Therefore during mobilization there is a theoretical risk of circulating daratumumab binding to and having downstream effects on these cells. Graft failure is predominantly immune mediated, where recipient T cells play a dominant role in rejecting donor hematopoietic cells. In a median observation period of 930 days (range: 25–5272 days), 139 patients successfully achieved platelet engraftment (≥50.0 × 109/L). MSCs had no effect in two canine models of SCT using different MSC and HSC donor sources. Learn about our remote access options, Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. Donor-derived BM MSCs also had no impact on engraftment in a canine leukocyte antigen-identical transplant model using nonmyeloablative conditioning (1 Gray), a model in which costimulation (CTLA4) blockade or anti-CD154 has been successful. Hematopoietic stem cells (HSCs) have been shown to express CD38 on the cell surface. Ahmed et al.124 reported that cytokine-activated CD34+ cells (with IL-3, IL-6 and SCF) showed irreversible impaired homing ability, possibly through the induction of pro-apoptotic genes such as Fas/CD95.125 Furthermore, Zheng et al. Daratumumab in untreated newly diagnosed multiple myeloma. In murine models, syngeneic murine BM-derived MSCs significantly increase donor murine HSC engraftment, whereas donor-derived MSCs significantly decrease engraftment, and third-party MSCs have no effect.23 In contrast, in a NOD/SCID model, autologous or allogeneic MSCs comparably increase myeloid engraftment of human CD45+ cells. Clinically, this is very relevant since it is possible that the manipulation of SDF-1/CXCR-4 interactions, as well as the simultaneous infusion of stromal cells with the hematopoietic component, could improve the outcome of human BM transplantations.127 In fact, several studies are currently underway taking advantage of the MSC in autologous and allogeneic transplantation.48, Karen C. Young MD, Cleide Suguihara MD, PhD, in The Newborn Lung: Neonatology Questions and Controversies (Second Edition), 2012.

2002 May 1;20(9):2344-52. doi: 10.1200/JCO.2002.09.138. Homing and nurturing procedures may be relatively inexpensive to perform and more widely utilized without extensive ex vivo maneuvers or experience. Clinical predictors of delayed engraftment following autologous hematopoietic cell transplantation (AHCT) are poorly described in the literature. Rates of bacteremia did not differ significantly between the two groups (25% in the daratumumab group vs 16% in the no daratumumab group, P = .4). Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. The negative effects of daratumumab on engraftment may lead to complications, such as increased rates of febrile neutropenia and more prolonged hospitalization.

Other studies have focused on the impact of cytokine exposure on the homing mechanism. Please check your email for instructions on resetting your password. Only few patients received cyclophosphamide for mobilization (one in the daratumumab group and three in the other group). Donor-derived alveolar macrophages, lymphocytes, dendritic cells, and leukocytes are readily detected in the lung. Median platelet engraftment was delayed by 1 day, although this was not statistically significant (median of 18 days vs 17 days, P = .12) (Figure 1). Register to receive personalised research and resources by email, Prediction of delayed platelet engraftment after autologous stem cell transplantation for B-cell non-Hodgkin lymphoma. Our study is limited by its retrospective nature, the small sample size for patients who received daratumumab, and a lack of uniformity in selecting patients to receive daratumumab during induction. In patients receiving daratumumab, the median time for neutrophil engraftment was 3 days later than patients who did not receive daratumumab (median of 19 days vs 16 days, P = .017) (Figure 1). However, severe immunosuppression is also a consequence of both allogeneic and autologous BM transplantation, resulting from damage to normal barriers such as skin and mucosal linings, loss of phagocytic cells, loss of lymphoid function, and the use of immunosuppressive regimens to prevent or treat GVHD. Both human placental and BM MSCs also significantly decrease single-cord dominance in this model. Since the bone marrow contributes its precursors to alveolar macrophages, disorders related to abnormalities in alveolar macrophage function, including many storage diseases and pulmonary alveolar proteinosis, may be amenable to cellular and genetic therapy. Combinations of these procedures may result in greater improvement in engraftment capacity than any one procedure itself. One approach is the upregulation of CXCR4 expression, which is expressed on CD34+ progenitor cells, to increase marrow homing. COVID-19 is an emerging, rapidly evolving situation. and you may need to create a new Wiley Online Library account. Despite this, our case series provides the first report of daratumumab leading to delayed engraftment post transplant in myeloma patients, receiving it prior to stem cell collection.

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