martin, Peter, Martinex-Calle, Nicolas, Montoto, Silvia, Naik, Seema, Palmisiano, Neil, Peace, David, Phillips, Elizabeth H, Phillips, Tycel J., Portell, Craig A., Reddy, Nishitha, Santarsieri, Anna, Yazdy, Maryam Sarraf, Smeland, Knut B., Smith, Scott E., Smith, Stephen D., Sundaram, Suchitra, Venugopal, Parameswaran, Zayac, Adam, Zhang, Xiao-Yin, Zhu, Catherine, Cheah, Chan Yoon, El-Galaly, Tarec Christoffer, and Evens, Andrew M.

Published
2020
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18. Burkitt Lymphoma International Prognostic Index

Author

Olszewski, Adam J., primary, Jakobsen, Lasse H., additional, Collins, Graham P., additional, Cwynarski, Kate, additional, Bachanova, Veronika, additional, Blum, Kristie A., additional, Boughan, Kirsten M., additional, Bower, Mark, additional, Dalla Pria, Alessia, additional, Danilov, Alexey, additional, David, Kevin A., additional, Diefenbach, Catherine, additional, Ellin, Fredrik, additional, Epperla, Narendranath, additional, Farooq, Umar, additional, Feldman, Tatyana A., additional, Gerrie, Alina S., additional, Jagadeesh, Deepa, additional, Kamdar, Manali, additional, Karmali, Reem, additional, Kassam, Shireen, additional, Kenkre, Vaishalee P., additional, Khan, Nadia, additional, Kim, Seo-Hyun, additional, Klein, Andreas K., additional, Lossos, Izidore S., additional, Lunning, Matthew A., additional, Martin, Peter, additional, Martinez-Calle, Nicolas, additional, Montoto, Silvia, additional, Naik, Seema, additional, Palmisiano, Neil, additional, Peace, David, additional, Phillips, Elizabeth H., additional, Phillips, Tycel J., additional, Portell, Craig A., additional, Reddy, Nishitha, additional, Santarsieri, Anna, additional, Sarraf Yazdy, Maryam, additional, Smeland, Knut B., additional, Smith, Scott E., additional, Smith, Stephen D., additional, Sundaram, Suchitra, additional, Zayac, Adam S., additional, Zhang, Xiao-Yin, additional, Zhu, Catherine, additional, Cheah, Chan Y., additional, El-Galaly, Tarec C., additional, and Evens, Andrew M., additional

Published
2021
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19. Minimal relapse risk and early normalization of survival for patients with Burkitt lymphoma treated with intensive immunochemotherapy : an international study of 264 real-world patients

Author

Jakobsen, Lasse H., Ellin, Fredrik, Smeland, Knut B., Wästerlid, Tove, Christensen, Jacob H., Jorgensen, Judit M., Josefsson, Pär L., Ovlisen, Andreas K., Holte, Harald, Blaker, Yngvild N., Grauslund, Jacob H., Bjorn, Jon, Molin, Daniel, Lagerlöf, Ingemar, Smedby, Karin E., Colvin, Katherine, Thanarajasingam, Gita, Maurer, Matthew J., Habermann, Thomas M., Song, Kevin W., Zhu, Katie Y., Gerrie, Alina S., Cheah, Chan Y., El-Galaly, Tarec C., Jakobsen, Lasse H., Ellin, Fredrik, Smeland, Knut B., Wästerlid, Tove, Christensen, Jacob H., Jorgensen, Judit M., Josefsson, Pär L., Ovlisen, Andreas K., Holte, Harald, Blaker, Yngvild N., Grauslund, Jacob H., Bjorn, Jon, Molin, Daniel, Lagerlöf, Ingemar, Smedby, Karin E., Colvin, Katherine, Thanarajasingam, Gita, Maurer, Matthew J., Habermann, Thomas M., Song, Kevin W., Zhu, Katie Y., Gerrie, Alina S., Cheah, Chan Y., and El-Galaly, Tarec C.

Abstract

Non-endemic Burkitt lymphoma (BL) is a rare germinal centre B-cell-derived malignancy with the genetic hallmark of MYC gene translocation and with rapid tumour growth as a distinct clinical feature. To investigate treatment outcomes, loss of lifetime and relapse risk in adult BL patients treated with intensive immunochemotherapy, retrospective clinic-based and population-based lymphoma registries from six countries were used to identify 264 real-world patients. The median age was 47 years and the majority had advanced-stage disease and elevated LDH. Treatment protocols were R-CODOX-M/IVAC (47%), R-hyper-CVAD (16%), DA-EPOCH-R (11%), R-BFM/GMALL (25%) and other (2%) leading to an overall response rate of 89%. The two-year overall survival and event-free survival were 84% and 80% respectively. For patients in complete remission/unconfirmed, the two-year relapse risk was 6% but diminished to 0 center dot 6% for patients reaching 12 months of post-remission event-free survival (pEFS12). The loss of lifetime for pEFS12 patients was 0 center dot 4 (95% CI: -0 center dot 7 to 2) months. In conclusion, real-world outcomes of adult BL are excellent following intensive immunochemotherapy. For pEFS12 patients, the relapse risk was low and life expectancy similar to that of a general population, which is important information for developing meaningful follow-up strategies with increased focus on survivorship and less focus on routine disease surveillance.

Published
2020
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22. Nationwide Investigation of Patient Trajectories in Mantle Cell Lymphoma - Initial Data from the Swedish MCL Complete Project

Author

Jerkeman, Mats, primary, Palsdottir, Thorgerdur, additional, Glimelius, Ingrid, additional, Albertsson-Lindblad, Alexandra, additional, Weibull, Caroline, additional, Ellin, Fredrik, additional, Sonnevi, Kristina, additional, Lewerin, Catharina, additional, Brandefors, Lena, additional, and Smedby, Karin E., additional

Published
2020
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24. Laminin [alpha]1 globular domains 4-5 induce fetal development but are not vital for embryonic basement membrane assembly

Author

Scheele, Susanne, Falk, Mats, Franzen, Ahnders, Ellin, Fredrik, Ferletta, Maria, Lonai, Peter, Andersson, Bjorn, Timpl, Rupert, Forsberg, Erik, and Ekblom, Peter

Subjects
Developmental biology -- Research, Laminin -- Research, Science and technology
Abstract

During early mouse embryogenesis, each laminin (Lm) chain of the first described Lm, a heterotrimer of [alpha]1, [beta]1, and [gamma]1 chains (Lm-1), is essential for basement membrane (BM) assembly, which is required for pregastrulation development. Individual domains may have other functions, not necessarily structural. The cell binding C terminus of Lm [alpha]1 chain contains five Lm globular (LG) domains. In vitro, [alpha]1LG1-3 domains bind integrins, and [alpha]1LG4 binds dystroglycan, heparin, and sulfatides. A prevailing hypothesis is that [alpha]1LG4 is crucial as a structural domain for BM assembly, whereas integrin-binding sites conduct signaling. The in vivo role of [alpha]1LG4-5 (also called E3) has not been studied. Mice lacking [alpha]1LG4-5 were therefore made. Null embryos implanted, but presumptive epiblast cells failed to polarize and did not survive past day 6.5. BM components including truncated Lm [alpha]1 were detected in Reichert's membrane. Surprisingly, embryonic BM assembly between visceral endoderm and stem cells was normal in null embryos and in embryoid bodies of [alpha]1LG4-5-null embryonic stem cells. Yet, stem cells could not develop into polarized epiblast cells. Thus, [alpha]1LG4-5 provides vital signals for the conversion of stem cells to polarized epithelium. epiblast | epithelial polarity | stem cells | mouse development

Published
2005

25. Minimal relapse risk and early normalization of survival for patients with Burkitt lymphoma treated with intensive immunochemotherapy: an international study of 264 real‐world patients

Author

Jakobsen, Lasse H., primary, Ellin, Fredrik, additional, Smeland, Knut B., additional, Wästerlid, Tove, additional, Christensen, Jacob H., additional, Jørgensen, Judit M., additional, Josefsson, Pär L., additional, Øvlisen, Andreas K., additional, Holte, Harald, additional, Blaker, Yngvild N., additional, Grauslund, Jacob H., additional, Bjørn, Jon, additional, Molin, Daniel, additional, Lagerlöf, Ingemar, additional, Smedby, Karin E., additional, Colvin, Katherine, additional, Thanarajasingam, Gita, additional, Maurer, Matthew J., additional, Habermann, Thomas M., additional, Song, Kevin W., additional, Zhu, Katie Y., additional, Gerrie, Alina S., additional, Cheah, Chan Y., additional, and El‐Galaly, Tarec C., additional

Published
2020
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27. Inferior Outcomes for Older Patients in the Adolescent and Young Adult (AYA) Population with Burkitt Lymphoma Treated with Intensive Immunochemotherapy: An International Study of 108 Patients

Author

Ellin, Fredrik, primary, Smeland, Knut B., additional, Wästerlid, Tove, additional, Christensen, Jacob H., additional, Jørgensen, Judit, additional, Josefsson, Pär L., additional, Holte, Harald, additional, Blaker, Yngvild Nuvin, additional, Grauslund, Jacob H., additional, Bjoern, Jon, additional, Molin, Daniel, additional, Lagerlöf, Ingemar, additional, Ekstroem Smedby, Karin Ekstrom, additional, Colvin, Katherine, additional, Thanarajasingam, Gita, additional, Maurer, Matthew J, additional, Habermann, Thomas M., additional, Song, Kevin, additional, Zhu, Katie Yuan, additional, Gerrie, Alina S, additional, Cheah, Chan Y., additional, El-Galaly, Tarec Christoffer C., additional, and Jakobsen, Lasse H., additional

Published
2019
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28. Comparison of the NCCN‐IPI, the IPI and PIT scores as prognostic tools in peripheral T‐cell lymphomas

Author

Ellin, Fredrik, primary, Maurer, Matthew J., additional, Srour, Line, additional, Farooq, Umar, additional, Jerkeman, Mats, additional, Connors, Joseph M., additional, Smedby, Karin E., additional, Bennani, N. Nora, additional, Ansell, Stephen M., additional, Slack, Graham W., additional, Cerhan, James R., additional, Relander, Thomas, additional, Feldman, Andrew L., additional, and Savage, Kerry J., additional

Published
2019
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29. Normalization of Survival and No Relapses after One Year in Adult Burkitt Lymphoma Patients Treated with Intensive Immunochemotherapy: An International Study of 159 Real-World Patients

Author

Jakobsen, Lasse H., primary, Ellin, Fredrik, additional, Smeland, Knut B., additional, Wästerlid, Tove, additional, Christensen, Jacob H., additional, Jørgensen, Judit, additional, Josefsson, Pär L., additional, Holte, Harald, additional, Blaker, Yngvild N., additional, Grauslund, Jacob H., additional, Bjørn, Jon, additional, Molin, Daniel, additional, Lagerlöf, Ingemar, additional, Ekstroem Smedby, Karin, additional, Colvin, Katherine, additional, Thanarajasingam, Gita, additional, Gerrie, Alina S., additional, Cheah, Chan Y., additional, and El-Galaly, Tarec C., additional

Published
2018
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30. International Assessment of Event-Free Survival at 24 Months and Subsequent Survival in Peripheral T-Cell Lymphoma

Author

Maurer, Matthew J., primary, Ellin, Fredrik, additional, Srour, Line, additional, Jerkeman, Mats, additional, Bennani, N. Nora, additional, Connors, Joseph M., additional, Slack, Graham W., additional, Smedby, Karin E., additional, Ansell, Stephen M., additional, Link, Brian K., additional, Cerhan, James R., additional, Relander, Thomas, additional, Savage, Kerry J., additional, and Feldman, Andrew L., additional

Published
2017
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31. The Impact of Upfront Autologous Transplant on the Survival of Adult Patients with ALCL and PTCL-NOS According to Their ALK, DUSP22 and TP63 Gene Rearrangement Status - a Joined Nordic Lymphoma Group and Mayo Clinic Analysis

Author

Pedersen, Martin Bjerregård, primary, Relander, Thomas, additional, Lauritzsen, Grete Fossum, additional, Ellin, Fredrik, additional, Leppä, Sirpa, additional, Mannisto, Susanna, additional, Jantunen, Esa, additional, Ketterling, Rhett P., additional, Bedroske, Patrick, additional, Luoma, Ivy, additional, Sattler, Christopher, additional, Delabie, Jan M.A., additional, Sundstrom, Christer, additional, Sander, Birgitta, additional, Karjalainen-Lindsberg, Marja-Liisa, additional, Hamilton-Dutoit, Stephen, additional, Ehinger, Mats, additional, Vornanen, M, additional, Ralfkiaer, Elisabeth, additional, Boddicker, Rebecca, additional, Bennani, Nabila Nora, additional, Oishi, Naoki, additional, Moeller, Michael Boe, additional, Noergaard, Peter, additional, Cerhan, James R., additional, Maurer, Matthew J, additional, Liestol, Knut, additional, Toldbod, Helle, additional, Feldman, Andrew L, additional, and d'Amore, Francesco, additional

Published
2017
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32. Outcome of peripheral T-cell lymphoma in first complete remission:a Danish-Swedish population-based study

Author

Cederleuf, Henrik, Hjort Jakobsen, Lasse, Ellin, Fredrik, de Nully Brown, Peter, Stauffer Larsen, Thomas, Bøgsted, Martin, Relander, Thomas, Jerkeman, Mats, El-Galaly, Tarec Christoffer, Cederleuf, Henrik, Hjort Jakobsen, Lasse, Ellin, Fredrik, de Nully Brown, Peter, Stauffer Larsen, Thomas, Bøgsted, Martin, Relander, Thomas, Jerkeman, Mats, and El-Galaly, Tarec Christoffer

Abstract

In the present study, we investigate the outcome of 109 Danish and 123 Swedish patients with nodal PTCL in first complete remission (CR), and examine the impact of imaging-based follow-up (FU) strategies. The patients were selected by the following criteria: (a) newly diagnosed nodal PTCL from 2007 to 2012, (b) age ≥18 years, and (c) CR after CHOP or CHOEP therapy. FU guidelines in Sweden included symptom assessment, clinical examinations and blood tests at 3–4-month intervals for 2 years. FU strategies in Denmark was similar but included routine imaging, usually every 6 months for 2 years. Patients had fully comparable characteristics. Overall survival (OS) estimates for patients in CR were similar for all patients (p =.6) and in PTCL subtypes. In multivariate analysis, country of follow-up had no impact on OS. However, despite continuous CR for ≥2 years, the OS of PTCL remained inferior to a matched general population.

Published
2017

37. An International Assessment of Event-Free Survival at 24 Months (EFS24) and Subsequent Survival in Peripheral T-Cell Lymphoma

Author

Maurer, Matthew J, primary, Ellin, Fredrik, additional, Srour, Line, additional, Jerkeman, Mats, additional, Bennani, Nabila Nora, additional, Connors, Joseph M., additional, Smedby, Karin Ekstrom, additional, Ansell, Stephen, additional, Link, Brian K, additional, Cerhan, James R, additional, Relander, Thomas, additional, Savage, Kerry J, additional, and Feldman, Andrew L, additional

Published
2016
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38. Event-Free Survival at 12 Months and Subsequent Overall Survival in Patients with Peripheral T-Cell Lymphoma

Author

Maurer, Matthew J, primary, Ellin, Fredrik, additional, Cerhan, James, additional, Ansell, Stephen, additional, Link, Brian K, additional, Jerkeman, Mats, additional, Smedby, Karin E, additional, Thompson, Carrie A., additional, Macon, William, additional, Syrbu, Sergei, additional, Slager, Susan L., additional, Witzig, Thomas E., additional, Habermann, Thomas M., additional, Relander, Thomas, additional, and Feldman, Andrew L, additional

Published
2015
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40. Impact of comorbidity on survival in peripheral T-cell lymphomas: A Swedish Lymphoma Registry study.

Author

Ellin, Fredrik, Jerkeman, Mats, Törnqvist, Jenny, Brudin, Lars, and Relander, Thomas

Subjects
SURVIVAL analysis (Biometry), COMORBIDITY, TREATMENT effectiveness, ACQUISITION of data, T-cell lymphoma, DISEASE complications
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. [ABSTRACT FROM AUTHOR]

Published
2018
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41. Treatment outcome in T-cell lymphoblastic lymphoma in adults : a population-based study from the Swedish Lymphoma Registry

Author

Ellin, Fredrik, Jerkeman, Mats, Hagberg, Hans, Relander, Thomas, Ellin, Fredrik, Jerkeman, Mats, Hagberg, Hans, and Relander, Thomas

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.

Published
2014
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44. Hematopoietic cell transplants for T-cell lymphomas

Author

D'amore, Francesco, primary, Relander, Thomas, additional, Lauritzsen, Grete F., additional, Jantunen, Esa, additional, Mannisto, Susanna, additional, Meyer, Peter, additional, Ellin, Fredrik, additional, Pedersen, Martin Bjerregård, additional, and Toldbod, Helle, additional

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48. Defective heparan sulfate biosynthesis and neonatal lethality in mice lacking N-deacetylase/N-sulfotransferase-1

Author

Ringvall, Maria, Ledin, Johan, Holmborn, Katarina, van Kuppevelt, Toin, Ellin, Fredrik, Eriksson, Inger, Olofsson, Anne-Mari, Kjellén, Lena, Forsberg, Erik, Ringvall, Maria, Ledin, Johan, Holmborn, Katarina, van Kuppevelt, Toin, Ellin, Fredrik, Eriksson, Inger, Olofsson, Anne-Mari, Kjellén, Lena, and Forsberg, Erik

Abstract

Heparan sulfate is a sulfated polysaccharide present on most cell surfaces and in the extracellular matrix. In vivo functions of heparan sulfate can be studied in mouse strains lacking enzymes involved in the biosynthesis of heparan sulfate. Glucosaminyl N-deacetylase/N-suLfotransferase (NDST) catalyzes the first modifying step in the biosynthesis of the polysaccharide. This bifunctional enzyme occurs in several isoforms. We here report that targeted gene disruption of NDST-1 in the mouse results in a structural alteration of heparan sulfate in most basement membranes as revealed by immunohistochemical staining of fetal tissue sections using antibodies raised against heparan sulfate. Biochemical analysis of heparan sulfate purified from fibroblast cultures, lung, and liver of NDST-1-deficient embryos demonstrated a dramatic reduction in N-sulfate content. Most NDST-1-deficient embryos survive until birth; however, they turn out to be cyanotic and die neonatally in a condition resembling respiratory distress syndrome. In addition, a minor proportion of NDST-1 deficient embryos die during the embryonic period. The cause of the embryonic lethality is still obscure, but incompletely penetrant defects of the skull and the eyes have been observed.

Published
2000
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50. Evaluation of the NCCN-IPI As a Prognostic Tool in PTCLs

Author

Ellin, Fredrik, Maurer, Matthew J, Srour, Line, Farooq, Umar, Jerkeman, Mats, Connors, Joseph M, Smedby, Karin E, Bennani, Nabila Nora, Ansell, Stephen M, Slack, Graham W, Cerhan, James R., Relander, Thomas, Feldman, Andrew L, and Savage, Kerry J

Abstract

Background: The majority of systemic peripheral T-cell lymphomas (PTCLs) have an aggressive behavior and compared to diffuse large B-cell lymphoma, survival is inferior using standard anthracycline-based treatment. Patient and disease factors impact survival, and the International Prognostic Index (IPI) is the most widely used clinical tool for prognostication for aggressive lymphomas. The IPI has shown prognostic utility in some PTCL entities such as systemic anaplastic large cell lymphoma (ALCL) and PTCL not otherwise specified (PTCL NOS), but less usefulness for others such as angioimmunoblastic T-cell lymphoma (AITL) as well as the rarer predominantly extranodal PTCL subtypes. T-cell specific prognostic indices such as the Prognostic Index for PTCL-U (PIT) have been explored but the IPI remains the most commonly used prognostic tool. The NCCN-IPI prognostic index has recently been developed for DLBCL. The NCCN-IPI builds on much the same parameters as the IPI, but with age stratified into four groups, lactate dehydrogenase (LDH) ratio using the upper limit of normal (ULN) separated into three categories (<1 ULN, 1-3 ULN, >3 ULN) and it also incorporates specific extranodal sites (CNS, gastrointestinal, lung or bone marrow involvement) but not absolute number of sites, with a maximum score of 8 points. In this study we evaluated the NCCN-IPI in comparison to the IPI and PIT in the three main nodal PTCL subgroups: ALK-neg ALCL, AITL, and PTCL NOS.

Published
2017
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