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1.
The outcome and predictive model of allogeneic hematopoietic stem cell transplantation among elderly patients with severe aplastic anemia from the Chinese Blood and Marrow Transplant Registry Group
Xu, Z. L., Xu, L. P., Zhang, Y. C., Zhou, Y. H., Jiang, E. L., Zhang, J. P., Fu, B., Ouyang, G. F., Song, X. M., Zhang, X. J., et al
Haematologica. 2024
Abstract
Not available.
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2.
HLA class I allele loss and bone marrow transplantation outcomes in immune aplastic anemia
Zaimoku, Y., Katagiri, T., Nakagawa, N., Imi, T., Maruyama, H., Takamatsu, H., Ishiyama, K., Yamazaki, H., Miyamoto, T., Nakao, S.
Transplantation and cellular therapy. 2023
Abstract
BACKGROUND In patients with immune-mediated acquired aplastic anemia (AA), HLA class I alleles often disappear from the surface of hematopoietic progenitor cells, potentially enabling evasion from cytotoxic T-cell-mediated pathogenesis. While HLA class I allele loss has been studied in AA patients treated with immunosuppressive therapy (IST), its impact on allogeneic bone marrow transplantation (BMT) has not been thoroughly investigated. OBJECTIVE The purpose of this study was to evaluate the clinical implications of HLA class I allele loss in acquired AA patients undergoing allogeneic BMT. STUDY DESIGN This study enrolled acquired AA patients who underwent initial BMT from unrelated donors through the Japan Marrow Donor Program between 1993 and 2011. The presence of HLA class I allele loss due to loss of heterozygosity (HLA-LOH) was assessed using pretransplant blood DNA and correlated with clinical data obtained from the Japanese Transplant Registry Unified Management Program (TRUMP®). RESULTS A total of 432 patients with acquired AA were included in the study, and HLA-LOH was detected in 20 (11%) of the 178 patients available for the analysis. Patients with HLA-LOH typically presented with more severe AA at the diagnosis (P = 0.017) and received BMT earlier (P < 0.0001) than those without HLA-LOH. They also showed a slight but significant recovery in platelet counts from the diagnosis to BMT (P = 0.00085). However, HLA-LOH had no significant effect on the survival, engraftment, graft failure, chimerism status, graft-versus-host disease, or other complications following BMT, even when the 20 HLA-LOH(+) patients were compared with the 40 propensity score-matched HLA-LOH(-) patients. Nevertheless, patients lacking HLA-A*02:06 or HLA-B*40:02, the alleles most frequently lost and associated with a better IST response, showed higher survival rates than those lacking other alleles, with estimated 5-year overall survival rates of 100% and 44%, respectively (P = 0.0042). In addition, in a specific subset of HLA-LOH(-) patients showing clinical features similar to HLA-LOH(+) patients, the HLA-A*02:06 and HLA-B*40:02 allele genotypes correlated with better survival rates than other allele genotypes, with estimated 5-year overall survival rates of 100% and 43%, respectively (P = 0.0096). This genotype correlation, however, did not extend to all patients, suggesting that immunopathogenic mechanisms linked to the loss of certain HLA alleles, rather than the HLA genotypes themselves, influence survival outcomes. The survival benefit associated with the loss of these two alleles was confirmed by the multivariable Cox regression model. CONCLUSIONS The observed correlations between HLA loss and the pretransplant clinical manifestations and between loss of specific HLA class I alleles and survival outcomes in AA patients may improve patient selection for unrelated BMT and facilitate further investigations into the immune pathophysiology of the disease.
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3.
Comparison of haploidentical stem cell transplantation with post-transplant cyclophosphamide versus umbilical cord blood transplantation in adult patients with aplastic anemia
Onishi, Y., Mori, T., Yamazaki, H., Hiramoto, N., Zaimoku, Y., Kanaya, M., Matsue, K., Onizuka, M., Aotsuka, N., Uchida, N., et al
Transplantation and cellular therapy. 2023
Abstract
BACKGROUND Aplastic anemia patients who are refractory to immunosuppressive therapy or with very low neutrophil counts require allogeneic hematopoietic stem cell transplantation (HSCT). Umbilical cord blood transplantation (UCBT) has been a treatment option when an HLA-matched donor is not available, and HSCT from a related haploidentical donor using post-transplant cyclophosphamide (PTCY) for GVHD prophylaxis (PTCY-haplo) recently became another important approach. OBJECTIVE We aimed to compare the outcomes of PTCY-haplo and UCBT in adult patients with aplastic anemia in order to identify more effective and safer approaches for alternative donor transplantation. STUDY DESIGN Data in a nationwide registry were retrospectively analyzed to assess the outcomes of aplastic anemia patients aged ≥16 years who received PTCY-haplo or UCBT as first HSCT between 2016 and 2020. The primary endpoint was 1-year overall survival (OS) after HSCT. Secondary endpoints included 1-year failure-free survival (FFS), neutrophil and platelet engraftment, and acute and chronic GVHD. RESULTS Eighty-three patients who received PTCY-haplo (n = 24) and UCBT (n = 59) were eligible. One-year OS rates were 78.5% (95%CI, 55.7 - 90.5) in the PTCY-haplo group and 77.5% (95%CI, 64.5 - 86.3, P=0.895) in the UCBT group. One-year FFS rates were 78.7% (95%CI, 56.1 - 90.6) in the PTCY-haplo group and 62.2% (95%CI, 48.5 - 73.3, P=0.212) in the UCBT group. Among patients <40 years, the PTCY-haplo group had a significantly higher FFS rate; 92.9% (95%CI, 59.1 - 99.0) vs. 63.9% (95%CI, 43.2 - 78.7, P=0.047). Neutrophil and platelet engraftment rates were significantly higher in the PTCY-haplo group than in the UCBT group; 95.8% (95%CI, 73.9 - 99.4) vs. 78.0% (95%CI, 65.1 - 86.6, P<0.001) and 83.3% (95%CI, 61.5 - 93.4) vs. 72.9% (95%CI, 59.6 - 82.4, P=0.025). No significant difference was observed in the cumulative incidence of grade II-IV acute GVHD and chronic GVHD between the two groups. CONCLUSIONS Aplastic anemia patients achieved significantly higher neutrophil and platelet engraftment rates with PTCY-haplo than with UCBT. OS and the incidence of acute and chronic GVHD were similar between the two groups. In patients <40 years, the FFS rate was higher in the PTCY-haplo group. Therefore, PTCY-haplo is promising for alternative donor transplantation in adult patients with aplastic anemia.
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4.
Upfront unrelated donor Hematopoietic stem cell transplantation in patients with idiopathic aplastic anemia: a retrospective study of the Severe Aplastic Anemia Working Party of European Bone Marrow Transplantation
Petit, A. F., Kulasekararaj, A. G., Eikema, D. J., Maschan, A., Adjaoud, D., Kulagin, A., Grassi, A., Fagioli, F., Griskevicius, L., Snowden, J. A., et al
American journal of hematology. 2021
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5.
Haploidentical transplantation and posttransplant cyclophosphamide for treating aplastic anemia patients: a report from the EBMT Severe Aplastic Anemia Working Party
Prata, P. H., Eikema, D. J., Afansyev, B., Bosman, P., Smiers, F., Diez-Martin, J. L., Arrais-Rodrigues, C., Koc, Y., Poire, X., Sirvent, A., et al
Bone marrow transplantation. 2019
Abstract
In the absence of an HLA-matched donor, the best treatment for acquired aplastic anemia patients refractory to immunosuppression is unclear. We collected and analyzed data from all acquired aplastic anemia patients who underwent a haploidentical transplantation with posttransplant cyclophosphamide in Europe from 2011 to 2017 (n = 33). The cumulative incidence of neutrophil engraftment was 67% (CI95%: 51-83%) at D +28 and was unaffected by age group, stem cell source, ATG use, or Baltimore conditioning regimen. The cumulative incidence of grades II-III acute GvHD was 23% at D +100, and limited chronic GvHD was 10% (0-20) at 2 years, without cases of grade IV acute or extensive chronic GvHD. Two-year overall survival was 78% (64-93), and 2-year graft-versus-host disease-free survival was 63% (46-81). In univariate analysis, the 2-year OS was higher among patients who received the Baltimore conditioning regimen (93% (81-100) versus 64% (41-87), p = 0.03), whereas age group, stem cell source, and ATG use had no effect. Our results using unmanipulated haploidentical transplantation and posttransplant cyclophosphamide for treating refractory AA patients are encouraging, but warrant confirmation in a prospective study with a larger number of patients and longer follow-up.
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6.
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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7.
Haploidentical hematopoietic cell transplantation for severe acquired aplastic anemia: a case-control study of post-transplant cyclophosphamide included regimen vs. anti-thymocyte globulin & colony-stimulating factor-based regimen
Xu, L., Fu, B., Wang, W., Xu, Y., Wu, D., Wang, S., Liu, Q., Xia, L., Gao, S., Jiang, M., et al
Science China. Life sciences. 2019
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8.
Donor Telomere Length and Causes of Death after Unrelated Hematopoietic Cell Transplant in Patients with Marrow Failure
Gadalla, S. M., Aubert, G., Wang, T., Haagenson, M., Spellman, S. R., Wang, L., Katki, H. A., Savage, S. A., Lee, S. J.
Blood. 2018
Abstract
Previous studies suggest that longer donor leukocyte telomere length (TL) is associated with improved survival after hematopoietic cell transplant (HCT) in severe aplastic anemia (SAA). This study aimed to determine whether cell-specific lymphocyte TL are associated with certain post-HCT causes of death. We used flow cytometry and fluorescence in situ hybridization (flow FISH) to measure TL in donor total lymphocytes and subsets: naive enriched T-cells (CD45RA+CD20-), memory enriched T-cells (CD45RA-CD20-), NK-fully differentiated T cells (CD45RA+CD57+), and B cells (CD45RA+CD20+). Competing risks survival regression was used for cause-specific death analyses. Clinical data and biospecimens were available from the Center for International Blood and Marrow Transplant Research (CIBMTR) database and biorepository. The study included 197 patients who received unrelated donor HCT for SAA between 1988-2004. The median age at HCT was 15 years (range=0.5-40), and the median follow-up was 5 years (range <1 month - 20.7 years). Longer donor TL in all cell-subsets was associated with lower risk of all-cause mortality (p<0.01). In cause-specific mortality analyses, longer TL in B cells (HR=0.63, 95% CI=0.46-0.87, p=0.006), and possibly NK-fully differentiated T cells (HR=0.7, 95% CI=0.51-0.97, p=0.03) were associated with lower risk of infection-related death. Donor TL in other tested lymphocyte subsets were not statistically significantly associated with death from graft-versus-host disease or graft failure (p>0.05). Yet, a trend toward excess risk of graft-versus-host mortality was noted (HR-total lymphocyte TL=1.26, p=0.15). In conclusion, longer donor TL was associated with reduced infection-related deaths after HCT for SAA.
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9.
Impact of t-cell depletion strategies on outcomes following hematopoietic stem cell transplantation for idiopathic aplastic anemia: A study on behalf of the european blood and marrow transplant (ebmt) saa working party
Samarasinghe, S., Clesham, K., Iacobelli, S., Sbianchi, G., Knol, C., Hamladji, R. M., Socie, G., Aljurf, M., Koh, M., Sengeloev, H., et al
American journal of hematology. 2018
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Editor's Choice
Abstract
We retrospectively analyzed the outcomes of 1837 adults and children with severe aplastic anemia (SAA) who underwent matched sibling donor (MSD) and matched unrelated donor (MUD) haemopoietic stem cell transplantation (HSCT) between 2000 and 2013. Patients were grouped by transplant conditioning containing either ATG (n=1283), alemtuzumab (n=261) or no serotherapy (NS) (n=293). The risks of chronic GvHD were significantly reduced when ATG or alemtuzumab were compared to no serotherapy (p=0.021 and p=0.003, respectively). Acute GVHD was significantly reduced in favor of alemtuzumab compared to ATG (P=0.012) and no serotherapy (p < 0.001). By multivariate analysis, when compared to ATG, alemtuzumab was associated with a lower risk of developing acute (OR 0.262; 95% CI 0.14-0.47; p<0.001) and chronic GVHD (HR 0.58; 95% CI 0.35 - 0.94; p=0.027). OS was significantly better in ATG and alemtuzumab patients compared with no serotherapy (p=0.010 and p=0.025). Our data shows inclusion of serotherapy in MSD and MUD HSCT for patients with SAA reduces chronic GVHD and provides a survival advantage over patients not receiving serotherapy. Notably, alemtuzumab reduced the risk of acute and chronic GvHD compared to ATG and indicates that alemtuzumab might be the serotherapy of choice for MSD and MUD transplants for SAA. This article is protected by copyright. All rights reserved.
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10.
Upfront haploidentical transplant for acquired severe aplastic anemia: registry-based comparison with matched related transplant
Xu, L. P., Jin, S., Wang, S. Q., Xia, L. H., Bai, H., Gao, S. J., Liu, Q. F., Wang, J. M., Wang, X., Jiang, M., et al
Journal of hematology & oncology. 2017;10(1):25
Abstract
BACKGROUND Haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) is an alternative treatment method for severe aplastic anemia (SAA) patients lacking suitable identical donors and those who are refractory to immunosuppressive therapy (IST). The current study evaluated the feasibility of upfront haploidentical HSCT in SAA patients. METHODS We conducted a multicenter study based on a registry database. One hundred fifty-eight SAA patients who underwent upfront transplantation between June 2012 and September 2015 were enrolled. RESULTS Eighty-nine patients had haploidentical donors (HIDs), and 69 had matched related donors (MRDs) for HSCT. The median times for myeloid engraftment in the HID and MRD cohorts were 12 (range, 9-20) and 11 (range, 8-19) days, with a cumulative incidence of 97.8 and 97.1% (P=0.528), respectively. HID recipients had an increased cumulative incidence of grades II-IV acute graft-versus-host disease (aGVHD) (30.3 vs. 1.5%, P<0.001), grades III-IV aGVHD (10.1 vs. 1.5%, P=0.026), and chronic GVHD (cGVHD) (30.6 vs. 4.4%, P<0.001) at 1 year but similar extensive cGVHD (3.4 vs. 0%, P=0.426). The three-year estimated overall survival (OS) rates were 86.1 and 91.3% (P=0.358), while the three-year estimated failure-free survival (FFS) rates were 85.0 and 89.8% (P=0.413) in the HID and MRD cohorts, respectively. In multivariate analysis, survival outcome for the entire population was significantly adversely associated with increased transfusions and poor performance status pre-SCT. We did not observe differences in primary engraftment and survival outcomes by donor type. CONCLUSIONS Haploidentical SCT as upfront therapy was an effective and safe option for SAA patients, with favorable outcomes in experienced centers.