uu.seUppsala University Publications
Change search
Link to record
Permanent link

Direct link
BETA
Alternative names
Publications (10 of 32) Show all publications
Giebel, S., Marks, D. I., Boissel, N., Baron, F., Chiaretti, S., Ciceri, F., . . . Dombret, H. (2019). Hematopoietic stem cell transplantation for adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first remission: a position statement of the European Working Group for Adult Acute Lymphoblastic Leukemia (EWALL) and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplantation, 54(6), 798-809
Open this publication in new window or tab >>Hematopoietic stem cell transplantation for adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first remission: a position statement of the European Working Group for Adult Acute Lymphoblastic Leukemia (EWALL) and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)
Show others...
2019 (English)In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 54, no 6, p. 798-809Article, review/survey (Refereed) Published
Abstract [en]

Allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission is a standard of care for adult patients with Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) and high risk of relapse. However, the stratification systems vary among study groups. Inadequate response at the level of minimal residual disease is the most commonly accepted factor indicating the need for alloHSCT. In this consensus paper on behalf of the European Working Group for Adult Acute Lymphoblastic Leukemia and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation, we summarize available evidence and reflect current clinical practice in major European study groups regarding both indications for HSCT and particular aspects of the procedure including the choice of donor, source of stem cells and conditioning. Finally, we propose recommendations for daily clinical practice as well as for planning of prospective trials.

National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-387985 (URN)10.1038/s41409-018-0373-4 (DOI)000470103100003 ()30385870 (PubMedID)
Available from: 2019-06-27 Created: 2019-06-27 Last updated: 2019-06-27Bibliographically approved
Lennmyr, E., Karlsson, K., Ahlberg, L., Garelius, H., Hulegardh, E., Izarra, A. S., . . . Hallböök, H. (2019). Survival in adult acute lymphoblastic leukaemia (ALL): A report from the Swedish ALL Registry. European Journal of Haematology, 103(2), 88-98
Open this publication in new window or tab >>Survival in adult acute lymphoblastic leukaemia (ALL): A report from the Swedish ALL Registry
Show others...
2019 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 103, no 2, p. 88-98Article in journal (Refereed) Published
Abstract [en]

Objectives: As new, effective therapies emerge for acute lymphoblastic leukaemia (ALL), the results of clinical trials need to relate to standard of care.

Methods: We used the population-based Swedish ALL Registry to evaluate characteristics, treatment and long-term outcome in 933 patients with diagnosis between 1997 and 2015.

Results: The median age was 53 years. The frequency of Philadelphia (Ph)-positive leukaemia was 34% of examined B-ALL with a peak incidence at 50-59 years. Five-year overall survival (OS) improved between 1997-2006 and 2007-2015; in patients 18-45 years from 50% (95% CI 43-57) to 65% (95% CI 58-72), 46-65 years from 25% (95% CI 18-32) to 46% (95% CI 37-55) and >65 years from 7% (95% CI 2.6-11) to 11% (95% CI 5.9-16) (P < 0.05). Men with Ph-neg B-ALL 46-65 years had inferior OS compared with women (P < 0.01). Standardised mortality ratio was 5.7 (95% CI 5.0-6.3) for patients who survived 5 years from diagnosis. In multivariable analysis, Ph-positive disease was not associated with impaired prognosis but with lower risk of death in 2007-2015.

Conclusions: In a population-based cohort, OS has improved in adult ALL, especially for Ph-positive disease but for middle-aged men with Ph-negative B-ALL outcome was poor. Cure without late toxicity or relapse is still desired.

Place, publisher, year, edition, pages
WILEY, 2019
Keywords
acute lymphoblastic leukaemia, adult, Philadelphia-positive
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-390495 (URN)10.1111/ejh.13247 (DOI)000475475200003 ()31074910 (PubMedID)
Available from: 2019-08-12 Created: 2019-08-12 Last updated: 2019-09-17Bibliographically approved
Enblad, G., Karlsson, H., Gammelgård, G., Wenthe, J., Lövgren, T., Amini, R.-M., . . . Loskog, A. (2018). A Phase I/IIa Trial Using CD19-Targeted Third-Generation CAR T Cells for Lymphoma and Leukemia. Clinical Cancer Research, 24(24), 6185-6194
Open this publication in new window or tab >>A Phase I/IIa Trial Using CD19-Targeted Third-Generation CAR T Cells for Lymphoma and Leukemia
Show others...
2018 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 24, no 24, p. 6185-6194Article in journal (Refereed) Published
Abstract [en]

Purpose: The chimeric antigen receptor (CAR) T-cell therapy has been effective for patients with CD19(+) B-cell malignancies. Most studies have investigated the second-generation CARs with either CD28 or 4-1BB costimulatory domains in the CAR receptor. Here, we describe the first clinical phase I/IIa trial using third-generation CAR T cells targeting CD19 to evaluate safety and efficacy.

Patients and Methods: Fifteen patients with B-cell lymphoma or leukemia were treated with CAR T cells. The patients with lymphoma received chemotherapy during CAR manufacture and 11 of 15 were given low-dose cyclophosphamide and fludarabine conditioning prior to CAR infusion. Peripheral blood was sampled before and at multiple time points after CAR infusion to evaluate the persistence of CAR T cells and for immune profiling, using quantitative PCR, flow cytometry, and a proteomic array.

Results: Treatment with third-generation CAR T cells was generally safe with 4 patients requiring hospitalization due to adverse reactions. Six of the 15 patients had initial complete responses [4/11 lymphoma and 2/4 acute lymphoblastic leukemia (ALL)], and 3 of the patients with lymphoma were in remission at 3 months. Two patients are still alive. Best predictor of response was a good immune status prior to CAR infusion with high IL12, DC-Lamp, Fas ligand, and TRAIL. Responding patients had low monocytic myeloid-derived suppressor cells (MDSCs; CD14(+)CD33(+)HLA(-)DR(-)) and low levels of IL6, IL8, NAP3, sPDL1, and sPDL2.

Conclusions: Third-generation CARs may be efficient in patients with advanced B-cell lymphoproliferative malignancy with only modest toxicity. Immune profiling pre- and posttreatment can be used to find response biomarkers.

National Category
Cancer and Oncology Hematology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-372924 (URN)10.1158/1078-0432.CCR-18-0426 (DOI)000453267600012 ()30097433 (PubMedID)
Funder
Swedish Research CouncilAFA InsuranceSwedish Cancer Society
Available from: 2019-01-10 Created: 2019-01-10 Last updated: 2019-03-29Bibliographically approved
Mogensen, S. S., Harila-Saari, A., Makitie, O., Myrberg, I. H., Niinimaki, R., Vestli, A., . . . Frandsen, T. L. (2018). Comparing osteonecrosis clinical phenotype, timing, and risk factors in children and young adults treated for acute lymphoblastic leukemia. Pediatric Blood & Cancer, 65(10), Article ID e27300.
Open this publication in new window or tab >>Comparing osteonecrosis clinical phenotype, timing, and risk factors in children and young adults treated for acute lymphoblastic leukemia
Show others...
2018 (English)In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 65, no 10, article id e27300Article in journal (Refereed) Published
Abstract [en]

Background: Treatment-related osteonecrosis (ON) is a serious complication of treatment of acute lymphoblastic leukemia (ALL).

Procedure: This study included 1,489 patients with ALL, aged 1-45years, treated according to the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol, using alternate-week dexamethasone during delayed intensification, with prospective registration of symptomatic ON. We aimed at comparing risk factors, timing, and clinical characteristics of ON in children and young adults.

Results: ON was diagnosed in 67 patients, yielding a 5-year cumulative incidence of 6.3%, but 28% in female adolescents. Median age at ALL diagnosis was 12.1years and 14.9years for females and males, respectively. At ON diagnosis, 59 patients had bone pain (91%) and 30 (46%) had multiple-joint involvement. The median interval between ALL and ON diagnosis was significantly shorter in children aged 1.0-9.9years (0.7years [range: 0.2-2.1]) compared with adolescents (1.8years [range: 0.3-3.7, P<0.001]) and adults (2.1years [range: 0.4-5.3, P=0.001]). Female sex was a risk factor in adolescent patients (hazard ratio [HR]=2.1, 95% confidence interval [CI]: 1.1-4.2) but not in children aged 1.1-9.9years (HR=2.4, 95% CI: 0.9-6.2, P=0.08) or adults aged 19-45years (HR=1.1, 95% CI: 0.3-4.0). Age above 10years at ALL diagnosis (odds ratio [OR]=3.7, P=0.026) and multiple joints affected at ON diagnosis (OR=3.4, P=0.027) were risk factors for developing severe ON.

Conclusion: We provide a detailed phenotype of patients with ALL with symptomatic ON, including description of risk factors and timing of ON across age groups. This awareness is essential in exploring measures to prevent development of ON.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
acute lymphoblastic leukemia, osteonecrosis, phenotype, risk factors
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-362090 (URN)10.1002/pbc.27300 (DOI)000442500600038 ()29943905 (PubMedID)
Funder
Swedish Childhood Cancer Foundation
Available from: 2018-10-03 Created: 2018-10-03 Last updated: 2018-10-03Bibliographically approved
Kinch, A., Hallböök, H., Arvidson, J., Sällström, K., Bondeson, K. & Pauksen, K. (2018). Long-term outcome of Epstein-Barr virus DNAemia and PTLD with the use of preemptive rituximab following allogeneic HSCT. Leukemia and Lymphoma, 59(5), 1172-1179
Open this publication in new window or tab >>Long-term outcome of Epstein-Barr virus DNAemia and PTLD with the use of preemptive rituximab following allogeneic HSCT
Show others...
2018 (English)In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 59, no 5, p. 1172-1179Article in journal (Refereed) Published
Abstract [en]

We studied retrospectively the outcome of Epstein-Barr virus (EBV)-related disease with EBV monitoring and preemptive rituximab to prevent post-transplant lymphoproliferative disorder (PTLD) in 319 consecutive allogeneic stem cell transplantations 2004-2012. Patients who received anti-thymocyte globulin (ATG) or alemtuzumab were regarded as high-risk for PTLD (n = 214). EBV DNAemia ≥1000 copies/mL plasma was observed in 50 (23%) of the high-risk patients. Thirty-three of the high-risk (15%) and one of the low-risk (1%) patients received rituximab, in combination with reduction of immunosuppression (n = 24) or chemotherapy (n = 4). Although rituximab was initiated only 5 d after first EBV load ≥1000 copies/mL, 85% of the rituximab-treated patients developed symptoms (lymphadenopathy 50%, fever 76%, and encephalitis/meningitis 12%). Response-rate to EBV treatment was 88%. Overall survival at 1- and 5-year was 71 and 52% for rituximab-treated patients, which was not inferior to all other patients post-transplant. In conclusion, rituximab therapy for EBV DNAemia does not affect long-term survival negatively.

Keywords
EBV, PTLD, allogeneic HSCT, rituximab, survival
National Category
Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-343169 (URN)10.1080/10428194.2017.1365860 (DOI)000426933700017 ()28831836 (PubMedID)
Available from: 2018-02-26 Created: 2018-02-26 Last updated: 2018-05-16Bibliographically approved
Lennmyr, E. B., Kozlowski, P., Ahlberg, L., Bernell, P., Hulegardh, E., Izarra, A. S., . . . Hallböök, H. (2018). Real-world data on first relapse of acute lymphoblastic leukemia in patients > 55 years [Letter to the editor]. Leukemia and Lymphoma, 59(10), 2470-2473
Open this publication in new window or tab >>Real-world data on first relapse of acute lymphoblastic leukemia in patients > 55 years
Show others...
2018 (English)In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 59, no 10, p. 2470-2473Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
Taylor & Francis Group, 2018
National Category
Cancer and Oncology Hematology
Identifiers
urn:nbn:se:uu:diva-374878 (URN)10.1080/10428194.2017.1416369 (DOI)000455166400026 ()29345172 (PubMedID)
Funder
Thuréus stiftelse för främjande av geriatrisk forskningErik, Karin och Gösta Selanders Foundation
Available from: 2019-01-24 Created: 2019-01-24 Last updated: 2019-01-24Bibliographically approved
Toft, N., Birgens, H., Abrahamsson, J., Griškevičius, L., Hallböök, H., Heyman, M., . . . Schmiegelow, K. (2018). Results of NOPHO ALL2008 treatment for patients aged 1-45 years with acute lymphoblastic leukemia.. Leukemia, 32, 606-615
Open this publication in new window or tab >>Results of NOPHO ALL2008 treatment for patients aged 1-45 years with acute lymphoblastic leukemia.
Show others...
2018 (English)In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 32, p. 606-615Article in journal (Refereed) Published
Abstract [en]

Adults with acute lymphoblastic leukemia (ALL) do worse than children. From 7/2008 to 12/2014, Nordic and Baltic centers treated 1509 consecutive patients aged 1-45 years with Philadelphia chromosome-negative ALL according to the NOPHO ALL2008 without cranial irradiation. Overall, 1022 patients were of age 1-9 years (A), 266 were 10-17 years (B) and 221 were 18-45 years (C). Sixteen patients (three adults) died during induction. All others achieved remission after induction or 1-3 intensive blocks. Subsequently, 45 patients (12 adults) died, 122 patients relapsed (32 adults) with a median time to relapse of 1.6 years and 13 (no adult) developed a second malignancy. Median follow-up time was 4.6 years. Among the three age groups, older patients more often had higher risk ALL due to T-ALL (32%/25%/9%, P<0.001), KMT2A rearrangements (6%/5%/3%, P<0.001) and higher day 29 residual leukemia for B-lineage (P<0.001), but not T-ALL (P = 0.53). Event-free survival rates (pEFS(5y)) were 89 +/- 1% (A), 80 +/- 3% (B) and 74 +/- 4% (C) with significant differences only for non-high risk groups. Except for thrombosis, pancreatitis and osteonecrosis, the risk of 19 specified toxicities was not enhanced by age above 10 years. In conclusion, a pediatric-based protocol is tolerable and effective for young adults, despite their increased frequency of higher risk features.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-343170 (URN)10.1038/leu.2017.265 (DOI)000427041900004 ()28819280 (PubMedID)
Available from: 2018-02-26 Created: 2018-02-26 Last updated: 2018-05-23Bibliographically approved
Rank, C. U., Toft, N., Tuckuviene, R., Grell, K., Nielsen, O. J., Frandsen, T. L., . . . Schmiegelow, K. (2018). Thromboembolism in acute lymphoblastic leukemia: results of NOPHO ALL2008 protocol treatment in patients aged 1 to 45 years. Blood, 131(22), 2475-2484
Open this publication in new window or tab >>Thromboembolism in acute lymphoblastic leukemia: results of NOPHO ALL2008 protocol treatment in patients aged 1 to 45 years
Show others...
2018 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 131, no 22, p. 2475-2484Article in journal (Refereed) Published
Abstract [en]

Thromboembolism frequently occurs during acute lymphoblastic leukemia (ALL) therapy. We prospectively registered thromboembolic events during the treatment of 1772 consecutive Nordic/Baltic patients with ALL aged 1 to 45 years who were treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol (July 2008-April 2017). The 2.5-year cumulative incidence of thromboembolism (N = 137) was 7.9% (95% confidence interval [CI], 6.6-9.1); it was higher in patients aged at least 10 years (P < .0001). Adjusted hazard ratios (HRas) were associated with greater age (range, 10.0-17.9 years: HRa, 4.9 [95% CI, 3.1-7.8; P < .0001]; 18.0-45.9 years: HRa, 6.06 [95% CI, 3.65-10.1; P < .0001]) and mediastinal mass at ALL diagnosis (HRa, 2.1; 95% CI, 1.0-4.3; P = .04). In a multiple absolute risk regression model addressing 3 thromboembolism risk factors, age at least 10 years had the largest absolute risk ratio (RRage, 4.7 [95% CI, 3.1-7.1]; RRenlarged (lymph nodes), 2.0 [95% CI, 1.2-3.1]; RRmediastinal mass, 1.6 [95% CI, 1.0-2.6]). Patients aged 18.0 to 45.9 years had an increased hazard of pulmonary embolism (HRa, 11.6; 95% CI, 4.02-33.7; P < .0001), and patients aged 10.0 to 17.9 years had an increased hazard of cerebral sinus venous thrombosis (HRa, 3.3; 95% CI, 1.5-7.3; P = .003) compared with children younger than 10.0 years. Asparaginase was truncated in 38/128 patients with thromboembolism, whereas thromboembolism diagnosis was unassociated with increased hazard of relapse (P = .6). Five deaths were attributable to thromboembolism, and patients younger than 18.0 years with thromboembolism had increased hazard of dying compared with same-aged patients without thromboembolism (both P <= .01). In conclusion, patients aged at least 10 years could be candidates for preemptive antithrombotic prophylaxis. However, the predictive value of age 10 years or older, enlarged lymph nodes, and mediastinal mass remain to be validated in another cohort.

Place, publisher, year, edition, pages
AMER SOC HEMATOLOGY, 2018
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-358085 (URN)10.1182/blood-2018-01-827949 (DOI)000433990200010 ()29661787 (PubMedID)
Available from: 2018-08-30 Created: 2018-08-30 Last updated: 2018-08-30Bibliographically approved
Kozlowski, P., Lennmyr, E., Ahlberg, L., Bernell, P., Hulegårdh, E., Karbach, H., . . . Hallböök, H. (2017). Age but not Philadelphia positivity impairs outcome in older/elderly patients with acute lymphoblastic leukemia in Sweden. European Journal of Haematology, 99(2), 141-149
Open this publication in new window or tab >>Age but not Philadelphia positivity impairs outcome in older/elderly patients with acute lymphoblastic leukemia in Sweden
Show others...
2017 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 99, no 2, p. 141-149Article in journal (Refereed) Published
Abstract [en]

ObjectivesOlder/elderly patients with acute lymphoblastic leukemia (ALL) are poorly represented in clinical trials. MethodsUsing 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 55-85years, diagnosed with ALL 2005-2012. ResultsOf 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 35x10(9)/L and age 75years were adverse prognostic factors for OS, Ph+ was not. Male sex was an adverse prognostic factor in the 55-64 year age-group. ConclusionsWe 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.

Place, publisher, year, edition, pages
WILEY, 2017
Keywords
acute lymphoblastic leukemia, chemotherapy, elderly, epidemiology
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-329913 (URN)10.1111/ejh.12896 (DOI)000404936400005 ()
Available from: 2017-10-20 Created: 2017-10-20 Last updated: 2017-10-20Bibliographically approved
Kinch, A., Hallböök, H., Arvidson, J., Sällström, K., Bondeson, K. & Pauksen, K. (2017). Epstein-Barr virus-related disease after allogeneic HSCT and use of pre-emptive rituximab: Clinical Features And Outcome. Paper presented at 43rd Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation (EBMT), MAR 26-29, 2017, Marseille, FRANCE. Bone Marrow Transplantation, 52(Supplement: 1), S88-S88
Open this publication in new window or tab >>Epstein-Barr virus-related disease after allogeneic HSCT and use of pre-emptive rituximab: Clinical Features And Outcome
Show others...
2017 (English)In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 52, no Supplement: 1, p. S88-S88Article in journal, Meeting abstract (Other academic) Published
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-351609 (URN)10.1038/bmt.2017.132 (DOI)000424355300109 ()
Conference
43rd Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation (EBMT), MAR 26-29, 2017, Marseille, FRANCE
Note

In: Abstracts From The 43RD Annual Meeting Of The Europeansociety For Blood And Marrow Transplantation: Physicians—Oral Sessions (O011–O179).

Meeting Abstract: O132

Available from: 2018-06-08 Created: 2018-06-08 Last updated: 2018-06-08Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-5764-3213

Search in DiVA

Show all publications