Browsing by Subject "Chimerism"

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    Durable Chimerism and Long-Term Survival after Unrelated Umbilical Cord Blood Transplantation for Pediatric Hemophagocytic Lymphohistiocytosis: A Single-Center Experience.
    (Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2017-10) Patel, Sachit A; Allewelt, Heather A; Troy, Jesse D; Martin, Paul L; Driscoll, Timothy A; Prasad, Vinod K; Kurtzberg, Joanne; Page, Kristin M; Parikh, Suhag H
    Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder of immune dysregulation characterized by fever, hepatosplenomegaly, cytopenias, central nervous system disease, increased inflammatory markers, and hemophagocytosis. Currently, allogeneic hematopoietic stem cell transplantation is the only curative approach for patients with HLH, with reported survival ranging from 50% to 70% with myeloablative conditioning (MAC) regimens. However, donor availability and transplantation-related mortality associated with conventional MAC are major barriers to success. Unrelated umbilical cord blood transplantation (UCBT) provides a readily available alternative donor source for patients lacking matched related donors. Accordingly, we report the results of UCBT in 14 children treated between 1998 and 2016. All children received standard HLH chemotherapy before UCBT. The median age at diagnosis was 2.7 months (range, .8 to 10.4) and at transplantation was 7.5 months (range, 3.8 to 17). Ten patients received MAC with busulfan/cyclophosphamide/etoposide /antithymocyte globulin (ATG) (n = 5), busulfan/cyclophosphamide /ATG (n = 4), or busulfan /melphalan/ATG (n = 1). Four patients received reduced-toxicity conditioning (RTC) with alemtuzumab/fludarabine/melphalan/hydroxyurea ± thiotepa. Cord blood units were mismatched at either 1 (n = 9) or 2 (n = 5) loci and delivered a median total nucleated cell dose of 11.9 × 107/kg (range, 4.6 to 27.9) and CD34+ dose of 3.1 × 105/kg (range, 1.1 to 6.8). The cumulative incidence of neutrophil engraftment by day 42 was 78.6% (95% confidence interval [CI], 42.9% to 93.4%) with a median of 19 days (range, 13 to 27), and that for platelet (50,000) engraftment by day 100 was 64.3% (95% CI, 28.2% to 85.7%) with a median of 51 days (range, 31 to 94). Six patients developed either grade II (n = 5) or grade IV (n = 1) acute graft-versus-host disease (GVHD); no extensive chronic GVHD was seen. Ten patients (71.4%) are alive and well at a median of 11.2 years after transplantation (range, .85 to 18.25), 9 of whom maintain sustained full donor chimerism after a single UCBT, whereas 1 patient with autologous recovery after first UCBT with RTC has achieved full donor chimerism after a second UCBT with MAC. This series demonstrates that, in combination with standard HLH therapy, UCBT after MAC or RTC conditioning can provide long-term survival with durable complete donor chimerism comparable to that of conventional donors. UCBT should be considered for patients with HLH lacking a fully matched related or unrelated adult donor.
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    Standardizing Definitions of Hematopoietic Recovery, Graft Rejection, Graft Failure, Poor Graft Function, and Donor Chimerism in Allogeneic Hematopoietic Cell Transplantation: A Report on Behalf of the American Society for Transplantation and Cellular Therapy.
    (Transplantation and cellular therapy, 2021-08) Kharfan-Dabaja, Mohamed A; Kumar, Ambuj; Ayala, Ernesto; Aljurf, Mahmoud; Nishihori, Taiga; Marsh, Rebecca; Burroughs, Lauri M; Majhail, Navneet; Al-Homsi, A Samer; Al-Kadhimi, Zaid S; Bar, Merav; Bertaina, Alice; Boelens, Jaap J; Champlin, Richard; Chaudhury, Sonali; DeFilipp, Zachariah; Dholaria, Bhagirathbhai; El-Jawahri, Areej; Fanning, Suzanne; Fraint, Ellen; Gergis, Usama; Giralt, Sergio; Hamilton, Betty K; Hashmi, Shahrukh K; Horn, Biljana; Inamoto, Yoshihiro; Jacobsohn, David A; Jain, Tania; Johnston, Laura; Kanate, Abraham S; Kansagra, Ankit; Kassim, Adetola; Kean, Leslie S; Kitko, Carrie L; Knight-Perry, Jessica; Kurtzberg, Joanne; Liu, Hien; MacMillan, Margaret L; Mahmoudjafari, Zahra; Mielcarek, Marco; Mohty, Mohamad; Nagler, Arnon; Nemecek, Eneida; Olson, Timothy S; Oran, Betul; Perales, Miguel-Angel; Prockop, Susan E; Pulsipher, Michael A; Pusic, Iskra; Riches, Marcie L; Rodriguez, Cesar; Romee, Rizwan; Rondon, Gabriela; Saad, Ayman; Shah, Nina; Shaw, Peter J; Shenoy, Shalini; Sierra, Jorge; Talano, Julie; Verneris, Michael R; Veys, Paul; Wagner, John E; Savani, Bipin N; Hamadani, Mehdi; Carpenter, Paul A
    Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for certain hematologic malignancies and nonmalignant diseases. The field of allo-HCT has witnessed significant advances, including broadening indications for transplantation, availability of alternative donor sources, less toxic preparative regimens, new cell manipulation techniques, and novel GVHD prevention methods, all of which have expanded the applicability of the procedure. These advances have led to clinical practice conundrums when applying traditional definitions of hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism, because these may vary based on donor type, cell source, cell dose, primary disease, graft-versus-host disease (GVHD) prophylaxis, and conditioning intensity, among other variables. To address these contemporary challenges, we surveyed a panel of allo-HCT experts in an attempt to standardize these definitions. We analyzed survey responses from adult and pediatric transplantation physicians separately. Consensus was achieved for definitions of neutrophil and platelet recovery, graft rejection, graft failure, poor graft function, and donor chimerism, but not for delayed engraftment. Here we highlight the complexities associated with the management of mixed donor chimerism in malignant and nonmalignant hematologic diseases, which remains an area for future research. We recognize that there are multiple other specific, and at times complex, clinical scenarios for which clinical management must be individualized.