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Pre-transplant measurable residual disease (MRD) predicts relapse and outcome of allogeneic haematopoietic cell transplantation (allo-HCT). The impact of MRD on the outcomes of post-transplant cyclophosphamide (PTCy)-based allo-HCT from a matched unrelated donor (UD) is unknown. This study assessed the impact of MRD in acute myeloid leukaemia (AML) in the first complete remission (CR1). A total of 272 patients (MRD negative [MRD−], n = 165; MRD positive [MRD+], n = 107) with a median follow-up of 19 (range: 16–24) months were studied. The incidence of grades II–IV and grades III–IV acute GVHD at day 180 was 25.2% and 25% (p = 0.99), and 10.6% and 6.8% (p = 0.29), respectively, and 2-year chronic GVHD was 35% and 30.4% (p = 0.96) in MRD+ and MRD− cohorts, respectively. In multivariate analysis, MRD+ status was associated with a higher incidence of relapse (RI) (hazard ratio [HR] = 2.56, 95% CI: 1.39–4.72), lower leukaemia-free survival (LFS) (HR = 2.04, 95% CI: 1.23–3.39), overall survival (OS) (HR = 1.83, 95% CI: 1.04–3.25) and GVHD-free, relapse-free survival (GRFS) (HR = 1.69, 95% CI: 1.10–2.58). MRD status did not have a significant impact on non-relapse mortality (NRM), or acute or chronic GVHD risk. Among patients with AML undergoing UD allo-HCT with PTCy, pre-transplant MRD+ status predicted a higher relapse rate, lower LFS, OS and GRFS.

Background: Axicabtagen Ciloleucel (axi-cel) is approved in Europe for the treatment of adults with R/R large B-cell lymphoma (LBCL), primary mediastinal B-cell lymphoma (PMBCL) and transformed follicular lymphoma (tFL). In Spain, nationwide CAR-T administration requests are reviewed centrally within the Ministry of Health. We analyzed the real-world outcomes of patients treated with axicel under the commercial label in Spanish centers. Methods: Six designated centers for commercial CAR-T administration collected data on behalf of GETH-GELTAMO. Data were collected retrospectively from consecutive patients in whom apheresis was performed for axi-cel treatment from Febrruary-2019 to November-2020. CRS and ICANS were graded with the ASTCT consensus criteria. Response was assessed according to the Lugano criteria. Results: 106 patients with R/R lymphoma underwent apheresis for axi-cel. At data cutoff, 92 (87%) received infusion. The reasons for not undergoing infusion were progression-related death in 12 (86%), tumor lysis syndrome in 1 (7%) and complete response after bridging therapy in 1 (7%). Of note, 14 patients were conditioned and infused during the peak of COVID-19 epidemic in Spain (March-April 2020). Median time from Ministry approval to infusion was 54 days. Histology consisted of 74% DLBCL with 11% tFL, and 15% PMBCL. Disease status at lymphodepletion was PD in 69%, SD in 22% and PR in 9%. All patients received lymphodepletion. Median time from leukapheresis to start of lymphodepletion was 34 days. Median time from leukapheresis to infusion was 39 days. Median hospitalization period was 21 days. Any grade of CRS occurred in 86% of pts (18% grade 2, 6.5% grades 3-4). Tocilizumab was used in 58% of patients who developed CRS, corticosteroids in 19%. ICANS was diagnosed in 42.5% of pts (10% grade 2, 15% grade 3-4). Treatment for ICANS included corticosteroids in 78%, tocilizumab in 31%, siltuximab in 15%, and anakinra in 21%. ICU admission was needed in 20 patients (22%). 4 patients died in the context of ICANS, 1 due to CRS, and 1 due to infection. Of 80 patients evaluable and restaged at day 30, ORR was 78% with 40% CR, 38% PR, 11% PD and 11% SD or indeterminate. Of 58 patients evaluable at day 100, 66% had ongoing response (CR 48%, PR 18%). Of 23 patients evaluable at day 180, 65% presented CR. Of 39 patients who showed PR/SD at day 30, 9 (23%) converted to CR. After a median follow-up of 6.3 months, EFS and OS were 55.5% and 78%, respectively in the infused population, with an estimated median EFS and OS of 13.1 and 7.3 months. In the intention-to-treat analysis for all patients who underwent apheresis, median estimated OS and EFS were 12.3 (95%CI 8.9-15.7) and 6.6 months (95%CI 4.6-8.5), respectively (Figure 1). Conclusions: This Spanish multicenter retrospective analysis shows encouraging results of axi-cell treatment in patients with R/R aggressive B-cell lymphoma in the real-world setting. Significant toxicity events were less frequent than those reported in the pivotal trial, however events of mortality associated to toxicity occurred. With a limited follow-up time, response outcomes are favorable.

Background The use of haploidentical hematopoietic cell transplantation (haplo-HCT) with posttransplantation cyclophosphamide prophylaxis is gaining traction in patients with acute lymphoblastic leukemia (ALL). Methods The Acute Leukemia Working Party/European Society for Blood and Marrow Transplantation registry was used to evaluate the outcomes of adult patients with ALL who underwent haplo-HCT during 2011 through 2015 and compared them with the outcomes of those who underwent transplantation during 2016 through 2018. Results The analysis consisted of 195 patients, including 79 who underwent transplantation during 2011 through 2015 and 116 who underwent transplantation during 2016 through 2018. Overall, the 2-year leukemia-free survival and relapse incidence rates were 56.5% and 21%, respectively. The 100-day incidence of grade 2 through 4 acute graft-vs-host disease (GVHD) was 34.5%. The rates of nonrelapse mortality (NRM) and overall survival (OS) were 22.5% and 64.7%, respectively. Patients who underwent transplantation during 2016 through 2018 experienced improved rates of leukemia-free survival (64.9% vs 47.3%; P = .019) and OS (75.5% vs 53.5%; P = .006). Patients who underwent transplantation during 2016 through 2018 developed more grade 2 through 4 acute GVHD (42% vs 26.4%; P = .047). The incidence of relapse, GVHD-free/relapse-free survival, grade 3 and 4 acute GVHD, chronic GVHD, and extensive chronic GVHD did not differ significantly between groups. In multivariate analysis, more recently transplanted patients had a significantly reduced risk of NRM (hazard ratio, 0.44; 95% CI, 0.22-0.89; P = .022) and improved OS (hazard ratio, 0.47; 95% CI, 0.26-0.86; P = .014). A comparable analysis of patients who had acute myeloid leukemia during the same timeframes did not reveal any statistically significant differences in any outcomes. Conclusions The outcome of adult patients with ALL who receive posttransplant cyclophosphamide has improved over time, with an impressive 2-year OS of 75% and, most recently, an NRM rate of only 17%.

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.

The association of graft-versus-host disease (GVHD) and graft-versus-leukemia effect after stem-cell transplantation (SCT) is well established but with limited data in the setting of haploidentical SCT (haploSCT) with post-transplant cyclophosphamide (PTCy). We used a series of landmark analyses to investigate this association in 805 AML patients following haploSCT. On day +100, 707 patients were alive and leukemia-free, 500 had no prior acute GVHD, 137 had acute GVHD grade II and 70 had grade III-IV. Subsequent relapse rates were 20.3%, 23.2% and 15.0%, respectively (P = 0.52). Subsequent non-relapse mortality (NRM) was 8.6%, 17.8% and 38.6%, respectively (P 0.0001). Leukemia-free survival (LFS) was 71.0%, 59.0% and 46.3%, respectively (P 0.0001). Multivariate analysis showed that acute GVHD grade II and grade III-IV were not associated with relapse (HR 1.21, P = 0.37 and HR 1.03, P = 0.94), but were associated with increased NRM (HR 2.09, P = 0.005 and HR 6.41, P 0.0001) and lower LFS (HR 1.47, P = 0.02 and HR 2.59, P = 0.0001). Chronic GVHD was not associated with subsequent relapse. Extensive chronic GVHD was associated with higher NRM (HR 6.72, P 0.0001) and inferior LFS (HR 3.29, P = 0.0001). GVHD of any type or grade is not associated with lower relapse after haploSCT with PTCy. Severe forms are associated with higher NRM and lower survival.

The use of haplo-HCT with posttransplant cyclophosphamide (PT-Cy) is a new standard in the treatment of hematological diseases. A paucity of data exists on risk factors for engraftment failure in haplo-HCT with PT-Cy. We analyzed 1939 adults with acute myeloid leukemia (AML) who received a first haplo-HCT from 2010 to 2019. Status at haplo-HCT was first complete remission (CR1) in 72.5% of patients, secondary AML was reported in 9.9%. Median follow-up was 24.4 months and median age at haplo-HCT was 51 years. Stem cell source was bone marrow (BM) in 42% and peripheral blood stem cell (PBSC) in 58%, and 64% of patients received a myeloablative conditioning (MAC) regimen. Cumulative incidence of primary graft failure (GF) was 6%; GF was reported in 110 patients and 54 died before day +30 with no sign of cell recovery. Overall, 33 patients underwent a second HCT in a median time of 45 days and 13 were alive at last follow-up, the 2-year overall survival (OS) after second HCT being 32.4%. In multivariate analysis, factors independently associated with the risk of nonengraftment were: secondary AML (HR 1.30, p = 0.003), use of RIC (HR 1.22, p

Background There is no information on the impact of donor type in allogeneic hematopoietic stem cell transplantation (HCT) using homogeneous graft-versus-host (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy) in acute lymphoblastic leukemia (ALL). Methods We retrospectively analyzed outcomes of adult patients with ALL in CR1 that had received HCT with PTCy as GVHD prophylaxis from HLA-matched sibling (MSD) (n = 78), matched unrelated (MUD) (n = 94) and haploidentical family (Haplo) (n = 297) donors registered in the EBMT database between 2010 and 2018. The median follow-up period of the entire cohort was 2.2 years. Results Median age of patients was 38 years (range 18–76). Compared to MSD and MUD, Haplo patients received peripheral blood less frequently. For Haplo, MUD, and MSD, the cumulative incidence of 100-day acute GVHD grade II–IV and III–IV, and 2-year chronic and extensive chronic GVHD were 32%, 41%, and 34% (p = 0.4); 13%, 15%, and 15% (p = 0.8); 35%, 50%, and 42% (p = 0.01); and 11%, 17%, and 21% (p = 0.2), respectively. At 2 years, the cumulative incidence of relapse and non-relapse mortality was 20%, 20%, and 28% (p = 0.8); and 21%, 18%, and 21% (p = 0.8) for Haplo, MUD, and MSD, respectively. The leukemia-free survival, overall survival and GVHD-free, relapse-free survival for Haplo, MUD, and MSD was 59%, 62%, and 51% (p = 0.8); 66%, 69%, and 62% (p = 0.8); and 46%, 44%, and 35% (p = 0.9), respectively. On multivariable analysis, transplant outcomes did not differ significantly between donor types. TBI-based conditioning was associated with better LFS. Conclusions Donor type did not significantly affect transplant outcome in patient with ALL receiving SCT with PTCy.

BACKGROUND: The treatment of patients with Hodgkin lymphoma (HL) who develop disease progression after undergoing allogeneic stem cell transplantation (allo‐SCT) remains challenging. METHODS: The authors assessed outcomes in 184 adult patients with HL who developed disease recurrence or progression after a matched related or unrelated allo‐SCT at European Society for Blood and Marrow Transplantation–participating centers between 2010 and 2014. RESULTS: Eighty patients who received brentuximab vedotin (BV) salvage therapy were compared with 104 patients who did not. Patients in the BV group were younger (median age of 30 years vs 34 years) and were more likely to receive pretransplant BV (65% vs 46%) or posttransplant donor lymphocyte infusion (66% vs 33%). The 2 groups otherwise were comparable. Patients in the BV group received a median of 6 doses of posttransplant BV, resulting in a complete remission rate of 29%, a partial response rate of 45%, and a stable disease rate of 26%. Response to BV after allo‐SCT did not appear to be affected by receipt of pretransplant BV. Despite a longer median follow‐up for surviving patients in the BV group (33 months vs 23 months; P

BACKGROUND Incidence of graft-versus-host disease (GVHD) in haploidentical bone marrow (BM) transplants using posttransplantion cyclophosphamide (PT-Cy) is low, whereas GVHD using mobilized peripheral blood stem cells (PBSC) ranges between 30% and 40%. METHODS To evaluate the effect of stem cell source in haploidentical transplantation with PT-Cy, we analyzed 451 patients transplanted for acute myeloid leukemia or acute lymphoblastic leukemia reported to the European Society for Blood and Marrow Transplantation. RESULTS BM was used in 260 patients, and PBSC were used in 191 patients. The median follow-up was 21 months. Engraftment was lower in BM (92% vs 95%, P < 0.001). BM was associated with a lower incidence of stage II-IV and stage III-IV acute GVHD (21% vs 38%, P ≤ .01; and 4% vs 14%, P < .01, respectively). No difference in chronic GVHD, relapse, or nonrelapse mortality were found for PBSC or BM. The 2-year overall survival (OS) was 55% versus 56% (P = .57) and leukemia-free survival (LFS) was 49% versus 54% (P = .74) for BM and PBSC, respectively. On multivariate analysis, PBSC were associated with an increased risk of stage II-IV (hazard ratio [HR], 2.1; P < .001) and stage III-IV acute GVHD (HR, 3.8; P < .001). For LFS and OS, reduced intensity conditioning was the only factor associated with treatment failure (LFS: HR, 1.40; P = .04) and relapse (HR, 1.62; P = .02). CONCLUSION In patients with acute leukemia in first or second remission receiving haploidentical transplantation with PT-Cy, the use of PBSC increases the risk of acute GVHD, whereas survival outcomes are comparable. Cancer 2018;124:1428-37. © 2018 American Cancer Society.

The role of donor CMV serostatus in the setting of non T-cell depleted haplo-HSCT with post-transplant cyclophosphamide (PT-Cy) has not been specifically addressed so far. Here we analyzed the impact of the donor CMV serological status on the outcome of 983 CMV seropositive (CMV+), acute leukemia patients receiving a first, non T-cell depleted haplo-HSCT registered in the EBMT database. The 1-year NRM was 21.3% (95% CI: 18.4-24.8) and 18.8% (95% CI: 13.8-25.5) in the CMV D+/R+ and D-/R+ pairs, respectively (p = 0.40). Similarly, 1-year OS was 55.1% (95% CI: 50.1-58.0) and 55.7% (95% CI: 48.0-62.8) in the same groups (p = 0.50). The other main outcomes were comparable. No difference in NRM nor OS was observed after stratification for the intensity of conditioning and multivariate anaysis confirmed the lack of significant association with NRM or OS. In conclusion, the choice of a CMV-seronegative donor did not impair early survival of CMV-seropositive patients with acute leukemia after a first, non T-cell depleted haploidentical HSCT and PT-Cy among this series of 983 consecutive patients. Future research may focus on the assessment of the hierarchy of all the donor variables. © 2017 Macmillan Publishers Ltd., part of Springer Nature.

Allogeneic Hematopoietic Stem Cell Transplantation Provides Cure for Adult Patients with Hemophagocytic Lymphohistiocytosis (HLH) : A Retrospective Study of The Chronic Malignancies and Inborn ErrorsWorking Parties (CMWP and IEWP) of The EBMT

Three patients with extranodal peripheral T-cell lymphoma and a distinctive clinical presentation are described. They had acute onset of fever, weight loss, progressive liver failure, bleeding diathesis, pancytopenia, and myelodysplastic changes in the bone marrow. Each patient had one or more paraneoplastic complications: severe rhabdomyolysis with myoglobinuria and secondary renal failure, cutaneous vasculitis, gluten-sensitive enteropathy, polyserositis, and increased macrophages with hemophagocytic activity. They did not have peripheral lymphadenopathy. The complex clinical presentations simulated collagen vascular disorders, systemic infections, or severe liver disease rather than a malignant lymphoma. Routine histologic studies revealed a small population of lymphoma cells in the bone marrow, spleen, and liver. Immunophenotyping studies demonstrated their T-cell phenotype, and cytogenetic analysis showed the clonality in Patients 1 and 2; clonal T-cell receptor gene rearrangement was found in Patients 2 and 3. These studies should be considered in the evaluation of patients with constitutional symptoms, liver failure, coagulopathy, and pancytopenia even in the absence of peripheral lymphadenopathy.