Haematology includes both benign and malignant diseases. Among the benign are different forms of cytopenias, both hereditary and aquired, such as anaemias, neutropenias and thrombocytopenias, as well as iron metabolism disorders. *The malignant haematologic diseases constitute a heterogeneous group of cancer diseases which are usually caused by uncontrolled growth of blood cells. In most cases it is immature stem cells that have lost their growth regulation and/or their ability to differentiate into mature effector cells of either the myeloid or the lymphoid lineages. Such loss of control may give rise to both acute and chronic leukemias with overproduction of white blood cells but also to myeloproliferativa neoplasms with over-production of red cells and/or platelets. Our clinical oriented research is centered on leukemias, but also includes myeloproliferativa neoplasms, cancer anemia and supportive care. Through preclinical drug development, and the conduction of clinical trials as well as establishment of cancer registries we aim to develop new treatment strategies and better supportive care for patients.
The research is conducted by a number of teams, being formed from the knowledge basis of the most important disease fields in haematology.Currently we focus on the following areas;
- Development and testing of new drugs and therapy strategies in malignant haematological diseases; acute myelogenous leukaemia, acute lymphoblastic leukemia, myelodysplastic syndrome, chronic myelogenous leukaemia, chronic lymphocytic leukemia and multiple myeloma.
- Studies bases on the Swedish national, population based quality registries formalignant haematological diseases.
- Translational research in association with the regional biobank project U-CAN.
- Studies on myeloproliferativa neoplasms, cancer anaemia and supportive care.
An important part of the activities of the Haematology group is also leadership and participation in national and international research groups for initiating international studies, and for the development of treatment guidelines and Centres of clinical excellence.
Molecular studies and preclinical drug development in acute myeloid leukaemia (AML)
Anna Eriksson, Martin Höglund
In close collaboration with the Pharmacology Cancer group (prof Rolf Larsson) our focus is preclinical development of new drugs in AML. In particular, we are interested in investigating signal transduction inhibitors, “intelligent” drug combinations and in exploring the anti-leukemic efficacy of drugs previously used outside the cancer filed (“repositioning”). Key elements in this research are the application of information-rich compound libraries, clinically relevant tumour model systems (including primary tumour cells from well characterised patients) and high-throughput analytical capabilities in combination with bioinformatics expertise. Uppsala is leading centre in the first-in-man Phase I trial AKN-001, which is based preclinical work in our research group.
Sören Lehmann, Anna Eriksson, My Björklund, Albin Österros, Anne Neddermeyer
In November 2015 professor Sören Lehmann started to set up his lab group at the Rudbeck Laboratory focused on epigenetics and novel drug development in AML. The Lehmann group is a translational research group with research projects spanning from basic molecular characterization of AML through developing novel drugs to clinical trials and epidemiologic studies of AML. The molecular studies are focues on epigenetic aberrations in AML. The group currently consists of 11 persons with activity both in Uppsala and in Karolinska with successively increasing activity at Uppsala University.
Acute lymphoblastic leukaemia – national studies of toxicity, prognostic factors and treatment protocols
Emma Bergfelt, Helene Hallböök and Bengt Smedmyr
The Swedish Adult Lymphoblastic Leukaemia Group (SVALL), chairperson Hallböök, is a working group with responsibility for national guidelines and studies. We are evaluating the outcome of national treatment protocols in younger and elderly adults with ALL as well as the prognostic value of minimal residual disease (MRD) as analysed by advanced flow cytometry.
Studies on prognostication and resistance mechanisms in chronic lymphocytic leukemia (CLL)
Mattias Mattsson, Karin Larson and Martin Höglund
In close collaboration with professor Richard Rosenquist (Dept of Immunology, Genetics and Pathology), we are presently performing studies in CLL on prognostic and predictive biomarkers, clonal evolution and resistance in patients with advanced disease treated with the BCR inhibitors ibrutinib or idealisib. In another project, we aim to clinically and genetically characterise subsets of CLL with very good prognosis.
Population-based registry studies in CML, MDS, AML and ALL
Emma Bergfelt, Elisabeth Ejerblad, Martin Höglund, Helene Hallböök, Hans Hägglund and Gunnar Larfors
The Swedish population based registries in patients with haematological malignancies are internationally unique. Presently, more than 1000 patients with CML and more than 6000 patients with acute leukaemia are included. In a recent publication (Hoglund ta al, Blood 2013, 122, p 1284), we have shown that the estimated 5 yrs. survival for patients with CML is 80% and in certain diagnostic subgroups 95%. At present, our studies focus on the outcome of patients with secondary leukaemia, relapsed AML, patient related outcome measures (PROM) and the association of CML with other types of cancer. Using the Nordic Registry for Hematopoietic Stem Cell Donors (NRHSD) and linking it other national registries, we are studying short-term and possible long-term complications following donation of hematopoietic stem cells.
Chronic myelogenous leukaemia (CML)
Stina Söderlund, Ulla Olsson-Strömberg, and Bengt Simonsson
In collaboration with Dept. of Clinical Immunity we are investigating pre-existing and developing anti-tumour immunity during treatment with tyrosine kinase inhibitors (TKIs). Patients enrolled in clinical trials within a Nordic network are evaluated for immunological phenotype and function. Different TKIs are investigated, and the results are then correlated to TKI efficacy. We have investigated for the presence of immune escape mechanisms such as myeloid-derived suppressor cells and T regulatory cells. These results may aid the understanding of which patients that can benefit from TKI discontinuation.
Plasma cell disorders
Sara Rosengren, Torbjörn Karlsson and Kristina Carlson
Clinical studies on plasma cell disorders are performed in collaboration with the Nordic Myeloma Study Group and the Swedish Group for plasma cell disorders. In collaboration with the PET-imaging centre and cardiologic an imaging study of cardiac AL-amyloidosis has recently been performed.
Clinical and laboratory studies on infectious and haemorrhagic complications in patients treated for haematological malignancies
Tobias Svensson, Honar Cherif
We have recently conducted or are presently conducting several clinical and laboratory studies aiming to improve the diagnosis and management of these complications in patients receiving treatment for haematological cancers. These studies include for example: assessing the impact of IgG subgroup deficiency in patients with Chronic Lymphocytic Leukaemia (CLL); conjugated pneumococcal vaccination in patients with CLL; the use of the thrombopoietin receptor agonist eltrombopag in patients with high risk MDS with thrombocytopenia who are treated with azacitidine and a retrospective survey aiming to evaluate the clinical value of Bronhio-Alveolar-Lavage (BAL) in patients with haematological malignancies
Myeloproliferative neoplasms (MPN), cancer anaemia and supportive care
Elisabeth Ejerblad, Torbjörn Karlsson, Gunnar Birgegård, and Anncarin Svanberg
In MPN and cancer anaemia we are involved in several clinical trials including a large European multicentre study for long term follow-up of platelet-reducing therapy in essential thrombocythemia (ET), a 7-year prospective follow-up of ET patients treated with anagrelide, and a randomised phase II trial investigating the effect of IV iron alone in cancer patients with functional iron deficiency. As regards supportive care, we have previously shown that cryotherapy significantly reduces mucositis after high dose chemotherapy, and in two recently performed studies investigated the physiological mucosal effects on oral mucosa and the protective effect of a new saturated calcium-phosphate solution in addition to cryotherapy during chemotherapy.