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Graft-versus-host disease and relapse/rejection-free survival after allogeneic transplantation for idiopathic severe aplastic anemia: a comprehensive analysis from the SAAWP of the EBMT
Devillier, R., Eikema, D. J., Dufour, C., Aljurf, M., Wu, D., Maschan, A., Kulagin, A., Halkes, C. J. M., Collin, M., Snowden, J., et al
Haematologica. 2023
Abstract
Survival after Allo-HSCT for severe idiopathic aplastic anemia (SAA) has improved in recent years, approaching 75% at 5 years. However, an SAA-adapted composite endpoint, GVHD and relapse/rejection-free survival (GRFS), may more accurately assess patient outcomes beyond survival. We analyzed GRFS to identify risk factors and specific causes of GRFS failure. Our retrospective analysis from the SAAWP of the EBMT included 479 patients with idiopathic SAA who underwent Allo-HSCT in 2 conventional situations: i) upfront Allo-HSCT from a matched related donor (MRD) (upfront cohort), and ii) Allo-HSCT for relapsed or refractory SAA (rel/ref cohort). Relevant events for GRFS calculation included graft failure, grade 3-4 acute GVHD, extensive chronic GVHD, and death. In the upfront cohort (n=209), 5-year GRFS was 77%. Late Allo-HSCT (i.e., >6 months after SAA diagnosis) was the main poor prognostic factor, specifically increasing the risk of death as the cause of GRFS failure (HR: 4.08, 95% CI [1.41-11.83], p=0.010). In the rel/ref cohort (n=270), 5-year GRFS was 61%. Age was the main factor significantly increasing the risk of death (HR: 1.04, 95% CI [1.02-1.06], p.
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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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Unrelated cord blood transplantation in patients with acquired refractory aplastic anemia: a nationwide phase II study
Peffault de Latour, R., Chevret, S., Jubert, C., Sirvent, A., Galambrun, C., Ruggeri, A., Gandemer, V., Cornillon, J., Rialland, F., Dalle, J. H., et al
Blood. 2018
Abstract
Outcomes remain poor for patients with refractory severe aplastic anemia (SAA). Alternative donor transplantation may be considered, but results from previous studies have not been encouraging. We conducted a prospective nationwide phase II study to assess the efficacy and safety of unrelated cord blood transplantation (CBT) in patients with refractory SAA (APCORD protocol, NCT 01343953). To demonstrate a significant difference in one-year survival from 20% (null hypothesis) to 50% (alternative hypothesis), we needed to include 25 transplanted patients. Twenty-six patients (median age: 16 years) were therefore included. Eligibility criteria required one or two unrelated CB units, containing separately or together more than 4x10(7) frozen nucleated cells/kg recipient body weight. The conditioning regimen comprised fludarabine, cyclophosphamide, thymoglobulin and 2-Gy total body irradiation. With a median follow-up of 38.8 months, engraftment occurred in 23 patients (88%); cumulative incidences of grade II-IV acute and chronic GvHD were 45.8% and 36%, respectively. Twenty-three patients were alive at one year, with an overall survival rate of 88.5%, differing significantly from the expected 20% (p<0.0001) (84% overall survival at 2 years). CBT with units containing at least 4x10(7) frozen nucleated cells/kg is therefore a valuable curative option for young adults with refractory SAA and no available matched unrelated donors.
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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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Unrelated alternative donor transplantation for severe acquired aplastic anemia: a study from the French Society of Bone Marrow Transplantation and Cell Therapies and the EBMT Severe Aplastic Anemia Working Party
Devillier, R., Dalle, J. H., Kulasekararaj, A., D'Aveni, M., Clement, L., Chybicka, A., Vigouroux, S., Chevallier, P., Koh, M., Bertrand, Y., et al
Haematologica. 2016;101(7):884-90
Abstract
Unrelated allogeneic transplantation for severe aplastic anemia is a treatment option after immunosuppressive treatment failure in the absence of a matched sibling donor. Age, delay between disease diagnosis and transplantation, and HLA matching are the key factors in transplantation decisions, but their combined impact on patient outcomes remains unclear. Using the French Society of Bone Marrow Transplantation and Cell Therapies registry, we analyzed all consecutive patients (n=139) who underwent a first allogeneic transplantation for idiopathic severe aplastic anemia from an unrelated donor between 2000 and 2012. In an adjusted multivariate model, age over 30 years (Hazard Ratio=2.39; P=0.011), time from diagnosis to transplantation over 12 months (Hazard Ratio=2.18; P=0.027) and the use of a 9/10 mismatched unrelated donor (Hazard Ratio=2.14; P=0.036) were independent risk factors that significantly worsened overall survival. Accordingly, we built a predictive score using these three parameters, considering patients at low (zero or one risk factors, n=94) or high (two or three risk factors, n=45) risk. High-risk patients had significantly shorter survival (Hazard Ratio=3.04; P<0.001). The score was then confirmed on an independent cohort from the European Group for Blood and Marrow Transplantation database of 296 patients, with shorter survival in patients with at least 2 risk factors (Hazard Ratio=2.13; P=0.005) In conclusion, a simple score using age, transplantation timing and HLA matching would appear useful to help physicians in the daily care of patients with severe aplastic anemia. Copyright© Ferrata Storti Foundation.