Publications by authors named "Christian Reicherts"

7 Publications

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Blinatumomab or Inotuzumab Ozogamicin as Bridge to Allogeneic Stem Cell Transplantation for Relapsed or Refractory B-lineage Acute Lymphoblastic Leukemia: A Retrospective Single-Center Analysis.

Clin Lymphoma Myeloma Leuk 2020 10 3;20(10):e724-e733. Epub 2020 Jun 3.

Department of Medicine A - Hematology, Hemostaseology, Oncology, Pulmonology, University Hospital Münster, Münster, Germany. Electronic address:

Background: Blinatumomab and inotuzumab ozogamicin are now widely used to treat relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL).

Patients And Methods: We have reported the clinical course of 34 adult patients with r/r B-ALL receiving blinatumomab or inotuzumab ozogamicin at our institution from 2009 to 2019.

Results: Blinatumomab-based salvage therapy was applied for overt r/r B-ALL (n = 13) or minimal residual disease (MRD) positivity (n = 5). Of the 13 patients with r/r B-ALL, 9 (69%; 95% confidence interval [CI], 39%-91%) achieved complete remission (CR), with 78% of CR patients (95% CI, 40%-97%) reaching MRD negativity. MRD negativity was also achieved in all 5 patients treated for MRD positivity. The 1-year overall survival of patients receiving blinatumomab for r/r B-ALL and MRD positivity was 54% (n = 13; 95% CI, 26%-81%) and 80% (n = 5; 95% CI, 44-100), respectively. In the inotuzumab ozogamicin group, all 16 patients were treated for overt r/r B-ALL. The rate of CR was 94% (95% CI, 70%-100%), with 67% (95% CI, 38%-88%) of CR patients reaching MRD negativity. The 1-year OS after the first application of inotuzumab ozogamicin was 46% (95% CI, 18%-74%). Of those patients receiving blinatumomab and inotuzumab ozogamicin as a bridge-to-transplant strategy, 79% and 80%, respectively, proceeded to allogeneic stem cell transplantation. The most frequent drug-specific adverse events were similar to those previously reported, including cytokine release syndrome, capillary leak syndrome, and neurotoxicity for blinatumomab and transplant-associated veno-occlusive disease of the liver for inotuzumab ozogamicin.

Conclusion: Together with previous observations from phase III clinical trials, these data suggest that blinatumomab and inotuzumab ozogamicin are highly effective salvage regimens in r/r B-ALL.
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http://dx.doi.org/10.1016/j.clml.2020.05.022DOI Listing
October 2020

Long-term survival and polyclonal immunoglobulin reconstitution after allogeneic stem cell transplantation in multiple myeloma.

Ann Hematol 2020 Aug 22;99(8):1907-1915. Epub 2020 May 22.

Department of Medicine A, University Hospital Münster, Münster, Germany.

Despite significant progress made in the treatment of patients with multiple myeloma (MM) in the last decade, for patients with early relapse or rapidly progressing high-risk disease, allogeneic hematopoietic stem cell transplantation (SCT) might be an option leading to long-term survival. Here, we retrospectively analyzed the outcomes of 90 MM patients who received allogeneic SCT in our center between 1999 and 2017. We specifically assessed the association of impaired humoral immune reconstitution, referred to as immunoparesis, and post-transplant survival. Sixty-four patients received allogeneic SCT in relapse following 2-7 lines of therapy; 26 patients received upfront tandem autologous-allogeneic SCT. With a median follow-up of 76 months, OS and PFS were 52.6% (95% CI 42.9-64.3) and 36.4% (95% CI 27.6-47.9) at 2 years and 38.6% (95% CI 29.2-51.1) and 25.3% (95% CI 17.5-36.4) at 5 years, respectively. Receiving more than two therapy lines prior to transplantation was an independent risk factor for OS (HR 3.68, 95% CI 2.02-6.70) and PFS (HR 3.69, 95% CI 2.09-6.50). In a landmark analysis at day 200, prolonged immunoparesis was associated with reduced OS (HR 3.22, 95% CI 1.14-9.11). Allogeneic stem cell transplantation offers an additional treatment element that may lead to long-term remission in selected patients with poor prognosis, probably exploiting graft-versus-myeloma effects. Immunoparesis could potentially serve as an indicator for impaired survival following allogeneic transplantation, an observation to be further studied prospectively.
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http://dx.doi.org/10.1007/s00277-020-04068-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340674PMC
August 2020

Monitoring minimal residual/relapsing disease after allogeneic haematopoietic stem cell transplantation in adult patients with acute lymphoblastic leukaemia.

Bone Marrow Transplant 2020 07 30;55(7):1410-1420. Epub 2020 Jan 30.

Department of Medicine A/Haematology and Oncology, University of Muenster, Muenster, Germany.

Relapse after allogeneic haematopoietic stem cell transplantation (SCT) is a major cause of death in patients with acute lymphoblastic leukaemia (ALL). Here, we retrospectively analysed the contributions of lineage-sorted donor cell chimerism (sDCC) and quantitative PCR (qPCR) targeting disease-specific genetic rearrangements to detect minimal residual/relapsing disease (MRD) and predict impending relapse in 94 adult ALL patients after SCT. With a median follow-up of surviving patients (n = 61) of 3.3 years, qPCR and/or sDCC measurements turned positive in 38 patients (40%). Of these, 22 patients relapsed and 16 remained in complete remission. At 3 years, qPCR and/or sDCC positive patients showed an increased incidence of relapse (50% vs. 4%, p < 0.0001), decreased relapse-free survival (RFS, 40% vs. 85%, p < 0.0001), and decreased overall survival (OS, 47% vs. 87%, p 0.004). Both, qPCR and sDCC pre-detected 11 of 21 relapses occurring within the first two years after SCT and, overall, complemented for each other method in four of the relapsing and four of the non-relapsing cases. Patients receiving pre-emptive MRD-driven interventions (n = 11) or not (n = 10) showed comparable median times until relapse, RFS, and OS. In our single centre cohort, qPCR and sDCC were similarly effective and complementary helpful to indicate haematological relapse of ALL after SCT.
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http://dx.doi.org/10.1038/s41409-020-0801-0DOI Listing
July 2020

Cytomegalovirus retinitis in children and adolescents with acute leukemia following allogeneic hematopoietic stem cell transplantation.

Transpl Infect Dis 2019 Oct 13;21(5):e13089. Epub 2019 Aug 13.

Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Muenster, Germany.

Cytomegalovirus retinitis (CMVR) may occur after allogeneic hematopoietic stem cell transplantation (HSCT). However, little is known about its incidence, strategies for ophthalmic surveillance, and timely implementation of adequate antiviral treatment in pediatric allogeneic HSCT recipients. We provide a retrospective analysis of the epidemiology and clinical features of CMVR in pediatric allogeneic HSCT patients transplanted at our center over a 16-year period. Two patients of this cohort with leukemia are presented. Our analysis is supplemented by a systematic review on pediatric patients with leukemia and CMVR in the setting of allogeneic HSCT. The overall incidence of CMVR in our cohort was 1% (4/338) and 14.2% (3/21) in leukemic patients. In published cases, CMVR occurred at a median of 143 days after transplantation, and, in the majority of patients, was preceded by CMV detection in blood by a median of 93 days. Continued immune suppression following engraftment likely triggers CMVR. Preemptive treatment with ganciclovir as standard is usually successful. Foscarnet is used in case of resistance to ganciclovir or drug-induced granulocytopenia. Overall, CMVR after HSCT in pediatric leukemic patients is rare, but a potentially higher vulnerability of this population for involvement of the eye warrants a standardized ophthalmological examination plan.
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http://dx.doi.org/10.1111/tid.13089DOI Listing
October 2019

Phase I/II Trial of a Combination of Anti-CD3/CD7 Immunotoxins for Steroid-Refractory Acute Graft-versus-Host Disease.

Biol Blood Marrow Transplant 2019 04 3;25(4):712-719. Epub 2018 Nov 3.

Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands; Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address:

Effective therapies for treating patients with steroid-refractory acute graft-versus-host-disease (SR-aGVHD), particularly strategies that reduce the duration of immunosuppression following remission, are urgently needed. The investigated immunotoxin combination consists of a mixture of anti-CD3 and anti-CD7 antibodies separately conjugated to recombinant ricin A (CD3/CD7-IT), which induces in vivo depletion of T cells and natural killer (NK) cells and suppresses T cell receptor activation. We conducted a phase I/II trial to examine the safety and efficacy of CD3/CD7-IT in 20 patients with SR-aGVHD; 17 of these patients (85%) had severe SR-aGVHD, and all 20 patients had visceral organ involvement, including 18 (90%) with gastrointestinal (GI) involvement and 5 (25%) with liver involvement. A validated 2-biomarker algorithm classified the majority of patients (11 of 20) as high risk. On day 28 after the start of CD3/CD7-IT therapy, the overall response rate was 60% (12 of 20), with 10 patients (50%) achieving a complete response. The 6-month overall survival rate was 60% (12 of 20), including 64% (7 of 11) classified as high risk by biomarkers. The 1-week course of treatment with CD3/CD7-IT caused profound but transient depletion of T cells and NK cells, followed by rapid recovery of the immune system with a diverse TCR Vβ repertoire, and preservation of Epstein-Barr virus- and cytomegalovirus-specific T cell clones. Furthermore, our results indicate that CD3/CD7-IT appeared to be safe and well tolerated, with a relatively low prevalence of manageable and reversible adverse events, primarily worsening of hypoalbuminemia, microangiopathy, and thrombocytopenia. These encouraging results suggest that CD3/CD7-IT may improve patient outcomes in patients with SR-aGVHD.
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http://dx.doi.org/10.1016/j.bbmt.2018.10.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595479PMC
April 2019

High-dose melphalan-based sequential conditioning chemotherapy followed by allogeneic haematopoietic stem cell transplantation in adult patients with relapsed or refractory acute myeloid leukaemia.

Br J Haematol 2018 03 21;180(6):840-853. Epub 2018 Feb 21.

Department of Medicine A, University Hospital of Muenster, Muenster, Germany.

Considering the unsatisfactory results of salvage therapies for patients with relapsed/refractory acute myeloid leukaemia (R/R-AML), their value before allogeneic haematopoietic stem cell transplantation (HSCT) remains questionable. However, direct allogeneic HSCT following established conditioning regimens applied in patients with R/R-AML during active disease has been equally disappointing. In this retrospective observational study, high-dose melphalan, as part of a sequential preparative regimen, followed by a total body irradiation (4 × 2 Gy)-based or a treosulfan-based dose-adapted conditioning therapy for allogeneic HSCT was administered to 292 adult patients (median age 56 years, range 17-74) with primary refractory (144 patients), secondary refractory (97 patients) or relapsed AML (51 patients). Overall survival rates at 3 years were 34%, 29% and 41%, respectively. Risk factors associated with an inferior survival were higher age, transplantation from a human leucocyte antigen-mismatched donor and high disease burden. Patients transplanted with blast infiltration <20% showed a notable survival rate of 51% at 3 years. In particular, patients with primary refractory AML showed a more favourable outcome when transplanted early during their disease course. Thus, high-dose melphalan-based sequential conditioning chemotherapy followed by an allogeneic HSCT is feasible and enables long-term remission to be achieved in a substantial proportion of patients with active R/R-AML.
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http://dx.doi.org/10.1111/bjh.15137DOI Listing
March 2018