-
1.
Retrospective analysis of hematopoietic cell transplantation for blastic plasmacytoid dendritic cell neoplasm: conditioning intensity matters
Bruch, P. M., Dietrich, S., Finel, H., Boumendil, A., Greinix, H., Heinicke, T., Bethge, W., Beelen, D., Schmid, C., Martin, H., et al
Leukemia. 2022
Abstract
Blastic plasmacytoid dendritic cell neoplasia (BPDCN) is a rare myeloid malignancy with a generally poor prognosis. Although preliminary evidence suggests that hematopoietic cell transplantation (HCT) could improve outcome in patients with BPDCN, the individual contributions of conditioning and graft-versus-tumor (GVT) effects to HCT success are undefined. We present a retrospective study of 162 adult patients who underwent a first HCT (allogeneic 146, autologous 16) between 2009 and 2017, and were registered with the EBMT. Median age was 57 (range 20-73) years, and disease status at HCT was first complete remission (CR1) in 78%. Among patients receiving allogeneic HCT (alloHCT), myeloablative conditioning (MAC), reduced intensity conditioning (RIC) and in-vivo T-cell depletion (TCD) were used in 54%, 46%, and 59% respectively. Total body irradiation (TBI) was the conditioning backbone in 61% of MAC and 26% of RIC transplants. One-year overall survival (OS) and progression-free survival (PFS) rates were comparable after alloHCT and autologous HCT (autoHCT). Among alloHCT recipients, MAC with TBI significantly improved OS and PFS, independently of CR1, age, Karnofsky index and TCD. Accordingly, MAC (ideally based on TBI) should be preferred for alloHCT recipients with BPDCN. In patients who are not elegible for MAC alloHCT, autoHCT could be considered.
-
2.
Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?-A multicenter EBMT-PDWP study
Willasch, A. M., Peters, C., Sedlacek, P., Dalle, J. H., Kitra-Roussou, V., Yesilipek, A., Wachowiak, J., Lankester, A., Prete, A., Hamidieh, A. A., et al
Bone marrow transplantation. 2020
Abstract
Although most children with acute lymphoblastic leukemia (ALL) receive fractionated total body irradiation (FTBI) as myeloablative conditioning (MAC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT), it is an important matter of debate if chemotherapy can effectively replace FTBI. To compare outcomes after FTBI versus chemotherapy-based conditioning (CC), we performed a retrospective EBMT registry study. Children aged 2-18 years after MAC for first allo-HSCT of bone marrow (BM) or peripheral blood stem cells (PBSC) from matched-related (MRD) or unrelated donors (UD) in first (CR1) or second remission (CR2) between 2000 and 2012 were included. Propensity score weighting was used to control pretreatment imbalances of the observed variables. 3.054 patients were analyzed. CR1 (1.498): median follow-up (FU) after FTBI (1.285) and CC (213) was 6.8 and 6.1 years. Survivals were not significantly different. CR2 (1.556): median FU after FTBI (1.345) and CC (211) was 6.2 years. Outcomes after FTBI were superior as compared with CC with regard to overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), and nonrelapse mortality (NRM). However, we must emphasize the preliminary character of the results of this retrospective "real-world-practice" study. These findings will be prospectively assessed in the ALL SCTped 2012 FORUM trial.
-
3.
BEAM-Campath Allogeneic Stem Cell Transplant for Patients with Relapsed/Refractory Lymphoma: High Incidence of Long-Term Mixed Donor-Recipient Chimerism and the Response to Donor Lymphocyte Infusions
Burney, C., Wadhera, K., Breslin, P., Pearce, R., Wells, M., Alajangi, R., Protheroe, R., Marks, D. I., Griffin, J., Robinson, S.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020;26(12):2271-2278
Abstract
BiCNU (carmustine), etoposide, Ara-C, melphalan (BEAM) and Campath conditioning was developed to reduce the high transplant-related mortality in patients with lymphoma while delivering intensive antilymphoma immunotherapy, as well as to some extent a platform for allogeneic stem cell engraftment. Significant numbers of patients appeared to have persistent recipient-derived hematopoiesis, and therefore we retrospectively analyzed patients with lymphoma undergoing BEAM-Campath conditioned allogeneic stem cell transplantation at our center (2003 to 2017) to characterize the patterns of chimerism and patient outcomes. Chimerism was analyzed with short tandem repeat PCR. Mixed donor-recipient chimerism (MDRC) was defined as 5% to 94.9% donor. Fifty-two patients (n = 30 male), with a median age of 45 years, were identified with histologic diagnoses of Hodgkin lymphoma (n = 13), diffuse large B cell lymphoma (n = 7), low-grade non-Hodgkin lymphoma (n = 16), mantle cell lymphoma (n = 10), and T cell lymphoma (n = 6). Pretransplant, 93% achieved complete response (52%) or partial response (41%) with a median of 3 prior therapies (n = 3 prior autologous stem cell transplantation). Donors were Matched sibling donors (MSD) (n = 21), matched unrelated donors (MUD) (n = 24), miss-matched unrelated donors (MMUD) (n = 6), and syngeneic (n = 1). Acute graft-versus host disease (GVHD) developed in 52% (81% grade I to II) and chronic GVHD (83% extensive) in 12%. MDRC of T cells (MDRCt) developed in 62% (n = 32), and 29% (n = 15) developed MDRC of myeloid cells (MDRCm) at a median onset of 100 days. Donor lymphocyte infusion (DLI) was given to 17 patients, with a median starting dose of 1 × 10(6)/kg. The first DLI was given at a median of 225 days post-transplant (range, 99 days to 5.3 years). Of these, 9 developed acute post-DLI GVHD and 2 limited chronic GVHD. Conversion to full donor occurred in 47% MDRCt and 50% MDRCm. Multivariate analysis identified sibling donor type as associated with increased MDRCt (P = .035; hazard ratio [HR], 0.17) and reduced total nucleated cell dose with increased MDRCm (P = .021; HR, 0.76). The median follow-up was 6 years, and 2-year NRM cumulative incidence was 16% (95% confidence interval [CI], 7% to 27%). Ten-year progression and extensive GVHD-free survival was 45% (95% CI, 28% to 61%), and overall survival was 66% (95% CI, 50% to 78%). One-year landmark analysis identified no increased GVHD or relapse risk with MDRCt or MDRCm but reduced nonrelapse mortality (NRM) risk with MDRCt (P = .001). BEAM-Campath allografts for high-risk lymphoma achieve long-term disease-free survival with low rates of GVHD and transplant-related mortality. The frequent development of myeloid MDRC demonstrates that BEAM-Campath is a nonmyeloablative conditioning regimen in almost a third of patients. MDRCt is associated with reduced NRM, but neither MDRCt or MDRCm is associated with increased GVHD or relapse.
-
4.
Idelalisib exposure before allogeneic stem cell transplantation in patients with follicular lymphoma: an EBMT survey
Sellner, L., Schetelig, J., Koster, L., Choi, G., Blaise, D., Beelen, D., Schianca, F. C., Passweg, J., Schanz, U., Gyan, E., et al
Bone marrow transplantation. 2020
-
5.
PTCy-based haploidentical vs matched related or unrelated donor reduced-intensity conditioning transplant for DLBCL
Dreger, P., Sureda, A., Ahn, K. W., Eapen, M., Litovich, C., Finel, H., Boumendil, A., Gopal, A., Herrera, A. F., Schmid, C., et al
Blood advances. 2019;3(3):360-369
-
-
Free full text
-
Abstract
This study retrospectively compared long-term outcomes of nonmyeloablative/reduced intensity conditioning (NMC/RIC) allogeneic hematopoietic cell transplantation (allo-HCT) from a haploidentical family donor (haplo-HCT) using posttransplant cyclophosphamide (PTCy) with those of matched sibling donor (MSD) and matched unrelated donor (MUD) with or without T-cell depletion (TCD+/TCD-) in patients with relapsed diffuse large B-cell lymphoma (DLBCL). Adult patients with DLBCL who had undergone their first NMC/RIC allo-HCT between 2008 and 2015 were included. Recipients of haplo-HCT were limited to those receiving graft-versus-host disease (GVHD) prophylaxis with PTCy. GVHD prophylaxis in MSD was limited to calcineurin inhibitor (CNI)-based approaches without in vivo TCD, while MUD recipients received CNI-based prophylaxis with or without TCD. Outcome analyses for overall survival (OS) and progression-free survival (PFS), nonrelapse mortality (NRM), and disease relapse/progression were calculated. A total of 1438 patients (haplo, 132; MSD, 525; MUD TCD+, 403; and MUD TCD-, 378) were included. Patients with haplo donors were significantly older, had a better performance status and had more frequently received total body irradiation-based conditioning regimens and bone marrow grafts than MSD and MUD TCD+ or TCD-. 3-year OS, PFS, NRM and relapse/progression incidence after haplo-HCT was 46%, 38%, 22%, and 41%, respectively, and not significantly different from outcomes of matched donor transplants on multivariate analyses. Haplo-HCT was associated with a lower cumulative incidence of chronic GVHD compared with MSD, MUD TCD+/TCD-. NMC/RIC haplo-HCT with PTCy seems to be a valuable alternative for patients with DLBCL considered for allo-HCT but lacking a matched donor.
-
6.
Allogeneic hematopoietic stem cell transplantation for patients with relapsed/refractory systemic anaplastic large cell lymphoma. A retrospective analysis of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation
Domingo-Domenech, E., Boumendil, A., Climent, F., Socie, G., Kroschinsky, F., Finel, H., Vandenbergue, E., Nemet, D., Stelljes, M., Bittenbring, J. T., et al
Bone marrow transplantation. 2019
Abstract
Information regarding the curative role of allogeneic stem cell transplantation (allo-HCT) in systemic anaplastic large cell lymphoma (sALCL) is scarce. We analyzed the results of allo-HCT in patients with relapsed/refractory sALCL with special emphasis on the role of brentuximab vedotin (BV) as a bridge to allo-HCT. Forty-four patients (24 females, median age 38 years) with sALCL were included. Twenty-three patients (52%) received BV before allo-HCT; BV-treated patients were more heavily pretreated (≥3 lines of therapy in 74% vs. 38%, p = 0.04). Twenty-three patients (52%) were in complete remission (CR) at allo-HCT. Three-year nonrelapse mortality and incidence of relapse (IR) after allo-HCT were 7% and 40%, respectively. With a median follow-up of 39 (12-69) months for survivors, 3-year progression-free survival (PFS) and overall survival were 53% and 74%, respectively. Univariate analysis showed that heavily pretreated patients and those not in CR had a higher IR and a lower PFS. The use of BV before transplant did not impact on any of the outcomes. Allo-HCT is a curative therapeutic strategy in a significant proportion of patients with relapsed/refractory sALCL; BV does not seem to modify transplant-related outcomes but might be able to render more patients candidates for this curative treatment.
-
7.
Myeloablative and Reduced-intensity conditioned Allogeneic Haematopoietic Stem Cell Transplantation in Myelofibrosis: A Retrospective Study by the Chronic Malignancies Working Party of EBMT
McLornan, D., Szydlo, R., Koster, L., Chalandon, Y., Robin, M., Wolschke, C., Beelen, D., Socie, G., Bornhauser, M., Angelucci, E., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
Abstract
This retrospective study by the EBMT analysed the outcome of 2224 Myelofibrosis patients who underwent allogeneic stem cell transplantation (allo-SCT) between 2000-2014; 781 (35%) underwent myeloablative conditioning (MAC) and 1443 (65%) reduced intensity conditioning (RIC). Median patient age was 52.9 years (r, 18-74) and 57.5 years (range(r), 21-76) in the MAC and RIC cohorts respectively. Donor type was similar: matched sibling donors (MAC- 317 (41%)) and RIC- 552 (38%) and unrelated donors (UD; MAC (464 (59%); RIC- 891 (62%)). Median time to both neutrophil and platelet (>20x10(9)/L) engraftment did not differ between cohorts. Rates of grade II-IV acute (a) GVHD were 28% (MAC) and 31% (RIC; (p=ns). Cumulative cGVHD rates (limited/ extensive) were 22%/27% (MAC) and 19%/ 31% (RIC; p=0.10). Cumulative incidences of Non-relapse mortality (NRM) at 1, 3 and 5-years were: 25.5%, 32.2% and 34.6% (MAC) and 26.3%, 32.8% and 34.4% (RIC). There was a trend towards a higher relapse rate with RIC regimens compared to MAC (p=0.08); rates at 1, 3 and 5-years were: 10.9%, 17.2% and 20.1% (MAC) and 14%, 19.7% and 23.2% (RIC), respectively. No significant difference in 5yr probabilities of overall survival (OS) was noted: MAC 53.0% (95% confidence intervals (CI) 49.1-56.9) and RIC 51.0% (95% CI: 48.3-53.7); p=0.78. Regarding the composite end point of GVHD-free/relapse-free survival (GRFS), the unadjusted Kaplan-Meier estimate of 5-year GRFS was 32.4% (95% CI: 29.0-36.1) in the MAC group and 26.1% (95% CI: 23.9-28.2) in the RIC group (p=0.001). In the MAC cohort, multivariable analysis confirmed worse OS and NRM with older age (>50 yrs), using an unrelated donor and a Karnofsky Performance Status (KPS) of 80 or less. For the RIC cohort, worse OS and NRM was associated with age 60- 70 years when compared to younger recipients, use of a mismatched donor and poor performance status. In conclusion, although similar OS rates existed for both cohorts overall, this study suggests that MAC should still be used for younger individuals suitable for such an approach due to a trend towards less relapse and an overall suggested advantage of improved GRFS; albeit this should be examined in a more homogeneous cohort. RIC allo-SCT still offers significant survival advantage in the older, fitter MF allograft patient and optimisation to reduce significant relapse and NRM rates are required.
-
8.
Brentuximab vedotin for recurrent Hodgkin lymphoma after allogeneic hematopoietic stem cell transplantation: A report from the EBMT Lymphoma Working Party
Bazarbachi, A., Boumendil, A., Finel, H., Mohty, M., Castagna, L., Blaise, D., Peggs, K. S., Afanasyev, B., Diez-Martin, J. L., Corradini, P., et al
Cancer. 2018
Abstract
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<.001), approximately 34% of the original BV cohort were alive and in CR at the time of last follow-up versus 18% in the group that did not receive BV (P=.003). The use of BV before donor lymphocyte infusion was found to be associated with the highest probability of being alive and in CR (40%) at the time of last follow-up. Salvage BV appeared to have no effect on chronic graft-versus-host disease or 1-year overall survival from the time of disease recurrence after allo-SCT (76% vs 67%). CONCLUSIONS BV is a safe and effective salvage therapy for patients with HL who develop disease recurrence or progression after undergoing allo-SCT, even after prior exposure to BV.
-
9.
Brentuximab vedotin prior to allogeneic stem cell transplantation in Hodgkin lymphoma: a report from the EBMT Lymphoma Working Party
Bazarbachi, A., Boumendil, A., Finel, H., Mohty, M., Castagna, L., Peggs, K. S., Blaise, D., Afanasyev, B., Diez-Martin, J. L., Sierra, J., et al
British journal of haematology. 2018
Abstract
Brentuximab vedotin (BV) is an anti-CD30 antibody-drug conjugate. Preliminary data suggest that BV might improve outcomes after allogeneic stem cell transplantation (SCT) for Hodgkin lymphoma (HL) when used as pre-transplant salvage therapy. Between 2010 and 2014, 428 adult patients underwent an allogeneic SCT for classical HL at participating centres of the European Society for Blood and Marrow Transplantation. We compared the outcomes of 210 patients who received BV prior to allogeneic SCT with that of 218 patients who did not receive BV. The median follow-up for survivors was 41 months. Patients in the BV group were more heavily pre-treated (median pre-allograft treatment lines: 4 vs. 3). The two groups were comparable in terms of disease status, performance status, comorbidities, prior autologous SCT, type of donor, conditioning and in vivo T cell depletion. In multivariate analysis, pre-allograft BV had no impact on acute graft-versus-host disease (GVHD), non-relapse mortality, cumulative incidence of relapse, progression-free survival or overall survival (OS), but significantly reduced the risk of chronic GVHD (hazard ratio = 0.64; 95% confidence interval = 0.45-0.92; P < 0.02). Older age, poor performance status, use of pre-transplant radiotherapy and active disease at SCT adversely affected OS. Patients allografted for HL after prior exposure to BV do not have a superior outcome after allogeneic SCT except for a lower risk of chronic GVHD. However, BV may improve the outlook of allogeneic SCT by helping otherwise refractory patients to achieve a more favourable disease status, facilitating allotransplant success.