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  • 1. Arruda, L. C. M.
    et al.
    Gaballa, A.
    Uhlin, Michael
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biophysics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Graft γδ TCR Sequencing Identifies Public Clonotypes Associated with Hematopoietic Stem Cell Transplantation Efficacy in Acute Myeloid Leukemia Patients and Unravels Cytomegalovirus Impact on Repertoire Distribution2019In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 202, no 6, p. 1859-1870Article in journal (Refereed)
    Abstract [en]

    Although the impact of donor graft composition on clinical outcomes after hematopoietic stem cell transplantation (HSCT) has been studied, little is known about the role of intragraft γδ TCR repertoire on clinical outcomes following HSCT. Using a high-throughput sequencing platform, we sought to analyze the TCR γ-chain (TRG) repertoire of γδ T cells within donor stem cell grafts and address its potential impact on clinical response in the corresponding patients. A total of 20 peripheral blood stem cell grafts were analyzed, and donors were classified as CMV+/- The respective acute myeloid leukemia recipients were followed for disease relapse and acute graft-versus-host disease (aGvHD) development post-HSCT. In all samples, TRG repertoire showed a reduced diversity and displayed overrepresented clones. This was more prominent in grafts from CMV+ donors, which presented a more private repertoire, lower diversity, skewed distribution, and reduced usage of the V9-JP pairing. Grafts given to nonrelapse patients presented a more public repertoire and increased presence of long sequence clonotypes. Variable-joining gene segment usage was not associated with aGvHD development, but a higher usage of V2-JP1 pairing and lower usage of V4-J2/V5-J2/V8-JP2 were observed in grafts given to nonrelapse patients. Our work identified five private overrepresented and one public CDR3 sequence (CATWDGPYYKKLF) associated with CMV infection, in addition to 12 highly frequent public sequences present exclusively in grafts given to nonrelapse patients. Our findings show that, despite CMV infection reshaping the TRG repertoire, TRG composition is not associated with aGvHD development, and several public sequences are associated with clinical remission.

  • 2.
    Berglund, Sofia
    et al.
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Gaballa, Ahmed
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Sawaisorn, Piamsiri
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.;Mahidol Univ, Fac Med Technol, Ctr Res & Innovat, Bangkok, Thailand..
    Sundberg, Berit
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Uhlin, Michael
    KTH, School of Engineering Sciences (SCI), Applied Physics. Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.; Karolinska Univ Hosp, Dept Immunol & Transfus Med, Stockholm, Sweden..
    Expansion of Gammadelta T Cells from Cord Blood: A Therapeutical Possibility2018In: STEM CELLS INTERNATIONAL, ISSN 1687-966X, article id 8529104Article in journal (Refereed)
    Abstract [en]

    Gammadelta (gamma delta) T cells are found in both blood and tissues and have antiviral and antitumor properties. The frequency of gamma delta T cells in umbilical cord blood (UCB) is low, and the majority express delta 1, in contrast to blood, whereas the main subset is delta 2 gamma 9 T cells. UCB gamma delta T cells are functionally immature, which together with their scarcity complicates the development of UCB gamma delta T cell therapies. We aimed to develop an effective expansion protocol for UCB gamma delta T cells based on zoledronate and IL-2. We found that culture with 5 mu M zoledronate and 200 IU IL-2/ml medium for 14 days promoted extensive proliferation. The majority of the cultured cells were gamma 9 delta 2 T cells. The fold expansion of this, originally infrequent, subset was impressive (median and maximum fold change 253 and 1085, resp.). After culture, the cells had a polyclonal gamma delta T cell repertoire and the main memory subset was central memory (CD45RO(+) CD27(+)). The cells produced cytokines such as IL-1B, IL-2, and IL-8 and displayed significant tumor-killing capacity. These results show that development of in vitro expanded UCB gamma delta T cell therapies is feasible. It could prove a valuable treatment modality for patients after umbilical cord blood transplantation.

  • 3. Emelie, Radestad
    et al.
    Emma, Watz
    Sarah, Thunberg
    KTH, School of Engineering Sciences (SCI), Applied Physics. Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden.
    Mikael, Sundin
    Jonas, Mattsson
    Uhlin, Michael
    KTH, School of Engineering Sciences (SCI), Applied Physics. Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, SwedenKarolinska Univ Hosp, Dept Clin Immunol & Transfus Med, Huddinge, Sweden.
    Individualization of hematopoietic stem cell transplantation using alpha/ beta depletion2017In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 86, no 4, p. 338-338Article in journal (Other academic)
  • 4. Gaballa, Ahmed
    et al.
    Norberg, Anna
    Stikvoort, Arwen
    Mattsson, Jonas
    Sundberg, Berit
    Uzunel, Mehmet
    Remberger, Mats
    Uhlin, Michael
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Assessment of TREC, KREC and telomere length in long term survivors after allogeneic HSCT: the role of GVHD and graft source and evidence for telomere homeostasis in young recipients2017In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 86, no 4, p. 265-265Article in journal (Other academic)
  • 5.
    Nair, Deepika
    et al.
    Karolinska Inst, Dept Med Huddinge, Ctr Hematol & Regenerat Med, Stockholm, Sweden.;Karolinska Inst, Dept Med Biochem & Biophys, Div Biochem, Stockholm, Sweden..
    Radestad, Emelie
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Khalkar, Prajakta
    Karolinska Inst, Dept Med Biochem & Biophys, Div Biochem, Stockholm, Sweden..
    Diaz-Argelich, Nuria
    Karolinska Inst, Dept Med Biochem & Biophys, Div Biochem, Stockholm, Sweden.;Univ Navarra, Dept Organ & Pharmaceut Chem, Pamplona, Spain..
    Schroder, Axel
    Karolinska Inst, Dept Med Biochem & Biophys, Div Biochem, Stockholm, Sweden..
    Klynning, Charlotte
    Karolinska Univ Hosp, Dept Gynecol Oncol, Stockholm, Sweden..
    Ungerstedt, Johanna
    Karolinska Inst, Dept Med Huddinge, Ctr Hematol & Regenerat Med, Stockholm, Sweden.;Karolinska Univ Hosp, Hematol Ctr, Stockholm, Sweden..
    Uhlin, Michael
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biophysics.
    Fernandes, Aristi P.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Biochem, Stockholm, Sweden..
    Methylseleninic Acid Sensitizes Ovarian Cancer Cells to T-Cell Mediated Killing by Decreasing PDL1 and VEGF Levels2018In: Frontiers in Oncology, ISSN 2234-943X, E-ISSN 2234-943X, Vol. 8, article id 407Article in journal (Refereed)
    Abstract [en]

    Redox active selenium (Se) compounds at sub toxic doses act as pro-oxidants with cytotoxic effects on tumor cells and are promising future chemotherapeutic agents. However, little is known about how Se compounds affect immune cells in the tumor microenvironment. We demonstrate that the inorganic Se compound selenite and the organic methylseleninic acid (MSA) do not, despite their pro-oxidant function, influence the viability of immune cells, at doses that gives cytotoxic effects in ovarian cancer cell lines. Treatment of the ovarian cancer cell line A2780 with selenite and MSA increases NK cell mediated lysis, and enhances the cytolytic activity of T cells. Increased T cell function was observed after incubation of T cells in preconditioned media from tumor cells treated with MSA, an effect that was coupled to decreased levels of PDL1, HIF-1 alpha, and VEGF. In conclusion, redox active selenium compounds do not kill or inactivate immune cells at doses required for anti-cancer treatment, and we demonstrate that MSA enhances T cell-mediated tumor cell killing via PDL1 and VEGF inhibition.

  • 6. Nilsson, J.
    et al.
    Granrot, I.
    Mattsson, J.
    Omazic, B.
    Uhlin, Michael
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cellular Biophysics.
    Thunberg, Sarah
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cellular Biophysics.
    Functionality testing of stem cell grafts to predict infectious complications after allogeneic hematopoietic stem cell transplantation2017In: Vox Sanguinis, ISSN 0042-9007, E-ISSN 1423-0410, Vol. 112, no 5, p. 459-468Article in journal (Refereed)
    Abstract [en]

    Background and Objectives Allogeneic hematopoietic stem cell transplantation (HSCT) is a routine clinical procedure performed to treat patients with haematological malignancies, primary immune deficiencies or metabolic disorders. Infections during lymphopenia after allogeneic HSCT are associated with high mortality and morbidity. Typical infectious agents are Epstein-Barr virus, cytomegalovirus, herpes simplex virus, varicella-zoster virus and fungi. The study aim was to evaluate whether measurement of the responses of antigen-specific T-cells, recognizing infectious pathogens would correlate to protective functions in the stem cell recipient post-transplant. Materials and MethodsTwenty-one grafts were analysed by flow cytometry and cells were stimulated in vitro with relevant infectious antigens, followed by evaluation of T-cell proliferation and cytokine production. Results were compared to the recipients' clinical records 1-year post-transplantation. ResultsWe show that an extensive repertoire of transferred antigen-specific T-cells from allogeneic donor grafts against infectious agents, involved in post-transplant infections, are linked to an absence of infectious complications for the recipient up-to 1-year post-transplant. The protective effect was associated with antigen-specific T-cell proliferation and IL-1 secretion. Conclusion Our results suggest that assaying T-cell function before HSCT could determine individual risks for infectious complications and thus aid in clinical decision-making regarding prophylactic and pre-emptive anti-infective therapy.

  • 7.
    Radestad, Emelie
    et al.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Klynning, Charlotte
    Karolinska Univ Hosp, Dept Gynecol Oncol, Stockholm, Sweden..
    Stikvoort, Arwen
    Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Hematol, Amsterdam, Netherlands..
    Mogensen, Ole
    Karolinska Inst, Dept Womens & Childrens Hlth, Div Obstet & Gynecol, Stockholm, Sweden..
    Nava, Silvia
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Magalhaes, Isabelle
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
    Uhlin, Michael
    KTH, School of Engineering Sciences (SCI), Applied Physics. Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Immunol & Transfus Med, Stockholm, Sweden...
    Immune profiling and identification of prognostic immune-related risk factors in human ovarian cancer2019In: Oncoimmunology, ISSN 2162-4011, E-ISSN 2162-402X, Vol. 8, no 2, article id e1535730Article in journal (Refereed)
    Abstract [en]

    Suppression of immune reactivity by increased expression of co-inhibitory receptors has been discussed as a major reason as to why the immune system fails to control tumor development. Elucidating the co-inhibitory expression pattern of tumor-infiltrating lymphocytes in different cancer types will help to develop future treatment strategies. We characterized markers reflecting and affecting T-cell functionality by flow cytometry on lymphocytes isolated from blood, ascites and tumor from advanced ovarian cancer patients (n = 35). Significantly higher proportions of CD4+ and CD8+ T-cells expressed coinhibitory receptors LAG-3, PD-1 and TIM-3 in tumor and ascites compared to blood. Co-expression was predominantly observed among intratumoral CD8+ T-cells and the most common combination was PD-1 and TIM-3. Analysis of 26 soluble factors revealed highest concentrations of IP-10 and MCP-1 in both ascites and tumor. Correlating these results with clinical outcome revealed the proportion of CD8+ T-cells without expression of LAG-3, PD-1 and TIM-3 to be beneficial for overall survival. In total we identified eight immune-related risk factors associated with reduced survival. Ex vivo activation showed tumor-derived CD4+ and CD8+ T-cells to be functionally active, assessed by the production of IFN-gamma, IL-2, TNF-alpha, IL-17 and CD107a. Blocking the PD-1 receptor resulted in significantly increased release of IFN-. suggesting potential reinvigoration. The ovarian tumor environment exhibits an inflammatory milieu with abundant presence of infiltrating immune cells expressing inhibitory checkpoints. Importantly, we found subsets of CD8+ T-cells with double and triple expression of co-inhibitory receptors, supporting the need for multiple checkpoint-targeting agents to overcome T-cell dysfunction in ovarian cancer.

  • 8.
    Radestad, Emelie
    et al.
    Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Div Transplantat Surg, Stockholm, Sweden..
    Sundin, Mikael
    Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Div Pediat, Stockholm, Sweden.;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Hematol Immunol HSCT Sect, Stockholm, Sweden..
    Torlen, Johan
    Karolinska Univ Hosp, Cell Therapy & Allogene Stem Cell Transplantat, Stockholm, Sweden.;Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
    Thunberg, Sara
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences (SCI), Applied Physics.
    Önfelt, Björn
    KTH, School of Engineering Sciences (SCI), Applied Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Ljungman, Per
    Karolinska Univ Hosp, Cell Therapy & Allogene Stem Cell Transplantat, Stockholm, Sweden.;Karolinska Inst, Div Hematol, Dept Med, Stockholm, Sweden..
    Watz, Emma
    Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Div Transplantat Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Clin Immunol & Transfus Med, Stockholm, Sweden..
    Mattsson, Jonas
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.;Princess Margaret Canc Ctr, Div Med Oncol & Hematol, Toronto, ON, Canada.;Univ Toronto, Toronto, ON, Canada..
    Uhlin, Michael
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biophysics.
    Individualization of Hematopoietic Stem Cell Transplantation Using Alpha/Beta T-Cell Depletion2019In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 10, article id 189Article in journal (Refereed)
    Abstract [en]

    Allogeneic hematopoietic stem cell transplantation (HSCT) is associated with several potentially lethal complications. Higher levels of CD3+ T-cells in the graft have been associated with increased risk of graft-versus-host disease (GVHD), but also beneficial graft-versus-leukemia effect and reduced infections. To tackle post-transplant complications, donor lymphocyte infusions have been used but with an increased risk of GVHD. To reduce this risk, we performed depletion of alpha beta T-cells and treated 12 patients post-HSCT suffering from infections and/or poor immune reconstitution. The alpha beta T-cell depleted cell products were characterized by flow cytometry. The median log depletion of alpha beta T-cells was -4.3 and the median yield of gamma delta T-cells was 73.5%. The median CD34+ cell dose was 4.4 x 10(6)/kg. All 12 patients were alive 3 months after infusion and after 1 year, two patients had died. No infusion-related side effects were reported and no severe acute GVHD (grade III-IV) developed in any patient post-infusion. Overall, 3 months after infusion 11 out of 12 patients had increased levels of platelets and/or granulocytes. In conclusion, we describe the use of alpha beta T-cell depleted products as stem cell boosters with encouraging results.

  • 9. Stikvoort, Arwen
    et al.
    Chen, Yang
    Radestad, Emelie
    Karlsson-Torlen, Johan
    Tadepally, Lakshmikanth
    Bjorklund, Andreas
    Mikes, Jaromir
    Achour, Adnane
    Gertow, Jens
    Sundberg, Berit
    Remberger, Mats
    Sundin, Mikael
    Mattsson, Jonas
    Brodin, Petter
    Uhlin, Michael
    KTH, School of Engineering Sciences (SCI), Applied Physics. Karolinska Inst, Dept Med, Sci Life Lab, Stockholm, Sweden; Karolinska Univ Hosp, Dept Clin Immunol & Transfus Med, Huddinge, Sweden.
    Identifying cellular subsets diagnostic for severity chronic GVHD2017In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 86, no 4, p. 264-264Article in journal (Other academic)
  • 10. Stikvoort, Arwen
    et al.
    Chen, Yang
    Radestad, Emelie
    Torlen, Johan
    Lakshmikanth, Tadepally
    Bjorklund, Andreas
    Mikes, Jaromir
    Achour, Adnane
    Gertow, Jens
    Sundberg, Berit
    Remberger, Mats
    Sundin, Mikael
    Mattsson, Jonas
    Brodin, Petter
    Uhlin, Michael
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cellular Biophysics. Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Combining Flow and Mass Cytometry in the Search for Biomarkers in Chronic Graft-versus-Host Disease2017In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 8, article id 717Article in journal (Refereed)
    Abstract [en]

    Chronic graft-versus-host disease (cGVHD) is a debilitating complication arising in around half of all patients treated with an allogeneic hematopoietic stem cell transplantation. Even though treatment of severe cGVHD has improved during recent years, it remains one of the main causes of morbidity and mortality in affected patients. Biomarkers in blood that could aid in the diagnosis and classification of cGVHD severity are needed for the development of novel treatment strategies that can alleviate symptoms and reduce the need for painful and sometimes complicated tissue biopsies. Methods that comprehensively profile complex biological systems such as the immune system can reveal unanticipated markers when used with the appropriate methods of data analysis. Here, we used mass cytometry, flow cytometry, enzyme-linked immunosorbent assay, and multiplex assays to systematically profile immune cell populations in 68 patients with varying grades of cGVHD. We identified multiple subpopulations across T, B, and NK-cell lineages that distinguished patients with cGVHD from those without cGVHD and which were associated in varying ways with severity of cGVHD. Specifically, initial flow cytometry demonstrated that patients with more severe cGVHD had lower mucosal-associated T cell frequencies, with a concomitant higher level of CD38 expression on T cells. Mass cytometry could identify unique subpopulations specific for cGVHD severity albeit with some seemingly conflicting results. For instance, patients with severe cGVHD had an increased frequency of activated B cells compared to patients with moderate cGVHD while activated B cells were found at a reduced frequency in patients with mild cGVHD compared to patients without cGVHD. Moreover, results indicate it may be possible to validate mass cytometry results with clinically viable, smaller flow cytometry panels. Finally, no differences in levels of blood soluble markers could be identified, with the exception for the semi-soluble combined marker B-cell activating factor/B cell ratio, which was increased in patients with mild cGVHD compared to patients without cGVHD. These findings suggest that interdependencies between such perturbed subpopulations of cells play a role in cGVHD pathogenesis and can serve as future diagnostic and therapeutic targets.

  • 11.
    Stikvoort, Arwen
    et al.
    Karolinska Inst, Dept Oncol Pathol, SE-14186 Stockholm, Sweden..
    Gaballa, Ahmed
    Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden..
    Solders, Martin
    Karolinska Inst, Dept Lab Med, Stockholm, Sweden..
    Nederlof, Iris
    Karolinska Inst, Dept Oncol Pathol, SE-14186 Stockholm, Sweden..
    Önfelt, Björn
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Sundberg, Berit
    Karolinska Inst, Dept Oncol Pathol, SE-14186 Stockholm, Sweden..
    Remberger, Mats
    Karolinska Univ Hosp, CAST, Stockholm, Sweden..
    Sundin, Mikael
    Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden.;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Hematol Immunol HSCT Sect, Stockholm, Sweden..
    Mattsson, Jonas
    Karolinska Inst, Dept Oncol Pathol, SE-14186 Stockholm, Sweden.;Karolinska Univ Hosp, CAST, Stockholm, Sweden..
    Uhlin, Michael
    Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Clin Immunol & Transfus Med, Huddinge, Sweden..
    Risk Factors for Severe Acute Graft-versus-Host Disease in Donor Graft Composition2018In: Biology of blood and marrow transplantation, ISSN 1083-8791, E-ISSN 1523-6536, Vol. 24, no 3, p. 467-477Article in journal (Refereed)
    Abstract [en]

    Acute graft-versus-host disease (aGVHD) is 1 of the main major complications of post-hematopoietic stem cell transplantation (HSCT). Identifying patients at risk of severe aGVHD may lead to earlier intervention and treatment, resulting in increased survival and a better quality of life. We aimed to identify biomarkers in donor grafts and patient plasma around the time of transplantation that might be predictive of aGVHD development. We build on our previously published methods by using multiplex assays and multicolor flow cytometry. We identified 5 easily assessable cellular markers in donor grafts that combined could potentially be used to calculate risk for severe aGVHD development. Most noteworthy are the T cell subsets expressing IL-7 receptor-a (CD127) and PD-1. Additionally, we identified a potential role for elevated tumor necrosis factor-a levels in both graft and patient before HSCT in development of aGVHD. 

  • 12. Törlén, J.
    et al.
    Gaballa, A.
    Remberger, M.
    Mörk, L. -M
    Sundberg, B.
    Mattsson, J.
    Uhlin, Michael
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biophysics.
    Effect of Graft-versus-Host Disease Prophylaxis Regimens on T and B Cell Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation2019In: Biology of blood and marrow transplantation, ISSN 1083-8791, E-ISSN 1523-6536, Vol. 25, no 6, p. 1260-1268Article in journal (Refereed)
    Abstract [en]

    Lymphocyte reconstitution is pivotal for successful long-term outcome after allogeneic hematopoietic stem cell transplantation (HSCT), and conditioning regimen and post-transplantation immunosuppression are risk factors for prolonged immunodeficiency. Nevertheless, the effects of different immunosuppressive protocols on lymphocyte output and replicative capacity have not been investigated. Here we assessed T cell receptor excision circles (TREC), kappa-deleting recombination excision circles (KREC), and T cell telomere length (TL) as proxy markers for immune reconstitution in patients in a prospective randomized trial comparing graft-versus-host disease (GVHD) prophylaxis after transplantation (cyclosporine/methotrexate versus tacrolimus/sirolimus; n = 200). Results showed that medians of TREC, KREC, and TL were not significantly different between the prophylaxis groups at any assessment time point during follow-up (24 months), but the kinetics of TREC, KREC, and TL were significantly influenced by other transplantation-related factors. Older recipient age, the use of antithymocyte globulin before graft infusion, and use of peripheral blood stem cell grafts were associated with lower TREC levels, whereas acute GVHD transiently affected KREC levels. Patients with lymphocyte excision circle levels above the median at ≤6 months post-transplantation had reduced transplantation-related mortality and superior 5-year overall survival (P <.05). We noticed significant T cell telomere shortening in the patient population as a whole during follow-up. Our results suggest that lymphocyte reconstitution after transplantation is not altered by different immunosuppressive protocols. This study has been registered at ClinicalTrials.gov (identifier: NCT00993343). 

  • 13.
    Uhlin, Michael
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biophysics. Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Clin Immunol & Transfus Med, Stockholm, Sweden.
    Abumaree, Mohamed
    King Abdul Aziz Med City, King Abdullah Int Med Res Ctr, Stem Cells & Regenerat Med Dept, POB 22490, Riyadh 11426, Saudi Arabia.;Minist Natl Guard Hlth Affairs, POB 22490, Riyadh 11426, Saudi Arabia.;King Saud Bin Abdulaziz Univ Hlth Sci, King Abdulaziz Med City, Coll Sci & Hlth Profess, POB 3660, Riyadh 11481, Saudi Arabia.;Minist Natl Guard Hlth Affairs, POB 3660, Riyadh 11481, Saudi Arabia..
    Abdelalim, Essam M.
    Hamad Bin Khalifa Univ, Qatar Fdn, Qatar Biomed Res Inst, Diabet Res Ctr, Doha, Qatar..
    Therapeutic Use of Extraembryonic-Derived Tissues2018In: Stem Cells International, ISSN 1687-966X, article id 6082698Article in journal (Refereed)
  • 14.
    Wang, T.
    et al.
    Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Clin Immunol & Transfus Med, Stockholm, Sweden..
    Remberger, M.
    Karolinska Inst, Dept Pathol & Oncol, Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Allogene Stem Cell Transplantat CAST, Huddinge, Sweden..
    Nygell, U. Axdorph
    Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Clin Immunol & Transfus Med, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Haematol, Huddinge, Sweden..
    Sundin, M.
    Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden..
    Björklund, A.
    Karolinska Univ Hosp, Dept Haematol, Huddinge, Sweden..
    Mattsson, J.
    Karolinska Inst, Dept Pathol & Oncol, Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Allogene Stem Cell Transplantat CAST, Huddinge, Sweden..
    Uhlin, Michael
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biophysics. Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Clin Immunol & Transfus Med, Stockholm, Sweden.
    Watz, E.
    Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Clin Immunol & Transfus Med, Stockholm, Sweden..
    Change of apheresis device decreased the incidence of severe acute graft-versus-host disease among patients after allogeneic stem cell transplantation with sibling donors2018In: Transfusion, ISSN 0041-1132, E-ISSN 1537-2995, Vol. 58, no 6, p. 1442-1451Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The composition of the graft used for allogeneic hematopoietic stem cell transplantation (HSCT) is important for the treatment outcome. Different apheresis devices may yield significant differences in peripheral blood stem cell graft cellular composition. We compared stem cell grafts produced by Cobe Spectra (Cobe) and Spectra Optia (Optia) with use of the mononuclear cell (MNC) protocol, and evaluated clinical outcome parameters such as graft-versus-host disease (GvHD), transplant-related mortality (TRM), relapse, and overall survival.

    STUDY DESIGN AND METHODS: During 5 years, 31 Cobe Spectra and 40 Spectra Optia grafts were analyzed for CD34, CD3, CD4, CD8, CD19, and CD56 cell content. Clinical outcome parameters were correlated and compared between the two patient groups using different apheresis devices.

    RESULTS: Optia grafts contained fewer lymphocytes compared to Cobe (p<0.001). Optia grafts had a significantly lower incidence of acute GvHD Grades II through IV (Cobe 45% vs. Optia 23%; p=0.039) and TRM (16% vs. 2.5%; p<0.05) but higher chronic GvHD (32% vs. 67%; p=0.005) compared to Cobe grafts. Finally, the multivariate analysis showed a significant correlation among the different apheresis devices and both acute GvHD II through IV and severe chronic GvHD. The multivariate analysis also showed a significant correlation between the CD3+ cell dose and the incidence of severe acute GvHD.

    CONCLUSION: Optia-obtained grafts yielded a lower acute GvHD Grades II-IV and TRM risk, but had no impact on relapse or overall survival in this study. Understanding and further improvement of peripheral blood stem cell (PBSC) apheresis techniques may be used in the future to personalize HSCT by, for example, fine-tuning the GvHD incidence.

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