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  • 1.
    Bergfelt, E.
    et al.
    Haematology, Dept of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Kozlowski, Piotr
    Örebro University, School of Health Sciences.
    Ahlberg, L.
    Dept of Haematology, University Hospital of Linköping, Linköping, Sweden.
    Bernell, P.
    Div of Haematology, Dept of Medicine, Karolinska Institutet, Karolinska University, Stockholm, Sweden.
    Hulegårdh, E.
    Dept of Haematology and Coagulation, Sahlgrenska University Hospital, Göteborg, Sweden.
    Karbach, H.
    Dept of Haematology, Cancer Centre, University Hospital of Umeå, Umeå, Sweden.
    Karlsson, K.
    Dept of Haematology, Skåne University Hospital, Lund, Sweden .
    Tomaszewska-Toporska, B.
    Dept of Haematology, Skåne University Hospital, Lund, Sweden .
    Åström, Maria
    Örebro University, School of Medical Sciences.
    Hallböök, H.
    Haematology, Dept of Medical Sciences, Uppsala University, Uppsala, Sweden.
    RELAPSE OF ACUTE LYMPHOBLASTIC LEUKAEMIA IN OLDER/ELDERLY PATIENTS: A SWEDISH POPULATION-BASED STUDY2016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, no Suppl. 1, p. 34-35Article in journal (Other academic)
  • 2.
    Bergfelt, E.
    et al.
    Department of Medical Sciences, Haematology, Uppsala University, Uppsala, Sweden.
    Kozlowski, Piotr
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Åström, Maria
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Ahlberg, L.
    Department of Haematology, University Hospital of Linköping, Linköping, Sweden.
    Bernell, P.
    Dept Med, Div Haematol, Karolinska Univ Hosp, Karolinska Inst, Stockholm, Sweden.
    Hulegårdh, E.
    Department of Haematology and Coagulation, Sahlgrenska University Hospital, Göteborg, Sweden.
    Karbach, H.
    Ctr Canc, Dept Haematol, Umeå Univ Hosp, Umeå, Sweden.
    Karlsson, K.
    Department of Haematology, Skåne University Hospital, Lund, Sweden.
    Tomaszewska-Toporska, B.
    Department of Haematology, Skåne University Hospital, Lund, Sweden.
    Hallböök, H.
    Department of Medical Sciences, Haematology, Uppsala University, Uppsala, Sweden.
    Prognosis in older/elderly patients with acute lymphoblastic leukaemia diagnosed 2005-2012: results from a Swedish population-based study2015In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 100, no Suppl. 1, p. 202-202Article in journal (Other academic)
  • 3.
    Bergfelt, Emma
    et al.
    Department of Medical Sciences, Haematology, Uppsala University, Uppsala, Sweden.
    Kozlowski, Piotr
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Ahlberg, Lucia
    Department of Haematology, University Hospital of Linköping, Linköping, Sweden.
    Hulegårdh, Erik
    Department of Haematology and Coagulation, Sahlgrenska University Hospital, Göteborg, Sweden.
    Hägglund, Hans
    Division of Haematology, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Karlsson, Karin
    Department of Haematology, Skåne University Hospital, Lund, Sweden.
    Markuszewska-Kuczymska, Alicja
    Department of Haematology, Cancer Center, University Hospital of Umeå, Umeå , Sweden.
    Tomaszewska-Toporska, Beata
    Department of Haematology, Skåne University Hospital, Lund, Sweden.
    Smedmyr, Bengt
    Department of Medical Sciences, Haematology, Uppsala University, Uppsala, Sweden.
    Åström, Maria
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Amini, Rose-Marie
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Hallböök, Helene
    Department of Medical Sciences, Haematology, Uppsala University, Uppsala, Sweden.
    Satisfactory outcome after intensive chemotherapy with pragmatic use of minimal residual disease (MRD) monitoring in older patients with Philadelphia-negative B cell precursor acute lymphoblastic leukaemia: a Swedish registry-based study2015In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 32, no 4, article id 135Article in journal (Refereed)
    Abstract [en]

    The introduction of minimal residual disease (MRD) monitoring, in the Swedish national guidelines for acute lymphoblastic leukaemia, was evaluated in 35 patients aged 46-79 years (median 61), who were diagnosed from 2007 to 2011 and treated with high-intensity, block-based chemotherapy (ABCDV/VABA induction). Both a high complete remission rate (91 %) and acceptable overall survival (OS) rate (47 %) at 5 years were achieved. MRD by flow cytometry was measured in 73 % of the patients reaching complete remission after the first course, but was omitted by the clinicians for eight patients who were either over 70 years of age or already met conventional high-risk criteria. Factors negatively influencing OS were age over 65 years and WHO status >= 2. MRD < 0.1 % after induction had positive impact on continuous complete remission but not on OS. Only five patients were allocated to allogeneic haematopoietic stem cell transplantation in first remission, mainly due to conventional high risk factors. Thus, use of intensive remission induction therapy is effective in a selection of older patients. In a population for whom the possibilities of treatment escalation are limited, the optimal role of MRD monitoring remains to be determined.

  • 4.
    Kozlowski, Piotr
    Örebro University, School of Health Sciences.
    Prognostic factors, treatment and outcome in adult acute lymphoblastic leukemia: Population-based studies in Sweden2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Acute lymphoblastic leukemia (ALL) has poor prognosis in older/elderly adults and in high-risk/relapsed disease. Recommended treatment of ALL was evaluated (study I-IV). Data was obtained from the Swedish Acute Leukemia registries and from patient records.

    I. We assessed ALL relapse treatment and outcome in 76 patients aged 15-65 years (y). Complete remission (CR) was achieved in 50/71 patients (70%). Of them, 29 underwent allogeneic hematopoietic stem cell transplantation (hSCT). Five year overall survival (OS) was 15%, but close to 50% in 19 patients <35y after hSCT.

    II. We studied outcome of treatment with the Hyper-CVAD protocol in 19 of 24 patients with T-ALL aged 18-72y. CR was reached in 89%, but 5y leukemia-free survival was only 29%, and 20% in 15 patients not transplanted in CR1. Six patients received hSCT in CR2. Finally, 5y OS in all 19 patients was 47%. The only negative prognostic factor found was age ≥35y.

    III. We evaluated minimal residual disease (MRD) monitoring in 35 patients with Philadelphia (Ph) negative B-ALL aged 46-79y and treated with the ABCDV protocol. The CR rate was 91%. MRD was measured by flow cytometry in 73% in CR1 (MRD1) and omitted in those >70y or with high-risk ALL. Five patients received hSCT (only one due to MRD). Five year OS in the whole cohort was 47%. Continuous CR but not OS was improved in patients with MRD1 <0.1 %.

    IV. We studied 155 patients with ALL (Ph+ in 35%) aged 55-85y and treated with remission induction/palliation (124/31). Both, intensive, and palliative treatment resulted in the CR rates of 70/83/16% and 3y OS of 26/32/3%. OS was negatively influenced by age and platelet count ≤35×109/L (but not Ph+). OS was not enhanced by introduction of an age-adapted protocol.

    We concluded that intensive treatment with subsequent allogeneic hSCT is the most reasonable option in younger patients with ALL recurrence (I). Hyper-CVAD has low relapse-preventing efficacy (II). MRD guided intensification is probably feasible in only a minority of older patients (III). Prognosis in elderly ALL is poor, but no longer impaired by Ph+ (IV).

    List of papers
    1. High curability via intensive reinduction chemotherapy and stem cell transplantation in young adults with relapsed acute lymphoblastic leukemia in Sweden 2003-2007
    Open this publication in new window or tab >>High curability via intensive reinduction chemotherapy and stem cell transplantation in young adults with relapsed acute lymphoblastic leukemia in Sweden 2003-2007
    Show others...
    2012 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 97, no 9, p. 1414-1421Article in journal (Refereed) Published
    Abstract [en]

    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.

    Place, publisher, year, edition, pages
    Ferrata Storti Foundation, 2012
    Keywords
    Acute lymphoblastic leukaemia, Adults, Minimal residual disease, Flow cytometry
    National Category
    Hematology General Practice
    Identifiers
    urn:nbn:se:oru:diva-48485 (URN)10.3324/haematol.2011.057851 (DOI)000308908300022 ()22511497 (PubMedID)2-s2.0-84865851061 (Scopus ID)
    Available from: 2016-02-23 Created: 2016-02-23 Last updated: 2018-05-14Bibliographically approved
    2. High relapse rate of T cell acute lymphoblastic leukemia in adults treated with Hyper-CVAD chemotherapy in Sweden
    Open this publication in new window or tab >>High relapse rate of T cell acute lymphoblastic leukemia in adults treated with Hyper-CVAD chemotherapy in Sweden
    Show others...
    2014 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 92, no 5, p. 377-381Article in journal (Refereed) Published
    Abstract [en]

    Background: 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).

    Patients and methods: Between October 2002 and September 2006, 24 patients were diagnosed with T-ALL in Sweden; 19 were eligible for treatment with the protocol.

    Results: The median age was 32 yr (range 18-72 yr). Complete remission (CR) was obtained in 17 of 19 (89%) patients, and the treatment was relatively well tolerated. Allogeneic stem cell transplantation (SCT) was recommended in high-risk disease and was performed in four patients upfront. Two- and 5-yr leukemia-free survivals (LFS) in 17 patients with CR achievement were identical, at 29% (95% confidence interval [CI]: 8-51). Two- and 5-yr overall survival (OS) in whole cohort was 63% (95% CI: 42-85) and 47% (95% CI: 26-69), respectively. The 5-yr LFS for 15 patients who did not receive allogeneic SCT upfront were 20% (95% CI: 0-40), although 14 of 15 completed the protocol (eight cycles). Relapse occurred in 2 of 4 upfront-transplanted patients and in 12 of 15 patients treated with chemotherapy alone, six of whom received allogeneic SCT in CR2. Age ≥35 yr influenced OS negatively in univariate analysis (HR 5.1, 95% CI: 1.55-16.7).

    Conclusions: Hyper-CVAD treatment resulted in a high CR rate and appeared safe, but it showed poor efficacy at preventing relapse. Therefore, this treatment is no longer recommended for adults with T-ALL in Sweden.

    Place, publisher, year, edition, pages
    Wiley-Blackwell, 2014
    Keywords
    antineoplastic combined chemotherapy protocols; treatment outcome; precursor T-cell lymphoblastic leukemia-lymphoma; stem cell transplantation
    National Category
    Hematology General Practice
    Identifiers
    urn:nbn:se:oru:diva-48486 (URN)10.1111/ejh.12269 (DOI)000334267500002 ()24443846 (PubMedID)2-s2.0-84898801134 (Scopus ID)
    Available from: 2016-02-23 Created: 2016-02-23 Last updated: 2018-06-18Bibliographically approved
    3. Satisfactory outcome after intensive chemotherapy with pragmatic use of minimal residual disease (MRD) monitoring in older patients with Philadelphia-negative B cell precursor acute lymphoblastic leukaemia: a Swedish registry-based study
    Open this publication in new window or tab >>Satisfactory outcome after intensive chemotherapy with pragmatic use of minimal residual disease (MRD) monitoring in older patients with Philadelphia-negative B cell precursor acute lymphoblastic leukaemia: a Swedish registry-based study
    Show others...
    2015 (English)In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 32, no 4, article id 135Article in journal (Refereed) Published
    Abstract [en]

    The introduction of minimal residual disease (MRD) monitoring, in the Swedish national guidelines for acute lymphoblastic leukaemia, was evaluated in 35 patients aged 46-79 years (median 61), who were diagnosed from 2007 to 2011 and treated with high-intensity, block-based chemotherapy (ABCDV/VABA induction). Both a high complete remission rate (91 %) and acceptable overall survival (OS) rate (47 %) at 5 years were achieved. MRD by flow cytometry was measured in 73 % of the patients reaching complete remission after the first course, but was omitted by the clinicians for eight patients who were either over 70 years of age or already met conventional high-risk criteria. Factors negatively influencing OS were age over 65 years and WHO status >= 2. MRD < 0.1 % after induction had positive impact on continuous complete remission but not on OS. Only five patients were allocated to allogeneic haematopoietic stem cell transplantation in first remission, mainly due to conventional high risk factors. Thus, use of intensive remission induction therapy is effective in a selection of older patients. In a population for whom the possibilities of treatment escalation are limited, the optimal role of MRD monitoring remains to be determined.

    Keywords
    Acute lymphoblastic leukaemia, Adults, Minimal residual disease, Flow cytometry
    National Category
    Cancer and Oncology
    Research subject
    Oncology
    Identifiers
    urn:nbn:se:oru:diva-44342 (URN)10.1007/s12032-015-0582-2 (DOI)000351474100049 ()25796502 (PubMedID)
    Note

    Funding Agency:

    Lions Cancer Research Foundation, Uppsala

    Available from: 2015-04-20 Created: 2015-04-20 Last updated: 2018-06-29Bibliographically approved
    4. Age but not Philadelphia positivity impairs outcome in older/elderly patients with Acute Lymphoblastic Leukemia in the Swedish population
    Open this publication in new window or tab >>Age but not Philadelphia positivity impairs outcome in older/elderly patients with Acute Lymphoblastic Leukemia in the Swedish population
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    General Practice
    Identifiers
    urn:nbn:se:oru:diva-48533 (URN)
    Available from: 2016-02-23 Created: 2016-02-23 Last updated: 2018-01-10Bibliographically approved
  • 5.
    Kozlowski, Piotr
    et al.
    Örebro University, School of Health Sciences. Hematology Section, Department of Medicine.
    Bergfelt, Emma
    Hematology, Department of Medical Sciences, Uppsala University, Uppsala.
    Ahlberg, Lucia
    Department of Hematology, University Hospital of Linköping, Linköping.
    Bernell, Per
    Division of Hematology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm.
    Hulegårdh, Erik
    Department of Hematology and Coagulation, Sahlgrenska University, Göteborg.
    Karbach, Holger
    Department of Hematology, Cancer Center, University Hospital of Umeå, Umeå .
    Karlsson, Karin
    Department of Hematology, Skåne University Hospital, Lund.
    Tomaszewska-Toporska, Beata
    Department of Hematology, Skåne University Hospital, Lund.
    Åström, Maria
    Örebro University, School of Health Sciences. Hematology Section, Department of Medicine.
    Hallböök, Helene
    Hematology, Department of Medical Sciences, Uppsala University, Uppsala.
    Age but not Philadelphia positivity impairs outcome in older/elderly patients with Acute Lymphoblastic Leukemia in the Swedish populationManuscript (preprint) (Other academic)
  • 6.
    Kozlowski, Piotr
    et al.
    Örebro University, School of Health Sciences.
    Lennmyr, Emma
    Dept of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Ahlberg, Lucia
    University Hospital of Linköping, Linköping, Sweden.
    Bernell, Per
    Div of Hematology, Dept of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Hulegårdh, Erik
    Dept of Hematology and Coagulation, Sahlgrenska University Hospital, Göteborg, Sweden.
    Karbach, Holger
    Dept of Hematology, Cancer Center, University Hospital of Umeå, Umeå, Sweden.
    Karlsson, Karin
    Dept of Hematology and Oncology, Skåne University Hospital, Lund, Sweden.
    Tomaszewska-Toporska, Beata
    Dept of Hematology and Oncology, Skåne University Hospital, Lund, Sweden.
    Åström, Maria
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Hallböök, Heléne
    Dept of Medical Sciences, Uppsala University, Uppsala, Sweden.
    The Swedish Adult Acute Lymphoblastic Leukemia Group (SVALL), Group author
    Age but not Philadelphia positivity impairs outcome in older/elderly patients with acute lymphoblastic leukemia in Sweden2017In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 99, no 2, p. 141-149Article in journal (Refereed)
    Abstract [en]

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

    METHODS: Using Swedish national leukemia registries, we investigated disease/patient characteristics, treatment choices, outcome, and the impact of an age-adapted protocol (introduced in 2009) in this population-based study of patients aged 55-85 years, diagnosed with ALL 2005-2012.

    RESULTS: Of 174 patients, 82% had B-phenotype, 11% Burkitt leukemia (excluded), and 7% T-phenotype. Philadelphia chromosome positivity (Ph+) occurred in 35%. Of the 155 B- and T- ALL patients, 80% were treated with intensive protocols, and 20% with a palliative approach. Higher age and WHO performance status ≥2 influenced the choice of palliation. Intensive, palliative, and both approaches, resulted in complete remission rate 83/16/70%, and 3 year overall survival (OS) 32/3/26%. The age-adapted protocol did not improve outcome. With intensive treatment, platelet count ≤35 × 10(9) /L, and age ≥75 years were adverse prognostic factors for OS, Ph+ was not. Male sex was an adverse prognostic factor in the 55-64 year group.

    CONCLUSIONS: We report a high frequency of Ph+ in older/elderly patients, with no evidence of poorer outcome compared to Ph negative disease. Overall prognosis for elderly patients with ALL remains dismal, despite the use of age-adapted treatment. This article is protected by copyright. All rights reserved.

  • 7.
    Kozlowski, Piotr
    et al.
    Örebro University Hospital. Hematology Section, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Åström, Maria
    Örebro University Hospital. Hematology Section, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Ahlberg, Lucia
    Department of Hematology, University Hospital of Linköping, Linköping, Sweden.
    Bernell, Per
    Karolinska University Hospital, Stockholm, Sweden.
    Hulegårdh, Erik
    Department of Hematology and Coagulation, Sahlgrenska University, Göteborg, Sweden.
    Hägglund, Hans
    Karolinska University Hospital, Stockholm, Sweden.
    Karlsson, Karin
    Department of Hematology, Skåne University Hospital, Lund, Sweden.
    Markuszewska-Kuczymska, Alicja
    Department of Hematology, Cancer Center, University Hospital, Umeå, Sweden.
    Tomaszewska-Toporska, Beata
    Department of Hematology, Skåne University Hospital, Lund, Sweden.
    Smedmyr, Bengt
    Department of Hematology, Uppsala University, Uppsala, Sweden.
    Amini, Rose-Marie
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Hallböök, Helene
    Department of Hematology, Uppsala University, Uppsala, Sweden.
    High relapse rate of T cell acute lymphoblastic leukemia in adults treated with Hyper-CVAD chemotherapy in Sweden2014In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 92, no 5, p. 377-381Article in journal (Refereed)
    Abstract [en]

    Background: 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).

    Patients and methods: Between October 2002 and September 2006, 24 patients were diagnosed with T-ALL in Sweden; 19 were eligible for treatment with the protocol.

    Results: The median age was 32 yr (range 18-72 yr). Complete remission (CR) was obtained in 17 of 19 (89%) patients, and the treatment was relatively well tolerated. Allogeneic stem cell transplantation (SCT) was recommended in high-risk disease and was performed in four patients upfront. Two- and 5-yr leukemia-free survivals (LFS) in 17 patients with CR achievement were identical, at 29% (95% confidence interval [CI]: 8-51). Two- and 5-yr overall survival (OS) in whole cohort was 63% (95% CI: 42-85) and 47% (95% CI: 26-69), respectively. The 5-yr LFS for 15 patients who did not receive allogeneic SCT upfront were 20% (95% CI: 0-40), although 14 of 15 completed the protocol (eight cycles). Relapse occurred in 2 of 4 upfront-transplanted patients and in 12 of 15 patients treated with chemotherapy alone, six of whom received allogeneic SCT in CR2. Age ≥35 yr influenced OS negatively in univariate analysis (HR 5.1, 95% CI: 1.55-16.7).

    Conclusions: Hyper-CVAD treatment resulted in a high CR rate and appeared safe, but it showed poor efficacy at preventing relapse. Therefore, this treatment is no longer recommended for adults with T-ALL in Sweden.

  • 8.
    Kozlowski, Piotr
    et al.
    Hematology Section, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Åström, Maria
    Hematology Section, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Ahlberg, Lucia
    Department of Hematology, University Hospital of Linköping, Linköping, Sweden.
    Bernell, Per
    Karolinska University Hospital, Stockholm, Sweden.
    Hulegårdh, Erik
    Department of Hematology and Coagulation, Sahlgrenska Hospital, Gothenburg, Sweden.
    Hägglund, Hans
    Karolinska University Hospital, Stockholm, Sweden.
    Karlsson, Karin
    Department of Hematology, Skåne University Hospital, Lund, Sweden.
    Markuszewska-Kuczymska, Alicja
    Department of Hematology, Cancer Center, University Hospital, Umeå, Sweden.
    Tomaszewska-Toporska, Beata
    Department of Hematology, Skåne University Hospital, Lund, Sweden.
    Smedmyr, Bengt
    Department of Hematology, Uppsala University, Uppsala, Sweden.
    Hallböök, Helene
    Department of Hematology, Uppsala University, Uppsala, Sweden.
    High curability via intensive reinduction chemotherapy and stem cell transplantation in young adults with relapsed acute lymphoblastic leukemia in Sweden 2003-20072012In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 97, no 9, p. 1414-1421Article in journal (Refereed)
    Abstract [en]

    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.

  • 9.
    Lennmyr, Emma Bergfelt
    et al.
    Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Kozlowski, Piotr
    Department of Medicine.
    Ahlberg, Lucia
    Department of Hematology, University Hospital of Linköping, Linköping, Sweden.
    Bernell, Per
    Division of Hematology, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Hulegårdh, Erik
    Department of Hematology and Coagulation, Sahlgrenska University Hospital, Göteborg, Sweden.
    Izarra, Antonio Santamaria
    Department of Hematology, Cancer Center, University Hospital of Umeå, Umeå, Sweden.
    Karlsson, Karin
    Department of Hematology and Oncology, Skåne University Hospital, Lund, Sweden.
    Tomaszewska-Toporska, Beata
    Department of Hematology and Oncology, Skåne University Hospital, Lund, Sweden.
    Åström, Maria
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medicine.
    Hallböök, Helene
    Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Swedish Adult Acute Lymphoblastic Leukemia Group (SVALL), Group Author
    Real-world data on first relapse of acute lymphoblastic leukemia in patients >55 years2018In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 59, no 10, p. 2470-2473Article in journal (Refereed)
  • 10.
    Osterborg, Anders
    et al.
    Dept Haematol, Karolinska Univ Hosp, Stockholm, Sweden.
    Wierda, William G.
    M D Anderson Canc Ctr, Univ Texas, Houston TX, USA; Canc Therapy Res Ctr, San Antonio TX, USA.
    Mayer, Jiri
    Fac Hosp Brno, Dept Internal Med Haematooncol, University Hospital, Brno, Czech Republic.
    Hess, Georg
    Johannes Gutenberg Univ, Mainz, Germany.
    Hillmen, Peter
    Leeds Teaching Hosp, Leeds, England.
    Schetelig, Johannes
    Univ Klinickum Carl Gustav Carus, Dresden, Germany.
    Schuh, Anna
    Churchill Hosp, Oxford, England.
    Smolej, Lukas
    Fac Med Hradec Kralove, Univ Hosp, Hradec Kralove, Czech Republic; Charles Univ Prague, Hradec Kralove, Czech Republic.
    Beck, Christian
    Haematol Onkolog Inst, Moenchengladbach, Germany.
    Dreyfus, Brigitte
    Hop Jean Bernanrd, Poitiers, France.
    Hellman, Andrzej
    Akad Med Gdansku, Gdansk, Poland.
    Kozlowski, Piotr
    Örebro University Hospital.
    Pfreundschuh, Michael
    Univ Saarlandes Kliniken, Homburg, Germany.
    Rizzi, Rita
    Azienda ospedaliero-universitaria consorziale policlinico, Bari, Italy.
    Spacek, Martin
    Fak Nemocnice, Prague, Czech Republic..
    Phillips, Jennifer L.
    GlaxoSmithKline, Collegeville PA, USA.
    Gupta, Ira V.
    Williams, Vanessa
    Glaxo SmithKline, Durham NC, USA.
    Jewell, Roxanne C.
    Glaxo SmithKline, Durham NC ,USA..
    Nebot, Noelia
    Glaxo SmithKline, Durham NC, USA.
    Lisby, Steen
    Genmab AS, Copenhagen, Denmark.
    Dyer, Martin J. S.
    Ernest & Helen Scott Haematol Res Inst, Univ Leicester, Leicester, England.
    Ofatumumab retreatment and maintenance in fludarabine-refractory chronic lymphocytic leukaemia patients2015In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 170, no 1, p. 40-49Article in journal (Refereed)
    Abstract [en]

    There are limited data on retreatment with monoclonal antibodies (mAb) in patients with chronic lymphocytic leukaemia (CLL). In a pivotal study, ofatumumab (human anti-CD20 mAb) monotherapy demonstrated a 47% objective response rate (ORR) in fludarabine refractory CLL patients. From this study, a subset of 29 patients who had at least stable disease and then progressed were retreated with eight weekly ofatumumab infusions (induction treatment period), followed by monthly infusions for up to 2years (maintenance treatment period). The ORR after 8weeks of induction retreatment was 45% and 24% had continued disease control after maintenance at 52weeks. Efficacy and safety of the retreated patients were compared with their initial results in the pivotal study. Response duration was 241months vs. 68months; time to next therapy was 148months vs. 123months; and progression-free survival was 74months vs. 79months (medians). Upon retreatment, 72% had infusion reactions, mostly Grade 1-2. Three patients had fatal infections. In summary, ofatumumab retreatment and maintenance therapy was feasible in patients with heavily pretreated CLL and appeared to result in more durable disease control than initial ofatumumab treatment in this subset of patients who may have a more favourable disease profile.

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