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Dive into the research topics where Per Bernell is active.

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Featured researches published by Per Bernell.


European Journal of Haematology | 2013

Risk group assignment differs for children and adults 1–45 yr with acute lymphoblastic leukemia treated by the NOPHO ALL‐2008 protocol

Nina Toft; Henrik Birgens; Jonas Abrahamsson; Per Bernell; Laimonas Griskevicius; Helene Hallböök; Mats Heyman; Mette Holm; Erik Hulegårdh; Tobias Wirenfeldt Klausen; Hanne Vibeke Marquart; Olafur G. Jonsson; Ove Juul Nielsen; Petter Quist-Paulsen; Mervi Taskinen; Goda Vaitkeviciene; Kim Vettenranta; Ann Åsberg; Kjeld Schmiegelow

The prognosis of acute lymphoblastic leukemia is poorer in adults than in children. Studies have indicated that young adults benefit from pediatric treatment, although no upper age limit has been defined.


British Journal of Haematology | 2010

Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy

Michael Grövdal; Mohsen Karimi; Rasheed Khan; Anni Aggerholm; Petar Antunovic; Jan Astermark; Per Bernell; Lena-Maria Engström; Lars Kjeldsen; Olle Linder; Lars J Nilsson; Anna Olsson; Mette Holm; Jon Magnus Tangen; Jonas Wallvik; Gunnar Öberg; Peter Hokland; Sten Eirik W. Jacobsen; Anna Porwit; Eva Hellström-Lindberg

This prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5‐azacytidine for older patients with high‐risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS‐acute myeloid leukaemia syndromes in complete remission (CR) after induction chemotherapy. Sixty patients were enrolled and treated by standard induction chemotherapy. Patients that reached CR started maintenance therapy with subcutaneous azacytidine, 5/28 d until relapse. Promoter‐methylation status of CDKN2B (P15 ink4b), CDH1 and HIC1 was examined pre‐induction, in CR and 6, 12 and 24 months post CR. Twenty‐four (40%) patients achieved CR after induction chemotherapy and 23 started maintenance treatment with azacytidine. Median CR duration was 13·5 months, >24 months in 17% of the patients, and 18–30·5 months in the four patients with trisomy 8. CR duration was not associated with CDKN2B methylation status or karyotype. Median overall survival was 20 months. Hypermethylation of CDH1 was significantly associated with low CR rate, early relapse, and short overall survival (P = 0·003). 5‐azacytidine treatment, at a dose of 60 mg/m2 was well tolerated. Grade III‐IV thrombocytopenia and neutropenia occurred after 9·5 and 30% of the cycles, respectively, while haemoglobin levels increased during treatment. 5‐azacytidine treatment is safe, feasible and may be of benefit in a subset of patients.


Clinical Cancer Research | 2007

Negative effect of DNA hypermethylation on the outcome of intensive chemotherapy in older patients with high-risk myelodysplastic syndromes and acute myeloid leukemia following Myelodysplastic syndrome

Michael Grövdal; Rasheed Khan; Anni Aggerholm; Petar Antunovic; Jan Astermark; Per Bernell; Lena-Maria Engström; Lars Kjeldsen; Olle Linder; Lars J Nilsson; Anna Olsson; Jonas Wallvik; Jon Magnus Tangen; Gunnar Öberg; Sten Eirik W. Jacobsen; Peter Hokland; Anna Porwit; Eva Hellström-Lindberg

Purpose: Promoter hypermethylation of, for example, tumor-suppressor genes, is considered to be an important step in cancerogenesis and a negative risk factor for survival in patients with myelodysplastic syndromes (MDS); however, its role for response to therapy has not been determined. This study was designed to assess the effect of methylation status on the outcome of conventional induction chemotherapy. Experimental Design: Sixty patients with high-risk MDS or acute myeloid leukemia following MDS were treated with standard doses of daunorubicin and 1-β-d-arabinofuranosylcytosine. Standard prognostic variables and methylation status of the P15ink4b (P15), E-cadherin (CDH), and hypermethylated in cancer 1 (HIC) genes were analyzed before treatment. Results: Forty percent of the patients achieved complete remission (CR). CR rate was lower in patients with high WBC counts (P = 0.03) and high CD34 expression on bone marrow cells (P = 0.02). Whereas P15 status alone was not significantly associated with CR rate (P = 0.25), no patient with hypermethylation of all three genes achieved CR (P = 0.03). Moreover, patients with CDH methylation showed a significantly lower CR rate (P = 0.008), and CDH methylation retained its prognostic value also in the multivariate analysis. Hypermethylation was associated with increased CD34 expression, but not with other known predictive factors for response, such as cytogenetic profile. Conclusions: We show for the first time a significant effect of methylation status on the outcome of conventional chemotherapy in high-risk MDS and acute myelogenous leukemia following MDS. Provided confirmed in an independent study, our results should be used as a basis for therapeutic decision-making in this patient group.


European Journal of Haematology | 2002

Serum erythropoietin (EPO) levels correlate with survival and independently predict response to EPO treatment in patients with myelodysplastic syndromes

Jonas Wallvik; Leif Stenke; Per Bernell; Gunnar Nordahl; Erik Hippe; Robert Hast

Abstract: Treatment with recombinant erythropoietin (EPO) can alleviate anaemia in patients with myelodysplastic syndromes (MDS). The present study, based on a long‐term follow‐up of 68 MDS patients (26RA, 16 RAS, 26 RAEB) treated with EPO alone, pinpoints pre‐treatment variables associated with response induction, response duration and overall survival. Response, defined as an increase in haemoglobin >15 g L−1 or eliminated erythrocyte transfusion requirements, was observed in 22 of 66 (33%) evaluable patients. The median response duration was 15 (range 3–64 +) months. Using univariate logistic regression models, responders displayed significantly lower baseline serum EPO levels (S‐EPO), more often normal bone marrow blast cell content (RA/RAS vs. RAEB), normal cytogenetics and no need for erythrocyte transfusion. In a multiple logistic regression model, S‐EPO (P = 0.009), marrow blast content (P = 0.031) and erythrocyte transfusion need (P = 0.024) remained associated with response induction. The probability of response for a patient with S‐EPO >50 U L−1, RA/RAS and no transfusion need was 0.79 (0.53–0.93, 95% CI). The median overall survival time from start of EPO treatment was 26 months, significantly longer for responders than for non‐responders (49 vs. 18 months, P = 0.018). Survival was also predicted by baseline S‐EPO; patients with S‐EPO > 50 U L−1 (n = 50) had a median survival of 17 months, as compared to 65 months for those with S‐EPO >50 U L−1 (n = 14, P = 0.024). The international prognostic scoring system (IPSS) for MDS predicted survival (P = 0.003) and progression to acute leukemia (P < 0.001) but not response to EPO treatment. Furthermore, in a logistic regression model with S‐EPO and IPSS, S‐EPO (but not IPSS) was again a significant predictor for response (P = 0.007). Our data facilitate the optimal selection of MDS patients suitable for EPO treatment and pinpoint S‐EPO as a powerful predictor of response and overall survival in MDS.


British Journal of Haematology | 1996

Fluorescence in situ hybridization in combination with morphology detects minimal residual disease in remission and heralds relapse in acute leukaemia

Per Bernell; Ingrid Arvidsson; Björn Jacobsson; Robert Hast

Fluorescence in situ hybridization in combination with morphology (MGG/FISH) was used to detect minimal residual disease (MRD) in complete remission (CR) in 12 cases of acute leukaemia (six MDS‐AML, five de novo AML, one pre‐B ALL) with numerical chromosomal aberrations at diagnosis. Residual leukaemic cells could be detected in the remission bone marrows by MGG/FISH in five patients, whereas the other seven showed no abnormalities. All five patients with signs of MRD at CR relapsed in the bone marrow within 2–9 months, in contrast to two of seven with a normal finding by MGG/FISH at CR. In both these patients a second MGG/FISH analysis showed that a subpopulation of leukaemic blasts had reappeared, 4 and 5 months prior to the leukaemia becoming clinically overt. One patient suffered a CNS relapse, but without any evidence of bone marrow involvement. The remaining four patients with no evidence of MRD at CR were still in haematological remission at follow‐up after 4, 11, 12 and 13 months, respectively. We conclude that MGG/FISH seems to be a clinically useful method to detect MRD in acute leukaemia and to predict relapses, particularly when repeat studies are performed during CR.


Haematologica | 2012

High curability via intensive reinduction chemotherapy and stem cell transplantation in young adults with relapsed acute lymphoblastic leukemia in Sweden 2003–2007

Piotr Kozlowski; Maria Åström; Lucia Ahlberg; Per Bernell; Erik Hulegårdh; Hans Hägglund; Karin Karlsson; Alicja Markuszewska-Kuczymska; Beata Tomaszewska-Toporska; Bengt Smedmyr; Helene Hallböök

Background A minority of patients with adult acute lymphoblastic leukemia who relapse are rescued. The aim of this population-based study was to assess the results of reinduction treatment and allogeneic stem cell transplantation in patients in second complete remission. Design and Methods Between 2003–2007, 76 adults (<66 years) with relapsed acute lymphoblastic leukemia (Burkitt’s leukemia excluded) were prospectively reported to The Swedish Adult Acute Leukemia Registry and later evaluated. Results Reinduction with: (i) mitoxantrone, etoposide, and cytarabine (MEA); (ii) fludarabine, cytarabine, pegylated-asparaginase plus granulocyte colony-stimulating factor (FLAG-Asp); and (iii) cytarabine, betamethasone, cyclophosphamide, daunorubicin, and vincristine (ABCDV) resulted in complete remission in 6/9 (67%), 10/16 (63%) and 9/21 (43%) of the patients, respectively. Allogeneic stem cell transplantation was performed during second complete remission in 29 patients. Multivariate analysis regarding overall survival after relapse revealed that age over 35 years at diagnosis and relapse within 18 months were negative prognostic factors. Overall survival rates at 3 and 5 years were 22% (95% CI: 13–32) and 15% (95% CI: 7–24). Of 19 patients less than 35 years at diagnosis who underwent allogeneic stem cell transplantation in second remission, ten (53%) are still alive at a median of 5.5 years (range, 4.2–8.3) after relapse, whereas all patients over 35 years old at diagnosis have died. Conclusions Allogeneic stem cell transplantation remains the treatment of choice for young adults with relapsed acute lymphoblastic leukemia. Both (i) mitoxantrone, etoposide, and cytarabine and (ii) fludarabine, cytarabine, pegylated-asparaginase plus granulocyte colony-stimulating factor seem effective as reinduction treatments and should be further evaluated. New salvage strategies are needed, especially for patients over 35 years old at diagnosis.


Haematologica | 2008

An investigation into whether deletions in 9p reflect prognosis in adult precursor B-cell acute lymphoblastic leukemia: a multi-center study of 381 patients

Hareth Nahi; Hans Hägglund; Thomas Ahlgren; Per Bernell; Mats Hardling; Karin Karlsson; Vladimir Lazarevic; Mats Linderholm; Bengt Smedmyr; Maria Åström; Helene Hallböök

The findings of this study suggest that chromosomal abnormalities involving 9p may have a significant negative impact on survival in adult B-precursor acute lymphoblastic leukemia. In acute lymphoblastic leukemia, besides age and white cell count at diagnosis, the cytogenetic abnormalities t(9;22)/BCR-ABL and t(4;11)/MLL-AF4 are important prognostic markers and are often included in the treatment stratification of patients with adult acute lymphoblastic leukemia. Deletions in 9p are seen in about 9% of cases of adult acute lymphoblastic leukemia, but their prognostic impact has been controversial. Cytogenetic data from 381 patients diagnosed with B-precursor acute lymphoblastic leukemia were reviewed. Chromosomal analysis was successful in 240 cases. Of these cases, 18 (8%) had abnormalities in 9p and they were compared with patients with normal karyotypes and patients with t(9;22)/BCR-ABL. Patients with abnormalities of chromosome 9 showed significantly shorter overall survival compared with patients with normal karyotypes. In fact, overall survival was similar to that in the poor prognosis t(9;22)/BCR-ABL-positive group. Our data suggest that chromosomal abnormalities involving 9p may have a significant negative impact on survival in adult B-precursor acute lymphoblastic leukemia.


European Journal of Haematology | 2014

High relapse rate of T cell acute lymphoblastic leukemia in adults treated with Hyper-CVAD chemotherapy in Sweden

Piotr Kozlowski; Maria Åström; Lucia Ahlberg; Per Bernell; Erik Hulegårdh; Hans Hägglund; Karin Karlsson; Alicja Markuszewska-Kuczymska; Beata Tomaszewska-Toporska; Bengt Smedmyr; Rose-Marie Amini; Helene Hallböök

Hyper‐CVAD is widely used to treat acute lymphoblastic leukemia (ALL) and aggressive lymphomas. This multicenter, population‐based study assessed the efficacy of Hyper‐CVAD as first‐line therapy in patients with T‐cell ALL (T‐ALL).


European Journal of Haematology | 2017

Age but not Philadelphia positivity impairs outcome in older/elderly patients with acute lymphoblastic leukemia in Sweden

Piotr Kozlowski; Emma Lennmyr; Lucia Ahlberg; Per Bernell; Erik Hulegårdh; Holger Karbach; Karin Karlsson; Beata Tomaszewska-Toporska; Maria Åström; Helene Hallböök

Older/elderly patients with acute lymphoblastic leukemia (ALL) are poorly represented in clinical trials.


Leukemia & Lymphoma | 2018

Real-world data on first relapse of acute lymphoblastic leukemia in patients >55 years

Emma Lennmyr; Piotr Kozlowski; Lucia Ahlberg; Per Bernell; Erik Hulegårdh; Antonio Santamaria Izarra; Karin Karlsson; Beata Tomaszewska-Toporska; Maria Åström; Helene Hallböök

Emma Bergfelt Lennmyr , Piotr Kozlowski , Lucia Ahlberg, Per Bernell, Erik Hulegårdh, Antonio Santamaria Izarra, Karin Karlsson, Beata Tomaszewska-Toporska, Maria Åstr€ om and Helene Hallb€ o€ ok ; on behalf of the Swedish Adult Acute Lymphoblastic Leukemia Group, SVALL Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden; Department of Medicine, School of Medical Sciences, € Orebro University, € Orebro, Sweden; Department of Hematology, University Hospital of Link€oping, Link€oping, Sweden; Division of Hematology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Department of Hematology and Coagulation, Sahlgrenska University Hospital, G€oteborg, Sweden; Department of Hematology, Cancer Center, University Hospital of Umeå, Umeå, Sweden; Department of Hematology and Oncology, Skåne University Hospital, Lund, Sweden

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Erik Hulegårdh

Sahlgrenska University Hospital

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Anna Olsson

Sahlgrenska University Hospital

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