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Core-binding factor acute myeloid leukemia (CBF-AML) represents 12-15% of all AML cases. Although CBF positivity infers a survival advantage, overall survival (OS) remains dismal. Treatment is with cytarabine/anthracycline-based chemotherapy induction followed by high-dose cytarabine (HiDAC) consolidation. Allogeneic hematopoietic stem cell transplantation (allo-SCT) is reserved for relapse or for patients having not achieved MRD-negativity at high risk for relapse. The role of SCT in first complete remission (CR1) remains controversial and is considered in high risk conditions. In this retrospective, multi-national, European Society for Blood and Marrow Transplantation (EBMT)-based study, we identified 1901 patients with de novo CBF-AML who received an allo-SCT or autologous transplantation (ASCT) in CR1. 65.5% harbored t(8;21) and 34.4% inv(16). In this group, the majority (77%) were treated with allo-SCT in CR1. In multivariate analysis, treatment with allo-SCT was an independent and significant, negative predictor of NRM and OS (HR 4.26, p < 0.0001 and HR 1.67, p = 0.003) and among patients treated with allo-SCT, those treated with MSD had the best outcomes, comparable to those treated with ASCT. There was no interaction between the type of transplant and MRD status at time of SCT. In both, MRD-negative and MRD-positive groups, NRM was worse in the allo-SCT group (MRD-: 12.9% vs 5.2%, p = 0.007; MRD+: 10.6% vs 0%, p = 0.004). We therefore demonstrated that consolidation in CR1 with allo-SCT results in worse outcomes than ASCT. Whether consolidation with ASCT yields better outcomes than chemotherapy alone or chemotherapy in combination with Gemtuzumab Ozogamicin is yet to be investigated., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Choice of calcineurin inhibitor may impact the outcome of patients undergoing T-cell replete hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PT-Cy) and mycophenolate mofetil (MMF) for prophylaxis of graft-versus-host disease (GVHD). We retrospectively analyzed 2427 patients with acute myeloid leukemia (AML) in first remission transplanted from a haploidentical (n = 1844) or unrelated donor (UD, n = 583) using cyclosporine A (CSA, 63%) or tacrolimus (TAC, 37%) and PT-Cy/MMF. In univariate analysis, CSA and TAC groups did not differ in 2-year leukemia-free or overall survival, cumulative incidence (CI) of relapse or non-relapse mortality. CI of severe grade III-IV acute GVHD was lower with TAC (6.6% vs. 9.1%, p = 0.02), without difference in grade II-IV acute GVHD or grade III-IV acute GVHD/severe chronic GVHD, relapse-free survival (GRFS). In multivariate analysis, TAC was associated with a lower risk of severe grade III-IV acute GVHD solely with haploidentical donors (HR 0.64 [95% CI, 0.42-0.98], p = 0.04), but not UD (HR 0.49 [95% CI, 0.2-1.21], p = 0.12). There was no significant difference for chronic GVHD. In conclusion, PT-Cy/MMF-based GVHD prophylaxis resulted in favorable OS and GRFS, irrespective of the CNI added. In haploidentical HCT, TAC seemed to prevent severe acute GVHD more effectively than CSA without impact on other outcome parameters., (© 2024. The Author(s).)

We assessed outcomes of allogeneic transplantation (HSCT) in favorable risk AML in CR1 over 3 time periods. 1850 patients were included, 2005 to 2009- 222, 2010 to 2014 -392, and 2015 to 2021-1236; 526 with t (8:21), 625 with inv (16), and 699 with NPM1 mut FLT3 WT . Patients transplanted in 2015-2021 were older (p < 0.0001) with more patients ≥60 years of age (p < 0.0001). The most frequent diagnosis in 2015-2021 was NPM1 mut FLT3 WT vs. t (8:21) in the 2 earlier periods, (p < 0001). Haploidentical transplants (Haplo) increased from 5.9% to 14.5% (p < 0.0001). Graft-versus-host disease (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy) was more frequent in 2015-2021 vs. the other 2 periods (p < 0.0001). On multivariate analysis, incidence of total chronic GVHD was reduced in HSCTs performed ≥2015 vs. those performed in 2005-2009, hazard ratio (HR) = 0.74 (95% CI 0.56-0.99, p = 0.046) and GVHD-free, relapse-free survival (GRFS) improved for patients transplanted from 2010-2014 vs. those transplanted in 2005-2009, HR = 0.74 (95% CI 0.56-0.98, p = 0.037). Other HSCT outcomes did not differ with no improvement ≥2015. LFS, OS, and GRFS were inferior in patients with t (8:21) with HR = 1.32 (95% CI 1.03-1.68, p = 0.026), HR = 1.38 (95% CI 1.04-1.83, p = 0.027) and HR = 01.25 (95% CI 1.02-1.53, p = 0.035), respectively. In conclusion, this retrospective analysis of HSCT in patients with favorable risk AML, transplanted over 16 years showed an increased number of transplants in patients ≥60 years, from Haplo donors with PTCy. Most importantly, 3-year GRFS improved ≥2010 and total chronic GVHD reduced ≥2015, with no significant change in other HSCT outcomes., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

We compared transplantation (HSCT) outcomes in AML patients undergoing HSCT with post-transplant cyclophosphamide (PTCy) in first complete remission from 1065 young (<35 years) haploidentical (Haplo) donors (yHaplo) vs. 147 old (≥35 years) mismatched unrelated donors (oMMUD) (first comparison) and from 271 young (<35 years) MMUD (yMMUD) vs. 1315 old (≥35 years) Haplo donors (oHaplo) (second comparison). Acute graft-versus-host disease (aGVHD) grades II-IV were significantly lower in the yHaplo vs. oMMUD group (HR = 0.62, p = 0.007). There were no significant differences in chronic GVHD, non-relapse mortality (NRM), relapse incidence, leukemia-free survival, overall survival, and GVHD-free and relapse-free survival. As for the second comparison, more patients in the oHaplo group had de novo AML, 86.6% vs. 81.9% in the yMMUD group (p = 0.044), while myeloablative conditioning was used more frequently in the yMMUD group, 53.3% vs. 46.8% in the oHaplo group (p = 0.049). aGVHD grades II-IV and NRM were significantly lower in the yMMUD vs. oHaplo group (HR = 0.69, p = 0.013 and HR = 0.60, p = 0.022). All other transplant outcomes did not differ. In conclusion, HSCT from young alternative donors (<35 years) results in a lower incidence of grades II-IV aGVHD. In addition, NRM is lower in HSCT from yMMUD compared to HSCT from oHaplo., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) mutations have uncertain prognostic implications in AML. We investigate the impact IDH1 and IDH2 mutations in AML patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) in first complete remission (CR1). In total, 1515 adult patients were included, 15.91% (n = 241) carried IDH1 mutation (mIDH1), and 26.27% (n = 398) IDH2 mutation (mIDH2) and 57.82% (n = 876) had no-IDH mutation. NPM1 was frequently encountered with IDH1 mutation (no-IDH group, n = 217, 24.8%, mIDH1, n = 103, 42.7%, mIDH2, n = 111, 27.9%, p < 0.0001). At day 180, the cumulative incidence (CI) of grade II-IV acute graft-versus-host disease (GVHD) was significantly lower in mIDH1 and mIDH2 compared to no-IDH groups (Hazard ratio [HR] = 0.66 (95% CI 0.47-0.91), p = 0.011; HR = 0.73 (95% CI 0.56-0.96), p = 0.025, respectively). In the mIDH1 group, overall survival (OS) was improved compared to no-IDH (HR = 0.68 (95% CI 0.48-0.94), p = 0.021), whereas mIDH2 was associated with lower incidence of relapse (HR = 0.49 (95% CI 0.34-0.7), p < 0.001), improved leukemia free survival (LFS) (HR = 0.7 (95% CI 0.55-0.9), p = 0.004) and OS (HR = 0.74 (95% CI 0.56-0.97), p = 0.027). In the subgroup of NPM1 wild type, only IDH2 was associated with improved outcomes. In conclusion, our data suggest that IDH1 and IDH2 mutations are associated with improved outcomes in patients with AML undergoing allo-HCT in CR1., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

While post-transplant cyclophosphamide (PTCy) is commonly used as graft-versus-host disease (GvHD) prophylaxis in haploidentical stem cell transplantation (haplo-HSCT), its dose remains a matter of debate due to side effect concerns. Standard dose of 100 mg/kg associated with tacrolimus and post-engraftment anti-thymocyte globulin (ATG) was used as the reference GvHD prophylaxis in our center and had demonstrated encouraging results. Though PTCy 80 mg/kg was shown to be feasible in patients in reduced-intensity conditioning, whether it exerts equivalent GvHD prophylactic efficacy in myeloablative conditioning (MAC) setting has not been confirmed. Here, we retrospectively analyzed the efficacy and safety of PTCy 80 mg/kg combined with tacrolimus and post-engraftment ATG as GvHD prophylaxis in patients aged more than 55 years or with cardiac antecedents or HCT-CI score >2 undergoing haplo-HSCT with MAC. The cumulative incidence of grade III-IV aGvHD at day 100 and moderate-to-severe cGvHD at 1 year was 4.8% ± 3.4% and 19.9% ± 7.0%, respectively. When compared with patients receiving the reference regimen, patients from the PTCy 80 mg/kg group had similar incidence of GvHDs and survival as their younger counterparts. Thus, PTCy 80 mg/kg seems to be feasible for patients treated with MAC conditioning regimens in haplo-HSCT, inviting further investigation notably in frail patients., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Allogeneic stem cell transplantation (Allo-SCT) is the only rapidly available curative treatment modality in patients with severe sickle cell disease (SCD). The development of reduced-toxicity myeloablative conditioning (RT-MAC) regimen and the use of partially matched family donors with post-transplantation cyclophosphamide (PT-Cy) have widened the access to Allo-SCT. Antibodies against donor-specific HLA (DSA) increase the risk of engraftment failure in HLA mismatched Allo-SCT. We report the results of five patients with SCD, whereas three with DSA, who underwent an unmanipulated haploidentical stem cell transplantation (Haplo-SCT) after a busulfan-based RT-MAC regimen with PT-Cy. To reduce the risk of engraftment failure, a sequential two courses pharmacological pre-transplant immune suppression (PTIS) phase was added prior to the conditioning regimen. All patients engrafted successfully. The procedure was well tolerated. None of the patients developed acute GVHD, whereas one developed moderate chronic GVHD. After a median follow-up of 5 years (range, 2.2-9), all patients are free of pain with excellent quality of life. Our report shows that Haplo-SCT after a RT-MAC regimen is feasible and safe with stable long-term engraftment and excellent disease control. The risk of graft failure can be abrogated by adding a PTIS phase prior to initiating the conditioning regimen., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Obesity and diabetes can modulate immune responses, which may impact allogeneic HCT outcomes and GvHD. From the EBMT registry, we included 36,539 adult patients who underwent allogeneic HCT for a hematological malignancy between 2016 and 2020. Of these, 5228 (14%) had obesity (BMI ≥ 30 kg/m 2 ), 1415 (4%) had diabetes (requiring treatment with insulin or oral hypoglycemics), and 688 (2%) had obesity + diabetes pre-transplantation. Compared with patients without diabetes or obesity, the hazard ratio (HR) of grade II-IV acute GvHD was 1.00 (95% confidence interval [CI] 0.94-1.06, p = 0.89) for patients with obesity, 0.95 (CI 0.85-1.07, p = 0.43) for patients with diabetes, and 0.96 (CI 0.82-1.13, p = 0.63) for patients with obesity + diabetes. Non-relapse mortality was higher in patients with obesity (HR 1.08, CI 1.00-1.17, p = 0.047), diabetes (HR 1.40, CI 1.24-1.57, p < 0.001), and obesity + diabetes (HR 1.38, CI 1.16-1.64, p < 0.001). Overall survival after grade II-IV acute GvHD was lower in patients with diabetes (HR 1.46, CI 1.25-1.70, p < 0.001). Pre-transplantation diabetes and obesity did not influence the risk of developing acute GvHD, but pre-transplantation diabetes was associated with poorer survival after acute GvHD., (© 2023. The Author(s).)

Haploidentical stem cell transplantation (Haplo-SCT) using non-myeloablative conditioning regimen (NMAC) has extended the feasibility of allogeneic transplantation, notably in older patients. However, there is few data specifically focusing on patients aged 70 years and over with AML and MDS. Thus the benefit of transplantation in this population is still debated. Here we report our single center experience of peripheral blood Haplo-SCT with NMAC and post-transplantation cyclophosphamide in AML and MDS patients aged 70 years and over. We analyzed 50 patients (27 AML, 23 MDS) with a median age of 72 years (70-77), 12/50 (24%) with active disease at Haplo-SCT. Cumulative incidence of grade 3-4 acute and moderate or severe chronic GVHD were 6% and 25%, respectively. Non-relapse mortality (NRM) at day +100 was 0%. NRM, relapse, PFS and OS at 3 years were 16%, 18%, 66%, and 69%, respectively. Among patients who were disease free at 2 years post Haplo-SCT, 88% are living without immunosuppressive treatment. Peripheral blood Haplo-SCT is feasible in selected AML/MDS patients over 70 years, without any early NRM. It produces long-term disease control and survival. Thus, age by itself should not be considered as a formal barrier to Haplo-SCT., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Allogeneic hematopoietic cell transplantation is a potentially curative treatment in high-risk acute lymphoblastic leukemia (ALL). Conditioning regimens based on ≥12 Gray total body irradiation (TBI) represent the current standard in patients ≤45 years, whereas elderly patients frequently receive intermediate intensity conditioning (IIC) to reduce toxicity. To evaluate the role of TBI as a backbone of IIC in ALL, a retrospective, registry-based study included patients >45 years transplanted from matched donors in first complete remission, who had received either fludarabine/TBI 8 Gy (FluTBI8, n = 262), or the most popular, irradiation-free alternative fludarabine/busulfan, comprising busulfan 6.4 mg/kg (FluBu6.4, n = 188) or 9.6 mg/kg (FluBu9.6, n = 51). At two years, overall survival (OS) was 68.5%, 57%, and 62.2%, leukemia-free survival (LFS) was 58%, 42.7%, and 45%, relapse incidence (RI) was 27.2%, 40%, and 30.9%, and non-relapse-mortality (NRM) was 23.1%, 20.7%, and 26.8% for patients receiving FluTBI8Gy, FluBu6.4, and FluBu9.6, respectively. In multivariate analysis, the risk of NRM, acute and chronic graft-versus-host disease was not influenced by conditioning. However, RI was higher after FluBu6.4 (hazard ratio [HR] [95% CI]: 1.85 [1.16-2.95]), and LFS was lower after both FluBu6.4 (HR: 1.56 [1.09-2.23]) and FluBu9.6 (HR: 1.63 [1.02-2.58]) as compared to FluTBI8. Although only resulting in a non-significant advantage in OS, this observation indicates a stronger anti-leukemic efficacy of TBI-based intermediate intensity conditioning., (© 2023. The Author(s).)

We compared transplants (HSCT) from matched related siblings (MSD) with those from matched 10/10 and mismatched 9/10 unrelated (UD) and T-replete haploidentical (Haplo) donors in acute myeloid leukemia (AML) in first complete remission (CR1) achieved after two inductions, a known poor prognostic factor. One thousand two hundred and ninety-five patients were included: MSD (n = 428), UD 10/10 (n = 554), UD 9/10 (n = 135), and Haplo (n = 178). Acute GVHD II-IV was higher in all groups compared to MSD. Extensive chronic (c) GVHD was significantly higher in UD 9/10 (HR = 2.52; 95% CI 1.55-4.11, p = 0.0002) and UD 10/10 (HR = 1.48; 95% CI 1.03-2.13, p = 0.036) and cGVHD all grades were higher in UD 9/10 vs MSD (HR = 1.77; 95% CI 1.26-2.49, p = 0.0009). Non-relapse mortality was higher in all groups compared to MSD. Relapse incidence, leukemia-free, and overall survival did not differ significantly between donor types. Finally, GVHD-free relapse-free survival was lower in HSCT from UD 9/10 (HR = 1.56, 95% CI 1.20-2.03, p = 0.0009) but not in those from UD 10/10 (HR = 1.13, p = 0.22) and Haplo donors (HR = 1.12, p = 0.43) compared to MSD. In conclusion, in AML patients undergoing HSCT in CR1 achieved after two induction courses 10/10 UD and Haplo but not 9/10 UD donors are comparable alternatives to MSD., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Pre-transplant detectable measurable residual disease (MRD) is still associated with high risk of relapse and poor outcomes in acute myeloid leukemia (AML). We aimed at evaluating the impact of disease burden on prediction of relapse and survival in patients receiving allogeneic hematopoietic cell transplantation (allo-HCT) in first remission (CR1). We identified a total of 3202 adult AML patients, of these 1776 patients were in CR1 and MRD positive and 1426 patients were primary refractory at time of transplant. After a median follow-up of 24.4 months, non-relapse mortality and relapse rate were significantly higher in the primary refractory group compared to the CR1 MRD positive group (Hazards Ratio (HR) = 1.82 (95% CI: 1.47-2.24) p < 0.001 and HR = 1.54 (95% CI: 1.34-1.77), p < 0.001), respectively. Leukemia-free survival (LFS) and overall survival (OS) were significantly worse in the primary refractory group (HR = 1.61 (95% CI: 1.44-1.81), p < 0.001 and HR = 1.71 (95% CI: 1.51-1.94), p < 0.001, respectively). Our real-life data suggest that patients in CR1 and MRD positive at time of transplant could still be salvaged by allo-HCT with a 2-year OS of 63%, if negative MRD cannot be obtained and their outcomes are significantly better than patients transplanted with active disease., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life-threatening complication that can develop after hematopoietic cell transplantation (HCT). A new definition for diagnosis, and a severity grading system for SOS/VOD in adult patients, was reported a few years ago on behalf of the European Society for Blood and Marrow Transplantation (EBMT). The aim of this work is to update knowledge regarding diagnosis and severity assessment of SOS/VOD in adult patients, and also its pathophysiology and treatment. In particular, we now propose to refine the previous classification and distinguish probable, clinical and proven SOS/VOD at diagnosis. We also provide an accurate definition of multiorgan dysfunction (MOD) for SOS/VOD severity grading based on Sequential Organ Failure Assessment (SOFA) score., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Allogeneic transplantation (allo-HCT) is a curative treatment in CLL whose efficacy including the most severe forms had led to the 2006 EBMT recommendations. The advent after 2014 of targeted therapies has revolutionized CLL management, allowing prolonged control to patients who have failed immunochemotherapy and/or have TP53 alterations. We analysed the pre COVID pandemic 2009-2019 EBMT registry. The yearly number of allo-HCT raised to 458 in 2011 yet dropped from 2013 onwards to an apparent plateau above 100. Within the 10 countries who were under the EMA for drug approval and performed 83.5% of those procedures, large initial differences were found but the annual number converged to 2-3 per 10 million inhabitants during the 3 most recent years suggesting that allo-HCT remains applied in selected patients. Long-term follow-up on targeted therapies shows that most patients relapse, some early, with risk factors and resistance mechanisms being described. The treatment of patients exposed to both BCL2 and BTK inhibitors and especially those with double refractory disease will become a challenge in which allo-HCT remains a solid option in competition with emerging therapies that have yet to demonstrate their long-term effectiveness., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Allogeneic hematopoietic stem cell transplantation remains the best curative option for higher-risk myelodysplastic syndrome. The presence of monosomal karyotype and/or complex karyotype abnormalities predicts inferior survival after allo-SCT in MDS patients. Haploidentical allo-SCT has been increasingly used in acute leukemia (AL) and has similar results as using HLA-matched donors, but data on higher-risk MDS is sparse. We compared outcomes in 266 patients with higher-risk MDS after HLA-matched sibling donor (MSD, n = 79), HLA-matched unrelated donor (MUD, n = 139) and HLA haploidentical donor (HID, n = 48) from 2010 to 2019. Median donor age differed between the three groups (p < 0.001). The overall survival was significantly different between the three groups with a better OS observed in the MUD group (p = 0.014). This observation could be explained by a higher progression-free survival with MUD (p = 0.014). The cumulative incidence of grade 2-4 acute GvHD was significantly higher in the HID group (p = 0.051). However, in multivariable analysis, patients transplanted using an HID had comparable mortality to patients transplanted using a MUD (subdistribution hazard ratio [sHR]: 0.58 [0.32-1.07]; p = 0.080) and a MSD ([sHR]: 0.56 [0.28-1.11]; p = 0.094). MUD do not remain a significant positive predictor of survival, suggesting that beyond the donor-recipient HLA matching, the donor age might impact recipient outcome., (© 2023. The Author(s).)

Post-transplant cyclophosphamide (PTCy) is being increasingly used as graft-versus-host disease (GVHD) prophylaxis post allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML) transplanted in first complete remission (CR1). However, results may differ in patients transplanted in CR2. We retrospectively evaluated transplant outcomes of adult AML patients transplanted between 2010-2019 from 9-10/10 human leukocyte antigen (HLA)-matched unrelated donor (UD) in CR2. In total, 127 patients were included (median age 45.5 years, 54% male). Median follow-up was 19.2 months. Conditioning was myeloablative (MAC) in 50.4% and the graft source was peripheral blood in 93.7% of the transplants. Incidence of acute (a)GVHD II-IV and III-IV was 26.2% and 9.2%. Two-year total and extensive chronic (c)GVHD were 34.3% and 13.8 %, respectively. Two-year non-relapse mortality (NRM), relapse incidence (RI), leukemia-free survival (LFS), overall survival (OS), and GVHD-free, relapse-free survival (GRFS) were 17.2%, 21.1%, 61.7, %, 65.2%, and 49.3%, respectively. Time from diagnosis to transplant (>18 months) was a favorable prognostic factor for RI, LFS, OS, and GRFS while favorable risk cytogenetics was a positive prognostic factor for OS. The patient's age was a poor prognostic factor for NRM and cGVHD. Finally, the female-to-male combination and reduced intensity conditioning (RIC) were poor and favorable prognostic factors for cGVHD, respectively. We conclude that PTCy is an effective method for GVHD prophylaxis in AML patients undergoing allo-HCT in CR2 from UD., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of haematopoietic cell transplantation (HCT) conditioning. The DEFIFrance post-marketing registry study evaluated effectiveness and safety in patients who received defibrotide. It collected retrospective/prospective patient data from 53 French HCT centres from July 2014 to March 2020. Primary endpoints were survival and complete response (CR; total serum bilirubin <2 mg/dL, multiorgan failure resolution) at Day 100 post-HCT among patients with severe/very severe VOD/SOS. A secondary endpoint was evaluation of treatment-emergent serious adverse events (TESAEs) of interest. Of 798 patients analysed, 251 and 81 received defibrotide treatment for severe/very severe VOD/SOS and mild/moderate VOD/SOS post-HCT, respectively; 381 received defibrotide for VOD/SOS prophylaxis. In patients with severe/very severe VOD/SOS post-HCT, Kaplan-Meier-estimated CR at Day 100 was 74% (95% confidence interval [CI]: 66%, 81%). At Day 100, 137/251 (55%) were alive and in CR. Kaplan-Meier-estimated Day 100 post-HCT survival was 61% (95% CI: 55%, 67%) in patients with severe/very severe VOD/SOS. TESAEs of interest occurred in 29% of these patients; VOD/SOS-related mortality at 12 months was 15%. DEFIFrance represents the largest collection of real-world data on post-registration defibrotide use, supporting the real-world utility of defibrotide for patients with severe/very severe VOD/SOS post-HCT., (© 2022. The Author(s).)

Allogeneic hematopoietic cell transplantation (allo-HCT) with reduced intensity conditioning (RIC) is an option for elderly patients with acute lymphoblastic leukemia (ALL). We retrospectively compared results of RIC-allo-HCT from either a matched sibling donor (MSD, n = 209) or matched unrelated donor (MUD, n = 209) with autologous (auto, n = 142) HCT for patients aged 55 years or more treated in first complete remission (CR1) between 2000 and 2018. The probabilities of leukemia-free survival (LFS) at 5 years were 34% for RIC-allo-HCT versus 39% for auto-HCT (p = 0.11) while overall survival (OS) rates were 42% versus 45% (p = 0.23), respectively. The incidence of relapse (RI) and non-relapse mortality (NRM) was 41% versus 51% (p = 0.22) and 25% versus 10% (p = 0.001), respectively. In a multivariate model, using auto-HCT as reference, the risk of NRM was increased for MSD-HCT (Hazard ratio [HR] = 2.1, p = 0.02) and MUD-HCT (HR = 3.08, p < 0.001), which for MUD-HCT translated into a decreased chance of LFS (HR = 1.55, p = 0.01) and OS (HR = 1.62, p = 0.008). No significant associations were found with respect to the risk of relapse. We conclude that for patients with ALL in CR1, aged above 55 years, auto-HCT may be considered a transplant option alternative to RIC-allo-HCT, although its value requires verification in prospective trials., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Although post-transplant cyclophosphamide (PT-Cy) is effective for graft-versus-host disease (GVHD) prophylaxis, it is associated with toxicities, which might be dose-dependent. We compared the outcomes with PT-Cy at 80 mg/kg to those with PT-Cy at 100 mg/kg in elderly patients undergoing haploidentical hematopoietic cell transplantation (HCT). Inclusion criteria included peripheral blood stem cells, hematological malignancy, and age>65 years (or age>60 years if cardiac event history). Thirty-eight patients received PT-Cy at 80 mg/kg and 55 100 mg/kg, divided in two doses. The cumulative incidences (CI) of acute grade II-IV, acute grade III-IV, and moderate/severe chronic GVHD were 32%, 16%, and 13% with PT-Cy at 80 mg/kg compared to 33%, 13%, and 16% with 100 mg/kg, respectively. In multivariable analysis, reducing PT-Cy dose had no significant impact on GVHD. Neutrophil and platelet engraftments were significantly improved, and CI of BK virus-associated hemorrhagic cystitis was reduced with 80 mg/kg of PT-Cy compared to 100 mg/kg. At 2 years, non-relapse mortality was 16% and 31%, progression-free survival 65% and 49%, overall survival 70% and 56%, and GVHD-free, relapse-free survival 52% and 36% with 80 mg/kg and 100 mg/kg, respectively. Reducing PT-Cy dose to 80 mg/kg is safe and associated with improved hematological recovery and lower CI of hemorrhagic cystitis in elderly patients undergoing haploidentical HCT., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Trends in outcome of transplantation (HSCT) in secondary acute myeloid leukemia (sAML) are limited. We evaluated results of HSCT in 4224 patients with sAML in complete remission; 1337 were transplanted in 2000-2010 and 2887 in 2011-2020. Median age was 54 (range, 18-74) and 59 (range, 18-78) years, respectively (p < 0.0001). Donors were MSD in 65% vs. 37%, 10/10 UD in 27% vs. 50%, and 9/10 UD in 8% vs. 13%, respectively (p < 0.0001). Conditioning was myeloablative in 46% and 38%, respectively. Two-year non-relapse mortality (NRM) was lower in patients transplanted in 2011-2020 vs. those transplanted in 2000-2010, 18% vs. 21% (hazard ratio (HR) = 0.82, 95% CI: 0.68-0.9; p = 0.04) and modified GVHD-free, relapse-free survival (GRFS) (HR = 0.9, 95% CI: 0.81-0.99; p = 0.04) was better in patients transplanted in the 2011-2020 vs. those transplanted in 2000-2010. Two-year relapse incidence (RI) was similar between the 2 groups with 32% vs. 31%, (HR = 1.05, 95% CI: 0.9-1.22; p = 0.55). Likewise, leukemia-free survival (LFS) (HR = 0.95, 95% CI: 0.84-1.07; p = 0.38) and overall survival (OS) (HR = 0.93, 95% CI: 0.82-1.05; p = 0.26) were not significantly different between the two periods. In conclusion, Incidence of NRM has been significantly reduced and GRFS significantly increased in HSCT for sAML in the last 2 decades., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Donor selection may contribute to improve clinical outcomes of T cell-replete haploidentical stem cell transplantation (Haplo-SCT) with post-transplant cyclophosphamide (PT-Cy). Impact of second-degree related donor (SRD) was not fully elucidated in this platform. We retrospectively compared the outcome of patients receiving Haplo-SCT either from a SRD (n = 31) or a first-degree related donor (FRD, n = 957). Median time to neutrophil and platelet recovery did not differ between a SRD and a FRD transplant (p = 0.599 and 0.587). Cumulative incidence of grade II-IV acute graft-versus host disease (GVHD) and moderate-severe chronic GVHD was 13% and 19% after SRD vs 24% (p = 0.126) and 13% (p = 0.395) after FRD transplant. One-year cumulative incidence of non-relapse mortality (NRM) was 19% for SRD and 20% for FRD (p = 0.435) cohort. The 3-year probability of overall survival (OS) and progression-free survival (PFS) was 42% vs 55% (p = 0.273) and 49% vs 35% (p = 0.280) after SRD and FRD transplant, respectively. After propensity score adjustment or matched pair analysis, the outcome of patients receiving Haplo-SCT from a SRD or a FRD did not differ in terms of NRM, OS, PFS, acute and chronic GVHD. Our results suggest that a SRD is a viable option for Haplo-SCT with PT-Cy when a FRD is not available., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

In this registry-based study which includes acute myeloid leukemia patients who underwent a matched unrelated donor allogeneic peripheral-blood stem cell transplantation in complete remission and received post-transplant cyclophosphamide (PTCY) as graft-versus-host disease (GvHD) prophylaxis, we compared 421 recipients without anti-thymocyte globulin (ATG) with 151 patients with ATG. The only significant differences between PTCY and PTCY + ATG cohorts were the median year of transplant and the follow-up period (2017 vs 2015 and 19.6 vs 31.1 months, respectively, p < 0.0001). Overall, 2-year survival was 69.9% vs 67.1% in PTCY and PTCY + ATG, respectively, with deaths related to relapse (39% vs 43.5%), infection (21.9% vs 23.9%) or GvHD (17.1% vs 17.4%) not differing between groups. On univariate comparison, a significantly lower rate of extensive chronic GvHD was found when ATG was added (9.9% vs 21%, p = 0.029), a finding which was not confirmed in the multivariate analysis. The Cox-model showed no difference between PTCY + ATG and PTCY alone with respect to acute and chronic GvHD of all grades, non-relapse mortality, relapse, leukemia-free survival, overall survival, and GvHD-free-relapse-free survival between study cohorts. Our results highlight that the addition of ATG in PTCY does not provide any extra benefit in terms of further GvHD reduction, better GRFS or better survival., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

HLA-haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HCT) is frequently used as treatment for patients with active acute myeloid leukemia (AML). Here, we investigated whether 9/10 HLA-mismatched unrelated donor transplantation (MMUD-HCT) with post-transplant cyclophosphamide (PTCy) is an adequate alternative. Inclusion criteria in this retrospective registry study consisted of adult patients, first HCT with a Haplo donor or MMUD between 2010 and 2020 using PTCy as graft-versus-host disease (GVHD) prophylaxis, and primary refractory or relapsed disease. MMUD patients were pair-matched 1 to 2 with Haplo-recipients. A total of 73 MMUD patients met the inclusion criteria. Their data were compared to those of 146 Haplo patients in a matched-pair analysis. Median follow-up was 27 months in MMUD patients and 36 months in Haplo recipients. Two-year incidences of relapse and non-relapse mortality (NRM) were 40% and 18% in MMUD patients, respectively, versus 50% (P = 0.23) and 24% (P = 0.18) in Haplo recipients. Two-year leukemia-free survival (LFS) and overall survival (OS) was 42% and 46% in MMUD recipients, respectively, versus 26% (P = 0.1) and 28% (P = 0.061) in Haplo-patients. In conclusions, in AML patients with active disease at transplantation, MMUD-HCT results in at least comparable outcomes to Haplo-HCT when PTCy is applied., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

We compared transplantation outcomes of adult patients with AML that underwent cord blood transplantation (CBT) in CR1 following 1 versus 2 induction courses. Study included 325 patients, 243 (75%) with 1 and 82 (25%) with 2 induction courses. Engraftment was lower for patients achieving CR1 after 1 vs. 2 induction courses: 91% vs. 99% (p = 0.02). Incidence of acute GVHD was similar, 38% and 36% (p = 0.81), as was 2-year chronic GVHD at 23.4% and 27.5%, respectively (p = 0.65). Two-year non-relapse mortality (NRM), relapse incidence (RI), leukemia-free survival (LFS), overall survival (OS) and GVHD-free, relapse-free survival (GRFS) were not statistically different between patients achieving CR1 with 1 vs. 2 induction courses with 23% vs. 24% (p = 0.87), 25% vs. 30% (p = 0.4), 52% vs. 46% (p = 0.3), 59% vs. 50% (p = 0.2), and 44% vs. 41% (p = 0.66), respectively. Results were confirmed by multivariable analysis, NRM (hazard ratio (HR) = 1.1; 95% CI, 0.6-1.8, p = 0.7), RI (HR = 1.4; 95% CI, 0.9-2.3, p = 0.1), LFS (HR = 1.3; 95% CI, 0.9-1.8, p = 0.2), OS (HR = 1.3; 95% CI, 0.9-1.9, p = 0.1), and GRFS (HR = 1.1; 95% CI, 0.8-1.5, p = 0.5). Overall, outcomes of AML patients undergoing CBT in CR1 achieved after 1 or 2 induction courses are similar., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

The optimal conditioning regimen prior haploidentical stem cell transplantation (Haplo-SCT) with post transplantation cyclophosphamide (PT-Cy) for acute myeloid leukemia (AML) remains unknown. A non-myeloablative conditioning (NMAC) regimen (cyclophosphamide + fludarabine + TBI 2 Gy [CyFluTBI]) is a safe approach, but relapse incidence remains high in this setting. Alternatively, a reduced intensity conditioning (RIC) regimen combining thiotepa and reduced-dose busulfan with fludarabine (TBF) may decrease AML relapse. However, an excess of toxicity may counterbalance this potential benefit. We retrospectively compared CyFluTBI vs. TBF in CR AML patients who underwent Haplo-SCT with PT-Cy, in two different populations based on age. We analyzed 490 patients. In patients aged <60 years (n = 203), we observed a higher RI (HR = 3.59, 95% CI = 1.75-7.37, p < 0.01), lower LFS (HR = 1.98, 95% CI = 1.22-3.22, p < 0.01) and lower OS (HR = 1.73, 95% CI = 1.04-2.88, p = 0.04) in the CyFluTBI group, without significant difference in NRM. In older patients (n = 287), we observed that conditioning regimen did not significantly influence LFS (HR = 0.90, 95% CI = 0.56-1.44, p = 0.65), OS (HR = 0.81, 95% CI = 0.49-1.32, p = 0.39) and RI (HR = 1.78, 95% CI = 0.90-3.50, p = 0.10), but showed that CyFluTBI was associated with a significantly lower risk of NRM (HR = 0.48, 95% CI = 0.25-0.92, p = 0.03). Thus, younger patients seem to benefit from conditioning intensification from CyFluTBI to TBF regimens prior PT-Cy Haplo-SCT for CR AML, while older ones do not., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Non-T-cell depleted haploidentical hematopoietic cell transplantation (Haplo-HCT) is a unique transplantation setting in which several donors are available. We assessed the impact of donor kinship on outcome of Haplo-HCT with post-transplantation cyclophosphamide in a cohort of 717 acute leukemia patients. We compared sibling with parent donors in patients ≤45 years, and child with sibling donors in patients >45 years. Donor kinship was not associated with worse outcomes in multivariate analysis. For patients ≤45 years, the hazard ratio (HR) for leukemia-free survival (LFS), overall survival (OS), relapse incidence (RI), and chronic graft-versus-host disease (cGVHD) was 0.87 (p = 0.75), 1.19 (p = 0.7), 0.52 (p = 0.19), and 0.99 (p = 0.97) for parents versus siblings, respectively, and for patients >45 years the HR was 0.93 (p = 0.8), 0.98 (p = 0.94), 1.3 (p = 0.53), and 0.98 (p = 0.95) for children versus siblings, respectively. Univariate incidence of acute GVHD grade II-IV was significantly higher in patients transplanted from siblings versus children (p = 0.002). Factors associated with inferior outcome were advanced disease and earlier transplant. In patients ≤45 years, acute lymphocytic leukemia and peripheral blood stem cell graft were additional prognostic factors for OS. We did not find a significant impact of donor kinship on transplantation outcome when analyzing by age group (≤45 and >45 years)., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

There are no data indicating whether the number of induction courses needed to achieve first complete remission (CR1) is of prognostic significance in Haploidentical transplantation (HaploSCT). We compared transplantation outcomes of adults with AML that underwent HaploSCT in CR1, achieved following one or two induction courses. A total of 635 patients were included: 469 (74%) with 1 and 166 (26%) with two induction chemotherapy courses. A total of 429 (91.5%) and 151 (91%) patients had de novo AML and 40 (8.5%) and 15 (9%) had secondary AML (p = 0.84). Engraftment rates were 97.2 and 97.6%. Day 180 incidence of acute GVHD II-IV and III-IV was similar in both induction groups (31.1 and 34.8%, and 10 and 10.6 %), as was 2-4 year total and extensive chronic GVHD (33.7 and 36.5 %, and 12.2 and 12.1%), respectively. Two-year relapse incidence (RI) was higher while leukemia-free survival (LFS), overall survival (OS) and GVHD-free, relapse-free survival (GRFS) were inferior for patients achieving CR1 with 2 vs 1 course and were 29.1% vs 15.1%, 88 (p = 0.001), 56.2% vs 66.9% (p = 0.03), 58.8% vs 72.2% (p = 0.044) and 44% vs 55.6% (p = 0.013), respectively. Non-relapse mortality (NRM) did not differ, 18% vs 14.6% 90 (p = 0.25). These results were confirmed by multivariate analysis., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)