Outcomes and toxicity of allogeneic hematopoietic cell transplantation in chronic myeloid leukemia patients previously treated with second-generation tyrosine kinase inhibitors : a prospective non-interventional study from the Chronic Malignancy Working Party of the EBMT

Allogeneic hematopoietic cell transplantation (allo-HCT) remains a treatment option for patients with chronic myeloid leukemia (CML) who fail to respond to tyrosine kinase inhibitors (TKIs). While imatinib seems to have no adverse impact on outcomes after transplant, little is known on the effects of prior use of second-generation TKI (2GTKI). We present the results of a prospective non-interventional study performed by the EBMT on 383 consecutive CML patients previously treated with dasatinib or nilotinib undergoing allo-HCT from 2009 to 2013. The median age was 45 years (18-68). Disease status at transplant was CP1 in 139 patients (38%), AP or >CP1 in 163 (45%), and BC in 59 (16%). The choice of 2GTKI was: 40% dasatinib, 17% nilotinib, and 43% a sequential treatment of dasatinib and nilotinib with or without bosutinib/ponatinib. With a median follow-up of 37 months (1-77), 8% of patients developed either primary or secondary graft failure, 34% acute and 60% chronic GvHD. There were no differences in post-transplant complications between the three different 2GTKI subgroups. Non-relapse mortality was 18% and 24% at 12 months and at 5 years, respectively. Relapse incidence was 36%, overall survival 56% and relapse-free survival 40% at 5 years. No differences in post-transplant outcomes were found between the three different 2GTKI subgroups. This prospective study demonstrates the feasibility of allo-HCT in patients previously treated with 2GTKI with a post-transplant complications rate comparable to that of TKI-naive or imatinib-treated patients.Peer reviewe

Allogeneic hematopoietic cell transplantation in patients with chronic phase chronic myeloid leukemia in the era of third generation tyrosine kinase inhibitors : A retrospective study by the chronic malignancies working party of the EBMT

Peer reviewe

Validation of the transplant conditioning intensity (TCI) index for allogeneic hematopoietic cell transplantation

The intensity of the conditioning regimen given before allogeneic hematopoietic cell transplantation (allo-HCT) can vary substantially. To confirm the ability of the recently developed transplant conditioning intensity (TCI) score to stratify the preparative regimens of allo-HCT, we used an independent and contemporary patient cohort of 4060 transplant recipients with acute myeloid leukemia meeting inclusion criteria from the discovery study (allo-HCT in first complete remission, matched donor), but who were allografted in a more recent period (2018–2021) and were one decade older (55–75 years, median 63.4 years), we assigned them to a TCI category (low n = 1934, 48%; intermediate n = 1948, 48%, high n = 178, 4%) according to the calculated TCI score ([1–2], [2.5–3.5], [4–6], respectively), and examined the validity of the TCI category in predicting early non-relapse mortality (NRM), 2-year NRM and relapse (REL). In the unadjusted comparison, the TCI index provided a significant risk stratification for d100 and d180 NRM, NRM and REL risk. In the multivariate analysis adjusted for significant variables, there was an independent association of TCI with early NRM, NRM and REL. In summary, we confirm in contemporary treated patients that TCI reflects the conditioning regimen related morbidity and anti-leukemic efficacy satisfactorily and across other established prognostic factors.</p

Addition of Rituximab in Reduced Intensity Conditioning Regimens for B-Cell Malignancies Does Not Influence Transplant Outcomes: EBMT Registry Analyses Following Allogeneic Stem Cell Transplantation for B-Cell Malignancies

Rituximab (R) is increasingly incorporated in reduced intensity conditioning (RIC) regimens for allogeneic hematopoietic cell transplantation (alloHCT) in patients with B-cell malignancies, not only to improve disease control, but also to prevent graft-versus-host disease (GVHD). There are no randomized prospective data to validate this practice, although single center data and the CIBMTR analysis have shown promising results. We aimed at validation of these findings in a large registry study. We conducted a retrospective analysis using the EBMT registry of 3,803 adult patients with B-cell malignancies undergoing alloHCT (2001–2013) with either rituximab (R-RIC-9%) or nonrituximab (RIC-91%) reduced intensity regimens respectively. Median age and median follow up were 55 years (range 19.1–77.3) and 43.2 months (range 0.3–179.8), respectively. There was no difference in transplant outcomes (R-RIC vs RIC), including 1-year overall survival (69.9% vs 70.7%), 1-year disease-free survival (64.4% vs 62.2%), 1-year non-relapse mortality (21% vs 22%), and day-100 incidence of acute GVHD 2-4° (12% vs 12%). In summary, we found that addition of rituximab in RIC regimens for B-cell malignancies had no significant impact on major transplant outcome variables. Of note, data on chronic GVHD was not available, limiting the conclusions that can be drawn from the present study

Improved outcomes over time and higher mortality in CMV seropositive allogeneic stem cell transplantation patients with COVID-19; An infectious disease working party study from the European Society for Blood and Marrow Transplantation registry

Introduction: COVID-19 has been associated with high morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. Methods: This study reports on 986 patients reported to the EBMT registry during the first 29 months of the pandemic. Results: The median age was 50.3 years (min – max; 1.0 – 80.7). The median time from most recent HCT to diagnosis of COVID-19 was 20 months (min – max; 0.0 – 383.9). The median time was 19.3 (0.0 - 287.6) months during 2020, 21.2 (0.1 - 324.5) months during 2021, and 19.7 (0.1 – 383.9) months during 2022 (p = NS). 145/986 (14.7%) patients died; 124 (12.6%) due to COVID-19 and 21 of other causes. Only 2/204 (1%) fully vaccinated patients died from COVID-19. There was a successive improvement in overall survival over time. In multivariate analysis, increasing age (p<.0001), worse performance status (p<.0001), contracting COVID-19 within the first 30 days (p<.0001) or 30 – 100 days after HCT (p=.003), ongoing immunosuppression (p=.004), pre-existing lung disease (p=.003), and recipient CMV seropositivity (p=.004) had negative impact on overall survival while patients contracting COVID-19 in 2020 (p<.0001) or 2021 (p=.027) had worse overall survival than patients with COVID-19 diagnosed in 2022. Discussion: Although the outcome of COVID-19 has improved, patients having risk factors were still at risk for severe COVID-19 including death

Comparable Long-Term Outcome after Allogeneic Stem Cell Transplantation from Sibling and Matched Unrelated Donors in Patients with Acute Myeloid Leukemia Older Than 50 Years: A Report on Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

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 (PPeer reviewe

Impact of Donor Type in Patients with AML Given Allogeneic Hematopoietic Cell Transplantation After Low-Dose TBI-Based Regimen.

Background: We assessed the impact of donor type in acute myeloid leukemia (AML) patients transplanted with 2 Gy total body irradiation (TBI)-based nonmyeloablative conditioning regimen.Experimental Design: Data from 1,715 adult patients, with AML in CR1 or CR2 were included in this retrospective survey.Results: Donors consisted either of HLA-matched sibling donors (MSD, n = 701), 10/10 HLA-matched unrelated donors (MUD, n = 611), HLA-haploidentical donors (haplo, n = 112) or single or double umbilical cord bloods (CBT, n = 291). Chronic graft-versus-host disease (GVHD) was less frequent in CBT (28%) and in haplo (30%) patients than in MSD (50%) and MUD (51%) recipients (P < 0.001). Two-year incidence of relapse was 32%, 30%, 34%, and 34% in MSD, MUD, CBT and haplo patients, respectively (P = 0.7). Two-year overall (OS) and GVHD-free relapse-free survival (GRFS) were 59% and 29% in MSD patients, 56% and 39% in CBT recipients, 53% and 23% in MUD recipients, and 43% and 37% in haplo patients, respectively. In multivariate analyses, MUD patients had lower GRFS than MSD patients beyond day 100 (HR 1.3, P = 0.001) while CBT was associated with a better GRFS than MSD beyond day 100 (HR 0.6, P = 0.002).Conclusions: In this large cohort of AML patients transplanted following low-dose TBI-based conditioning, the relapse incidence was not affected by donor type suggesting that the intensity of GVL effects might be comparable with these four transplant approaches. Furthermore, CBT was associated with better GRFS beyond day 100 than MSD while the opposite was observed for MUD. Clin Cancer Res; 1-10. (c)2018 AACR