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1.
Comparison of fludarabine-based conditioning regimens in adult cord blood transplantation for myeloid malignancy: A retrospective, registry-based study
Kurita, N., Imahashi, N., Chiba, S., Tanaka, M., Kobayashi, H., Uchida, N., Kuriyama, T., Anzai, N., Nawa, Y., Nakano, N., et al
American journal of hematology. 2024
Abstract
Fludarabine/busulfan and fludarabine/melphalan are viable options as conditioning regimens. However, the optimal fludarabine-based conditioning in cord blood transplantation (CBT) remains unclear. Therefore, this retrospective, registry-based study aimed to analyze the impact of five fludarabine-containing conditioning regimens on 1395 adult patients (median age, 61 years) with acute myeloid leukemia, myelodysplastic syndrome, and chronic myeloid leukemia who underwent their first CBT. Treatment outcomes of fludarabine combined with melphalan (100-140 mg/m(2) ) and low-dose total body irradiation (TBI; FM140T); melphalan (80-99 mg/m(2) ) and TBI (FM80T); busulfan (12.8 mg/kg) and melphalan (FB4M); busulfan (12.8 mg/kg) and TBI (FB4T); and busulfan (6.4 mg/kg) and TBI (FB2T) were compared. The 3-year survival rate was 67%, 53%, 44%, 36%, and 39%, respectively (p < .0001). The FM140T survival rate was the most favorable after adjusting for confounders, and the hazard ratios (vs. FM140T) for overall mortality were as follows: FM80T, 1.6 (95% confidence interval [CI], 1.2-2.2); FB4M, 2.1 (95% CI, 1.6-2.8); FB4T, 2.7 (95% CI, 2.0-3.7); and FB2T, 2.2 (95% CI, 1.6-3.1). The better survival observed with FM140T, regardless of the disease, disease risk, age, or transplant year, was attributed to the lower relapse rate and lower non-relapse mortality (NRM) associated with fewer infectious deaths. Conversely, FB4T was associated with a higher relapse rate and higher NRM. The findings indicate that the outcomes of CBT in myeloid malignancies were highly dependent on both the alkylating agent and its dose in combination with fludarabine. Therefore, compared with fludarabine/busulfan-based conditioning, FM140T may be the preferred regimen.
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2.
Machine Learning Prediction Model for Neutrophil Recovery after Unrelated Cord Blood Transplantation
Kuwatsuka, Y., Kasajima, R., Yamaguchi, R., Uchida, N., Konuma, T., Tanaka, M., Shingai, N., Miyakoshi, S., Kozai, Y., Uehara, Y., et al
Transplantation and cellular therapy. 2024
Abstract
BACKGROUND Delayed neutrophil recovery is an important limitation to the administration of cord blood transplantation (CBT) and leaves the recipient vulnerable to life-threatening infection and increases the risk of other complications. OBJECTIVES A predictive model for neutrophil recovery after single-unit CBT was developed by using a machine learning method, which can handle large and complex datasets, allowing for the analysis of massive amounts of information to uncover patterns and make accurate predictions. STUDY DESIGN Japanese registry data, the largest real-world dataset of CBT, was selected as the data source. Ninety-eight variables with observed values for more than 80% of the subjects known at the time of CBT were selected. Model building was performed with a competing risk regression model with lasso penalty. Prediction accuracy of the models was evaluated by calculating area under curve (AUC) using a test dataset. The primary outcome was neutrophil recovery at day 28 (D28), and D14 and D42 were analyzed as secondary outcomes. RESULT The final cord blood engraftment prediction (CBEP) models included 2,991 single-unit CBT recipients with acute leukemia. Median AUC of a D28-CBEP lasso regression model run 100 times was 0.74, and those of D14 and D42 were 0.88 and 0.68, respectively. The D28-CBEP model predictivity was higher than four different legacy models that were separately constructed. CONCLUSIONS A highly predictive model for neutrophil recovery by 28 days after CBT was constructed using machine learning techniques. However, identification of significant risk factors was insufficient for outcome prediction for an individual patient, which is necessary for improving therapeutic outcomes. Notably, the prediction accuracy for days 14, 28, and 42 post-transplant decreased, and the model became more complex with more associated factors with increased time after transplantation.
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3.
Selection of cord blood unit by CD34(+) cell number, CFU-GM number and allele-level HLA matching in single cord blood transplantation
Morishima, Y., Watanabe-Okochi, N., Kai, S., Azuma, F., Kimura, T., Matsumoto, K., Hatasa, S., Araki, N., Miyamoto, A., Sekimoto, T., et al
Transplantation and cellular therapy. 2023
Abstract
BACKGROUND In Japan only single cord blood transplantations (CBTs) are typically performed and their number has increased over 23 years, with ongoing improvement in the results. CBTs with multiple HLA mismatches are usually employed due to a low HLA barrier, and lower engraftment rate is one of problems to overcome. OBJECTIVE Here, as part of efforts to improve guidelines for the selection and processing of cord blood units for transplantation, we sought to assess the present status of CBTs in Japan, and to elucidate factors contributing to the favorable outcomes, especially focusing on the selection by cell components of cord blood (CB) unit and HLA allele matching. STUDY DESIGN We conducted a nation-wide study analyzing 13,443 patients who underwent first CBT between in Japan between Dec 1997 - Dec 2019 using multivariate regression analysis. RESULTS Both patient and transplant related variables, such as age and HCT-CI scores, as well as selectable CB unit characteristics were included in the analysis. The interaction analysis elucidated that CB unit selection favoring larger numbers of CD34(+) cells /kg and CFU-GM number/kg, and not total nucleated cell number/kg contributed to improved engraftment after transplantation. Moreover, a higher CD34+ cell dose was associated with improved overall survival. Distinctive HLA allele matching was observed. 0-1 HLA allele mismatch between patient and donor had favorable engraftment and carried a significantly lower risk of acute GVHD and chronic GVHD, but had a significantly higher leukemia relapse rate, compared with a 3-HLA allele mismatch. HLA-DRB1 mismatches were associated with reduced risk of leukemia relapse. Notably, the number of HLA allele mismatches had no incremental effect on engraftment, acute and chronic GVHD, or relapse incidence. As a result, the 5-year overall survival did not differ significantly between patients receiving CB units with 0-7 HLA allele mismatches. Main points of CB unit selection: First, selection according to a higher number of CD34+/kg and then of CFU-GM/kg is recommended to obtain favorable engraftment. A unit with 0.5 x 10(5) CD34+/kg is minimally acceptable. For units with a CD34(+) cell dose of 0.5-1.0 x 10(5) cells/kg, applying the parameter of ≥20 - 50 x 10(3) CFU-GM/kg (66.5% of transplanted CB units in this cohort) is associated with a neutrophil engraftment rate of approximately 90%. A unit with ≥1.0 x 10(5) CD34(+)/kg can achieve a ≥90% mean neutrophil engraftment rate. Subsequently, HLA allele matching of HLA-A, -B, -C, -DRB1 at the 2-field level should be searched for unit with 0-1 HLA allele mismatch number in HVG direction for favorable engraftment. Unit with 2-6 HLA allele mismatches is acceptable in adult patients (15 y.-) and unit with 2-4 HLA allele mismatches in pediatric patients (0-14 y.). Unit with HLA-DRB1 and/or -B allele mismatch might not be preferable due to an increased GVHD risk. CONCLUSION Our analysis demonstrated that single CBT with the selection of adequate CD34(+)/kg and CFU-GM/kg, and HLA allele matching showed a favorable outcome not only in pediatric but also in adult patients.
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4.
Unrelated Donor Cord Blood Transplantation in Children: Lessons Learned Over 3 Decades
Kurtzberg, J., Troy, J. D., Page, K. M., El Ayoubi, H. R., Volt, F., Maria Scigliuolo, G., Cappelli, B., Rocha, V., Ruggeri, A., Gluckman, E.
Stem cells translational medicine. 2023;12(1):26-38
Abstract
Four decades ago, Broxmeyer et al. demonstrated that umbilical cord blood (CB) contained hematopoietic stem cells (HSC) and hypothesized that CB could be used as a source of donor HSC for rescue of myeloablated bone marrow. In 1988, Gluckman et al. reported the first successful matched sibling cord blood transplant (CBT) in a child with Fanconi Anemia. In 1991, Rubinstein et al. established an unrelated donor CB bank, and in 1993, the first unrelated CBT used a unit from this bank. Since that time, >40 000 CBTs have been performed worldwide. Early outcomes of CBT were mixed and demonstrated the importance of cell dose from the CB donor. We hypothesized that improvements in CB banking and transplantation favorably impacted outcomes of CBT today and performed a retrospective study combining data from Eurocord and Duke University in 4834 children transplanted with a single unrelated CB unit (CBU) from 1993 to 2019. Changes in standard transplant outcomes (overall survival [OS], disease free survival [DFS], acute and chronic graft-versus-host disease [GvHD], treatment related mortality [TRM], and relapse) over 3 time periods (1: <2005; 2: 2005 to <2010; and 3: >2010 to 2019) were studied. Increased cell dose and degree of HLA matching were observed over time. OS, times to engraftment, and DFS improved over time. The incidence of TRM and GvHD decreased while the incidence of relapse remained unchanged. Relative contributions of cell dose and HLA matching to transplant outcomes were also assessed and showed that HLA matching was more important than cell dose in this pediatric cohort.
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5.
Single-unit unrelated cord blood transplantation versus HLA-matched sibling transplantation in adults with advanced myelodysplastic syndrome: A registry-based study from the adult MDS working group of the Japanese society for transplantation and cellular therapy
Konuma, T., Itonaga, H., Shimomura, Y., Fujioka, M., Aoki, K., Uchida, N., Onizuka, M., Jinguji, A., Tanaka, M., Ueda, Y., et al
Hematological oncology. 2023
Abstract
Allogeneic hematopoietic stem cell transplantation (HCT) remains the only potential curative therapeutic modality for advanced myelodysplastic syndrome (MDS). Within HCT, the advancement of cord blood transplantation (CBT) procedures has resulted in a drastic expansion of CBT as a donor source for MDS. However, data comparing matched sibling donors (MSDs) HCT with CBT for advanced MDS, which was defined as refractory anemia with an excess of blasts (RAEB)-1 and RAEB-2 according to the World Health Organization classification at the time of HCT, have not been explored. We retrospectively compared survival and other posttransplant outcomes in 999 adult patients with advanced MDS after receiving allogeneic HCT in Japan between 2011 and 2020, using either MSD (n = 331) or single-unit unrelated cord blood (UCB) (n = 668). In the multivariate analysis, there were no significant differences in overall survival (hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.90-1.34; P = 0.347), disease-free survival (HR, 1.01; 95% CI, 0.84-1.23; P = 0.845), relapse (HR, 0.88; 95% CI, 0.68-1.15; P = 0.370), or non-relapse mortality (HR, 1.15; 95% CI, 0.87-1.50; P = 0.310) between MSD recipients and UCB recipients. UCB was significantly associated with lower neutrophil (HR, 0.28; 95% CI, 0.24-0.33; P < 0.001) and lower platelet (HR, 0.29; 95% CI, 0.23-0.36; P < 0.001) recovery compared to MSD. UCB was significantly associated with a lower incidence of chronic graft-versus-host disease (GVHD) (HR, 0.57; 95% CI, 0.44-0.75; P < 0.001) and extensive chronic GVHD (HR, 0.46; 95% CI, 0.32-0.67; P < 0.001) compared to MSD. Similar results were observed after adjusting for differences between MSD and UCB recipients by propensity score matching analysis. Our study demonstrated that single CBT and MSD HCT had similar survival outcomes for adult patients with advanced MDS despite the lower hematopoietic recovery in CBT recipients and higher chronic GVHD in MSD recipients.
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6.
Effect of Graft-versus-Host Disease on Post-Transplantation Outcomes following Single Cord Blood Transplantation Compared with Haploidentical Transplantation with Post-Transplantation Cyclophosphamide for Adult Acute Myeloid Leukemia
Konuma, T., Matsuda, K., Shimomura, Y., Tanoue, S., Sugita, J., Inamoto, Y., Hirayama, M., Ara, T., Nakamae, H., Ota, S., et al
Transplantation and cellular therapy. 2023;29(6):365.e1-365.e11
Abstract
The possibility that HLA mismatches could reduce relapse after alternative HLA-mismatched allogeneic hematopoietic cell transplantation (HCT) is an attractive concept for treating acute myeloid leukemia (AML). However, it remains unclear whether the prognostic effect of graft-versus-host disease (GVHD) on survival differs between recipients of single-unit cord blood transplantation (CBT) and recipients of haploidentical HCT using post-transplantation cyclophosphamide (PTCy-haplo-HCT) for AML. The objective of this retrospective study was to compare the effect of acute GVHD and chronic GVHD on post-transplantation outcomes between recipients of CBT and recipients of PTCy-haplo-HCT. We retrospectively evaluated the effect of acute and chronic GVHD on post-transplantation outcomes following CBT and PTCy-haplo-HCT in adults with AML (n = 1981) between 2014 and 2020 using a Japanese registry database. In univariate analysis, the probability of overall survival was significantly greater in patients who developed grade I-II acute GVHD (P < .001, log-rank test) and limited chronic GVHD (P < .001, log-rank test) among CBT recipients, but these effects were not significant among PTCy-haplo-HCT recipients. In multivariate analysis, in which the development of GVHD was treated as a time-dependent covariate, the effect of grade I-II acute GVHD on reducing overall mortality differed significantly between CBT and PTCy-haplo-HCT (adjusted hazard ratio [HR] for CBT, .73, 95% confidence interval [CI], .60 to .87; adjusted HR for PTCy-haplo-HCT, 1.07; 95% CI, .70 to 1.64; P for interaction = .038). Our data demonstrate that grade I-II acute GVHD was associated with a significant improvement in overall mortality in adults with AML receiving CBT but not in recipients of PTCy-haplo-HCT.
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7.
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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8.
Comparative analysis of the variability of the human leukocyte antigen peptide-binding pockets in patients with acute leukaemia
Boukouaci, W., Rivera-Franco, M. M., Volt, F., Wu, C. L., Rafii, H., Cappelli, B., Scigliuolo, G. M., Kenzey, C., Ruggeri, A., Rocha, V., et al
British journal of haematology. 2022
Abstract
The association between acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) and the human leukocyte antigens (HLA) has rarely been studied in terms of diversity of peptide-binding pockets. The objective of this study was to analyse whether motifs of HLA class I and class II peptide-binding pockets and/or their amino acid positions were differentially associated with ALL and AML. We included 849 patients from the Eurocord/European Blood and Marrow Transplant registry. The HLA peptide-binding pockets whose amino acid variability was analysed were B and F for HLA class I, P4, P6, and P9 for HLA-DRB1, and P4 and P9 for HLA-DQB1. The motif RFDRAY in P4 of HLA-DRB1*16:01/02/03/05 alleles and the motif YYVSY in P9 of HLA-DQB1*05:02/04/05 alleles, were statistically associated with ALL (corrected p value [p(c) ] = 0.001 and p(c) = 0.035 respectively). The frequency of serine 57 in the P9 of HLA-DQB1 was higher in ALL (odds ratio 2.09, 95% confidence interval: 1.27-3.44; p(c) = 0.037). Our analysis suggests that specific motifs in terms of HLA class II pockets and amino acids might be unique to ALL. The associations identified in this study encourage further investigation oF the role of HLA peptide-binding pockets and their amino acids in immune processes underpinning acute leukaemia and ultimately in immunotherapy settings.
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9.
Effect of multiple HLA-locus mismatches on outcomes after single cord blood transplantation
Kanda, J., Hirabayashi, S., Yokoyama, H., Kawase, T., Tanaka, H., Uchida, N., Taniguchi, S., Takahashi, S., Onizuka, M., Tanaka, M., et al
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND Effect of single or multiple mismatches at each HLA locus on outcomes after cord blood transplantation (CBT) is controversial. OBJECTIVE We analyzed the effects of single or multiple HLA-locus mismatches on the outcomes after single CBT using a Japanese registry data from the Japan Society for Hematopoietic Cell Transplantation (JSHCT). STUDY DESIGN Patients with acute leukemia and myelodysplastic syndromes, aged 16 years or older, who underwent their first CBT between 2003 and 2017 (n = 4,074) were included. The effect of the number of HLA-locus mismatches (0, 1, and 2, for the HLA-A, -B, -C, and -DRB1 loci) on outcomes was analyzed after adjusting for other significant variables. RESULTS The median age of the patients was 54 years. Median total nucleated and CD34 cell doses were 2.6 × 10(7)/kg and 0.8 × 10(5)/kg, respectively. The number of CBTs with single or double mismatches were 2,099 and 292 for HLA-A locus, 2,699 and 341 for HLA-B locus, 2,555 and 609 for HLA-C locus, and 2,593 and 571 for HLA-DRB1 locus, respectively. Single and double HLA-DRB1 mismatches were associated with a higher risk of grade II-IV acute graft-versus-host disease (GVHD, single: HR 1.29, P<0.001, double: HR 1.49, P<0.001, trend-P: P<0.001). Single and double mismatches at HLA-DRB1 as well as single mismatches at HLA-A and HLA-B were also associated with grade III-IV acute GVHD. Single and double HLA-B mismatches and double HLA-DRB1 mismatches were associated with a high risk of non-relapse mortality. On the other hand, double mismatches at HLA-A or HLA-DRB1 and single mismatches at HLA-B were associated with a lower risk of relapse. CONCLUSION HLA-DRB1 double mismatch was associated with high risks of grade II-IV and III-IV acute GVHD and non-relapse mortality but lower risk of relapse. Not only the locus mismatch but also the number of mismatches may be considered in cord blood unit selection.
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10.
Unrelated cord blood transplantation in children, adolescents, and young adults with acute leukemia or myelodysplastic syndrome: a retrospective comparative study from the French Society for Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) between Real-World Data and previously reported results of a Randomized Clinical Trial
Teyssier, A. C., Michel, G., Jubert, C., Rialland, F., Visentin, S., Ouachée, M., Bilger, K., Gandemer, V., Beguin, Y., Marie-Cardine, A., et al
Transplantation and cellular therapy. 2022
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Editor's Choice
Abstract
BACKGROUND We previously reported results of a French randomized clinical trial (RCT) comparing the risk of transplantation failure (including transplant-related mortality (TRM), engraftment failure, and autologous recovery) in single and double unrelated cord blood (UCB) transplantation in children and young adults with hematologic malignancies. We concluded that single-UCB transplantation with an adequate cell dose is the standard of care, leading to a 70% two-year overall survival (OS). It remains unclear, however, whether RCT participants have better outcomes than comparable patients not treated in the setting of a clinical trial. We previously reported results of a French randomized clinical trial (RCT) comparing the risk of transplantation failure (including transplant-related mortality (TRM), engraftment failure, and autologous recovery) in single and double unrelated cord blood (UCB) transplantation in children and young adults with hematologic malignancies. We concluded that single-UCB transplantation with an adequate cell dose is the standard of care, leading to a 70% two-year overall survival (OS). It remains unclear, however, whether RCT participants have better outcomes than comparable patients not treated in the setting of a clinical trial. We compared the characteristics and outcomes of RCT participants (n = 137) to a Francophone population-based registry of patients (real-world (RW) group) fulfilling the eligibility criteria used in our RCT and transplanted with one or two UCB units after a myeloablative conditioning (MAC) regimen between March 2015 (end of inclusion in the RCT) and February 2019 (n = 141). The primary endpoint was the two-year cumulative incidence (CI) of transplantation strategy failure as defined in our RCT. The two groups were comparable in terms of age, disease distribution, hematologic status at transplantation, follow-up, and HLA compatibility. Patients in the RW group were more likely to be transplanted with a single-unit UCB (87.9% versus 49.6%, p < 0.001) and to receive a radiation-free regimen (39.0% vs. 60.6%, p < 0.001). The two-year CI of transplantation strategy failure, TRM, and the two-year probability of OS were similar between the two groups, although the relapse risk was higher in the RW group (31.2% ± 7.7% vs. 20.4% ± 6.8%, p = 0.01), resulting in a significantly lower DFS (59.2% ± 8.4% vs. 69.3% ± 8.0%, p = 0.047). This difference remained statistically significant only in the group of patients with acute lymphoid leukemia (ALL) who did not receive the conditioning regimen recommended by the RCT (fludarabine 75 mg/m2, total body irradiation 12 Gy, cyclophosphamide 120 mg/kg). The results of our RCT appear to be reproducible in real-world conditions, provided that the same cord blood selection criteria and conditioning regimen are used. OBJECTIVES AND STUDY DESIGN We compared the characteristics and outcomes of RCT participants (n = 137) to a Francophone population-based registry of patients (real-world (RW) group) fulfilling the eligibility criteria used in our RCT and transplanted with one or two UCB units after a myeloablative conditioning (MAC) regimen between March 2015 (end of inclusion in the RCT) and February 2019 (n = 141). The primary endpoint was the two-year cumulative incidence (CI) of transplantation strategy failure as defined in our RCT. RESULTS The two groups were comparable in terms of age, disease distribution, hematologic status at transplantation, follow-up, and HLA compatibility. Patients in the RW group were more likely to be transplanted with a single-unit UCB (87.9% versus 49.6%, p < 0.001) and to receive a radiation-free regimen (39.0% vs. 60.6%, p < 0.001). The two-year CI of transplantation strategy failure, TRM, and the two-year probability of OS were similar between the two groups, although the relapse risk was higher in the RW group (31.2% ± 7.7% vs. 20.4% ± 6.8%, p = 0.01), resulting in a significantly lower DFS (59.2% ± 8.4% vs. 69.3% ± 8.0%, p = 0.047). This difference remained statistically significant only in the group of patients with acute lymphoid leukemia (ALL) who did not receive the conditioning regimen recommended by the RCT (fludarabine 75 mg/m2, total body irradiation 12 Gy, cyclophosphamide 120 mg/kg). CONCLUSION The results of our RCT appear to be reproducible in real-world conditions, provided that the same cord blood selection criteria and conditioning regimen are used.
PICO Summary
Population
Children, adolescents and young adults with acute leukaemia or myelodysplastic syndrome
Intervention
Participants in a randomised controlled trial (RCT) (n=137)
Comparison
Patients from a real-world cohort reported to a Francohpone regisistry, receiving onr or two cord blood units after myeloablative conditioning (RW group, n=141)
Outcome
The two groups were comparable in terms of age, disease distribution, hematologic status at transplantation, follow-up, and HLA compatibility. Patients in the RW group were more likely to be transplanted with a single-unit UCB (87.9% versus 49.6%) and to receive a radiation-free regimen (39.0% vs. 60.6%). The two-year CI of transplantation strategy failure, Transplant related mortality, and the two-year probability of overall survival were similar between the two groups, although the relapse risk was higher in the RW group (31.2% ± 7.7% vs. 20.4% ± 6.8%), resulting in a significantly lower DFS (59.2% ± 8.4% vs. 69.3% ± 8.0%). This difference remained statistically significant only in the group of patients with acute lymphoid leukemia (ALL) who did not receive the conditioning regimen recommended by the RCT (fludarabine 75 mg/m2, total body irradiation 12 Gy, cyclophosphamide 120 mg/kg).