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Salvage therapy with basiliximab and etanercept for severe steroid-refractory acute graft-versus-host disease
Freyer, C. W., Gier, S., Carulli, A., Gill, S. I., Hexner, E. O., Loren, A. W., Martin, M. E., Porter, D. L.
American journal of hematology. 2022
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Efficiency and Toxicity of Ruxolitinib as the Salvage Treatment in Steroid-Refractory Acute Graft-Versus-Host Disease after Haplo-Identical Stem Cell Transplantation
Liu, Y., Fan, Y., Zhang, W., Chen, J., Cheng, Q., Ma, X., Lin, Z., Wu, D., Xu, Y.
Transplantation and cellular therapy. 2021;27(4):332.e1-332.e8
Abstract
Haplo-identical stem cell transplantation (haplo-SCT) for hematological malignancies has ushered in a new era in which everyone has a potential donor. However, the occurrence of steroid-refractory acute graft-versus-host disease (SR-aGVHD), with no priority among second-line therapies, leads to late mortality after haplo-SCT. Ruxolitinib is the first drug recommended for SR-aGVHD. Here, we report the outcome data from 40 patients after haplo-SCT following the Beijing Protocol who had received ruxolitinib as a salvage therapy for grades II to IV SR-aGVHD in our center between November 2017 and May 2019. The overall response rate was 85% (34/40; 95% confidence interval [CI], 73.4% to 96.6%), including 25 patients with complete response. The median time to first response was 10 days. The levels of inflammatory cytokines and T cell activation declined, and the percentage of regulatory T cells increased. The rate of GVHD relapse was 26.5% (9/34; 95% CI, 10.8% to 42.1%) in responders. Cytomegalovirus reactivation and cytopenia were the major adverse events after ruxolitinib was begun (57.5% and 60%, respectively). The 6-month overall survival estimate was 56.8% (95% CI, 41.5% to 72.1%), and the event-free survival was 45% (95% CI, 29.7% to 60.3%). Liver GVHD was associated with a worse response rate and poor survival. Collectively, ruxolitinib could be an effective treatment for SR-aGVHD patients after haplo-SCT.
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A study of human leukocyte antigen-haploidentical hematopoietic stem cells transplantation combined with allogenic mesenchymal stem cell infusion for treatment of severe aplastic anemia in pediatric and adolescent patients
Ding, L., Han, D. M., Zheng, X. L., Yan, H. M., Xue, M., Liu, J., Zhu, L., Li, S., Mao, N., Guo, Z. K., et al
Stem cells translational medicine. 2021;10(2):291-302
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Abstract
The clinical applications of human leukocyte antigen (HLA) haploidentical hematopoietic stem cells transplantation (haplo-HSCT) have offered most of the young severe aplastic anemia (SAA) patients an opportunity to accept curative therapy at the early stage of bone marrow lesions. However, the outcome of juvenile SAA patients received haplo-HSCT remain to be improved due to high incidence of graft failure and graft vs host disease (GVHD). Mesenchymal stem cells (MSCs) have been characterized by their hematopoiesis-supporting and immunomodulatory properties. In the current study, we designed a combination of haplo-HSCT with allogenic MSC for treatment of SAA in pediatric and adolescent patients and evaluated its effects. Juvenile patients (<18 years) with SAA (n = 103) were given HLA-haploidentical HSC combined with allogenic MSC after a conditioning regimen consisting of busulfan, cyclophosphamide, fludarabine, and antithymocyte globulin and an intensive GVHD prophylaxis, including cyclosporine, short-term methotrexate, mycophenolate mofetil, and basiliximab. Neutrophil engraftment was achieved in 102 of 103 patients in a median time of 14.3 days (range 9-25 days). The median time of platelet engraftment was 25.42 days (range 8-93 days). The cumulative incidence of II-IV acute GVHD at day +100 was 26.32% ± 0.19% and III-IV acute GVHD was 6.79% ± 0.06% at day +100, respectively. The cumulative incidence of chronic GVHD was 25.56% ± 0.26%. The overall survival was 87.15% ± 3.3% at a median follow-up of 40 (1.3-98) months. Our data suggest that cotransplantation of HLA-haploidentical HSC and allogenic mesenchymal stem cell may provide an effective and safe treatment for children and adolescents with SAA who lack matched donors.
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Ruxolitinib is an effective salvage treatment for multidrug-resistant graft-versus-host disease after haploidentical allogeneic hematopoietic stem cell transplantation without posttransplant cyclophosphamide
Zhao, J. Y., Liu, S. N., Xu, L. P., Zhang, X. H., Wang, Y., Chen, Y. H., Liu, K. Y., Huang, X. J., Mo, X. D.
Annals of hematology. 2020
Abstract
The purpose of our study is to identify the efficacy of ruxolitinib in human leukocyte antigen (HLA) haploidentical hematopoietic stem cell transplantation (haplo-HSCT) recipients with multidrug-resistant (MDR)-graft-versus-host disease (GVHD, n = 34). MDR-GVHD was defined as GVHD showing no improvement after at least 3 types of treatments. The median number of previous GVHD-therapies was 4 for both MDR-acute GVHD (aGVHD) and MDR-chronic GVHD (cGVHD). For MDR-aGVHD (n = 15), the median time to response was 10 days (range 2 to 65), and the overall response rate (ORR) was 60.0% (9/15), including 40.0% (6/15) complete response (CR) and 20.0% (3/15) partial response (PR). The 1-year probability of overall survival after ruxolitinib was 66.7%. The rates of hematologic and infectious toxicities were 73.3% and 46.7% after ruxolitinib treatment. For MDR-cGVHD (n = 19), the median time to response was 29 days (range 6 to 175), and the ORR was 89.5% (17/19), including 26.3% (5/19) CR and 63.2% (12/19) PR. All patients remained alive until our last follow-up. The rates of hematologic and infectious toxicities were 36.8% and 47.4% after ruxolitinib treatment. Ruxolitinib is an effective salvage treatment for MDR-GVHD in haplo-HSCT recipients.
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Ruxolitinib Combined with Corticosteroids as First-line Therapy for Acute Graft Versus Host Disease in Haploidentical Peripheral Blood Stem Cell Transplant Patients
Hou, C., Dou, L., Jia, M., Li, F., Wang, S., Gao, X., Wang, L., Jin, X., Wang, L., Gao, C., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
Abstract
Corticosteroids are used as first-line treatment for acute GVHD. However, they are effective in only about half of patients. This study prospectively evaluated Ruxolitinib combined with 1 mg/kg methylprednisolone in the initial treatment of acute GVHD. A total of 32 patients were enrolled. Acute GVHD involved skin (53.1%), gastrointestinal tract (68.8%) and liver (6.0%). The complete response rate at day 28 was 96.9%. The 1-year and 2-year cumulative incidence rates of chronic GVHD were 9.4% and 13.8%, respectively. The 1- year cumulative incidence of non-relapse mortality was 8.7%. The Kaplan-Meier curve estimated 1-year overall survival after transplantation at 73.4%. This prospective study suggested that patients with acute GVHD showed a high response rate to Ruxolitinib (5 mg daily) combined with 1 mg/kg/day methylprednisolone. The novel regimen spared steroid exposure, alleviated toxicity and resulted in long-term survival.
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Basiliximab as treatment of steroid-refractory acute graft-versus-host disease in pediatric patients after haploidentical hematopoietic stem cell transplantation
Tang, F. F., Cheng, Y. F., Xu, L. P., Zhang, X. H., Yan, C. H., Han, W., Chen, Y. H., Huang, X. J., Wang, Y.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
Abstract
Basiliximab has been used successfully as a second-line treatment for steroid-refractory (SR) acute graft-versus-host disease (aGVHD) in adult patients after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) but has not been studied separately in the pediatric setting. We retrospectively reviewed 100 pediatric patients after haplo-HSCT receiving basiliximab for grades II (57%), III (27%), and IV (16%) SR-aGVHD between January 2015 and December 2017. The median number of basiliximab doses was 4 (range, 2-9). The day 28 overall response rate (ORR) was 85%, with complete response (CR) in 74% of patients, partial response (PR) in 11% of patients, and no response in 15% of patients. The day 28 ORR was 94.6% in skin SR-aGVHD, 81.6% in gut SR-aGVHD, and 66.7% in liver SR-aGVHD. Infectious complications included bacterial infection (11%), presumed or documented fungal infections (7%), CMV viremia (53%), EBV viremia (11%), HHV-6 viremia (7%), and HSV viremia (1%). The 3-year overall survival (OS), disease-free survival (DFS), nonrelapse mortality (NRM), and relapse rates between responders and nonresponders were 81.3% vs. 46.7% (P<0.001), 79.0% vs. 46.7% (P=0.001), 6.1% vs. 33.3% (P<0.001), and 14.9% vs. 20.0% (P=0.46), respectively. We conclude that basiliximab is an effective second-line agent for pediatric patients with SR-aGVHD after haplo-HSCT, particularly for skin SR-aGVHD.
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Cotransplantation of bone marrow-derived mesenchymal stem cells in haploidentical hematopoietic stem cell transplantation in patients with severe aplastic anemia: an interim summary for a multicenter phase II trial results.[Erratum appears in Bone Marrow Transplant. 2017 Jul;52(7):1080; PMID: 28677684]
Liu, Z., Zhang, Y., Xiao, H., Yao, Z., Zhang, H., Liu, Q., Wu, B., Nie, D., Li, Y., Pang, Y., et al
Bone Marrow Transplantation. 2017;52(5):704-710
Abstract
Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for severe aplastic anemia (SAA) is mainly limited by the high incidence of graft failure and GvHD. Mesenchymal stem cells (MSCs) have been shown to support hematopoiesis in vivo and to display potent immunosuppressive effects to prevent or treat GvHD after HSCT. In a multicenter phase II trial, we developed an approach with co-transplantation of MSCs in patients undergoing haplo-HSCT. Forty-four patients with SAA were included. The conditioning regimen included busulfan, cyclophosphamide and thymoglobulin (ATG). The recipients received cyclosporin A (CsA), mycophenolate mofetil and short-term methotrexate for GvHD prophylaxis. Three out of 44 patients, who died early before hematopoietic engraftment, were not assessed. Evaluable patients (97.6%; 40/41) achieved hematopoietic reconstitution and sustained full donor chimerism. The median time for myeloid engraftment was 12 days (range 8-21 days) and for platelet engraftment was 19 days (range 8-154 days). The incidence was 29.3% for grade II-IV acute GvHD and 14.6% for chronic GvHD. The overall survival was 77.3% with a median 12-month (range 0.9-30.8) follow-up for surviving patients. These data suggest that co-transplantation of MSCs could reduce the risk of graft failure and severe GvHD in haplo-HSCT for SAA.