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Mixed chimerism after allogeneic hematopoietic stem cell transplantation for severe aplastic anemia
Zhang, Y., Li, Y., Wu, L., Zhou, M., Wang, C., Mo, W., Chen, X., Xu, S., Zhou, R., Wang, S., et al
Hematology (Amsterdam, Netherlands). 2021;26(1):435-443
Abstract
A retrospective study on 287 patients with SAA who underwent allo-HSCT between October 2012 and January 2020 was conducted to explore the outcomes, risk factors and treatment options for MC. Among 287 AA patients who excluded Fanconi anemia (FA), Congenital dyskeratosis (DKC), Paroxysmal nocturnal hemoglobinuria (PNH), etc.112 underwent matched sibling donor (MSD)-HSCT, 91 matched unrelated donor-HSCT and 84 haploidentical-HSCT. Patients were divided into the following 4 groups: group 1: Donor chimerism (DC); group 2: MC without cytopenia; group 3: MC with cytopenia; group 4: secondary graft failure (SGF). Compared with the other three groups, SGF predicted a poor prognosis of SAA (P< 0.001). In addition, SGF was associated with the early (within 3 months after transplantation) presence of MC and the high levels of MC. Uni- and multivariate logistic regression analysis showed that donor/recipient sex-mismatching and CTX?+?ATG regimen were high-risk factors for MC. Of note, in MC patients with cytopenia (group 3), the effective response rate reached 55% (6/11) following enhanced immunosuppression combined with cellular therapy, while only one of the four was effective who received enhanced immunosuppression alone. SGF was associated with poor prognosis, early presence of MC and increased levels of recipient chimerism. The donor/recipient sex-mismatching and CTX?+?ATG regimen based MSD-HSCT were risk factors for MC. Cellular therapy could improve the effective response rate of patients with progressive MC.
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The incidence, clinical outcome and protective factors of mixed chimerism following hematopoietic stem cell transplantation for severe aplastic anemia
Xu, Z. L., Cheng, Y. F., Zhang, Y. Y., Mo, X. D., Han, T. T., Wang, F. R., Yan, C. H., Sun, Y. Q., Chen, Y. H., Tang, F. F., et al
Clinical transplantation. 2020;:e14160
Abstract
OBJECTIVES The aim of our study was to determine possible predictors and clinical course of mixed chimerism (MC) in aplastic anemia after transplantation. METHODS A total of 207 transplants were obtained from haploidentical donors (HID) using busulfan (Bu), cyclophosphamide (Cy) and anti-thymocyte globulin (ATG) regimens, and 69 transplants from matched related donors (MRD) and 29 transplants from unrelated donors (URD) using Cy/ATG regimens were obtained. RESULTS Incidences of MC were 1.93±0.01%, 20.29±0.01%, and 35.71±0.01% in HID, MRD and URD transplantation (P<0.001). In multivariate analysis, incidence of MC was significantly higher in patients without adding Bu in conditioning (P<0.001) and receiving a lower number of CD3+ cells in graft (P = 0.042). MC was associated with significantly lower II-IV aGvHD (3.70% vs. 27.7%, P = 0.007), but higher secondary graft rejection rates (14.8% vs. 0.4%, P<0.001) and poorer overall survival (72.7±8.9% vs. 89.6±2.0%, P = 0.011) than those of donor chimerism cohort. CONCLUSIONS MC was an unsettling status even in non-malignancy. Haploidentical transplantation with more intense regimen by adding Bu to Cy and ATG was associated with reduced MC following HSCT for SAA. An intensified regimen should be explored in matched related or unrelated donors.
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Mixed chimerism and secondary graft failure in allogeneic hematopoietic stem cell transplantation for aplastic anemia
Kako, S., Yamazaki, H., Ohashi, K., Ozawa, Y., Ota, S., Kanda, Y., Maeda, T., Kato, J., Ishiyama, K., Matsuoka, K. I., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
Abstract
Mixed chimerism (MC) and/or secondary graft failure (SGF) with recipient- or donor-type chimerism is a major obstacle in allogeneic transplantation for aplastic anemia (AA). From a registry database in Japan, patients with AA aged more than 15 years who underwent a first allogeneic bone marrow or peripheral blood transplantation between 2000 and 2014 and achieved engraftment were included in this study. MC that did not require either granulocyte-colony stimulating factor (G-CSF) or transfusion support (Group 1), MC (not SGF) that required G-CSF and/or transfusion support (Group 2), SGF with MC or complete recipient-type chimerism (Group 3), and SGF with complete donor-type chimerism (Group 4) developed in 26, 16, 19, and 17 patients, respectively. The overall median follow-up period for survivors was 1727 days. The overall survival rate (OS) was 90.4% at 1 year and 83.5% at 5 years in patients without MC or SGF (n=340), which was not different from OS in Group 1 or 2. However, inferior OS was observed in Group 3 (1 year: 52.1%, 5 years: 52.1%) and Group 4 (1 year: 82.4%, 5 years: 56.3%). In multivariate analyses, the use of fludarabine (Flu) and the absence of irradiation in conditioning were associated with the development of SGF with MC or complete recipient-type chimerism, and the use of Flu in conditioning was associated with SGF with complete donor-type chimerism. In conclusion, the use of Flu may affect the occurrence of SGF with both recipient- and donor-type chimerism.
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Late chimerical status after bone marrow transplantation in severe aplastic anemia according to two different preparatory regimens
Quiroga, M., Pereira, N. F., Bitencourt, M. A., Bonfim, C., Monteiro, M. G. M., Pasquini, R.
Hematology, transfusion and cell therapy. 2018;40(2):112-119
Abstract
Background: This study investigated the influence of two conditioning regimens on the chimerical status of 104 patients with acquired severe aplastic anemia. Methods: Patients were monitored for at least 18 months after related bone marrow transplantation and reaching partial or complete hematologic recovery. Group I patients (n = 55) received 200 mg/kg cyclophosphamide alone and Group II (n = 49) received 120 mg/kg cyclophosphamide associated with 12 mg/kg busulfan. Patients were classified in three chimerism levels according to the percentage of donor cells in the peripheral blood. Results: Chimerism ≤50% occurred in 36.4% of Group I and none of Group II; chimerism 51-90% was found in 20.0% of Group I and 10.2% of Group II; and chimerism >90% was found in 43.6% of Group I versus 89.8% of Group II. A significant association (p-value < 0.001) was found between conditioning type and chimerism levels. A higher number of infused cells was associated with higher levels of chimerism only in Group I (p-value = 0.013). Multivariate analysis showed that chimerism >90% is associated with the cyclophosphamide plus busulfan conditioning (p-value < 0.001) and higher number of infused cells (p-value = 0.009), suggesting that these factors are predictive of graft outcome. Regarding hematological recovery, higher chimerism levels were associated with higher neutrophil (p-value = 0.003) and platelet counts (p-value < 0.001) in Group I only. These results show that myeloablative conditioning favors full donor chimerism and non-myeloablative conditioning predisposes to mixed chimerism or autologous recovery of hematopoiesis. Conclusion: These data show that autologous recovery depends on the intensity of immunosuppression and that the immunosuppressive function of cyclophosphamide alone can induce this type of hematopoietic recovery.