0000000000284989
AUTHOR
Peter Bader
Long-Term Outcome of Preemptive Immunotherapy Based on Post-Transplant Chimerism and MRD Monitoring after Allogeneic Stem Cell Transplantation in Children with Acute Lymphoblastic Leukemia: A Single Center Experience
Abstract Introduction: Mixed chimerism (MC) and minimal residual disease (MRD) strongly predict risk for relapse in children with acute lymphoblastic leukemia (ALL) following allogeneic stem cell transplantation (allo-SCT). Preemptive immunotherapy (IT), e.g. withdrawal of immunosuppression (WD-IS) or donor lymphocyte infusion (DLI) guided by chimerism and MRD monitoring can prevent impending relapse in allo-SCT recipients. In this study we retrospectively analyzed chimerism and MRD monitoring and the effect of preemptive IT in all pts undergoing allo-SCT for ALL in our institution. Patients: Between January 2005 and July 2014, a total of 89 children and adolescents (median age 11.5; range …
Pre-Emptive Immunotherapy for Clearance of Molecular Disease in Childhood Acute Lymphoblastic Leukemia after Transplantation
Abstract Monitoring of minimal residual disease (MRD) or chimerism may help guide pre-emptive immunotherapy (IT) with a view to preventing relapse in childhood acute lymphoblastic leukemia (ALL) after transplantation. Patients with ALL who consecutively underwent transplantation in Frankfurt/Main, Germany between January 1, 2005 and July 1, 2014 were included in this retrospective study. Chimerism monitoring was performed in all, and MRD assessment was performed in 58 of 89 patients. IT was guided in 19 of 24 patients with mixed chimerism (MC) and MRD and by MRD only in another 4 patients with complete chimerism (CC). The 3-year probabilities of event-free survival (EFS) were .69 ± .06 for …
Phase I/II Study of the Deacetylase Inhibitor Panobinostat As Maintenance Therapy after an Allogeneic Stem Cell Transplantation in Patients with High-Risk MDS or AML: The Panobest-Trial
Abstract Background: Leukemic relapse and graft-versus-host disease (GvHD) remain major obstacles after an allogeneic stem cell transplantation (HSCT). Panobinostat is a potent inhibitor of class I, II and IV deacetylases and has shown antileukemic as well as immunomodulatory activity. The hypothesis of our phase I/II PANOBEST trial was that panobinostat can effectively prevent relapse in patients (pts) with high-risk (HR) myeloid diseases while simultaneously reducing GvHD. We aimed to determine dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of panobinostat in adult pts with HR acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS…
Enhancing the Activation and Releasing the Brakes: A Double Hit Strategy to Improve NK Cell Cytotoxicity Against Multiple Myeloma
Natural killer (NK) cells are innate lymphocytes with a strong antitumor ability. In tumor patients, such as multiple myeloma (MM) patients, an elevated number of NK cells after stem cell transplantation (SCT) has been reported to be correlated with a higher overall survival rate. With the aim of improving NK cell use for adoptive cell therapy, we also addressed the cytotoxicity of patient-derived, cytokine-stimulated NK cells against MM cells at specific time points: at diagnosis and before and after autologous stem cell transplantation. Remarkably, after cytokine stimulation, the patients' NK cells did not significantly differ from those of healthy donors. In a small cohort of MM patients…
Treatment of relapse after allogeneic stem cell transplantation in children and adolescents with ALL: the Frankfurt experience
Therapy for post-transplant relapse of paediatric ALL is limited. Standardised curative approaches are not available. We hereby describe our local procedure in this life-threatening situation. A total of 101 ALL patients received their first allogeneic stem cell transplantation (SCT) in our institution. After relapse, our primary therapeutic goal was to cure the patient with high-dose chemotherapy or specific immunotherapy (HDCHT/SIT) followed by a second SCT from a haploidentical donor (transplant approach). If this was not feasible, low-dose chemotherapy and donor lymphocyte infusions (LDCHT+DLI) were offered (non-transplant approach). A total of 23 patients suffered a post-transplant rel…