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1.
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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Comparison of anti-thymocyte globulin-based immunosuppressive therapy and allogeneic hematopoietic stem cell transplantation in patients with transfusion-dependent non-severe aplastic anaemia: a retrospective study from a single centre
Shen, Y., Li, Y., Liu, Q., Liu, W., Yu, Q., Hu, H., Liu, S., Dong, J., Xu, M., Hong, Y., et al
Annals of medicine. 2023;55(2):2271475
Abstract
OBJECTIVES The selection and timing of anti-thymocyte globulin (ATG)-based immunosuppressive therapy (IST) or allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with transfusion-dependent non-severe aplastic anemia (TD-NSAA) pose significant clinical challenges. This study aims to compare the efficacy and long-term outcomes of the two treatments in TD-NSAA. METHODS Patients who underwent ATG-based IST or allo-HSCT between July 2011 and December 2019 were reviewed. We gathered their clinical information, treatment response, survival data, and subsequently analysed the associated risk factors. RESULTS A total of 97 TD-NSAA patients were reviewed, and 55 patients who underwent either ATG-based IST (n = 27) or allo-HSCT (n = 28) were enrolled. We observed a significant disparity in the 12-month overall response rate (ORR) (48.1% in IST vs 78.6% in HSCT, p < 0.05), but not in five-year overall survival (OS) and event-free survival (EFS). Multivariate Cox regression analysis identified the transfusion of ≥78.75 units of red blood cells (RBCs) as the sole independent risk factor for OS (HR: 17.04, p = 0.039) in the IST group. For the HSCT group, disease duration (DD) ≥20 months and transfusion of ≥78.75 units of RBCs predicted an adverse EFS. Frontline IST exhibited superior 12-month ORR (68.8% vs 18.2%, p = 0.018) and five-year EFS when compared to non-frontline. Patients with a DD ranging from 6 to 20 months displayed a better EFS (p = 0.016) in HSCT group than those in the ATG-based IST group. CONCLUSIONS Prior treatment history, disease duration, and serum ferritin levels should be carefully weighed when making the choice between ATG-based IST and allo-HSCT for TD-NSAA. The selection and timing of anti-thymocyte globulin (ATG)-based immunosuppressive therapy (IST) or allogeneic hematopoietic stem cell transplantation (allo-HSCT) present notable clinical challenges for individuals with transfusion-dependent non-severe aplastic anaemia (TD-NSAA).In terms of treatment outcomes, allo-HSCT exhibited a higher 12-month overall response rate (ORR) in comparison to ATG-based IST among TD-NSAA patients. Nevertheless, comparable rates of 5-year overall survival (OS) and event-free survival (EFS) were observed between the two therapeutic approaches.Several factors warrant consideration when deliberating between ATG-based IST and allo-HSCT for TD-NSAA. These factors include the patient’s prior treatment history, disease duration, number of packed red cell transfusions received, and serum ferritin levels. eng
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Comparison of Haploidentical Hematopoietic Stem Cell Transplant With or Without Unrelated Cord Blood Infusion in Severe Aplastic Anemia: Outcomes of a Multicenter Study
Lei, M., Zhang, Y., Jiao, W., Li, X., Zhou, H., Wang, Q., Qiu, H., Tang, X., Han, Y., Fu, C., et al
Frontiers in Immunology. 2022;13:912917
Abstract
The purpose of this study in severe aplastic anemia (SAA) patients was to compare the feasibility and efficacy of haploidentical hematological stem cell transplantation combined with a single unrelated cord blood (UCB) infusion (Haplo-cord-HSCT) or haplo-identical HSCT (Haplo-HSCT) alone. The five-year graft-versus-host disease (GVHD)-free or failure-free survival (GFFS) was similar between the two groups (72.4 ± 3.4% vs. 65.4 ± 5.2%, P = 0.178); however, the five-year overall survival (OS) was more favorable in the Haplo-cord-HSCT group than that in the Haplo-HSCT group (84.0 ± 2.8% vs. 72.6 ± 4.9%, P = 0.022), as was transplantation-related mortality (16.4% vs. 27.4%, P = 0.039). Multivariate analysis showed that Haplo-cord HSCT was the only independent determinant of increased OS (P = 0.013). Explorative subgroup analysis showed that only an Human leukocyte antigen-A (HLA-A) allele match between UCB and the recipient was a beneficial factor for GFFS in the Haplo-cord-HSCT group (P = 0.011). In the haplo-cord with an HLA-A match (n = 139) or mismatch (n = 32) or Haplo-HSCT groups, a haplo-cord HLA-A allele match was associated with lower I-IV and III-IV acute GVHD. The haplo-cord with an HLA-A match subgroup also had higher five-year OS than the Haplo-HSCT group (85.4 ± 3.0% vs. 72.6 ± 4.9%, P = 0.013), and higher five-year GFFS than the Haplo-cord HLA-A allele mismatch subgroup (76.2 ± 3.6% vs. 56.3 ± 8.8%, P = 0.011). These findings suggest that the coinfusion of a single UCB potentially improves survival of Haplo-HSCT in SAA patients and that an HLA-A allele-matched UCB is the preferred option.
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Matched related transplantation versus immunosuppressive therapy plus eltrombopag for first-line treatment of severe aplastic anemia: a multicenter, prospective study
Liu, L., Lei, M., Fu, R., Han, B., Zhao, X., Liu, R., Zhang, Y., Jiao, W., Miao, M., Zhang, F., et al
Journal of hematology & oncology. 2022;15(1):105
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Editor's Choice
Abstract
This study prospectively compared the efficacy and safety between matched related donor-hematopoietic stem cell transplantation (MRD-HSCT) (n = 108) and immunosuppressive therapy (IST) plus eltrombopag (EPAG) (IST + EPAG) (n = 104) to determine whether MRD-HSCT was still superior as a front-line treatment for patients with severe aplastic anemia (SAA). Compared with IST + EPAG group, patients in the MRD-HSCT achieved faster transfusion independence, absolute neutrophil count ≥ 1.0 × 10(9)/L (P < 0.05), as well as high percentage of normal blood routine at 6-month (86.5% vs. 23.7%, P < 0.001). In the MRD-HSCT and IST + EPAG groups, 3-year overall survival (OS) was 84.2 ± 3.5% and 89.7 ± 3.1% (P = 0.164), whereas 3-year failure-free survival (FFS) was 81.4 ± 4.0% and 59.1 ± 4.9% (P = 0.002), respectively. Subgroup analysis indicated that the FFS of the MRD-HSCT was superior to that of the IST + EPAG among patients aged < 40 years old (81.0 ± 4.6% vs. 63.7 ± 6.5%, P = 0.033), and among patients with vSAA (86.1 ± 5.9% vs. 54.9 ± 7.9%, P = 0.003), while the 3-year OS of the IST + EPAG was higher than that of the MRD-HSCT among the patient aged ≥ 40 years old (100.0 ± 0.0% vs. 77.8 ± 9.8%, P = 0.036). Multivariate analysis showed that first-line MRD-HSCT treatment was associated favorably with normal blood results at 6-month and FFS (P < 0.05). These outcomes suggest that MRD-HSCT remains the preferred first-line option for SAA patients aged < 40 years old or with vSAA even in the era of EPAG.
PICO Summary
Population
Adults with severe aplastic anaemia (n=212)
Intervention
Matched related donor stem cell transplantation (MRD-HSCT, n=108)
Comparison
Immunosuppressive therapy plus eltrombopag (IST + EPAG, n=104)
Outcome
Compared with IST + EPAG group, patients in the MRD-HSCT achieved faster transfusion independence, absolute neutrophil count ≥ 1.0 × 10(9)/L, as well as high percentage of normal blood routine at 6-month (86.5% vs. 23.7%). In the MRD-HSCT and IST + EPAG groups, 3-year overall survival (OS) was 84.2 ± 3.5% and 89.7 ± 3.1%, whereas 3-year failure-free survival (FFS) was 81.4 ± 4.0% and 59.1 ± 4.9%, respectively. Subgroup analysis indicated that the FFS of the MRD-HSCT was superior to that of the IST + EPAG among patients aged < 40 years old (81.0 ± 4.6% vs. 63.7 ± 6.5%), and among patients with vSAA (86.1 ± 5.9% vs. 54.9 ± 7.9%), while the 3-year OS of the IST + EPAG was higher than that of the MRD-HSCT among the patient aged ≥ 40 years old (100.0 ± 0.0% vs. 77.8 ± 9.8%). Multivariate analysis showed that first-line MRD-HSCT treatment was associated favorably with normal blood results at 6-month and FFS.
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Severe aplastic anemia patients with infection who received an allogeneic hematopoietic stem cell transplantation had a better chance: Long-term outcomes of a multicenter study
Liu, L., Miao, M., He, H., Wang, S., Zhang, Y., Guo, A., Jiao, W., Lei, M., Cai, Y., Shangguan, X., et al
Frontiers in immunology. 2022;13:955095
Abstract
BACKGROUND AND AIMS How to select the treatment is a challenge for the management of acquired patients with infections. This study aimed at comparing the outcomes of SAA with infections who had an allogeneic hematopoietic stem cell transplantation (allo-HSCT) with that of patients who had an infection and received non-HSCT therapy. METHODS We retrospectively compared the outcomes of patients with acquired SAA and infections who had an allo-HSCT (n = 141) with that of patients who had an infection and received non-HSCT therapy (n = 186) between July 2004 and January 2020. RESULTS The treatment-related mortality (TRM) of grade 1-2 infections in the HSCT and non-HSCT groups was 24.99% and 13.68%, respectively (P = 0.206), while the TRM of grade 3-4 infections was lower in the HSCT group than that observed in the non-HSCT group (18.54% vs. 33.33%, P = 0.036). At 6 months post-treatment, 91.30% patients in the HSCT group and 8.78% patients in the non-HSCT group had achieved a normal blood profile (P < 0.0001). The time required to discontinue transfusions of red blood cells and platelets in the non-HSCT group was longer than in the HSCT group (P < 0.0001). Estimated overall survival (OS) at 6 years was similar in the two groups (75.5% ± 3.9% vs. 76.3% ± 3.1%, P = 0.996), while the estimated failure-free survival (FFS) at 6 years was 75.2% ± 3.8% in the HSCT group and 48.9% ± 3.7% in the non-HSCT group (P < 0.0001). Multivariate analysis showed that younger age, lower grade of infection (grade 1-2), and SAA (vs. very SAA) were favorable factors for OS (P < 0.05), and that the choice of HSCT and younger age were favorable factors for FFS (P < 0.0001). CONCLUSION These results suggest that allo-HSCT has a better chance of a successful outcome than non-HSCT in SAA patients with an infection.
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Inefficacy of Immunosuppressive Therapy for Severe Aplastic Anemia Progressing From Non-SAA: Improved Outcome After Allogeneic Hematopoietic Stem Cell Transplantation
Liu, L., Zhao, X., Miao, M., Zhang, Y., Jiao, W., Lei, M., Zhou, H., Wang, Q., Cai, Y., Zhao, L., et al
Frontiers in oncology. 2021;11:739561
Abstract
BACKGROUND AND AIMS This study aimed at comparing the efficacy and safety of severe aplastic anemia (SAA) cases that had met the criteria for SAA at the time of diagnosis (group A) with SAA that had progressed from non-SAA (NSAA) (group B), both undergoing first-line immunosuppressive therapy (IST). Additionally, group B was compared with SAA that had progressed from NSAA and who had been treated by allogeneic hematopoietic stem cell transplantation (allo-HSCT) (group C). METHODS We retrospectively compared 608 consecutive patients in group A (n = 232), group B (n = 229) and group C (n = 147) between June 2002 and December 2019. Six months after treatment, the rate of overall response and the fraction of patients who had achieved normal blood values, treatment-related mortality (TRM), secondary clonal disease, 5-year overall survival (OS) and failure-free survival (FFS) were indirectly compared between group A and group B, group B and group C. RESULTS Six months after treatment, the rate of overall response and the fraction of patients who had achieved normal blood values in group A was higher than in group B (65.24% vs. 40.54%, P < 0.0001; 23.33% vs. 2.25%, P < 0.0001); the same was true for group C (92.50% vs. 2.25%, P < 0.0001). The rate of relapse in group B was higher than in group C (P < 0.0001), but there were no differences in TRM and secondary clonal disease (P > 0.05). There were no differences in estimated 5-year OS between groups A and B (83.8% ± 2.6% vs. 85.8% ± 2.6%, P = 0.837), or between B and C (85.8% ± 2.6% vs. 77.9% ± 3.4%, P = 0.051). The estimated 5-year FFS in groups A and C was higher than for group B (57.1% ± 3.3% vs. 39.7% ± 3.4%, P < 0.001; 76.7% ± 3.5% vs. 39.7% ± 3.4%, P < 0.0001). CONCLUSION These results indicate that IST is less effective in SAA progressing from non-SAA but allo-HSCT can improve outcomes.
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A comparative study of porcine antihuman lymphocyte globulin versus antithymocyte globulin-fresenius in an allogeneic hematopoietic cell transplantation conditioning regimen for severe aplastic anemia
Zhang, Y., Liu, L., Si, Y., Miao, M., Qiu, H., Tang, X., Han, Y., Fu, C., Jin, Z., Chen, S., et al
Hematology (Amsterdam, Netherlands). 2021;26(1):741-750
Abstract
OBJECTIVES To compare the outcomes of antihuman T lymphocyte globulin (ATG-F) and porcine antihuman lymphocyte globulin (p-ALG) as part of a conditioning regimen in hematopoietic stem cell transplantation (HSCT) for severe aplastic anemia (SAA). METHODS we performed a retrospective analysis, evaluating the outcome of patients with SAA who received ATG-F based conditioning (n?=?26) with those receiving p-ALG conditioning (n?=?34). RESULTS The median time to neutrophil engraftment was 11 days (range, 8?-?38) and 11 days (range, 9?-?24) in the p-ALG and ATG-F groups (P?=?0.857); the median platelet engraftment time was 15 (range, 9?-?330) days and 13 (range, 10?-?56) days (P?=?0.155). There were no significant differences in grades II?-?IV acute graft-versus-host disease (aGVHD), grades III?-?IV aGVHD, chronic GVHD (cGVHD), and the moderate-severe cGVHD between the ATG-F and p-ALG groups (P>0.05). DISCUSSION Patients in the ATG-F group functioned significantly better on role-physical (P?=?0.006), general health (P?=?0.029), and physical component summary (P?=?0.009). The estimated overall survival and failure free survival rates at 5 years were 88.5%?±?6.3% vs. 82.4%?±?6.5% (P?=?0.515), 84.6%?±?7.1% vs. 79.4%?±?6.9%, respectively (P?=?0.579). The infection rates were 61.53% and 47.05%, respectively (P?=?0.265). CONCLUSION As part of the conditioning regimen, p-ALG achieved a similar efficacy as ATG-F without increasing the incidence of transplantation complications in SAA patients.
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Comparison of two different rabbit antithymocyte globulin (r-ATG) preparations:Thymocyte r-ATG versus T lymphoblast cell line r-ATG in allogeneic hematopoietic stem cell transplantation for acquired severe aplastic anemia: propensity score-matched analysis
Liu, L., Xu, G., Zhang, Y., Jiao, W., Lei, M., Zhou, H., Wang, Q., Qiu, H., Tang, X., Han, Y., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
Abstract
We retrospectively analyzed the outcomes of 214 severe aplastic anemia (SAA) patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) with rabbit antithymocyte globulin (r-ATG) or ATG-Fresenius (ATG-F). Using propensity score matching, we performed a case-control study comparing 44 and 23 patients in the r-ATG and ATG-F groups, respectively. The median time for myeloid engraftment was 11 vs. 11 days (P?=?0.368) and for platelet engraftment was 11 vs. 13 days (P?=?0.030) in the r-ATG and ATG-F groups, respectively. The r-ATG group showed a lower incidence of grades III-IV acute graft-versus-host disease (aGVHD) than the ATG-F group (2.27% vs. 17.39%, P?=?0.026). Similar outcomes were observed between the r-ATG and ATG-F groups for infection rate (59.09% vs. 56.52%, P?=?0.840), grades II-IV aGVHD (20.45% vs. 21.74%, P?=?0.948), overall incidence of chronic GVHD (26.83% vs. 22.73%, P?=?0.704), moderate-severe chronic GVHD (9.76% vs. 13.64%, P?=?0.648), and transplantation-related mortality (11.36% vs. 4.35%, P?=?0.614). There was no statistical difference in 5-year overall survival (86.40% vs. 95.7%, P?=?0.245), GVHD-free, failure-free survival (77.30% vs. 78.30%, P?=?0.986), or health-related quality of life (P ? 0.05) between the r-ATG and ATG-F.
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9.
Comparison of efficacy and health-related quality of life of first-line haploidentical hematopoietic stem cell transplantation with unrelated cord blood infusion and first-line immunosuppressive therapy for acquired severe aplastic anemia
Liu, L., Zhang, Y., Jiao, W., Zhou, H., Wang, Q., Jin, S., Cai, Y., Zhao, L., Shangguan, X., Liu, Z., et al
Leukemia. 2020
Abstract
We retrospectively compared the efficacy and health-related quality of life (HRQoL) of (1) first-line haploidentical hematopoietic stem cell transplantation (haplo-HSCT, n = 146) combined with unrelated cord blood (UCB) infusion and (2) first-line immunosuppressive therapy (IST, n = 219) in acquired severe aplastic anemia (SAA) patients. At 6 months post treatment, 90.30% patients in the haplo-HSCT group and 18.78% patients in the IST group achieved normal blood routine (P < 0.0001). The time required to discontinue red blood cells and platelets transfusion in the IST group were longer than in the haplo-HSCT group (P < 0.0001). The estimated overall survival at 4 years was similar (80.1 +/- 3.5% vs. 80.1 +/- 3.0%, P = 0.726); the estimated failure-free survival (FFS) at 4 years was 77.8 +/- 3.7% in the haplo-HSCT group and 48.0 +/- 3.6% in the IST group (P < 0.0001). Patients treated with haplo-HSCT scored significantly better in the HRQoL than treated with IST (P < 0.0001). In the multivariate analysis, first-line haplo-HSCT was the favorable factor for FFS and HRQoL (P < 0.0001). These results suggest that first-line haplo-HSCT combined with UCB infusion might provide a better chance of success and HRQoL than first-line IST for SAA patients.
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10.
Combination of haploidentical haematopoietic stem cell transplantation with an unrelated cord-blood unit in patients with severe aplastic anemia: a report of 146 cases
Liu, L., Zhang, Y., Jiao, W., Zhou, H., Wang, Q., Qiu, H., Tang, X., Han, Y., Fu, C., Jin, Z., et al
Bone marrow transplantation. 2020
Abstract
We analyzed the outcomes of 146 severe aplastic anemia (SAA) patients who received a combination of haploidentical haematopoietic stem cell transplantation (haplo-HSCT) and an unrelated cord-blood (UCB) unit between September 2011 and December 2017. One hundred and seventeen patients underwent transplantation as first-line therapy. Seven patients experienced early mortality, and among the evaluable 139 patients, one patient experienced primary graft failure (GF), while the other 138 patients achieved successful haploidentical donor engraftment; additionally, three patients experienced secondary GF. Six patients demonstrated delayed platelet recovery, and three patients demonstrated platelet GF. The median time for myeloid and platelet engraftment was 11 (range: 9-28) days and 15 (range: 9-330) days, respectively. With a median follow-up of 40 (range: 18-93) months, the cumulative incidences were 31.43% and 10.00% for grades II-IV and grades III-IV acute graft-versus-host disease (GVHD), respectively. The cumulative incidences of chronic GVHD (cGVHD) and moderate-severe cGVHD were 36.23% and 11.71%, respectively. There was no patient relapse. The probabilities of 4-year overall survival and GVHD-free, failure-free survival were 81.4 +/- 3.3% and 69.2 +/- 3.9%, respectively. These encouraging preliminary results indicated that haplo-HSCT combined with the infusion of UCB is a feasible choice for SAA patients without matched donors.