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1.
Cord blood transplantation for AML: Comparable LFS in patients with de novo versus secondary AML in CR1, an ALWP/EBMT study
Baron, F., Nagler, A., Galimard, J. E., Sanz, J., Versluis, J., Forcade, E., Chevallier, P., Sirvent, A., Anthias, C., Kuball, J., et al
British journal of haematology. 2023
Abstract
We investigated whether secondary versus de novo acute myeloid leukaemia (AML) would be associated with poor outcomes in adult acute AML patients in first complete remission (CR1) receiving unrelated cord blood transplantation (CBT). This is a retrospective study from the acute leukaemia working party of the European Society for Blood and Marrow Transplantation. Inclusion criteria included adult at first allogeneic haematopoietic cell transplantation between 2000 and 2021, unrelated single or double unit CBT, AML in CR1, no ex vivo T-cell depletion and no post-transplant cyclophosphamide. The primary end-point of the study was leukaemia-free survival (LFS). A total of 879 patients with de novo (n = 696) or secondary (n = 183) AML met the inclusion criteria. In multivariable analyses, sAML patients had non-significantly different LFS (HR = 0.98, p = 0.86), overall survival (HR = 1.07, p = 0.58), relapse incidence (HR = 0.74, p = 0.09) and non-relapse mortality (HR = 1.26, p = 0.13) than those with de novo AML. Our results demonstrate non-significantly different LFS following CBT in adult patients with secondary versus de novo AML.
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2.
Outcomes of graft failure after umbilical cord blood transplantation in acute leukemia: a study from Eurocord and the Acute Leukemia Working Party of the EBMT
Baron, F., Ruggeri, A., Peczynski, C., Labopin, M., Bourhis, J. H., Michallet, M., Chevallier, P., Sanz, J., Forcade, E., Saccardi, R., et al
Bone marrow transplantation. 2023
Abstract
Graft failure has remained a limitation of umbilical cord blood transplantation (CBT). Here, we assessed the outcomes of patients who experienced graft failure after CBT. Inclusion criteria were patients (age ≥ 18 years) experiencing graft failure after unrelated CBT (single or double) between 2005 and 2016, for acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL), no prior allogeneic or autologous transplantation, no other stem cell product. The study included 87 patients. At 1-year, cumulative incidence of relapse and nonrelapse mortality (NRM) was 35% and 37%, respectively. One-year overall survival (OS) and progression-free survival (PFS) was 40% and 29%, respectively. Forty-six patients underwent a salvage second transplantation with 1-year and 2-year OS and PFS from second transplantation 41% and 34% for OS, and 37% and 34% for PFS, respectively. In multivariate analysis, complete remission (CR) at CBT (HR = 0.45, 95% CI 0.25-0.83, P = 0.01) and reduced-intensity conditioning (HR = 0.51, 95% CI 0.29-0.91, P = 0.023) were associated with better OS. In conclusion, in this retrospective study, we observed that approximately one-quarter of patients experiencing graft failure after CBT remained alive without relapse 2 years later.
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3.
Cord blood transplantation for adult lymphoid neoplasms in Europe and Japan
Watanabe, M., Kanda, J., Volt, F., Ruggeri, A., Suzuki, R., Rafii-Elayoubi, H., Kimura, F., Cappelli, B., Kondo, E., Scigliuolo, G. M., et al
Blood advances. 2023
Abstract
With the aim of identifying the different characteristics and prognostic factors of cord blood transplantation (CBT) in adult patients with lymphoid neoplasms in Europe and Japan, we conducted a collaborative study between European and Japanese registries. Patients aged 18-75 years receiving their first CBT (Europe: single CBT, n=192; double CBT, n=304; Japan: single CBT, n=1150) in 2000-2017 were analyzed. The number of patients with Hodgkin's lymphoma was higher in Europe (26% vs 5%) while that with mature T/NK-cell neoplasms was higher in Japan (20% vs 35%). The Japanese cohort comprised more elderly patients (>=50) (59% vs 39%) with higher refined disease risk index (rDRI) (high-very high: 49% vs 14%). High-very high rDRI (vs. low rDRI) was associated with inferior OS in common (Europe: HR 1.87 p=0.001; Japan: HR 2.34, p<0.001) with higher progression/relapse risks (Europe: HR 2.04, p=0.007; Japan: HR 2.96, p<0.001). Total body irradiation (TBI)-containing conditioning regimens contributed to superior OS both in Europe (vs TBI-RIC, non TBI-RIC: HR 1.93, p<0.001; non TBI-MAC: HR 1.90, p=0.003) and in Japan (non TBI-RIC: HR 1.71, p<0.001; non TBI-MAC: HR 1.50, p=0.007). The impact of HLA mismatches (>=2) on OS differed (Europe: HR 1.52, p=0.007; Japan: HR 1.18, p=0.107). Despite the different patient-disease-transplant characteristics, poor survival of patients receiving CBT for lymphoid neoplasms, especially in those with high rDRI was observed in both registries. The different impact of HLA mismatches on survival in the two registries calls attention to the fundamental differences among these populations. TBI should be considered in conditioning regimens.
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4.
Outcomes of subsequent neoplasms after umbilical cord blood transplantation in Europe
Rafii, H., Ruggeri, A., Kenzey, C., Sanz, J., Peffault de Latour, R., Esquirol, A., Michel, G., Chevallier, P., Rubio, M. T., Cornelissen, J. J., et al
Blood advances. 2022
Abstract
Subsequent neoplasms (SNs) compromise long-term survivors after hematopoietic cell transplantion. We performed a retrospective analysis of SNs in a cohort of 10358 recipients of umbilical cord blood transplantation (UCBT) reported to Eurocord/EBMT registries from 1988 to 2018. A total of 233 patients developed SNs. Median age at UCBT was 31 years (y) (0.3-69), and 84 were pediatric patients. Indications for UCBT were malignant hematological diseases in 199 patients (85%). Three groups of SNs were observed. Post-transplant lymphoproliferative disorders (PTLD) were reported in 145 patients in a median of 4 months after UCBT. Of these, 9/145 patients died from relapse, 83/145 from PTLD, and 24/145 from transplant-related causes. At last follow-up, 29/145 were alive; 5y-overall survival (OS) after PTLD diagnosis was 21±3%. Acute leukemia / myelodysplasia (AL/MDS) was diagnosed in 23 patients in a median of 28 months after UCBT and included 3 donor-cell AL. Four of 23 patients died from relapse of primary disease, 8/23 from progression of SNs, and 4/23 from TRM. Seven patients were alive at last follow-up; 5y-OS after AL/MDS diagnosis was 36±10%. Solid tumors (ST) were reported in 65 patients in a median of 54 months after UCBT. Most common tumor sites were lung, thyroid, bone and soft tissue. A total of 33/65 patients died (26 due to ST, 6 to relapse of primary disease, 1 cause missing). At last follow-up, 32/65 patients were alive; 5y-OS after the diagnosis of ST was 51±6%. In conclusion, despite their poor outcomes, SNs that occur after UCBT are extremely rare. Identification of associated risk factors and early detection may help to improve OS.
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5.
Outcome of human umbilical cord blood stem cell transplantation (CBT) for acute myeloid leukemia in patients achieving first complete remission after one versus two induction courses: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)
Nagler, A., Labopin, M., Cornelissen, J. J., Forcade, E., Chevallier, P., Fegueux, N., Sierra, J., Desmier, D., Labussière-Wallet, H., Byrne, J. L., et al
Bone marrow transplantation. 2022
Abstract
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.
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6.
Salvage haploidentical or cord-blood allogeneic stem cell transplantation after a prior alternative allograft in hematologic malignancies: a retrospective study from the SFGM-TC
Cavalieri, D., Rubio, M. T., Corriger, A., Pereira, B., Cabrespine, A., Robin, M., Labussière-Wallet, H., Calleja, A., Forcade, E., Chevallier, P., et al
European journal of haematology. 2022
Abstract
BACKGROUND Haploidentical (haplo-) donors and cord-blood (CB) stem cells provide alternative transplant options in patients lacking an HLA-matched donor. In case of relapse or graft failure after a first alternative allogeneic hematopoietic stem cell transplant (HSCT), a second alternative HSCT (HSCT2) is rarely considered due to a high risk of toxicity. METHODS A retrospective French multicenter study was performed, including patients with hematologic malignancies who underwent two consecutive HSCT from alternative donors. All data were exported from the national ProMISE database between 2000 and 2016. RESULTS Forty-three patients (61.4%) received a CB-HSCT2 and 27 (38.6%) a haplo-HSCT2. Indications for HSCT were graft failure (51.4%) or disease progression (48.6%). Two-years probabilities of overall survival, progression-free survival and toxicity-related mortality were 18.5%, 17.8% and 55.8%, respectively. In multivariate analysis, complete remission status at HSCT2 and year of HSCT2 ≥2012 were significantly associated with a better outcome (with respectively hazard ratio (HR)=0.42, p=0.002 and HR=0.5, p=0.051). CONCLUSIONS Neither the indication of HSCT2 nor the source of stem cell was more advantageous towards overall patient survival. A salvage haploidentical or cord-blood stem cell transplantation is a high-risk procedure, that may be considered for patients achieving a complete remission before receiving the second HSCT.
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7.
Allogeneic hematopoietic cell transplantation with cord blood versus mismatched unrelated donor with post-transplant cyclophosphamide in acute myeloid leukemia
Dholaria, B., Labopin, M., Sanz, J., Ruggeri, A., Cornelissen, J., Labussière-Wallet, H., Blaise, D., Forcade, E., Chevallier, P., Grassi, A., et al
Journal of hematology & oncology. 2021;14(1):76
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Editor's Choice
Abstract
BACKGROUND Allogeneic hematopoietic cell transplantation (allo-HCT) using a mismatched unrelated donor (MMUD) and cord blood transplantation (CBT) are valid alternatives for patients without a fully human leukocyte antigen (HLA)-matched donor. Here, we compared the allo-HCT outcomes of CBT versus single-allele-mismatched MMUD allo-HCT with post-transplant cyclophosphamide (PTCy) in acute myeloid leukemia. METHODS Patients who underwent a first CBT without PTCy (N?=?902) or allo-HCT from a (HLA 9/10) MMUD with PTCy (N?=?280) were included in the study. A multivariate regression analysis was performed for the whole population. A matched-pair analysis was carried out by propensity score-based 1:1 matching of patients (177 pairs) with known cytogenetic risk. RESULTS The incidence of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) at 6 months was 36% versus 32% (p?=?0.07) and 15% versus 11% (p?=?0.16) for CBT and MMUD cohorts, respectively. CBT was associated with a higher incidence of graft failure (11% vs. 4%, p?0.01) and higher 2-year non-relapse mortality (NRM) (30% vs. 16%, p?0.01) compared to MMUD. In the multivariate analysis, CBT was associated with a higher risk of, NRM (HR?=?2.09, 95% CI 1.46-2.99, p?0.0001), and relapse (HR?=?1.35, 95% CI 1-1.83, p?=?0.05), which resulted in worse leukemia-free survival (LFS) (HR?=?1.68, 95% CI 1.34-2.12, p?0.0001), overall survival (OS) (HR?=?1.7, 95% CI 1.33-2.17, p?0.0001), and GVHD-free, relapse-free survival (GRFS) (HR?=?1.49, 95% CI 1.21-1.83, p?0.0001) compared to MMUD. The risk of grade II-IV acute GVHD (p?=?0.052) and chronic GVHD (p?=?0.69) did not differ significantly between the cohorts. These results were confirmed in a matched-pair analysis. CONCLUSIONS CBT was associated with lower LFS, OS, and GRFS due to higher NRM, compared to MMUD allo-HCT with PTCy. In the absence of a fully matched donor, 9/10 MMUD with PTCy may be preferred over CBT.
PICO Summary
Population
Patients with acute myeloid leukaemia (n=1182)
Intervention
First cord blood transplant without post-transplant cyclophosphamide (CBT, n=902)
Comparison
Allogeneic haematopoietic stem cell transplantation usinga mismatched unrelated donor with post-transplant cyclophosphamide (MMUD, n=280)
Outcome
The incidence of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) at 6 months was 36% versus 32% and 15% versus 11% for CBT and MMUD cohorts, respectively. CBT was associated with a higher incidence of graft failure (11% vs. 4%) and higher 2-year non-relapse mortality (NRM) (30% vs. 16%) compared to MMUD. In the multivariate analysis, CBT was associated with a higher risk of, NRM (HR=2.09), and relapse (HR=1.35), which resulted in worse leukemia-free survival (LFS) (HR=1.68), overall survival (OS) (HR=1.7), and GVHD-free, relapse-free survival (GRFS) (HR=1.49) compared to MMUD. The risk of grade II-IV acute GVHD and chronic GVHD did not differ significantly between the cohorts. These results were confirmed in a matched-pair analysis.
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Optimizing selection of double cord blood units for transplantation of adult patients with malignant diseases
Fatobene, G., Volt, F., Moreira, F., Mariano, L., Chevallier, P., Furst, S., Labussière-Wallet, H., de la Tour, R. P., Deconinck, E., Cluzeau, T., et al
Blood advances. 2020;4(24):6327-6335
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Abstract
Double-unit unrelated cord blood transplantation (DUCBT) is an option in patients for whom a single unit is not sufficient to provide an adequate number of cells. As current guidelines on UCB unit selection are mainly based on single-unit UCB data, we performed a retrospective analysis of 1375 adult recipients of DUCBT for hematologic malignancies to determine optimal criteria for graft selection. Cryopreserved total nucleated cells (TNCs; =3.5 vs >3.5 × 107/kg: hazard ratio [HR], 1.53; 30% vs 45%; P = .01), number of HLA mismatches (=2 vs 0-1: HR, 1.28; 42% vs 48%; P = .01), and ABO compatibility (minor/major ABO incompatibility vs compatibility: HR, 1.28; P = .04) were independent risk factors for OS. Cryopreserved CD34+ cell dose =0.7 × 105/kg in the winning UCB was associated with improved OS (HR, 1.34; P = .03). Low TNC (=3.5 × 107/kg) and CD34+ (=1.4 × 105/kg) cell doses were related to decreased neutrophil recovery (HR, 0.65 [P = .01] and HR, 0.81 [P = .01], respectively). DUCBT recipients with =2 HLA mismatches had a higher incidence of grade II-IV and III-IV acute graft-versus-host disease (HR, 1.26 [P = .03] and 1.59 [P = .02], respectively). Low TNC dose (HR, 1.57; P = .02) and receiving UCB with =2 HLA mismatches (HR, 1.35; P = .03) were associated with increased transplant-related mortality. Our data support selecting adequately HLA-matched UCB units with a double-unit cryopreserved TNC dose >3.5 × 107/kg and CD34+ cell dose of =0.7 × 105/kg per unit in DUCBT candidates.
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Outcomes of advanced Hodgkin lymphoma after umbilical cord blood transplantation: a Eurocord and EBMT Lymphoma and Cellular Therapy & Immunobiology Working Party study
Paviglianiti, A., Maio, K. T., Rocha, V., Gehlkopf, E., Milpied, N., Esquirol, A., Chevallier, P., Blaise, D., Gac, A. C., Leblond, V., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
Abstract
Allogeneic stem cell transplantation is an alternative for patients with relapsed or refractory Hodgkin lymphoma (HL) but only limited data on unrelated umbilical cord blood transplantation (UCBT) are available. We analyzed 131 adults with HL who underwent UCBT in EBMT centers from 2003 to 2015. Disease status at UCBT was complete remission (CR) in 59 (47%) and almost all patients had received a previous autologous stem cell transplantation. The 4-year PFS and OS were 26% (95% CI 19-34%) and 46% (95% CI 37-55%), respectively. Relapse incidence was 44% (95% CI 36-54%) and non-relapse mortality (NRM) was 31% (95% CI 23-40%) at 4 years. In multivariate analysis, refractory/relapsed disease status at UCBT was associated with increased relapse incidence (HR=3.14 [95% CI 1.41-7.00], p=0.005) and NRM (HR=3.61 [95% CI 1.58-8.27], p=0.002), lower PFS (HR=3.45 [95% CI 1.95-6.10], p<0.001) and OS (HR=3.10 [95% CI 1.60-5.99], p=0.001). Conditioning regimen with cyclophospamide+fludarabine+2Gy total body irradiation (Cy+Flu+2 GyTBI) was associated with decreased risk of NRM (HR=0.26 [95% CI 0.10-0.64], p=0.004). Moreover, Cy+Flu+2 GyTBI conditioning regimen was associated with a better OS (HR=0.25 [95% CI 0.12-0.50], p<0.001) and PFS (HR=0.51 [95% CI 0.27-0.96], p=0.04). UCBT is feasible in heavily pretreated patients with HL. The reduced intensity conditioning regimen with Cy+flu+2 GyTBI is associated with a better OS and NRM. However, outcomes are poor in patients not in CR at UCBT.
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Cord blood transplantation is associated with good outcomes in secondary Acute Myeloid Leukemia in first remission
Baron, F., Labopin, M., Ruggeri, A., Volt, F., Mohty, M., Blaise, D., Chevallier, P., Sanz, J., Fegueux, N., Cornelissen, J. J., et al
Journal of internal medicine. 2018
Abstract
BACKGROUND We conducted a retrospective survey within the European Society for Blood and Marrow Transplantation (EBMT) registry to assess the outcomes of cord blood transplantation (CBT) in secondary acute myeloid leukemia (sAML). METHODS Inclusion criteria consisted of ≥ 18 years of age, sAML, first CBT between 2002 and 2016, and either first complete remission (CR) or active disease at CBT. RESULTS One hundred forty six patients met the study inclusion criteria. Status at transplantation was first CR (n=97), primary refractory sAML (n=30) or relapsed (n=19) sAML. Neutrophil engraftment was achieved in 118 patients while the remaining 25 patients (17%) failed to engraft. This include 13% of patients transplanted in first CR versus 30% of those transplanted with active disease (P=0.008)). Two-year incidences of relapse were 25% in first CR patients versus 36% in those with advanced disease (P=0.06) while 2-year incidences of nonrelapse mortality were 35% and 49% (P=0.03), respectively. At 2-year overall survival, leukemia-free survival and graft-versus-host disease (GVHD)-free relapse free survival were 42% versus 19% (P<0.001), 40% versus 16% (P<0.001), and 26% versus 12% (P=0.002) in first CR patients versus those with advanced disease, respectively. CONCLUSIONS We report here the first study of CBT in a large cohort of sAML patients. Main observation was that CBT rescued approximately 40% of patients with sAML in first CR. This article is protected by copyright. All rights reserved.