Pulmonary Hemorrhage in Pediatric Hematopoietic Stem Cell Transplant Recipients: A Single-Center Retrospective Study.

OBJECTIVES: Pulmonary hemorrhage (PH) is a serious complication posthematopoietic stem cell transplant (HSCT). In view of limited available pediatric data, we performed a retrospective study to describe epidemiology, management, and outcomes of PH post-HSCT in children in our national center. DESIGN: Retrospective study. SETTING: Academic children's hospital (2000-2015). SUBJECTS: Children (< 18 yr) with PH and requiring PICU care post-HSCT. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The historical prevalence of PH in our center was 2.7% (31/1,148). Twenty patients had a concomitant infection, 15 had bacterial infection, 8 had viral infection, and 3 patients had a fungal infection. With a median follow-up time of 60 months, 7 of 31 patients were alive. Early PH (< 40 d post-HSCT) was associated with improved survival (6/15 vs 1/16, p = 0.035). Patients who received high-dose pulsed corticosteroid had improved survival when compared with those who did not (7/22 vs 0/9, p = 0.0012); this also applied to the subgroup of patients with a concomitant infection (5/15 vs 0, p = 0.001). None of the patients who survived had measurable respiratory sequelae. CONCLUSIONS: PH is a rare but serious complication after HSCT. Corticosteroids were associated with improved survival even in patients with a concomitant infection.

Intractable abdominal pain as the sole symptom of Varicella Zoster reactivation after allogeneic stem cell transplantation: brief case report and review of the literature.

After primary infection, Varicella Zoster (VZV) persists in sensory dorsal root ganglia and may be reactivated in periods of diminished T-cell immunity. Varicella Zoster reactivation post allogenic stem cell transplantation (HSCT) can be challenging to diagnose as it does not always present with characteristic skin lesions. We describe a pediatric patient who presented with isolated severe abdominal pain with no other symptoms. Cutaneous lesions appeared only 10 days later resulting in delayed diagnosis and treatment. He was successfully treated with intravenous acyclovir and recovered after a prolonged hospital stay with post-herpetic neuralgia. Abdominal pain in children post HSCT has a broad differential and VZV reactivation should be considered even in absence of cutaneous lesions. Early diagnosis and treatment are essential to reduce VZV-related morbidity and mortality. In this article we present a case report and review clinical presentation and outcome of similar cases in the literature.

Three-year results from phase I of ZUMA-4: KTE-X19 in pediatric relapsed/refractory acute lymphoblastic leukemia.

Here we present the 3-year results of ZUMA-4, a phase I/II multicenter study evaluating the safety and efficacy of KTEX19, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in pediatric/adolescent patients with relapsed/refractory B-cell acute lymphoblastic leukemia. Phase I explored two dose levels and formulations. The primary endpoint was the incidence of dose-limiting toxicities. Thirty-one patients were enrolled; KTE-X19 was administered to 24 patients (median age 13.5 years, range 3-20; median follow-up 36.1 months). No dose-limiting toxicities were observed. All treated patients had grade ≥3 adverse events, commonly hypotension (50%) and anemia (42%). Grade 3 cytokine release syndrome rates were 33% in all treated patients, 75% in patients given the dose of 2×106 CAR T cells/kg, 27% in patients given the dose of 1×106 cells/kg in the 68 mL formulation, and 22% in patients given the dose of 1×106 cells/kg in the 40 mL formulation; the percentages of patients experiencing grade ≥3 neurologic events were 21%, 25%, 27%, and 11% respectively. Overall complete remission rates (including complete remission with incomplete hematologic recovery) were 67% in all treated patients, 75% in patients given 2×106 CAR T cells/kg, 64% in patients given 1×106 cells/kg in the 68 mL formulation, and 67% in patients given 1×106 cells/kg in the 40 mL formulation. Overall minimal residual diseasenegativity rates were 100% among responders; 88% of responders underwent subsequent allogeneic stem-cell transplantation. In the 1×106 (40 mL) group (recommended phase II dose), the median duration of remission censored at allogeneic stem-cell transplantation and median overall survival were not reached. Pediatric/adolescent patients with relapsed/refractory B-cell acute lymphoblastic leukemia achieved high minimal residual disease-negative remission rates with a manageable safety profile after a single dose of KTE-X19. Phase II of the study is ongoing at the dose of 1×106 CAR T cells/kg in the 40 mL formulation. ClinicalTrials.gov: NCT02625480.

Abatacept-based Graft-Versus-Host Disease Prophylaxis in Haplo-identical Hematopoietic Cell Transplant in a High-risk Cohort.

BACKGROUND: There is insufficient guidance in using posttransplant cyclophosphamide in patients with organ dysfunctions. Abatacept (Aba), a T cell costimulation blockade, has recently been shown to prevent severe acute graft-versus-host disease (GVHD). OBSERVATION: We report adding Aba as GVHD prophylaxis in 4 pediatrics patients who received haplo-hematopoietic cell transplantation. Two patients had grade 2 acute GVHD and 2 had mild chronic GVHD. All 4 patients are alive with full donor chimerism, and 3 are off immunosuppressants. CONCLUSION: An Aba-based regimen can result in reliable engraftment and acceptable GVHD when concerns of organ dysfunction prevents the use of posttransplant cyclophosphamide in haplo-hematopoietic cell transplantation.

Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia.

BACKGROUND: In a single-center phase 1-2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). METHODS: We conducted a phase 2, single-cohort, 25-center, global study of tisagenlecleucel in pediatric and young adult patients with CD19+ relapsed or refractory B-cell ALL. The primary end point was the overall remission rate (the rate of complete remission or complete remission with incomplete hematologic recovery) within 3 months. RESULTS: For this planned analysis, 75 patients received an infusion of tisagenlecleucel and could be evaluated for efficacy. The overall remission rate within 3 months was 81%, with all patients who had a response to treatment found to be negative for minimal residual disease, as assessed by means of flow cytometry. The rates of event-free survival and overall survival were 73% (95% confidence interval [CI], 60 to 82) and 90% (95% CI, 81 to 95), respectively, at 6 months and 50% (95% CI, 35 to 64) and 76% (95% CI, 63 to 86) at 12 months. The median duration of remission was not reached. Persistence of tisagenlecleucel in the blood was observed for as long as 20 months. Grade 3 or 4 adverse events that were suspected to be related to tisagenlecleucel occurred in 73% of patients. The cytokine release syndrome occurred in 77% of patients, 48% of whom received tocilizumab. Neurologic events occurred in 40% of patients and were managed with supportive care, and no cerebral edema was reported. CONCLUSIONS: In this global study of CAR T-cell therapy, a single infusion of tisagenlecleucel provided durable remission with long-term persistence in pediatric and young adult patients with relapsed or refractory B-cell ALL, with transient high-grade toxic effects. (Funded by Novartis Pharmaceuticals; ClinicalTrials.gov number, NCT02435849 .).

Peripheral venous catheter collection of immune effector cells and hematopoietic stem cells is feasible and safe in older pediatric patients.

BACKGROUND: The Collection of hematopoietic stem cells (HSC) and immune effector cells (IEC) has unique challenges in children. To maintain adequate blood flow, central venous catheters (CVCs) remain the standard of care in many centers, but are associated with procedural risks and increased resource utilization. The goal of this study was to determine feasibility and safety of peripheral venous catheter (PVC) cell collection in older children. METHODS: Patients and donors requiring venous access with weight >25 kg, age >8 years were screened for PVC collection via 18G PVCs. Those with poor venous access (on history/exam/pre-screening ultrasound) or unable to maintain suitable procedural position were excluded. Comparison was made to CVC collections in a matched patient cohort. RESULTS: Thirty-eight individuals were screened and met age/weight criteria for PVC collection. Five did not have PVC collection attempted due to poor access (n = 4) or behavioral concerns (n = 1). Thirty-three had PVC collection attempt (HSC = 22; IEC = 11) with median age 15.3 year (range 9.7-18.0) and weight 58.5 kg (range 27.9-115.4). Thirty-two of 33 (97%) patients were collected successfully by PVC without adverse events. Comparing PVC to matched CVC collection cohort (n = 18), there was no significant difference in flow rate (48.2 mL/h vs 53.9 mL/h, p = 0.12), collection time (266 min vs 262 min, p = 0.85) or collection efficiency (IEC/CD3 60.9% vs 60.8% p = 0.99; HSC/CD34 53.6% vs 41.3% p = 0.05). CONCLUSION: PVC collection of HSC and IEC is feasible and safe in older children with comparable collection efficiency to CVC collections. Ultrasound screening may reduce failure rates. PVC collections can reduce the risk of CVC insertions and associated healthcare costs.

Early signs of metabolic syndrome in pediatric central nervous system tumor survivors after high-dose chemotherapy and autologous stem-cell transplantation and radiation.

PURPOSE: Cancer survivors treated with stem-cell transplant (SCT) and radiation therapy are at a high risk for late effects including the metabolic syndrome. This study reviewed the prevalence of the metabolic syndrome in pediatric central nervous system (CNS) tumor survivors treated with autologous SCT and craniospinal radiation. METHODS: A prospective, cross-sectional study in pediatric CNS tumor patients, who underwent a one-time evaluation at least 18 months post-autologous SCT for the presence of components of metabolic syndrome: obesity, hypertension, hyperlipidemia, and abnormal glucose levels. RESULTS: Twelve patients were evaluated, and two (16%) met full criteria for the metabolic syndrome. Seven patients (58%) had at least one component of metabolic syndrome: elevated glucose levels in 8% (1/12), obesity 17% (2/12), hypertriglyceridemia 17% (2/12), and reduced HDL cholesterol in 25% (3/12). None had hypertension. Nine patients (75%) demonstrated abnormal fasting lipid profiles with elevated total cholesterol levels, although only 25% (3/12) fulfilled criteria for a diagnosis of dyslipidemia. CONCLUSION: Pediatric CNS tumor survivors treated with autologous SCT and craniospinal radiation are at risk for early signs of metabolic syndrome, most commonly hyperlipidemia. Further studies evaluating the progression of these early signs to full criteria for the metabolic syndrome diagnosis are required.

Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis.

Isolated neuroinflammatory disease has been described in case reports of familial hemophagocytic lymphohistiocytosis (FHL), but the clinical spectrum of disease manifestations, response to therapy and prognosis remain poorly defined. We combined an international survey with a literature search to identify FHL patients with (i) initial presentation with isolated neurological symptoms; (ii) absence of cytopenia and splenomegaly at presentation; and (iii) systemic HLH features no earlier than 3 months after neurological presentation. Thirty-eight (20 unreported) patients were identified with initial diagnoses including acute demyelinating encephalopathy, leukoencephalopathy, CNS vasculitis, multiple sclerosis, and encephalitis. Median age at presentation was 6.5 years, most commonly with ataxia/gait disturbance (75%) and seizures (53%). Diffuse multifocal white matter changes (79%) and cerebellar involvement (61%) were common MRI findings. CSF cell count and protein were increased in 22/29 and 15/29 patients, respectively. Fourteen patients progressed to systemic inflammatory disease fulfilling HLH-2004 criteria at a mean of 36.9 months after initial neurological presentation. Mutations were detected in PRF1 in 23 patients (61%), RAB27A in 10 (26%), UNC13D in 3 (8%), LYST in 1 (3%), and STXBP2 in 1 (3%) with a mean interval to diagnosis of 28.3 months. Among 19 patients who underwent HSCT, 11 neurologically improved, 4 were stable, one relapsed, and 3 died. Among 14 non-transplanted patients, only 3 improved or had stable disease, one relapsed, and 10 died. Isolated CNS-HLH is a rare and often overlooked cause of inflammatory brain disease. HLH-directed therapy followed by HSCT seems to improve survival and outcome.

Effect of different conditioning regimens on survival and engraftment for children with hemophagocytic lymphohistiocytosis undergoing allogeneic hematopoeitic stem cell transplantation: A single institution experience.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH), a rare hyperinflammatory immuneregulatory disorder, is a challenge in hematopoietic stem cell transplantation (HSCT) because of the high rate of mixed chimerism, relapse, and graft failure (GF) unless intensive myeloablative regimens are used. However, historically conventional myeloablative regimens (conv MA) are associated with high toxicity and mortality. PROCEDURE: We retrospectively compared transplant outcomes between three preparative regimens of varying intensities: Conv MA (n = 15), reduced-intensity conditioning (RIC, n = 12), and a treosulfan-based reduced-toxicity conditioning (RTC, n = 9). RESULTS: Patients in the RIC cohort had a higher incidence of mixed donor chimerism and five patients (42%) developed secondary GF (P = .002) compared to the other two regimens. There was a higher incidence of veno-occlusive disease and intensive care unit (ICU) admissions in the Conv MA cohort. With the RTC regimen, there was a similar 2-year overall survival (89, 73, and 83%; P = .87), but improved compound EFS (lack of relapse, GF, second transplant or additional donor cell infusions, or death; 89, 73, and 42%, P = .041) in RTC, Conv MA, and RIC regimen, respectively. CONCLUSIONS: The intensity of the preparative regimen has a significant impact on outcome of HSCT for HLH. The newly described treosulfan-based RTC provides for a stable graft with a reasonable toxicity profile.

Novel c.G630A TCIRG1 mutation causes aberrant splicing resulting in an unusually mild form of autosomal recessive osteopetrosis.

Autosomal recessive osteopetrosis (ARO) is a severe genetic bone disease characterized by high bone density due to mutations that affect formation or function of osteoclasts. Mutations in the a3 subunit of the vacuolar-type H+ -ATPase (encoded by T-cell immune regulator 1 [TCIRG1]) are responsible for ~50% of all ARO cases. We identified a novel TCIRG1 (c.G630A) mutation responsible for an unusually mild form of the disease. To characterize this mutation, osteoclasts were differentiated using peripheral blood monocytes from the patient (c.G630A/c.G630A), male sibling (+/+), unaffected female sibling (+/c.G630A), and unaffected parent (+/c.G630A). Osteoclast formation, bone-resorbing function, TCIRG1 protein, and mRNA expression levels were assessed. The c.G630A mutation did not affect osteoclast differentiation; however, bone-resorbing function was decreased. Both TCIRG1 protein and full-length TCIRG1 mRNA expression levels were also diminished in the affected patient's sample. The c.G630A mutation replaces the last nucleotide of exon 6 and may cause splicing defects. We analyzed the TCIRG1 splicing pattern between exons 4 to 8 and detected deletions of exons 5, 6, 7, and 5-6 (ΔE56). These deletions were only observed in c.G630A/c.G630A and +/c.G630A samples, but not in +/+ controls. Among these deletions, only ΔE56 maintained the reading frame and was predicted to generate an 85 kDa protein. Exons 5-6 encode an uncharacterized portion of the cytoplasmic N-terminal domain of a3, a domain not involved in proton translocation. To investigate the effect of ΔE56 on V-ATPase function, we transformed yeast with plasmids carrying full-length or truncated Vph1p, the yeast ortholog of a3. Both proteins were expressed; however, ΔE56-Vph1p transformed yeast failed to grow on Zn2+ -containing plates, a growth assay dependent on V-ATPase-mediated vacuolar acidification. In conclusion, our results show that the ΔE56 truncated protein is not functional, suggesting that the mild ARO phenotype observed in the patient is likely due to the residual full-length protein expression.

Lymphocyte subset at time of Epstein-Barr viremia post-allogeneic hematopoietic stem cell transplantation in children may predict development of post-transplant lymphoproliferative disease: CD8:CD20 ratio as a sensitive predictor.

EBV-associated PTLD following allogeneic HSCT is a serious complication associated with significant mortality. In this retrospective study, we evaluated whether lymphocyte subset numbers and CD8:CD20 ratio at time of EBV viremia in children undergoing allogeneic HSCT could predict development of PTLD. Absolute lymphocyte count, lymphocyte subsets, and CD8:CD20 ratio at the time of EBV viremia were analyzed. Patients who were treated preemptively with rituximab for high blood EBV viral load were excluded. Out of 266 patients transplanted during the study period, 26 patients were included in the analysis. Patients were divided into two cohorts; cohort 1 included patients with EBV-associated PTLD (n = 5; four with proven, one with probable PTLD). Cohort 2 included patients with EBV viremia without PTLD (n = 21). Lymphocyte recovery was slower in the PTLD group. CD8:CD20 ratio was significantly lower in the PTLD group (median 0.15) compared to the non-PTLD group (median 2.4, P = .012). Using the ROC curve and 1 as the cutoff value, CD8:CD20 ratios were analyzed. In the PTLD group, 4/5 patients (80%) had a ratio <1 whereas in the non-PTLD group, all 21 patients had a ratio >1. Sensitivity and specificity were 80% and 100%, respectively. Negative and PPVs were 95% and 100%, respectively. Profoundly low T-cell count and CD8:CD20 ratio may be used to predict development of PTLD in the context of EBV viremia in children post-allogeneic HSCT. Further studies are needed to validate this finding.

Hemophagocytic lymphohistiocytosis is a sign of poor outcome in pediatric Epstein-Barr virus-associated post-transplant lymphoproliferative disease after allogeneic hematopoietic stem cell transplantation.

EBV-related PTLD developing after HSCT is a potentially life-threatening disease. HLH is uncommon after allogeneic HSCT. Data on outcome of patients with PTLD and concomitant HLH after allogeneic HSCT are limited. In this retrospective study, we collected demographic, clinical, laboratory, and outcome data for 408 patients who underwent allogeneic HSCT from 2006 to 2015. Graft source included CB (n = 135; 33.1%), PBSCs (n = 34; 8.3%), and BM (n = 239; 58.6%). Eight out of 408 patients (2%) developed EBV-PTLD with a median age at HSCT of 5.9 years (range: 2.3-17.3). All eight patients received ATG as part of the conditioning regimen. Graft source was PBSC in three patients (37.5%), BM in four patients (50%), and CB in one patient (12.5%). Donors were matched unrelated in five patients (62.5%) and matched sibling in three patients (37.5%). Seven out of eight patients developed EBV-PTLD within the first 100-day post-HSCT. Lymph node biopsy revealed early lesions in three patients, polymorphic in three patients, and monomorphic PTLD in two patients. Three patients (37.5%) died within 1 month of EBV-PTLD diagnosis. All deceased patients developed HLH manifestations with two of them meeting HLH diagnostic criteria and one having an incomplete workup. PTLD after allogeneic HSCT with manifestations of HLH is associated with high mortality. Early identification and treatment of EBV-PTLD seems imperative to control the disease, especially if signs of HLH are evolving.

Comparison between intermittent and continuous leukapheresis protocols for autologous hematopoietic stem cell collections in children.

BACKGROUND: Peripheral hematopoietic stem cell (HSC) collections are needed for autologous hematopoietic stem cell transplantation (HSCT). Since 2015, our institution has utilized a secondary chamber mononuclear cell (MNC) protocol on the Spectra Optia apheresis system. Recently, a new continuous mononuclear collection protocol (CMNC) was developed for the same device. As there is limited data available regarding the use of the CMNC protocol in children, we compared collection efficiency (CE2), side effects, and clinical feasibility between the two protocols in patients <18 years old. STUDY DESIGN AND METHODS: We prospectively collected clinical, laboratory, and technical collection data from HSC collection procedures performed with the Spectra Optia apheresis system utilizing the CMNC protocol. Data were compared to retrospectively collected data utilizing the MNC protocol. Data collection included donor demographics, precollection peripheral CD34+ cell counts, total CD34+ cells collected, collection efficiency, side effects, and collection product characteristics. RESULTS: A total of 96 HSC collection procedures were performed on 79 pediatric patients utilizing either the MNC (61 patients) or CMNC (18 patients) protocol. The collection efficiencies were comparable between MNC and CMNC cohorts (52.9% vs 54.9%, P = 0.711). Platelet loss was significantly lower in the CMNC cohort (P = 0.002), especially in children weighing <15 kg. Product volumes were higher with CMNC. No significant collection-related side effects were noted with either protocol. CONCLUSIONS: MNC and CMNC protocols have comparable collection efficiencies and are both feasible and safe for the use in children. Centers may choose between the methods depending on clinical needs.

The yield of monitoring adenovirus in pediatric hematopoietic stem cell transplant patients.

Human adenovirus (HAdV) is recognized as a serious pathogen after allogeneic hematopoietic stem cell transplantation (HSCT), causing morbidity and mortality. Currently, there is no universal agreement regarding routine HAdV surveillance after HSCT. We assessed the impact of HAdV weekly monitoring by polymerase chain reaction (PCR) on HAdV viremia rates and the risk factors that influence survival. Three-hundred and fifty-six pediatric allogeneic HSCT were done between 2007 and 2015. Until July 2011, HAdV testing was performed based on clinical suspicion (cohort 1, n = 175) and from August 2011, weekly blood-HAdV monitoring was done (cohort 2, n = 181) until day +100. Twenty-three patients (4 [2.3%] from cohort 1 and 19 [10.5%] from cohort 2, p = .001) were found with HAdV viremia and seven of them died. Both cohorts had a similar incidence of HAdV-associated mortality (3/175; 1.7% in cohort 1 and 4/181; 2.2% in cohort 2). Respiratory failure was the cause of death in all patients. Clinical symptoms appeared prior to or within 5 days of HAdV detection in cohort 2. In summary, weekly monitoring was associated with higher detection of HAdV. The study could not assess survival benefit due to small numbers of HAdV-positive cases. In many instances, symptoms occurred with the development of positive HAdV blood PCR results and hence, symptomatology could have triggered the test. Future studies are needed to provide data that help establishing a uniform approach for regular monitoring of HAdV post-transplant.

Efficacy of high-dose steroids for bronchiolitis obliterans syndrome post pediatric hematopoietic stem cell transplantation.

BOS is the pulmonary manifestation of cGvHD post-allogeneic HSCT. Survival and treatment of this often fatal complication have not improved over the last 20 years and there is no clear standard of care. For the past 10 years, BOS was treated in our center with monthly cycles of HDPS. We reviewed the outcomes of patients with post-HSCT BOS who met the diagnostic criteria for BOS as per the NIH consensus and were treated with at least one cycle of methylprednisolone at a dose of 10-30 mg/kg/d×3 d. We collected demographic and clinical data, responses to treatment and results of pulmonary function tests at several time points. Between January 2007 and January 2014, 12 patients were treated with HDPS for post-HSCT BOS. Five patients (42%) had a good response to treatment; four patients (33%) stabilized with moderate lung disease; and three patients (25%) progressed to end-stage disease. No significant acute side effects attributable to the HDPS treatment were identified. HDPS may be an effective treatment option for all but the most severely ill patients with post-HSCT BOS.

Collection of hematopoietic stem cells and immune effector cells in small children.

Apheresis procedures are standard of care for a wide range of indications in children, collection of hematopoietic stem cells being the most frequent one. With increasing numbers of hematopoietic stem cell transplants, advances in graft manipulation techniques and the development of innovative therapies using immune effector cells and gene therapy, apheresis within the pediatric population is growing in demand. While young children have higher circulating white blood cell counts and robustly mobilize hematopoietic stem cells, apheresis machines were designed for use within the adult population and apheresis procedures in children, particularly small children, can be more challenging as vascular access, collection techniques and impact of extracorporeal volumes increase the rate of adverse events. In this article we review topics of particular relevance to hematopoietic stem cell and immune effector cell collections in small children.

Optimizing autologous nonmobilized mononuclear cell collections for cellular therapy in pediatric patients with high-risk leukemia.

BACKGROUND: The manufacturing of cellular products for immunotherapy, such as chimeric antigen receptor T cells, requires successful collection of mononuclear cells. Collections from children with high-risk leukemia present a challenge, especially because the established COBE Spectra apheresis device is being replaced by the novel Spectra Optia device (Optia) in many institutions. Published experience for mononuclear cell collections in children with Optia is lacking. Our aim was to compare the two collection devices and describe modified settings on the Optia to optimize mononuclear cell collections. STUDY DESIGN AND METHODS: As a quality initiative, we retrospectively collected and compared data from mononuclear cell collections on both devices. Collected data included patient's clinical characteristics; collection parameters, including precollection lymphocyte/CD3 counts, total blood volumes processed, runtimes, and side effects (including complete blood count and electrolyte changes); and product characteristics, including volumes and cell counts. Collection efficiencies and collection ratios were calculated. RESULTS: Twenty-six mononuclear cell collections were performed on 20 pediatric patients: 11 with COBE and 15 with Optia. Adequate mononuclear cell products were successfully collected with a single procedure from all patients except one, with mean calculated mononuclear cell collection efficiency that was significantly higher from Optia collections compared with COBE collections (57.9 ± 4.6% vs 40.3 ± 6.2%, respectively; p = 0.04). CD3-positive yields were comparable on both machines (p = 0.34) with significantly smaller blood volumes processed on Optia. Collected products had larger volumes on Optia. No significant side effects attributed to the procedure were noted. CONCLUSION: Mononuclear cell apheresis using the Optia device in children is more efficient and is as safe as that with the COBE device.

Comparison of two apheresis systems for autologous stem cell collections in pediatric oncology patients.

BACKGROUND: Peripheral stem cell collections can be challenging in the pediatric population and respective experience is limited. Since February 2015 our institution is utilizing the new Spectra Optia (Optia) apheresis device, which has replaced the former COBE Spectra (COBE) device. As a quality initiative we collected and compared collection efficiency (CE2) and other collection variables between the two devices. STUDY DESIGN AND METHODS: In this retrospective study we collected and compared clinical, laboratory, and technical collection data from stem cell collection procedures done with the Optia and COBE devices. The collected data included patient demographics, precollection peripheral CD34+ cell counts, total CD34+ cells collected, complete blood count, electrolytes before and after collection, side effects attributed to the collection, total blood volumes processed (TBVs), collection times, and calculated CE2 and collection ratios. RESULTS: Forty-one collection procedures performed on 29 pediatric patients with the Optia device were compared to 41 collections performed on 27 patients with the COBE device. The TBVs through the Optia device were significantly smaller than the COBE (3.9 ± 0.2 × TBV vs. 5.5 ± 0.1 × TBV, respectively; p < 0.001), requiring significantly less anticoagulant and providing similar amounts of stem cells while collection times were significantly shorter (mean, 238 ± 9 min vs. 264 ± 9 min, respectively; p < 0.05). Collections on the Optia caused significantly smaller reductions of plasma calcium and magnesium. No significant side effects attributed to the procedure were noted. CONCLUSION: Stem cell apheresis with the Optia device in children is safe and feasible with smaller blood volumes with shorter collection times.

Eltrombopag for secondary failure of platelet recovery post-allogeneic hematopoietic stem cell transplant in children.

Secondary failure of platelet engraftment occurs in 20% of patients undergoing allogeneic HSCT and is associated with poor outcome. Currently, there are no guidelines for treatment of late thrombocytopenia and platelet transfusion is the mainstay of treatment. Here, we describe the use of Eltrombopag to treat secondary failure of platelet recovery following HSCT in a child with severe aplastic anemia. Eltrombopag resulted in recovery of platelet count with no need for platelet transfusion support with no reported side effects. Eltrombopag may be used successfully in children with secondary failure of platelet recovery post-HSCT for SAA.

Successful Myeloablative Matched Unrelated Donor Hematopoietic Stem Cell Transplantation in a Young Girl With GATA2 Deficiency and Emberger Syndrome.

Patients with GATA2 (Emberger syndrome) deficiency needs early hematopoietic stem cell transplant (HSCT) before evolving in to myelodysplastic syndrome or acute myeloid leukemia and with time given compromised organ dysfunction leads to increase regimen-related toxicities. Most published cases have used nonmyeloablative conditioning regimens, show higher incidences of rejection and relapse rates and umbilical cord blood transplant has been reported to be suboptimal in patients with GATA2 deficiency because of longer period of engraftment leads to more infections and mortality. We report a 4.5-year-old girl with GATA2 deficiency who underwent matched unrelated donor HSCT utilizing a myeloablative conditioning regimen including intravenous busulfan (total dose of 12.8 mg/kg) and fludarabine (total dose of 160 mg/m) She tolerated the conditioning regimen and bone marrow infusion well. Her initial chimerism was mixed (90% donor), cyclosporine was gradually weaned and discontinued at day+85 and this resulted in conversion to full-donor chimerism. Bone marrow assessment 3 months post-HSCT revealed normal hematopoiesis and absence of monosomy 7. At 20 months of follow-up she had full-donor chimerism with complete reconstitution of the all hematopoietic stem cells. Myeloablative matched unrelated donor HSCT represents an effective option for cure in patients with GATA2 deficiency and Emberger syndrome.