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International audience; Data regarding the safety and efficacy of reduced-toxicity conditioning regimen (RTC) prior to allogeneic stem cell transplantation (allo-SCT) to treat hematological malignancies in pediatric patients are limited. This prospective multicenter, phase 2 trial investigated a RTC regimen based on the combination of intravenous busulfan (3.2 mg/kg/d x 4 days), fludarabine (30 mg/m2/d x 5 days) and antithymocyte globulin (Thymoglobulin®, Genzyme; 5 mg/kg total dose) with the aim of delivering high dose myeloablation that would allow optimal disease control while minimizing toxicity, in a subgroup of children at very high risk of non-relapse mortality (NRM). The primary endpoint was NRM at 1 year after allo-SCT. A total of 48 high risk patients were included (median age, 13 years; range, 3-24). At 1 year, the cumulative incidence of recurrence/disease progression and NRM were 33% and 8%, respectively. With a median follow-up of 23 months, the Kaplan-Meier estimates of overall survival (OS) and disease-free survival (DFS) at 1 year were 69% and 58%, respectively. We conclude that the RTC regimen used in this prospective trial is safe, with a

Inotuzumab Ozogamicin is a CD22-directed antibody conjugated to calicheamicin, approved in adults with relapsed or refractory (R/R) B cell acute lymphoblastic leukemia (BCP-ALL). Patients aged 1–18 years, with R/R CD22 + BCP-ALL were treated at the RP2D of 1.8 mg/m2. Using a single-stage design, with an overall response rate (ORR) ≤ 30% defined as not promissing and ORR > 55% as expected, 25 patients needed to be recruited to achieve 80% power at 0.05 significance level. Thirty-two patients were enrolled, 28 were treated, 27 were evaluable for response. The estimated ORR was 81.5% (95%CI: 61.9–93.7%), and 81.8% (18/22) of the responding subjects were minimal residual disease (MRD) negative. The study met its primary endpoint. Median follow up of survivors was 16 months (IQR: 14.49–20.07). One year Event Free Survival was 36.7% (95% CI: 22.2–60.4%), and Overall Survival was 55.1% (95% CI: 39.1−77.7%). Eighteen patients received consolidation (with HSCT and/or CAR T-cells therapy). Sinusoidal obstructive syndrome (SOS) occurred in seven patients. MRD negativity seemed correlated to calicheamicin sensitivity in vitro, but not to CD22 surface expression, saturation, or internalization. InO was effective in this population. The most relevant risk was the occurrence of SOS, particularly when InO treatment was followed by HSCT.

Ten to fifteen percent of children with acute lymphoblastic leukemia (ALL) relapse following treatment. Of these, less than 2% display ophthalmic relapses, which owing to their scarcity, are largely undocumented, leaving clinicians with few diagnostic and therapeutic recommendations, despite serious functional sequelae. We conducted a French multicenter retrospective study to collect all clinical, radiological, biological, and therapeutic data, and outcomes for children with ALL ophthalmic relapses. From 2000 to 2020, 20 ophthalmic relapses occurring after first-line therapy performed before January 1

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of haematopoietic cell transplantation (HCT) conditioning. The DEFIFrance post-marketing registry study evaluated effectiveness and safety in patients who received defibrotide. It collected retrospective/prospective patient data from 53 French HCT centres from July 2014 to March 2020. Primary endpoints were survival and complete response (CR; total serum bilirubin

To obtain a national overview of the epidemiology and management of invasive fungal infections (IFIs) in France for severely immunocompromised children who were treated for acute leukemia or had undergone allogeneic hematopoietic stem cell transplantation (a-HSCT).We performed a national multicenter retrospective study to collect epidemiologic data for proven and probable IFIs in children with acute leukemia under first- line or relapse treatment or who had undergone a-HSCT. We also conducted a prospective practice survey to provide a national overview of IFI management in pediatric hematology units.From January 2014 to December 2017, 144 cases of IFI were diagnosed (5.3%) in 2721 patients, including 61 cases of candidiasis, 60 cases of aspergillosis, and 23 cases of infection with "emergent" fungi, including 10 cases of mucormycosis and 6 cases of fusariosis. The IFI rate was higher in patients with acute myelogenous leukemia (12.9%) (OR, 3.24; 95% CI, 2.15-4.81; P.0001) compared with the rest of the cohort. Patients undergoing a-HSCT had an IFI rate of only 4.3%. In these patients, the use of primary antifungal prophylaxis (principally fluconazole) was associated with a lower IFI rate (OR, 0.28; 95% CI, 0.14-0.60; P = 4.90 ×10The emerging fungi and new antifungal resistance profiles uncovered in this study should be considered in IFI management in immunocompromised children.

Better knowledge of genetic aberrations in pediatric acute myeloid leukemia is essential to adapt treatment intensity. RUNX1 mutations are well described in adult AML and known to be associated with a poor outcome. In children, first studies showed similar results but because of their low frequency, prognosis impact remains unclear. RUNX1 deletions have rarely been described. Among 386 children enrolled in the French ELAM02 trial, we observed 29 (8%) patients with RUNX1 abnormalities: 24 mutations and 5 deletions. We found no significant association with any clinical presentation. RUNX1 alteration was more likely associated with AML0 cytological subtype; often presented with normal karyotype but no rearrangement classified as good prognosis markers (KMT2A or CBF-AML). RUNX1 mutated patients had higher number of co-mutations, such as FLT3-ITD, EZH2 and BCOR mutations but were never associated with NPM1 or CEBPA. Five years EFS was 32.5% for RUNX1 mutated and deleted patients versus 61.4% for RUNX1 wild type (p=0.003), and OS was 33.6% versus 75.7% (p

No data on inotuzumab ozogamicin (InO) in infant acute lymphoblastic leukaemia (ALL) have been published to date. We collected data internationally on infants/young children (+ blasts was 72% (range 40–100%, n = 9). The median dose in the first course was 1.74 mg/m2 (fractionated). Seven patients (47%) achieved complete remission; one additional minimal residual disease (MRD)-positive patient became MRD-negative. Six-month overall survival was 47% (95% confidence interval [CI] 27–80%). Two patients developed veno-occlusive disease after transplant. Further evaluation of InO in this subgroup of ALL is justified.

Medication non-adherence (NA) after allogeneic hematopoietic cell transplantation (allo-HCT) can lead to serious complications. This study assesses NA in French adult and pediatric recipients and identifies factors associated with NA. In accordance with the EMERGE and STROBE guidelines, a cross sectional multicentric survey was conducted. We used a self-reported questionnaire that was adapted to adults and pediatrics and that could provide a picture of all three phases of medication adherence: initiation, implementation, persistence. We enrolled 242 patients, 203 adults (mean age: 51 years old, 50.7% male) and 39 children (mean age: 9 years old, 56.4% female). Reported NA was estimated at about 75% in both populations, adults and pediatrics. In adults, the univariate analysis showed that patients less than 50 years old (P = 0.041), (i) treated with cyclosporine (P = 0.02), (ii) treated with valacyclovir/acyclovir (P = 0.016), and (iii) experiencing side effects (P = 0.009), were significantly more non-adherent. In multivariate analysis, only recipient age was significantly associated to NA (P = 0.05). The limited size of the pediatric population did not allow us to draw any statistical conclusion about this population. To the best of our knowledge, this is the first study in France on NA in allo-HCT recipients. Our results highlight the age factor as the only factor related to NA. Further studies are needed to confirm our observations and refine results in pediatric populations, currently most at risk of medication NA.

International audience; Purpose: In the acute lymphoblastic leukemia (ALL) landscape, adolescents and young adults (AYA) often present high-risk diseases and increased chemotherapy-related toxicity. Studies analyzing the outcomes of AYA after hematopoietic stem cell transplantation (HSCT) are scarce. Our study aimed to compare the outcomes of children and AYA with ALL after HSCT and to determine the factors influencing potential differences.Method: 891 patients, from the SFGM-TC registry, aged between 1 and 25 years who received HSCT between 2005 and 2012 were included. The outcomes of AYA were compared to the ones of their younger counterparts.Results: Five-year OS and GRFS were lower in AYA: 53.1% versus 64% and 36% versus 47% (p = 0.0012 and p = 0.007, respectively). WhileCIR was similar in both groups, 5 year-treatment related mortality was higher in AYA: 19% versus 13% (p = 0.04). The lower GRFS in AYA was mainly explained by a higher chronic graft versus host disease (cGvHD) incidence: 32% versus 19% (p < 0.001). Use of peripheral blood stem cells and use of anti-thymoglobulin appeared to be the main factors impacting cGvHD occurrence in AYA.Conclusion: AYA have worse outcomes than children after HSCT for ALL because of a greater risk of TRM due to cGvHD. HSCT practices should be questioned in this population.Keywords: Acute lymphoblastic leukemia; Adolescents and young adults; Graft versus host disease; Hematopoietic stem cell transplantation.

International audience; Background Since the introduction of tyrosine kinase inhibitors (TKIs), the profile of pediatric relapse of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) has changed. However, the management of pediatric Ph+ ALL relapses is not currently standardized. Procedure We retrospectively analyzed the therapeutic strategies and outcomes of pediatric Ph+ ALL patients in first relapse who were initially treated with a TKI-containing regimen in one of the French pediatric hematology centers from 2004 to 2019. Results Twenty-seven children experienced a Ph+ ALL relapse: 24 (89%) had an overt relapse and three a molecular relapse. Eight involved the central nervous system. A second complete remission (CR2) was obtained for 26 patients (96%). Induction consisted of nonintensive chemotherapy for 13 patients (48%) and intensive chemotherapy for 14 (52%). Thirteen patients (48%) received consolidation. Allogenic hematopoietic stem cell transplantation (alloHSCT) was performed for 21 patients (78%). The TKI was changed for 23 patients (88%), mainly with dasatinib (n = 15). T315I was the most common mutation at relapse (4/7). The 4-year event-free survival and survival rates were 60.9% and 76.1%, respectively. Survival was positively associated with alloHSCT in CR2. Conclusion We show that pediatric first-relapse Ph+ ALL reinduces well with a second course of TKI exposure, despite the use of different therapeutic approaches. The main prognostic factor for survival was alloHSCT in CR2. Because of the small size of the cohort, we could not draw any conclusions about the respective impact of TKIs, but the predominance of the T315I mutation should encourage careful consideration of the TKI choice.

International audience; 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 1 or 2 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 2-year cumulative incidence (CI) of transplantation strategy failure as defined in our RCT. The 2 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< .001) and to receive a radiation-free regimen (39.0% versus 60.6%, P< .001). The 2-year CI of transplantation strategy failure, TRM, and the 2-year probability of OS were similar between the 2 groups, although the relapse risk was higher in the RW group (31.2% ± 7.7% versus 20.4% ± 6.8%, P= .01), resulting in a significantly lower disease-free survival (DFS) (59.2% ± 8.4% versus 69.3% ± 8.0%, P= .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.

International audience; Among 143 patients with elastase, neutrophil-expressed (ELANE)-related neutropenia enrolled in the French Severe Chronic Neutropenia Registry, 94 were classified as having severe chronic neutropenia (SCN) and 49 with cyclic neutropenia (CyN). Their infectious episodes were classified as severe, mild or oral, and analysed according to their natural occurrence without granulocyte-colony stimulating factor (G-CSF), on G-CSF, after myelodysplasia/acute leukaemia or after haematopoietic stem-cell transplantation. During the disease’s natural history period (without G-CSF; 1913 person-years), 302, 957 and 754 severe, mild and oral infectious events, respectively, occurred. Among severe infections, cellulitis (48%) and pneumonia (38%) were the most common. Only 38% of episodes were microbiologically documented. The most frequent pathogens were Staphylococcus aureus (37·4%), Escherichia coli (20%) and Pseudomonas aeruginosa (16%), while fungal infections accounted for 1%. Profound neutropenia (3000/mm(3) ) and neutropenia subtype were associated with high risk of infection. Only the p.Gly214Arg variant (5% of the patients) was associated with infections but not the overall genotype. The first year of life was associated with the highest infection risk throughout life. G-CSF therapy achieved lower ratios of serious or oral infectious event numbers per period but was less protective for patients requiring >10 µg/kg/day. Infections had permanent consequences in 33% of patients, most frequently edentulism.

Background: There are currently few data on the outcome of acute myeloid leukemia (AML) in adolescents and young adults (AYAs) after allogeneic HSCT. The aim of this study is to describe the outcome and its specific risk factors for children, AYAs and adults after a first allogeneic HSCT for AML. Methods: In this retrospective study, we compared the outcome of AML patients receiving a first allogeneic HSCT between 2005 and 2017 according to their age at transplantation’s time: children (Results: With a median follow-up of 4.37 years (min-max 0.18 – 14.73 years), the probability of 2 year-overall survival (OS) was 71.4% in children, 61.1% in AYAs and 62.9% in adults (p=0.0009 for intergroup difference). Both relapse and non-relapse mortality (NRM) Cumulative Incidence (CI) estimated at 2 years were different between the age groups (30.8% for children, 35.2% for AYAs and 29.4% for adults - p=0.0254, and 7.0% for children, 10.6% for AYAs and 14.2% for adults, pConclusion: Age is an independent risk factor for NRM and extensive chronic GVHD. This study suggests that AYAs AML patients should be treated with chemotherapy-based MAC regimen and bone marrow as stem cells source.

Relapsed B-lineage acute lymphoblastic leukemia (ALL) in children is associated with poor prognosis. Therefore, it seems essential to stratify patients according to prognostic factors in order to adapt therapies. The evaluation of minimal/measurable residual disease (MRD) during chemotherapy constitutes the most powerful prognostic factor in all age groups, indeed, patients with early low MRD having better outcomes. New immunotherapies based on monoclonal antibodies have recently been developed and are giving promising results in chemoresistant forms with limited toxicities. Indeed, CD20, CD38, CD22 and, less developed, HER2/neu constitute therapeutic targets. However, few studies have reported on the expression level of these markers and compared it to the normal counterpart, precursor B-cells or hematogones. Such investigations would be useful to appreciate the potential efficacy of immunotherapies targeting these markers. Moreover, it could help for the detection of minimal/measurable residual disease during follow-up. A cohort of 125 B-ALL patients (1-25 years old) was retrospectively enrolled in this study, treated between January 2011 and February 2020. Samples collected from bone marrow or peripheral blood were studied in multiparameter flow cytometry (MFC). Cells were analyzed with a Canto II flow cytometer (BD Biosciences), and Diva (BD Biosciences) software was used to assess the expression of the antigenic markers. The same MFC assay had been performed over the whole period, allowing for fluorescence intensities comparison. Additionally, results from 36 normal bone marrow samples were examined, to compare the level of antigen expression by hematogones. CD20, CD38 and CD22 were expressed in respectively 53.6%, 99.2% 98.4% of the cases, rather homogeneously and at intermediate levels. The mean fluorescence intensity of CD38 was much higher on hematogones than blasts, which made it a leukemia-associated immunophenotype (LAIP) for 101 patients (81.4%). HER2/neu, a marker of breast cancer also expressed in a subset of ALL, was present in 16 samples (13.4%), but not detectable on hematogones, and can thus always be considered a LAIP. Interestingly, in this subgroup, patients had a significantly lower 5-year EFS compared to patients without expression of HER2/neu (63% versus 80.5%, p=0.02) (Figure 1). No significant difference in the expression of tested potential therapeutic markers was found between age groups. In conclusion, these 4 antigens have sufficient expression intensities to make them potential therapeutic targets, which could be an interesting alternative for the treatment of refractory/relapsed childhood B-ALL. For example, trastuzumab could be a potential immunotherapy in the HER2/neu expressing group, especially regarding their poorer prognosis. Moreover, CD38 and HER2/neu are good candidates for monitoring MRD. These results are of interest as it has been shown that monitoring MRD early was prognostic on patients' outcome. Figure Disclosures Chevallier: Incyte Corporation: Honoraria.

Leukaemia results from a malignant proliferation of cells in the bone marrow. The prognosis is defined by the disease's biological characteristics. Treatment is based on chemotherapy. In cases of high-risk leukaemia, an allograft may be proposed. The arrival of targeted therapies and immunotherapy has revolutionised the prognosis of the disease. The challenge of the next few years will be to define the place of these therapies.

Resume Introduction La leucemie aigue lymphoblastique de l’enfant refractaire ou en rechute est de pronostic pejoratif et justifie d’une consolidation par allogreffe. La negativation de la maladie residuelle pre-greffe est un facteur pronostique majeur. Le blinatumomab, anticorps bi-specifique CD19+/CD3+, a permis l’obtention d’une remission complete cytologique et moleculaire avant allogreffe chez des adultes presentant une leucemie aigue lymphoblastique B refractaire. Cette etude retrospective analyse les resultats d’une cohorte de patients pediatriques ayant pu beneficier du blinatumomab dans le cadre d’une structuration interregionale. Materiel et methode Les patients âges de 0 a 23 ans provenant des 7 centres de l’interregion Ouest, presentant une leucemie aigue lymphoblastique B refractaire ou en rechute, ayant ete traites par blinatumomab au CHU de Nantes de janvier 2015 a janvier 2018, ont ete inclus. L’efficacite du traitement en termes de remission complete, maladie residuelle et survie globale ainsi que la tolerance ont ete analyses. Resultats Apres blinatumomab, treize patients sur 18 ont ete mis en remission complete, avec une maladie residuelle negative pour 10 d’entre eux. Finalement, quatorze patients ont pu etre greffes a Nantes ou a Rennes. Huit patients sur les 14 allogreffes ont obtenu une remission complete prolongee. En termes de tolerance, aucun evenement grave, en particulier neurologique ou psychiatrique n’a ete observe. Conclusion Grâce au travail en reseau, l’ensemble des patients provenant de l’interregion Ouest ont pu etre traites par blinatumomab a Nantes. Le blinatumomab a permis d’obtenir des conditions hematologiques favorables a la realisation d’une allogreffe en termes de remission complete et maladie residuelle, avec une tolerance clinique satisfaisante.

Resume De nouvelles strategies therapeutiques sont necessaires pour ameliorer la survie des enfants et adolescents ayant un cancer de haut risque, et reduire les sequelles liees aux traitements. Les traitements d’immunotherapie, diriges contre les cellules tumorales et/ou le systeme immunitaire afin d’induire ou d’amplifier une reponse antitumorale effectrice, ont un succes croissant en oncologie chez l’adulte. Sur la base des resultats obtenus avec les anticorps anti-GD2 dans le neuroblastome, le rituximab dans les lymphomes B matures, les inhibiteurs des points de controle immunitaires dans certains lymphomes et notamment le lymphome de Hodgkin, et avec le blinatumomab et les lymphocytes T genetiquement modifies ciblant le CD19 (CD19 CAR T) dans les leucemies aigues lymphoblastiques B, l’immunotherapie a demontre des succes irrefutables en pediatrie. Cependant, ces resultats sont actuellement limites a une minorite de patients et d’histologies. Les essais effectues et en cours ont souvent evalue un seul type d’immunotherapie a la fois, en situation de maladie refractaire ou en rechute, mais il est probable que les combinaisons d’immunotherapies ayant des mecanismes d’action differents ou avec d’autres classes de traitements antitumoraux seront additives, voire synergiques. Le developpement de cette nouvelle classe de medicaments pose de nombreux defis : mieux evaluer la reponse sous traitement, definir les doses et les schemas optimaux d’administration, traiter les toxicites immuno-mediees, surveiller la toxicite a long terme chez l’enfant, et, enfin, mieux comprendre les strategies d’evasion immunitaire specifiques des cancers pediatriques afin de developper des immunotherapies efficaces.

Background There are currently few data on the outcome of acute myeloid leukemia (AML) in adolescents after allogeneic HSCT. The aim of this study is to describe the outcome and its specific risk factors for children, adolescents and young adults after a first allogeneic HSCT for AML. Methods In this retrospective study, we compared the outcome of AML patients receiving a first allogeneic HSCT between 2005 and 2017 according to their age at transplantation’s time: children (n = 564), adolescent and post-adolescent (APA) patients (15–25 years, n = 647) and young adults (26–40 years; n = 1434). Results With a median follow-up of 4.37 years (min–max 0.18–14.73 years), the probability of 2-year overall survival (OS) was 71.4% in children, 61.1% in APA patients and 62.9% in young adults (p = 0.0009 for intergroup difference). Both relapse and non-relapse mortality (NRM) Cumulative Incidence (CI) estimated at 2 years were different between the age groups (30.8% for children, 35.2% for APA patients and 29.4% for young adults—p = 0.0254, and 7.0% for children, 10.6% for APA patients and 14.2% for young adults, p p Conclusion Age is an independent risk factor for NRM and extensive chronic GVHD. This study suggests that APA patients with AML could be beneficially treated with a chemotherapy-based MAC regimen and bone marrow as a stem cells source.

Graft-versus-host disease (GVHD) is the most common complication after allogeneic hematopoietic cell transplantation (allo-HCT) with a frequency range of 30% to 50%. GVH is the leading cause of non-relapse-related deaths and a cause early mortality. Gastro-intestinal (GI) GVH results in digestive manifestations that involve the small intestine and the colon. The patient may then have diarrhea, intestinal bleeding, abdominal pain but also clinical signs such as nausea and vomiting may lead to anorexia. GI-GVHD promotes undernutrition as well as significant losses of vitamins and trace elements. In the case of post-transplant diarrhea, differential diagnosis can include GI-GVHD, infection and drug toxicity. Although, corticosteroids w/wo calcineurin inhibitors represent the standard of care in first line treatment, there is no consensus regarding salvage therapy in case of corticoresistant GI-GVH. In addition, assessment of early nutritional status would help combating undernutrition, which is an independent risk factor for mortality in patients with GI-GVHD. In this workshop of the Fancophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) we focused on the management of patients developing GI-GVHD following allo-HCT.

International audience; ELANE neutropenia is associated with myelodysplasia and acute leukemia (MDS–AL), and severe infections. Because the MDS–AL risk has also been shown to be associated with exposure to GCSF, since 2005, in France, patients receiving high daily GCSF doses (>15 μg/kg/day) are eligible for HSCT, in addition to classic indications (MDS–AL or GCSF refractoriness). We analyzed the effect of this policy. Among 144 prospectively followed ELANE-neutropenia patients enrolled in the French Severe Congenital Neutropenia Registry, we defined two groups according to period: “before 2005” for those born before 2005 and followed until 31/12/2004 (1588 person-years); and “after 2005” comprised of those born after 2005 or born before 2005 but followed after 2005 until 31/03/2019 (1327 person-years). Sixteen of our cohort patients underwent HSCT (14 long-term survivors) and six developed MDS–ALs. Six leukemic transformations occurred in the before-2005 group and none after 2005 (respective frequencies 3.8 × 10–3 vs. 0; P

International audience; Background We conducted a national multicenter retrospective study in France to evaluate the efficacy and tolerance of ruxolitinib in children with steroid-refractory acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplant. Procedure Patients were recruited from the 15 pediatric transplantation centers. Transplanted patients were eligible if they met the following criteria aged = 2, and treated with ruxolitinib for steroid-refractory aGVHD. Results Twenty-nine patients received ruxolitinib for steroid-refractory aGVHD. Six patients achieved a complete response at day 28 after the start of treatment but finally 19 patients (65.5%) achieved a complete response (CR) with a median delay of 41 days (5-93 days). Two patients had a partial response. All patients who achieved CR or partial response discontinued corticosteroid treatment. Eight patients showed treatment failure. The overall response rate was 72.4%. Twenty-three of 29 patients were alive at a median follow-up of 685 days (177-1042 days) after the hematopoietic stem cell transplantation. Viral replication was observed in 41.4% of cases. We did not observe severe hematological adverse events and cytopenia requiring a modification of ruxolitinib doses always resolved. The median initial dose of ruxolitinib was 12.6 mg/m(2)/day with an important range. We could not demonstrate any relationship between initial dose and effectiveness. Conclusion Ruxolitinib may constitute a promising second-line treatment for children with steroid-refractory aGVHD that should be validated in a prospective large-scale pharmacokinetic and efficacy trial.

Leukaemia results from a malignant proliferation of cells in the bone marrow. The prognosis is defined by the disease's biological characteristics. Treatment is based on chemotherapy. In cases of high-risk leukaemia, an allograft may be proposed. The arrival of targeted therapies and immunotherapy has revolutionised the prognosis of the disease. The challenge of the next few years will be to define the place of these therapies.

Introduction: Adolescents and Young Adults (AYA) represent a specific population in the Acute Lymphoblastic Leukemia (ALL) landscape, often presenting high-risk diseases and increased chemotherapy-related toxicities. Indications of Hematopoietic Stem Cell Transplantation for pediatric patients (HSCT) have been restricted to those with early poor response to chemotherapy. The same trend has led to a decrease of HSCT indications in AYAs, which are nevertheless still more frequent than in younger counterpart. Outcomes of AYAs after HSCT seemed to be worse than the ones of children in two previous studies published in 2013 and 2014. In Minneapolis, the decrease of overall survival in AYA was attributed to an excess of Treatment Related mortality (TRM) (28% versus 14%; p=0.04), but because of small numbers, factors influencing TRM were not identified. Our study aimed to compare, in a large cohort, the outcomes of children and AYA with ALL after HSCT and to determine factors influencing potential differences. Material and Methods: All patients aged between 1 and 25 years, reported in the SFGM-TC (Francophone Society of bone marrow transplantation and cellular therapy) registry, who received a first HSCT in treatment for ALL between 2005 and 2012 were included. The AYA group was defined by age range between 15 and 25 years old, according to European studies and the SFGM-TC. Data about diagnosis and transplantation procedure were prospectively collected in the registry. Before transplant procedure, patients or their parents/guardians provide a signed consent in order to be included in the registry. Results: 891 patients were included, 494 children and 397 AYA. Median time of follow up was 45.6 months (0 to 114). HSCT was performed in first CR for 56.8% of the AYAs, whereas 57.5% of children received HSCT in second CR or more advanced phase (p Five-year OS was lower in AYA 53.1% versus 64% (p = 0.0012) and we confirmed higher 5-years TRM in AYA 19% versus 13% (p=0.04). TRM incidence markedly rose after 10 years of age (from 9% before 10 years old to 20% between 10 and 15 years, and 17% after 15 years). Graft versus host disease and Relapse Free Survival probability (GRFS) was lower in AYA: 36% versus 47% (p=0.007), while Cumulative Incidence of Relapse (CIR) and acute Graft versus Host Disease (GvHD) incidence were both similar in our two groups: 32% and 61% in AYAs versus 27% and 59% in children, (p=0.19 and p=0.62), respectively. Thus, chronic GvHD, which occurred more frequently in AYA than in children (32% versus 19%, p In our multivariate analysis, two factors were associated with higher risk of cGvHD: use of PBSC as stem cell source (HR 1.41 [0.96-2.07], p=0.083), and absence of ATG use (HR associated with use of ATG: 0.62 [0.42-0.92], p=0.017) (Figure 3). Of note a subgroup analysis in patients who received a bone marrow transplant after a MAC, showed no TRM difference between AYA and children. Conclusion: AYA or patients aged more than 10 years, compared to ones aged less than 10 years have a worse outcome after HSCT for ALL. Excess of death in this specific population is mainly due cGvHD. Transplantation practices in those patients, particularly choice of stem cells source and GvHD prophylaxis, should be discussed. Their treatment adherence should also be questioned and reinforced by development of multidisciplinary teams. Figure 1 Figure 1. Disclosures Peffault De Latour: Pfizer: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Amgen: Consultancy, Other, Research Funding; Jazz Pharmaceuticals: Honoraria; Alexion, AstraZeneca Rare Disease: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding. Forcade: Novartis: Other: travel grant.

Background: Pediatric patients younger than two years of age with acute myeloid leukemia (AML) commonly receive a chemotherapy-based myeloablative conditioning regimen before allogeneic hematopoietic stem cell transplantation (HSCT). The optimal choice of cytotoxic agents is still controversial. Methods: A retrospective EBMT-registry based study was conducted to investigate the impact of different chemotherapy-based conditionings on the outcomes in young children. Children younger than two years of age receiving a first HSCT of bone marrow (BM), peripheral blood stem cells (PBSC) or cord blood (CB) from matched siblings (MSD) or unrelated donors (UD) in first complete remission (CR1) between 2000 and 2019 were included. Busulfan/Cyclophosphamide (BuCy) and BuCy/Melphalan (BuCyMel) were the most frequent combinations on which this analysis focused. The primary endpoint was leukemia-free survival (LFS). Multivariate analysis adjusting for differences between the conditioning regimens and risk factors influencing outcome was performed using the Cox's proportional hazards regression model. Results: 289 patients (56% male) transplanted at a median age of 1.2 years (IQR 0.9-1.6) after BuCy (164, 57%) or BuCyMel (125, 43%) were included. 184 (64%) patients received BM, 71 (24%) CB and 34 (12%) PBSC from UD (201, 70%) and MSD (88, 30%). In-vivo T-cell-depletion (TCD) was performed in 160 (58%, missing data 14) of the HSCTs with anti-thymocyte-globulin (ATG, 153) or alemtuzumab (7). Ex-vivo TCD was performed in 13 (5%, missing data 3) of the HSCTs. Graft-versus-host-disease (GvHD)-prophylaxis was Cyclosporin-A-based in 90% of the HSCTs. Median follow-up (FU) was 4.9 years (95% CI 3.9-5.5). After a median FU of 4 years, 4-y-LFS after BuCyMel (74.3%, 95% CI 65.1-81.4) was significantly better compared to BuCy (59.7%, 95% CI 51.2-67.2), hazard ratio (HR) 0.56 (95% CI 0.35-0.90, P=0.02). Overall survival (4-y-OS) after BuCyMel (77.2%, 95% CI 68.1-84.0) was significantly better compared to BuCy (66.6%, 95% CI 58.0-73.8), HR=0.58 (95% CI 0.35-0.97, P=0.04). No significant differences were found in the probability of relapse (4-y-RI (whole cohort) 26.2% (95% CI 21.0-31.7), HR of BuCyMel 0.59 (95% CI 0.34-1.02), P=0.06), non-relapse mortality (4-y-NRM (whole cohort) 7.8% (95% CI 5.0-11.4), HR of BuCyMel 0.49 (95% CI 0.19-1.24), P=0.13) and incidence of acute grade II-IV GvHD at day 100 (day-100-aGvHD II-IV (whole cohort) 36.8% (95% CI 31.2-42.5), HR of BuCyMel 0.59 (95% CI 0.35-1.01), P=0.06). Incidence of chronic GvHD (4-y-cGvHD (whole cohort)) was 9.8% (95%-CI 6.3-14.2). The donor type had no significant influence on the outcome. Conclusion: Bu-based conditionings of HSCT for infants with AML at high risk of relapse offer a high probability of cure. Conditioning with three alkylators (BuCyMel) resulted in better LFS and OS compared with two alkylators (BuCy) without significantly increasing the risk of both NRM and aGvHD. Future trials will evaluate the impact of the more recently introduced alkylator Treosulfan within the conditioning of HSCT in pediatric AML. Disclosures Peters: Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Travel grants. Locatelli: Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Miltenyi: Speakers Bureau; Medac: Speakers Bureau; Jazz Pharamceutical: Speakers Bureau; Takeda: Speakers Bureau. Moraleda: Pfizer: Other: Educational Grants, Research Funding; Sanofi: Other: Educational Grants, Research Funding; MSD: Other: Educational Grants, Research Funding; ROCHE: Consultancy, Honoraria, Other: Educational Grants, Research Funding; Takeda: Consultancy, Honoraria, Other: Educational Grants, Research Funding; Sandoz: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: Educational Grants, Research Funding; Gilead: Consultancy, Honoraria, Other: Educational Grants, Research Funding; Jazz Pharmaceuticals: Consultancy, Honoraria, Other: Educational Grants, Research Funding; NovoNordisk: Other: Educational Grants, Research Funding; Janssen: Other: Educational Grants, Research Funding; Celgene: Other: Educational Grants, Research Funding; Amgen: Other: Educational Grants, Research Funding. Biffi: BlueBirdBio: Consultancy, Other: Advisory Board. Corbacioglu: Gentium/Jazz Pharmaceuticals: Consultancy, Honoraria.

Background: Inotuzumab ozogamicin (InO) was well tolerated and demonstrated anti-leukemia activity in heavily pre-treated pediatric patients (pts) with CD22-positive relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) in the Phase (Ph) I ITCC-059 study. With the established recommended phase 2 dose (RP2D) (1.8 mg/m2/course, as in adults) a consecutive Ph II study has been performed, sponsored by Erasmus MC and supported by Pfizer (NTR57360). Study design: Pts aged 1-18 years with R/R CD22+ BCP-ALL were included after informed consent was obtained. Key inclusion criteria included, M2/M3 marrow and adequate liver and kidney function. Overall response rate (ORR) was the primary endpoint, and included CR, CRp (ANC >500/µL but PLT ≤50.000/µL) and CRi (ANC ≤500/µL and/or PLT ≤50,000/µL). Secondary endpoints included safety, minimal residual disease (MRD) levels and durability of response. The study consisted of a single-stage design to test the null hypothesis (H0) ORR ≤30% and the alternative hypothesis of ORR >55%. With 25 pts, the study had 80% power to reject H0 at a significance level of 0.05. Central MRD analysis by flow cytometry was considered negative if Results: 32 pts were enrolled (Jun 2019-Apr 2020), including 2 screen failures and 2 pts who did not start treatment due to rapidly progressive disease. The median age of the 28 treated pts was 7.5 years (range 1-17); 19 pts were male (68%); 6 (21.5%) were primary refractory, 16 (57%) had ≥2nd relapse and 6 (21.5%) had 1st relapse post-HSCT (median 2 prior regimens, range 2-7). 50% of the pts had received a previous HSCT, 3 (11%) CAR T-cell therapy and 7 (25%) blinatumomab. Median baseline WBC was 3.1 x109/L (range 0.7-132). At time of data snapshot, 48 courses of InO were administered (range 1-4 per pt); one pt was still receiving InO. Disease response was not assessed in 1 pt (discontinued early due to sinusoidal obstruction syndrome (SOS)), 27 pts were evaluable for efficacy analyses. Twenty-two pts achieved a response (ORR 81.5%; 95% CI 61.9%, 93.7%), all after the first cycle (CR n=14, CRp n=1, CRi n=7). Hence, the primary objective was achieved (P-value When combining these results with pts treated at the RP2D in the Ph I study (n=13), 33/40 (82.5%) achieved a response (94% of whom achieved MRD-negativity). Of 9 primary refractory patients included in Ph I and II, 3 (33%) did not respond to InO. The median follow-up time was 7.3 months (mo). The EFS at 6 and 12 mo was 57.9% (95% CI: 40.3−83.3) and 24.8% (95% CI: 9.8−62.9); and OS at 6 and 12 mo was 61.6% (95% CI: 43.3−87.8) and 54.8% (95% CI: 35.9−83.6), respectively. The median EFS was reached at 6.34 mo (95% CI 2.53, NA). The cumulative incidence of non-response or relapse was 32% and 57% at 6 and 12 mo; 3 pts died in CR (2 due to HSCT complications, 1 due to neurological deterioration considered related to previous CNS leukemia and prolonged intrathecal treatment). Nine of 22 responding pts underwent HSCT (median 35 days after the last InO dose, range 20-72); 4 are still in CR. Three responders received consolidation with CAR T (52, 55 and 215 days after last Ino dose), all are still in CR. Four cases of VOD/SOS were reported. One case occurred during InO treatment (gr 3, resolved). Three of 9 transplanted pts (33%) developed post-HSCT SOS. None of these pts received prophylactic defibrotide. One pt, previously transplanted and treated with CAR T, received 1 course of InO prior to a second HSCT and developed SOS (gr 3), ongoing at the time of death due to multiorgan failure. The other 2 pts developed gr 2 SOS after 2 and 3 courses of InO before their first HSCT, both events resolved. All pts had at least 1 adverse event (AE) during the study and 19 pts reported at least 1 of gr 3-4 AE. The most common AE was fever. Detailed data will be presented at the meeting. Conclusion: InO was well tolerated in this Ph II study which confirmed remarkable activity in these heavily pretreated pts. The ORR was 81.5% with 95% MRD-negativity; 55% of pts remained alive after 1 year. Twelve pts proceeded to consolidation treatment (either HSCT or CAR T). In contrast with the Ph I cohort (where no pts developed SOS post 7 HSCTs), 3 cases of SOS were recorded here after 9 HSCTs. A Ph I cohort of this study combining InO with chemotherapy in R/R pediatric ALL is ongoing. Disclosures Brivio: Pfizer Inc.: Other: Erasmus MC received institutional funding for the study from Pfizer. Rossig:BMS: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Genetech: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; EUSA Pharma: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria. Sleight:Pfizer Inc.: Current Employment. Reinhardt:Novartis: Membership on an entity's Board of Directors or advisory committees; CLS Behring: Research Funding; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Roche: Research Funding; bluebird bio: Membership on an entity's Board of Directors or advisory committees. von Stackelberg:Morphosys: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, advisory committees and speakers bureau, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, advisory committees and speakers bureau, Speakers Bureau; Jazz: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, advisory committees and speakers bureau, Speakers Bureau; Shire: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, advisory committees and speakers bureau, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, advisory committees and speakers bureau, Speakers Bureau. Zwaan:Servier, Sanofi, Daiichi Sankyo, Novartis, Janssen, Roche, Incyte, Pfizer, Celgene: Consultancy; Pfizer, Celgene, BMS: Research Funding; Jazz Pharmaceuticals: Other: Travel funding.

Acute complications requiring admission to pediatric intensive care unit (PICU) are frequent for children with cancer. Our objective was to determine early prognostic factors of mortality in a cohort of children with cancer hospitalized in PICU for acute complications and particularly to assess whether the delay before admission to a PICU is an early predictor of mortality. We conduct a retrospective multicenter analysis. All patients transferred in PICU for acute complications between January 2002 and December 2012 were included. One-month mortality of the 224 patients analyzed was 24.5%. Delay before PICU admission was a significant prognostic factor of 1-month mortality with nonsurvivors experiencing a longer median delay than survivors (24 vs. 12 h, respectively, P

Relapses of acute lymphoblastic leukemia (ALL) early after hematopoietic stem cell transplantations in children are uncommon but associated with a very poor prognosis. Whereas there are no current recommendations for the management of these relapses, the children's quality of life is an important issue. We studied the outcomes, including 1-year overall survival, complete remission, and quality of life, of 19 children with ALL who relapsed within the first year after their transplantation treated in the 5 participating centers between 2000 and 2011 Patients were distributed as follows: supportive care only (group A), outpatient treatment (mainly steroid and vincristine, group B), or intensive inpatient treatment (group C). There were no significant differences in 1-year overall survival (31.5% for the entire cohort) or remission rate for time between transplantation and relapse (6 months or 6 to 12 months), transplantation or disease characteristics, or treatment group. However, time spent in hospital (for treatment and complications) significantly differed between treatment groups B and C (20.8% ± 13.0 versus 59.1% ± 32.9, respectively; P.05). No differences in organ toxicities, school attendance, or Lansky scores were found between treatment groups. Our sample size-limited data indicate, in a prepersonalized medicine era, that children treated with steroid and vincristine have the same prognosis as those treated with intensive therapy, but they may benefit from improved quality of life. Nevertheless, new therapeutic strategies are required and future prospective trials would help to establish recommendations.

International audience; Allogeneic stem cell transplantation (allo-SCT) has become an essential component of the treatment for a variety of diseases in pediatric patients. During the past decades, advances in the transplant technology, availability of hematopoietic stem cells and supportive care not only have resulted in improved outcomes, but also have expanded the transplant options. However, these features have been studied mainly in adult populations. This investigation analyzed changes in patient profile, transplantation, graft characteristics and outcome among 250 children and adolescent patients who received allo-SCT in a single center between 1983 and 2010. In the 2000–2010, compared with the 1983–1999 period, a significantly higher 5-year overall survival (64% versus 52%, P=0.03) was observed together with a significant decrease of non-relapse mortality (27% versus 9%, P=0.0002). The progression-free survival was comparable between the two periods (49% versus 57%; P=0.17). The 5-year cumulative incidence of relapse was 24% between 1983 and 1999, and 34% between 2000 and 2010 (P=0.08). Major advances in supportive care practice have been made over the past decade, resulting in a significant survival benefit for the pediatric population undergoing allo-SCT. However, post-transplant relapse remains the leading cause of failure of this therapeutic approach, and preventing relapse represents a major challenge today

International audience; Peripheral T-cell lymphoma carries a poor prognosis. To document a possible graft-versus-lymphoma effect in this setting, we evaluated the impact of immunomodulation in 63 patients with peripheral T-cell lymphoma who relapsed after allogeneic transplant in 27 SFGM-TC centers. Relapse occurred after a median of 2.8 months. Patients were then treated with non-immunologic strategies (chemotherapy, radiotherapy) and/or immune modulation (donor lymphocyte infusions (DLI) and/or discontinuation of immunosuppressive therapy). Median overall survival (OS) after relapse was 6.1 months (DLI group: 23.6 months, non-DLI group: 3.6 months). Among the 14 patients who received DLI, 9 responded and 2 had stable disease. Among the remaining 49 patients, a complete response accompanied by extensive chronic GvHD was achieved in two patients after tapering of immunosuppressive drugs. Thirty patients received radio-chemotherapy, with an overall response rate of 50%. In multivariate analysis, chronic GvHD (odds ratio: 11.25 (2.68–48.21), P=0.0009) and skin relapse (odds ratio: 4.15 (1.04–16.50), P=0.043) were associated with a better response to treatment at relapse. In a time-dependent analysis, the only factor predictive of OS was the time from transplantation to relapse (hazards ratio: 0.33 (0.17–0.640), P=0.0009). This large series provides encouraging evidence of a true GvL effect in this disease

Background: Inotuzumab ozogamicin (InO) is a CD22-directed monoclonal antibody linked to calicheamicin. It is approved for adults with relapsed/refractory (R/R) CD22+ B-cell precursor acute lymphoblastic leukemia (BCP-ALL) at the dose of 1.8 mg/m2/course fractionated at day 1, 8 and 15 (Kantarjian, NEJM, 2016). The pediatric experience with InO is still limited. Patients (pts) We collected cases of infants and young children diagnosed with R/R ALL and treated with InO via a compassionate access program. Methods: Participating international pediatric oncology centers submitted retrospective demographic, outcome, and toxicity data on infants (age Results: Between 2015 and 2019, 9 infants and 3 children (1.0-2.9 years of age) were diagnosed with ALL and later on received 1-3 cycles of InO due to R/R disease. At the time of InO treatment 1 pt was At the start of InO, 8 (67%) pts had an M3 bone marrow status, 2 (17%) an M2 and 2 an M1 with MRD positivity. CD22 expression was reported in 7/12 pts: in 3 cases >90% of blasts expressed CD22, the others ranging from 52% to 80%. In total 21 courses were administered (60 doses; 3 courses not completed), median administered dose of InO per course 1.74 mg/m2 (divided in 3 weekly doses, with the loading dose at D1 of cycle 1): 6 pts received 1.8 mg/m2 (adult approved dose), 4 intermediate dosages as 1.5 or 1.6 mg/m2, 1 1.4 mg/m2 and 1 1.2 mg/m2. The dose was based on BSA; 0.07 mg/Kg/course was the median pro-Kg dose administered (higher than in adults). 6 pts (50%) achieved a complete remission (CR) (3 after 1 course and 3 after 2-3 courses), 1 additional MRD-positive pt. turned MRD-negative ( Only limited data about toxicity were reported in our records, although hematologic toxicity was the most common (thrombocytopenia in 33% of pts). 1 case of neurotoxicity described as toxic leukoencephalopathy was reported after 1 course of InO, causing death in CR. 1 pt. developed severe veno-occlusive disease (VOD) after HSCT performed in PR, which was fatal. Conclusions: Single agent InO in infants and younger children had a CR rate of 58% in this cohort of heavily pretreated pts. Even with a median dose close to the adult recommended starting dose, InO appeared to be well tolerated, allowing a subsequent HSCT in 5 pts. While taking into account the lower CD22 expression showed by MLL-r pts, further investigation with InO treatment might be valuable in this subgroup of ALL pts with a particular dismal prognosis. Disclosures Pieters: medac: Consultancy; jazz farmaceuticals: Consultancy. Zwaan:Celgene: Consultancy, Research Funding; Roche: Consultancy; Sanofi: Consultancy; Novartis: Consultancy; Daiichi Sankyo: Consultancy; Servier: Consultancy; BMS: Research Funding; Pfizer: Consultancy, Research Funding; Janssen: Consultancy; Jazz pharmaceuticals: Other: Travel support; Incyte: Consultancy. OffLabel Disclosure: Inotuzumab ozogamicin (InO) is a CD22-directed monoclonal antibody linked to calicheamicin. It is approved for adults with relapsed/refractory (R/R) CD22+ B-cell precursor acute lymphoblastic leukemia (BCP-ALL) at the dose of 1.8 mg/m2/course fractionated at day 1, 8 and 15 (Kantarjian, NEJM, 2016). The pediatric experience with InO is still limited. Patients (pts)

Relapsed/refractory acute lymphoblastic leukemia (ALL) in children has a pejorative prognosis and justifies to be treated by hematopoietic stem cell transplantation (HSCT). A minimal residual disease (MRD) before transplantation is a major part of prognosis. Blinatumomab, a bispecific antibody CD19Patients between 0 and 23 years old, from the 7 centers of the french "Grand Ouest" interregional network, treated by blinatumomab for a relapsed or refractory ALL, from January 2015 to January 2018, were included. The efficiency of blinatumomab was assessed in terms of complete remission, minimal residual disease, overall survival, and tolerability of treatment.Thirteen of 18 patients achieved a complete remission, with negative minimal residual disease for ten of them. Fourteen patients proceeded to stem cell transplantation,. Eight out of 14 patients obtained long term remission after HSCT. As far as tolerance is concerned, no serious adverse event, neurological or psychiatric disorder, was observed.Thanks to an interregional network collaboration, all children with high risk ALL coming from the western french interregion could be treated by blinatumomab. Blinatumomab offered good hematological conditions to undergo HSCT with a good tolerability.

Outcomes remain poor for refractory severe aplastic anemia (SAA) patients. Alternative donor transplantation may be considered, but results from previous studies are not encouraging. We conducted a prospective nationwide phase 2 study to assess unrelated cord blood (CB) transplantation (CBT) efficacy and safety in refractory SAA patients (Aplastic Anemia and Cord Blood Transplantation protocol). To demonstrate a significant difference in 1-year survival from 20% (null hypothesis) to 50% (alternative hypothesis), we needed to include 25 transplanted patients and therefore included 26 (median age, 16 years). Eligibility criteria required 1 or 2 unrelated CB units, containing separately or together >4 × 107 frozen nucleated cells (NCs) per kilogram of recipient body weight. Conditioning regimen comprised fludarabine (FLU), cyclophosphamide (CY), antithymocyte globulin (ATG), and 2-Gy total body irradiation (TBI). With a median follow-up of 38.8 months, engraftment occurred in 23 patients (88%); cumulative incidences of grade II-IV acute and chronic graft-versus-host disease were 45.8% and 36%, respectively. Twenty-three patients were alive at 1 year, with an 88.5% overall survival (OS) rate, differing significantly from the expected 20% (P < .0001; 84% OS at 2 years). CBT with units containing ≥4 × 107 frozen NCs per kilogram is therefore a valuable curative option for young adults with refractory SAA and no available matched unrelated donors. This trial was registered at www.clinicaltrials.gov as #NCT01343953.