Umbilical Cord Blood Group Research Articles

The efficacy and safety of third-party umbilical blood/umbilical cord mesenchymal stem cell assisted related haploid hematopoietic stem cell transplantation in pediatric patients with acute leukemia: an observational study.

There is limited data on third-party umbilical cord blood (UCB) or mesenchymal stem cell (MSC) transplantation-assisted haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in pediatric patients. To evaluate the efficacy and safety of UCB and MSC transplantation-assisted haplo-HSCT in pediatric patients with acute leukemia (AL). Observational study. Clinical data of 152 children with AL undergoing haplo-HSCT at the Children's Hospital of Soochow University between January 2020 and June 2022 were collected. The patients were divided into the haplo-HSCT + UCB group (n = 76), haplo-HSCT + MSC group (n = 31), and haplo-HSCT group (n = 45). Hematopoietic reconstruction time, complications within 30 days after transplantation, and survival and recurrence at 3 years after transplantation were compared among the groups. Multivariate analysis revealed that haplo-HSCT with MSC and human leukocyte antigen (HLA) matching ⩾6/10 were independent factors reducing engraftment syndrome (ES) incidence. There were no significant differences among the groups in the hematopoietic reconstruction time or incidence of complications within 30 days after transplantation (p > 0.05). Overall survival, relapse-free survival, cumulative incidence of relapse, cumulative incidence of hematological relapse, and 3-year transplant-related mortality were not significantly different (p > 0.05). The incidence of adverse reactions in the haplo-HSCT + UCB group was 97.3% within 4 h after UCB infusion, with a particularly high occurrence rate of 94.7% for hypertension. No transfusion-related adverse reactions occurred after the transfusion of umbilical cord MSC in the haplo-HSCT + MSC group. MSC-assisted haplo-HSCT can reduce ES incidence after transplantation in pediatric patients with AL. UCB infusion is associated with a high incidence of reversible hypertension. However, no adverse reactions were observed in umbilical cord MSC transfusion.

Impact of the source of hematopoietic stem cells on immune reconstitution after transplantation: A systematic review.

Hematopoietic stem cell (HSC) transplantation's success lies in its ability to induce immune reconstitution. To date, there is no review published to compare the immune reconstitution among the three sources of HSC: umbilical cord blood (UCB), bone marrow (BM), and peripheral blood (PB). The review aims to analyze the kinetic of immune reconstitution among UCB, PB, and BM in HSC transplant patients by focusing on natural killer (NK) cells, B and T lymphocytes, and neutrophils. A systematic review was conducted through five databases, searching for clinical trials and randomized control trials (RCTs) which analyze the kinetics of immune reconstitution in at least two sources. Selected studies were assessed with Cochrane RoB 2.0. This review included 14 studies, with a total of 2539 subjects. The PB group achieved the fastest time to neutrophil recovery, while the B-cell count was the highest in the UCB group. The T-cell count is the lowest in the BM group, and the NK-cell count does not differ significantly among the three HSC sources. Among the three sources of HSC, there is no superior HSC source for any immune reconstitution parameter. More studies must be conducted to compare the immune reconstitution and clinical outcomes of all HSC sources in specific diseases.

CD44, CD90 and CD96 expression in immune thrombocytopenia purpura (ITP) patients

ABSTRACT Studying the expression of hematopoietic stem cell markers from different sources might be useful in understanding stem cell biology in different niche conditions. The study aimed to assess the difference in cell surface markers (CD44, CD90, CD96) on hematopoietic stem cells in three different niche conditions; umbilical cord blood (UCB), normal bone marrow (NBM) and bone marrow samples from idiopathic (immune) thrombocytopenic purpura (IBM). This study was conducted on 300 cases divided into three study groups; 100 umbilical cord blood units collected from mothers undergoing cesarian section in gynecology and obstetrics department, 100 bone marrow samples from idiopathic (immune) thrombocytopenic purpura patients collected from university children hospital and 100 normal bone marrow samples with no evidence of disease in bone marrow tissue. CD44 was significantly elevated in UCB and NBM groups compared to IBM group (<0.001). There was also a significant elevation of CD90 and CD96 in IBM group compared to NBM group and UCB (<0.001). CD90 and CD96 play a role in the pathogenesis of ITP disorder and could be applied as a targeted therapy to improve the outcome of this disease.

The frequencies of lymphocyte subsets on “day 30″ correlate with the clinical outcome of pediatric hematopoietic stem cell transplantation

We aimed to determine the relationship between lymphocyte subsets on day 30 (D30) and prognosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children. We retrospectively examined the clinical outcomes and lymphocyte subsets on D30 after allo-HSCT in 115 pediatric patients at the Children's Hospital of Soochow University between January 2016 and June 2019. Measurements were performed using flow cytometry on D30. Lymphocyte subsets were compared among the umbilical cord blood (UCB) (n = 22), HLA-matched sibling donor (MSD) (n = 14), haploidentical donor transplantation (HID) (n = 57), and unrelated donor transplantation (UD) (n = 22) groups. The relationships between the frequencies and counts of lymphocyte subsets and clinical outcomes were analyzed. T and B cell counts were the highest in the MSD group compared to the other groups, and natural killer cell counts were the highest in the UCB group. Lymphocyte subsets on D30 after allo-HSCT were correlated with the occurrence of acute (aGVHD) and chronic graft versus host disease (cGVHD). A high frequency of B cells (≥4.65%) was associated with the development of severe aGVHD. High frequencies of CD4+T (≥10.25%) were correlated with extensive cGVHD. Moreover, a high frequency of CD4+T cells (≥9.80%) was correlated with GVHD-free and failure-free survival (GFFS) after allo-HSCT. However, on D30, there were no statistically significant correlations between viral infections and lymphocyte subsets. The frequencies of lymphocyte subsets on D30 after allo-HSCT are good indicators of prognosis after allo-HSCT in children.

CT-314 Multicenter Long-Term Follow Up of Allogeneic Hematopoietic Stem Cell Transplantation With Omidubicel: A Pooled Analysis of Five Prospective Clinical Trials

Allogeneic hematopoietic stem cell transplantation (allo-HCT) with umbilical cord blood (UCB) is limited by the low number of hematopoietic stem cells. Omidubicel is an ex-vivo expanded stem cell product derived from UCB. Prospective clinical trials have demonstrated faster engraftment and fewer infections with omidubicel compared to UCB, but long-term outcomes are unknown. This is a pre-specified pooled secondary analysis of long-term outcomes with allo-HCT using omidubicel from 5 multicenter prospective trials. Patients transplanted with omidubicel in one randomized phase III and four single-arm trials between 2006 and 2020 were followed for up to 10 years post-transplant. Twenty-six international academic transplant centers. Among 116 patients transplanted with either standalone omidubicel (n=92) or omidubicel with supplementary UCB (n=24), 97 (83.6%) engrafted with omidubicel, 11 (9.5%) with UCB, 2 mixed chimerism, 1 unevaluable, and 5 (4.3%) primary graft failure. This study included all patients aside from those engrafted with UCB (n=105). Median age was 42 (range, 2-62), 52.4% male, 30.5% non-white, and 30.5% high/very-high disease risk indices. Most common diseases were AML (40.1%), ALL (26.7%), MDS (13.3%), and sickle cell disease (7.6%). Median follow-up was 22.0 months (range, 0.3-122.5). The 3-year OS and DFS were 62.5% (95%CI, 53.4-73.2) and 56.2% (95%CI, 47.0-67.1), respectively. Common causes of death included disease relapse (n=16) and infection (n=11). Three-year cumulative incidences of chronic GVHD and relapse were 37.8% (95%CI, 27.9-47.6) and 24.3% (95%CI, 16.1-33.3), respectively. Durable trilineage hematopoiesis was observed for up to 10 years. Similarly, median numbers of lymphoid subsets, including CD3+, CD4+, CD8+ T cells, CD19+ B cells, and CD16+/CD56+ NK cells were maintained within normal range for up to 8 years. Secondary graft failure was noted in 5 patients, 3 of whom underwent a second allo-HCT. Secondary hematologic malignancies included donor-derived myeloid neoplasm (dd-MN) (n=1; 40 months post-transplant) and PTLD (n=2; 17 and 20 months), with one death attributed to PTLD. Notably, there was also one case of dd-MN in the control UCB group of the phase III study. Omidubicel demonstrated durable long-term hematopoiesis and immune competence. One case of dd-MN was observed with both omidubicel and control UCB.

Abstract 8 Health-Related Quality of Life (HRQL) Following Transplantation with Omidubicel Versus Umbilical Cord Blood (UCB) in Patients with Hematologic Malignancies: Results from a Phase III Randomized, Multicenter Study

IntroductionOmidubicel, an advanced cell therapy used for allogeneic hematopoietic stem cell transplant has demonstrated faster hematopoietic recovery, shorter hospitalization, and lower rates of bacterial, viral, and invasive fungal infections compared with umbilical cord blood (UCB) in a phase III randomized trial (NCT02730299;Blood 2021;138:1429).ObjectiveThe objective was to compare changes in health-related quality of life (HRQL) between treatment groups in the phase III trial.MethodsPatients who received protocol-defined treatment and provided HRQL evaluations at baseline and ≥1 follow-up visit were analyzed. Outcomes included Functional Assessment of Cancer Therapy General (FACT-G) domain scores for physical, social/family, functional and emotional well-being, and EQ-5D-3L index scores, at days 42, 100, 180, and 365 post-transplant. HRQL changes from baseline were compared using mixed effect models with repeated measures, adjusting for age, sex, race, region, primary diagnosis, HCT comorbidity index, and baseline HRQL score. Average HRQL over time was compared using the area under the curve (AUC) of mean HRQL trajectories in each treatment group.ResultsSeventy-five patients (omidubiceln = 37, UCB n = 38) provided HRQL data for inclusion and were representative of the full randomized population (N = 125) at baseline. Median age was 38 years, and 41% were female. During the first year post-transplant, patients receiving omidubicel had numerically superior average FACT-G domain and EQ-5D-3L index scores compared with UCB, with mean differences across time points ranging from 1.4 to 3.1 for physical well-being, 0 to 1.3 for social/family well-being, 0.5 to 1.4 for emotional well-being, 1.6 to 3.2 for functional well-being, and 0.03 to 0.09 for the EQ-5D-3L index score. Minimal clinically important differences (MCIDs) were exceeded at ≥1 time point for mean physical and functional well-being (MCIDs = 2 units) and for the EQ-5D-3L (MCID = 0.07 units). Initial mean declines in HRQL occurred for all measures at day 42 and were consistently numerically smaller in the omidubicel group than in the UCB group. Averaging across the first year post-transplant, patients receiving omidubicel had significantly improved HRQL for physical and functional well-being domains (P < .05 for comparison of AUCs).DiscussionAlong with faster time to engraftment, lower infection risk, and shorter hospitalization, omidubicel was associated with meaningfully greater preservation or improvement of important HRQL domains compared with UCB.

Abstract 9 Hematopoietic Stem Cell Transplantation (HSCT) with Omidubicel Leads to Robust Recovery and Diversity of T Cells

IntroductionOmidubicel is a cell therapy used for allogeneic hematopoietic stem cell transplant. A phase III randomized study (NCT02730299) comparing omidubicel to umbilical cord blood (UCB) demonstrated faster hematopoietic recovery, lower rates of infection, shorter hospitalization time (Horwitz et al.Blood. 2021;138[16]:1429-1440) and robust immune reconstitution (Szaboles et al. Trans Cell Ther. 2022;28[suppl]:S5).ObjectiveWe now characterize T-cell development reflected by T-cell receptor excision circles (TREC) and T-cell receptor (TCR) diversity in omidubicel and UCB-transplanted patients (pts).MethodsGenomic DNA was extracted from peripheral blood mononuclear cells. TREC was quantified by real-time quantitative PCR. TREC copies (T) were standardized to β actin transcripts (B), and T/B ratio was normalized per µg of DNA. TCR diversity was measured using a total of 76 T-cell receptor β locus (TRB) genes. Human T-cell receptor β repertoire was quantified using AmpliSeq for Illumina Immune Repertoire Plus SR assay. TCRβ metrics quantified the number of clones, Shannon’s entropy, clonality, evenness, convergency, and Gini indexes.ResultsA total of 37 pts from 15 sites were included, 17 transplanted with omidubicel and 20 with UCB. Median CD3+ cell dose was lower for pts transplanted with omidubicel (1.8 × 106 cells/kg; range: 1.2-7.6) than with UCB (6.0 × 106 cells/kg, range: 1.7-10.2). Patients transplanted with omidubicel and UCB had similar TREC and recent thymic emigrants (RTE) counts in peripheral blood at days 100 and 180. At day 365, RTEs were higher in omidubicel (113 ± 85 cells/µL) than UCB (41 ± 15 cells/µL, P = .047). Median T/B ratio was 223 for omidubicel and 124 for UCB. There was no significant difference in TCR repertoire diversity between the omidubicel and UCB groups.DiscussionPts transplanted with omidubicel had robust and diverse T-cell reconstitution. Higher numbers of de-novo thymus educated T-cells in peripheral blood at 1 year suggest faster thymopoiesis in patients transplanted with omidubicel than with UCB. These data are further evidence for the robust immune reconstitution in patients treated with omidubicel and provide mechanistic rationale for the lower infection rates and improved outcomes in these patients.

Comparison of clinical outcomes between unrelated single umbilical cord blood and "ex-vivo" T-cell depleted haploidentical transplantation in children with hematological malignancies.

Over the last two decades, umbilical cord blood (UCB) and haploidentical transplantation (HaploHSCT) have emerged as alternative sources of hematopoietic stem cell for allogeneic transplantation. There are few retrospective studies and no prospective studies comparing both types of alternative transplantation in pediatric patients. We analyzed the data of 134 children with hematological malignancies who received a hematopoietic stem cell transplantation from a single umbilical cord blood (UCB) (n = 42) or an "ex-vivo" T-cell depleted transplant from a haploidentical-related donor (HaploHSCT) (n = 92) between 1996 and 2014. Hematological recovery was faster after HaploHSCT than the UCB transplant group (median times to neutrophil and platelet recovery: 13 vs. 16days, 10 vs. 57days, respectively) (P < 0.001). The HaploHSCT group had a significantly early immune reconstitution based on NK and CD8 + T cells compared with the UCB group. However, after thefirst year post-transplantation, HaploHSCT had a lower number of CD4 + T and B lymphocytes compared with the UCB transplant recipients. The cumulative incidence of TRM was 29±8% in the HaploHSCT group versus 40±5% in the UCB group. Relapse incidence was 21±7% in the HaploHSCT group and 19±8% in the UCB group. Probability of DFS was 58±8% in the HaploHSCT group versus 40±9% in the UCB group (P = 0.051). TCD haploidentical transplant is associated with advantages in terms of engraftment and early immune reconstitution kinetics. TCD haploidentical transplant was associated with lower incidence of infectious and non-infectious complications, especially in the early phases of the transplant compared with UCB transplant recipients. However, there are no advantages in transplant outcomes compared with UCB transplant.

Allogeneic Hematopoietic Cell Transplantation from Alternative Donors in Acute Myelogenous Leukemia: A Comparative Analysis

In the absence of HLA-matched related and unrelated donors, alternative donors must be found for patients in need of allogeneic hematopoietic cell transplantation (HCT). There are at least 3 donor options: a mismatched unrelated donor (MMUD), umbilical cord blood (UCB), and a haploidentical related donor (haplo); however, the optimal alternative donor type remains to be established. This study aimed to address how the outcomes of patients receiving these 3 alternative donor HCTs differ, and whether these outcomes change over time post-transplantation. We retrospectively analyzed Japanese nationwide transplantation registry data of adults with acute myelogenous leukemia (AML) undergoing allogeneic HCT while in first complete remission (CR) from an MMUD with a 7/8 match at the allele level (n=601), with UCB (n=1110), or from a haploidentical related donor (n=221) between 2007 and 2018. For patients who underwent transplantation between 2007 and 2014, the 3-year overall survival (OS) for the MMUD, UCB, and Haplo groups was 60%, 54%, and 47%, respectively (P=.022). For those who underwent transplantation between 2015 and 2018, the 3-year OS in these groups was 60%, 66%, and 63%, respectively (P=.693). Multivariate analysis revealed that the risks of both overall mortality and nonrelapse mortality (NRM) were significantly lower in the later period than in the earlier period in the UCB group (hazard ratio [HR], 0.66 [P < .001] for OS; HR, 0.64 [P < .001] for NRM) and the Haplo group (HR, 0.58 [P=.019 for OS; HR, 0.39 [P=.004] for NRM), but not in the MMUD group (HR, 1.07 [P=.631] for OS; HR, 1.26 [P=.175] for NRM). The results of a test for interaction showed a significant difference in the effect of transplantation period on OS and NRM between the MMUD and UCB groups (P=.014 for OS; P=.004 for NRM) and between the MMUD and Haplo groups (P=.034 for OS; P=.003 for NRM). These findings demonstrate the recent improvements in the outcomes of UCB and Haplo transplantations in patients with AML in first CR that have resulted in a similar OS in patients undergoing HCT with grafts from MMUDs, UCB, and haploidentical donors in the later period of the study.

Prospective Comparison Of Five Viral Infections (HHV6, CMV, EBV, ADV, BKv) After Umbilical Cord Blood (UCB) Vs PBSC Reduced-Intensity Conditioning Allogeneic Stem Cell Transplantation (allo-SCT) In Adults

Viral infections are well-known complications after allo-SCT and are responsible for morbidity and mortality in patients. Previous retrospective studies have reported a strong association between HHV6 infection and the use of umbilical cord blood (UCB) as stem cell source for allo-SCT. To better define the characteristics and consequences of HHV6 infection after UCB allo-SCT, we conducted the first prospective study comparing the frequencies of HHV6 infections and of 4 other viral reactivations (cytomegalovirus (CMV), Epstein Barr virus (EBV), adenovirus (ADV) and BK virus (BKv)) in 65 adults receiving either UCB allo-SCT (n=31) or unrelated PBSC allo-SCT (n= 34) after a reduced intensity conditioning regimen. Except graft source, characteristics of patients were similar between UCB vs PBSC groups in terms of sex, age at transplant, type of disease and disease status at transplant.Viral loads were measured in whole blood (608 samples) before the graft and at least once a month up to six months post-graft. Data were analysed for correlation with various clinical/biological events occurring after the graft (engraftment, hematopoietic and immune reconstitutions, GVHD, deaths or the five considered viral infections).Frequency of HHV-6 infections was significantly higher in the UCB group (83.9% vs 21.2%; p<0.0001). In this context, HHV-6 reactivations were observed mainly during the first month post-transplant occurring earlier (p<0.0001) and with a longer duration (median: 148 days vs 31 days) in the UCB group. However, there was no difference regarding viral loads between both groups. Neutrophils and platelets recoveries were significantly delayed in HHV-6 positive patients (median: 20 days vs 15 days, p=0.002; and 40 days vs 12 days; p=0.0001, respectively), especially when HHV-6 reactivations occurred before the end of aplasia (median: 28 days vs 17 days; p=0.0054 and 56 days vs 15 days; p=0.0006). The delayed recoveries was accordingly associated with a higher need for units of red blood cells and platelet packs in infected patients (median number of transfused units per patient: 8 vs 2; p=0.006 and 11 vs 1; p<0.0001, respectively). Moreover, HHV-6 infection was not associated with higher incidence of acute GHVD, CMV reactivations, relapses or death.Regarding the four other viral infections, we observed a significant higher frequency of EBV reactivations in PBSC allo-SCT recipients (70.6% vs 25.8%; p=0.0003) but similar incidence of CMV infections between both groups. ADV infections were observed only in 4 UCB allo-SCT cases. Finally, BKv reactivations studied up to 2 months post-graft were significantly more frequent in the UCB group (51.6% vs 23.5%; p=0.019).In conclusion, we prospectively confirm here a specific relationship between HHV6 and BKv infections and UCB allo-SCT. The pattern of immune reconstitution and the multivariate analyses are on-going and will be presented at the meeting. Disclosures:Moreau:CELGENE: Honoraria, Speakers Bureau; JANSSEN: Honoraria, Speakers Bureau.

Graft-Versus-Host Disease (GVHD)-Free Relapse-Free Survival (GRFS) and Chronic Gvhd (CRFS) in Alternative Donor Hematopoietic Cell Transplantation (HCT) in Adults

BACKGROUNDGRFS is a composite endpoint developed by the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) to reflect the major outcomes post HCT. Events in GRFS include grade 3-4 acute GVHD (aGVHD 3-4), systemic therapy-requiring chronic GVHD (cGVHD), relapse, or death. We reported that bone marrow (BM) grafts from matched sibling donor (MSD) led to best GRFS at 1-and 2-years compared with peripheral blood (PB) grafts from any donor or umbilical cord blood (UCB). (Holtan et. al. Blood 2015 & Mehta et.al. Haematologica. 2016) These studies excluded haploidentical (haplo) and mismatched (MM)-HCT. The outcomes of this composite endpoint in alternative donor HCT is unknown. Here, we analyzed GRFS and chronic GVHD-free relapse-free survival (CRFS) among alternative donor HCT (UCBT, haplo, one-antigen MM (7/8)-BM or 7/8-PB HCT) for patients with no MSD or matched unrelated donor. METHODSPatients with acute myeloid leukemia (AML) or acute lymphoblastic leukemia in remission, chronic myeloid leukemia or myelodysplastic syndrome who received alternative donor HCT from 2000-2014 were included. Only those haplo patients who received post-HCT cyclophosphamide and only those UCBT done using fludarabine, cyclophosphamide and total body irradiation myeloablative (MA) or reduced intensity (RIC) with or without antithymocyte globulin (ATG) were analyzed. Exclusion criteria were prior autologous or allogeneic HCT, ex-vivo T-cell depletion or CD34 selection and those with UCB unit <4/6 HLA match. Multivariable analysis was done using Cox's proportional hazards (PH) modeling with time-dependent adjustments as needed for stepwise modeling, selecting factors using a threshold of 0.05 for both entry and retention in the model. CRFS was defined survival without cGVHD or relapse. RESULTS2198 patients were analyzed, including UCBT (n=838), haplo (n=159), 7/8-BM (n=241) and 7/8-PB (n=960). Groups (except haplo) were further divided by conditioning and ATG use [Table 1]. AML was most common diagnosis (52%). As expected, patients who received MA conditioning were younger (median 35-43 years) than those who got RIC (median 58-61 years). 81% of UCB group received double cord. Most patients in haplo group received BM graft (71%), and a majority (82%) were from 2012-2014; consequently, follow-up of haplo group (median 25 months) was shorter than others (49-96 months).In multivariate analysis of early post-HCT outcomes (within 4.5 months) adjusted for year of HCT and other covariates, as compared to haplo, UCB, 7/8-BM (MA, no ATG) and 7/8-PB had inferior GRFS. However, beyond 4.5 months, haplo, UCB and 7/8-BM (MA +/- ATG) had similar GRFS while 7/8-PB had inferior GRFS. [Fig 1] Likewise, beyond 4.5 months, as compared to haplo, CRFS was similar in UCB and 7/8-BM (MA +/-ATG), while 7/8-PB had inferior CRFS.As compared to Haplo, risk of aGVHD was significantly higher in all groups, except UCB (RIC + ATG) and the risk of cGVHD (beyond 4.5 months) was higher in 7/8-BM (MA, no ATG) and 7/8-PB but similar in UCB and 7/8-BM (MA + ATG). As compared to haplo, risk of relapse was significantly lower after UCB (MA), 7/8-BM (MA +ATG) and 7/8-PB (MA, no ATG), similar in UCB (RIC + ATG), 7/8-BM (MA, no ATG), 7/8-PB (MA + ATG) and 7/8-PB (RIC +/-ATG) and higher in UCB (RIC, no ATG). Haplo had superior disease free survival compared to UCB, 7/8-PB (MA, no ATG) and 7/8-PB (RIC + ATG), but it was similar in 7/8-PB (MA + ATG) and 7/8-BM (MA +/-ATG). Similarly, haplo had superior overall survival compared to any other group. CONCLUSIONLong-term morbidity and mortality as measured by GRFS and CRFS are similar in UCBT, haplo and 7/8 BM groups. The use of 7/8-PB should be avoided given substantially poor GRFS and CRFS. As 7/8-BM group included only younger patients who received MA conditioning, no conclusion can be drawn about its outcome in older patients, for whom either haplo or UCB remain as the preferred donor source. These outcomes may also be a reflection of different GVHD prophylaxis regimens rather than donor type. Ongoing randomized comparison of UCBT versus haplo in the BMT CTN 1101 trial will prospectively evaluate these two groups. [Display omitted] DisclosuresHoltan:Incyte: Other: One-time advisory board member. Arora:Takeda Oncology: Consultancy.

Eltrombopag for thrombocytopenia in 24 children after hematopoietic stem cell transplantation

Objective: To evaluate the efficacy and safety of eltrombopag for children with thrombocytopenia after hematopoietic stem cell transplantation (HSCT). Methods: Clinical data of 24 patients with thrombocytopenia after HSCT,who were treated with eltrombopag in the Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University from August 1, 2018 to April 1, 2019 were analyzed retrospectively. The response rate and adverse reactions of eltrombopag were evaluated. Patients were divided into groups by source of hematopoietic stem cells (umbilical cord blood group and peripheral stem cell group) and type of disease (malignant and non-malignant disease group) and the clinical outcomes between groups were compared. Rank Sum test was used for comparisons between groups. Results: Among 24 cases, 15 were males and 9 females, the age of starting eltrombopag was 7.7 (2.6-13.7) years, the time of eltrombopag treatment after HSCT was 27.5 (8.0-125.0) days, the time from treatment to complete response (CR) was 23.5 (6.0-83.0) days, with the treatment course 36.5 (8.0-90.0) days. The total dose of eltrombopag was 1 400(200-5 900) mg. Complete response rate was 92% (22/24),without eltrombopag related adverse reactions. Comparing with peripheral stem cell group (n=8), the course and total dose of eltrombopag in umbilical cord blood group (n=16) were significantly reduced(24.5 (8.0-81.0) vs. 65.5 (35.0-90.0) d, Z=-3.004, P=0.002; 900.0 (200.0-3 850.0) vs. 2 862.5 (1 175.0-5 900.0) mg, Z=-2.604, P=0.007), but no significant differences were found in the time from treatment to complete response, platelet count after 2 weeks of eltrombopag withdrawal or platelet count at the end point of follow-up (all P>0.05). Comparing malignant patients (n=12) and non-malignant patients (n=12), no significant differences were found in the time from treatment to complete response, course, total dose, platelet count after 2 weeks of eltrombopag withdrawal, and platelet count at the end point of follow-up in non-malignant patients (all P>0.05). Conclusion: Eltrombopag is safe and maybe effective for thrombocytopenia after HSCT, especially for umbilical cord blood transplantation.

Alternative Donor Hematopoietic Cell Transplantation for Pediatric, Adolescent and Young Adult with Hematological Diseases

Hematopoietic cell transplantation (HCT) is the only potential curative option for many advanced hematologic diseases. Pediatrics, adolescent and young adult (PAYA) patients overall have less pre-HCT comorbidity or organ toxicity and lower transplant related morbidity and mortality risk compared to older adults. As such, a higher percentage of patients in this age group tend to receive myeloablative conditioning (MAC) over non-myeloablative regimens. Current alternative donor sources when a matched sibling donor (MSD) is not available include matched unrelated (MUD), umbilical cord blood (UCB), and haploidentical (Haplo) donors. While there are accumulating data comparing the HCT outcomes between MUD vs. Haplo or UCB in adult patients, the data are sparse in PAYA patients. In this retrospective study, we reviewed 314 consecutive patients aged 1-39 years who underwent their first allogeneic HCT using MAC at City of Hope between 1/2005-7/2018. Patients who received HCT from a matched sibling donor were excluded. Patients received HCT from either an 8/8 HLA MUD (n=196 [BM= 27%, PBSC= 73%]), UCB (n=83 [single: n=30, double: n=53]) or Haplo (n=35) donor. The most used MAC regimens were fractionated total body irradiation-based (n=234, 74%). All Haplo recipients got post-HCT cyclophosphamide (PTCy) as GVHD prophylaxis. To adjust for the difference in transplant era between UCB (predominantly performed in earlier years) and Haplo (carried out predominantly in more recent years) the comparative analyses were focused on Haplo or UCB vs. MUD. Univariate and multivariable Cox regression models were used to assess the impact of patient, disease, and treatment factors on overall survival (OS), progression-free survival (PFS), relapse/progression (RP), and non-relapse mortality (NRM). Median age of patients at the time of HCT was 24 years (range: 0.7-39), with 55% of patients being male. KPS was ≥80% in 88% of the patients and 25% had HCT-CI ≥ 2. The most common diagnoses included: ALL (48%), AML (41%), and MDS/CML (11%). DRI was high/very high in 44% of patients. Groups were balanced in general but patients in the Haplo group had higher HCT-CI (median: 2, p&amp;lt;0.01), more frequently had high/very high disease risk (49%, p&amp;lt;0.01) and higher KPS ≥80% (77%, p&amp;lt;0.01). Neutrophil engraftment was achieved at a median of 23 days (range: 10-94) in the UCB, 16 days (range: 12-32) in the Haplo and 15 days (range: 10-33) in the MUD (p&amp;lt;0.01). After a median follow up duration of 36 months (range: 5.9-36), 3-year OS was inferior among recipients of UCB-HCT (53%, 95% CI: 42-63) compared with the MUD (63%, 95% CI: 56-70; p=0.03), while similar between Haplo (62%, 95% CI:41-78) and MUD (p=0.82). The lower OS in UCB group was primarily due to the significantly higher NRM at 3 years (34%, 95% CI: 24-44) compared with the MUD (16%, 95%CI: 11-22, p&amp;lt;0.01); and 3-year NRM was not significantly different between Haplo (18%,95%CI: 6-34) and MUD (p= 0.99). On the contrary, the cumulative incidence of relapse (CIR) at 3 years was significantly lower in the UCB group (14%, 95%CI: 8-24) compared to MUD (29%, 95%CI: 23-36, p=0.01); the difference in CIR was not significant between Haplo (29%, 95% CI: 16-51) and MUD (p=0.81). PFS at 3 years was not significantly different among the three donor groups (p=0.43). Cumulative incidence of day 100 acute GvHD grade 2-4 was 61% (95% CI: 55-66) in the whole cohort, with no significant difference among the three groups (p=0.27). Cumulative incidence of chronic GVHD at 3 years was higher in the MUD group (66%: 95%CI: 59-72) compared to UCB (45%, 95%CI: 34-56, P&amp;lt;0.01) and Haplo (47%, 95% CI: 28-64, P=0.01). By multivariable analysis, patients with high/very high disease risk had worse OS (HR=1.8, 95% CI: 1.2-2.6, p&amp;lt;0.01) and PFS (HR=1.8, 95% CI: 1.3-2.5, p&amp;lt;0.01) and higher R/P (HR=2.3, 95% CI: 1.4-3.6, p&amp;lt;0.01). Neither Cord nor Haplo was significantly associated with OS compared with MUD when adjusted for Age, HCT CI, DRI, KPS, and HCT Era. In conclusion, our results indicated that in PAYA patients without a suitable MSD, outcomes of Haplo HCT are comparable to MUD HCT. By univariate analysis, UCB HCT was associated with a lower relapse rate compared to MUD. However, survival was worse in recipients of UCB HCT due to the higher NRM, possibly resulted from more infections and engraftment delays in these patients. Figure 1 Disclosures Ali: Incyte Corporation: Consultancy. Nakamura:Viracor: Consultancy; Kadmon Corporation: Other: Advisory board meeting; NapaJen Pharma: Consultancy; Celgene: Other: Support on seminar; Magenta Therapeutics: Other: Advisory board meeting; Alexion: Other: Support on a meeting presentation; Merck: Other: advisory board meeting; Kyowa-Kirin: Other: Support on a meeting presentation. Al Malki:Jazz Pharmacuticals, Inc: Consultancy; Neximmune: Consultancy; Rigel Pharma: Consultancy.

Efficacy analysis of haploidentical allogeneic hematopoietic stem cell transplantation combined with third-party umbilical cord blood infusion in treatment of high-risk lymphoblastic malignancies

Objective To evaluate the efficacy of haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HSCT) combined with third-party umbilical cord blood (UCB) infusion in treatment of high-risk lymphoblastic malignancies. Methods The clinical data of 20 patients with high-risk lymphoblastic malignancies who received Haplo-HSCT from April 2012 to April 2015 in Shanghai General Hospital were retrospectively analyzed, which were compared with the data from 15 patients who underwent matched unrelated donor HSCT (MUD-HSCT) or 14 matched sibling donor HSCT (MSD-HSCT) during the same period. The efficacy of Haplo-HSCT combined with UCB infusion in treatment of high-risk lymphoblastic malignancies was evaluated. The preparative regimen mainly consisted of teniposide, cyclophosphamide and total body irradiation (TBI). Graft versus host disease (GVHD) preparative regimen included cyclosporine and a short term of methotrexate. The patients who received Haplo-HSCT combined with UCB infusion and MUD-HSCT were treated with antithymocyte globulin (ATG). Results After the transplantation, one patient in MUD-HSCT group and one in MSD-HSCT group died within 21 days, and other patients were engrafted successfully. The median time of neutrophil engraftment was 13 days (10-18 d), 12 days (9-16 d) and 12 days (9-14 d) in Haplo-HSCT + UCB group, MUD-HSCT group and MSD-HSCT group, respectively; the median time of platelets engraftment was 11 days (9-18 d), 12 days (10-23 d) and 12 days (9-14 d), respectively. There were 10, 3, 3 cases of grade Ⅱ-Ⅳ acute GVHD at day 100 in the three groups, respectively, and there were 6, 4, 3 cases of chronic GVHD in the three groups, respectively. The 2-year cumulative incidence of relapse was 40.6%, 66.2% and 26.7%, respectively. The predicted 2-year overall survival rate was 37.9%, 42.9% and 55.4%, respectively. All these data had no significant difference (all P > 0.05). Conclusion The efficacy of Haplo-HSCT combined with UCB infusion is similar to that of MUD-HSCT or MSD-HSCT in treatment of high-risk lymphoblastic malignancies, which should be recommended to the patients with high-risk lymphoblastic malignancies and without matched donors. Key words: Lymphoblastic malignancies; Allogeneic hematopoietic stem cell transplantation; Fetal blood

Comparison of Haploidentical Transplantation with Post-Transplantation Cyclophosphamide and Umbilical Cord Blood Transplantation in Children and Adolescents with Hematologic Malignancies after Targeted Busulfan-Based Myeloablative Conditioning Using Intensive Pharmacokinetic Monitoring

Introduction: Haploidentical related donor (Haplo) and umbilical cord blood (UCB) stem cell sources represent common alternative donor strategies used when a matched sibling donor or matched unrelated donor is not available for hematopoietic stem cell transplantation (HSCT). The aim of this study was to compare the results of graft source on outcome of children and adolescents with hematologic malignancies after Haplo and UCB transplantation in the setting of targeted busulfan-based myeloablative conditioning using intensive pharmacokinetic (PK) monitoring.Patients and methods: We retrospectively analyzed outcomes in 140 pediatric patients with hematologic malignancies who received allogeneic HSCT from Haplo donors (n=36), UCB (n=24), and unrelated donors (n=80) in Seoul National University Children's Hospital from January 2009 to February 2018. Because UCB transplantation had been conducted until 2016 while Haplo transplantation using posttransplantation cyclophosphamide (PTCy) was started from 2014 in our institution, differences over time of HSCT must be considered to compare them. Therefore, unrelated HSCT group was divided into Unrelated A group (n=51) who received HSCT from 2009 to 2013 and Unrelated B group (n=29) from 2014, which were compared first with the purpose of using them as a control to compare Haplo and UCB groups. Patients who received the first allogenic HSCT using an intensive PK monitoring, targeted busulfan-based myeloablative conditioning were included. The majority of UCB and unrelated groups received busulfan, fludarabine ± etoposide regimen with antithymocyte globulin. For graft-versus-host disease (GVHD) prophylaxis, cyclosporine and mycophenolate mofetil were used in UCB group while tacrolimus and methotrexate in unrelated groups. Busulfan, fludarabine and cyclophosphamide with PTCy, tacrolimus and methotrexate for GVHD prophylaxis were used in Haplo group.Results: First of all, Unrelated A group was compared to Unrelated B group. The median follow-up time were 5.7 years (0.2-9.5) and 1.8 years (0.3-4.5) in the Unrelated A and Unrelated B groups, respectively. The event-free survival (EFS) rates at 2 years (78.1±5.8% versus 72.3±9.1%, P=0.917) and overall survival (OS) rates at 2 years (83.7±5.3% versus 77.8±9.1%, P=0.874) in Unrelated A and B groups were similar. Under the assumption that there was no significant survival difference over time of HSCT from 2009 to 2013 and that from 2014 in our institution, the outcomes of Haplo and UCB groups were compared subsequently. The median follow-up time were 4.8 years (0.1-9.3) and 1.8 years (0.3-4.5), respectively. The median time to neutrophil and platelet recovery were 15 days (13-21) versus 14 days (12-40) (P=0.059), and 27 days (13-71) versus 46 days (21-77) (P<0.001) in Haplo and UCB groups, respectively. Engraftment failure occurred in 1 patient of UCB group. The cumulative incidence (CI) rates of acute GVHD grade II-IV, grade III-IV, and extensive chronic GVHD in Haplo and UCB groups were 38.9% versus 54.2% (P=0.479), 2.8% versus 29.2% (P=0.004), and 11.7% versus 12.5% (P=0.906), respectively. The CI rates of nonrelapse mortality were significantly lower in Haplo group (0% versus 33.6%, P<0.001), while the relapse incidences were not different (18.3% versus 8.6%, P=0.272). The event-free survival (EFS) rates at 2 years (79.3±7.0% versus 54.2±10.2% %, P=0.034) and overall survival (OS) rates at 2 years (85.8±6.7% versus 65.7±9.9%, P=0.029) in Haplo and UCB groups were significantly different.Conclusion: In this study, the CI rates of nonrelapse mortality and acute GVHD III-IV was lower in Haplo group than in UCB transplants, which translates into a better EFS and OS rate in Haplo group. Our results suggest that haploidentical HSCT with PTCy using intensive PK monitoring, targeted busulfan-based myeloablative conditioning regimen is a safe and promising alternative option for patients with hematological malignancies who lack an HLA-matched donor. DisclosuresNo relevant conflicts of interest to declare.

Dendritic Cell Recovery Impacts Outcomes after Umbilical Cord Blood and Sibling Donor Transplantation for Hematologic Malignancies

Dendritic cells (DCs) orchestrate immune responses after allogeneic hematopoietic cell transplantation (HCT). We studied the association of donor myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) recovery in the landmark analysis of umbilical cord blood (UCB) and matched related donor (RD) HCT. Eighty patients (42 UCB and 38 RD recipients) with a day 100 blood sample were included in the analysis. Median age was 51 years (range, 20 to 71). Most patients had acute leukemia (50%) or lymphoma (23%) and received reduced-intensity conditioning (75%). After transplantation, UCB recipients had higher DC counts than RD recipients reaching normal levels at day 100 after transplantation (UCB median 4.7 cells/µL versus RD median 1.7 cells/µL). UCB recipients with high day 100 pDCs levels (≥ median) had 2-fold lower risk of relapse compared with those with pDClow (14% versus 28%, P = .29) and a trend to improved 1-year survival in multivariate analysis with hazard ratio of .22 (95% confidence interval, .04 to 1.05; P = .057). Cytomegalovirus (CMV) reactivation had adverse impact on DC reconstitution at day 100 in both UCB and RD groups and almost exclusively affected the mDC subset (CMV reactivation: mDC 3.2 cells/µL versus no CMV reactivation: 7.8 cells/µL; P = .004). Collectively, these data suggest that high levels of circulating pDCs at day 100 after UCB transplantation confer a survival advantage at 1 year.

Similar Survival after Umbilical Cord Blood (UCB) and HLA-Matched Adult Donor Transplantation By Disease Risk Index (DRI) Assignment

DRI incorporates both disease type and status at transplant and was found to be strong independent predictor of survival after allogeneic (allo) hematopoietic cell transplantation (HCT). Using the refined DRI assignment, we compared survival outcomes of UCB transplant (n=548: 314 with 5-6/6 and 231 with 4/6 HLA-matched units) to 8/8 HLA-matched adult donor HCT (n=528: 446 sibling and 82 unrelated; 78 bone marrow [BM] and 450 peripheral blood [PB] grafts) for hematological malignancies from 2000-2013. UCB and adult (BM/PB) groups had similar patient and transplant characteristics except UCB patients were slightly younger (47.5 year vs. 50.5 year; p <0.01), had more comorbid conditions at HCT (37.0% vs. 28.2% HCT-CI ≥3; p =0.03), and were more likely to receive reduced intensity conditioning regimen (67.7% vs. 55.9%; p <0.01). Three DRI groupings were identified: low risk (LR, 83 UCB and 110 BM/PB), intermediate risk (IR, 369 UCB and 329 PB) and high/very high risk (HR, 96 UCB and 89 BM/PB) groups. Adjusted estimates of OS at 2 years were similar with UCB or adult donors for all DRI groups (Figure). Multiple regression analysis compared outcomes of UCB with matched adult donor in each DRI group (Table). After adjusting for age and conditioning, grade III-IV acute GVHD incidence in all DRI groups was similar with both donor types. In contrast, UCB resulted in significantly lower rates of chronic GVHD in all DRI groups. Importantly, donor type was not an independent predictor of either TRM or relapse in any DRI group. In the LR-DRI group DFS was inferior with UCB, but in IR- and HR-DRI donor type had no influence on DFS after adjusting for comorbidities and CMV serostatus. Our data demonstrates that UCB is a valid alternative donor type for alloHCT, particularly those with IR and HR DRI. UCB grafts yield survival similar to matched adult donor alloHCT when DRI is considered. Low chronic GVHD risk makes UCB particularly attractive graft source for older patients.Table 1Adjusted clinical outcomes by graft source based on DRIDRIGroupGraftSourceNaGVHDGrade III-IVcGVHDTRMRelapseDFSOSHR(95%CI)PHR(95%CI)PRR(95%CI)PRR(95%CI)PHR*(95%CI)PHR†(95%CI)PLow riskBM/PB UCB110 831.0 0.68 (0.36-1.26).821.0 0.32 (0.18-0.57)<.011.0 1.47 (0.72-3.00).291.0 1.83 (0.96-3.48).071.0 1.70 (1.06-2.72).031.0 1.34 (0.75-2.41).32Intermediate RiskBM/PB UCB329 3691.0 1.01 (0.73-1.39).961.0 0.50 (0.38-0.67)<.011.0 1.08 (0.76-1.52).661.0 0.95 (0.72-1.26).741.0 0.91 (0.74-1.14).421.0 1.17 (0.91-1.50).23High/very- high riskBM/PB UCB89 961.0 0.75 (0.39-1.45).401.0 0.76 (0.60-0.96).021.0 1.57 (0.85-2.90).151.0 0.68 (0.41-.110).121.0 1.06 (0.73-1.54).761.0 1.36 (0.90-2.06).15HR indicates hazard ratio; RR, relative risk. *Denotes hazard ratio of death/relapse. †Denotes hazard ratio of death. [Display omitted] DisclosuresBachanova:Seattle Genetics Inc.: Consultancy, Research Funding.

Involvement of Immune Responses in the Efficacy of Cord Blood Cell Therapy for Cerebral Palsy.

This study evaluated the efficacy of umbilical cord blood (UCB) cell for patients with cerebral palsy (CP) in a randomized, placebo-controlled, double-blind trial and also assessed factors and mechanisms related to the efficacy. Thirty-six children (ages 6 months to 20 years old) with CP were enrolled and treated with UCB or a placebo. Muscle strength and gross motor function were evaluated at baseline and 1, 3, and 6 months after treatment. Along with function measurements, each subject underwent (18)F-fluorodeoxyglucose positron emission tomography at baseline and 2 weeks after treatment. Cytokine and receptor levels were quantitated in serial blood samples. The UCB group showed greater improvements in muscle strength than the controls at 1 (0.94 vs. -0.35, respectively) and 3 months (2.71 vs. 0.65) after treatment (Ps<0.05). The UCB group also showed greater improvements in gross motor performance than the control group at 6 months (8.54 vs. 2.60) after treatment (P<0.01). Additionally, positron emission tomography scans revealed decreased periventricular inflammation in patients administered UCB, compared with those treated with a placebo. Correlating with enhanced gross motor function, elevations in plasma pentraxin 3 and interleukin-8 levels were observed for up to 12 days after treatment in the UCB group. Meanwhile, increases in blood cells expressing Toll-like receptor 4 were noted at 1 day after treatment in the UCB group, and they were correlated with increased muscle strength at 3 months post-treatment. In this trial, treatment with UCB alone improved motor outcomes and induced systemic immune reactions and anti-inflammatory changes in the brain. Generally, motor outcomes were positively correlated with the number of UCB cells administered: a higher number of cells resulted in better outcomes. Nevertheless, future trials are needed to confirm the long-term efficacy of UCB therapy, as the follow-up duration of the present trial was short.

Unrelated hematopoietic stem cell transplantation in the pediatric population: single institution experience.

ObjectiveHematopoietic stem cell transplantation has been successfully used to treat the pediatric population with malignant and non-malignant hematological diseases. This paper reports the results up to 180 days after the procedure of all unrelated hematopoietic stem cell transplantations in pediatric patients that were performed in one institution.MethodsA retrospective review was performed of all under 18-year-old patients who received unrelated transplantations between 1995 and 2009. Data were analyzed using the log-rank test, Cox stepwise model, Kaplan–Meier method, Fine and Gray model and Fisher's exact test.ResultsThis study included 118 patients (46.8%) who received bone marrow and 134 (53.2%) who received umbilical cord blood transplants. Engraftment occurred in 89.47% of the patients that received bone marrow and 65.83% of those that received umbilical cord blood (p-value < 0.001). Both neutrophil and platelet engraftments were faster in the bone marrow group. Acute graft-versus-host disease occurred in 48.6% of the patients without statistically significant differences between the two groups (p-value = 0.653). Chronic graft-versus-host disease occurred in 9.2% of the patients with a higher incidence in the bone marrow group (p-value = 0.007). Relapse occurred in 24% of the 96 patients with malignant disease with 2-year cumulative incidences of 45% in the bone marrow group and 25% in the umbilical cord blood group (p-value = 0.117). Five-year overall survival was 47%, with an average survival time of 1207 days, and no significant differences between the groups (p-value = 0.4666).ConclusionDespite delayed engraftment in the umbilical cord blood group, graft-versus-host disease, relapse and survival were similar in both groups.

Similar Outcome Using Sibling, Unrelated Donor, and Cord Blood Grafts after Reduced-Intensity Conditioning in Children: A Retrospective Study from the SFGM-TC

Reduced intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT) is increasingly used in children, especially in those who have been heavily pre-treated or who have received prior autologous or allo-SCT. Of note, use of cord blood as stem cell source is currently a standard of care in pediatric patients lacking a sibling or an unrelated donor. Currently, comparison between matched siblings (SIB), unrelated donors (URD), or umbilical cord blood (UCB) allo-SCT has not yet been reported in the RIC setting in children.Here, we compared reduced-intensity conditioning allo-SCT performed between January 1998 and December 2012 in 124 consecutive children (<18 years) with a median age of 12.8 years (males, n=69). Disease included acute leukemia (n=78), myelodysplastic syndrome (MDS)/myeloproliferative disorder (MPD)/chronic myeloid leukemia (CML) (n=22) and lymphoma (n=24). Status at transplant were as follows: complete remission (CR), n=84, (CR1 n=22, CR2 n=35, CR3 n=20, missing n=7); partial response n=6; primary induction failure n=8; relapse or progression n=19, up-front (MDS) n=2, chronic phase (CML) n=2, missing n=3. Twenty-five patients had received a previous auto-SCT and 44 a previous allo-SCT. Clinical data were prospectively collected using ProMISe (Project Manager Internet Server), an internet-based data registry system shared by all SFGM-TC centres. Type of donor included SIB (n = 32), URD (n = 56), or UCB (n = 36, single n=23; double n=13). The three groups were well balanced in terms of gender, diagnosis, status at transplant, median follow-up, previous transplant status, median time interval between disease diagnosis and allo-SCT, period of transplant, patients aged < or >= 10 years at time of transplant. Regarding RIC regimen, fludarabine and iv busulfan was the most commonly used regimen for SIB and URD cases while it was fludarabine + low-dose total body irradiation (Minneapolis approach) for UCB patients. The use of in-vivo T cell depletion (ATG) was significantly less frequent in the UCB group (16.7% vs 53.1% (SIB) vs 66.1% (URD), p<0.0001). Considering the whole cohort, cumulative incidence of engraftment was 81.4%. With a median follow-up of 49 months (range: 7-163), 5-year overall (OS) and disease free (DFS) survival rates were 40% (31-50) and 39% (31-48), respectively. 5-year cumulative incidences of relapse (RI) and non-relapse mortality (NRM) were 43% (34-52) and 17% (11-24), respectively, while 2-year incidence of chronic GVHD was 20% (12-29).Engraftment rates were similar between the three groups: 93.3% (SIB) vs 86.8% (URD) vs 77.1% (UCB), p=0.10. The 5-year cumulative incidences of NRM were 13%, 18%, and 19% with SIB, URD, and UCB transplantation, respectively (p=0.73). The 5-year DFS rates were 42% (24-59), 36% (23-48), and 43% (27-60) with SIB, URD, and UCB transplantation, respectively (p=0.70). The 5-year OS rates were 40% (22-59), 40% (27-53), and 38% (17-60) with SIB, URD, and UCB transplantation, respectively (p=0.94). Finally, grade 2-4 acute GVHD and 2-year incidence of chronic GVHD were similar between the three groups: 29.6% (SIB) vs 32.1% (URD) vs 38.2% (UCB), p=0.75; and 10% (SIB) vs 23% (URD) vs 24% (UCB), p=0.51.In multivariate analysis, donor type had no significant impact on overall survival (SIB vs URD, HR: 1.19; 95%CI: 0.61-2.33, p=0.61; SIB vs UCB, HR: 1.28; 95%CI: 0.69-2.37, p=0.43) while a diagnosis of MDS/MPD/CML was independently associated with better OS (HR: 2.49; 95%CI: 1.17-5.29, p=0.02).In conclusion, despite evident limitations due to the retrospective setting of this study, results from this national survey support the recommendation to consider any stem cell source (SIB donor, URD, or UCB) in children candidate for a RIC allo-SCT. DisclosuresBeguin:Amgen: Consultancy, Speakers Bureau; Vifor: Consultancy, Speakers Bureau.