Thoralf Lange

Asklepios Klinik Weißenfels

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Dietger Niederwieser

University Hospital Leipzig

115

Haifa Kathrin Al‐Ali

University Hospital in Halle

Michael Cross

University Hospital Leipzig

Georg‐Nikolaus Franke

University Hospital Leipzig

Andreas Hochhaus

Jena University Hospital

Rainer Krahl

Leipzig University

Michael W. Deininger

Versiti Blood Center of Wisconsin

Vladan Vučinić

University Hospital Leipzig

Wolfram Pönisch

Leipzig University

Brenda M. Sandmaier

Fred Hutch Cancer Center

Cooperative Institutions

Leipzig University

198

University Hospital Leipzig

131

Heidelberg University

127

University Hospital Heidelberg

Charité - Universitätsmedizin Berlin

Oregon Health & Science University

Fred Hutch Cancer Center

Praxis für Hämatologie und Onkologie

University of Washington

Goethe University Frankfurt

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Data from Detection of Mutant Free Circulating Tumor DNA in the Plasma of Patients with Gastrointestinal Stromal Tumor Harboring Activating Mutations of CKIT or PDGFRA

Jacqueline Maier Thoralf Lange Irina Kerle Katja Specht Melanie Bruegel

<div>AbstractPurpose: In gastrointestinal stromal tumor (GIST), there is no biomarker available that indicates success or failure of therapy. We hypothesized that tumor-specific v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (CKIT)- or platelet-derived growth factor receptor-α (PDGFRA)–mutant DNA fragments can be detected and quantified in plasma samples of patients with GIST.Experimental Design: We prospectively collected 291 plasma samples from 38 subjects with GIST harboring activating mutations of CKIT or PDGFRA detected in tumor tissue, irrespective of current disease status or treatment. We used allele-specific ligation PCR to detect mutant free circulating DNA (fcDNA).Results: We were able to detect fcDNA harboring the tumor mutation in 15 of 38 patients. Patients with active disease displayed significantly higher amounts of mutant fcDNA compared with patients in complete remission (CR). The amount of mutant fcDNA correlated with disease course. We observed repeated positive test results or an increase of mutant fcDNA in five patients with progressive disease or relapse. A decline of tumor fcDNA or conversion from positive to negative was seen in five patients responding to treatment. A negative to positive conversion was seen in two patients with relapse and one patient with progression. In two cases, we aimed to identify additional mutations and found four additional exchanges, including mutations not known from sequentially conducted tumor biopsies.Conclusions: Our results indicate that fcDNA harboring tumor-specific mutations in the plasma of patients with GIST can be used as tumor-specific biomarker. The detection of resistance mutations in plasma samples might allow earlier treatment changes and obviates the need for repeated tumor biopsies. Clin Cancer Res; 19(17); 4854–67. ©2013 AACR.</div>

PDGFRA

Stromal tumor

10.1158/1078-0432.c.6520988.v1

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Quality of life in patients with metastatic colorectal cancer receiving maintenance therapy after first-line inductive treatment: A quality of life sub-analysis of the AIO KRK 0207 phase III trial

Annals of Oncology (2016)

Julia Quidde S. Hegewisch Becker Ullrich Graeven C. Lerchenmueller B. Killing

Clinical endpoint

Maintenance therapy

10.1093/annonc/mdw370.105

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Citations (2)

Treatment of Myeloid and Lymphoid Malignancies with Highly Purified Alloreactive CD56+CD3− NK-Cells and Haploidentical Stem Cell Transplantation: Promising Results of a Phase I Study.

Blood (2005)

Chiara Gentilini Urte Hilbers G. Hartung Thoralf Lange Constanze Kliem

ThioTEPA

10.1182/blood.v106.11.2906.2906

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Citations (1)

Treatment Free Remission after Nilotinib Plus Peg-Interferon Alpha Induction and Peg-Interferon Alpha Maintenance Therapy for Newly Diagnosed Chronic Myeloid Leukemia Patients; The Tiger Trial

Blood (2023)

Andreas Hochhaus Andreas Burchert Susanne Saußele Gabriela M. Baerlocher Jiřı́ Mayer

Tolerability

Maintenance therapy

10.1182/blood-2023-182792

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Citations (7)

Non-Myeloablative Allografting from HLA-Identical Sibling Donors for Treatment of CML.

Blood (2004)

Fábio R. Kerbauy Thoralf Lange Ted Gooley Judith A. Shizuru Jerald P. Radich

Total body irradiation

Immunosuppression

Treosulfan

Donor lymphocyte infusion

10.1182/blood.v104.11.2316.2316

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Citations (1)

Low Level BCR-ABL Mutations Below the Detection Limit of Current Standard Screening Techniques Occur Predominantly in the CD34+ Progenitor Cell Compartment in Chronic Phase CML Patients At Diagnosis. A Substudy of the ENEST1st Trial

Blood (2012)

Jacqueline Maier Karoline Schubert Michael Cross Sabine Leiblein Kathrin Wildenberger

Imatinib Mesylate

10.1182/blood.v120.21.1671.1671

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Citations (1)

Prognostic Value of Multi-Drug Resistance 1 Gene (MDR1) Expression in Newly Diagnosed Patients with Chronic Myeloid Leukemia on Nilotinib Treatment—a Subanalysis of the ENEST1st Study

Blood (2014)

Christian Dietz Michael Lauseker Benjamin Hanfstein Philippe Rousselot Thoralf Lange

Imatinib Mesylate

ABL

Clinical endpoint

10.1182/blood.v124.21.3144.3144

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Citations (1)

Non‐myeloablative allogeneic haematopoietic cell transplantation for relapsed diffuse large B‐cell lymphoma: a multicentre experience

British Journal of Haematology (2008)

Andrew R. Rezvani L. Norasetthada Ted Gooley Mohamed L. Sorror M Bouvier

Patients with relapsed diffuse large B-cell lymphoma (DLBCL) who have failed or are ineligible for autologous haematopoietic cell transplantation (HCT) have a poor prognosis. We examined the outcomes of non-myeloablative allogeneic HCT in this setting. Thirty-one patients with DLBCL and one patient with Burkitt lymphoma received allogeneic HCT following 2 Gy total body irradiation with or without fludarabine. Median age was 52 years. Twenty-four patients (75%) had undergone prior autologous HCT. Disease status at HCT was complete response (14/32, 44%), partial response (9/32, 28%), or refractory (9/32, 28%). Cumulative incidences of acute graft-versus-host disease (GVHD) grades II-IV, grades III-IV, and chronic GVHD were 53%, 19%, and 47% respectively. With a median follow-up of 45 months, 3-year estimated overall (OS) and progression-free survival (PFS) was 45% and 35% respectively. Three-year cumulative incidences of relapse and non-relapse mortality were 41% and 25% respectively. In multivariate models, chemosensitive disease and receipt of >or=4 lines of treatment before HCT were associated with better OS. Patients with chemosensitive disease had 3-year OS and PFS of 56% and 43% respectively. Non-myeloablative allogeneic HCT can produce long-term disease-free survival in patients with chemosensitive relapsed DLBCL who have failed or are ineligible for autologous HCT.

Cumulative incidence

Total body irradiation

Hematology

10.1111/j.1365-2141.2008.07365.x

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Citations (102)

Nilotinib Vs Nilotinib Plus Pegylated Interferon α (Peg-IFN) Induction and Nilotinib or Peg-IFN Maintenance Therapy for Newly Diagnosed BCR-ABL1 Positive Chronic Myeloid Leukemia Patients in Chronic Phase (TIGER Study): The Addition of Peg-IFN Is Associated with Higher Rates of Deep Molecular Response

Blood (2019)

Andreas Hochhaus Andreas Burchert Susanne Saußele Gabriela M. Baerlocher Tim H. Brümmendorf

Tolerability

Pegylated interferon

Discontinuation

10.1182/blood-2019-130043

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Citations (13)

Determination of Saliva Trough Levels for Monitoring Voriconazole Therapy in Immunocompromised Children and Adults

Therapeutic Drug Monitoring (2010)

Claudia Michael Uta Bierbach Katrin Frenzel Thoralf Lange Nadežda Basara

To evaluate the reliability and practical use of saliva for therapeutic drug monitoring of the antifungal agent voriconazole in immunocompromised patients, a paired-sample study was conducted. Plasma and saliva trough levels were measured in seven children and nine adults who required treatment for the prevention or therapy of systemic fungal infections. The pediatric patients received a voriconazole dosage of 7 mg/kg intravenously twice a day. Adults were treated with two loading doses of 6 mg/kg intravenously followed by a maintenance dose of 4 mg/kg intravenously twice a day. Based on 104 paired plasma/saliva specimens, we found a significant correlation between the voriconazole concentrations in blood and saliva (r > 0.95). The median saliva/plasma voriconazole concentration ratio was 0.34 in children and 0.40 in adults. Intra- and interpatient variability in the saliva/plasma ratios were 22% and 23% in children and 16% and 24% in adults, respectively. Thirty-three percent of plasma trough levels were below 1.0 microg/mL or above 6.0 microg/mL and occurred in six pediatric and four adult patients. Monitoring of salivary concentrations proved to be a realistic alternative in patients when blood drawing is difficult. Especially in therapeutic drug monitoring, an easier sample collection being noninvasive and painless is more acceptable to patients, particularly children.

Therapeutic Drug Monitoring

Trough level

Trough Concentration

10.1097/ftd.0b013e3181cff20d

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Citations (13)