21 research outputs found
Efficacy and safety of daratumumab in pure red cell aplasia after allogeneic transplantation:Dutch real-world data
R-CEOP as first-line treatment for anthracycline-ineligible patients with diffuse large B-cell lymphoma
Second autologous haematopoietic stem cell transplantation in systemic sclerosis-a case report
Identification of a Small Subpopulation of Candidate Leukemia-Initiating Cells in the Side Population of Patients with Acute Myeloid Leukemia
Allogeneic Stem Cell Transplantation Platforms With Ex Vivo and In Vivo Immune Manipulations: Count and Adjust
Various allogeneic (allo) stem cell transplantation platforms have been developed over the last 2 decades. In this review we focus on the impact of in vivo and ex vivo graft manipulation on immune reconstitution and clinical outcome. Strategies include anti-thymocyte globulin- and post-transplantation cyclophosphamide-based regimens, as well as graft engineering, such as CD34 selection and CD19/αβT cell depletion. Differences in duration of immune suppression, reconstituting immune repertoires, and associated graft-versus-leukemia effects and toxicities mediated through viral reactivations are highlighted. In addition, we discuss the impact of different reconstituting repertoires on donor lymphocyte infusions and post allo pharmacological interventions to enhance tumor control. We advocate for precisely counting all graft ingredients and therapeutic drug monitoring during conditioning in the peripheral blood, and for adjusting dosing accordingly on an individual basis. In addition, we propose novel trial designs to better assess the impact of variations in transplantation platforms in order to better learn from our diversity of “counts” and potential “adjustments.” This will, in the future, allow daily clinical practice, strategic choices, and future trial designs to be based on data guided decisions, rather than relying on dogma and habits
Cancer Therapy-Related Cardiac Dysfunction of Nonanthracycline Chemotherapeutics. What Is the Evidence?
Cancer therapy–related cardiac dysfunction (CTRCD) is one of the most concerning cardiovascular side effects of cancer treatment. Important reviews within the field of cardio-oncology have described various agents to be associated with a high risk of CTRCD, including mitomycin C, ifosfamide, vincristine, cyclophosphamide, and clofarabine. The aim of this study was to provide insight into the data on which these incidence rates are based. We observed that the reported cardiotoxicity of mitomycin C and ifosfamide is based on studies in which most patients received anthracyclines, complicating the interpretation of their association with CTRCD. The high incidence of vincristine-induced cardiotoxicity is based on an incorrect interpretation of a single study. Incidence rates of clofarabine remain uncertain due to a lack of cardiac screening in clinical trials. The administration of high-dose cyclophosphamide (>1.5 g/m2/day) is associated with a high incidence of CTRCD. Based on our findings, a critical re-evaluation of the cardiotoxicity of these agents is warranted
P717: AG946, A PYRUVATE KINASE (PK) ACTIVATOR IMPROVES PK PROPERTIES AND RED BLOOD CELL (RBC) METABOLISM UPON EX VIVO TREATMENT OF RBCS FROM PATIENTS WITH MYELODYSPLASTIC SYNDROMES
Efficacy and safety of daratumumab in pure red cell aplasia after allogeneic transplantation:Dutch real-world data
Efficacy and safety of daratumumab in pure red cell aplasia after allogeneic transplantation:Dutch real-world data
The novel AML stem cell-associated antigen CLL-1 aids in discrimination between normal and leukemic stem cells
In CD34+ acute myeloid leukemia (AML), the malignant stem cells reside in the CD38+ compartment. We have shown before that the frequency of such CD34+CD38- cells at diagnosis correlates with minimal residual disease (MRD) frequency after chemotherapy and with survival. Specific targeting of CD34+CD38+ cells might thus offer therapeutic options. Previously, we found that C-type lectin-like molecule-1 (CLL-1) has high expression on the whole blast compartment in the majority of AML cases. We now show that CLL-1 expression is also present on the CD34+CD38- stem-cell compartment in AML (77/89 patients). The CD34+CLL-1+ population, containing the CD34 +CD38-CLL-1+ cells, does engraft in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice with outgrowth to CLL-1+ blasts. CLL-1 expression was not different between diagnosis and relapse (n = 9). In remission, both CLL-1- normal and CLL-1 + malignant CD34+CD38- cells were present. A high CLL-1+ fraction was associated with quick relapse. CLL-1 expression is completely absent both on CD34+CD38- cells in normal (n = 11) and in regenerating bone marrow controls (n = 6). This AML stem-cell specificity of the anti-CLL-1 antibody under all conditions of disease and the leukemia-initiating properties of CD34+CLL-1+ cells indicate that anti-CLL-1 antibody enables both AML-specific stem-cell detection and possibly antigen-targeting in future