Publications by authors named "Tanja Gromke"

8 Publications

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Fertility preservation and fulfillment of parenthood after treatment of hematological malignancies: results from the 'Aftercare in Blood Cancer Survivors' (ABC) study.

Int J Clin Oncol 2020 Jun 5;25(6):1187-1194. Epub 2020 Mar 5.

Department of Hematology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany.

Purpose: Treatment of hematological malignancies carries the risk of lasting sterility. We aimed to identify fertility-related unmet needs.

Methods: The 'Aftercare in Blood Cancer Survivors' study is a cohort study of hematological patients who were in treatment-free remission for ≥ 3 years or stable under continuous oral medication. Female patients age 18-45 years and male patients age 18-65 years without a history of pre-treatment infertility were asked to answer a structured questionnaire including questions addressing fertility issues. Multivariable analyses were performed to detect risk factors.

Results: Of 1562 study participants, 1031 met the inclusion criteria for the fertility sub-study. A high proportion of patients (72.4%) received information about the risk of losing fertility, but only a minority (15%) took steps to preserve it. Female and older patients were less likely to be informed. A post-treatment wish for parenthood was expressed by 19.3% of patients. It was strongly associated with childlessness at time of diagnosis and could be fulfilled by 29.4%. Fulfillment of desired parenthood increased with increasing time from diagnosis and was low after allogeneic transplantation.

Conclusions: Female and older hematological patients are less likely to be informed about fertility-related issues than other patients. With societal changes towards first parenthood at higher age, the proportion of patients desiring a child after treatment is likely to increase. Fulfillment of desired parenthood remains challenging, especially after allogeneic transplantation.

Implications For Cancer Survivors: In patients likely to express a wish for post-treatment parenthood, fertility-related issues should routinely be addressed before gonadotoxic treatment is started.
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June 2020

Standardized monitoring of cytomegalovirus-specific immunity can improve risk stratification of recurrent cytomegalovirus reactivation after hematopoietic stem cell transplantation.

Haematologica 2021 Feb 1;106(2):363-374. Epub 2021 Feb 1.

Dpt of Internal Medicine III, Hematology and Oncology, University Medical Center Regensburg, Germany.

Recurrence of cytomegalovirus reactivation remains a major cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation. Monitoring cytomegalovirus-specific cellular immunity using a standardized assay might improve the risk stratification of patients. A prospective multicenter study was conducted in 175 intermediate- and high-risk allogeneic hematopoietic stem cell transplant recipients under preemptive antiviral therapy. Cytomegalovirus-specific cellular immunity was measured using a standardized IFN-γ ELISpot assay (T-Track® CMV). Primary aim was to evaluate the suitability of measuring cytomegalovirus-specific immunity after end of treatment for a first cytomegalovirus reactivation to predict recurrent reactivation. 40/101 (39.6%) patients with a first cytomegalovirus reactivation experienced recurrent reactivations, mainly in the high-risk group (cytomegalovirus-seronegative donor/cytomegalovirus-seropositive recipient). The positive predictive value of T-Track® CMV (patients with a negative test after the first reactivation experienced at least one recurrent reactivation) was 84.2% in high-risk patients. Kaplan-Meier analysis revealed a higher probability of recurrent cytomegalovirus reactivation in high-risk patients with a negative test after the first reactivation (hazard ratio 2.73; p=0.007). Interestingly, a post-hoc analysis considering T-Track® CMV measurements at day 100 post-transplantation, a time point highly relevant for outpatient care, showed a positive predictive value of 90.0% in high-risk patients. Our results indicate that standardized cytomegalovirus-specific cellular immunity monitoring may allow improved risk stratification and management of recurrent cytomegalovirus reactivation after hematopoietic stem cell transplantation. This study was registered at as #NCT02156479.
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February 2021

Endoscopic and Histological Findings Are Predicted by Fecal Calprotectin in Acute Intestinal Graft-Versus-Host-Disease.

Dig Dis Sci 2016 07 19;61(7):2019-26. Epub 2016 Mar 19.

Department of Bone Marrow Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Germany.

Background: Gastrointestinal graft-versus-host-disease (GI-GVHD) is a major cause of nonrelapse mortality after hematopoietic stem cell transplantation (HSCT) necessitating endoscopic examinations and biopsies for diagnosis. Fecal calprotectin (CPT) has been widely used in gastrointestinal inflammation, but comprehensive data in GI-GVHD are lacking.

Aims: We aimed to identify an association of CPT with endoscopic findings, mucosal damage and symptoms for diagnosing and monitoring acute GI-GVHD.

Methods: Symptoms were prospectively evaluated in 110 consecutive HSCT recipients by standardized questionnaires and Bristol Stool Scale (BSS). CPT was assayed by ELISA. Symptom assessment and CPT were performed weekly and with onset of first symptoms. GVHD was diagnosed according to the Glucksberg criteria and by endoscopic biopsies. Patients with GI-GVHD received standard high-dose corticosteroid therapy and follow-up CPT, and symptom evaluation was performed after 28 days. Patients not responding to steroid treatment were re-evaluated by colonoscopy.

Results: GI-GVHD was diagnosed in 40 patients. Twelve patients with GI symptoms and CMV colitis and 24 patients with isolated skin GVHD were included as control subjects. CPT was significantly higher in GI-GVHD compared to skin GVHD and CMV colitis. Endoscopic findings, histological grading, abdominal cramps, diarrhea, urgency and BSS correlated with CPT. At follow-up, CPT correlated with abdominal cramps, diarrhea, urgency and BSS. In steroid refractory patients, CPT level was still significantly associated with severity of mucosal damage.

Conclusion: CPT predicts endoscopic and histological findings in GI-GVHD and correlates with lower GI symptoms. It enables to discriminate GVHD from CMV colitis and to monitor therapeutic success.
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July 2016

CD34+ highly enriched allogeneic stem cell transplantation in a patient with mixed phenotype acute leukemia and Fusarium solani sepsis.

Ann Hematol 2016 Jan 18;95(1):155-156. Epub 2015 Sep 18.

Department of Bone Marrow Transplantation, University Hospital, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.

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January 2016

Hematopoietic stem-cell transplantation for advanced systemic mastocytosis.

J Clin Oncol 2014 Oct 25;32(29):3264-74. Epub 2014 Aug 25.

Celalettin Ustun, Ryan Shanley, Gregory Vercellotti, and Daniel Weisdorf, University of Minnesota, Minneapolis; William J. Hogan, Mayo Clinic, Rochester, MN; Andreas Reiter and Sebastian Kreil, Universitätsmedizin Mannheim, Mannheim; Herrad Baurmann, Stiftung Deutsche Klinik für Diagnostik, Wiesbaden; Bernd Gruhn, Jena University Hospital, Jena; Tanja Gromke, University of Essen, Essen; Eva Maria Wagner, Universitätsmedizin Mainz, Mainz; Martin Bornhäuser, Universitätsklinikum Dresden, Dresden; Christoph Schmid, Klinikum Augsburg, Ausburg, Germany; Bart L. Scott and H. Joachim Deeg, University of Washington, Seattle, WA; Ryotaro Nakamura, City of Hope National Medical Center, Duarte; Vinod Pullarkat, University of Southern California, Los Angeles, CA; Gandhi Damaj, Université de Caen, Faculté de Médecine, Caen; Faezeh Legrand, Nice University Hospital, Nice, and Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC); Ibrahim Yakoub-agha, Centre Hospitalier Régionale Universitaire, Lille; Olivier Hermine, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Necker Enfants-Malades, Université Paris 5 Faculté de Médecine et AP-HP Necker-Enfants Malades, and Centre de Référence des Mastocytoses, Paris, France; Miguel-Angel Perales and Esperanza B. Papadopoulos, Memorial Sloan-Kettering Cancer Center; Tsiporah Shore, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY; Robert Stuart, Medical University of South Carolina, Charleston, SC; Michael Doubek, Masaryk University, Brno, Czech Republic; Jack W. Hsu, University of Florida, Gainesville, FL; Eleni Tholouli, Manchester Royal Infirmary, Manchester, United Kingdom; Lucy A. Godley, University of Chicago, Chicago, IL; Livio Pagano, Università Cattolica del Sacro Cuore, Milan; Maria Teresa Van Lint, Istituto Di Ricovero e Cura a Carattere Scientifico San Martino-IST, Genova, Italy; Andrew Gilman, Levine Children's Hospital, Charlotte, NC; Tor Shwayder, Henry F

Purpose: Advanced systemic mastocytosis (SM), a fatal hematopoietic malignancy characterized by drug resistance, has no standard therapy. The effectiveness of allogeneic hematopoietic stem-cell transplantation (alloHCT) in SM remains unknown.

Patients And Methods: In a global effort to define the value of HCT in SM, 57 patients with the following subtypes of SM were evaluated: SM associated with clonal hematologic non-mast cell disorders (SM-AHNMD; n = 38), mast cell leukemia (MCL; n = 12), and aggressive SM (ASM; n = 7). Median age of patients was 46 years (range, 11 to 67 years). Donors were HLA-identical (n = 34), unrelated (n = 17), umbilical cord blood (n = 2), HLA-haploidentical (n = 1), or unknown (n = 3). Thirty-six patients received myeloablative conditioning (MAC), and 21 patients received reduced-intensity conditioning (RIC).

Results: Responses in SM were observed in 40 patients (70%), with complete remission in 16 patients (28%). Twelve patients (21%) had stable disease, and five patients (9%) had primary refractory disease. Overall survival (OS) at 3 years was 57% for all patients, 74% for patients with SM-AHNMD, 43% for those with ASM, and 17% for those with MCL. The strongest risk factor for poor OS was MCL. Survival was also lower in patients receiving RIC compared with MAC and in patients having progression compared with patients having stable disease or response.

Conclusion: AlloHCT was associated with long-term survival in patients with advanced SM. Although alloHCT may be considered as a viable and potentially curative therapeutic option for advanced SM in the meantime, given that this is a retrospective analysis with no control group, the definitive role of alloHCT will need to be determined by a prospective trial.
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October 2014

Dynamic International Prognostic Scoring System scores, pre-transplant therapy and chronic graft-versus-host disease determine outcome after allogeneic hematopoietic stem cell transplantation for myelofibrosis.

Haematologica 2012 Oct 4;97(10):1574-81. Epub 2012 Apr 4.

Department of Bone Marrow Transplantation, WTZ, University Hospital of Essen, Essen, Germany.

Background: Myelofibrosis is a myeloproliferative stem cell disorder curable exclusively by allogeneic hematopoietic stem cell transplantation and is associated with substantial mortality and morbidity. The aim of this study was to assess disease-specific and transplant-related risk factors that influence post-transplant outcome in patients with myelofibrosis.

Design And Methods: We retrospectively assessed 76 consecutive patients with primary (n=47) or secondary (n=29) myelofibrosis who underwent bone marrow (n=6) or peripheral blood stem cell (n=70) transplantation from sibling (n=30) or unrelated (n=46) donors between January 1994 and December 2010. The median follow-up of surviving patients was 55 ± 7.5 months.

Results: Primary graft failure occurred in 5% and the non-relapse mortality rate at 1 year was 28%. The relapse-free survival rate was 50% with a relapse rate of 19% at 5 years. The use of pharmacological pre-treatment and the post-transplant occurrence of chronic graft-versus-host disease were significant independent unfavourable risk factors for post-transplant survival in multivariate analysis. Using the Dynamic International Prognostic Scoring System for risk stratification, low-risk patients had significantly better overall survival (P=0.014, hazard ratio 1.4) and relapse-free survival (P=0.02, hazard ratio 1.3) compared to the other risk groups of patients. The additional inclusion of thrombocytopenia, abnormal karyotype and transfusion need (Dynamic International Prognostic Scoring System Plus) resulted in a predicted 5-year overall survival of 100%, 51%, 54% and 30% for low, intermediate-1, intermediate-2 and high-risk groups, respectively. The relapse incidence was significantly higher in the absence of chronic graft-versus-host disease (P=0.006), and pharmacological pre-treatment (n=43) was associated with reduced relapse-free survival (P=0.001).

Conclusions: The data corroborate a strong correlation between alloreactivity and long-term post-transplant disease control and confirm an inverse relationship between disease stage, pharmacotherapy and outcome after allogeneic hematopoietic stem cell transplantation for myelofibrosis. The Dynamic International Prognostic Scoring System was demonstrated to be useful for risk stratification of patients with myelofibrosis who are to undergo hematopoietic stem cell transplantation.
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October 2012

Early human cytomegalovirus replication after transplantation is associated with a decreased relapse risk: evidence for a putative virus-versus-leukemia effect in acute myeloid leukemia patients.

Blood 2011 Aug 3;118(5):1402-12. Epub 2011 May 3.

Department of Bone Marrow Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

The impact of early human cytomegalovirus (HCMV) replication on leukemic recurrence was evaluated in 266 consecutive adult (median age, 47 years; range, 18-73 years) acute myeloid leukemia patients, who underwent allogeneic stem cell transplantation (alloSCT) from 10 of 10 high-resolution human leukocyte Ag-identical unrelated (n = 148) or sibling (n = 118) donors. A total of 63% of patients (n = 167) were at risk for HCMV reactivation by patient and donor pretransplantation HCMV serostatus. In 77 patients, first HCMV replication as detected by pp65-antigenemia assay developed at a median of 46 days (range, 25-108 days) after alloSCT. Taking all relevant competing risk factors into account, the cumulative incidence of hematologic relapse at 10 years after alloSCT was 42% (95% confidence interval [CI], 35%-51%) in patients without opposed to 9% (95% CI, 4%-19%) in patients with early pp65-antigenemia (P < .0001). A substantial and independent reduction of the relapse risk associated with early HCMV replication was confirmed by multivariate analysis using time-dependent covariate functions for grades II to IV acute and chronic graft-versus-host disease, and pp65-antigenemia (hazard ratio = 0.2; 95% CI, 0.1-0.4, P < .0001). This is the first report that demonstrates an independent and substantial reduction of the leukemic relapse risk after early replicative HCMV infection in a homogeneous population of adult acute myeloid leukemia patients.
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August 2011

Differential phosphorylation of IRS-1 and IRS-2 by insulin and IGF-I receptors.

Arch Physiol Biochem 2006 Feb;112(1):37-47

Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Düsseldorf, Germany.

The specific contribution of insulin and IGF-I receptors to IRS-protein activation remains elusive. We studied the signalling properties of AspB10-insulin, an analog with enhanced affinity for the IGF-I receptor, in comparison to native insulin using primary human skeletal muscle cells. In myoblasts regular insulin and AspB10-insulin were equipotent in stimulating the IRS cascade, whereas this analog induced a significantly higher Shc phosphorylation. Phosphorylation of IRS-1 in response to insulin was inhibited equally by blocking either the insulin or the IGF-I receptor. IRS-1 activation by AspB10-insulin was only inhibited by blocking the IGF-I receptor. IRS-2 phosphorylation induced by both insulin and AspB10-insulin was nearly insensitive to blocking the insulin receptor, being predominantly mediated by the IGF-I receptor. We conclude that in myoblasts IRS-2, but not IRS-1, functions as preferred substrate for the IGF-I receptor. These data suggest a specific role for IRS-2 in growth and differentiation of human skeletal muscle.
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February 2006