ALBERT

Description: Standard therapy in the United States for malignancy-associated hyperuricemia consists of hydration, alkalinization, and allopurinol. Urate oxidase catalyzes the enzymatic oxidation of uric acid to a 5 times increased urine soluble product, allantoin. Rasburicase is a new recombinant form of urate oxidase available for clinical evaluation. This multicenter randomized trial compared allopurinol to rasburicase in pediatric patients with leukemia or lymphoma at high risk for tumor lysis. Patients received the assigned uric acid-lowering agent for 5 to 7 days during induction chemotherapy. The primary efficacy end point was to compare the area under the serial plasma uric acid concentration curves during the first 96 hours of therapy (AUC0-96). Fifty-two patients were randomized at 6 sites. In an intent-to-treat analysis, the mean uric acid AUC0-96 was 128 ± 70 mg/dL.hour for the rasburicase group and 329 ± 129 mg/dL.hour for the allopurinol group (P 

Description: Allogeneic stem cell transplantation (AlloSCT) from HLA-matched unaffected sibling donors (MSD) has been successful for high-risk SCD, and is the only known curative therapy (Freed/Cairo et al, BMT, 2012). We have recently demonstrated 100% event free survival and absence of sickle cell symptoms following reduced toxicity conditioning and HLA matched sibling bone marrow or cord blood AlloSCT (Bhatia/Cairo et al, BMT, 2014). However, 5 out of 6 children who might benefit from this therapy lack an HLA matched family donor. Identifiable matched unrelated adult donors (URD) in this ethnic group are extremely limited and results from unrelated cord blood transplants are poor (Radhakrishnan K/Cairo et al., BBMT 2013, Kamani et al., BBMT, 2012). We previously demonstrated the use of positive CD34 selection followed by T cell add back (2 x 105 CD3/kg) from unrelated donors in pediatric recipients with both malignant and nonmalignant disease lead to 100% engraftment with minimal acute GVHD (aGVHD). In a high-risk FHI TCD thalassemia study, 16/22 cases engrafted without aGVHD and with 90% overall survival (Sodani et al., Blood, 2010). FHI TCD AlloSCT could expand the donor pool and improve outcomes for patients with high risk SCD. This SCD consortium trial is investigating the safety, feasibility, EFS, donor chimerism, graft failure, aGVHD and chronic GVHD (cGVHD), and infectious mortality after FHI TCD AlloSCT in high-risk SCD patients (Figure 1). High risk features included one or more of the following: ≥1 CVA, ≥2 ACS, ≥3 VOC in past 2 years, or 2 abnormal TCDs. Patients (2-20.99 yrs) without an 8/8 HLA MSD or URD and who have ≥1 high-risk SCD features were eligible. Patients received hydroxyurea 60 mg/kg/d and azathioprine 3mg/kg/d, day -59 – day -11, fludarabine (30mg/m2/d x5d), busulfan (3.2 mg/kg/d x4d [

Description: The risk of developing post transplant lymphoproliferative disease (PTLD) following solid organ transplantation (SOT) in children is in large part dependent on the specific organ transplanted and the degree of immune suppression post SOT (Webber et al Lancet 2006; Dharnidharka et al Transplantation 2001; Newell et al Transplantation 1996). However, the importance of expression of CD20 and/or Epstein-Barr virus (EBV) as prognostic factors for development and survival of pediatric PTLD after SOT in young patients are poorly understood. We previously demonstrated the safety and efficacy of cyclophosphamide, prednisone and rituximab (CPR) in CD20+ PTLD (Orjuela/Cairo, CCR 2005). We now report on our experience in children, adolescents and young adults with PTLD following SOT treated at a single institution from 1990–2008 and on the prognostic significance of expression of CD20 and EBV in this population. 45 SOT pts (28 heart, 11 liver, 6 kidney) were diagnosed with PTLD (53.3 % female) at a mean onset of 45±43 months (mo) post primary SOT (4–153). Three patients had multiple SOT. Age at diagnosis of PTLD ranged from14 to 287 mo with mean 118 (SD=77) mo. EBV and CD20 status were evaluated in all evaluable tumor sites. CD20 status was categorized as positive when all tumor sites expressed CD20 (by IHC) and negative when only some or no tumor sites expressed CD20. EBV status was categorized as positive when any tumor sites were EBV positive (by ISH), and negative when no tumor sites were EBV positive. Of 40 evaluable tumors (11 monomorphic, 19 polymorphic, 5 early lesions, 2 T-cell lymphomas, and 3 rarer types (2 HD, 1 multiple myeloma like), 32 (80%) had detectable EBV, while 28 (70%) were classified as CD20 positive. EBV expression was unrelated to age at SOT. Those patients whose PTLD expressed CD20 and/or EBV had shorter time interval between last SOT and the onset of PTLD (CD20 positive vs negative (mean±SD): 28±31 mo vs 64±44 mo, p

Description: Purpose: To determine the safety and efficacy of high dose cyclophosphamide, BCNU and etoposide (CBV) chemotherapy followed by autologous non-purged PBSCT in children with Hodgkin’s (HD) and non-Hodgkin’s lymphoma (NHL) who have either failed primary induction therapy or have experienced a first relapse. Methods: At study entry, patients received 2–4 courses of reinduction therapy as determined by the local institution. When a CR or PR was achieved, G-CSF mobilized PBSCs were harvested and patients underwent autologous PBSCT after a preparative therapy of cyclophosphamide 6000 mg/m2, BCNU 450–300 mg/m2, and etoposide 2400 mg/m2. Patients were to receive a set dose of 5x106 CD34 cells/kg. Patients were followed for disease status and toxicities. 69 patients (38 HD, 31 NHL) were entered onto study between April 1998 and June 2002. Survival statistics were calculated as Kaplan Meier estimates. Results: 41/69 (27/38 HD, 14/31 NHL) achieved a CR/PR at the conclusion of reinduction; 14 failed due to PD; 7 had SD; 7 were inevaluable. 38 patients (27 HD, 11 NHL) proceeded to autologous PBSCT. Overall 28/38 (20 HD, 8 NHL) of the transplanted patients survive and 21/28 (15 HD, 6 NHL) are progression free. The survival rates at 12 months and 24 months were 88%(±6) (HD 92%(±6), NHL 78%(±14)) and 73%(±10) (HD 76%(±11), NHL 65%(±22)), respectively. The rates of PFS at 12 months and 24 months were 65%(±8)(HD 72%(±9); NHL 46%(±17)) and 53%(±11) (HD 56%(±12); NHL 46%(±19)), respectively. 10 patients died after PBSCT. The causes of death were PD (N=5), infection (N=4), and toxicity (N=1). The first 17 patients received BCNU 450 mg/m2 and 8 of these experienced grade 3 or 4 pulmonary or renal toxicity. The dose was thus dropped to 300 mg/m2 and an additional 21 patients underwent PBSCT and 3 of these patients developed grade 3 or 4 pulmonary or renal toxicity. The incidence of grade 3 or 4 pulmonary of renal toxicity at 300mg/m2 was significantly lower than that at 450 mg/m2 (p=0.04, Fisher’s exact test). Conclusions: For children with primary resistant or first relapsed lymphoma who achieve a CR or PR after reinduction, CBV preparative therapy followed by PBSCT for children with primarily resistant or relapsed lymphoma results in an acceptable survival but a lower PFS due to a high relapse rate following transplant. A BCNU dose of 300 mg/m2, but not a dose of 450 mg/m2 is well tolerated by these heavily treated patients.

Description: Abstract 2069 Over the past decade there has been a shift in treating pediatric patients with RTC followed by allogeneic stem cell transplantation (alloSCT) for malignant and non-malignant diseases (Satwani/Cairo et al, BBMT 2005). Advantages of RTC over MAC include reduced acute short- and long-term late complications, reduced risk of infections, and improved survival. However, relatively little is known about the impact of RTC on the longitudinal quality of life (QOL) of these patients following alloSCT. The objective of this study was to compare the physical, emotional, and social functioning of children who received RTC versus MAC regimens prior to and after alloSCT. Hierarchical linear modeling (HLM) was used to explore trends in the PedsQL 4.0 physical, emotional, and social functioning and select individual items of 80 children ≥ 5 years of age undergoing alloSCT between Nov. 2002 and Dec. 2008. QOL was assessed once pre-alloSCT and on days 100, 180, 365, and 730, post-alloSCT. In addition, post hoc exploratory analyses were performed to further evaluate the effect of RTC and MAC regimens on QOL outcomes. If significant between- or within-group differences were observed for any of the three sub-scales, HLM procedures were performed for each sub-scale item to identify the item(s) affected by treatment. Since post hoc analyses were exploratory no adjustments were made in the alpha level. This secondary data analysis was not powered to detect statistically significant differences. Effect size (ES) calculations were included to describe the magnitude of change in scores from baseline and were calculated using the within patient standard deviation (SD), whereas the magnitude of the difference in scores between RTC and MAC regimens were calculated using the between group SD and interpreted according to Cohen's thresholds. Mean age: 12.67 years; malignant/non-malignant 59%/41%; RTC/MAC 54%/46%. There was no significant difference (p = 0.87) between the baseline mean emotional functioning scores of patients treated with RTC (M = 75.90) or MAC (M = 75.30). In addition, there was no appreciable difference (p = 0.08) in the slope function between these two groups. Similarly, the baseline mean social functioning scores did not differ (p = 0.51) between groups with the RTC patients (M = 81.62) having equivalent function to MAC patients (M = 83.73). Furthermore, the rate of change over time between the two groups was not significantly different (p = 0.96). However, a significant change from baseline in overall physical functioning was estimated for RTC (M = 66.84) compared to MAC (M = 68.05) with RTC improving at a rate of 0.48 points per month (ppm)/ 5.82 points per year (ppy) and MAC improving by 0.04ppm/ 0.52ppy (t = 2.34; p = 0.02) (Figure 1). At 2-years post-alloSCT a moderate difference was estimated (ES = 0.71 SD) with RTC scoring 9.35 points higher than MAC. Post hoc analyses of physical functioning items revealed baseline impairments in lifting something heavy for both RTC (M = 55.55) and MAC (M = 56.06). However, the RTC group rapidly improved by 7.12ppm (t = 2.07; p = 0.03) with no lifting problems estimated by 6-months post-alloSCT. MAC improved by 1.27ppm, with some lifting difficulties predicted throughout the follow-up period. A large effect size difference in lifting scores was estimated at 2-years post-alloSCT with MAC scoring 6.74 SD lower than RTC. Greater improvements in fatigue scores were predicted for RTC (M = 60.11; 3.39ppm) compared with MAC (M = 65.19; 2.46ppm) (p 〉 0.05) with no fatigue estimated by 1-year post-alloSCT for both groups. RTC pain scores improved from baseline by 2.82ppm (M = 66.02) and 5.35ppm for MAC (M = 66.95). No difficulties with pain were estimated by 1-year for RTC and by 6-months for MAC. Emotional and social functioning were not influenced by the intensity of conditioning regimen received. Deficits in physical functioning appeared transient with most perturbations expressed in the acute post-alloSCT period. RTC versus MAC prior to AlloSCT in pediatric recipients was associated with significantly fewer deficits and faster recovery in overall physical functioning, strength, and fatigue. This study highlights the importance of including QOL as part of the treatment investigations to further define outcomes that are related to the intensity of conditioning regimens used in pediatric alloSCT.Figure 1:Estimated change in physical functioning between RTC vs. MAC in pediatric alloSCT recipientsFigure 1:. Estimated change in physical functioning between RTC vs. MAC in pediatric alloSCT recipients Disclosures: No relevant conflicts of interest to declare.

Description: BACKGROUND: Primary Mediastinal large B-cell lymphoma (PMBL) and Hodgkin lymphoma (HL) are two of the most common malignancies among adolescents and young adults (AYA). PMBL and HL share similar molecular features by gene expression profiling and pathogenesis (Rosenwald et al., J Exp Med., 2003). HL represents only approximately 4-5% of all cancers in children younger than 15 years of age, but is the most common cancer in the 15-35 yrs AYA group. While the prognosis is excellent with AYA HL, there are significant late effects secondary to chemoradiotherapy and therefore new targeted agents are needed to avoid these morbid late effects in HL (Hochberg/Cairo et al., Br. J. Haem., 2009). Frequent gains of chromosome 9p exhibit higher Janus Kinase 2 (JAK2) transcript levels with increased JAK2 activity (Bentz et al., Genes Chromosomes Cancer, 2001), suggesting aberrant activity of JAK2 and Signal Transducer and Activator of Transcription (STAT) pathways, which may in part play an important role in the pathogenesis of HL and PMBL. Ruxolitinib is a potent and selective JAK1/JAK2 inhibitor against myeloproliferative neoplasms (MPNs) that consistently exhibits dysregulation of the JAK1/JAK2 pathway, including those MPNs with a JAK2V617F mutation. Ruxolitinb also inhibits JAK2/STAT5 signaling in vitro and in a murine model of MPN (Quintas-Cardama et al., Blood, 2010). OBJECTIVES: We hypothesize that ruxolitinib may potentially function as targeted therapeutic agent for both PMBL and HL and therefore, investigated the efficacy of ruxolitinib in PMBL and HL cells xenografted into NSG mice. METHODS: Cell proliferation and apoptosis analysis were assessed using MTS and Caspase-3/7 assay (Promega), respectively. The expression of protein was examined by immunoblotting and statistical significance was determined by Student t-test. Karpas-1106P PMBL cell line and L-428 HL cell line were stably transfected with a firefly luciferase expression plasmid (ffluc-zeo), kindly provided by Laurence Cooper MD, PhD. The six to eight weeks old Female NSG (NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ) mice were from Jackson laboratory. The ffluc-zeo NSG mice were irradiated (2.5 Gy) and then were subcutaneously injected with 1x106 ffluc-zeo Karpas-1106P or L-428 tumor cells. Tumor burden and tumor progression were monitored by bioluminescence imaging (BLI) using the Xenogen IVIS-200 (Caliper Life Sciences) for up to 60 days. Mice were orally gavaged with either vehicle or ruxolitinib (45.0mg/kg or 90.0mg/kg) (generously provided by Incyte Corporation, Wilmington, DE, USA) for 21 days. Survival rates were analyzed by the Kaplan-Meier method and differences evaluated by log-rank test using the Prism Version 6.0 software. RESULTS: We observed that ruxolitinib significantly decreased the phosphorylation of STAT3, -5 and -6 in Karpas-1106P PMBL and L-428 HL cells. The reduction in cell proliferation by 10uM ruxolitinib are 41% in Karpas-1106P (p

Description: Abstract 3504 The only known curative therapy for patients with SCD is a matched family donor AlloSCT (Walters et al, NEJM, 1996). Complications after myeloablative AlloSCT are numerous and include death, graft versus host disease (GVHD), and infections, making reduced toxicity conditioning regimens more appealing. A major obstacle allowing most SCD patients to undergo SCT is the lack of an unaffected, HLA-matched identical sibling (Bhatia et al, BMT, 2008). Umbilical cord blood (UCB) has been proven to be an excellent alternate donor source that can safely reconstitute hematopoiesis after AlloSCT in pediatric recipients with non-malignant conditions (Cairo et al, BBMT, 2008). In this study, we report the results of a RTC regimen followed by an AlloSCT from matched family and unrelated UCB donors in selected patients with symptomatic SCD. Between August 27, 2004 and March 2, 2010, 18 patients (14M:2F) with symptomatic SCD (HbSS=10, HbSC=4, HbSßThal=4) underwent an AlloSCT. Indications for SCT included: ACS (n=8), CVA (n=2), multiple VOC (n=9), splenic sequestration (n=6) and retinopathy (n=1). Conditioning was Bu (4mg/kg × 4d 〈 4 yrs and 12.8mg/kg × 4d 〉 4 yrs), Flu (30mg/m2 × 6d), and Alemtuzumab (2mg/m2 × 1d, 6mg/m2 × 2d, and 20mg/m2 × 2d). Median age was 6.29 yrs(1.3–19.2). Median follow-up was 26 months. Donor sources: 8-6/6 HLA-matched sibling bone marrow (BM), 2–6/6 sibling UCB, 1–6/6, 4–5/6 and 3–4/6 unrelated UCB. Donors were HbAA (n=13), HbAC (n=1), HbAS(n=3), or ßThal trait (n=1). Sibling BM recipients received a median total nucleated cell (TNC) dose/kg of 7.16 × 108 (range 2.27–11.31) and a median CD34 cell dose/kg of 5.38 × 106 (range 1.50–6.83). Recipients of related or unrelated UCB received a median TNC dose/kg of 4.35 × 107 (range 3.40–9.10) and a median CD34 cell dose/kg of 2.21 × 105 (range 0.60–7.94). All received tacrolimus and mycophenolate mofetil as GVHD prophylaxis (Bhatia/Cairo et al, BBMT, 2009) and phenytoin or keppra as seizure prophylaxis for 180 days post SCT. Patients receiving sibling donor AlloSCT had a median time to neutrophil engraftment of 16 days (range 13–41). Among evaluable unrelated UCBT recipients, median time to neutrophil engraftment was 34 days (range 27–47). Four patients (all unrelated UCBT) experienced primary graft failure at day +60 post-SCT secondary to CMV (n=2), adenovirus, and low Bu Css levels with early withdrawal of MMF. Patients with sibling donors had a median time to platelet engraftment of 26 days (range 17–75). Of evaluable unrelated UCB recipients, median time to platelet engraftment was 54 days (range 43–70). Patients achieved mean whole blood donor chimerism of 71.0, 79.6, 85.7, 92.9, 90.7% and 93.2% at days 30, 60, 100, 180, 365 and 730 post-transplant, respectively. Mean erythroid (CD71) donor chimerism at these time points was 78.1, 81.1, 86.6, 90.5, 87.9% and 94.0%, respectively. Patients with non-sickle cell trait donors had median HbS levels of 0% at 1 yr (n=8) and 2 yrs (n=3) post-SCT; those with sickle cell trait donors had median HbS levels of 38.3% at 1 yr (n=3) and 39% at 2yrs (n=3) post-SCT. Among evaluable patients, the Kaplan-Meier probability of grade II-IV acute GVHD is 33.3% and of chronic GVHD is 8.3%. Among the ten donor-recipient pairs in which at least one member of the pair had CMV positivity, four experienced CMV reactivation on days +13, +26, +30 and +32 (BM: n=2, unrelated UCB: n=2). Of the four patients with primary graft failure (all unrelated UCBT recipients), one resumed chronic transfusions, two died of complications from disseminated CMV and adenoviral infections, and one received a second myeloablative SCT 1 yr after initial SCT and died of fungal sepsis. Among all patients, the Kaplan-Meier probability of OS is 81.8% (100% with sibling donors, 62.5% with UCB donors) and of EFS is 77.8% (100% with sibling donors, 50% with UCB donors) with none of these patients showing any evidence of SCD symptomatology post-SCT. The longest follow-up is 2134 days. In summary, we report the largest experience of RTC and matched family AlloSCT in selected children with symptomatic SCD with persistent long-term donor chimerism and absence of SCD symptoms or progression of disease. However, with the high incidence of viral infections and toxic deaths following unrelated UCBT, it is too premature to extend this treatment option to those SCD patients lacking a sibling donor. Disclosures: No relevant conflicts of interest to declare.

Description: Background: Myeloablative conditioning (MAC) and reduced toxicity conditioning (RTC) followed by UCBT (matched at 4-6/6 HLA loci) in children with malignant and non-malignant diseases is safe and effective (Wagner/Cairo et al, Blood, 1996; Geyer/Cairo et al, BJH, 2011). However, there is a low concentration of CD34+ hematopoietic progenitor cells (HPCs) in banked UCB (Cairo/Kurtzberg et al, Transfusion, 2005) compared to bone marrow or peripheral blood, leading to delayed hematopoietic reconstitution and 10-20% incidence of graft failure (Cairo et al, Blood, 1997; Cairo et al, Transfusion, 2005; Satwani/Cairo et al, BBMT, 2013). Human placenta-derived stem cells (HPDSCs) are rich in HPCs and HPC colony forming unit capabilities, low in HLA Class I and II expression, low in T-cell content, and have regenerative, anti-inflammatory, and immunosuppressive properties (Cairo et al, BMT, 2015). Mendez-Ferrer et al have demonstrated that HPDSCs enhance in-vivo engraftment when combined with UCBT in NOD-SCID animals (Mendez-Ferrero et al, Nature, 2010). Objective: To determine the safety of administering unrelated donor HPDSC in conjunction with unrelated single or double UCBT following MAC or RTC in children and adults with malignant and non-malignant diseases and to determine the time to hematopoietic engraftment, immune reconstitution and probability of donor chimerism. Methods: Patients ≤55 years of age with malignant and non-malignant diseases with a single UCB 5-6/6 HLA match and TNC ≥ 3.5x 107/kg, or double UCB 4-6/6 HLA match and combined TNC 〉5.0 x 107/kg are eligible. HLA typing was performed by serology for Class I A and B and by high resolution DNA typing of DRB1. Patients received either fully myeloablative or reduced toxicity pre-UCBT conditioning as indicated for the targeted disease followed by single or double UCB plus HPDSC infusion. All patients received filgrastim (G-CSF) starting at least 24 hours after the HPDSC infusion until myeloid engraftment and GVHD prophylaxis with tacrolimus or cyclosporine plus mycophenolate mofetil. Results: Twenty one patients have been enrolled to date: mean age 11 (0.31-34.9) years, 11 males, 10 females. Fourteen subjects had malignancies (relapsed/refractory or hypodiploid precursor B-ALL (n=7), relapsed/refractory or high risk AML (n=5), T-cell ALL induction failure (n=1), and T-cell lymphoblastic lymphoma (n=1)) and seven had non-malignant disorders (adrenoleukodystrophy (n=1), chronic granulomatous disease (n=1), congenital amegakaryocytic thrombocytopenia (n=1), bone marrow failure (n=1), SCID (n=1), severe aplastic anemia (n=1), and dyskeratosis congenita (n=1)). Fourteen patients received single UCBT followed by HPDSC infusion, and seven patients received double UCBT followed by HPDSC infusion. There were no severe adverse events associated with the HPDSC infusions. Median time to neutrophil and platelet engraftment were 22 (13-53) and 45 (20-98) days post UCBT, respectively. Mean percent of whole blood donor chimerism at days 30, 60, 100 and 180 were 97% (SEM 1.25), 99%, (SEM 0.36), 99% (SEM 0.39), and 97.9 (SEM 1.31), respectively. Average percent of whole blood HPDSC chimerism was

Description: Background SCD is a chronic debilitating disease secondary to frequent veno-occlusive events resulting in chronic organ damage, including cerebral vasculopathy, acute chest syndrome (ACS), pulmonary hypertension and a significantly shortened life-span (Bunn et al, NEJM, 1997; Lanzkron et al, PHR, 2013; Platt et al, NEJM, 1994). Importantly, SCD survivors also develop significant defects in neurocognition, especially processing speed and have a poor HRQL (Stotesbury et al, Neurology, 2018); Vichinsky et al, JAMA, 2010; Panepinto et al, BJH, 2005). To date the only cure for SCD patients has been HLA matched sibling AlloSCT following either myeloablative (MAC) or reduced toxicity conditioning (RTC), (Walters et al, NEJM, 1996; Bhatia/Cairo et al, BMT, 2014; Talano/Cairo et al, EJH, 2015; Gluckman et al, Blood, 2017). Unfortunately, only approximately 15% of patients have an unaffected HLA matched sibling donor (Mentzer et al, AJPHO, 1994). We previously demonstrated the safety and efficacy of CD34 enrichment and mononuclear cell (MNC) addback (2 x 105 CD3/kg) in pediatric matched unrelated donor recipients (Geyer/Cairo et al, BJH, 2012). We now report the long term results of MAC and familial HISCT utilizing CD34 enrichment and MNC (CD3) addback in high risk SCD recipients. Methods SCD patients with one or more high risk features (cerebral vasculopathy, repetitive ACS, repetitive VOC, abnormal TCD requiring RBC TX) underwent MAC and parental HISCT consisting of hydroxyurea, azathioprine, fludarabine, busulfan, cyclophosphamide, thiotepa, r-ATG and TLI and PBSCT utilizing CD34 enrichment (10x106 CD34/kg) (Miltenyi®) and MNC addback (2x105 CD3/kg) and tacrolimus AGVHD prophylaxis x 100 days as we have previously described (Talano/Cairo et al, ASH, 2017). Donor chimerism in WBC and RBC (CD71) enriched fractions was determined centrally as we have previously described (Geyer/Cairo et al, BJH, 2012). AGVHD & CGVHD were determined utilizing the Glucksberg and NIH consensus criteria, respectively. Transthoracic echocardiogram, TRJ velocity, PFTs, MRI/MRA were performed at baseline and 2 years. Neurocognitive testing utilizing DIVERGT screening was performed at baseline and 2 years as we have previously described (Vichinsky et al, JAMA, 2010; Krull et al, JCO, 2008). HRQL testing utilized the CHRIS-General and CHRIs-HSCT (age appropriate) at baseline and Days +45, 100, 180, 365 and 730 post HISCT as we have previously described (Kelly/Parsons et al, PBC, 2012). Results Among the 19 HISCT recipients, the mean±SEM age was 13.1±1.2 years (3.3-20.0) years, gender 12/7 (M/F). There were 18 parental haploidentical donors with mean±SEM age of 41.3±1.8 (30-55) years, gender 15/3 (F/M). The mean±SEM CD34 enriched PBSC infused was 10.94±0.4x106/kg and MNC addback (2 x 105 CD3/kg). The median time to neutrophil and platelet engraftment was day +9 and +19, respectively. The 1yr mean±SEM whole WBC and RBC (CD71) mixed donor chimerism was 97.1±1.4 and 96.4±2.0%, respectively. The cumulative incidence of grade II-IV AGVHD and CGVHD was 6.2% and 6.7%, respectively (Figure 1A). The probability of 1yr EFS was 90% (CI95 64-97%). In comparison from baseline to 2yr post HISCT, PFTs were stable to improved with a significant improvement in conductance (sGAW) (p