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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.
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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3.
Feasibility of thoracic CT in assessing anemia for aplastic anemia patients undergoing allogeneic hematopoietic stem cell transplantation
Chen, D., Guo, Y., Liu, W., Yuan, Z., Mo, W., Wei, X.
Journal of X-ray science and technology. 2023;31(1):199-209
Abstract
BACKGROUND Anemia is an important clinical symptom for aplastic anemia (AA) patients who are suffered with peripheral pancytopenia. OBJECTIVE To evaluate the accuracy of diagnosing anemia with non-invasive chest computed tomography (CT) for AA patients. METHODS The CT attenuation of left ventricular (LV) cavity and interventricular septum (IVS) on unenhanced thoracic CT images of AA patients are retrospectively analyzed, including 84 AA patients in pre-transplant and 1-month (n = 82), 2-month (n = 72), 3-month (n = 75), 6-month (n = 74) and 12-month (n = 70) followed patients in post-transplant. The difference (IVS-LV) and ratio (LV/IVS) of the CT attenuation between LV cavity and interventricular septum are calculated. Serum hemoglobin is estimated within 24 hours of CT imaging. The CT attenuations of IVS-LV and LV/IVS are correlated with hemoglobin, and their variation tendency is analyzed during the treatment of a-HSCT. A receiver operating characteristic (ROC) curve analysis is then performed for the diagnosis of anemia. RESULTS The CT attenuations of IVS-LV and LV/IVS well correlate with hemoglobin (r = -0.618 and 0.628, respectively, P < 0.001). The variation tendency of IVS-LV and LV/IVS is similar to that of hemoglobin with opposite directions during one-year follow-up of a-HSCT. When a threshold of CT attenuation of IVS-LV and LV/IVS is set at 11.5HU and 0.77, respectively, both the sensitivity and specificity in diagnosing anemia are good (74.7% and 73.8% in CT attenuation of IVS-LV; 77.4% and 70.4% in LV/LVS, respectively). CONCLUSIONS Both CT attenuation of LV/IVS and IVS-LV had similar accuracy in diagnosing anemia for AA patients. The non-invasive chest CT can offer a new possibility to complementarily evaluate anemia for AA patients in the diagnostic radiology reports.
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4.
Incidence and risk factors for secondary graft failure in uniformly treated patients with severe aplastic anemia receiving fludarabine and cyclophosphamide for conditioning and matched sibling bone marrow graft as stem cell source
Kotb, A., Alzahrani, H., Alahmari, A., Syed Osman, Ahmed, Alhayli, S., Shaheen, M., Chaudhri, N., Alsharif, F., Hanbali, A., Alfraih, F., et al
Cytotherapy. 2023
Abstract
BACKGROUND AIMS Graft failure after allogeneic transplant for aplastic anemia is problematic. The risk of graft failure depends on multiple variables, including the preparative regimen, donor type, stem cell dose and source among other variables. METHODS We performed a retrospective analysis of patients with aplastic anemia who underwent matched-sibling allogeneic transplant at a single center. RESULTS We identified 82 patients who fit the inclusion criteria. One had primary graft failure and was excluded from this analysis. The recipient median age was 22 years. The donor median age was 23 years. The median time from diagnosis to transplant was 1.6 months. The median number of red cell transfusions before transplant was nine. The median number of platelet transfusions before transplant was 18. Thirteen patients developed secondary graft failure, with a cumulative incidence at 5 years of 16% and median time to develop secondary graft failure of 129 days. All patients engrafted with a median time for neutrophil engraftment of 19 days and a median time for platelet engraftment of 22 days. The survival of patients with or without secondary graft failure was not different. Major or bidirectional ABO incompatibility and older recipient age were statistically significantly associated with greater risk of secondary graft failure. CONCLUSIONS Secondary graft failure is a significant complication after allogeneic transplant for SAA. Identification of recipients at risk and mitigating the potential risks of this complication is warranted.
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5.
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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6.
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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7.
Prognostic Impact of Quantifying Sarcopenia and Adipopenia by Chest CT in Severe Aplastic Anemia Patients Treated With Allogeneic Hematopoietic Stem Cell Transplantation
Chen, D., Yuan, Z., Guo, Y., Mo, W., Liu, W., Liang, D., Chen, A., Zhang, Y., Zhang, N., Wei, X.
Academic radiology. 2022
Abstract
RATIONALE AND OBJECTIVES To investigate the prognostic role of chest CT-defined sarcopenia and adipopenia in severe aplastic anemia (SAA) patients treated with hematopoietic stem cell transplantation (HSCT). MATERIALS AND METHODS This was a retrospective study of 123 consecutive SAA patients treated with HSCT. CT imaging was performed to quantify the pectoralis muscle (including major and minor) index (PMI) and the corresponding subcutaneous adipose tissue index (SAI). Sarcopenia and adipopenia were defined as PMI and SAI lower than the respective sex-specific medians. Correlations of the PMI and SAI with anthropometric indexes were calculated. Transplant-related outcomes were compared between the sarcopenia and adipopenia groups. Prognostic factors for overall survival (OS) and fail-free survival (FFS) were identified by Cox regression and were used to create a nomogram. The accuracy of the nomogram was evaluated by ROC curves. RESULTS PMI showed good correlation with BMI and fat-free mass index (p < 0.001). SAI correlated with BMI and fat mass index (p < 0.001). The sarcopenia group (47.2%) had a significantly worse 3-year OS (90.8% vs. 77.6%, p = 0.045) and 3-year FFS (89.2% vs. 74.1%, p = 0.035) than the nonsarcopenia group. Sarcopenia status and diagnostic category were used to construct the nomogram of OS, as these were independent prognostic factors in the multivariate analysis for OS and FFS (p < 0.05). The area under the curve of the nomogram at one year and three years was 0.801 and 0.721, respectively. CONCLUSION Sarcopenia indicates a poor prognosis in SAA patients undergoing HSCT. Intensive supportive care is suggested for SAA patients with sarcopenia before transplantation.
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8.
The Incidence, Outcomes, and Risk Factors of Secondary Poor Graft Function in Haploidentical Hematopoietic Stem Cell Transplantation for Acquired Aplastic Anemia
Lin, F., Han, T., Zhang, Y., Cheng, Y., Xu, Z., Mo, X., Wang, F., Yan, C., Sun, Y., Wang, J., et al
Frontiers in immunology. 2022;13:896034
Abstract
Secondary poor graft function (sPGF) increases the risk of life-threatening complications after hematopoietic stem cell transplantation (HSCT). The incidence, clinical outcomes, and risk factors of sPGF have not been elucidated in haploidentical (haplo-) HSCT for acquired aplastic anemia (AA) patients. We retrospectively reviewed 423 consecutive AA patients who underwent haplo-HSCT between January 2006 and December 2020 and report a 3-year cumulative incidence of 4.62% (95% confidence interval [CI]: 3.92%-10.23%) of sPGF. While no primary PGF occurred. The median time to sPGF was 121 days (range 30-626 days) after transplantation. To clarify the risk factors for sPGF, 17 sPGF cases and 382 without PGF were further analyzed. Compared to patients without PGF, the 2-year overall survival was significantly poorer for sPGF patients (67.7% vs 90.8%, p =.002). Twelve sPGF patients were alive until the last follow-up, and 7 achieved transfusion independency. The multivariable analyses revealed that later neutrophil engraftment (OR 2.819, p=.049) and a history of refractory cytomegalovirus viremia (OR=7.038, p=.002) post-transplantation were associated with sPGF. There was weak evidence that a history of grade 3-4 acute graft-versus-host disease increased the risk of sPGF (p=.063). We advocated better post-transplantation strategies to balance the risk of immunosuppression and viral reactivation for haplo-HSCT in AA patients.
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9.
The impact of pre-transplant serum ferritin on haploidentical hematopoietic stem cell transplant for acquired severe aplastic anemia in children and adolescents
Lin, F., Zuo, Y., Zhang, Y., Cheng, Y., Han, T., Mo, X., Suo, P., Sun, Y., Tang, F., Wang, F., et al
Pediatric blood & cancer. 2022;:e29845
Abstract
Haploidentical hematopoietic stem cell transplant (haplo-HSCT) provides an important alternative for children and adolescents with acquired severe aplastic anemia (SAA) lacking of matched donors. To test whether pre-transplant serum ferritin (SF) represents a candidate predictor for survival and a potential biomarker for graft-versus-host disease (GvHD) in pediatric haplo-HSCT, we retrospectively evaluated 147 eligible patients with SAA who underwent haplo-HSCT. The patients were divided into the low-SF group (< 1000 ng/ml) and the high-SF group (≥ 1000 ng/ml). We found that SF ≥1000 ng/ml independently increased the risk of grade II-IV aGvHD (HR = 2.596, 95% CI 1.304-5.167, p = .007) and grade III-IV aGvHD (HR = 3.350, 95% CI 1.162-9.658, p = .025). Similar probabilities of transplant-related mortality at 100 days were observed in the two groups (6.19 ± 2.45% vs 8.00 ± 3.84%, p = .168). The 2-year overall survival (85.29 ± 3.89% vs 92.00 ±3.84%, p = .746) and failure-free survival (83.23% ± 4.08% vs 83.37 ± 6.27%, p = .915) were comparable. GvHD-/failure-free survival were 60.06 ± 5.10% and 75.56 ± 6.87%, respectively (p = .056). In conclusion, the elevated pre-transplant SF level is associated with higher incidences of grade II-IV aGvHD and grade III-IV aGvHD. However, it is not associated with worse survival after haplo-HSCT for children and adolescent patients with SAA. This article is protected by copyright. All rights reserved.
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10.
Comparable clinical outcomes of haploidentical hematopoietic stem cell transplantation in patients with hepatitis-associated aplastic anemia and non-hepatitis-associated aplastic anemia
Ma, X., Zuo, Y., Xu, Z., Zhang, Y., Cheng, Y., Han, T., Suo, P., Sun, Y., Tang, F., Wang, F., et al
Annals of hematology. 2022
Abstract
Hepatitis-associated aplastic anemia (HAAA), a rare subtype of aplastic anemia (AA), is defined as bone marrow failure occurring after acute hepatitis. Severe HAAA requires immunosuppressive therapy (IST) or hematopoietic stem cell transplantation (HSCT) as lifesaving treatment. The outcomes of HAAA patients who underwent haploidentical hematopoietic stem cell transplantation (haplo-HSCT) have not been systematically evaluated. We retrospectively compared the characteristics of 15 patients with HAAA and 60 non-hepatitis-associated aplastic anemia (non-HAAA) patients, all 75 of whom underwent haplo-HSCT in our hospital between January 2006 and October 2021. The median ages of the patients were 18 years old (range, 3-36) for HAAA patients and 13 years (range, 2-45) for non-HAAA patients (p = 0.693). The median time for neutrophil engraftment was 14 days (range, 11-22) in the HAAA group and 12 days (range, 10-21) in the non-HAAA group (p = 0.363). At the time of analysis, 15 HAAA patients and 58 non-HAAA patients were alive, and their median follow-up times were 37 (range, 3-87) months and 31 (range, 2-110) months (p = 0.347), respectively. There were no significant differences in the three-year overall survival (OS) rates (100% vs. 96.7 ± 0.33%, P = 0.638) or liver event-free survival (LEFS) (80.0 ± 0.17% vs. 76.7 ± 0.19%, P = 0.747) between the two groups. Despite the small number of HAAA patients due to the rarity of the disease, these results, such as the similar incidence rates of 3-year OS and fewer liver events than expected, suggest that haplo-HSCT is a feasible treatment for HAAA a when there are no human leukocyte antigen (HLA)-matched donors available and has a low risk of transplant-related mortality and complications.