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Total body irradiation-containing conditioning regimens without antithymocyte globulin in adults with aplastic anemia undergoing umbilical cord blood transplantation
Hiramoto, N., Yamazaki, H., Nakamura, Y., Uchida, N., Murata, M., Kondo, T., Yoshioka, S., Eto, T., Nishikawa, A., Kimura, T., et al
Annals of hematology. 2021
Abstract
Thus far, there have been no large cohort studies on total body irradiation (TBI)-containing conditioning regimens without antithymocyte globulin (ATG) in adults with aplastic anemia (AA) undergoing umbilical cord blood (UCB) transplantation (UCBT). We retrospectively analyzed 115 adults with idiopathic AA undergoing UCBT using TBI-containing reduced-intensity conditioning (RIC) regimens without ATG between 2000 and 2018 on behalf of the Adult Aplastic Anemia Working Group of the Japanese Society for Hematopoietic Cell Transplantation. We then compared transplantation outcomes between a fludarabine (Flu)- and melphalan (Mel)-based regimen (FM) and a Flu- and cyclophosphamide (Cy)-based regimen (FC). The median patient age at UCBT was 41 years. The median total nucleated cell and total CD34(+) cell doses in a UCB unit at cryopreservation were 2.5?×?10(7)/kg and 0.7?×?10(5)/kg, respectively. The median follow-up period for survivors was 47 months. The cumulative incidence rate of neutrophil engraftment was 76.5%, and the 4-year overall survival (OS) rate was 64.3%. In multivariate analysis, the covariates that were significantly associated with a higher neutrophil engraftment were total CD34(+) cell dose in an UCB unit (=?0.7?×?10(5)/kg; hazard ratio, 0.57, P?=?0.01) and total dose of TBI (4 Gy of TBI; hazard ratio, 0.32, P?=?0.01). There was no significant difference in the cumulative incidence of neutrophil engraftment and the 4-year OS between the FM and FC groups. In conclusion, TBI-containing RIC regimens without ATG are suitable for adults with AA undergoing UCBT. There were no significant differences in transplantation outcomes between the FM and FC groups.
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Comparison of the Kinetics of Hematologic Recovery in Aplastic Anemia After Total Nodal Irradiation Between Helical Tomotherapy and Conventional Radiotherapy
Hong, J. H., Jang, H., Choi, B. O., Kang, Y. N., Song, J. H.
International journal of radiation oncology, biology, physics. 2021;111(3s):e310
Abstract
PURPOSE/OBJECTIVE(S): Total nodal irradiation (TNI) followed by antithymocyte globulin (ATG) has been using as the conditioning regimen before allogeneic hematopoietic stem cell transplantation (HSCT) in aplastic, severe aplastic, and very sever aplastic anemia. As technology developed in radiotherapy, helical tomotherapy has been applied to TNI. This study compares the kinetics of hematologic changes after TNI between helical tomotherapy and 3D conformal radiotherapy (3DRT) in aplastic anemia patients. MATERIALS/METHODS Between January 2010 and December 2020, 34 patients underwent TNI before HSCT. According to different radiotherapy methods, patients were divided into two groups: 16 patients (3DRT) and 18 patients (Tomotherapy). For one month after TNI, hematologic values including absolute neutrophil counts (ANC), absolute lymphocyte counts (ALC), platelet counts, and hemoglobin counts were reviewed and analyzed. RESULTS All but one patient achieved engraftment successfully with neutrophils (median 12 days, range 4 ~ 19) and platelets (median 14 days, range 7 ~ 66). Median age at TNI was 37.3 years (range, 19.4 ~ 64.6). TNI dose was 750cGY in single fraction while two patients were treated with 700cGY. 15 patients were treated as second allogenic HSCT after graft failure. All hematologic value changes including ANC, ALC, platelet and hemoglobin didn't show significant difference between two groups (P?=?0.185, P?=?0.287, P?=?0.127, and P?=?0.244). ANC showed lowest value at nine days after TNI in both group and recovered afterwards, while ALC showed lowest value at three days after TNI. Platelet showed lowest value at nine days after TNI in 3DRT, and 12 days after in tomotherapy. Successful engraftment of ANC between two groups weren't significantly different (P?=?0.320), though, successful engraftment of platelet between two groups showed significant difference (P?=?0.003), CONCLUSION The kinetics of hematologic values after TNI using tomotherapy and 3DRT didn't show significant difference. The method of radiotherapy needs to be decided carefully, considering other factors including economic evaluation, side effects, and outcomes. It needs further studies.
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Outcomes of haploidentical stem cell transplantation using total body irradiation (600 cGy) and fludarabine with ATG in adult patients with severe aplastic anemia: A prospective phase II study
Lee, S. E., Min, G. J., Park, S. S., Park, S., Yoon, J. H., Shin, S. H., Cho, B. S., Eom, K. S., Kim, Y. J., Lee, S., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
Abstract
The aim of this study is to verify the feasibility of rabbit ATG (Thymoglobulin(R)) (5 mg/kg) in combination with 600 cGy fractionated total body irradiation (fTBI; 200cGy, 3 times) and fludarabine (Flu, 150 mg/m(2)) as a conditioning regimen for haploidentical stem cell transplantation from a related mismatched donor (Haplo-SCT) in adult patients with severe aplastic anemia (SAA). We analyzed 47 consecutive patients who underwent Haplo-SCT, including 24 patients from our previous pilot report. The median age was 36.0 years (17-61) and 25 (53%) patients had very SAA (VSAA) at transplantation. All patients achieved primary engraftment. The cumulative incidence of acute GVHD (grade ≥2) and chronic GVHD (≥ moderate) was 27.7% at 100 days and 13.5% at 3 years, respectively. With a median follow-up of 32.3 months, the 3-year probability of overall survival and failure-free survival was 91.0% and 88.6%, respectively. The 3-year GVHD- and failure-free survival (GFFS) was 71.6%. Offspring donor and lower comorbidity index were independent factors correlated with higher GFFS in multivariate analysis. In conclusion, the outcomes of Haplo-SCT with fTBI 600 cGy/Flu/ATG-5 indicate that Haplo-SCT can be an effective alternative option when fully matched donors are not available, or for patients with VSAA who need an urgent transplant.
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Excellent outcomes of hematopoietic stem cell transplantation with total nodal irradiation and antithymocyte globulin conditioning in severe aplastic anemia with advanced age and/or severe comorbidity
Park, S. S., Min, G. J., Park, S., Lee, S. E., Yoon, J. H., Cho, B. S., Eom, K. S., Kim, Y. J., Lee, S., Min, C. K., et al
Bone marrow transplantation. 2019