Adenosine deaminase-2 (ADA2) deficiency (DADA2) is associated with early onset polyarteritis nodosa and vasculopathy. Classic presentation includes livedo reticularis, vasculitis, and stroke. However, the phenotype and disease severity are variable. We present a 5-year-old female who presented with features that mimicked autoimmune lymphoproliferative syndrome (ALPS) in the absence of classic features of DADA2. Exome sequencing identified a novel homozygous splicing variant in ADA2 c.882-2A > G. Patient responded to anti- tumor necrosis factor medication and is in complete remission. Hematologists should be aware of various hematological presentations of DADA2, including ALPS-like disorder, that might lack vasculitis and livedo reticularis to prevent delay in initiating optimal therapy.

Sickle cell disease (SCD) is one of the most common inherited disorders in Saudi Arabia with nearly 60,000 affected individuals (Alsultan et al. Ped. Transplant. 2016). Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment in SCD. A recent international survey showed excellent long-term survival of SCD patients after HLA-identical sibling HSCT; however, patients aged 16 years or older had higher risk of GVHD and mortality (Gluckman et al. Blood 2017). HLA-identical related HSCT in adult SCD patients using non-myeloablative (NMA) conditioning consisting of alemtuzumab, 300 cGy total body irradiation (TBI), and sirolimus was successful in establishing long term stable donor chimerism with minimal toxicity and GVHD (Hsieh et. al. JAMA 2014). In this study, we reviewed the outcome of SCD patients who underwent transplant at our institution using standard protocols (NMA regimen in patients ≥14 years and myeloablative regimen in < 14 years) to address whether age remains a risk factor that influences HSCT outcome in SCD. Children (<14 years) with severe SCD received myeloablative conditioning using one of two regimens: first regimen was cyclophosphamide (Cy) 200mg/kg, busulfan (Bu) 16mg/kg, and thymoglobulin (ATG) 10mg/kg and recently we use thiotepa 8mg/kg, Bu 16mg/kg, and fludarabine (Flu) 160mg/m2. Bu pharmacokinetics was performed to target AUC of 900-1350 µmol/L.min. GVHD prophylaxis included cyclosporine and methotrexate 10mg/m2 on day +1, +3, and +6. Bone marrow was the source of stem cells in all pediatric patients. Cyclosporine was continued during the first-year post HSCT and tapered slowly afterward based on donor chimerism. Adult patients (≥14 years) received hydroxyurea at maximum tolerated dose and hypertransfusion for 2-3 months with iron chelation if indicated prior to HSCT followed by NMA conditioning consisting of alemtuzumab (1mg/kg divided over 5 days on day -7 to -3) and TBI 300 cGy with testicular shielding in males on day -1. Sirolimus was used as GVHD prophylaxis starting day -2 and continued for at least one-year post HSCT with subsequent taper based on donor chimerism. Stem cells source was GCSF mobilized peripheral blood stem cells in all adult patients targeting cell dose of CD34 10X106/kg based on recipient weight. All SCD patients underwent exchange transfusion prior to HSCT to achieve HbS <30%. Hemoglobin was maintained between 9-11 g/dL and platelet count > 50,000/uL during HSCT. Supportive care included penicillin V, acyclovir, antifungal, and Pneumocystis jiroveci pneumonia prophylaxis. Levetiracetam was used as seizure prophylaxis. Strict monitoring of blood pressure and magnesium was performed. Graft failure and death from any cause were considered as events. A total of 51 patients with severe SCD were transplanted at our center, 17 children and 34 adults. Patient and transplant characteristics are summarized in Table. Indications for HSCT included recurrent severe pain crisis (n=33), stroke (n=14), avascular necrosis (n=2), sickle cell hepatopathy (n=1), and priapism (n=1). All patients engrafted successfully for both neutrophil and platelets. There was no acute or chronic GVHD among adult patients. Two pediatric patient had mild grade I acute GVHD in the skin that was controlled with topical treatment and none of pediatric patients had chronic GVHD. Three adult patients developed secondary graft failure on day 61, 170, and 225 post transplant with aplastic marrow in two patients despite full donor chimerism and autologous recovery in the third patient. Among the two patients who had aplastic anemia, one died secondary to sepsis and one underwent successful second transplant using cyclophosphamide, Flu, and ATG. Thirty-one adults have stable donor chimerism. Event free survival (EFS) at 2 years was 90% in adult patients and 100% in children (P=0.3). Overall survival (OS) at 2 years was 97% in adults and 100% in children (P=0.4). Median follow up duration was 416 days (range, 61-1256) in adults and 203 (range, 30-2505) days in children. We demonstrated that age-adapted approach in guiding the choice of conditioning regimen intensity in severe SCD is associated with excellent outcome and minimal risk of graft rejection, GVHD, and transplant-related mortality. This real world data is important to encourage patients and transplant physicians to consider this curative treatment. Longer follow up duration is needed to confirm our findings. Disclosures No relevant conflicts of interest to declare.

retrospectively captured on IRB approved protocol. Acute kidney injury (AKI) was defined at multiple time points post-HCT using the standardized criteria: Kidney Disease: Improving Global Outcomes (KDIGO). Interval differences between values were analyzed using Wilcoxon rank sum testing and categorical variables were analyzed using chisquare analysis. Results: Ninety-eight patients were included in the study: allogeneic (n = 96) and autologous (n = 2), mean age 8.7 years, of whom 50% were African American, 3% Asian, 21% Caucasian, 13% Latino, and 13% mixed race. Forty-seven percent of patients developed AKI within the first 2 years of HCT. Increased risk for AKI was associated with a lower pre-transplant creatinine level (P = .001), abnormal pre-transplant BUN (P = .019) and an unrelated donor (P = .022) while preparative regimen intensity, race, or primary disease were not. Twenty-six percent of patients developed AKI within 30 days of HCT. Evaluating outcomes at 1 year after HCT, of those with stage 1 AKI: 10% had reduced GFR and 37% died, while 14% had reduced GFR and 43% had died for patients with AKI stage 2 or 3. The absence of AKI by day 30 was associated with 24% reduced GFR and 8% death at 1-year after HCT. Overall, those with AKI at any time in the first year post-HCT had a 3.7 fold increased risk of death compared to those without. For patients who required renal replacement therapy (RRT, n = 8), the risk of death was 19.5 fold greater compared to those who did not. In the 25% of patients who survived RRT, both recovered renal function within 2 years. Conclusion: Acute kidney injury is common after pediatric HCT, and may be associated with low creatinine, abnormal BUN, and unrelated donor pre-HCT. Early-onset AKI post HCT is associated with an increased risk of mortality. These data should be validated in a larger prospective study but may offer opportunities to intervene and enhance outcomes.

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Coronavirus pandemic is the present concern worldwide. The virus is transmitted via a droplet route; however, transmission through blood products had not been reported. We present a 22-month-old boy with leukemia who developed fever and liver veno-occlusive disease 22 days post allogeneic hematopoietic stem cell transplantation coincidently after receiving apheresis platelets from a donor who tested positive for COVID-19 shortly after donation. The patient's nasal swab and blood PCRs remained negative two weeks after the event. Although this case did not show viral transmission through platelet transfusion, objective donor screening and viral deactivating techniques are practical options to ensure safety.

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Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for primary hemophagocytic lymphohistiocytosis (HLH). Conventional myeloablative conditioning regimen using busulfan, cyclophosphamide with or without etoposide was associated with high rate of transplant-related mortality (Horne et al. BJH 2005). Reduced intensity conditioning (RIC) is used in HLH to minimize transplant-related toxicities. The use of alemtuzumab, fludarabine, and melphalan in HLH was associated with low mortality; however, mixed donor chimerism and graft failure were frequent (Allen et al. Blood 2018). A recent report in 25 HLH patients who underwent HSCT from HLA matched donors using targeted busulfan (45-65 mg/L X h), fludarabine, and serotherapy resulted in adequate stable donor chimerism, no graft rejection, and no mortality (Felber et al. Blood Adv. 2020). In this study, we reviewed the outcome of 16 HLH patients who underwent HSCT from HLA matched donors using RIC. All patients were initially treated using HLH-2004 protocol. They subsequently underwent HSCT from 10/10 HLA matched related or unrelated donor using RIC regimens. We initially used AFM conditioning regimen that included alemtuzumab (1 mg/kg), fludarabine (150 mg/m2), and melphalan (140 mg/m2) with or without thiotepa (10 mg/kg). GVHD prophylaxis included cyclosporine (CSA) and steroids. Given the high rate of low donor chimerism with AFM regimen, we subsequently used BF conditioning regimen that included busulfan (weight-based dosing for total of 16 doses) and fludarabine (160 mg/m2). Therapeutic drug monitoring of busulfan was performed. Thymoglobulin (10 mg/kg) was added in matched unrelated donor (MUD). GVHD prophylaxis included CSA and steroids in matched related donors (MRD) and CSA and methotrexate in MUD. Bone marrow was the stem cell source in all patients except one who underwent second transplant using peripheral blood stem cells. Supportive care was consistent among all patients. Defibrotide prophylaxis was administered to prevent sinusoidal obstruction syndrome (SOS). Donor chimerism &lt;5% from whole blood or &lt;20% in T-cell, graft failure, and death from any cause were considered as events. A total of 16 HSCT transplants were performed, 5 received AFM regimen and 11 received BF regimen. Patient and transplant characteristics are shown in Table. All patients had successful neutrophil and platelet engraftments. Among the five patients who underwent AFM conditioning, one patient with SH2D1A mutation is 8 years post transplant with stable full donor chimerism and another patient with PRF1 mutation who received AFM with thiotepa has stable sufficient donor chimerism 3 years post transplant. Both patients did not require donor leukocyte infusions (DLI). The remaining 3 patients had declining donor chimerism beyond the first year of transplant despite the frequent use of DLI, one of them had disease reactivation and underwent second HSCT using BF regimen. Event free survival (EFS) at 3 years was 60% and overall survival (OS) was 100%. Among the 11 patients who underwent BF regimen, 7 were transplanted using MRD and 4 MUD. The median cumulative area under the curve of busulfan was 64 mg/L X h (range, 56-73). Median donor myeloid chimerism was 97% (range, 83-100) and median T-cell chimerism was 78% (range, 40-93). One patient who underwent MUD had grade III acute GVHD and none had chronic GVHD. Two patients had mild SOS. There were no events among BF group with median follow up duration of 393 days (151-2080). The use of BF regimen in HLH was associated with excellent outcome and stable donor chimerism with no graft failure in comparison to AFM regimen. Longer follow up is needed to confirm our findings. Disclosures No relevant conflicts of interest to declare.