Christiane Dobbelstein

Publications of Christiane Dobbelstein

• Immunosuppressive Therapy for Myelodysplastic Syndromes.

  Authors: Christiane Dobbelstein, Arnold Ganser

  Current pharmaceutical design. 05/2012;

  Myelodysplastic syndromes (MDS) comprise a heterogeneous group of diseases characterized by bone marrow failure, marrow dysplasia, and a tendency to evolve to acute leukemia. Pathophysiologically,Myelodysplastic syndromes (MDS) comprise a heterogeneous group of diseases characterized by bone marrow failure, marrow dysplasia, and a tendency to evolve to acute leukemia. Pathophysiologically, low risk MDS are separated from the high risk category by an increased rate of apoptosis of the bone marrow cells which causes the morphological paradoxon of a peripheral cytopenia and hypercellular bone marrow known as ineffective hematopoesis. Laboratory findings and clinical evidence suggest that some patients with myelodysplastic syndrome have immunologically mediated disease. MDS shares some of the features of acquired aplastic anemia and up to 30% of patients with MDS respond to immunosuppressive treatment. In the last decades, significant advances have been made in the diagnostic and prognostic classifications of myelodysplastic syndromes. While allogeneic transplantation still offers the only available option with a probability of cure in a minority of patients, the mainstay of therapy in low-risk patients remains supportive care, stimulation of ineffective hematopoiesis with growth factors, and immunomodulatory therapy. However, the correct selection of patients for the respective therapeutic intervention continues to be an enormous challenge as this will decide about the probability of therapeutic efficacy. This is important not only because of the high costs involved but also because of the possible side effects that can be difficult to manage. Here we review the pathophysiologic basis for the use of immunosuppressive agents in MDS and summarize the trials leading to the establishment of these therapy strategies in a subgroup of low-risk MDS patients.

• Immunosuppressive therapy for patients with myelodysplastic syndrome: a prospective randomized multicenter phase III trial comparing antithymocyte globulin plus cyclosporine with best supportive care--SAKK 33/99.

  Authors: Jakob R Passweg, Aristoteles A N Giagounidis, Mathew Simcock, Carlo Aul, Christiane Dobbelstein, Michael Stadler, Gert Ossenkoppele, Wolf-Karsten Hofmann, Kristina Schilling, André Tichelli, Arnold Ganser

  Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 01/2011; 29(3):303-9.

  Immunosuppressive treatment is reported to improve cytopenia in some patients with myelodysplastic syndrome (MDS). Combined antithymocyte globulin (ATG) and cyclosporine (CSA) is most effective inImmunosuppressive treatment is reported to improve cytopenia in some patients with myelodysplastic syndrome (MDS). Combined antithymocyte globulin (ATG) and cyclosporine (CSA) is most effective in patients with immune-mediated marrow failure. This trial was designed to assess the impact of immunosuppression on hematopoiesis, transfusion requirements, transformation, and survival in patients with MDS randomly assigned to 15 mg/kg of horse ATG for 5 days and oral CSA for 180 days (ATG+CSA) or best supportive care (BSC), stratified by treatment center and International Prognostic Scoring System (IPSS) risk score. Primary end point was best hematologic response at 6 months. Eligible patients had an Eastern Cooperative Oncology Group performance status of ≤ 2 and transfusion dependency of less than 2 years in duration. Between 2000 and 2006, 45 patients received ATG+CSA (median age, 62 years; range, 23 to 75 years; 56% men) and 43 patients received BSC (median age, 65 years; range, 24 to 76 years; 81% men). IPSS score was low, intermediate-1, intermediate-2, high, and not evaluable in eight, 24, seven, one, and five patients on ATG+CSA, respectively, and eight, 25, five, zero, and five patients on BSC, respectively. Refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess of blasts (RAEB) -I, RAEB-II, and hypoplastic disease were present in 21, six, nine, zero, and nine patients on ATG+CSA, respectively, and 18, eight, 11, two, and four patients on BSC, respectively. By month 6, 13 of 45 patients on ATG+CSA had a hematologic response compared with four of 43 patients on BSC (P = .0156). Two-year transformation-free survival (TFS) rates were 46% (95% CI, 28% to 62%) and 55% (95% CI, 34% to 70%) for ATG+CSA and BSC patients, respectively (P = .730), whereas overall survival (OS) estimates were 49% (95% CI, 31% to 66%) and 63% (95% CI, 42% to 78%), respectively (P = .828). This open-label randomized phase III trial demonstrates that ATG+CSA treatment seems to be associated with hematologic response in a subset of patients without apparent impact on TFS and OS.

• Complete cytogenetic remission after decitabine treatment in a patient with secondary AML harbouring high p15 ( INK4b ) gene methylation and high global DNA methylation.

  Authors: Ulrich Lehmann, Christiane Dobbelstein, Martin Fenner, Daniel Römermann, Britta Hasemeier, Kathleen Metzig, Doris Steinemann, Guntram Büsche, Jürgen Krauter, Arnold Ganser, Hans Kreipe

  Annals of hematology. 09/2008;