ALBERT

Description: Adoptive immunotherapy with transplant donor derived virus specific T cells is an effective strategy for the treatment of CMV viremia and disease arising after an allogeneic hematopoietic stem cell (HSCT). This approach is not readily applicable if the donor is seronegative or not available to provide lymphocytes for in vitro expansion for CMV specific cytotoxic T lymphocytes (CMV-CTL) lines or if the CMV CTL lines derived from non-identical donors are restricted by non-shared HLA alleles. We and others have previously presented results indicating that treatment with in vitro expanded CMV-CTLs derived from an HLA partially matched third party donors can effectively treat CMV infections in the post-transplant setting. However, the patient population most likely to benefit from this approach has not been well defined. Patients at especially high risk of succumbing to CMV infection include those who acquire resistance to antiviral therapy. We now present results of treatment with banked off-the-shelf third party CMVpp65 specific CTLs in patients with genetically defined mutations in the UL54 DNA polymerase and UL97 kinase CMV genes predicting resistance to antiviral agents. Fifteen recipients of HSCT with mutations defined prior to the start of cell therapy were treated. All 15 had mutations associated with resistance to ganciclovir. Overall 5 had resistance to ganciclovir, foscarnet and cidofovir, 5 had resistance to ganciclovir and foscarnet, one had resistance to ganciclovir and cidofovir and 4 had resistance to ganciclovir alone. Third party CMV-CTLs were selected on the basis of HLA matching at high resolution at a minimum of 2/8 recipient alleles and HLA restriction of the T cells by one or more HLA alleles present in the patient. CMV-CTLS were selected from a bank of 132 lines generated under GMP conditions from normal HSCT donors specifically consented for use of their T cells in patients other than the designated transplant recipient. These 15 patients had a median age of 60.5 (7.4-70.1) years and started therapy with CMV-CTLs a median of 157 (70-564) days after reactivation of CMV. Four of these patients had CMV disease while 11 were treated for viremia alone. Prior therapy in this cohort included foscarnet (N=15) ganciclovir and/or valganciclovir (N=14) and cidofovir and/or brincidofovir (N=9). Each cycle of CMV-CTLs consisted of 3 weekly infusions of 1x106 T-cells/kg/infusion. These 15 patients received a median of 2 (1-3) cycles of CMV-CTLs. CMV-CTLs were well tolerated and there were limited toxicities. Six patients experienced AEs of which one grade 3 and one grade 4 AE were deemed possibly related to infusions with CMV-CTLs. Overall 11/15 (73.3%) patients responded to CMV-CTL therapy including 2 patients with disease with 6 CRs and 5 PRs. Overall survival at 6 months in the 11 responders and 4 non-responders was 72.7% and 25.0% respectively. Within the 6 month follow-up one of the 11 responding patients died of CMV while 3 of the 4 non-responding patients died of CMV. These results indicate that third party donor derived "off-the-shelf" CMV-CTLs can effectively treat CMV viremia or disease in patients not responding to antiviral therapy with demonstrated genetic resistance to antiviral agents. Figure 1. Figure 1. Disclosures Doubrovina: Atara Biotherapeutics: Consultancy, Research Funding. Hasan:Atara Biotherapeutics: Consultancy, Research Funding. Koehne:Atara Biotherapeutics: Consultancy.

Description: Introduction: Allogeneic hematopoietic stem cell transplantation (Allo-HCT) is the only curative treatment for myelodysplastic syndrome (MDS). The portion of patients referred for transplant and the proportion who are subsequently transplanted is unknown. Aim: Tostudy the frequency of allo-HCT in pts with MDS and identify factors associated with transplant referral and barriers to transplant. Methods: Pts were included if they were under the age of 75 and seen at our center by a leukemia physician between 2008-2015 and within 6 months of MDS diagnosis. Pts were eligible for allo-HCT if they did not have major organ dysfunction, i.e. left ventricular ejection fraction 2mg/dL, FEV1

Description: Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is the only curative treatment for myelodysplastic syndrome (MDS). Relapse, infections and graft-versus-host disease (GvHD) are the main causes of treatment failure. We compared the outcomes of patients receiving T cell depleted (TCD) grafts at Memorial Sloan-Kettering Cancer Center (MSKCC) with patients receiving unmodified grafts at MD Anderson Cancer Center (MDACC) for advanced MDS (RAEB-1 and 2). Adult patients transplanted between 2001 -2012 were included in this retrospective analysis. All recipients of TCD grafts (N=60) received myeloablative conditioning (MAC) and antithymocyte globulin (ATG) to prevent graft rejection. None of them received post-transplant GvHD prophylaxis. Of the 129 recipients of unmodified grafts, 87 received MAC and 42 reduced intensity conditioning (RIC); GvHD prophylaxis consisted of tacrolimus and mini-dose methotrexate in the majority of patients (N=113). ATG was given to all matched unrelated donor (MUD) recipients. Patients in the unmodified group had more therapy-related MDS (MDS-t), very poor risk cytogenetics by IPSS-R at diagnosis and bone marrow (BM) blast count 〉5% at transplant. Only the TCD group had mismatched donors (Table 1). Univariate analysis identified a lower incidence of grade II-IV acute GvHD in the TCD group with 100-day cumulative incidence (CI) of 13.3% vs. 34.1% in the unmodified group (p=0.031). There was no difference in grade III-IV acute GvHD with a 10% CI in both groups at day-100 (p=0.546). The incidence of chronic GvHD was lower in the TCD group with a CI at 3-yrs of 3.4% vs. 44.3% in the unmodified group (p 〈 0.001). The non-relapse mortality (NRM) in both groups was similar. CIs at day 100, 1yr, and 3 yrs in the TCD group were 8.3%, 20.2% and 32.7% vs. 12.4%, 22.5% and 28.1% in the unmodified group (p=0.628). Relapse was lower in the TCD group, with CI at 1 and 3 yrs of 8.5% and 15.5%, vs. 31.0% and 39.4% in the unmodified group (p=0.002). Since the unmodified recipients had worse disease characteristics, further analyses in patients with good/intermediate risk cytogenetic showed that the relapse incidence was similar between these subgroups, with 3-yr CIs of 7.9% in TCD vs. 18% in unmodified group (p=0.185). The most common causes of death in the TCD group were infections (32%) and relapse (28%), while in the unmodified group it was relapse (55%), GVHD (20%) and infections (13%). Considering the differences in disease characteristics between the groups, multivariate regression models were performed for relapse-free survival (RFS) and overall survival (OS) adjusting for MDS-t, high-risk cytogenetics at diagnosis and high blast count at HSCT. No significant differences were observed between the groups for RFS (HR=1.44, p=0.128) and OS (HR= 1.35, p=0.236) (Table 2). High-risk cytogenetics at diagnosis (very poor risk) was the only significant prognostic factor for RFS (HR=5.32, p

Description: Twenty five patients have been enrolled on this trial to date. There were 14 males and 11 females aged 0.6–54 years. Patients’ diagnoses and stage included: NHL in CR2 or refractory (n=2), AML (n=7), including 5 pts with secondary AML, ALL 〉 CR3 (n=4), CML in CP2 (N=1) and high risk MDS (n=11) including 5 pts with secondary MDS. Eight pts had a matched related donor, 14 pts an unrelated donor and 3 pts a mismatched related donor. Cytoreduction consisted of busulfan (Bu) (0.8–1 mg/Kg/dose x 10 doses), melphalan (Mel) (70 mg/Kg/day x 2) and fludarabine (Flu) (25 mg/m2/day x 5). Graft rejection prophylaxis included rabbit ATG (Thymoglobulin) (2.5 mg/Kg/day x 2). Four pts tolerated only one of two doses of the ATG, 2 pts received equine ATG and one pt Alemtuzumab. Twenty one pts received G-CSF mobilized peripheral blood stem cell transplants that were T-cell depleted by CD34 selection and E-rosetting while the other four pts received Soybean agglutinin E-rosette depleted marrow grafts. Cell doses were 1.3–20.5 x 106 CD34 cells/Kg. and 0 -100 x 103 CD3 cells/Kg. Engraftment occurred in 24 pts. One pt suffered a graft failure; This pt had initial low busulfan levels, and received bone marrow derived stem cells with a low cell dose from a 5/6 HLA-matched unrelated donor. Acute graft-versus-host disease occurred in four pts: grade 1 (n=2) and grade 2 (n=2) and no pts developed any grade 3-4 severe GvHD. Two patients were diagnosed with chronic GvHD: localized (n=1) and extensive (n=1). Two patients developed sepsis early post BMT, with secondary multi organ failure and early mortality, while for the rest of the patients, regimen-related toxicity was acceptable. Relapse occurred in 9 pts. Mortality included 7 pts from relapse, two pts from sepsis and multi-organ failure, 3 pts from infections, and one pt from unknown causes. The overall survival (OS) and disease-free survival (DFS) at 2 yrs for the entire patient cohort were respectively 44% and 42 %; The DFS was 50% for patients with secondary MDS or AML. In summary, the cytoreduction with Bu Mel and Flu allowed consistent engraftment of T-cell depleted grafts and was associated with acceptable outcome for patients with secondary MDS or AML.

Description: Abstract 1942 BACKGROUND: Poor graft function without immune rejection, defined as persistent cytopenias with a hypocellular marrow and full donor chimerism, is a life-threatening complication after allogeneic HSCT. Treatment options include supportive therapy with transfusions and growth factors, vs administration of additional HSCs from the same donor without any conditioning (stem cell boost). The use of unmanipulated boosts increases the risk of development or worsening of GvHD by virtue of infusing mature T cells. The aim of this retrospective study was to evaluate the efficacy and safety of TCD boosts in patients with PGF. PATIENT AND METHODS: Between January 1992 and December 2007, 35 patients from a single center with PGF following either an unmanipulated (10) or a TCD (25) allogeneic HCST received a TCD HSC boost collected from the original donor. T cells were removed ex-vivo from marrow grafts with soybean lectin agglutinin and sheep red blood cells (sRBC) rosetting and from peripheral blood stem cell grafts by positive selection with a CD34 antibody (Isolex) followed by sRBC rosetting. HSC donors were matched related (21), mismatched related (5) and unrelated (9). Indication for first transplant included: aplastic anemia (2), non-Hodgkin's lymphoma (5) and myeloid malignancies (28). The preparative regimen was myeloablative for all recipients of unmanipulated grafts and for 22 of 25 recipients of TCD grafts. With the exception of one patient, the cell dose as measured by total nucleated cell dose/kg or CD34 cells/kg was adequate. Following the initial transplant, all patients had partial or complete recovery of blood counts and full donor chimerism documented by karyotype, FISH analysis or DNA polymorphism. The median time from first transplant to the diagnosis of PGF was 4.5 months (0.72-90.7). Etiologies of PGF included: viral infection and anti-virals (10), bacterial sepsis (3), Mycobacterial infection (4), low cell dose (1), GvHD 12, and idiopathic (5). None of the patients had evidence of relapse or progression of their underlying disease. All patients received a TCD boost from the original donor; with 21 patients receiving bone marrow and 14 receiving PB HSC. RESULTS: Seven patients died before day 21 post boost and were not evaluable for blood count improvement. Improvement (PLT〉50,000/μL, ANC〉500/μL) occurred in 20 of the 28 evaluable patients (71.4 %) at a median time of 3.2 months; 17 of them (60.7%) had a more substantial improvement (PLT ≥100,000/μL and ANC31000/μL) at a median of 8.81 months. TCD boost infusions were well tolerated with no significant adverse events. Also, no new onset GvHD occurred after TCD boosts; although two patients with preexisting GvHD flared. The median survival for all patients following TCD boosts was 21.47 months (range: 1.84–208.45). The 2-year and 5-year survivals were 48.6% and 37.1% respectively. The 2-year survival for patients who had improvement of their counts was 90% and for those who remained pancytopenic despite the boost was 18%. The 2-year survival according to etiology was 52.9% for the infection group, 50% for the idiopathic and low cell dose, and 33.3% for the GvHD group. Patients were also analyzed according to their medical condition prior to receiving the boost and were separated into four groups based on organ function (serum creatinine ≥ 2; total bilirubin ≥ 2; need for mechanical ventilation) and infection status. Group A: outpatient with no infection and no organ dysfunction (9); group B: hospitalized but afebrile with no infection or organ dysfunction (7); group C: febrile or documented infection but preserved organ function (8); group D: organ dysfunction with or without a concurrent infection (11). The 2-year survival for each group was 55.6%, 85.7%, 50%, and 9%, respectively. Patients with organ dysfunction with or without concurrent infection had the lowest survival. Causes of death included: GvHD (10), infection (5), relapse (4), organ failure (3), and poor graft function (1). CONCLUSION: Treatment of PGF with a TCD HSC boost from the original donor is safe and effective with minimal risk of GvHD. Medical status at the time of the boost infusion had a significant impact on outcome. A TCD boost should be considered early in the course of PGF as once complications of persistently low blood counts occur the potential for benefit sharply declines. Disclosures: Small: Pfizer, Inc: Equity Ownership, family member employed by Pfizer, Inc. Perales:Pfizer, Inc: Equity Ownership.

Description: Curative strategies for hematologic malignancies include alloHSCT, which has become a treatment option for older pts, as well as those with more extensive prior therapy and comorbidities. This has stimulated research on the development of less toxic but comparably effective approaches to transplantation at the level of cytoreduction, alternate graft sources, graft manipulation, and GvHD prophylaxis. To this end, between 7/2001 and 12/2005, we administered TCD HSCTs, derived from HLA-M or HLA-MM URDs, to 36 adult pts as treatment for a variety of hematologic malignancies on a clinical trial. The conditioning regimen was designed to reduce regimen related toxicity while preserving adequate immunosuppression to allow for engraftment. The TCD grafts allowed transplantation across HLA disparate pt-donor pairs without the use of additional renal and hepatotoxic GvHD prophylaxis. The conditioning regimen consisted of hyperfractionated total body irradiation (HFTBI) (1375 cGy), thiotepa (5mg/kg) x 2d, fludarabine (25mg/m2) x 5d and antithymocyte globulin (ATG) x 2d. HLA typing was performed by DNA SSOP analyses for A,B,C, DRB1, and DQB1, and donors were matched at ≥8 of 10 alleles. Pts received TCD-PBSC (n=29) or TCD-BM (n=7) from HLA-M (21 pairs) or HLA-MM (15 pairs) URDs. PBSCs were TCD by Isolex 300i CD34+ selection followed by sheep E-rosette depletion, and BMs were depleted with soybean agglutination and sheep E-rosette depletion. The median age was 40.6 (range 18–63)yrs; 10 pts ≥ 50 yrs. Diseases included AML and ALL CR1 (only standard or high risk), AML and ALL CR2, ALL ≥ CR3, acute biphenotypic leukemia, CML in CP, MDS, T-PLL. The median followup is 22 (range 6–55) mos. All evaluable pts engrafted neutrophils, 31 of 35 evaluable pts engrafted platelets. Four pts died of complications prior to platelet engraftment, including one pt with late graft failure. The 100d non-relapse mortality was 20% with most (〉50%) deaths due to infection. The incidence of acute (a) grade II–III and chronic (c) GvHD was low for the entire group of 36 pts at 11% and 28%, respectively, when compared to that of unmodified transplantation. The incidence of aGvHD was 14% and 7%, and cGvHD (majority - limited) was 26% and 30% for HLA-M and HLA-MM transplant pairs, respectively. Estimated 3 yr DFS is 60% for both HLA-M and HLA-MM transplants, and 83% for standard risk and 41% for high risk disease pts. Only one pt has relapsed. These results indicate that a transplantation strategy using HFTBI, thiotepa, fludarabine and ATG followed by TCD PBSC or BM, but without posttransplant immunomodulating agents, is well-tolerated in an older patient group (median age 40 yrs) even with HLA-MM URDs. Although this approach appears to provide an antileukemic effect for acute leukemia pts transplanted in remission of acute leukemia, this will need to be confirmed with longer followup.

Description: Abstract 3080 As compared to single-unit CBT, DCBT may improve engraftment and protect against relapse. Therefore, we have adopted DCBT for both children and adults with acute leukemia, myelodysplasia (MDS), and myeloproliferative diseases (MPD). However, determinants of disease-free survival (DFS) have yet to be fully established. Furthermore, whether DFS after DCBT is comparable in patients of European and non-European ancestry is of special interest. Therefore, we analyzed the DFS of 75 DCBT recipients with acute leukemia in morphologic remission or aplasia (n = 69), and MDS/MPD with ≤ 5% blasts (n = 6) transplanted from 10/2005-4/2011. Nearly all patients had high-risk disease. Children 0–15 years (n = 23) had the following characteristics: median age 9 years (range 0.9–15); median weight 37 kg (range 7–72); 30% European; and 26% CMV sero-positive. Diagnoses were 43% AML (or biphenotypic), 52% ALL, and 4% MDS/MPD, and all received high-dose conditioning. The children received grafts with a median infused TNC × 107/kg of 3.3 (larger unit) and 2.6 (smaller unit), and 2% of units were 6/6 HLA-A, -B antigen, -DRB1 allele matched, 63% 5/6, and 35% 4/6. Adults ≥ 16 years (n = 52) had the following characteristics: median age 41 years (range 16–69); median weight 69 kg (range 47–105); 48% European; 69% CMV sero-positive; and diagnoses were 63% AML (or biphenotypic), 27% ALL, and 10% MDS/MPD. Fifty percent received high-dose and 50% reduced intensity conditioning. Their units had a median infused TNC/kg of 2.7 and 1.9, and 3% were 6/6 HLA-matched, 47% 5/6, and 50% 4/6. All patients (pediatric and adult) received calcineurin-inhibitor/ mycophenolate mofetil immunosuppression, and none received anti-thymocyte globulin. Sustained donor neutrophil engraftment was seen in 91% of children and 94% of adults at medians of 20 and 26 days, respectively. The incidence of grade II-IV acute GVHD by day 180 was 44% in children and 58% in adults. Day 100 transplant-related mortality (TRM) was 9% in children and 19% in adults. The 2-year relapse incidence was 9% in children and 6% in adults. With a median follow-up of survivors of 26 months (range 4–70), 2-year Kaplan-Meier estimate of DFS was 78% in children and 64% in adults (Figure). Differences in survival by age did not reach significance. Univariate analysis of variables potentially influencing 2-year DFS (with log rank estimates of significance) in all patients is shown in the Table. There were no differences in 2-year DFS according to ancestry, remission status, and conditioning intensity. There was also no difference in 2-year DFS according to engrafting unit-recipient HLA-match (4-6/6 or 10 allele), or engrafting unit infused TNC dose/kg. However, patients who were CMV seronegative had a higher 2-year DFS (85% vs 55%, p = 0.018). Multivariate analysis revealed recipient CMV serostatus was a predictor of DFS independent of patient age, and its effect was mediated by an influence on TRM. We have previously shown that DCBT extends transplant access to minority patients. We now demonstrate that DCBT can achieve high and comparable DFS in both European and non-European pediatric and adult patients with acute leukemia and MDS/MPD. While these are very encouraging results further investigation in racial/ethnic sub-groups is needed. Nonetheless, our findings support DCBT as an immediate alternative therapy for high-risk acute leukemia in patients without suitable unrelated volunteer donors, especially given the very low incidence of relapse. Disclosures: No relevant conflicts of interest to declare.

Description: The risk of developing an EBV-LPD is highest in recipients of an unrelated or HLA-mismatched related TCD HCT, with a reported incidence of 10–23%. Although treatment with anti-B cell monoclonal antibodies and/or adoptive immunotherapy can be curative, these therapies are not always effective and can cause fatal tumor lysis syndrome. We have previously shown that the risk of developing an EBV-LPD after a TCD HCT is greatest within the first 2 to 6 months post HCT, and in patients whose circulating CD4 cell counts are less than 200/ul. We therefore developed a phase I pilot trial to investigate the feasibility of 6 monthly doses of rituximab for the prevention of EBV-LPD. Eligibility included hepatitis B surface antigen negative recipients of a TCD HCT from an unrelated or HLA mismatched related donor, EBV seropositive donor and/or host, ANC of 〉1500 cells/ul, documentation of remission, negative EBV viremia at baseline, and lack of ongoing infection at the time of enrollment. Patients received a maximum of 6 consecutive monthly doses of rituximab (375 mg/m2/dose) starting approximately 1 month post HCT. Less than six monthly doses were given if the patient developed a circulating CD4 cell count 〉 200/ul sooner than 7 months post transplant. To date, 22 patients (4–68 years of age, median 19.5 years) have been enrolled on this IRB approved trial, 20 of whom have completed therapy. Rituximab was well tolerated. The main side effect potentially related to rituximab was reversible neutropenia (n=5), which resulted in cessation of treatment as per protocol after the 2nd (n=1), 3rd (n=1), or 4th (n=1) dose. To date, none of the 22 patients on trial have developed an EBV-LPD compared to 10.1% of patients who received an unrelated or HLA MM-related TCD HCT during the same time interval but did not receive prophylactic rituximab. Although 2 patients had prolonged shedding of parainfluenza virus (n=1) or RSV (n=1) from the upper respiratory tract, there was no significant increase in viral or bacterial infections in patients who received rituximab prophylaxis. No patient on trial developed a fatal infection. Eighteen of 22 patients enrolled on trial are alive at a median of 14.5 months post HCT. One patient died of GVHD and 3 high risk patients succumbed to relapse. In evaluable patients, recovery of normal numbers of circulating B cells occurred between 5 and 12 months after the last dose of rituximab. This trial suggests that monthly rituximab can be safely given during the first 6 months after a TCD HCT, resulting in a decreased incidence of EBV-LPD. Larger trials investigating the optimum number and timing of Rituximab doses required to prevent this complication are needed as are studies evaluating recovery of specific B cell function in recipients of rituximab after allogeneic HCT.

Description: Antithymocyte globulin (ATG) has been used in allogeneic stem-cell transplantation to prevent graft rejection and graft-versus-host disease (GvHD). Its use, however, has been associated with delayed T-cell reconstitution and prolonged susceptibility to opportunistic infections (OIs) especially in patients undergoing T cell–depleted (TCD) transplantation. Recently, a prospective trial was conducted in 52 adult patients (median age, 47 years) with various hematologic malignancies undergoing TCD transplantation from HLA-matched related donors without the use of ATG. The cytoreductive regimen consisted of hyperfractionated total body irradiation (HFTBI), thiotepa, and fludarabine. The preferred source of the graft was peripheral blood stem cells (PBSCs). No additional graft rejection or GvHD prophylaxis was given. All evaluable patients engrafted without any immune-mediated graft rejections. Disease-free survival (DFS) at 3 years was 61% in all patients, and 70% in patients with standard-risk disease. Acute GvHD was limited to grade 2 in 8% and chronic GvHD in 9% of patients. Life-threatening OIs occurred in 3 of 52 patients and was fatal in 1. This study demonstrates durable engraftment with a low incidence of GvHD despite the lack of ATG, as well as the curative potential of this regimen.

Description: Strict HLA-match using high resolution typing for HLA-A,B,C,DRB1 improves unrelated volunteer donor (URD) hematopoietic stem cell (HSC) transplant outcome but limits the number of suitable donors. In contrast, CB transplantation (CBT) is associated with a greatly reduced HLA-match requirement which may extend the donor pool. Therefore, we prospectively evaluated donor availability in 309 patients [median age 46 (range 1–71 years)] with high-risk hematologic malignancies between 10/05–5/08 with the hypothesis that CB would extend transplant access. Adequate donor-recipient HLAmatch was ≥/10 HLA-A,B,C,DRB1,DQ alleles for a T cell depleted or ≥9/10 alleles for an unmodified URD graft. Adequate CB units were ≥4/6 HLA-A,B antigen, DRB1 allele matched and ≥1.5 × 107/nucleated cells/kg/unit and double unit grafts were used to augment engraftment. URDs had priority as HSC source; CB was chosen if no suitable URD was available in the required time period. While 28 patients with suitable URDs had no CB search, the results of the 281 patients with both URD and CB formal search/confirmatory typing are shown in Table 1. This combined search group had highly diverse ancestry with only 60 (21%) of northwestern (NW) European origin and 99 (35%) were non-European. 9–10/10 URDs were available for the majority of NW, Eastern and mixed Europeans but not for Southern or non-European patients. Notably, CB extended HSC availability to all and especially Southern European, Asian, African, and Hispanic patients with no Asian patient being without a CB graft. Table 1: Comparison of Formal Search for Both URD and CB by Patient Ancestry Best URD NW Europe (n=60) East Europe (n=40) South Europe (n=39) Mix: Europe (n=43) Asian (n=19) African (n=33) Hispanic (n=36) Middle East (n=6) Mix: Non-Europe (n=5) 9–10/10 53 (88%) 33 (82%) 23 (59%) 31 (72%) 4 (21%) 14 (42%) 16 (44%) 5 (83%) 3 (60%) ≤8/10 7 (12%) 7 (18%) 16 (41%) 12 (28%) 15 (79%) 19 (58%) 20 (56%) 1(17%) 2 (40%) Best CB 5–6/6 48 (80%) 30 (75%) 20 (51%) 30 (70%) 14 (74%) 19 (58%) 22 (61%) 4 (67%) 4 (80%) 4/6 11 (18%) 8 (20%) 13 (33%) 12 (28%) 5 (26%) 6 (18%) 10 (28%) 2 (33%) 0 (0%) No CB 1 (2%) 2 (5%) 6 (16%) 1 (2%) 0 (0%) 8 (24%) 4 (11%) 0 (0%) 1 (20%) The ancestry of the 201 patients who were transplanted and the 15 not transplanted due to lack of suitable graft is shown in Table 2. The remaining 93 patients were not transplanted for other reasons. Table 2: Patient Ancestry if Transplanted or No Graft 8–10/10 URD (n=149) 4–6/6 CB (n=52) No graft (n=15) NW Europe 47 (32%) 4 (8%) 1 (7%) East Europe 27 (18%) 6 (12%) 0 (0%) South Europe 15 (10%) 8 (15%) 3 (20%) Mix:Europe 27 (18%) 8 (15%) 1 (7%) Asian 6 (4%) 7 (13%) 0 (0%) African 11 (7%) 10 (19%) 6 (40%) Hispanic 10 (7%) 8 (15%) 3 (20%) Middle East 5 (3%) 1 (2%) 0 (0%) Mix:Non-Europe 1 (1%) 0 (0%) 1 (7%) URD transplant recipients were predominantly (68%) NW, Eastern, or mixed European with Asian, African and Hispanic patients combined accounting for only 18%. In contrast, only 4 (8%) of CBT recipients were NW European. While these patients received CB due to urgency (n=1), patient preference (n=1), or MD preference over mismatched URD (n=2), the remaining 48 (92%) of CBT recipients including 15% Southern Europeans and 49% non-Europeans (13% Asian, 19% African, 15% Hispanic, 2% Middle Eastern) did not have other donor options. Of 15 patients (5% of the 309 total) not transplanted due to lack of any HSC source 10 were non-European including 6 of African ancestry. Notably, the median weight of this “no graft” group [87kg (range 66–151)] was significantly higher than CBT [70kg (range 13–109)] recipients (p