M Stern

Publications (46)150.75 Total impact

• Article: Sicca symptoms and their impact on quality of life among very long-term survivors after hematopoietic SCT.

  T Daikeler, M Mauramo, A Rovó, M Stern, J Halter, A Buser, A Tyndall, P Häusermann, A Gratwohl, A Tichelli, M T Brennan, T Waltimo
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  ABSTRACT: The objective of this prospective cross-sectional case-control study was to examine the prevalence of dryness symptoms and its impact on quality of life (QoL) among very long-term survivors after hematopoietic SCT (HSCT) in comparison with their respective sibling donors. Forty-four allogeneic HSCT recipients with a long-term survival (median: 17.5; range: 11-26 years) were included. Their respective, HLA-identical sibling donors served as controls. Clinical examinations included saliva flow rates (SFR) and the Schirmer's test. The presence of sicca symptoms of mouth, eyes and skin were inquired. The social functioning (SF)-36 questionnaire was applied. Recipients had lower (P<0.01) unstimulated and stimulated mean SFR than donors. Schirmer's test results <5 mm was found in 45% of the recipients in comparison with 27% of the donors (P=0.07). Xerostomia (34 vs 4 subjects), xerophtalmia (23 vs 3) and dry skin (32 vs 12) were reported more often by the recipients than donors (P<0.001). Sicca symptoms and their objective findings correlated with QoL. The mean SF-36 scores of the donors were significantly higher than those of the recipients for physical component summary. In conclusion, sicca symptoms are common amongst long-term survivors of HSCT and affect remarkably the QoL.Bone Marrow Transplantation advance online publication, 7 January 2013; doi:10.1038/bmt.2012.260.
  Bone marrow transplantation 01/2013; · 3.00 Impact Factor
• Article: Haematopoietic stem cell transplantation: activity in Switzerland compared with surrounding European countries.

  J Passweg, H Baldomero, M Bargetzi, C Bucher, Y Chalandon, M A Duchosal, A Gratwohl, T Güngör, U Hess, K Leibundgut, G Nicoloso de Faveri, H Ozsahin, T Pabst, C Renner, M Stern, G Stussi, U Schanz, G R O U P For The Sbst Swiss Blood Stem Cell Transplantation
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  ABSTRACT: Haematopoietic stem cell transplantation (HSCT) is a highly specialised procedure used to treat malignancies of the lymphohaematopoietic system as well as some acquired and inherited disorders of the blood. This analysis by the Swiss Blood Stem Cell Transplantation Group, based on data from 2008-2011, describes, treatment rates in Switzerland for specific indications and compares this with data from Germany, France, Italy and the Netherlands, corrected for the size of the population. Differences in transplant rates, in rates for particular indications, and in the use of specific transplant technologies such as use of unrelated donors, use of cord blood or mismatched family donors are described. These data are put in correlation with donor availability from international registries and with number of transplant teams and number of procedures per team all corrected for population size.
  Schweizerische medizinische Wochenschrift 01/2013; 143. · 1.68 Impact Factor
• Article: Pre-emptive immunotherapy with purified natural killer cells after haploidentical SCT: a prospective phase II study in two centers.

  M Stern, J R Passweg, S Meyer-Monard, R Esser, T Tonn, J Soerensen, M Paulussen, A Gratwohl, T Klingebiel, P Bader, A Tichelli, D Schwabe, U Koehl
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  ABSTRACT: Adoptive immunotherapy with allogeneic purified natural killer (NK) cell products might exert graft-versus-tumor alloreactivity with little risk of GVHD. In a prospective phase II study in two centers, we administered purified NK cell products to high-risk patients treated with haploidentical T-cell-depleted SCT. Sixteen patients received a total of 29 NK cell infusions on days +3, +40 and +100 after transplantation. Median doses (and ranges) of infused NK- and T-cells per product were 1.21 (0.3-3.8) × 10(7)/kg and 0.03 (0.004-0.72) × 10(5)/kg, respectively. With a median follow-up of 5.8 years 4/16 patients are alive. Cause of death was relapse in five, GVHD in three, graft failure in three, and transplant related neurotoxicity in one patient. Four patients developed acute GVHDgrade II, all receiving a total of 0.5 × 10(5) T cells/kg. Compared with historical controls, NK cell infusions had no apparent effect on the rates of graft failure or relapse. Adoptive transfer of allogeneic NK cells is safe and feasible, but further studies are needed to determine the optimal dose and timing of NK cell therapy. Moreover, NK cell activation/expansion may be required to attain clinical benefit, while careful consideration must be given to the number of T cells infused.Bone Marrow Transplantation advance online publication, 3 September 2012; doi:10.1038/bmt.2012.162.
  Bone marrow transplantation 09/2012; · 3.00 Impact Factor
• Article: Allo-SCT for multiple myeloma in the era of novel agents: a retrospective study on behalf of Swiss Blood SCT.

  S Gerull, M Stern, A Ben Aissa, M G Manz, U Schanz, G Stussi, Y Chalandon, J Passweg, B Mohty
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  ABSTRACT: Despite the introduction of novel drugs, cure of multiple myeloma remains rare. Allo-SCT can induce long-term remission, but randomized studies in advanced disease are lacking and the influence of novel drugs remains unclear. In our retrospective analysis of all patients with myeloma allografted in Switzerland, 95 patients were transplanted between 1988 and 2011. Most patients were heavily pre-treated, and 53% received novel drugs before transplant. In all, 51% were allografted after relapse or progression. Transplant trends changed over time with an increase in reduced intensity conditioning and unrelated donors. At the time of analysis 47 patients remained alive, with a median follow-up of survivors of 53 months. Acute GVHD II-IV and chronic GVHD (cGVHD) occurred in 49% and 53%, respectively; TRM at 5 years was 18%. Five-year OS and PFS were 51% and 29%, respectively. Patients who received transplant upfront vs after relapse had a significantly better outcome, as well as those who had a related donor and achieved CR post transplant. We found no impact of pre-treatment with novel drugs or cGVHD. Although long-term remission following allo-SCT can be achieved, GVHD and TRM remain major limitations. Our series suggests that benefit is highest when allo-SCT is used early in the disease.Bone Marrow Transplantation advance online publication, 3 September 2012; doi:10.1038/bmt.2012.167.
  Bone marrow transplantation 09/2012; · 3.00 Impact Factor
• Article: A polymorphism affecting HLA-C surface expression associates with herpes simplex virus and cytomegalovirus immunoglobulin G seropositivity.

  H N Charoudeh, K Schmitter, A Buser, A Gonzalez, M Stern
  Tissue Antigens 06/2012; 80(3):263-4. · 2.59 Impact Factor
• Article: Prognostic impact of iron parameters in patients undergoing allo-SCT.

  G N Bazuaye, A Buser, S Gerull, A Tichelli, M Stern
  Bone marrow transplantation 04/2012; 47(4):616. · 3.00 Impact Factor
• Article: Natural killer cell immunity after transplantation.

  G Terszowski, J R Passweg, M Stern
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  ABSTRACT: Transplantation immunology has traditionally focused on adaptive, i.e., T- and B-cell reactions. More recently, natural killer (NK) cells were also recognised as playing an important role after transplantation of solid organs and haematopoietic stem cells. NK cells recognise "cell stress" induced by viral replication and tumour transformation via activating receptors, and are negatively regulated by the interaction between inhibitory molecules and autologous human leukocyte antigens (HLA). The most important inhibitory molecules belong to the family of killer cell immunoglobulin-like receptors (KIR). Differences in the inhibitory KIR/HLA interaction between stem cell donor and patient may lead to beneficial NK cell alloreactivity, resulting in specific graft-versus-tumour reactions, which occur in the absence of graft-versus-host disease. The immaturity of NK cells produced by the stem cell graft early after transplantation has led to different approaches of adoptive transfer of NK cells to further increase tumour control. The function and role of activating KIR receptors is less clear. Recent data have suggested, that activating KIR may also contribute to anti-tumour immunity after stem cell transplantation, as patients transplanted from donors carrying high numbers of activating KIR receptor genes show reduced relapse rates. In particular, protection from post-transplant disease relapse was demonstrated in transplants carried out from donors carrying the activating KIR2DS1 receptor, if the recipients also expressed the KIR2DS1 ligand HLA-C2. In conclusion, NK cells have been firmly established in the last two decades as relevant players in transplant immunology, which can critically determine the outcome of haematopoietic stem cell grafts.
  Schweizerische medizinische Wochenschrift 01/2012; 142. · 1.68 Impact Factor
• Article: Hematopoietic stem cell transplantation: a review and recommendations for follow-up care for the general practitioner.

  Jr Passweg, J Halter, C Bucher, S Gerull, D Heim, A Rovó, A Buser, M Stern, A Tichelli
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  ABSTRACT: The first hematopoietic stem cell transplantation (HSCT), the replacement of the hematopoietic system, by hematopoietic stem cells from the patient (autologous HSCT) or from another person (allogeneic HSCT), was performed almost 45 years ago. Today autologous HSCT is used to bridge hematopoietic failure after high dose chemotherapy for the treatment of selected hematopoietic and non-hematopoietic tumours. Allogeneic HSCT is used to treat congenital or acquired marrow failure, and, more commonly, to exploit the graft versus tumour effect of allogeneic cells against high risk hematologic malignancies. In 2010, 30,000 patients were treated with HSCT (12,000 allogeneic and 18,000 autologous HSCT) in Europe. Substantial progress has been made in the field of allogeneic HSCT in the last decade. First the article describes advances in patient and donor selection, the current concepts of choosing the optimal stem cell source and the most appropriate preparative regimen. Furthermore, recent advances in supportive care are described. We describe how these innovations have allowed indications for allogeneic HSCT to be expanded. Finally, prospects for future developments will be outlined.
  Schweizerische medizinische Wochenschrift 01/2012; 142. · 1.68 Impact Factor
• Article: Acute phase after haematopoietic stem cell transplantation: bleeding and thrombotic complications.

  L Graf, M Stern
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  ABSTRACT: The transplantation of allogeneic or autologous haematopoietic stem cells is an established treatment for many malignant and non-malignant diseases of the bone marrow. Intensive cytoreductive regimens administered before transplantation induce prolonged and severe cytopenia of all haematopoietic lineages. Thrombocytopenia leads to an increased risk of bleeding, which may be further aggravated by consumption of plasmatic factors as a result of tumour lysis or after antibody administration. At the same time, patients after transplantation are also at increased risk of thrombotic complications. Endothelial damage induced by radio- and chemotherapy, indwelling catheters, prolonged immobilization and a high incidence of systemic infection all contribute to the frequent occurrence of thromboembolic events in this population. This review discusses the incidence and risk factors for haemorrhagic and thrombotic complications after stem cell transplantation. Special emphasis is given to complications occurring specifically in the context of transplantation such as diffuse alveolar haemorrhage, haemorrhagic cystitis, veno-occlusive disease, and transplant associated microangiopathy.
  Hamostaseologie 01/2012; 32(1):56-62. · 1.19 Impact Factor
• Article: Peri-transplantation sorafenib for relapsed/refractory FLT3-ITD positive AML

  A. Plessl, J. Halter, C. Bucher, M. Stern, S. Gerull, B. Mueller, J. Passweg, D. Heim
  Bone Marrow Transplantation. 01/2012; 47:S101-S101.
• Article: Volume reduction and complete red blood cell depletion of bone marrow harvest for haematopoietic stem cell transplantation with a new processing system, Sepax 2

  T. Lehmann, A. Buser, C. Bucher, S. Gerull, L. Graf, D. Heim, A. Rovo, J. Sigle, M. Stern, D. Tsakiris, J. Passweg, A. Tichelli
  Bone Marrow Transplantation. 01/2012; 47:S254-S254.
• Article: Allogeneic stem cell transplantation for relapsed/refractory lymphoma after conditioning with BEAM/Fludarabine/TBI - an analysis of 50 consecutive patients

  A. O'Meara, J. Halter, D. Heim, S. Gerull, C. Bucher, J. Passweg, A. Buser, M. Stern
  Bone Marrow Transplantation. 01/2012; 47:S441-S442.
• Article: Serious transplant-related toxicity in patients with Hodgkin's disease previously treated with brentuximab vedotin - a case series

  J. Engels, M. Stern, C. Bucher, J. Halter, D. Heim, J. Passweg, S. Gerull
  Bone Marrow Transplantation. 01/2012; 47:S443-S443.
• Article: Busulfan-based versus total body irradiation-based myelo-ablative conditioning in patients with AML: reduction of acute graft-versus-host disease incidence, mucositis and duration of hospitalisation

  C. Bucher, W. Krenger, S. Dertschnig, M. Stern, S. Gerull, D. Heim, J. Halter, A. Buser, T. Lehmann, L. Graf, A. Rovo, A. Tichelli, J. Passweg
  Bone Marrow Transplantation. 01/2012; 47:S12-S12.
• Article: T-cell depletion in allogeneic stem cell transplantation for myelofibrosis: the Swiss experience

  A. Casini, M. Andres, S. Gerull, S. Masouridi, B. Mohty, C. Bucher, M. Stern, E. Roosnek, G. Nair, U. Schanz, J. Passweg, Y. Chalandon, Swiss Blood Stem Cell Transplantat
  Bone Marrow Transplantation. 01/2012; 47:S312-S312.
• Article: Telomeric rather than centromeric activating KIR genes protect from cytomegalovirus infection after kidney transplantation.

  M Stern, K Hadaya, G Hönger, P-Y Martin, J Steiger, C Hess, J Villard
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  ABSTRACT: Cytomegalovirus (CMV) infection is a common complication after organ transplantation. Previous studies have demonstrated that activating killer-cell immunoglobulin-like receptors (KIR) may reduce the rate of CMV infection. KIR genes can be divided into haplotype A (containing a fixed set of inhibitory receptors) and haplotype B (carrying additional activating KIR genes). The KIR locus is divided into a centromeric and a telomeric portion, both of which may carry A or B haplotype motifs. We studied a cohort of 339 kidney transplant recipients to elucidate which KIR genes protect from CMV infection. CMV infection occurred in 139 patients (41%). Possession of telomeric (hazard ratio 0.64, 95% confidence interval 0.44-0.94, p = 0.02) but not centromeric (HR 0.86, 95% CI 0.60-1.23, p = 0.41) B motifs was associated with statistically significant protection from CMV infection. Due to linkage disequilibrium, we were not able to identify a single protective gene within the telomeric B complex (which may contain the KIR2DS1, KIR3DS1, KIR2DL5A and KIR2DS5 genes). The presence of known or putative ligands to activating KIR did not significantly modify the influence of telomeric B group genes. We confirm that B haplotypes protect from CMV infection after kidney transplantation and show that this arises from telomeric B haplotype genes.
  American Journal of Transplantation 06/2011; 11(6):1302-7. · 6.39 Impact Factor
• Source

  Available from: Maja Weisser

  Article: Pre-emptive diagnosis and treatment of fungal infections--evaluation of a single-centre policy.

  T Schneider, J Halter, D Heim, J Passweg, M Stern, A Tichelli, M Weisser, S Gerull
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  ABSTRACT: Invasive fungal disease (IFD) remains a significant cause of mortality in haematology patients. Management strategies range from empiric therapy to pre-emptive approaches. Prophylaxis with mould-active agents has been evaluated, but the optimal strategy remains unclear. We present here a retrospective analysis of the pre-emptive strategy implemented at our institution. We analysed 348 consecutive neutropenic episodes in 234 patients. The main elements of our pre-emptive strategy included twice-weekly Galactomannan testing and weekly computed tomography (CT) scan. Antifungal prophylaxis usually consisted of fluconazole (400 mg once weekly). Antifungal treatment was started if criteria for IFD (including possible) were fulfilled. Along with the incidence of antifungal treatment and IFD, we also analysed the adherence to the strategy. Adherence was good but suboptimal with 81% of CT scans having been performed at an interval of 10 days or less. Concerning antifungal treatment, in 56 episodes the patient was receiving a mould-active agent as secondary prophylaxis. Antifungal treatment was started during 39% of the remaining episodes. In all, 109 cases of IFD were diagnosed, 51 being probable or proven. Forty-nine patients died before day 100, IFD directly caused or contributed to death in six patients. Two cases of IFD were diagnosed post-mortem and were missed by our pre-emptive strategy. Our pre-emptive strategy is feasible and safe with an acceptable rate of IFD and associated mortality, while avoiding anti-fungal treatment in a significant proportion of patients. The exact role of pre-emptive treatment compared with systematic mould-active prophylaxis can only be determined in a well-designed randomized trial.
  Clinical Microbiology and Infection 05/2011; 18(2):189-94. · 4.54 Impact Factor
• Article: Cyclosporine levels and rate of graft rejection following non-myeloablative conditioning for allogeneic hematopoietic SCT.

  S Gerull, C Arber, C Bucher, A Buser, A Gratwohl, J Halter, D Heim, A Tichelli, M Stern
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  ABSTRACT: Hematopoietic SCT (HSCT) after non-myeloablative conditioning is associated with reduced TRM, and increased risk of graft rejection. Although preclinical data have shown the importance of post transplant immunosuppression in achieving engraftment, little is known about the role of CSA in the clinical setting of non-myeloablative transplantation. In a retrospective analysis of patients treated with allogeneic HSCT after fludarabine and 2 Gy TBI, 15 of 77 evaluable patients (20%) experienced primary (n=2) or secondary graft rejection at a median of 66 days post transplant. Mean day 1-28 CSA trough levels were inversely associated with day 28 chimerism (median 99, 85 and 70% for mean CSA <300, 300-600 and >600 ng/mL, respectively; P=0.003). A similar association was observed for the cumulative incidence of graft rejection, which occurred in 8% (<300 ng/mL), 26% (300-600 ng/mL) and 50% (>600 ng/mL, P=0.005) of patients. The detrimental effect of high CSA levels on engraftment was confirmed in multivariable models and was found to operate comparably in sibling and unrelated donor transplants. Impairment of donor T-cell function by high serum levels of CSA might account for this finding, which should be verified in a larger patient group to better understand the role of CSA in non-myeloablative transplantation.
  Bone marrow transplantation 05/2011; 46(5):740-6. · 3.00 Impact Factor
• Article: Graft source determines human hematopoietic progenitor distribution pattern within the CD34(+) compartment.

  C Arber, J Halter, M Stern, A Rovó, A Gratwohl, A Tichelli
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  ABSTRACT: The CD34(+) compartment of grafts for clinical allogeneic hematopoietic cell transplantation (HCT) is very heterogeneous. It contains hematopoietic stem cells and several different progenitor cell populations. This study assesses (1) the content of these populations in clinical grafts from G-CSF-mobilized PBMCs, BM and cord blood, (2) the functional correlation of the graft composition with time to engraftment of neutrophils, platelets and reticulocytes and (3) donor age-related changes. Quantitative flow cytometry showed that the distribution of the progenitor subsets differed significantly between the graft sources and that donor age-related changes occur. In patients after myeloablative allogeneic HCT, accelerated platelet and reticulocyte engraftment correlated with the content of common myeloid and/or megakaryocyte erythroid progenitors in the graft. These findings show that a better understanding of the progenitor compartment in human hematopoietic grafts could lead to improved strategies for the development of cellular therapies, for example in situations where platelet engraftment is delayed.
  Bone marrow transplantation 05/2011; 46(5):650-8. · 3.00 Impact Factor
• Article: High-dose melphalan with or without stem cell support before myeloablative allo-SCT for remission induction in patients with advanced relapsed or refractory AML.

  A O'Meara, T Pabst, D Heim, S Gerull, C Bucher, J Halter, C Arber, A Rovò, A Tichelli, A Gratwohl, M Stern
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  ABSTRACT: Treatment strategies for relapsed/refractory AML are limited and disappointing. Recently, high-dose melphalan (HDM) chemotherapy and autologous hematopoietic SCT (HSCT) has been proposed for AML re-induction. We investigated the impact of HDM remission induction in highly advanced relapsed/refractory AML patients planned for allogeneic HSCT. A total of 23 patients with relapsed/refractory AML were prospectively scheduled for HDM with or without stem cell support followed by myeloablative allogeneic HSCT. Patients included nine individuals with a history of previous HSCT (seven allogeneic, two autologous). A total of 18 patients (78%) achieved a leukemia-free state and an additional four had substantial reduction of the initial leukemia burden warranting treatment continuation. There were no differences between patients with or without immediate stem cell support regarding mucositis or other organ toxicity. A total of 20 patients proceeded to myeloablative allogeneic HSCT. Outcome of allogeneic HSCT was poor: 11 patients (55%) relapsed, 7 patients (35%) died from TRM and only 2 patients (10%) were alive at the last follow-up. Our study shows that HDM is effective in inducing a leukemia-free state in patients with highly advanced relapsed/refractory AML. Leukemia burden reduction with HDM, however, did not translate into improved OS.
  Bone marrow transplantation 05/2011; 46(5):636-40. · 3.00 Impact Factor