Axel Zander - Academia.edu (original) (raw)
Papers by Axel Zander
Journal of pain and symptom management, Jan 12, 2017
Due to toxicity and invasiveness, allogeneic HSCT causes severe and longstanding symptom burden. ... more Due to toxicity and invasiveness, allogeneic HSCT causes severe and longstanding symptom burden. Longitudinal studies on symptoms and symptom clusters (SC) would be helpful to optimize symptom control, but are rare to date. To investigate stability of symptoms, extract time stable SC and to determine their priority in symptom management. In this multicenter study, patients diagnosed with hematological cancer were assessed before conditioning (T0) and three months (T1), one year (T2) and five years (T3) after transplantation. Symptoms were assessed with the EORTC-QLQ-C30. Symptoms were stable when rated as present at three consecutive time points. Applying factor analysis, stable SC were composed of symptoms loading on the same factor across all time points. Priority in symptom management was derived from a combination of severity and predictive power for quality of life (QoL). 239 patients participated at T0, 150 (63 %) at T1, 102 (43 %) at T2 and 45 (19 %) at T3. We identified thre...
Journal of hematology & oncology, Jan 24, 2017
Primary refractory acute myeloid leukemia (PRF-AML) is associated with a dismal prognosis. Alloge... more Primary refractory acute myeloid leukemia (PRF-AML) is associated with a dismal prognosis. Allogeneic stem cell transplantation (HSCT) in active disease is an alternative therapeutic strategy. The increased availability of unrelated donors together with the significant reduction in transplant-related mortality in recent years have opened the possibility for transplantation to a larger number of patients with PRF-AML. Moreover, transplant from unrelated donors may be associated with stronger graft-mediated anti-leukemic effect in comparison to transplantations from HLA-matched sibling donor, which may be of importance in the setting of PRF-AML. The current study aimed to address the issue of HSCT for PRF-AML and to compare the outcomes of HSCT from matched sibling donors (n = 660) versus unrelated donors (n = 381), for patients with PRF-AML between 2000 and 2013. The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used wh...
Breast Cancer Research, 2001
Background: Disruption of the balance between apoptosis and proliferation is considered to be an ... more Background: Disruption of the balance between apoptosis and proliferation is considered to be an important factor in the development and progression of tumor. In this study we determined the in vivo cell kinetics along the spectrum of apparently normal epithelium, hyperplasia, preinvasive lesions and invasive carcinoma, in breast tissues affected by fibrocystic changes in which preinvasive and/or invasive lesions developed, as a model of breast carcinogenesis. Materials and method: A total of 32 areas of apparently normal epithelium and 135 ductal proliferative and neoplastic lesions were studied. More than one epithelial lesion per case was analyzed. The apoptotic index (AI) and the proliferative index (PI) were expressed as the percentage of TUNEL (TdT-mediated dUTP-nick end-labelling) and Ki-67 positive cells, respectively. The proliferative/apoptotic index (P/A) was calculated for each case. Results: Statistical analysis demonstrated significant differences among the tissue groups for both indices (P < 0.0001). The Als and PIs were significantly higher in hyperplasia than in apparently normal epithelium (P = 0.04 and P = 0.0005, respectively), in atypical hyperplasia than in hyperplasia (P = 0.01 and P = 0.04, respectively) and in invasive carcinoma than in in situ carcinoma (P = 0.0001 and P < 0.0001, respectively). The two indices were similar in atypical hyperplasia and in in situ carcinoma. The P/A index increased significantly from normal epithelium to hyperplasia (P = 0.01) and from preinvasive lesions to invasive carcinoma (P = 0.04), whereas it was decreased (NS) from hyperplasia to preinvasive lesions. A strong positive correlation between the Als and the Pls was found (r = 0.83; P < 0.0001). Conclusion: These findings suggest accelerating cell turnover along the continuum of breast carcinogenesis. Atypical hyperplasias and in situ carcinomas might be kinetically similar lesions. In the transition from normal epithelium to hyperplasia and from preinvasive lesions to invasive carcinoma, the net growth of epithelial cells results from a growth imbalance in favour of proliferation. In the transition from hyperplasia to preinvasive lesions there is an imbalance in favour of apoptosis.
This study reports outcomes of allogeneic hematopoietic stem cell transplantation with reduced-in... more This study reports outcomes of allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning (RIC) in 186 patients with chronic myeloid leukemia (CML) from the European Group for Blood and Marrow Transplantation (EBMT). The median age was 50 years, and 64% were in first chronic phase (CP1), CP2 13%, accelerated phase 17%, and blast crises 6%. The median EBMT transplant score was 3. The day 100 transplantation-related mortality (TRM) was 6.1% (confidence interval [CI], 3.4%-11%) but rose to 23.3% (CI, 14%-27%) at 2 years. Fludarabine, busulfan, and antithymocyte globulin (Fd/Bu/ATG) was associated with the lowest TRM of 11.6% (CI, 4.7%-11%) at 1 year. Acute graft-versus-host disease (GvHD) grade II to IV occurred in 32% and chronic GvHD in 43% (extensive in 24%). ATG was associated with a lower incidence of chronic GvHD (cGvHD). The overall survival (OS) and progression-free survival (PFS) at 3 years were 58% (CI, 50%-66%) and 37% (CI, 30%-45%), respectively. Adverse OS was associated with advanced disease (relative risk [RR], 3.4). PFS was inferior in advanced disease (RR, 2.7) and a trend to improved outcomes with Fd/Bu/ATG (RR, 0.58). RIC allografts are feasible in CML in first or second CP. Since no other RIC regimen demonstrated superiority, Fd/Bu/ATG should be considered as baseline in future prospective trials.
Anticancer Research, Apr 1, 2014
Background: Treatment for advanced pancreatic cancer is still very unsatisfactory. Treosulfan is ... more Background: Treatment for advanced pancreatic cancer is still very unsatisfactory. Treosulfan is an alkylating agent used for conventional, as well as high-dose chemotherapy regimens, whereby plasma concentrations over 500 μg/ml can be achieved. We investigated the effects of treosulfan on pancreatic cancer cell lines. Materials and Methods: Using Panc-1, MIA PaCa-2 and Capan-2 cell lines, we investigated the in vitro cytotoxicity of treosulfan-alone and in combination with gemcitabine, 5-fluorouracil or irradiation. Results: Treosulfan was potently cytotoxic against all pancreatic cancer cell lines at all concentrations (1-100 μg/ml). Combination of treosulfan and gemcitabine revealed strong synergistic effects independent of the sequence of drug administration. Similarly, synergism was observed with irradiation. Combination of treosulfan and 5-fluorouracil revealed antagonism. Conclusion: Treosulfan effectively kills pancreatic carcinoma cells in vitro and has synergistic activity in combination with gemcitabine and irradiation. These results warrant further investigation of treosulfan in the treatment of pancreatic cancer.
Clin Exp Med, 2010
The close association of the myeloproliferative neoplasms with the activating non-receptor tyrosi... more The close association of the myeloproliferative neoplasms with the activating non-receptor tyrosine kinase JAK2V617F mutation is well established. To further clarify the pathomechanisms of this mutation in patients with myelofibrosis, we performed screening with quantitative real-time PCR for the respective mutation in in vitro expanded bone marrow (BM) mesenchymal stromal cells (MSCs) and compared the results with BM/peripheral blood (PB). Eight patients with primary/secondary myelofibrosis were investigated before (n = 4) or after allogeneic stem cell transplantation (n = 4). All patients had systemic evidence of the JAK2V617F mutation in BM/PB (mutation ratios 0.2-23.5) at the time of investigation in contrast to negative results in the MSCs (n = 7) or a very low (0.004) mutation ratio (n = 1) which was probably due to hematopoietic contamination. The four patients post-transplant had systemic donor chimerism between 96.5 and 100% in BM/PB, while MSCs showed no evidence of donor-specific alleles. In conclusion, in myelofibrosis, the JAK2V617F mutation is restricted to hematopoietic cells, and cannot explain the stromal alterations being observed in this disorder. Further, the MSCs remain of recipient origin after allogeneic SCT, which might contribute to the increased risk of graft dysfunction or failure in myelofibrosis patients after allogeneic transplantation.
Annals of Hematology, Jan 27, 2009
Polyclonal antithymocyte globulins (ATGs) are used in organ and allogeneic stem cell transplantat... more Polyclonal antithymocyte globulins (ATGs) are used in organ and allogeneic stem cell transplantation mainly due to their immunomodulatory potential. Since ATGs contain antibodies against antigens expressed on various hematopoetic cells, it is not surprising that they induce cell death not only in healthy T-, B-, NK, and dendritic cells but also in malignant cells of lymphatic and to a lesser extent of myeloid lineage. The cytotoxic and antiproliferative effects of ATGs in malignant B-cells have been known for many years, without attracting clinical attention due to the advent of monoclonal antibodies like rituximab. Recent data indicate a potential role of ATGs in the therapy of multiple myeloma, a disease in which monoclonal serotherapy has been rather unsuccessful. This review discusses available data demonstrating the cytotoxic effects of ATGs and envisages a possible new role of these polyclonal antibodies in the therapy of hematological malignancies.
Leukemia, 2004
... (multiple letters) (2). Peggs, K and Mackinnon, S and Ayuk, FA and Zander, AR and Kröger, N (... more ... (multiple letters) (2). Peggs, K and Mackinnon, S and Ayuk, FA and Zander, AR and Kröger, N (2004) Graft-versus-myeloma: Are durable responses a clinical reality following donor lymphocyte infusion? (multiple letters) (2). Leukemia , 18 (9) 1541 - 1543. ...
J Hematother Stem Cell Res, 2003
High incidence of aspergillosis on transplant units or hematological wards without HEPA air condi... more High incidence of aspergillosis on transplant units or hematological wards without HEPA air conditioning during periods of demolishing or construction has been reported by several investigators. Here we report monitoring of fungal air contamination during a period of construction on a stem cell transplantation ward using the gravity air-setting plate (GASP) method. Fungal air contamination in HEPA-conditioned patient rooms was constantly low, independent from construction activity. Outside of the patient rooms at the ward&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s corridor, the fungal load was significantly higher with some peak values. Outside the transplant unit measures of construction led to a significant increase of fungal spore concentration in air. Transplant activity was not reduced during construction and patients were nursed strictly under HEPA conditions. Patients were monitored prospectively for incidence of infections since 1990 and data of patients grafted during construction (n = 28) were compared to those grafted outside building activity (n = 652). An increase of aspergillosis during construction could be clearly excluded. It can be concluded: Nursing of patients undergoing stem cell transplantation in HEPA-conditioned rooms is an effective protection against acquisition of aspergillus-infection, even under environmental conditions with increased air contamination by conidia. The gravity air-setting plate (GASP) method is not expensive and easy to use and allows reliable and quantitative aerobiological spore monitoring.
Haematologica, 2005
CIC 279). © F e r r a t a S t o r t i F o u n d a t i o n | 970 | haematologica/the hematology jo... more CIC 279). © F e r r a t a S t o r t i F o u n d a t i o n | 970 | haematologica/the hematology journal | 2005; 90(7) B. Hertenstein et al.
Bone Marrow Transplant, 2008
Allogeneic SCT is important in myelodysplastic syndrome, the BCR-ABL-negative chronic myeloprolif... more Allogeneic SCT is important in myelodysplastic syndrome, the BCR-ABL-negative chronic myeloproliferative diseases (CMPDs) and in poor-risk AML. Techniques to monitor the minimal residual disease, for example, by PCR or immunophenotyping gain increasing importance in the post transplantation period as basis for improved and earlier therapeutic interventions in impending relapse. Recent markers such as the NPM1 mutations in AML or the JAK2V617F mutation in the CMPD can be exactly quantified by real-time PCR and were evaluated for their prognostic value in the post transplantation phase and for their utility to plan adoptive immunotherapy in case of molecular relapse. With respect to chimerism, new and very sensitive methods were introduced, for example, quantitative assessment of genetic polymorphisms by real-time PCR, but also methods here are still highly individualized. Only in CML, where SCT focuses now on poor-risk cases or cases of tyrosine kinase inhibitor failure, follow-up schedules are standardized. Standardization of the different diagnostic techniques and of the intervals in the post transplantation period is urgently needed also in other myeloid malignancies and should be focus of future studies.
Ash Annual Meeting Abstracts, Nov 16, 2005
ABSTRACT
Haematologica the Hematology Journal, Feb 1, 2007
Monitoring of serum free immunoglobulin light chains (FLC) in 26 myeloma patients who achieved im... more Monitoring of serum free immunoglobulin light chains (FLC) in 26 myeloma patients who achieved immunofixation negativity after allografting showed a decrease of FLC at a median of 128 days before immunofixation negativity. In patients who subsequently relapsed, a 25% increase of FLC was observed at a median of 98 days before immunofixation positivity.
Infusionstherapie Und Transfusionsmedizin, 1999
ABSTRACT High-dose therapy with subsequent allogeneic or autologous transplantation of haemopoiet... more ABSTRACT High-dose therapy with subsequent allogeneic or autologous transplantation of haemopoietic progenitor cells has proved to be an important therapy for patients with haematological malignancies, certain non-haematological cancers and several nonmalignant disorders such as severe aplastic anaemia. Allogeneic and autologous transplantation are associated with specific complications. One major problem after allotransplantation is the graft versus host disease with jaundice, diarrhoea and erythema. The major problem of autologous stem cell transplantation is a potential reinfusion of contaminating tumor cells. Allogeneic transplantation has been refined, and an approach to modulate graft versus host disease is a partial or complete lymphocyte depletion. Especially in the allogeneic setting, the field of cell therapy for modulation of graft versus host disease and treatment of transplant-related complications is expanding. For autologous transplantation different techniques to purge autografts from malignant contaminants have been developed. These cell selection techniques consist of immunological, biological, cultural, chemotherapeutical and physical techniques. This article reviews techniques currently used for graft engineering in bone marrow and blood stem cell transplantation.
Very little is known about the number and function of immunosuppressive CD4 + CD25 + FOXP3 + T re... more Very little is known about the number and function of immunosuppressive CD4 + CD25 + FOXP3 + T regulatory cells (Treg) in the human bone marrow and it is unclear whether bone marrow-residing Treg are capable of regenerating following allogeneic stem cell transplantation. This is particularly surprising since the bone marrow represents a major priming site for T-cell responses and Treg play important roles in the prevention of T-cell-mediated graft-versus-host disease and in promoting tumor escape from T-cell-dependent immunosurveillance.
Stem Cells and Development, 2016
Mesenchymal stromal/stem cells (MSCs) constitute progenitor cells that can be isolated from diffe... more Mesenchymal stromal/stem cells (MSCs) constitute progenitor cells that can be isolated from different tissues. Based on their immunomodulatory and neuroprotective functions, MSC-based cell-therapy approaches have been suggested to antagonize inflammatory activity and neuronal damage associated with autoimmune disease of the central nervous system (CNS), e.g. multiple sclerosis (MS). Intravenous MSC transplantation was reported to ameliorate experimental autoimmune encephalomyelitis (EAE), the murine model of MS, within days after transplantation. However, systemic distribution patterns and fate of MSCs after administration, especially their potential to migrate into inflammatory lesions within the CNS, remain to be elucidated. This question has of recent become particularly important, since therapeutic infusion of MSCs is now being tested in clinical trials with MS-affected patients. Here we made use of the established EAE mouse model to investigate migration and therapeutic efficacy of murine bone-marrow derived MSCs. Applying a variety of techniques, including magnetic-resonance imaging, immunohistochemistry, fluorescence in-situ hybridization, and quantitative PCR we found no evidence for immediate migration of infused MSC into the CNS of treated mice. Moreover, in contrast to other studies, transplanted MSCs did not ameliorate EAE. In conclusion, our data does not provide substantiation for a relevant migration of infused MSCs into the CNS of EAE mice supporting the hypothesis that potential therapeutic efficacy could be based on systemic effects. Evaluation of possible mechanisms underlying the observed discrepancies in MSC-treatment outcomes between different EAE models demands further studies.
Journal of pain and symptom management, Jan 12, 2017
Due to toxicity and invasiveness, allogeneic HSCT causes severe and longstanding symptom burden. ... more Due to toxicity and invasiveness, allogeneic HSCT causes severe and longstanding symptom burden. Longitudinal studies on symptoms and symptom clusters (SC) would be helpful to optimize symptom control, but are rare to date. To investigate stability of symptoms, extract time stable SC and to determine their priority in symptom management. In this multicenter study, patients diagnosed with hematological cancer were assessed before conditioning (T0) and three months (T1), one year (T2) and five years (T3) after transplantation. Symptoms were assessed with the EORTC-QLQ-C30. Symptoms were stable when rated as present at three consecutive time points. Applying factor analysis, stable SC were composed of symptoms loading on the same factor across all time points. Priority in symptom management was derived from a combination of severity and predictive power for quality of life (QoL). 239 patients participated at T0, 150 (63 %) at T1, 102 (43 %) at T2 and 45 (19 %) at T3. We identified thre...
Journal of hematology & oncology, Jan 24, 2017
Primary refractory acute myeloid leukemia (PRF-AML) is associated with a dismal prognosis. Alloge... more Primary refractory acute myeloid leukemia (PRF-AML) is associated with a dismal prognosis. Allogeneic stem cell transplantation (HSCT) in active disease is an alternative therapeutic strategy. The increased availability of unrelated donors together with the significant reduction in transplant-related mortality in recent years have opened the possibility for transplantation to a larger number of patients with PRF-AML. Moreover, transplant from unrelated donors may be associated with stronger graft-mediated anti-leukemic effect in comparison to transplantations from HLA-matched sibling donor, which may be of importance in the setting of PRF-AML. The current study aimed to address the issue of HSCT for PRF-AML and to compare the outcomes of HSCT from matched sibling donors (n = 660) versus unrelated donors (n = 381), for patients with PRF-AML between 2000 and 2013. The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used wh...
Breast Cancer Research, 2001
Background: Disruption of the balance between apoptosis and proliferation is considered to be an ... more Background: Disruption of the balance between apoptosis and proliferation is considered to be an important factor in the development and progression of tumor. In this study we determined the in vivo cell kinetics along the spectrum of apparently normal epithelium, hyperplasia, preinvasive lesions and invasive carcinoma, in breast tissues affected by fibrocystic changes in which preinvasive and/or invasive lesions developed, as a model of breast carcinogenesis. Materials and method: A total of 32 areas of apparently normal epithelium and 135 ductal proliferative and neoplastic lesions were studied. More than one epithelial lesion per case was analyzed. The apoptotic index (AI) and the proliferative index (PI) were expressed as the percentage of TUNEL (TdT-mediated dUTP-nick end-labelling) and Ki-67 positive cells, respectively. The proliferative/apoptotic index (P/A) was calculated for each case. Results: Statistical analysis demonstrated significant differences among the tissue groups for both indices (P < 0.0001). The Als and PIs were significantly higher in hyperplasia than in apparently normal epithelium (P = 0.04 and P = 0.0005, respectively), in atypical hyperplasia than in hyperplasia (P = 0.01 and P = 0.04, respectively) and in invasive carcinoma than in in situ carcinoma (P = 0.0001 and P < 0.0001, respectively). The two indices were similar in atypical hyperplasia and in in situ carcinoma. The P/A index increased significantly from normal epithelium to hyperplasia (P = 0.01) and from preinvasive lesions to invasive carcinoma (P = 0.04), whereas it was decreased (NS) from hyperplasia to preinvasive lesions. A strong positive correlation between the Als and the Pls was found (r = 0.83; P < 0.0001). Conclusion: These findings suggest accelerating cell turnover along the continuum of breast carcinogenesis. Atypical hyperplasias and in situ carcinomas might be kinetically similar lesions. In the transition from normal epithelium to hyperplasia and from preinvasive lesions to invasive carcinoma, the net growth of epithelial cells results from a growth imbalance in favour of proliferation. In the transition from hyperplasia to preinvasive lesions there is an imbalance in favour of apoptosis.
This study reports outcomes of allogeneic hematopoietic stem cell transplantation with reduced-in... more This study reports outcomes of allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning (RIC) in 186 patients with chronic myeloid leukemia (CML) from the European Group for Blood and Marrow Transplantation (EBMT). The median age was 50 years, and 64% were in first chronic phase (CP1), CP2 13%, accelerated phase 17%, and blast crises 6%. The median EBMT transplant score was 3. The day 100 transplantation-related mortality (TRM) was 6.1% (confidence interval [CI], 3.4%-11%) but rose to 23.3% (CI, 14%-27%) at 2 years. Fludarabine, busulfan, and antithymocyte globulin (Fd/Bu/ATG) was associated with the lowest TRM of 11.6% (CI, 4.7%-11%) at 1 year. Acute graft-versus-host disease (GvHD) grade II to IV occurred in 32% and chronic GvHD in 43% (extensive in 24%). ATG was associated with a lower incidence of chronic GvHD (cGvHD). The overall survival (OS) and progression-free survival (PFS) at 3 years were 58% (CI, 50%-66%) and 37% (CI, 30%-45%), respectively. Adverse OS was associated with advanced disease (relative risk [RR], 3.4). PFS was inferior in advanced disease (RR, 2.7) and a trend to improved outcomes with Fd/Bu/ATG (RR, 0.58). RIC allografts are feasible in CML in first or second CP. Since no other RIC regimen demonstrated superiority, Fd/Bu/ATG should be considered as baseline in future prospective trials.
Anticancer Research, Apr 1, 2014
Background: Treatment for advanced pancreatic cancer is still very unsatisfactory. Treosulfan is ... more Background: Treatment for advanced pancreatic cancer is still very unsatisfactory. Treosulfan is an alkylating agent used for conventional, as well as high-dose chemotherapy regimens, whereby plasma concentrations over 500 μg/ml can be achieved. We investigated the effects of treosulfan on pancreatic cancer cell lines. Materials and Methods: Using Panc-1, MIA PaCa-2 and Capan-2 cell lines, we investigated the in vitro cytotoxicity of treosulfan-alone and in combination with gemcitabine, 5-fluorouracil or irradiation. Results: Treosulfan was potently cytotoxic against all pancreatic cancer cell lines at all concentrations (1-100 μg/ml). Combination of treosulfan and gemcitabine revealed strong synergistic effects independent of the sequence of drug administration. Similarly, synergism was observed with irradiation. Combination of treosulfan and 5-fluorouracil revealed antagonism. Conclusion: Treosulfan effectively kills pancreatic carcinoma cells in vitro and has synergistic activity in combination with gemcitabine and irradiation. These results warrant further investigation of treosulfan in the treatment of pancreatic cancer.
Clin Exp Med, 2010
The close association of the myeloproliferative neoplasms with the activating non-receptor tyrosi... more The close association of the myeloproliferative neoplasms with the activating non-receptor tyrosine kinase JAK2V617F mutation is well established. To further clarify the pathomechanisms of this mutation in patients with myelofibrosis, we performed screening with quantitative real-time PCR for the respective mutation in in vitro expanded bone marrow (BM) mesenchymal stromal cells (MSCs) and compared the results with BM/peripheral blood (PB). Eight patients with primary/secondary myelofibrosis were investigated before (n = 4) or after allogeneic stem cell transplantation (n = 4). All patients had systemic evidence of the JAK2V617F mutation in BM/PB (mutation ratios 0.2-23.5) at the time of investigation in contrast to negative results in the MSCs (n = 7) or a very low (0.004) mutation ratio (n = 1) which was probably due to hematopoietic contamination. The four patients post-transplant had systemic donor chimerism between 96.5 and 100% in BM/PB, while MSCs showed no evidence of donor-specific alleles. In conclusion, in myelofibrosis, the JAK2V617F mutation is restricted to hematopoietic cells, and cannot explain the stromal alterations being observed in this disorder. Further, the MSCs remain of recipient origin after allogeneic SCT, which might contribute to the increased risk of graft dysfunction or failure in myelofibrosis patients after allogeneic transplantation.
Annals of Hematology, Jan 27, 2009
Polyclonal antithymocyte globulins (ATGs) are used in organ and allogeneic stem cell transplantat... more Polyclonal antithymocyte globulins (ATGs) are used in organ and allogeneic stem cell transplantation mainly due to their immunomodulatory potential. Since ATGs contain antibodies against antigens expressed on various hematopoetic cells, it is not surprising that they induce cell death not only in healthy T-, B-, NK, and dendritic cells but also in malignant cells of lymphatic and to a lesser extent of myeloid lineage. The cytotoxic and antiproliferative effects of ATGs in malignant B-cells have been known for many years, without attracting clinical attention due to the advent of monoclonal antibodies like rituximab. Recent data indicate a potential role of ATGs in the therapy of multiple myeloma, a disease in which monoclonal serotherapy has been rather unsuccessful. This review discusses available data demonstrating the cytotoxic effects of ATGs and envisages a possible new role of these polyclonal antibodies in the therapy of hematological malignancies.
Leukemia, 2004
... (multiple letters) (2). Peggs, K and Mackinnon, S and Ayuk, FA and Zander, AR and Kröger, N (... more ... (multiple letters) (2). Peggs, K and Mackinnon, S and Ayuk, FA and Zander, AR and Kröger, N (2004) Graft-versus-myeloma: Are durable responses a clinical reality following donor lymphocyte infusion? (multiple letters) (2). Leukemia , 18 (9) 1541 - 1543. ...
J Hematother Stem Cell Res, 2003
High incidence of aspergillosis on transplant units or hematological wards without HEPA air condi... more High incidence of aspergillosis on transplant units or hematological wards without HEPA air conditioning during periods of demolishing or construction has been reported by several investigators. Here we report monitoring of fungal air contamination during a period of construction on a stem cell transplantation ward using the gravity air-setting plate (GASP) method. Fungal air contamination in HEPA-conditioned patient rooms was constantly low, independent from construction activity. Outside of the patient rooms at the ward&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s corridor, the fungal load was significantly higher with some peak values. Outside the transplant unit measures of construction led to a significant increase of fungal spore concentration in air. Transplant activity was not reduced during construction and patients were nursed strictly under HEPA conditions. Patients were monitored prospectively for incidence of infections since 1990 and data of patients grafted during construction (n = 28) were compared to those grafted outside building activity (n = 652). An increase of aspergillosis during construction could be clearly excluded. It can be concluded: Nursing of patients undergoing stem cell transplantation in HEPA-conditioned rooms is an effective protection against acquisition of aspergillus-infection, even under environmental conditions with increased air contamination by conidia. The gravity air-setting plate (GASP) method is not expensive and easy to use and allows reliable and quantitative aerobiological spore monitoring.
Haematologica, 2005
CIC 279). © F e r r a t a S t o r t i F o u n d a t i o n | 970 | haematologica/the hematology jo... more CIC 279). © F e r r a t a S t o r t i F o u n d a t i o n | 970 | haematologica/the hematology journal | 2005; 90(7) B. Hertenstein et al.
Bone Marrow Transplant, 2008
Allogeneic SCT is important in myelodysplastic syndrome, the BCR-ABL-negative chronic myeloprolif... more Allogeneic SCT is important in myelodysplastic syndrome, the BCR-ABL-negative chronic myeloproliferative diseases (CMPDs) and in poor-risk AML. Techniques to monitor the minimal residual disease, for example, by PCR or immunophenotyping gain increasing importance in the post transplantation period as basis for improved and earlier therapeutic interventions in impending relapse. Recent markers such as the NPM1 mutations in AML or the JAK2V617F mutation in the CMPD can be exactly quantified by real-time PCR and were evaluated for their prognostic value in the post transplantation phase and for their utility to plan adoptive immunotherapy in case of molecular relapse. With respect to chimerism, new and very sensitive methods were introduced, for example, quantitative assessment of genetic polymorphisms by real-time PCR, but also methods here are still highly individualized. Only in CML, where SCT focuses now on poor-risk cases or cases of tyrosine kinase inhibitor failure, follow-up schedules are standardized. Standardization of the different diagnostic techniques and of the intervals in the post transplantation period is urgently needed also in other myeloid malignancies and should be focus of future studies.
Ash Annual Meeting Abstracts, Nov 16, 2005
ABSTRACT
Haematologica the Hematology Journal, Feb 1, 2007
Monitoring of serum free immunoglobulin light chains (FLC) in 26 myeloma patients who achieved im... more Monitoring of serum free immunoglobulin light chains (FLC) in 26 myeloma patients who achieved immunofixation negativity after allografting showed a decrease of FLC at a median of 128 days before immunofixation negativity. In patients who subsequently relapsed, a 25% increase of FLC was observed at a median of 98 days before immunofixation positivity.
Infusionstherapie Und Transfusionsmedizin, 1999
ABSTRACT High-dose therapy with subsequent allogeneic or autologous transplantation of haemopoiet... more ABSTRACT High-dose therapy with subsequent allogeneic or autologous transplantation of haemopoietic progenitor cells has proved to be an important therapy for patients with haematological malignancies, certain non-haematological cancers and several nonmalignant disorders such as severe aplastic anaemia. Allogeneic and autologous transplantation are associated with specific complications. One major problem after allotransplantation is the graft versus host disease with jaundice, diarrhoea and erythema. The major problem of autologous stem cell transplantation is a potential reinfusion of contaminating tumor cells. Allogeneic transplantation has been refined, and an approach to modulate graft versus host disease is a partial or complete lymphocyte depletion. Especially in the allogeneic setting, the field of cell therapy for modulation of graft versus host disease and treatment of transplant-related complications is expanding. For autologous transplantation different techniques to purge autografts from malignant contaminants have been developed. These cell selection techniques consist of immunological, biological, cultural, chemotherapeutical and physical techniques. This article reviews techniques currently used for graft engineering in bone marrow and blood stem cell transplantation.
Very little is known about the number and function of immunosuppressive CD4 + CD25 + FOXP3 + T re... more Very little is known about the number and function of immunosuppressive CD4 + CD25 + FOXP3 + T regulatory cells (Treg) in the human bone marrow and it is unclear whether bone marrow-residing Treg are capable of regenerating following allogeneic stem cell transplantation. This is particularly surprising since the bone marrow represents a major priming site for T-cell responses and Treg play important roles in the prevention of T-cell-mediated graft-versus-host disease and in promoting tumor escape from T-cell-dependent immunosurveillance.
Stem Cells and Development, 2016
Mesenchymal stromal/stem cells (MSCs) constitute progenitor cells that can be isolated from diffe... more Mesenchymal stromal/stem cells (MSCs) constitute progenitor cells that can be isolated from different tissues. Based on their immunomodulatory and neuroprotective functions, MSC-based cell-therapy approaches have been suggested to antagonize inflammatory activity and neuronal damage associated with autoimmune disease of the central nervous system (CNS), e.g. multiple sclerosis (MS). Intravenous MSC transplantation was reported to ameliorate experimental autoimmune encephalomyelitis (EAE), the murine model of MS, within days after transplantation. However, systemic distribution patterns and fate of MSCs after administration, especially their potential to migrate into inflammatory lesions within the CNS, remain to be elucidated. This question has of recent become particularly important, since therapeutic infusion of MSCs is now being tested in clinical trials with MS-affected patients. Here we made use of the established EAE mouse model to investigate migration and therapeutic efficacy of murine bone-marrow derived MSCs. Applying a variety of techniques, including magnetic-resonance imaging, immunohistochemistry, fluorescence in-situ hybridization, and quantitative PCR we found no evidence for immediate migration of infused MSC into the CNS of treated mice. Moreover, in contrast to other studies, transplanted MSCs did not ameliorate EAE. In conclusion, our data does not provide substantiation for a relevant migration of infused MSCs into the CNS of EAE mice supporting the hypothesis that potential therapeutic efficacy could be based on systemic effects. Evaluation of possible mechanisms underlying the observed discrepancies in MSC-treatment outcomes between different EAE models demands further studies.