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Background We and others have previously reported the safety of allogeneic stem cell transplantation in children with SCD without sibling HLA matched bone marrow donors who commonly have SCDT. The majority of the sibling donors donated bone marrow and received G-CSF mobilized PBSCs (Bhatia/Cairo et al, BMT 2014; Gluckman et al, Blood 2017). Furthermore, only 14-18% of siblings can serve as donors based on HLA match and presence of SCD (Mentzer, Am J Ped Hem/Onc 1994; Walters, BBMT 1996). Unrelated cord blood as a donor source for SCD patients was associated with unacceptable primary graft failure rates (Radhakrishnan/Cairo, BBMT 2013). MUD HSCT resulted in unacceptably high rates of CGVHD (Shenoy et al, Blood 2016). Parental FHI SCDT PBSCs represent an alternative donor source. However, little is known about G-CSF PBSC mobilization in older donors with SCDT. GCSF mobilization of PBSC in homozygous SCD patients in the past has been reported to be associated with major toxicity and death (Adler et al, Blood 2001). Objective To determine if FHI PBSC mobilization in older adult donors with SCDT is safe and effective. Methods Eighteen FHI donors with SCDT received 15mg/kg/d GCSF divided BID x4 days. PBSC leukapheresis on day 5, repeating qd until 10 × 106 CD34/kg and 2 × 105 CD3/kg (minimum) were cryopreserved. CD34+ enrichment utilized the CliniMACS® System (generously provided by Miltenyi), with 2 × 105 CD3/kg T-cell add-back before HSCT as we have previously described (Geyer/Cairo, BJH 2011). Donor chimerism assays for whole blood CD3, CD71, and CD56 were performed post-HSCT. Results Fifteen female/3 male FHI donors with SCDT were mobilized: mean age 41 yrs (30-55). The most common donor side effect was grade 1 bone pain (n = 11). Other side effects were grade 1 nausea/vomiting (n = 3), grade 1 headache (n = 2), grade 1 dizziness (n = 1), grade 1 fatigue (n = 2), grade 1 abdominal pain (n = 2), grade 3 bone pain (n = 1), and grade 3 thrombocytopenia (n = 1). The mean ± SEM cryopreserved CD34 count was 12.9 ± 0.8 × 106/kg recipient wt with the mean ± SEM yield 533.69 ± 48.9 × 106. Mean ± SD log T-cell (CD3) depletion was 4.84 ± 0.58 (Fig. 1). 100% of patients achieved neutrophil engraftment at a median of 9 days (range 6-13), and 92.1% of patients achieved platelet engraftment at a median of 19 days (range 8-90) (Fig 2A/2B, respectively). Mean ± SEM Blood and CD71+ (RBC) donor chimerism was 97 · 1 ± 1.4 and 96 · 4 ± 2.0%, respectively. Conclusion These data suggest that adult FHI stem cell donors with SCDT undergoing GCSF mobilization for PBSC collection is safe and well-tolerated with only minor temporary adverse events. PBSC collection and CD34 enrichment was effective and resulted in successful SCD recipient engraftment and long-term donor chimerism. Further studies are needed to evaluate the long-term outcome of high-risk SCD patients undergoing FHI AlloHSCT R01FD004090. [ABSTRACT FROM AUTHOR]

Myeloablative conditioning and allogeneic hematopoietic stem cell transplant (alloHSCT) in children with acute myeloid leukemia (AML) in first complete remission (CR1) may be associated with significant acute toxicity and late effects. Reduced-intensity conditioning (RIC) and alloHSCT in children is safe, feasible, and may be associated with less adverse effects. Gemtuzumab ozogamicin (GO) induces a response in 30% of patients with CD33 + relapsed/refractory AML. The dose of GO is significantly lower when combined with chemotherapy. We examined the feasibility and toxicity of RIC alloHSCT followed by GO targeted immunotherapy in children with CD33 + AML in CR1/CR2. Conditioning consisted of fludarabine 30 mg/m 2 × 6 days, busulfan 3.2 to 4 mg/kg × 2 days ± rabbit antithymocyte globulin 2 mg/kg × 4 days followed by alloHSCT from matched related/unrelated donors. GO was administered ≥60 days after alloHSCT in 2 doses (8 weeks apart), following a dose-escalation design (4.5, 6, 7.5, and 9 mg/m 2 ). Fourteen patients with average risk AML received RIC alloHSCT and post-GO consolidation: median age 13.5 years at transplant (range, 1 to 21), male-to-female 8:6, and disease status at alloHSCT 11 CR1 and 3 CR2. Eleven patients received alloHSCT from 5-6/6 HLA-matched family donors: 8 received peripheral blood stem cells, 2 received bone marrow, and 1 received related cord blood transplantation. Three patients received an unrelated allograft (two 4-5/6 and one 9/10) from unrelated cord blood unit and bone marrow, respectively. Neutrophil and platelet engraftment was observed in all assessable patients (100%), achieved at median 15.5 days (range, 7 to 31) and 21 days (range, 10 to 52), respectively. Three patients received GO at dose level 1 (4.5 mg/m 2 per dose), 5 at dose level 2 (6 mg/m 2 per dose), 3 at dose level 3 (7.5 mg/m 2 per dose), and 3 at dose level 4 (9 mg/m 2 per dose). Three of 14 patients received only 1 dose of GO after alloHSCT. One patient experienced grade III transaminitis, which resolved; no grade IV transaminitis, no grade III/IV hyperbilirubinemia, or sinusoidal obstructive syndrome were observed. The second dose of GO was given at median of 143 days (range, 120 to 209) after alloHSCT. Probability of grades II to IV acute and chronic graft-versus-host disease were 21% and 33.5%, respectively. Probability of overall survival after RIC alloHSCT and GO consolidation at 1 and 5 years was 78% and 61%, respectively. Probability of 5-year event-free survival after RIC alloHSCT and GO consolidation in patients in CR1 was 78%. No dose-limiting toxicities probably or directly related to GO were observed in this cohort. This preliminary data demonstrate that RIC followed by alloHSCT and consolidation with GO appears to be safe in children and adolescents with CD33 + AML in CR1/CR2. A phase II trial is currently underway investigating this approach with a GO dose of 9 mg/m 2 per dose. [ABSTRACT FROM AUTHOR]

Sickle cell disease (SCD) is a hemoglobinopathy and vasculopathy resulting in vaso-occlusive crises, chronic end-organ damage, and shortened life span. The only curative therapy is allogeneic stem cell transplant (AlloSCT) (Talano/Cairo, EJH, 2015). Unfortunately, only approximately 16% of the sickle cell population has an HLA matched unaffected sibling (Bhatia/Cairo, BMT, 2014). We have demonstrated the safety and efficacy of familial haploidentical transplants (FHI) in this population with 100% engraftment (Cairo et al, JAMA Peds, 2019). However, the incidence of sinusoidal obstructive syndrome (SOS) in SCD AlloSCT recipients is approximately 32% (McPherson, BMT, 2011). Defibrotide primarily targets endothelium and can reduce endothelial cell injury (Falanga et al, Leukemia, 2003 and Scallia et al, Clin Pharm, 1996). Corbaciolgu et al (Lancet 2012) demonstrated the safety and efficacy of prophylactic defibrotide in high-risk pediatric AlloSCT recipients to significantly reduce the incidence of SOS. To determine the safety and efficacy of defibrotide prophylaxis for SOS in children, adolescents and young adults (CAYA) with high-risk SCD following MAC and FHI AlloSCT, utilizing CD34+ selection with CD3 addback. Patients with SCD aged 2 to 35 years with high-risk SCD (stroke, ≥2 acute chest syndrome in past 2 years, ≥3 pain crises in last 2 years, abnormal TCD study, ≥1 silent infarct lesion on MRI) were enrolled after being consented (NCT02675959). Patients were in two cohorts (2 to 17.99 years and 18 to 34.99 years of age) for age-based analysis and treatment (Table 1 and 2). All patients received a MAC regimen prior to receipt of an FHI with CD34+ selection and CD3 addback peripheral blood stem cell transplantation (PBSCT), as we have already demonstrated (Cairo et al, ASH, 2018). Defibrotide was given day -10 during conditioning through day +21 following transplant. Baseline studies of organ function and biomarkers were obtained prior to transplantation. We have enrolled eight patients, five in cohort 1 (median age 9.9 years) and three in cohort 2 (median age of 24 years) with a gender ratio (M/F) of 4/4. Patients had hemoglobin SS (n=7) or hemoglobin SC (n=1). Patients had either a maternal (n=7) or sibling (n=1) donor. Patients had early neutrophil engraftment (median day +11 (day +7 to day +14)). All tolerated 109 ± 11doses of defibrotide. There were no severe adverse or bleeding events probably or directly related to defibrotide. No patient developed SOS. The preliminary data suggests defibrotide is safe and well tolerated in CAYA patients with high-risk SCD following MAC and FHI AlloSCT, utilizing CD34+ selection with CD3 addback. A larger cohort and/or follow-up will be required to confirm these preliminary findings. Supported by FDA R01FD004090 and Jazz Pharmaceuticals. [ABSTRACT FROM AUTHOR]

There is an increase in utilizing matched unrelated donors (MUD) & haploidentical donors over the past 20 years (Cairo et al, Biol Blood and Marrow Transplant , 2008). However both of these allogeneic donor sources are associated with severe acute graft -versus -host diseases. We have previously reported the success of CD34 enrichment utilizing the Isolex® device (Geyer/Cairo et al, British Journal of Hematology , 2012). Positive selection of CD34+ cells with the CliniMACS® system has been shown as a highly effective technique for obtaining a T-lymphocyte-depleted product. We report our results with 55 procedures performed in the last two years at our Cell and Tissue Engineering Laboratory. To evaluate the impact of overnight storage on cell recovery, viability and sterility before processing, as well as to evaluate the CD34 +cells recovery in the final product. From October 2017 to August 2019, after consent, 37 donors were mobilized with G-CSF. Fifty-five leukapheresis harvests were performed using the Spectra Optia® Apheresis System. Twenty-six were stored overnight at 4°C before processing using the CliniMACS® device. WBC counts were performed using the Sysmex XE hematology analyzer. Phenotypic analysis was performed with a FACSCalibur BD flow cytometer on samples from leukapheresis products at the day of collection (Day 0), before processing (Day 1) and after the selection. The WMC Microbiology Laboratory performed the sterility testing using BACTEC FX System. Twenty-six products were stored overnight before processing with a mean ±sem nucleated cells (NC) of 19 × 108/kg (± 2.66) and CD34+ cells of 13.8 x106/kg (± 2.93) at Day 0 and NC of 16.2 × 108/kg (± 2.62) and CD34+ cells of 13.9 x106/kg (± 3.03) at Day 1. NC and CD34+ cells content were not significantly different at Day 0 and Day 1 (respectively p =0.95 and p =0.98). The median CD34 viability at Day 1 was 99% (range 93-99%). The sterility testing were all negative. Fifty-five products showed a median starting cellularity of 8.45 × 106 CD34+ cells (range 1.4-60.3 × 106). The median post selection CD34+ cells was 6.62 × 106 (range 1.2-46.2 × 106). The mean ±sem CD34 recovery was 9.64 × 106/kg (± 1.2) (Figure 1A) with a purity of 98.5%. The final T cell reduction was a mean ±sem of 0.38 × 105/kg (± 0.08) (Figure 1B). A mean ±sem of 9.75 × 106/kg (± 0.84) of CD34+ cells was infused. To enhance engraftment, 2 × 105/kg CD3+cells were added back to the selected product. All patients engrafted at a median time of 11 days. No patient developed an infusion reaction. Overnight storage of peripheral blood stem cells does not affect CD34+ cells enrichment, viability nor safety of the leukapheresis product. Our median of 80% of CD34 recovery is higher than the recovery of previous studies (Cairo et al, JAMA Pediatrics, 2019). These data demonstrate that CD34 enrichment on the following day using CliniMACS® device is reproducible and safe in pediatric and adult allogeneic recipients. [ABSTRACT FROM AUTHOR]

The cognitive and neurological impairments associated with SCD that are due to cerebral vascular injury have been well documented (DeBaun et al, Blood, 2012). Brain abnormalities are evident on neuroimaging and cognitive domains in the areas of attention, memory, processing speed, executive functioning, and lower general intellectual functioning. Processing speed in particular is a vulnerable domain, with deficits mediating difficulties across other domains and is independently decreased in SCD patients unrelated to overt or silent infarctions (Stotesbury et al, Neurology, 2018). Van der Land et al suggests that there is a relationship between white matter tissue integrity and cognitive morbidity in SCD patients (British Journal of Hematology, 2015). Previous studies following reduced toxicity conditioning and matched sibling BMT in patients with SCD have demonstrated stable to improved CNS functioning (Walters et al, 2010, Biol BMT; Bhatia et al, BMT, 2014). We aimed to determine changes in neuroimaging and neurocognitive sequelae in individuals with high-risk SCD prior to and following myeloimmunoablative conditioning (MIAC) and FHI AlloSCT utilizing CD34 enrichment and T cell addback. Haploidentical stem cell transplant with MIAC with CD34 enrichment was performed as previously described by Cairo et al (JAMA Peds, 2019). Participants had a baseline, 1 year and 2 year MRI that were reviewed by blinded central neuroimaging, neurocognitive screener (DIVERGT, Krull, et al) and an abbreviated, standardized neurocognitive test battery (IQ, memory, attention, language, motor, processing speed) over three time points (baseline, Day +365 and Day +730). Neurocognitive domain scores were calculated for each area of functioning in patients at each timepoint. Nineteen SCD patients were enrolled and received transplant (12 males, 7 females, mean age, 13.5, range 3-21). At baseline, seven patients had evidence of an overt stroke and four patients had evidence of a silent infarct. At 1 and 2 years post-transplant, there were no new overt and/or silent infarcts, and no new cerebral vasculopathy. Intellectual functioning, memory, language and attention/executive function remained stable to improved at year one and two, respectively (Table 1). Most importantly, processing speed was significantly improved at 2 years versus baseline (p<0.026). Language functioning approached significance at 2 years versus baseline (p<0.144) (Figure 1). These preliminary studies suggest that MIAC followed by FHI AlloSCT utilizing CD34 enrichment and CD3 addback is protective against further CNS injury. Early HSCT has the potential to decrease or prevent cognitive decline and even improve neurocognitive functioning in high risk SCD recipients (supported by R01FD004090). [ABSTRACT FROM AUTHOR]

Background Myeloablative (MAC) or reduced toxicity conditioning (RTC) followed by UCBT in children with malignant and non-malignant diseases is safe and effective (Geyer/Cairo, BJH 2011). However, concentration of CD34+ HPCs in UCB is low, leading to delayed hematopoietic reconstitution and high incidence of engraftment failure (Satwani/Cairo, BBMT 2013). HPDSCs are rich in HPCs, low in HLA Class I/II expression and T-cells, and have regenerative, anti-inflammatory, and immunosuppressive properties (Liao/Cairo, Stem Cells Translational Medicine 2018). Objective To determine the safety and efficacy of HPDSC with UCBT in children with malignant and non-malignant diseases. Design/Method 4-6/6 HLA matched UCB with TNC ≥ 5 × 107/kg (4/6 HLA match) or ≥ 3.5 × 107/kg (5-6/6 HLA match) were included. Patients received MAC or RTC followed by UCB plus HPDSC infusion. GVHD prophylaxis consisted of tacrolimus and mycophenolate mofetil as previously described (Bhatia/Cairo, BBMT 2009). Results To date, 28 patients ≤18 years were enrolled, 15 males and 13 females. Mean age in years ± SD was 6.8±5.5. There were 12 patients with non-malignant disease including ALD (2), CAT (1), CGD (1), SCID (2), dyskeratosis congenita (1), congenital neutropenia (1), SAA (2), LCH (1), and SDS (1) and 16 patients with malignant disease including pre B-cell ALL- CR1 (4), pre B-cell ALL - CR2 (4), T-cell ALL – CR1 (1), AML-CR1 (4), JMML-CR1 (1), TLL - CR1 (1), and BL - CR2 (1). Mean UCB TNC±SD and CD34±SD infused were 7.7 × 107±5.0/kg and 0.48 × 106±0.59/kg, respectively. There were no SAEs associated with HPDSC infusions. Four patients were removed prior to day 180 due to progressive disease (1) and engraftment failure necessitating alternative treatment (3). Probability of neutrophil engraftment was 89.2%, median day 22 (13-53). Of neutrophil engrafted evaluable patients (n=22), the probability of platelet engraftment by day 100 was 90.9%, median day 42 (20-98). Of neutrophil engrafted, evaluable patients at day 30, 60, 100 and 180, mean whole blood UCB chimerism was 92, 99, 96 and 99%, respectively. Average whole blood HPDSC chimerism was <1% at day 30 and not detected beyond day 60. The probability of grade 2-4 aGVHD at day 100 was 17.3% (CI 95 : 0.9-51.9). Of patients without grade 2-4 aGVHD, normalization of CD3+, CD19+, and CD56+ cells occurred by day 100, and CD8+ and CD4+ cells by day 270. The probability of OS at 1 year was 78.0% (CI 95 : 55.0-90.2). Deaths occurred due to systemic adenovirus (3), RSV (1) and relapse (1). Conclusions These results suggest that UCBT with HPDSC is safe and well tolerated, has a lower than expected probability of Grade 2-4 aGVHD, and results in robust immune reconstitution. A larger cohort and longer follow-up is required to determine the clinical significance of these findings. [ABSTRACT FROM AUTHOR]

MAC or RTC followed by UCB donor allo-HSCT in children with malignant and non-malignant diseases is safe and effective (Geyer/Cairo, BJH 2011). However, concentration of CD34+ HPCs in UCB is low, leading to delayed hematopoietic reconstitution and high incidence of engraftment failure (Satwani/Cairo, BBMT 2013). HPDSCs are rich in HPCs, low in HLA Class I/II expression and T-cells, and have regenerative, anti-inflammatory, and immunosuppressive properties (Liao/Cairo, Stem Cells Trans Med 2018). To determine the safety and efficacy of HPDSCs plus UCB for allo-HSCT in children. UCB with TNC ≥ 5 × 107/kg (4/6 HLA match) or ≥ 3.5 × 107/kg (5-6/6 HLA match) were included. Patients received MAC or RTC followed by UCB plus HPDSC infusion. GVHD prophylaxis consisted of tacrolimus and MMF as previously described (Bhatia/Cairo, BBMT 2009). Twenty-eight patients ≤18 years were enrolled, 15 males. Mean age± SD was 6.8±5.5 years, (4 months-12 years). There were 12 patients with non-malignant diseases including ALD (2), CAT (1), CGD (1), SCID (2), DC (1), CN (1), SAA (2), LCH (1), and SDS (1) and 16 patients with malignant diseases including B-ALL- CR1 (4), B-ALL - CR2 (4), T-ALL – CR1 (1), AML-CR1 (4), JMML-CR1 (1), TLL - CR1 (1), and BL - CR2 (1). There were 13, 9, and 5 patients with 6/6, 5/6, and 4/6 HLA match, respectively. Mean UCB TNC±SD and CD34+ cell dose±SD infused were 0.77±0.5 × 108/kg and 0.48±0.59 × 106/kg, respectively. Mean HPDSC TNC±SD and CD34+ cell±SD dose were 0.96±3.51 × 108/kg and 0.05±0.05 × 106/kg, respectively. There were no SAEs associated with HPDSC infusions. Four patients were withdrawn for administration of alternative therapy after engraftment failure (3) or relapse (1). Probability of neutrophil engraftment by day 42 was 78.6%, median day 22 (13-53). Probability of platelet engraftment by day 100 in neutrophil engrafted patients was 86.4%, median day 42 (35-98) (Figure 1). Mean UCB chimerism was 92, 99, 96 and 99% at day 30, 60, 100 and 180, respectively. Average HPDSC chimerism was <1% at day 30 and not detected beyond day 60. Probability of grade 2-4 and 3-4 aGVHD by day 100 were 18.2% and 13.6%, respectively. Of patients without grade 2-4 aGVHD, normalization of CD3+, CD19+, and CD56+ cells occurred by day 100, and CD8+ and CD4+ cells by day 270. Probability of OS at day 180 was 86.9%. Deaths occurred due to adenovirus (3) and RSV (1). One of 16 patients with malignant disease relapsed by day 180. These results suggest that UCB plus HPDSCs for Allo-HSCT is safe and well tolerated. Median day to platelet engraftment was lower than previously reported using UCB alone (Geyer/Cairo.BJH 2011). Probability of Grade 2-4 aGVHD was lower than previously reported using UCB alone, possibly due to the immunomodulatory effect of HPDSCs (Geyer/Cairo.BJH 2011). A larger cohort and longer follow-up is required to determine clinical significance. [ABSTRACT FROM AUTHOR]

Allogeneic stem cell transplantation (AlloSCT) from an HLA-matched sibling donor is the only known curative therapy in high-risk SCD patients (Talano/Cairo, EJH , 2015). Unfortunately only about 15% of high-risk SCD patients have an HLA-matched unaffected sibling donor. T cell depletion has been employed to reduce AGVHD. We reported a very low incidence of GVHD in pediatric recipients receiving CD34 enriched HPC products with PBMNC addback from MUD donors (Geyer/Cairo et al, BJH, 2012). Rapid NK cell reconstitution after AlloSCT is associated with a significant improvement in 1yr OS (Pical-Izard, BBMT , 2015). Recently, we reported promising results for high-risk SCD patients at 1 yr follow-up after FHI CD34 enriched/PBMNC with addback with the probability of 1-yr OS 88.2% (Cairo, et al, JAMA Peds, 2019). To investigate donor chimerism, immune reconstitution and the incidence of GVHD in high-risk SCD patients following AlloSCT using FHI CD34 enrichment/PBMNC (2 × 105 CD3/kg) addback. CD34 cells were enriched using the CliniMACS® system, kindly provided by Miltenyi Biotec, with a target dose of 10 × 106 CD34+ cells/kg. PBMNC were added back to the final CD34 product at a dose of 2 × 10*5 CD3/kg. Whole blood and CD71-enriched erythroid lineage chimerism were determined by STR. Immune cell, subset reconstitution, NK function, CD107a and granzyme B were assessed by flow cytometry as previously described (Geyer/Cairo et al. BJH , 2012, Chu/Cairo et al, Can Imm Res , 2015). The cumulative incidence of grade II-IV and late AGVHD was 6.2 % and moderate and/or severe CGVHD incidence was 6.7%, respectively (Fig. 1A). There was 100% engraftment of neutrophils and platelets. The median day post-HISCT to neutrophil and platelet engraftment was +9 and +19, respectively. Whole blood donor chimerism (mean±SEM) at 1-yr, 2-ys, and 3-ys post-HISCT was 97±1%, 97±1%, 97±1%, respectively (Fig.1B). Donor chimerism for CD71-enriched erythroid lineage cells (mean±SEM) at 1-yr, 2-yrs, 3-yrs post-HISCT was 97±2%, 98±1%, 98±1%, respectively (Fig.1B). The time to recovery of minimal normal levels for CD3 (800 cells/ul), CD4 (400 cells/ul), CD8 (200 cells/ul), & CD19 cells (200 cells/ul), was approximately 365, 365, 270, and 60 days post-HISCT, respectively (Fig.1C). NK reconstitution was rapid and peaked at d+30 (36±9%) with higher level of activating receptors NKp46, NKG2D & KIR2DS and inhibitory receptors NKG2A, CD94 and KIR2DL2/3. NK cytotoxicity against K562 (E:T = 10:1) peaked at d+30 and d+180 vs pre-transplant (p<0.01) with enhanced CD107a (Fig. 1D). The PBMNC addback facilitated rapid donor chimerism & immune reconstitution with a low probability of Grade II-IV AGVHD. The rapid NK reconstitution may have in part contributed to the excellent 1yr OS in this study (FDA R01FD004090 (MSC)). This approach is comparable to the method of CD3 TCRa/b-CD19 depletion. [ABSTRACT FROM AUTHOR]

Sixty to seventy percent of patients undergoing HLA identical transplants will develop grade II-IV acute GVHD, despite using prophylactic immunosuppressants. Several studies have demonstrated that manipulation utilizing ex-vivo CD34+ positively selected grafts result in 4-5 log T-cell depletion with limited T-cell add back follow with early engraftment and decreased aGVHD (Silva et al, Blood Journal , 2015 & Chakrabarti et al, BMT , 2003). We previously demonstrated the safety and efficiency of CD34+ enriched cells with 2 × 105 CD3 (MNC)/kg add back in pediatric SCD patients resulting in rapid engraftment, donor chimerism, and low incidence of aGVHD (Geyer/Cairo et al, BJH , 2012). Utilizing CD34+ cell selection, children, adolescents, and adults with a matched or partially matched family donor or matched unrelated donors allogeneic PB-HPC transplant can safely receive and tolerate with a low incidence of serious (Grade III/IV) acute and chronic GVHD. Patients received CD34+ enriched products processed by using the CliniMACS CD34+ Reagent System (Miltenyi Biotec, Bergisch Gladbach, Germany). The CD34+ enriched HPC product was either a fresh infusion or cryopreserved and stored until time of transplantation. A target of 5 × 106 CD34+enriched/kg recipient weight with a T cell add back of 2 × 105 CD3+/kg (MNC) was infused. Sixteen patients underwent BMT with median age of 55 years (23 months to 71 years). Patients' disease status was as follows: complete remission (CR) 2 in four AML patients, CR1 in 9 AML patients, Lymphohistiocytosis (n=1), Macrophage Activating Syndrome (n=1), CR2 in one Non-Hodgkins Lymphoma patient. Nine patients received 10/10 HLA-matched unrelated donor BMT, two 9/10 HLA-matched unrelated donors, five had 6/6 HLA-matched sibling transplant. PB-HPC products contained 0.59 × 1010 CD3/kg (±0.23), and 6.77 × 106 CD34/kg (±1.27). After CD34 enrichment, the PB-HPC CD34% recovery was 73.1±3.08% with a log T cell depletion of 4.9 (±0.11). The target transplant dose per patient was 5 × 106 CD34 enriched/kg. Sixteen and patients had myeloid and 13 patients had platelet engraftment with a median of 11.5 days and 16 days, respectively (Fig. 1a and Fig. 1b). Two patients died prior to platelet engraftment one due to multi-organ system failure following septic shock and the other patient due to refractory AML. One patient died after myeloid and platelet engraftment secondary to disease progression. Early and late peripheral blood chimerism were ≥ 98.4% at 19.9 days (±12) and 92.5% at 180 days (n=4). The probability of grade II-IV aGVHD was 20% (CI 95 : 0.1-66.9) (Fig 2). One patient had grade II skin aGVHD and one patient had grade II gut aGVHD. No patient had cGVHD. This study demonstrates the safety and efficiency of CD34+ enriched PB-HPC products with T-cell addback in AlloSCT recipients with a low probability of acute GVHD. [ABSTRACT FROM AUTHOR]