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Introduction: For the majority of patients with acute myeloid leukemia (AML) an allogeneic stem cell transplant (SCT) in first complete remission (CR) is preferred. However, whether the number of courses required to achieve CR has a prognostic impact is unclear. It is unknown which factors remain important in patients requiring more than one course of induction to attain remission. Methods: This Acute Leukaemia Working Party study from the European Society for Blood and Marrow Transplantation identified adults who received an allograft in first CR from either a fully matched sibling or 10/10 or 9/10 human leucocyte antigen (HLA)‐matched unrelated donor (HLA‐A, HLA‐B, HLA‐C, HLA‐DR, or HLA‐DQ). Univariate and multivariate analyses were undertaken to identify the prognostic impact of one or two courses of induction to attain CR. Results: A total of 4995 patients were included with 3839 (77%) patients attaining a CR following one course of induction chemotherapy (IND1), and 1116 patients requiring two courses (IND2) to attain CR. IND2 as compared to IND1 was a poor prognostic factor in a univariate analysis and remained so in a multivariate Cox model, resulting in an increased hazard ratio of relapse (1.38; 95% confidence interval [CI], 1.16–1.64; p =.0003) and of death (1.27; 95% CI, 1.09–1.47; p =.002). Adverse prognostic factors in a multivariate analysis of the outcomes of patients requiring IND2 included age, FLT3‐ITD, adverse cytogenetics, and performance status. Pretransplant measurable residual disease retained a prognostic impact regardless of IND1 or IND2. Conclusion: Initial response to chemotherapy as determined by number of courses to attain CR, retained prognostic relevance even following SCT in CR. Patients requiring two courses of induction to attain complete remission (CR) have a higher incidence of relapse and inferior survival as compared to those who require one course. Pretransplant measurable residual disease remains important in predicting outcomes following an allogeneic stem cell transplant in those requiring two courses of induction to achieve CR. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to compare two immunosuppressive strategies, based on the use of either rabbit antithymocyte globulin (ATG) or posttransplant cyclophosphamide (PTCY), as a prophylaxis of graft‐versus‐host disease (GVHD) for patients with acute lymphoblastic leukemia (ALL) in first complete remission who underwent hematopoietic cells transplantation from matched unrelated donors. Methods: Overall, 117 and 779 adult patients who received PTCY and ATG, respectively, between the years 2015 and 2020 were included in this retrospective study. The median patient age was 40 and 43 years in the PTCY and ATG groups, respectively, and 37% and 35% of patients, respectively, had Philadelphia chromosome‐positive ALL. Results: In univariate analysis, the cumulative incidence of acute and chronic GVHD did not differ significantly between the study groups. The cumulative incidence of relapse at 2 years was reduced in the PTCY group (18% vs. 25%; p =.046) without a significant impact on nonrelapse mortality (11% vs. 16% in the ATG group; p =.29). The rates of leukemia‐free survival (LFS) and overall survival were 71% versus 59%, respectively (p =.01), and 82% versus 74%, respectively (p =.08). In multivariate analysis, the receipt of ATG compared with PTCY was associated with a reduced risk of extensive chronic GVHD (hazard ratio, 0.54; 95% confidence interval, 0.3–0.98; p =.04) and an increased risk of low LFS (hazard ratio, 1.57; 95% confidence interval, 1.01–2.45; p =.045). Conclusions: The receipt of ATG compared with PTCY, despite the reduced risk of extensive chronic GVHD, is associated with inferior LFS in adults with ALL who undergo hematopoietic cell transplantation from 10/10 human leukocyte antigen‐matched unrelated donors. These findings warrant verification in prospective trials. In this registry‐based study, the authors demonstrate that, for adult patients with acute lymphoblastic leukemia who undergo hematopoietic cell transplantation from 10/10 human leukocyte antigen‐matched unrelated donors, immunosuppression based on posttransplant use of cyclophosphamide is associated with improved leukemia‐free survival compared with protocols that include antithymocyte globulin. These findings suggest preferential use of posttransplant cyclophosphamide in this setting. [ABSTRACT FROM AUTHOR]

Background: Allogeneic hematopoietic cell transplantation (allo‐HCT) is the only cure for acute myeloid leukemia (AML) in second complete remission (CR2). Patients lacking a matched sibling donor (MSD) receive transplants from matched unrelated donors (MUDs), mismatched unrelated donors (MMUDs), haploidentical (haplo) donors, or cord blood. Methods: This is a retrospective, registry‐based European Society for Blood and Marrow Transplantation study that investigates changes in patient‐ and transplant‐related characteristics and posttransplant outcomes over time. Results: We identified 3955 adult patients (46.7% female; median age, 52 years [range, 18–78 years]) with AML in CR2 first transplanted between 2005 and 2019 from a MUD 10/10 (61.4%), MMUD 9/10 (21.9%), or haplo donor (16.7%) and followed for 3.7 years. A total of 725 patients were transplanted between 2005 and 2009, 1600 between 2010 and 2014, and 1630 between 2015 and 2019. Over the three time periods, there was a significant increase in patient age (from 48.7 to 53.5 years; p <.001), use of a haplo donor (from 4.6% to 26.4%; p <.001), and use of posttransplant cyclophosphamide (from 0.4% to 29%; p <.001). There was a significant decrease in total body irradiation and in vivo T‐cell depletion. In multivariate analysis, transplants performed more recently had better outcomes. Leukemia‐free survival (hazard ratio [HR], 0.79; p =.002) and overall survival (HR, 0.73; p <.001) increased over time. Similarly, nonrelapse mortality (HR, 0.64; p <.001) decreased over time. We also observed better graft‐vs‐host disease (GVHD) rates (acute GVHD II–IV: HR, 0.78; p =.03; GVHD‐free, relapse‐free survival: HR, 0.69; p <.001). Conclusions: Even in the absence of an MSD, outcomes of allo‐HCT in CR2 for AML have significantly improved over time, with most favorable outcomes achieved with a MUD. Allogeneic transplantation remains the only curative option for patients with acute myeloid leukemia in second complete remission, with significant changes in patient and transplant characteristics and posttransplant outcomes over time. Even in the absence of matched sibling donors, outcomes have improved over time, with the best outcomes achieved with matched unrelated donors. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: Optimal donor choice for a second allogeneic haematopoietic cell transplant (allo‐HCT) in relapsed acute myeloid leukaemia (AML) remains unknown. We compared overall survival (OS) using registry data from the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT) involving 455 adults who received a second allo‐HCT from a human leucocyte antigen (HLA)‐matched unrelated (MUD) (n = 320) or a haploidentical (n = 135) donor. Eligibility criteria required adults aged ≥18 years who received a second allo‐HCT for treating AML relapse between 2005 and 2019. The primary end‐point was OS. There was no statistically significant difference in the median (interquartile range) age between the groups, MUD 46 (35–58) versus haploidentical 44 (33–53) years (P = 0·07). The median OS was not different between the MUD and the haploidentical groups (10 vs. 11 months, P = 0·57). Similarly, the 2‐year OS was 31% for the MUD and 29% for the haploidentical donor groups. The OS was worse if the procedure was performed with active AML [hazard ratio (HR) 1·42, 95% confidence interval (CI) 1·07–1·89; P = 0·02]. Conversely, a longer time from first allo‐HCT to relapse (>13·2 months) was associated with better OS (HR 0·50, 95% CI 0·37–0·69; P < 0·0001). The results of the present analysis limit the ability to recommend one donor type over another when considering a second allo‐HCT for relapsed AML. Our findings highlight that best OS is achieved when receiving the second allo‐HCT in complete remission. [ABSTRACT FROM AUTHOR]

BACKGROUND: Graft‐versus‐host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Addition of antithymocyte globulin (ATG) or post‐transplantation cyclophosphamide (PTCY) to standard immunosuppressive agents reduces GVHD in different donor settings. METHODS: We compared the outcomes of adults with acute myeloid leukemia undergoing allo‐HSCT from HLA‐identical sibling donors after the use of PTCY (n = 197) or ATG (n = 1913). RESULTS: Patients in the PTCY group were younger than those in the ATG group (median age, 47 vs 54 years; P <.01). Peripheral blood was the most frequently used stem cell source, being significantly more frequent in the ATG group than in the PTCY group (95% vs 70% P <.01). The conditioning regimen was more frequently myeloablative in the PTCY group than in the ATG group (59% vs 48%; P <.01). Time to neutrophil engraftment was shorter in the ATG group than in the PTCY group (17 vs 20 days; P <.01). No differences were observed according to the other transplantation outcomes, except for chronic GVHD of all grades and extensive chronic GVHD at 2 years, which were significantly lower in the ATG group compared with the PTCY group (P <.02). CONCLUSION: PTCY is feasible in an HLA‐identical sibling setting, and despite similar outcomes, ATG may be associated with lower incidence of chronic GVHD. Addition of antithymocyte globulin (ATG) or post‐transplantation cyclophosphamide (PTCY) to standard immunosuppressive agents in patients who received a transplant from an HLA‐identical sibling donor is feasible and allows low rates of graft‐versus‐host disease (GVHD).When compared with PTCY, the use of ATG is associated with lower cumulative incidence of chronic GVHD. [ABSTRACT FROM AUTHOR]

Limited data are currently available on the outcome of patients with acute myeloid leukemia (AML) undergoing allogeneic stem cell transplantation (allo‐SCT) with a reduced performance status. We herein present the results of a registry study on 2,936 AML patients undergoing allo‐SCT in first remission (CR1) with a Karnofsky Performance Status (KPS) score less than or equal to 80%. Two‐year leukemia‐free survival (LFS), overall survival (OS) and graft‐versus‐host disease (GVHD)‐free, and relapse‐free survival (GRFS) rates were 54%, 59%, and 41%, respectively. In multivariable analysis, patients with a KPS score = 80% had lower non‐relapse mortality (NRM) and superior OS in comparison to patients with a KPS score <80% (p < 0.001). In the subgroup of patients with a KPS score =80%, a reduced‐intensity conditioning (RIC) regimen was associated with an increased risk of relapse (p = 0.002) and lower GRFS (p < 0.001) compared to myeloablative conditioning (MAC). Differently, in patients with a KPS score <80%, a RIC regimen resulted in lower NRM (p < 0.001), whereas relapse incidence did not differ, thus leading to an improved GRFS (p = 0.008) as compared to MAC. A transplant from a matched sibling donor (MSD) was associated with a reduced incidence of grade III‐IV acute GVHD (p < 0.01) and NRM (p < 0.01) in comparison to other donor types. In conclusion, allo‐SCT appears feasible in AML patients with a jeopardized KPS score. Survival is significantly affected by the conditioning intensity, which should be adjusted according to the severity of KPS impairment. [ABSTRACT FROM AUTHOR]

Background: The use of post-transplant cyclophosphamide (PTCy) is highly effective in preventing graft-versus-host disease (GVHD) in the haploidentical (Haplo) transplant setting and is being increasingly used in matched sibling (MSD) and matched unrelated (MUD) transplants. There is no information on the impact of donor types using homogeneous prophylaxis with PTCy. Methods: We retrospectively compared outcomes of adult patients with acute myeloid leukemia (AML) in first complete remission (CR1) who received a first allogeneic stem cell transplantation (SCT) with PTCy as GVHD prophylaxis from MSD (n = 215), MUD (n = 235), and Haplo (n = 789) donors registered in the EBMT database between 2010 and 2017. Results: The median follow-up was 2 years. Haplo-SCT carried a significantly increased risk of acute grade II–IV GVHD (HR 1.6; 95% CI 1.1–2.4) and NRM (HR 2.6; 95% CI 1.5–4.5) but a lower risk of relapse (HR 0.7; 95% CI 0.5–0.9) that translated to no differences in LFS (HR 1.1; 95% CI 0.8–1.4) or GVHD/relapse-free survival (HR 1; 95% CI 0.8–1.3). Interestingly, the use of peripheral blood was associated with an increased risk of acute (HR 1.9; 95% CI 1.4–2.6) and chronic GVHD (HR 1.7; 95% CI 1.2–2.4) but a lower risk of relapse (HR 0.7; 95% CI 0.5–0.9). Conclusions: The use of PTCy in patients with AML in CR1 receiving SCT from MSD, MUD, and Haplo is safe and effective. Haplo-SCT had increased risk of acute GVHD and NRM and lower relapse incidence but no significant difference in survival. [ABSTRACT FROM AUTHOR]

Background: In adult patients with acute myeloid leukemia (AML), a matched sibling donor (MSD) is considered the first choice for an allogeneic transplantation. However, a female donor for a male recipient is a poor prognostic factor. The authors compared haploidentical (HAPLO) donors with female MSDs.Methods: In total, 834 men underwent allogenic transplantation from a female MSD, and 232 men underwent allogenic transplantation from a HAPLO donor. Of these, 86% of HAPLO recipients and 3% of MSD recipients received graft-versus-host disease (GVHD) prophylaxis posttransplantation with high-dose cyclophosphamide. A significant qualitative interaction was observed between donor type and cytogenetics, Therefore, the analyses were stratified on cytogenetics.Results: Of the men with intermediate-risk AML, 638 received transplantation from a female MSD, and 160 received transplantation from a HAPLO donor. In multivariate analysis, poor risk factors were a HAPLO donor versus an MSD for nonrelapse mortality (hazard ratio [HR], 1.7; P = .02) and patient age for nonrelapse mortality and overall survival (HR, 1.22 [P = .02] and 1.15 [P = .02], respectively). HAPLO transplantation resulted in less chronic GVHD (HR, 0.43; P < 10-4 ) but lower leukemia-free survival (HR, 1.7; P = .04). The GVHD/relapse-free survival (GRFS) was not different. Of the men with high-risk AML, 196 received transplantation from a female MSD, and 72 received transplantation from a HAPLO donor. By multivariate analysis, HAPLO recipients had a lower incidence of relapse (HR, 0.40; P = .004), better leukemia-free survival (HR, 0.46; P = .003), better overall survival (HR, 0.43; P = .003), and better GRFS (HR, 0.54; P = .006).Conclusions: In men who have intermediate-risk AML, allogenic transplantation from a sister MSD or a HAPLO donor produces similar GRFS. However, in men who have high-risk AML, a HAPLO donor combined with prophylactic high-dose cyclophosphamide posttransplantation may be a better choice. [ABSTRACT FROM AUTHOR]

Second allogeneic stem-cell transplantation (SCT2) is a therapeutic option for patients with AML relapsing after a first transplant. Prior studies have shown similar results after SCT2 from the same or different donor; however, there are limited data on second non-T-depleted haplo-identical transplant in this setting. We retrospectively analyzed SCT2 outcomes in 556 patients, median age 46 years, relapsing after first transplant given in CR1. Patients were divided into three groups based on SCT2 donor (donor2): same donor (n = 163, sib/sib-112, UD/UD-51), different matched donor (n = 305, sib/different sib-44, sib/UD-93, UD/different UD-168), or haplo-donor (n = 88, sib/haplo-45, UD/haplo-43). Two-year leukemia-free survival (LFS) rate after SCT2 was 23.5%, 23.7%, and 21.8%, respectively (P = 0.30). Multivariate analysis showed no effect of donor2 type on relapse: hazard ratio (HR) 0.89 (P = 0.57) and 1.11 (P = 0.68) for different donor and haplo-donor compared to same donor, respectively. However, donor2 did predict for non-relapse mortality (NRM) after SCT2: HR 1.21 (P = 0.50) and 2.08 (P = 0.03), respectively, and for LFS: HR 1.00 (P = 0.97) and 1.43 (P = 0.07), respectively. In conclusion, SCT2 with the same or different matched donor is associated with similar outcomes in patients with relapsed AML. Non-T-depleted haplo-identical transplant may be associated with higher NRM, similar relapse rate and with no better results in this setting. [ABSTRACT FROM AUTHOR]

Reduced-intensity conditioning ( RIC)-allo SCT is increasingly used for acute myelogenous leukemia. Limited data are available for the comparison of peripheral blood stem cells with bone marrow for RIC-allo SCT. We used the European Group for Blood and Marrow Transplantation ( EBMT) ALWP data to compare the outcome of mobilized peripheral blood stem cells ( PBSC) ( n = 1430) vs. bone marrow ( BM) ( n = 107) for acute myelogenous leukemia ( AML) patients with complete remission that underwent RIC-allo SCT from compatible sibling donors. The leukemia features, the disease status, and the time from diagnosis were similar between the two groups. Engraftment was achieved in 99% and 93% in the PBSC and BM groups, respectively ( P < 0.0001). The day of engraftment was significantly earlier for the PBSC vs. the BM group, 15 (1-59) and 19 (5-69), respectively ( P < 0.001). Acute GVHD, severe GVHD (grade III-IV) and chronic GVHD did not differ between the groups. leukemia-free survival ( LFS), relapse, and non-relapsed mortality ( NRM) were 51 ± 2%, 32 ± 1%, and 17 ± 1% vs. 50 ± 6%, 38 ± 6%, and 12 ± 3% for the PBSC and BM groups, respectively. Our results indicate faster engraftment, but no difference in GVHD, LFS, relapse, and NRM when comparing PBSC to BM grafts from sibling donors following RIC conditioning. This is the first study comparing PBSC to BM grafts in the RIC setting, analyzing a homogeneous population of patients with AML in remission. Whether PBSC should be preferred for advanced phases of the disease, where the outcome is dominated by relapse incidences, needs further investigation. [ABSTRACT FROM AUTHOR]

High-dose cytarabine is currently used in combination with anthracycline in the treatment of acute myeloblastic leukaemia (AML). Moreover, high-dose cytarabine has been reported to produce long-term disease-free survival in a proportion of patients, especially in certain subtypes of AML. However, it remains unknown whether the outcome of patients undergoing allogeneic or autologous stem cell transplantation is influenced by previous treatment with high-dose cytarabine. To this end, 1672 patients with AML in first remission who were reported to the Acute Leukaemia Working Party registry of the European Group for Blood and Marrow Transplantation (EBMT) and who were transplanted between 1980 and 1995 were analysed according to the dose intensity of cytarabine given at induction and/or consolidation. Autologous stem cell transplantation (ABMT) was performed in 846 patients and allogeneic bone marrow transplantation (BMT) in 826 patients. This study shows that the dose of cytarabine (Ara-C) given at induction and/or consolidation did not influence the relapse incidence in patients subsequently allografted or autografted. In addition, it did not give any advantage in terms of overall outcome. Therefore, high-dose (HD) Ara-C may not be needed for patients who have a planned stem cell transplantation (SCT) as post-remission therapy. Nevertheless, HD Ara-C may be utilized in certain subtypes of AML that are believed to be curable by chemotherapy alone. [ABSTRACT FROM AUTHOR]

Examines the effect of the administration of high-dose recombinant Interleukin-2 (rIL-2) in patients with refractory or relapsed acute leukemia.

The absolute number of infused CD34+ donor cells represents a critical step towards the achievement of durable marrow engraftment after allogeneic hematopoietic stem cell transplantation (HSCT). Previous observations have reported controversial conclusions on the impact of CD34+ cell doses and post-transplant clinical end-points. We conducted a retrospective analysis on 414 adult patients (median age 54 years; range, 18-74) with acute myeloid leukemia (AML) in first (70%) and second (30%) complete remission who had received a T-cell replete allogeneic HSCT from a haploidentical donor, using peripheral blood stem cells (PBSC), between 2006-2018, based on ALWP-EBMT registry data. Graft vs. host disease (GVHD) prophylaxis was post-transplant cyclophosphamide (PT-Cy)-based in 293 (71%) patients and anti-lymphocyte serum (ATG)-based in 121 (29%) patients. Conditioning was myeloablative in 179 (43%) patients and reduced-intensity in 235 (57%) patients. Median number of infused CD34+ cells was 6.58 × 106/kg (range, 2.2-31.2). After a median follow-up of 23.3 months (range, 12.1-41.8) 2-year overall survival (OS) was 64.5% (95% CI 59.3-69.7) with a leukemia-free survival (LFS) of 57.3% (95% CI 51.8-62.7) and non-relapse mortality (NRM) of 23.3% (95% CI: 19.0-27.7). The cumulative incidence of grade II-IV and III-IV acute GVHD at day-100 were 32.3% (95% CI: 27.8 - 36.9) and 14.6% (95% CI: 11.3 - 18.2), respectively. Incidence of 2-years chronic GVHD overall and extensive were 36.3% (95% CI: 30.9 - 41.6) and 14.4% (95% CI: 10.7 - 18.6), respectively. GVHD-free/relapse-free survival was 43.5% (95% CI: 38 - 48.9) at 2-years. We found the optimal CD34+/kg threshold defining high-dose (n= 334) versus low-dose (n= 80) to be 4.96 × 106, using the Hothorn and Zeileis method (Hothorn, T. and Zeileis, A. Biometrics 2008;64(4):1263–1269). Recipients of > 4.96 × 106/kg CD34+ cells experienced lower NRM (hazard ratio [HR] 0.48; 95% CI: 0.29-0.75) and prolonged LFS (HR 0.62; 95% CI 0.43-0.90) and OS (HR 0.59; 95% CI: 0.40-0.87) than recipients of ≤ 4.96 × 106/kg CD34+ cell dose. Patients who received ATG as GVHD prophylaxis experienced less grades II-IV acute GVHD respect those in the PT-Cy cohort (HR 0.56; 95% CI: 0.36-0.87) without any differences in grades III-IV acute GVHD incidence at day 100 between the two groups. On Cox analysis, a female donor to male recipient combination was associated with higher extensive chronic GVHD incidence compared to other donor-recipient sex combinations, with CD34+ categorized according to the optimal threshold of 4.96 × 106 (HR 2.21; 95% CI: 1.23-3.97; p= 0.008). AML patients who underwent a PBSC T-cell replete HSCT from haploidentical donors receiving ≥ 4.96 × 106 CD34+/kg cells experienced a lower NRM and extended survival rates compared to those receiving ≤ 4.96 × 106/kg CD34+. The latter findings may have a significant practical impact and can guide prospective approaches. [ABSTRACT FROM AUTHOR]

• Outcomes of 122 haploidentical hematopoietic cell transplantations with post-transplantation cyclophosphamide for T cell acute lymphoblastic leukemia are reported. • Survival was mostly affected by disease status, being significantly better in first complete remission • Outcomes were not affected by conditioning, calling into question the need for total body irradiation. Allogeneic hematopoietic cell transplantation (HCT) is recommended in high-risk patients with T cell acute lymphoblastic leukemia (T-ALL). For patients without an HLA-identical donor, haploidentical (haplo-) HCT is becoming the leading source of stem cell donation. However, data are scarce on predictive factors for outcome in that setting. We identified 122 adults (20% female; median age, 31 years; range, 18 to 68 years) with T-ALL who underwent haplo-HCT with post-transplantation cyclophosphamide (ptCy) between 2010 and 2017. The median duration of follow-up of living patients was 23 months. The 2-year incidences of relapse and nonrelapse mortality were 45% and 21%, respectively. The 2-year leukemia-free survival (LFS), overall survival (OS), and graft-versus-host disease, relapse-free survival (GRFS) were 34%, 42%, and 27%, respectively. The 2-year LFS and OS were highly influenced by disease status at transplantation, being 49% and 55%, respectively, for patients in first complete remission (CR1); 34% and 50%, respectively, for those in second CR (CR2); and 8% and 12%, respectively, for patients with active disease. On multivariate analysis, only disease status was found to affect LFS and OS. Transplantation in CR2 negatively affected LFS, whereas active disease at the time of haplo-HCT negatively affected LFS and OS. In conclusion, haplo-HCT with ptCy produced encouraging results in this challenging disease, particularly when performed in patients in CR. Despite the limitation of the small sample size, our results were not affected by the type of conditioning, calling into question the need for total body irradiation-based myeloablative conditioning in that setting. [ABSTRACT FROM AUTHOR]

• Marked improvement has been achieved in recent years in stem cell transplantation (SCT) from unrelated donors. • Long-term outcome is equivalent after SCT from unrelated and sibling donors. • Patients who are leukemia-free 2 years after SCT can expect a favorable outcome. Allogeneic stem cell transplantation (SCT) is potentially curative therapy in acute myeloid leukemia (AML). Marked improvement has been achieved with SCT from matched unrelated donors (MUDs) in recent years. However, there are limited data comparing the long-term outcomes (beyond 10 years) after SCT from sibling donors and MUDs in older patients with AML. We analyzed these outcomes in a large cohort of patients with AML (n = 1134), age ≥50 years, who were alive and leukemia-free 2 years after SCT from matched siblings (n = 848) or MUDs (n = 286), with a median follow-up of 8.9 years. The median age was 56 and 58 years after SCT from siblings and MUDs, respectively (P =.005). In the sibling group, 77%, 12%, and 11% were in first complete remission (CR1), second complete remission (CR2), and active leukemia at SCT compared with 50%, 25%, and 25% in the MUD group, respectively (P <.001). Sixty-one percent of siblings and 62% of MUDs had reduced-intensity conditioning (P =.78). The 10-year leukemia-free survival (LFS) of patients surviving leukemia-free 2 years after SCT was 72% and 62%, respectively (P =.30). Multivariate analysis identified active leukemia at SCT (hazard ratio [HR], 1.86; P =.0001) or CR2 (HR, 1.51; P =.02) compared with CR1, female recipients (HR, 0.71; P =.006), adverse cytogenetics (HR, 2.52; P =.01), and prior graft-versus-host disease (HR, 1.31; P =.04) as independent factors predicting LFS. Donor and conditioning type were not significant. The cumulative incidence was 15% and 17% (P =.97) for late relapse mortality and 13% and 21% for late nonrelapse mortality, respectively (P =.15). In conclusion, long-term LFS is similar, and patients who are leukemia-free 2 years after SCT can expect favorable outcomes with both donor types. [ABSTRACT FROM AUTHOR]

Highlights • Umbilical cord blood transplantation (UCBT) offers high survival rates in children and young adults with acute leukemia. • Even with positive pretransplantation minimal residual disease (MRD), UCBT leads to high cure rate. • Double UCBT may have a better graft-versus-leukemia effect in patients with MRD. ABSTRACT We previously reported in a French prospective randomized study that transplantation of 2 unrelated cord blood (UCB) units instead of 1 unit does not decrease the risk of transplantation failure but may enhance alloreactivity. Here we evaluated the influence of pretransplantation minimal residual disease (MRD) on leukemia relapse and survival after single- versus double-UCB transplantation (UCBT). Among 137 children and young adults who underwent UCBT in this randomized study, 115 had available data on MRD assessment done immediately before initiation of the pretransplantation conditioning regimen. MRD was considered positive at a level of ≥10−4, which was the case of 43 out of 115 patients. Overall, the mean 3-year survival probability was 69.1 ± 4.4%, and it was not significantly influenced by the MRD level: 70.7 ± 5.4% in MRD-negative (<10−4) patients (n = 72), 71.1 ± 9.4% in MRD-positive patients with 10−4 ≤ MRD <10−3 (n = 26) and 58.8 ± 11.9% in MRD-positive patients with ≥10−3 (n = 17). In the MRD-positive group, the mean risk of relapse was significantly lower in the double-UCBT arm compared with the single-UCBT arm (10.5 ± 7.2% versus 41.7 ± 10.4%; P =.025) leading to a higher mean 3-year survival rate (82.6 ± 9.3% versus 53.6 ± 10.3%; P =.031). This difference was observed only in patients who had not received antithymocyte globulin during their conditioning regimen. In the MRD-negative group, there was no differencebetween the single- and the double-UCBT arms. We conclude that even in cases of positive pretransplantation MRD, UCBT in children and young adults with acute leukemia yields a high cure rate, and that a double-unit strategy may enhance the graft-versus-leukemia effect and survival in these patients. [ABSTRACT FROM AUTHOR]

Usually, after double umbilical cord blood transplantation (DUCBT), only 1 of the transplanted units persists in the long term. The characteristics of the winning cord blood unit (W-CBU) that determine unit dominance and how they influence the outcomes of DUCBT remain unclear. We retrospectively analyzed 347 patients with acute leukemia transplanted with a DUCBT (694 CBU) from 2005 to 2013 who had documented neutrophil engraftment and a W-CBU identified by chimerism analysis, to identify unit characteristics impacting on dominance. Median age at DUCBT was 40 years and median follow-up was 35 months. Among W-CBUs, 41% were ≥5/6 HLA matched to the recipient and 59% were ≤4/6. Multivariate analysis indicated that ≤4/6 HLA-matched W-CBUs led to lower leukemia-free survival (44% versus 56%; hazard ratio [HR], 1.5; P  = .032) and overall survival (49% versus 62%; HR, 1.5; P  = .028), increased nonrelapse mortality (26% versus 18%; HR, 1.9; P  = .027), and acute graft-versus-host disease (46% versus 35%; HR, 1.7; P  = .013). We were unable to predict unit dominance, but we demonstrated that outcomes were strongly influenced by the degree of HLA mismatch between W-CBU and recipient. Therefore, selection of both units with the lower number of HLA mismatches with the recipient is indicated. [ABSTRACT FROM AUTHOR]

Transplantation of 2 unrelated cord blood (UCB) units instead of 1 has been proposed to increase the cell dose. We report a prospective randomized study, designed to compare single- vs double-UCB transplantation in children and young adults with acute leukemia in remission or myelodysplasia. Eligible patients had at least two 4-6 HLA-identical UCBs with >3×107 nucleated cells/kg for the first and>1.5×107 for the second. The primary end point was the 2-year cumulative incidence of transplantation strategy failure, a composite end point including transplant-related mortality (TRM), engraftment failure, and autologous recovery. Randomized patients who did not proceed to transplantation due to refractory disease were considered transplantation failures. A total of 151 patients were randomized and included in the intent-to-treat analysis; 137 were transplanted. Double-UCB transplantation did not decrease transplantation strategy failure (23.4% ± 4.9% vs 14.9%±4.2%). Two-year posttransplant survival, disease-free survival, and TRM were 68.8%±6.0%, 67.6%±6.0%, and 5.9%±2.9% after single-unit transplantation compared with 74.8%±5.5%, 68.1%±6.0%, and 11.6% ± 3.9% after double-unit transplantation. The final relapse risk did not significantly differ, but relapses were delayed after double-unit transplantation. Overall incidences of graft-versus-host disease (GVHD) were similar, but chronic GVHD was more frequently extensive after double-UCB transplantation (31.9%±5.7% vs 14.7%±4.3%, P=.02). In an exploratory subgroup analysis, we found a significantly lower relapse risk after double-unit transplantation in patients receiving total body irradiation without antithymocyte globulin (ATG), whereas the relapse risk was similar in the group treated with busulfan, cyclophosphamide, and ATG. Single-UCB transplantation with adequate cell dose remains the standard of care and leads to low TRM. Double-unit transplantation should be reserved for patients who lack such units. This trial was registered at www.clinicaltrials.gov as #NCT01067300. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic cell transplantation is a potentially curative treatment in patients with acute myeloid leukemia. Recent advances in the field of hematopoietic cell allografting have resulted in a practice shift, favoring less intense preparative regimens. We present results of a retrospective comparative analysis of two preparative regimens, namely FB2 (IV fludarabine plus IV busulfan 6.4 mg/kg ± 10%) and FB4 (IV fludarabine plus IV busulfan 12.8 mg/kg ±10%), in patients with acute myeloid leukemia undergoing hematopoietic cell allografting in second complete remission at EBMT participating centers. Between 2003 and 2010, 128 AML patients in second complete remission were allografted following a preparative regimen of FB2 ( n = 88) or FB4 ( n = 40). The median time-to-neutrophil engraftment was similar whether patients received FB2 (16 (5–38) days) or FB4 (16 (9–29) days), p = 0.45. A multivariate analysis showed that use of FB4 resulted in improved 2-year leukemia-free (HR = 0.44 (95%CI = 0.21, 0.94), p = 0.03) and overall survival (HR = 0.38 (95%CI = 0.16, 0.86), p = 0.02). Cumulative incidence of non-relapse mortality (2-year) for all patients was 21% (95%CI = 14–28%). Our analysis suggests that FB4 improves 2-year leukemia-free and overall survival in AML allografted in second complete remission. A confirmatory randomized controlled trial that compares these two preparative regimens (FB2 vs. FB4) in AML in CR2 is definitely warranted. [ABSTRACT FROM AUTHOR]

We analyzed 661 adult patients who underwent single-unit (n = 226) or double-unit (n = 435) unrelated cord blood transplantation (UCBT) following a reduced-intensity conditioning (RIC) consisting of low-dose total body irradiation (TBI), cyclophosphamide, and fludarabine (Cy/Flu/TBI200). Eighty-two patients received rabbit antithymocyte globulin (ATG) as part of the conditioning regimen (ATG group), whereas 579 did not (non-ATG group). Median age at UCBT was 54 years, and diagnoses were acute leukemias (51%), myelodysplastic syndrome/myeloproliferative neoplasm (19%), and lymphoproliferative diseases (30%). Forty-four percent of patients were transplanted with advanced disease. All patients received ≥4 antigens HLA-matched UCBT. Median number of collected total nucleated cells was 4.4 × 107/kg. In the ATG group, on 64 evaluable patients, ATG was discontinued 1 (n = 27), 2 (n = 20), or > 2 days before the graft infusion (n = 17). In multivariate analyses, the use of ATG was associated with decreased incidence of acute graft-versus-host disease (hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.17-0.55; P < .0001), higher incidence of nonrelapse mortality (HR, 1.68; 95% CI, 1.16-2.43; P = .0009), and decreased overall survival (HR, 1.69; 95% CI, 1.19-2.415; P = .003). Collectively, our results suggest that the use of ATG could be detrimental, especially if given too close to graft infusion in adults undergoing UCBT following Cy/Flu/TBI200 regimen. [ABSTRACT FROM AUTHOR]

We report here the results of a retrospective study designed to evaluate outcome of patients with AML with KPS score ≤80% following allo-SCT. The analysis included adult AML patients undergoing allo-SCT in CR1 between 2000 and 2018, with a KPS score at the time of transplant between 50% and 80%. A total of 2,963 patients were identified. Median age at transplant was 55 years (18-77 years). The KPS score was 80% in 85% of the patients and <80% in 15% of the patients. Cytogenetic risk was good, intermediate or poor in 6%, 68% and 26% of the patients, respectively. Donor type was sibling (MSD), matched (10/10 UD), mismatched (9/10 UD) unrelated, haploidentical (haplo) or cord blood (CB) in 47%, 35%, 8%, 6% and 4% of patients. Conditioning was myeloablative (MAC) or reduced-intensity (RIC) in 42% and 58% of patients. Stem cell source was PBSC or BM in 84% and 14% of the patients, respectively. Cumulative incidence of grade II-IV acute GVHD (aGvHD) and chronic GVHD (cGvHD) was 26% and 38%, respectively. Non-relapse mortality (NRM) and relapse incidence (RI) at 2 years were 19% and 27%. Leukemia-free survival (LFS), overall survival (OS) and GVHD-free, relapse-free survival (GRFS) rates were 54%, 59% and 41%, respectively. On multivariate analysis, transplant from a MSD was associated with a reduced risk of aGvHD (10/10 UD HR 1.8, 9/10 UD HR 2.4, haplo HR 1.9, CB HR 3.4, p<10−4) and NRM (10/10 UD HR 1.4, 9/10 UD HR 2.4, haplo HR 1.8, CB HR 2, p<10−3, MSD as reference) as compared to all other donor types. Patients with KPS score of 80% had significantly lower NRM and improved survival as compared to patients with KPS<80%. Other factors independently associated with improved OS were younger age, female sex, good or intermediate risk cytogenetics and de-novo AML. In order to compare outcome following MAC and RIC conditioning regimens the analysis was restricted to patients receiving transplant from MSD or UD. Patients with a KPS score of 80% or <80% were analyzed separately. In the group of patients with a KPS score of 80%, a RIC regimen was associated with higher RI (HR 1.4, p<0.01), higher incidence of severe cGVHD (HR 1.6, p<0.001), and inferior GRFS (HR 1.3, p<0.001) as compared to MAC. NRM was not significantly different following RIC or MAC in this population. In contrast, in patients with a KPS score <80%, RIC was associated with lower NRM (HR 0.3, p<0.0001) and better LFS (HR 0.6, p<0.01), OS (HR 0.5, p<0.0001) and GRFS (HR 0.6, p<0.01) as compared to MAC. In conclusion, allo-SCT is feasible in patients with acute myeloid leukemia in first remission and KPS score ≤80%, with acceptable NRM and survival rates. In patients with a KPS score of 80% a MAC regimen was associated with lower relapse rate, similar NRM and better GRFS as compared to RIC, while in patients with a KPS score <80% RIC was associated with reduced NRM and improved OS. In addition, transplant from a MSD was associated with reduced risk of NRM and aGVHD rates as compared to other donor types. [ABSTRACT FROM AUTHOR]