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1.
Bone marrow graft versus peripheral blood graft in haploidentical hematopoietic stem cells transplantation: a retrospective analysis in1344 patients of SFGM-TC registry
Lacan, C., Lambert, J., Forcade, E., Robin, M., Chevallier, P., Loron, S., Bulabois, CÉ, Orvain, C., Ceballos, P., Daguindau, E., et al
Journal of hematology & oncology. 2024;17(1):2
Abstract
The use of peripheral blood (PB) or bone marrow (BM) stem cells graft in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis remains controversial. Moreover, the value of adding anti-thymoglobulin (ATG) to PTCy is unknown. A total of 1344 adult patients received an unmanipulated haploidentical transplant at 37 centers from 2012 to 2019 for hematologic malignancy. We compared the outcomes of patients according to the type of graft, using a propensity score analysis. In total population, grade II-IV and III-IV acute GVHD (aGVHD) were lower with BM than with PB. Grade III-IV aGVHD was lower with BM than with PB + ATG. All outcomes were similar in PB and PB + ATG groups. Then, in total population, adding ATG does not benefit the procedure. In acute leukemia, myelodysplastic syndrome and myeloproliferative syndrome (AL-MDS-MPS) subgroup receiving non-myeloablative conditioning, risk of relapse was twice greater with BM than with PB (51 vs. 22%, respectively). Conversely, risk of aGVHD was greater with PB (38% for aGVHD II-IV; 16% for aGVHD III-IV) than with BM (28% for aGVHD II-IV; 8% for aGVHD III-IV). In this subgroup with intensified conditioning regimen, risk of relapse became similar with PB and BM but risk of aGVHD III-IV remained higher with PB than with BM graft (HR = 2.0; range [1.17-3.43], p = 0.012).
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2.
Non-T-depleted haploidentical transplantation with post-transplant cyclophosphamide in patients with secondary versus de novo AML in first complete remission: a study from the ALWP/EBMT
Nagler, A., Labopin, M., Blaise, D., Raiola, A. M., Corral, L. L., Bramanti, S., Sica, S., Kwon, M., Koc, Y., Pavlu, J., et al
Journal of hematology & oncology. 2023;16(1):58
Abstract
We compared outcomes of adult patients with secondary acute myeloid leukemia (sAML) versus de novo AML after non-T-depleted haploidentical stem cell transplant (HaploSCT) with post-transplant cyclophosphamide (PTCy). Seventeen hundred and eleven AML patients (sAML-231, de novo-1480) in first complete remission transplanted from 2010 to 2021, were included. Patients with de novo AML were younger, median age 55.8 versus 60.8 years, p < 0.0001, had better transplantation comorbidity index (HCT-CI) ≥ 3 21.3% versus 40.8%, p < 0.0001 and Karnofsky performance status (KPS) with KPS ≥ 90 in 78% versus 68.5%, respectively, p = 0.002. The two patient groups did not differ with respect to gender, cytomegalovirus serostatus, and cell source. Median time from diagnosis to HaploSCT was 5.2 versus 4.9 months, respectively, p = 0.005. Fewer sAML patients received myeloablative conditioning 35.1% versus 50.1%, p < 0.0001. Two hundred and eleven sAML and 410 de novo AML patients were included in the matched-pair analysis matching two de novo AML with each sAML. No significant difference was observed in any transplantation outcome parameter between the sAML versus de novo AML groups. Two-year non-relapse mortality and relapse incidence did not differ with HaploSCT for de novo versus sAML; 21.4% versus 21%, hazard ratio (HR) = 0.98, p = 0.9 and 23.4% versus 20.6%, HR = 0.92, p = 0.67, respectively. Two-year leukemia-free survival, overall survival, and graft-versus-host disease (GVHD)-free, relapse-free survival were also not different between the de novo AML and sAML groups 55.2% versus 58.4%, HR = 0.95, p = 0.67; 61.4% versus 66.4%, HR = 0.91, p = 0.51 and 46.3% versus 48.2%, HR = 0.92, p = 0.48, respectively. Similarly, the incidence of engraftment as well as acute and chronic GVHD was similar between the 2 cohorts. In conclusion, HaploSCT with PTCy may be able to overcome the bad prognosis of sAML as results are not significantly different to those of HaploSCT in de novo AML.
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3.
Incidence and impact of fungal infections in post-transplant Cyclophosphamide (PTCy)-based graft-versus-host disease prophylaxis and haploidentical hematopoietic cell transplantation: A CIBMTR analysis
Papanicolaou, G. A., Chen, M., He, N., Martens, M. J., Kim, S., Batista, M. V., Bhatt, N. S., Hematti, P., Hill, J. A., Liu, H., et al
Transplantation and cellular therapy. 2023
Abstract
BACKGROUND Fungal infections (FI) after allogeneic hematopoietic cell transplant (HCT) are associated with increased morbidity and mortality. Neutropenia, HLA mismatch, graft versus host disease (GVHD), and viral infections are risk factors for FI. OBJECTIVES The objectives of this CIBMTR registry study were to compare the incidence and density of FI occurring within 180 days after HCT in matched sibling (Sib) transplants receiving either calcineurin inhibitor (CNI)-based or PTCy-based GVHD prophylaxis and related haploidentical transplants receiving PTCy, and to examine the impact of FI by day 180 on transplant outcomes. STUDY DESIGN Patients who received their first HCT between 2012 and 2017 for acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndromes and received related haploidentical transplant with PTCy (HaploCy, N = 757) or Sib transplant with PTCy (SibCy, N = 403) or CNI (SibCNI, N = 1605) were analyzed. The incidence of FI by day 180 post-HCT was calculated as a cumulative incidence with death as the competing risk. The association of FI on overall survival (OS), non-relapse mortality (NRM), chronic GVHD, and relapse at 2 years post HCT were examined in Cox proportional hazards regression models. Factors significantly associated with the outcome variable at a 1% level were kept in the final model. RESULTS By Day 180 post HCT, 56 (7%) HaploCy, 24 (6%), SibCy, and 59 (4%) SibCNI developed ≥1 FI (<0.001). The cumulative incidence (99% confidence interval) of yeast FI was 5.2% (3.3-7.3), 2.2% (0.7-4.5), and 1.9% (1.1-2.9) (p=.001), and mold FI was 2.9% (1.5-4.7). 3.7% (91.7-6.6) and 1.7% (1.0-2.6) (p=0.040) for HaploCy, SibCy, and SibCNI, respectively. FI were associated with an increased risk of death with an adjusted hazard ratio [HR] (99% confidence interval) of 4.06 (2.2-7.6); 4.7(2.0-11.0) and 3.4 (1.8-6.4) for HaploCy; SibCy and SibCNI compared with SibCNI without FI, respectively (p<.0001; for all). Similar associations were noted for transplant-related mortality. FI did not impact relapse or chronic GVHD. CONCLUSIONS Rates of FI by Day 180 ranged between 1.9-5.2% for yeast and 1.7%-3.7% for molds across the 3 cohorts. Use of PTCy was associated with higher rates of yeast infections only in Haplo HCT and mold infections in Haplo and Sib HCT. Presence of FI by Day 180 was associated with increased risk for overall mortality and transplant-related mortality at 2 years regardless of donor or PTCy. While rates of FI were low with PTCy, FI were associated with increased risk of death, underscoring the need for improved management strategies.
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4.
Second haploidentical stem cell transplantation (HAPLO-SCT2) after relapse from a first HAPLO-SCT in acute leukaemia-a study on behalf of the Acute Leukaemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT)
Filippini Velázquez, G., Labopin, M., Tischer, J., Raiola, A. M., Angelucci, E., Kulagin, A. D., Galieni, P., Bermúdez, A., Bulabois, C. E., Kröger, N., et al
Bone marrow transplantation. 2023
Abstract
For patients with acute myeloid and lymphoblastic leukaemia (AML/ALL) lacking a matched sibling or unrelated donor, haploidentical stem cell transplantation (HAPLO-SCT) is increasingly used. However, available data on the treatment of relapse after HAPLO-SCT, including feasibility and efficacy of a second HAPLO-SCT (HAPLO-SCT2), is scarce. Hence, adults with AML/ALL, that had undergone HAPLO-SCT2 without ex-vivo manipulation after haematologic relapse from HAPLO-SCT1 were selected for a retrospective registry analysis. Eighty-two patients (AML, n = 63, ALL, n = 19, median follow-up: 33 months) were identified. Engraftment rate was 87%. At day +180, cumulative incidences of acute GvHD II-IV°/chronic GvHD were 23.9%/22.6%, respectively. Two-year overall survival/leukaemia-free survival (OS/LFS) were 34.3%/25.4%; 2-year non-relapse mortality (NRM) and relapse incidence (RI) were 17.6% and 57%. Leukaemia was the most frequent cause of death. Separated by disease, 2-year OS/LFS/NRM/RI were 28.7%/22.3%/16.2%/61.6% in AML, and 55.3%/38.4%/23.5%/38.2% in ALL patients. In a risk-factor analysis among patients with AML, stage at HAPLO-SCT1 and HAPLO-SCT2, and interval from HAPLO-SCT1 to relapse significantly influenced outcome. Our data demonstrate that HAPLO-SCT2 is a viable option in acute leukaemia relapse after HAPLO-SCT1. Engraftment, toxicity, risk factors and long-term outcome are comparable to data reported after allo-SCT2 in a matched donor setting.
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5.
Expanding donor options: haploidentical transplant recipients also highly likely to have a 7/8 matched unrelated donor
Fingerson, S., Maiers, M., Bolon, Y. T., Devine, S. M., Spellman, S. R.
Blood advances. 2023
Abstract
The use of haploidentical related donor (HRD) hematopoietic cell transplants (HCT) in the United States (US) grew >4x in the last decade, driven mainly by use of post-transplant cyclophosphamide (PTCy) based graft-versus-host-disease prophylaxis. However, not all patients have a suitable HRD available. In this study, we explored the existence of unrelated donors (URDs) on the NMDP Registry at the 8/8 or 7/8 match level for patients receiving HRD HCT in the US and reported to the CIBMTR from 2013-2020. The data consists of 9696 HRD HCT recipients aged 0-87. The NMDP Search Prognosis score and a Search Simulation were run for each recipient to calculate estimated counts of 8/8 and 7/8 matches on the registry. NMDP search prognosis score varied by patient ancestry, with 27.5% non-Hispanic white HRD recipients having a good score compared to 4.6% of African-American recipients. Overall, 34% of recipients had ≥18/8 URD and 84% had ≥17/8 URD. Recipients of older HRDs (age >35) had between 20-65% likelihood of ≥5existing 7/8 URDs age ≤35. Donor selection practices varied among the 10 highest volume HRD centers, where 6 had >20% chance of an existing 8/8 URD for their HRD recipients whereas 4 had low likelihood of identifying an 8/8 URD. In conclusion, while most US patients undergoing HRD HCT do not have an existing 8/8 URD, the majority have an existing 7/8 URD. Studies comparing outcomes in patients receiving either HRD or 7/8 URD HCT and PTCy-based GVHD prophylaxis may be warranted.
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6.
Mild Acute Graft-Versus-Host Disease Improves Outcomes After HLA-Haploidentical-Related Donor Transplantation Using Posttransplant Cyclophosphamide and Cord Blood Transplantation
Wada, F., Kanda, J., Kamijo, K., Nishikubo, M., Yoshioka, S., Ishikawa, T., Ueda, Y., Akasaka, T., Arai, Y., Izumi, K., et al
Cell transplantation. 2023;32:9636897231194497
Abstract
Haploidentical-related donor transplantation using posttransplant cyclophosphamide (PTCy-haplo) and cord blood transplantation (CBT) are valid alternatives for patients with hematological malignancies when HLA-matched donor transplantation (MDT) is unavailable. However, the effects of graft-versus-host disease (GVHD) on outcomes after these transplants have not been fully elucidated. Therefore, we evaluated the effects of acute and chronic GVHD on transplant outcomes after PTCy-haplo transplants and compared them with CBT and MDT. We included a total of 914 adult patients with hematological malignancies in the Kyoto Stem Cell Transplantation Group registry who received PTCy-haplo (N = 120), CBT (N = 402), and MDT (N = 392), and achieved neutrophil engraftment. A multivariate analysis revealed that grade I-II acute GVHD improved of overall survival (OS) after PTCy-haplo [hazard ratio (HR) = 0.39, P = 0.018] and CBT (HR = 0.48, P < 0.001), but not after MDT (HR = 0.80, P = 0.267) compared with patients without acute GVHD. Grade I-II acute GVHD had a trend toward reducing the risk of nonrelapse mortality (NRM) after PTCy-haplo (HR = 0.13, P = 0.060) and this positive effect was significant after CBT (HR = 0.39, P = 0.003). A negative impact of grade III-IV acute GVHD on NRM was observed after CBT and MDT, but not after PTCy-haplo. Limited chronic GVHD had a positive impact on OS after CBT and MDT, but not after PTCy-haplo. In conclusion, mild acute GVHD improved outcomes after PTCy-haplo and CBT, and limited chronic GVHD improved outcomes after CBT and MDT. These data indicated that the effects of GVHD on transplant outcomes depended on transplant platforms.
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7.
Incidence of cutaneous graft-versus-host disease in a Singapore academic medical centre - A retrospective cohort study
Tan, W. H., Ho, A., Kadir, H. A., Zin, T. K., Jordan, H. C. C., Lee, H. Y., Pang, S. M., Yeo, Y. W., Choo, K. J. L., Oh, C. C.
The Australasian Journal of Dermatology. 2023;64(1):e26-e33
Abstract
BACKGROUND Cutaneous graft-versus-host disease (GVHD) is common in allogeneic haematopoietic stem cell transplantation. HLA mismatch is the most significant determinant of GVHD. Our study aimed to compare the incidence of cutaneous GVHD haploidentical (Haplo) and matched donors in an Asian population. METHODS Retrospective cohort study of the 2015-2019 bone marrow transplant registry was conducted in a transplant centre. We compared the incidence of cutaneous GVHD in Haplo with allogeneic matched unrelated donor (MUD) and matched-sibling donor (MSD) transplant recipients. Secondary objectives include acute and chronic GVHD incidence, dermatology referrals, and histological findings. RESULTS One hundred and seventy-nine out of 203 cases were reviewed; 17 (9.5%) Haplo, 80 (44.7%) MUDs and 82 (45.8%) MSDs. The median follow-up for Haplo, MUD and MSD was 15.2, 34.2 and 35.7 months, respectively. Haplo had a higher cumulative incidence of cutaneous GVHD than MUD and MSD (p = 0.053). Chronic GVHD was only reported in MSD. The most common histology was vacuolar interface changes (13 [44.8%]) with a wide range of onset post-transplant (19-456 days). CONCLUSIONS Haplo donors may have a higher GVHD incidence than MUD and MSD in our predominantly Asian cohort. This information may be helpful when counselling patients pre-transplant. Further prospective studies are required.
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8.
Peripheral Blood Haploidentical Allogeneic Stem Cell Transplantation in Older Adults with Acute Myeloid Leukemia and Myelodysplastic Syndromes Demonstrates Long Term Survival, Results from the Australasian Bone Marrow Transplant Recipient Registry
Abadir, E., Othman, J., Kwan, J., Gottlieb, D. J., Kennedy, G. A., Bajel, A., Doocey, R., Perera, T., Watson, A. M., Bardy, P. G., et al
Transplantation and cellular therapy. 2023
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Editor's Choice
Abstract
BACKGROUND There is a limited body of evidence for Haploidentical Hematopoietic Stem Cell Transplantation (Haplo-HSCT) in older patients. Previous studies have used a high proportion of bone marrow derived grafts and a variety of conditioning regimens. In Australia and New Zealand, Haplo-HCST is predominantly performed using peripheral blood (PB) with universal use of post-transplant cyclophosphamide (PTCy). OBJECTIVE To characterize the outcomes of older recipients undergoing Haplo-HSCT for Acute Myeloid Leukaemia (AML) and Myelodysplastic Syndromes (MDS). STUDY DESIGN Data was collected through the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) for patients aged 65 or older receiving a PB Haplo-HSCT for AML/MDS between January 2010 and July 2020 Results: A total of 44 patients were included in the analysis. The median follow-up time was 377 days. The median age was 68 (range 65-74) with a median Karnofsky Performance Status of 90. Thirty patients (68.2%) had AML while 14 (31.8%) had MDS. The median donor age was 40. The most common conditioning regimen was non-myeloablative fludarabine, cyclophosphamide and TBI (75%), the remainder of the patients received either melphalan or busulfan based regimens, the majority were reduced intensity with only 2 patients undergoing myeloablative conditioning. All patients received post-transplant cyclophosphamide and mycophenolate mofetil with the majority also receiving tacrolimus (90.5%) and the remainder receiving cyclosporin (9.5%). No patients received anti-thymocyte globulin. Neutrophil engraftment was achieved in 97.6% of patients, at a median of 18 days while platelet engraftment was achieved in 92.7% of patients at a median of 28 days. The cumulative incidences of CMV reactivation and CMV disease were 52.5% and 5.1% at 1 year. The incidence of grade 2-4 acute Graft Versus Host Disease (GVHD) was 18.2%. The incidence of chronic GVHD at 2 years was 40.7%, with extensive chronic GVHD occurring in 17.7% of patients. The incidences of relapse and non-relapse mortality (NRM) at 2 years were 8.8% and 20.7% respectively. The leading causes of death were infection (64.7%) followed by relapse (14.2%). The 2-year overall survival was 74%. Relapse free survival and GVHD free, relapse free survival at 2 years was 70% and 48%. CONCLUSION Haplo-HSCT using a peripheral blood graft and PTCy GVHD prophylaxis demonstrates long-term disease control with acceptable rates of NRM for older patients with AML/MDS.
PICO Summary
Population
Adults aged 65 years and older with acute myeloid leukaemia or myelodysplastic syndrome, and reported to the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) (n=44)
Intervention
Peripheral blood haploidentical transplant between January 2010 and July 2020
Comparison
None
Outcome
Neutrophil engraftment was achieved in 97.6% of patients, at a median of 18 days while platelet engraftment was achieved in 92.7% of patients at a median of 28 days. The cumulative incidences of CMV reactivation and CMV disease were 52.5% and 5.1% at 1 year. The incidence of grade 2-4 acute Graft Versus Host Disease (GVHD) was 18.2%. The incidence of chronic GVHD at 2 years was 40.7%, with extensive chronic GVHD occurring in 17.7% of patients. The incidences of relapse and non-relapse mortality (NRM) at 2 years were 8.8% and 20.7% respectively. The leading causes of death were infection (64.7%) followed by relapse (14.2%). The 2-year overall survival was 74%. Relapse free survival and GVHD free, relapse free survival at 2 years was 70% and 48%.
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9.
Similar outcomes following non-first-degree and first-degree related donor haploidentical hematopoietic cell transplantation for acute leukemia patients in complete remission: a study from the Global Committee and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
Ye, Y., Labopin, M., Chen, J., Gulbas, Z., Zhang, X., Koc, Y., Blaise, D., Ciceri, F., Polge, E., Houhou, M., et al
Journal of Hematology & Oncology. 2023;16(1):25
Abstract
There are situations where non-first-degree (NFD) related donors have to be considered as alternatives to first-degree (FD) related donors for haploidentical hematopoietic cell transplantation (HAPLO). However, the efficacy of these NFD related transplants remains uncertain. All consecutive adult patients (≥ 18 years) with acute myelogenous leukemia (AML) or acute lymphocytic leukemia (ALL) in CR who underwent a first HAPLO between 2010 and 2021 in the European Society for Blood and Marrow Transplantation (EBMT) registry were analyzed. Exact matching and propensity score matching was used. The NFD-to-FD ratio was 1:3. 2703 patients (AML: n = 2047; ALL: n = 656) in CR received a first HAPLO from either NFD (n = 154) or FD (n = 2549) related donors in 177 EBMT centers. 123 NFD and 324 FD HAPLO were included for analysis after matching. Median patient age was 35.6 and 37.2 for the NFD and FD cohorts, respectively. Both cohorts reached good engraftment rates (NFD: 95.7% vs. FD, 95.6%; p = 0.78). The 2-year relapse incidence (NFD, 21.1% vs. FD, 22.6%; p = 0.84) and non-relapse mortality (NRM) (NFD, 13.2% vs. FD, 17.7%; p = 0.33) were not significantly different. The 2-year overall survival (OS) (NFD, 71.8% vs. FD, 68.3%; p = 0.56), leukemia-free survival (LFS) (NFD, 65.7% vs. FD, 59.7%; p = 0.6) and graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) (NFD, 50.9% vs. FD, 47.8%; p = 0.69) also showed no significant differences. The two cohorts showed no difference in terms of cumulative day 180 grade II-IV, grade III-IV acute GVHD, 2-year cumulative incidences of chronic and extensive chronic GVHD. For HAPLO in patients with acute leukemia, NFD related donors could be equivalent substitutions when FD related donors are not available.
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10.
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.