GVHD And Relapse-free Survival Research Articles

CAST Regimen for GvHD Prophylaxis: A CIBMTR Propensity Score-Matched Analysis

Previously, we reported excellent results with the combination of post-transplant cyclophosphamide (PTCy), abatacept, and a short course of tacrolimus (CAST) for the prevention of graft-versus-host disease (GvHD) following peripheral blood haploidentical transplantation. To further substantiate these results, we performed a propensity score-matched analysis. Patients enrolled in the CAST trial were matched with patients from a contemporaneous cohort from the Center for International Blood and Marrow Transplant Research database who received PTCy, tacrolimus, and mycophenolate mofetil, using nearest neighbor propensity score matching. An excellent balance between pairs was achieved as measured by the density distribution and standardized differences of covariates (median 0.09). The rates of acute GvHD grades II to IV at day +120 and 1-year GvHD- and relapse-free survival were 16.7% and 66.7% in the CAST cohort versus 28.6% and 47.6% in the control group, respectively. This trend did not reach statistical significance (P = .14 and .07), possibly due to the small numbers of patients and events. On the other hand, CAST was associated with a statistically significant reduction in the incidence of relapse (9.5% versus 26.2%, P = .045) with improved disease-free survival (85.7% versus 61.9%, P = .01). Our data provides a strong impetus to examine CAST in a randomized clinical trial.

Post-transplantation cyclophosphamide and cyclosporine A versus methotrexate and cyclosporine A for graft-versus-host disease prophylaxis after allogeneic peripheral stem cell transplantation in adult acute myeloid leukemia patients

BackgroundDifferent prophylactic protocols are available for preventing graft-versus-host disease (GVHD) after matched sibling donor (MSD) allogeneic hematopoietic cell transplantation (allo-HCT). This study aimed to compare the effectiveness of post-transplantation cyclophosphamide plus cyclosporine A (PT-CY/CSA) versus methotrexate plus CSA (MTX/CSA) as GVHD prophylaxis protocols in adult acute myeloid leukemia (AML) patients who received peripheral blood stem cells (PBSC) from fully matched donors. MethodsThe 1-year outcomes of 89 patients treated with PT-CY/CSA and 90 patients treated with MTX/CSA who had MSD allo-HCT for AML using unmanipulated mobilized PBSC were examined and compared. ResultsThe cumulative incidence of acute GVHD at 100 days was considerably lower in the PT-CY/CSA group (4% vs 19.3%, p = 0.002), however there were no statistically significant difference in the cumulative incidence of chronic GVHD at 1-year (19.6% vs 37.4%, p = 0.053). Significant delays in neutrophil and platelet engraftments were reported in the PT-CY/CSA group (17 vs 12 days) and (13 vs 12 days), respectively (p < 0.001). The cumulative incidences of relapse (19.1% vs 13.7%, p = 0.470), overall survival (79.1% vs 77.3%, p = 0.986), non-relapse mortality (16.5% vs 16.8%, p = 0.837), and the GVHD and relapse-free survival (GRFS) (53.7% vs 46.6%, p = 0.478) did not differ statistically at 1-year. ConclusionPT-CY/CSA demonstrated a significant decrease in the rate of acute GVHD. However, it was associated with engraftment delay.

Impact of the Type of Tyrosine Kinase Inhibitor (imatinib or dasatinib) Used Before allo-HCT on Outcome of Patients with Philadelphia-Positive Acute Lymphoblastic Leukemia. A Study on Behalf of the Acute Leukemia Working Party of the EBMT

The use of tyrosine kinase inhibitors (TKIs) during induction and consolidation, followed by allogeneic hematopoietic cell transplantation (allo-HCT), is a standard of care for patients with Philadelphia (Ph)-positive acute lymphoblastic leukemia (ALL). The goal of this study was to compare results of allo-HCT according to the type of TKI used pre-transplant, either imatinib, dasatinib or both. This was a retrospective, registry-based analysis including adult patients with Ph-positive ALL treated with allo-HCT between years 2010-2022. The analysis included 606 patients pre-treated with imatinib, 163 with dasatinib and 94 with both imatinib and dasatinib. Allo-HCTs were performed in first complete remission from either unrelated (56%), matched sibling (36%) or haploidentical donors (8%). Relapse incidence at 2 years was 26% in the imatinib group and 21% in the dasatinib group and 19% in the imatinib + dasatinib group (P = .06) while non-relapse mortality was 19%, 15%, and 23%, respectively (P = .37). No significant differences were found for leukemia-free survival (55% vs. 63% vs. 58%, P = .11) and overall survival (72% vs. 76% vs. 65%, P = .32). The incidence of grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD was comparable across study groups, while the incidence of grade 3-4 acute GVHD was significantly increased for patients pre-treated with dasatinib alone (20%) than in the imatinib group (10%) or imatinib + dasatinib group (13%) (P = .002). On multivariate analysis a chance of GVHD and relapse-free survival (GRFS) was significantly decreased while the risk of grade 3-4 acute GVHD was increased for the dasatinib compared to imatinib group (hazard ratio, HR = 1.27, P = .048 and HR = 2.26, P = .0009, respectively). This study provides no evidence for the advantage of one TKI over another in terms of LFS and OS. However, the use of dasatinib is associated with increased risk of severe acute GVHD and decreased GRFS.

The impact of MICB mismatches in unrelated haematopoietic stem cell transplantation.

MICA polymorphisms have been associated with increased incidence of acute GvHD and adverse outcome in allogeneic haematopoietic stem cell transplantation (HSCT). MICB is another expressed member of MHC class I-related chain genes and its impact on HSCT outcome is yet to be fully defined. We typed a large cohort of patients and donors for MICB polymorphisms and investigated the impact of MICB matching on outcome after unrelated HSCT. 69.2% of the patients were 10/10 human leukocyte antigen (HLA) matched and 30.8% were 9/10 HLA matched. MICB typing was performed using a short amplicon-based NGS typing assay on the Illumina MiSeq platform. Differences in proteins were considered as mismatches. MICA polymorphisms were identified as possible confounder and were therefore included as parameter in the multivariate analyses. Due to the strong linkage disequilibrium with the classical HLA-genes, sub-stratification for HLA matching status was necessary, and no effect of MICB mismatches was seen in the 10/10 HLA matched group when compared to the MICB matched cases. However, in the 9/10 HLA matched group, MICB mismatched cases showed significantly worse disease free survival (DFS), GvHD and relapse free survival (GRFS) compared to the MICB matched cases (DFS: HR 1.24, p = 0.011; GRFS: HR 1.26, p = 0.002). MICA mismatches had no impact on any outcome parameter. According to our findings, effects previously attributed to MICA differences may have been confounded by MICB polymorphisms. We show that MICB differences contribute a small but relevant effect in 9/10 HLA-matched transplantations, which in turn highlights the possible usefulness of MICB typing in donor selection among similarly suitable 9/10 matched donors, especially when HLA-B mismatches have to be accepted.

Prognostic impact of the conditioning intensity on outcomes after allogeneic transplantation for MDS with low blasts: a nationwide retrospective study by the adult MDS working group of the Japan Society for Transplantation and Cellular Therapy.

Poor prognostic factors, such as transfusion dependency and chromosomal risk, need to be considered in the indication of allogeneic hematopoietic cell transplantation (allo-HCT) for patients harboring myelodysplastic syndromes with less than 5% marrow blasts (MDS-Lo). We analyzed the post-transplant outcomes of 1229 MDS-Lo patients who received myeloablative (MAC)(n = 651), reduced-intensity (RIC)(n = 397), and non-myeloablative conditioning (NMAC) regimens (n = 181). The multivariate analysis revealed that the RIC group had better chronic graft-versus-host disease (GVHD)- and relapse-free survival (CRFS) (P = 0.021), and GVHD- and relapse-free survival (GRFS) than the MAC group (P = 0.001), while no significant differences were observed between the NMAC and MAC groups. In the subgroup analysis, the MAC group has better overall survival (P = 0.008) than the RIC group among patients with an HCT-comorbidity index (HCT-CI) score of 0, while the RIC group had better overall survival (P = 0.029) than the MAC group among those with an HCT-CI score ≥3. According to the type of conditioning regimen, total body irradiation 12 Gy-based MAC regimen showed better OS and CRFS than the other MAC regimen, and comparable outcomes to the RIC regimen. In conclusion, the RIC and NMAC regimens are promising options for MDS-Lo patients in addition to the MAC regimen.

Alternative donor transplantation for severe aplastic anemia: a comparative study of the SAAWP EBMT

AbstractSelecting the most suitable alternative donor becomes challenging in severe aplastic anemia (SAA) when a matched sibling donor (MSD) is unavailable. We compared outcomes in patients with SAA undergoing stem cell transplantation (SCT) from matched unrelated donors (MUD) (n = 1106), mismatched unrelated donors (MMUD) (n = 340), and haploidentical donors (Haplo) (n = 206) registered in the European Society for Blood and Marrow Transplantation database (2012-2021). For Haplo SCT, only those receiving posttransplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis were included. Median age was 20 years, and the median time from diagnosis to transplantation 8.7 months. Compared with MUD, MMUD (hazard ratio [HR], 2.93; 95% confidence interval [CI], 1.52-5.6) and Haplo (HR, 5.15; 95% CI, 2.5-10.58) showed significantly higher risks of primary graft failure. MUD had lower rates of acute GVHD compared with MMUD and Haplo (grade 2-4: 13%, 22%, and 19%, respectively; P < .001; grade 3-4: 5%, 9%, and 7%, respectively; P = .028). The 3-year nonrelapse mortality rate was 14% for MUD, 19% for MMUD, and 27% for Haplo (P < .001), whereas overall survival and GVHD and relapse-free survival (GRFS) rates were 81% and 73% for MUD, 74% and 65% for MMUD, and 63% and 54% for Haplo, respectively (P < .001). In addition to donor type, multivariable analysis identified other factors associated with GRFS such as patient age, performance status, and interval between diagnosis and transplantation. For patients with SAA lacking an MSD, our findings support MUDs as the preferable alternative donor option. However, selecting between an MMUD and Haplo donor remains uncertain and requires further exploration.

Pretransplant Blinatumomab Improves Outcomes in B Cell Acute Lymphoblastic Leukemia Patients Who Undergo Allogeneic Hematopoietic Cell Transplantation

BackgroundBlinatumomab, a bispecific monoclonal antibody, effectively controls refractory B cell acute lymphoblastic leukemia (ALL) and promotes measurable residual disease (MRD) negativity. This study investigated the impact of pretransplant blinatumomab on allogeneic hematopoietic cell transplantation (HCT) outcomes in B cell ALL patients. MethodsWe analyzed the effect of pretransplant blinatumomab on transplant outcomes of 117 adults undergoing allogeneic HCT for B cell ALL at Princess Margaret Hospital, Toronto, between 2010 and 2021. Outcomes assessed included overall survival (OS), graft-versus-host disease and relapse-free survival (GRFS), cumulative incidences of relapse (CIR), and nonrelapse mortality (NRM). ResultsThe median follow-up was 36 months. Thirty-one participants (26.5%) received blinatumomab. Blinatumomab group had higher proportions of individuals with high disease risk index, primary induction failure and was more likely to receive dual T cell depletion with antithymocyte globulin and post-transplant cyclophosphamide. Two-year OS, GRFS, NRM, and CIR in the blinatumomab and nonblinatumomab groups were, respectively: 65.4% versus 45.6% (P = .05), 42.2% versus 17.3% (P = .01), 3.2% versus 43.0% (P = .007) and 34.4% versus 14.4% (P = .02). Blinatumomab was associated with a lower incidence of day-100 grade 2 to 4 and grade 3 to 4 acute graft-versus-host disease (aGVHD): 27.5% versus 56.7% (P = .009), and 10.9% versus 34.7% (P = .04), respectively. Multivariate analysis confirmed the association between pretransplant blinatumomab and improved OS and NRM. ConclusionsPretransplant blinatumomab is associated with improved OS and lower risk of NRM in B cell ALL patients undergoing allogeneic HCT, likely reflecting lower burden of treatment-related toxicity in this population. Larger prospective trials are warranted to validate our findings.

Post-transplant cyclophosphamide versus anti-thymocyte globulin after reduced intensity peripheral blood allogeneic cell transplantation in recipients of matched sibling or 10/10 HLA matched unrelated donors: final analysis of a randomized, open-label, multicenter, phase 2 trial

The use of post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis is not established after reduced intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) from fully matched donors. This was a randomized, open-label, multicenter, phase 2 trial. All patients received a RIC regimen with fludarabine, intravenous busulfan for 2 days (Flu-Bu2), and a peripheral blood stem cell (PBSC) graft from a matched related or 10/10 HLA-matched unrelated donor. Patients were randomly assigned to receive anti-thymocyte globulin (ATG) 5 mg/kg plus standard GVHD prophylaxis or PTCy 50 mg/kg/d at days +3 and +4 plus standard GVHD prophylaxis. The primary endpoint was the composite endpoint of GVHD- and relapse-free survival (GRFS) at 12 months after HSCT. Eighty-nine patients were randomly assigned to receive either PTCy or control prophylaxis with ATG. At 12 months, disease-free survival was 65.9% in the PTCy group and 67.6% in the ATG group (P = 0.99). Cumulative incidence of relapse, non-relapse mortality, and overall survival were also comparable in the two groups. GRFS at 12 months was 54.5% in the PTCy group versus 43.2% in the ATG group (P = 0.27). The median time to neutrophil and platelet count recovery was significantly longer in the PTCy group compared to the ATG group. Except for day +30, where EORTC QLQ-C30 scores were significantly lower in the PTCy compared to the ATG group, the evolution with time was not different between the two groups. Although the primary objective was not met, PTCy is effective for GVHD prophylaxis in patients receiving Flu-Bu2 conditioning with a PBSC graft from a fully matched donor and was well tolerated in term of adverse events and quality of life. This trial was registered at clinicaltrials.gov: NCT02876679.

Impact of Conditioning Intensity and Regimen on Outcomes after Unrelated Cord Blood Transplantation for Patients with Myelodysplastic Syndrome

Introduction Allogeneic hematopoietic stem cell transplantation (allo-HSCT) provides curative outcomes in patients with myelodysplastic syndromes (MDS). Unrelated cord blood transplantation (CBT) is an alternative donor option in MDS patients who lack an HLA-matched donor, and the increased availability of CBT expand indications for allo-HSCT in MDS patients. Because concerns have been expressed regarding decreased hematopoietic recovery and increased relapse after CBT, many studies have been conducted to develop the conditioning regimen in CBT. The optimal intensity of conditioning regimen needs to be addressed based on patient- and disease-related factors. However, the optimal intensity of conditioning regimen in CBT for MDS remains unclear. We here conducted a nationwide retrospective study to clarify the optimal conditioning intensity for MDS in CBT. Methods This study included patients diagnosed with de novo MDS according to the WHO classification. The clinical data of 856 de novo MDS patients (i) who were 16-69 years old and (ii) who underwent their initial single-unit CBT between 2001 and 2020 were collected from the Japanese Data Center for Hematopoietic Cell Transplantation. Cox proportional hazards regression models were used to evaluate variables potentially affecting overall survival (OS), chronic graft-versus-host disease (GVHD)- and relapse-free survival (CRFS), and GVHD- and relapse-free survival (GRFS). Fine and Gray proportional hazards models were used to evaluate variables potentially affecting cumulative incidences of relapse (CIR) and non-relapse mortality (NRM), using cumulative incidence curves to accommodate competing events. Results In this study, 501 and 355 patients received myeloablative conditioning (MAC) and reduced-intensity conditioning (RIC), respectively. The median age at CBT was 53 (range,17-69) and 62 years (range,18-69) in MAC and RIC groups, respectively. The most frequently used MAC regimen consisted of total body irradiation &amp;gt;8 Gy-based regimen (n=209, 41.7%), followed by fludarabine (Flu) with myeloablative doses of busulfan (Bu 9.6 to 12.8 mg/kg)-based regimen (n=93, 18.6%). The most frequently used RIC regimen consisted of Flu with reduced doses (80 to 120 mg/m 2) of melphalan-based regimen (n=245, 96.1%), followed by Flu with reduced doses of Bu (6.4 mg/kg)-based regimen (n=63, 17.7%). The 3-year OS were 44.3 % and 48.8 % in MAC and RIC groups, respectively; the 3-year CRFS were 33.8 and 37.2%; the 3-year GRFS were 19.2 % and 26.9%; the 3-year CIR were 27.1% and 30.0%; and the 3-year NRM were 18.6% and 18.2 %. The univariate analysis revealed that RIC group tended to correlate with higher GRFS than MAC group (Hazard ratio (HR) 0.86 [95% confidential interval 0.74-1.00]; P=0.057), but there was no significant difference of OS (HR 0.95 [0.79-1.13]; P=0.552), CRFS (HR 0.95 [0.80-1.12]; P=0.522), CIR (HR 1.11 [0.87-1.41]; P=0.401) and NRM (HR 0.96 [0.77-1.20]; P=0.735) between MAC and RIC groups. The multivariate analyses confirmed the better GRFS in RIC group than MAC group (HR, 0.73 [0.61-0.89]; P=0.001). Apart from the conditioning intensity, the following six factors were associated with worse overall mortality: patient's age (40-60 years; P=0.039 and &amp;gt;60 years; P&amp;lt;0.001), patient's sex (male; P=0.038), performance status (PS) at CBT (PS 2-4; P=0.033), hematopoietic cell transplantation-specific comorbidity index (HCT-CI) (HCT-CI ≥3; P=0.035), high number of platelet transfusion before HSCT (≥20 times; P&amp;lt;0.001) , and cytogenetic risk group (poor risk; P=0.001). We next performed the subgroup analysis stratified by the patient's characteristic affecting OS, such as age, sex, PS, HCT-CI, the number of platelet transfusion, and cytogenetic risks. The subgroup analysis showed the better OS (HR, 0.74 [0.59-0.92]; P&amp;lt;0.007), CRFS (HR 0.74, [0.60-0.94]; P=0.012), and GRFS (HR 0.62, [0.50-0.78]; P&amp;lt;0.001) of RIC group than MAC group among patients with patients aged &amp;gt;60 years, but no significant impact on CIR and NRM. Conclusion This study showed no significant difference of OS, CRFS, CIR and NRM between MAC and RIC groups, but RIC group correlated with better GRFS in the entire population. Furthermore, the subgroup analysis showed that RIC regimen may be preferable for patient aged &amp;gt;60 years. These findings would improve the management for CBT candidates with MDS.

Outcomes of Allogeneic Transplantation for Adult T-Cell Leukemia/Lymphoma in Adolescents and Young Adult (AYA) and Young Patients

Introduction Allogeneic hematopoietic stem cell transplantation (allo-HSCT) provides a durable remission for patients with adult T-cell leukemia/lymphoma (ATL). Reduced-intensity regimens (RIC) have been increasingly used in ATL patients due to their old age and higher non-relapse mortality. However, the role of RIC regimen has not been fully evaluated among ATL patients aged &amp;lt;50 years. We here conducted a nationwide study to evaluate the prognostic impact of conditioning intensity on the post-transplant outcomes in ATL patients aged &amp;lt;50 years. Methods The clinical data of patients aged &amp;lt;50 years who underwent their first allo-HSCT between January 2001 and December 2020 were collected from the Transplant Registry Unified Management Program of the Japan Society for Hematopoietic Cell Transplantation. Cox proportional hazards regression models were used to evaluate variables potentially affecting overall survival (OS), graft-versus-host disease (GVHD)- and relapse-free survival (GRFS), and chronic GVHD-free survival (CRFS). Fine and Gray proportional hazards models were used to evaluate variables potentially affecting cumulative incidences of relapse (CIR) and non-relapse mortality (NRM). CIR and NRM were estimated using cumulative incidence curves to accommodate competing events. A two-sided P-value ≤0.05 was considered to be significant. To examine the effect modification, a threshold for P interaction &amp;lt;0.10 was used to indicate significant differences across prespecified subgroups. Results This study included 73 and 330 patients who were &amp;lt;40 years old (adolescents and young adults [AYA] patients) and 40-49 years old (young patients), respectively. In AYA patients, the median age at HSCT was 36 years (range, 20-39). RIC regimen was used in 16 out of 57 AYA patients (21.9%), and in 74 out of 330 young patients (22.4%) (P=1.000). There was no significant difference of the patient characteristics regarding comorbidity, performance status at HSCT, disease status, clinical subtype, and donor type. The estimated 3-year OS rates were 61.8% and 43.1% in AYA and young patients, respectively (P=0.005); the estimated 3-year CRFS rates were 35.8% and 22.6% in AYA and young patients, respectively (P=0.008); and the estimated 3-year GRFS rates were 26.7% and 15.1% in AYA and young patients, respectively (P=0.006). The estimated 3-year CIR were 36.3% and 39.3% in AYA and young patients, respectively (P=0.407); and the estimated 3-year NRM were 17.0% and 23.4% in AYA and young patients, respectively (P=0.113). In addition, the use of RIC regimen was associated with lower NRM than that of MAC regimen (P=0.015), but there was no significant difference of OS, CRFS, GRFS, and CIR between MAC and RIC regimens. The multivariate analyses revealed that young patients were significantly associated with worse OS (Hazard ratio (HR) [95% confidential interval], 1.62 [1.10-2.39]; P=0.015), CRFS (HR, 1.51 [1.10-2.06]; P=0.010), and GRFS (HR, 1.49 [1.11-1.99]; P=0.008) than AYA patients. The utilization of RIC regimen was significantly associated with lower NRM (HR, 0.46 [0.24-0.86]; P=0.015). To find the optimal selection of conditioning intensity (MAC vs. RIC) by patient's age, we next evaluated the effect modification. In the subgroup analysis, there was significant interaction of conditioning intensity with patient's age (P interaction=0.002) in NRM but not in OS, CRFS, GRFS, and CIR. Among AYA patients, the estimated 1-year NRM were 12.5% and 18.8% in MAC and RIC regimens, respectively (P=0.085). Among young patients, the estimated 1-year NRM were 23.5% and 8.2% in MAC and RIC regimens, respectively (P&amp;lt;0.001). Conclusion The present study clarified that AYA patients exhibited better post-transplant outcomes than young patients, indicating the prognostic value of patient's age in ATL patients aged &amp;lt;50 years. Moreover, no significant differences were observed in OS, CRFS, GRFS, and CIR between RIC and MAC regimens, but the utilization of RIC regimen would reduce the risk of non-relapse death among young patients. These facts suggested that RIC regimen could be an alternative option for ATL patients aged 40-49 years.

Score to Guide Donor Choice in Haploidentical Stem Cell Transplant Using Post-Transplant Cyclophosphamide for Patients with Acute Myeloid Leukemia: A Study from the Acute Leukemia Working Party of the EBMT

Introduction: There is paucity of information to guide selection of the most appropriate stem cell donor for haploidentical (Haplo) hematopoietic stem cell transplant (HSCT). Patients and Methods: We retrospectively analyzed the characteristics of haploidentical family donors that may affect transplant outcomes in patients with acute myeloid leukemia (AML) who received graft-versus-host disease (GVHD) prophylaxis with postransplant cyclophosphamide (PTCy) registered in the EBMT database. The primary endpoint was GVHD and relapse-free survival (GRFS). Results: Overall, 2200 patients were included with a median age of 56 years (range, 18-75); 1742 (79%) were in complete remission and 1246 (56.6) received reduced intensity conditioning. Regarding donors, the median age was 37 years (range, 8-71), 820 (37%) were females of which 458 (21%) were used for male recipients, 1252 (57%) had positive CMV serostatus, 1631 (74%) donated peripheral blood (PB) and 1638 (75%) had ≥ 4/8 HLA mismatch with the recipient. 100-day acute GVHD grade II-IV and III-IV and 2-year chronic and chronic extensive GVHD were 28% (95% CI 26-30), 11% (95% CI 10-12), 33% (95% CI 31-35) and 14% (95% CI 12-15), respectively. After median follow-up of 24 months, the cumulative incidence of relapse and non-relapse mortality (NRM) and the probability of leukemia-free survival (LFS), overall survival (OS) and GRFS were 26% (95% CI 24-28), 22% (95% CI 20-24), 52% (95% CI 50-55), 57% (95% CI 55-60) and 41% (95% CI 39-43), respectively. In multivariable analysis, donor-related risk factors with a negative impact on GRFS were older age (HR 1.1; 95% CI 1.04-1.15), use of PB (HR 1.19; 95% CI 1.04-1.37), and female donors to male recipients (HR 1.25; 95% CI 1.09-1.43). We further developed a score that distinguished 4 groups with 0 (241), 1 (913), 2 (863) or 3 (183) donor-related risk factors. GRFS was 57% (95% CI 50-63), 43% (95% CI 39-46), 37% (95% CI 33-40), and 30% (95% CI 23-38), respectively (P &amp;lt; 0.001) (Figure 1). The score was also able to stratify risk groups for acute and chronic GVHD, NRM, LFS and OS. Conclusion: Donor variables have an important impact on AML patient's outcome after Haplo-HSCT using PTCy. With three simple donor characteristics, age, gender and stem cell source, we were able to generate a score that may help to select the most appropriate donor in clinical practice.

Prognostic Impact of Conditioning Intensity on Outcomes after Allogeneic Transplantation for MDS with Low Blasts

Introduction Allogeneic hematopoietic stem cell transplantation (allo-HSCT) provides curative outcomes in patients with myelodysplastic syndromes (MDS). The blast percentage in MDS is one of the important factors to utilize allo-HSCT, and the other disease-related factors, such as transfusion dependency and chromosomal risk, are crucial to consider whether patients harboring MDS with less than 5% of marrow blasts (MDS-Lo) undergo to allo-HSCT. However, the prognostic impacts of conditioning intensity in MDS-Lo patients are still unclear. We here conducted a nationwide retrospective study to clarify the prognostic factor and investigate the optimal conditioning intensity for MDS-Lo. Methods In this study, patients diagnosed as the other than refractory anemia with excess blasts (RAEB)-1 and -2 according to the WHO classification (marrow blasts &amp;lt;5% and peripheral blood blasts &amp;lt;1%) were considered to be MDS-Lo. The clinical data of 1,229 de novo MDS-Lo patients (i) who had stayed MDS-Lo from diagnosis to transplantation and (ii) who underwent their initial allo-HSCT between January 2001 and December 2020 were collected from the Transplant Registry Unified Management Program of the Japan Society for Hematopoietic Cell Transplantation. Cox proportional hazards regression models were used to evaluate variables potentially affecting overall survival (OS), chronic graft-versus-host disease (GVHD)-free survival (CRFS), and GVHD- and relapse-free survival (GRFS). Fine and Gray proportional hazards models were used to evaluate variables potentially affecting cumulative incidences of relapse (CIR) and non-relapse mortality (NRM), using cumulative incidence curves to accommodate competing events. Results In a total of 1,229 patients, 651, 397, and 181 patients received myeloablative conditioning (MAC), reduced-intensity conditioning (RIC), and non-myeloablative conditioning (NMAC) groups, respectively. The estimated 3-year OS rates were 63.3%, 61.0%, and 69.7% in MAC, RIC, and NMAC groups, respectively; the estimated 3-year CRFS rates were 41.1%, 43.9%, and 47.2% in MAC, RIC, and NMAC groups, respectively; the estimated 3-year GRFS rates were 27.5%, 33.4%, and 35.4% in MAC, RIC, and NMAC groups, respectively; the estimated 3-year CIR were 11.9%, 14.2%, and 16.0% in MAC, RIC, and NMAC groups, respectively; and the estimated 3-year NRM were 29.8%, 31.0%, and 24.7% in MAC, RIC, and NMAC groups, respectively. The multivariate analyses revealed four factors affecting lower OS: older recipient's age (Hazard ratio (HR) [95% confidential interval], 1.70 [1.28-2.24]; P&amp;lt;0.001 for 40-59 years)(HR, 2.32 [1.71-3.15]; P&amp;lt;0.001 for 60 years or older), performance status 2-4 at HSCT (HR, 1.84 [1.32-2.57]; P&amp;lt;0.001), the history of infection before HSCT (HR, 2.12 [1.55-2.89]; P&amp;lt;0.001), and high number of red blood cell (RBC) transfusion before HSCT (HR, 1.65 [1.35-2.02]; P&amp;lt;0.001). These factors also negatively affected CRFS, GRFS, and NRM. In addition, poor cytogenetic risk group was associated with worse OS (HR, 1.66 [1.32-2.09]; P&amp;lt;0.001), CRFS (HR, 1.48 [1.22-1.80]; P&amp;lt;0.001), and GRFS (HR, 1.36 [1.14-1.64]; P=0.001) but not CIR. There was no significant difference of OS, CRFS, GRFS, CIR, and NRM in either RIC or NMAC group compared to MAC group. We next performed the subgroups analysis based on the prognostic factors. The subgroup analysis for the comparison between MAC and RIC regimens showed the better OS of MAC regimen among patients with low number of RBC transfusion (HR, 1.33 [1.01-1,75]; P=0.039). The subgroup analysis for the comparison between RIC and NMAC regimens revealed the better OS of NAMC regimen among patients aged &amp;lt;40 years (HR, 0.43 [0.19-0.96]; P=0.038), no history of infection (HR, 0.67 [0.50-0.91]; P=0.009), and good cytogenetic risk (HR, 0.54 [0.38-0.83]; P=0.004). Conclusion This study showed the prognostic factors on the post-transplant outcomes among MDS-Lo patients, and no significant difference of conditioning intensity in the entire population. Furthermore, we found the factors (the number of RBC transfusion, patient's age, the history of infection, and cytogenetic risk) potentially affecting the selection of conditioning intensity. These findings would improve the management for transplant candidates with MDS-Lo.

Post-transplantation cyclophosphamide combined with tacrolimus and low-dose post-engraftment anti-thymoglobulin as GVHD prophylaxis for patients undergoing peripheral blood stem cell transplantation from haploidentical family donor: A single center analysis.

Post-transplantation cyclophosphamide (PT-Cy) use is a recent graft-versus-host disease (GVHD) prophylaxis strategy for patients undergoing allogeneic stem cell transplantation (allo-HSCT). PT-Cy combined with two immunosuppressants is now widely used after haplo-identical (haplo) and HLA-matched peripheral blood stem cell (PBSC) transplantations with promising GVHD and relapsefree survival (GRFS) probabilities. Although appealing, these results may benefit from improvement notably outside matched sibling donor transplantation, and should be investigated in various ethnic populations. Therefore, we report our experience of GVHD prophylaxis regimen combining PT-Cy and tacrolimus with addition of post-engraftment low-dose anti-thymocyte globulin (ATG) in allogeneic stem cell transplantation from haplo-identical donors (Haplo). Sixtyseven patients were included in the analysis. All patients received myeloablative or intensified sequential conditioning regimen. The median follow-up was 521 (range, 10~991) days. The cumulative incidences of 100-day grade II-IV acute GVHD was 14.9±4.4%, and no case of grade III-IV acute GVHD was documented. The cumulative incidences of 2-yearchronic GVHD and moderate-to-severe chronic GVHD were 25.4±5.4% and 11.9±4%, respectively. The non-relapse mortality at day+100 and 2year were 7.5±3.2% and 9.0±3.5%, respectively. The cumulative incidence of relapse at 2year was 16±6.4%. The 2-year probability of DFS and OS were 73.8% (95%CI, 61.5~88.4%) and 72.5% (95% CI, 57.1~92.1%), respectively. The 2-year GRFS was estimated as 63.6% (95%CI, 50.6~80%). Our results suggested that a combination of PT-Cy, tacrolimus, and low-dose post-engraftment ATG was a promising GVHD prophylaxis with low incidence of acute GVHD in the haplo-transplantation setting.

Post-transplant cyclophosphamide for GVHD prophylaxis in pediatrics with chronic active Epstein-Barr virus infection after haplo-HSCT

BackgroundChronic active Epstein-Barr virus infection (CAEBV) is a rare but life-threatening progressive disease. Human leukocyte antigen (HLA)-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is the best choice as sometimes HLA-matched donor is not accessible. However, graft-versus-host-disease (GVHD) following transplantation remains a major cause of treatment failure and elevated mortality. Post-transplant cyclophosphamide (PTCy) has recently emerged for effective GVHD prophylaxis in a haploidentical setting in many hematologic malignancies. Here, we report the performance of PTCy for GVHD prophylaxis in a series of CEABV patients treated with haplo-HSCT.MethodsConsecutive pediatric CAEBV patients who were treated with haplo-HSCT and give PTCy for GVHD prophylaxis were analyzed. 1-year GVHD and relapse-free survival (GRFS), overall survival (OS) and cumulative incidence of moderate-to-severe chronic GVHD (cGVHD) were estimated.ResultsA total of 8 patients ranging from 2 to 15 years old were included. Among them, 4 patients had early complications after haplo-HSCT. Counts of T-cell subsets increased within 6 months post transplantation, indicating an immune reconstitution. Only 1 patient developed grade II acute GVHD, and 2 patients had moderate cGVHD. One patient died from diffuse alveolar hemorrhage within the first year after transplantation. The 1-year GRFS rate, OS rate and cumulative incidence of moderate-to-severe cGVHD were 62.5%, 87.5% and 25.0%, respectively.ConclusionOur findings suggest that, among CAEBV patients treated with haplo-HSCT, PTCy may be an alternative choice for the prevention of GVHD.

High-Risk Cytokine Profiles Predict Lower Survivals in AML after Allotransplantation

Introduction: In a context of allogeneic hematopoietic stem cell transplantation (Allo-HSCT) for acute myeloid leukemia (AML), the impact of peripheral cytokine levels has been poorly studied so far. Methods: The aim of this prospective study (NCT02693899) was to analyze peripheral levels of 8 cytokines in 35 AML patients (pts) before conditioning (BC) then at Day (D) 0, 30, 60 and 100 post-Allo-HSCT by comparison to median levels from 20 healthy controls (16 males, median age 48.5 yo). ELISA (Bio-Techne, Minneapolis, MN) was used to assay the levels of FLt3-ligand (FL), TNF-alpha, stem-cell factor (SCF), c-kit, IL-1 beta, IL-6, IL-10 and granulocyte-monocyte colony-stimulating factor (GM-CSF). A total of 1313 and 157 samples were analyzed in pts and controls, respectively. The impact of BC, D0 and D30 levels and secretion (secretors = pts with detectable cytokine levels) on overall (OS), disease free (DFS) and GVHD and relapse free survival (GRFS) was also assessed. Results: Pts characteristics and cytokine levels are given in Tables 1 and 2. At D0, IL-6 (p=0.0006), FL (p<0.001) and SCF (p=0.003) levels were significantly higher in pts than controls. This remained true for SCF levels on D30 (p=0.0009), D60 (p=0.001) and D100 (p=0.01). Median GM-CSF and c-kit levels were significantly lower in pts at any time (p<0.001). Two-by-two paired cytokine comparisons showed no correlation, especially considering c-kit and its ligand SCF. ELN2017 classification and disease-risk index (DRI) were significantly associated with OS and LFS by univariate analysis (UA), only the former remaining associated with both OS (HR 8.51; 95%CI 1.18-61.54, p=0.034) and LFS (HR 8.10; 95%CI 1.20-54.82, p=0.032) in multivariate analysis (MA). Only SCF, IL-6 and c-kit levels impacted survivals. Higher pre-transplant SCF levels were associated with lower OS (p=0.02), DFS (p=0.01) and GRFS (P<0.001) by UA and remained associated with lower GRFS (HR 3.19; 95%CI 1.48-6.88, p=0.003) in MA, with a trend for lower LFS (HR 1.96; 95%CI 0.94-4.08, p=0.07). There was also an association between the absence of SCF secretion and better OS, LFS and GRFS (p=0.02, p=0.02, p=0.03) while c-kit secretion was associated with better OS (p=0.03) in UA. This remained true in MA for OS (HR 0.30; 95%CI 0.10-0.92, p=0.03) and there was a trend between no SCF secretion and GRFS (HR 0.45; 95%CI 0.18-1.14, p=0.09) by MA. Higher IL-6 levels at D0 were associated with lower OS (p=0.01) by UA and lower LFS both by UA (p=0.01) and MA (HR: 2.83; 95%CI: 1.04-7.70, p=0.04), with a trend for lower OS (HR: 2.55; 95%CI: 0.90-7.29, p=0.07) in MA. ROC curve analysis identified 7pg/mL as the best cut-off for D0 IL-6 levels which resulted, for pts under this level, in significantly better 4-year OS (80% (62-1) vs 35.7% (18-69), p=0.02) and LFS (73.3% (54-99) vs 28.6% (13-63) p=0.01; Figure). For alive patients at D30, higher c-kit and lower SCF levels were associated with better OS (p=0.003 and p=0.01) and LFS (p=0.009 and p=0.04) by UA while c-kit levels remained associated with LFS (HR: 0.37; 95%CI: 0.17-0.80, p=0.01) by MA. The absence of SCF secretion was associated with better OS (p=0.03) and a trend for better LFS (p=0.07). c-kit secretion was associated with better OS (p=0.008), LFS (p=0.01) and a trend for better GRFS (p=0.07). Only c-kit secretion remained associated with better OS (HR: 0.15; 95%CI: 0.04-0.57, p=0.005), LFS (HR: 0.19; 95%CI: 0.06-0.62, p=0.006) and GRFS (HR: 0.40.95%CI: 0.16-1.00, p=0.05) by MA. Conclusion: In this cohort, early higher IL-6 and SCF and lower c-kit levels appeared to be significantly associated with lower survivals in AML pts after Allo-HSCT. These high-risk cytokine profiles might allow to propose therapeutic intervention to decrease relapses in selected pts, either by modulating cytokine levels or by starting early maintenance treatment post-Allo-HSCT. These results have to be confirmed on larger studies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Orca-Q Demonstrates Favorable GvHD-and-Relapse-Free Survival in Haploidentical Transplants without Post-Transplant Cyclophosphamide

^Salhotra, Srour, Lowsky and Abedi contributed equally Background: Allogeneic hematopoietic stem cell transplantation (alloHSCT) can be curative for a variety of malignant and nonmalignant disorders, but until recent years, access has been limited to patients with HLA-matched donors. The increased utilization of post-transplant cyclophosphamide (PTCy) has enabled patients to receive alloHSCT with haploidentical (haplo) related donors; however, high rates of cGVHD following myeloablative conditioning (MAC) regimens and high rates of relapse following reduced intensity conditioning regimens have been observed with this approach. Thus, GVHD-and-relapse free survival (GRFS) rates in this population at 1-year post-transplant remain low. Haplo alloHSCT with PTCy is also associated with high incidence of cytokine release syndrome (CRS) and infections. Orca-Q -an investigational precision engineered cell therapy- represents an alternative strategy which may be administered with single agent prophylaxis and does not require PTCy. The cellular composition of Orca-Q consists of enriched CD34+ stem cells combined with specific T- cell subsets and is intended to reconstitute the blood and immune systems. Orca-Q is hypothesized to reduce GVHD, relapse, and serious infections. Methods: Adult patients (18 to 65 years) with high-risk hematologic malignancies undergoing myeloablative conditioning (MAC) alloHSCT were enrolled between January 2019 to July 2022 on the haplo donor dose expansion arm of a multicenter phase 1 study of Orca-Q (NCT03802695). Haplo was defined as ≥ 4/8 but < 7/8 matched related donor at HLA-A, -B, -C, and -DRB1 typed using DNA-based high-resolution. Patients received only single agent tacrolimus (starting on day -1 and taper day +60 if no GVHD) as GVHD prophylaxis. PTCy was not permitted. The Orca-Q drug product was manufactured centrally at Orca Bio Manufacturing Site in Sacramento, CA from G-CSF mobilized peripheral blood apheresis. Results: The Orca-Q drug product was successfully manufactured and delivered to all subjects with a vein-to-vein time of less than 72 hours. A total of 21 patients (11 AML, 8 ALL, 2 CML in blast crisis) with > 30 days of follow up were included in this analysis. All were 4/8 HLA match at HLA-A, -B, C, and DRB1. Median age of subjects was 44 years (range 21 - 63) and median follow-up was 333 days (range 39 - 1020). Disease risk index (DRI) score was available in 20 showing 2 very high, 3 high, 13 intermediate, and 2 low risk categories. The M:F ratio was 12:9. Patients received either TBI (n=13) or non-TBI (n=8) based MAC regimens. 2 patients had Gr 1 CRS (CTCAE v5). Median neutrophil and platelet engraftment times were 13 days (range 8 - 25) and 16 days (range 12 - 25), respectively. 1 secondary engraftment failure was observed. The estimated incidence of BMT CTN MOP3 infections was 27% at 1 year. The estimated incidence of gr 2-4 aGVHD at 6 months was 14% which compares favorably with literature reports of 21% to 63% for gr 2-4 aGVHD in patients undergoing haplo transplant with PTCy-based prophylaxis.[1-5] Likewise, gr 3-4 aGVHD was rare with Orca-Q with only 1 case of gr 3 aGVHD and no gr 4 aGVHD. Of the 16 patients who had at least 3 months follow up, only 1 developed mild cGVHD. No patients had moderate-to-severe cGVHD, a notable improvement compared to historic rates of 24% to 31% for moderate-to-severe cGVHD with PTCy, despite the fact that Orca-Q patients receive only single agent GVHD prophylaxis.[1-4] 2 patients experienced disease relapse and there was a total of 5 deaths (2 due to relapse, 1 Aspergillus pulmonary infection, 1 respiratory failure associated with renal failure, and 1 COVID infection). GVHD-and-relapse free survival (GRFS) was 71% at 1 year with Orca-Q (Figure 1) which compares favorably to a GRFS of 46% reported by Sanz in the context of MAC haplo alloHSCT with PTCy.[2] Conclusions: Initial Orca-Q data demonstrates good clinical outcomes with single agent tacrolimus and no PTCy or MMF. Patients treated with Orca-Q experienced a low adverse event profile, low incidence and severity of both aGVHD and cGVHD, and improved GRFS rates, offering a potential new treatment option for patients undergoing haplo alloHSCT. This phase 1 study of Orca-Q continues to enroll patients with haplo donors across the US. References (1) Gooptu, M., et al. (2) Sanz, J., et al. (3) Wagner, J.E., et al. (4) Baker, M., et al. (5) Bashey, A., et al. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Post-Transplantation Cyclophosphamide Combined with Tacrolimus and Low-Dose Post-Engraftment Anti-Thymoglobulin As Gvhd Prophylaxis for Patients Undergoing Peripheral Blood Stem Cell Transplantation from Haplo Donors: A Single Center Analysis

Post-transplantation cyclophosphamide (PT-Cy) use is a recent graft-versus-host disease (GVHD) prophylaxis strategy for patients undergoing allogeneic stem cell transplantation (allo-HSCT). PT-Cy combined with two immunosuppressants is now widely used after haplo-identical (haplo) and HLA-matched peripheral blood stem cell (PBSC) transplantations with promising GVHD and GVHD and relapse-free survival (GRFS) probabilities. Although appealing, these results may benefit from improvement notably outside matched sibling donor transplantation, and should be investigated in various ethnic populations. Therefore, we report our experience of GVHD prophylaxis regimen combining PT-Cy and tacrolimus with addition of post-engraftment low-dose anti-thymocyte globulin (ATG) in allogeneic stem cell transplantation from haplo-identical donors (Haplo). Fifty-three patients were included in the analysis. All patients received myeloablative or intensified sequential conditioning regimen. The median follow-up was 397 (range, 191~762) days. The cumulative incidences of 100-day grade II-IV acute GVHD was 9.4±4.1%, and no case of grade III-IV acute GVHD was documented. The cumulative incidences of 1-year chronic GVHD and moderate-to-severe chronic GVHD were 18.9±5.4% and 7.5±3.7%, respectively. The non-relapse mortality at day+100 and 1 year were 9.4±4.4% and 11.3±4.4%, respectively. The cumulative incidence of relapse at 1 year was 3.8±2.7%. The 1-year probability of DFS and OS were 84.5% (95%CI, 75.2~95.0%) and 88.7% (95% CI, 80.5~97.6%), respectively. The 1-year GRFS was estimated as 75.0% (95%CI, 64.1~87.8%). Our results suggested that a combination of PT-Cy, tacrolimus, and low-dose post-engraftment ATG was a promising GVHD prophylaxis with low incidence of acute GVHD in the haplo-transplantation setting. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Fludarabine and antithymocyte globulin-based conditioning regimen combined with post-transplantation cyclophosphamide for haploidentical allogeneic hematopoietic stem cell transplantation in patients with high-risk acute myeloid leukemia and myelodysplastic syndrome

IntroductionRelapse and graft-versus-host disease (GVHD) are the important complications influencing mortality for patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). GVHD prophylaxis based on post-transplant cyclophosphamide (PTCy) or antithymocyte globulin (ATG) is widely used in haploidentical HSCT (haplo-HSCT). ObjectiveWe developed a modified intensified conditioning regimen including fludarabine (Flu) and investigated the effect of ATG-PTCy combination on transplant outcomes in high-risk AML and MDS compared with those patients who received only ATG as GVHD prophylaxis. MethodsA total of 80 patients with high-risk AML and MDS were divided into two groups and assigned to one-to-one pairing. ResultsThe modified ATG-PTCy group had more infused mononuclear cells, CD34-positive cells and CD3-positive cells than those in the ATG group (P < 0.05). The amount of platelet transfusion was higher in the ATG group than the modified ATG-PTCy group [2 (range, 1–6) U vs 2 (range, 1–5) U, P = 0.005]. The median of platelet recovery was better in the modified ATG-PTCy group than in the ATG group (12 days vs 13 days,P = 0.041). The infection rates of bacteria, fungi and virus at 100 days after transplantation were similar in both groups. Compared with the ATG group, individuals who received the modified ATG-PTCy regimen had higher 2-year GVHD- and relapse-free survival(GRFS) [60.0% (95%CI, 44.9–75.1%) vs 34.8% (95%CI, 19.9–49.7%), P = 0.028]; lower 180-day incidence of II-IV acute GVHD (aGVHD) [15.0% (95%CI, 4.0–26.0%) vs 39.8% (95%CI, 23.9–55.7%), P = 0.029]; lower 1-year incidence of moderate to severe chronic GVHD (cGVHD) [2.9% (95%CI, 2.0–3.8%) vs 19.6% (95%CI, 5.3–33.9%), P = 0.039]; and without an increase in the 2-year cumulative incidence of relapse (CIR) [19.5% (95%CI, 6.6–32.4%) vs 30.4% (95%CI, 15.3–45.5%), P = 0.291]. ConclusionsHigh-dose stem cells can promote blood cell implantation. The modified ATG-PTCy combination was associated with decreased risk of aGVHD and cGVHD, no increased risk of recurrence, and improved GRFS. It represents an effective strategy for high risk AML and MDS.

Triple post transplant cyclophosphamide (PTCY) based GVHD prophylaxis: HLA matched versus HLA haploidentical transplants.

We report a retrospective analysis of 198 allogeneic hematopoietic stem cell transplant (HSCT) recipients with post-transplant cyclophosphamide (PTCY), cyclosporine and mycophenolate mophetil as graft-versus-host-disease (GVHD) prophylaxis: the donors were HLA-matched (n = 78), or haploidentical relatives (HAPLO) (n = 120). The two groups were comparable except for older age in the HAPLO group. The main diagnosis were acute leukemia (57%) and myelofibrosis (21%). In the HLA-matched and HAPLO group the outcomes were as follows: aGVHD grade II-IV, 10% vs 27% (p = 0.005); moderate-severe cGVHD, 4% vs 19% (p = 0.004); transplant related mortality (TRM) at 1 year 10% vs 21% (p = 0.04); relapse at 1 year 24% vs 10% (p = 0.051) respectively. Disease free survival (DFS) at 1 year was 65% for matched and 68% for HAPLOs (p = 0.85). DFS and OS were independently predicted by age over 60 and higher DRI, whether the only independent predictive variable for GVHD and relapse free survival (GRFS) was age over 60. In conclusion: given the same PTCY based, GVHD prophylaxis, HLA-mismatched grafts are exposed to a higher risk of acute and chronic GVHD. This translates in increased TRM. DFS is comparable for HLA matched and HAPLO grafts.

Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia with Hyperdiploid Complex Karyotype: A Study from the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT)

Introduction: Cytogenetics remains one of the most important prognostic factors in acute myeloid leukemia (AML) patients, even for outcomes after allogeneic hematopoietic cell transplantation (allo-HCT). Complex karyotype (CK) constitutes a cytogenetic category with a very adverse prognosis in this setting. However, CK is a heterogenous and loosely defined category which comprises a high diversity of cytogenetic subtypes, which is highly enriched with specific cytogenetic subtypes characterized by losses of chromosomal material at critical regions known to confer a poor prognosis per se, such as monosomal karyotype, del(7q)/-7, del(5q)/-5 or abnormalities leading to 17p region loss. On the contrary, rare AML cases characterized with only multiple numerical abnormalities known as pure hyperdiploid karyotype (HDK), have a controversial prognosis. We hypothesized that pure complex HDK AML has a distinct and much better prognosis after allo-HCT compared to non-HDK, CK AML.Methods: We selected from the EBMT registry adult patients with AML and a full cytogenetic report. HDK was defined by the presence of 49 chromosomes or more. Patients were then stratified by pure HDK (pHDK) and HDK with other cytogenetic abnormalities (HDK+), characterized by HDK and the presence of a prognostic-defining cytogenetic abnormality such as del(5q)/-5, del(7q)/-7, del(17p)/-17/i(17q), inv(3q21-26)/t(3;3)(q21;q26) or t(9;22). We included only first allo-HCT from a sibling or unrelated donor (UD) performed between 2000 and 2018.Results: A total of 236 patients were identified as having HDK. There were 95 pHDK and 141 HDK+. Median age at transplantation was 53 years (range, 18-74) and median follow-up was 43 months (range, 35-56). A diagnosis of secondary AML was reported in 48 patients (20%). At the time of allo-HCT, 180 patients (76%) were in first remission (CR1), and 56 were beyond CR1 (24%). Eighty-five (39%) patients received an allo-HCT from a sibling donor, with more matched unrelated donors (MUD) in HDK+ patients (p=0.02). Most patients (70%) had a Karnofsky performance status (KPS) score of more than 90% at the time of transplantation. A myeloablative conditioning regimen was administered in 46% of the patients. In vivo T-cell depletion was part of the regimen in 66% of the patients. The most frequent trisomies were trisomy 8, 21, 13, and 22.The 2-year probability of non-relapse mortality (NRM) was 26% for the entire cohort. The 2-year probability of LFS was 50% for pHDK and 31% for HDK+ (p=0.003). The 2-year probability of overall survival (OS) was 57% for pHDK and 36% for HDK+ (p=0.007). The 2-year cumulative incidence of relapse (RI) was 22% for pHDK and 44% for HDK+ (p=0.001) (Figure 1). The cumulative incidence of grade II-IV acute graft-versus-host disease (GvHD) and chronic GvHD was 34% and 33%, respectively, for the entire cohort. Finally, the 2-year probability of GvHD and relapse-free survival (GRFS) was 36% for pHDK and 21% for HDK+ (p=0.01). On multivariate analysis, pHDK remained associated with significantly better LFS, OS and GRFS and higher RI (all p-values<0.004). Age was associated with lower OS (p=0.05). Being in remission at the time of allo-HCT was associated with better LFS, OS and GRFS, and lower NRM and RI (all p-values<0.02). Secondary AML, donor type, KPS, and conditioning regimen intensity were not associated with any outcome in multivariate analysis.Conclusions: AML with pHDK has a better outcome after allo-HCT in terms of RI, LFS, OS and GRFS. pHDK AML constitutes probably a distinct cytogenetic entity from HDK+ or other non-hyperdiploid CK AML. CK remains a strong indication for allo-HCT, but the type of abnormalities included in CK significantly influences the outcome and should guide how to manage patients after allo-HCT in terms of immunosuppression withdrawal or prophylactic/preemptive post-transplant interventions such as use of hypomethylating agents or donor lymphocyte infusions. [Display omitted] DisclosuresLabopin: Jazz Pharmaceuticals: Honoraria. Ganser: Jazz Pharmaceuticals: Honoraria; Novartis: Honoraria; Celgene: Honoraria. Socie: Alexion: Research Funding. Forcade: Novartis: Other: travel grant. Chalandon: Incyte, BMS, Pfizer, Abbie, MSD, Roche, Novartis, Gilead, Amgen, Jazz, Astra Zenec: Other: Travel EXpenses, Accomodation; Incyte, BMS, Pfizer, Abbie, MSD, Roche, Novartis, Amgen: Other: Advisory Board; Incyte: Speakers Bureau. Yakoub-Agha: Jazz Pharmaceuticals: Honoraria. Kröger: Novartis: Research Funding; Riemser: Honoraria, Research Funding; Sanofi: Honoraria; Neovii: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; Gilead/Kite: Honoraria; Celgene: Honoraria, Research Funding; AOP Pharma: Honoraria. Esteve: Jazz: Consultancy; Bristol Myers Squibb/Celgene: Consultancy; Abbvie: Consultancy; Novartis: Consultancy, Research Funding; Astellas: Consultancy; Pfizer: Consultancy; Novartis: Research Funding. Mohty: Sanofi: Honoraria, Research Funding; Pfizer: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Jazz: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gilead: Honoraria; Celgene: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Astellas: Honoraria; Amgen: Honoraria; Adaptive Biotechnologies: Honoraria.