Terumo BCT Research Articles

Experience with COVID-19 convalescent plasma provides vital guidance to future pandemics.

Experience with COVID-19 convalescent plasma provides vital guidance to future pandemics.

Therapeutic plasma exchange in HELLP syndrome: A life savior.

BACKGROUND:HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome occurs in about 0.5%–0.9% of all pregnancies, but its prevalence is higher in patients with severe preeclampsia, accounting for a substantial maternal and perinatal morbidity and mortality. According to the latest American Society for Apheresis guidelines, Therapeutic plasma exchange (TPE) performed for postpartum cases and antepartum HELLP syndrome cases fall in Categories III and IV, respectively.MATERIALS AND METHODS:Retrospective analysis was done at our tertiary care center from January 2014 to June 2019 for patients diagnosed with HELLP syndrome. Clinical data for age, gestational age at the time of diagnosis, type of delivery, outcome of pregnancy, history of preeclampsia /eclampsia, hemoglobin levels, AST, ALT, LDH, platelet counts, prothrombin time, activated partial thromboplastin time, international normalised ratio, complete blood count, was obtained from patients' electronic medical records. The TPE was initiated within 24 hrs of diagnosis. All TPE was done on Spectra Optia apheresis system (Terumo BCT, Inc, USA). Statistical testing was conducted with the statistical package for the social science system version SPSS 20.0 and R-3.2.0. Continuous variables were expressed as mean±SD and were compared between Pre and Post TPE records of patients by using the paired T test.RESULTS:Nine patients fulfilled the criteria of HELLP syndrome. Seven (77.8%) were diagnosed in the postpartum period and 2 (22.2%) during the second trimester. Out of the total nine patients, two patients (22.2%) recovered completely and were discharged on day 15 ± 7 days, whereas 4 (44.4%) patients were discharged on day 21 ± 7 days with the advice of hemodialysis. Two (22.2%) patients had an intrauterine death and were discharged 3–4 days after the demise. In all these patients (except one), the TPE was initiated within 24 h of the diagnosis. A significant increase in platelet count and decrease in the lactate dehydrogenase levels (P < 0.05) was observed post TPE.CONCLUSION:Our data showed that TPE improved the treatment outcome in patients with HELLP syndrome despite being a Category III and IV indication among postpartum and antenatal females, respectively. However, a timely diagnosis and management are of paramount importance for a favorable outcome. TPE needs to be performed within 24 h of the diagnosis postdelivery when the patient is not responsive to the usual therapies, especially in class I HELLP syndrome.

Retention of hemostatic and immunological properties of frozen plasma and COVID-19 convalescent apheresis fresh-frozen plasma produced and freeze-dried in Canada.

Randomized clinical trial data show that early plasma transfusion may save lives among trauma patients. Supplying plasma in remote environments is logistically challenging. Freeze-dried plasma (FDP) offers a possible solution. A Terumo BCT plasma freeze-drying system was evaluated. We compared pooled frozen plasma (FP) units with derived Terumo BCT FDP (TFDP) units and pooled COVID-19 convalescent apheresis fresh-frozen plasma (CC-AFFP) with derived CC-TFDP units. Parameters measured were: coagulation factors (F) II; V; VII; VIII; IX; XI; XIII; fibrinogen; Proteins C (PC) and S (PS); antithrombin (AT); α2 -antiplasmin (α2 AP); ADAMTS13; von Willebrand Factor (vWF); thrombin-antithrombin (TAT); D-dimer; activated complement factors 3 (C3a) and 5 (C5a); pH; osmolality; prothrombin time (PT); and activated partial thromboplastin time (aPTT). Antibodies to SARS-CoV-2 in CC-AFFP and CC-TFDP units were compared by plaque reduction assays and viral protein immunoassays. Most parameters were unchanged in TFDP versus FP or differed ≤15%. Mean aPTT, PT, C3a, and pH were elevated 5.9%, 6.9%, 64%, and 0.28 units, respectively, versus FP. CC-TFDP showed no loss of SARS-CoV-2 neutralization titer versus CC-AFFP and no mean signal loss in most pools by viral protein immunoassays. Changes in protein activities or clotting times arising from freeze-drying were <15%. Although C3a levels in TFDP were elevated, they were less than literature values for transfusable plasma. SARS-CoV-2-neutralizing antibody titers and viral protein binding levels were largely unaffected by freeze-drying. In vitro characteristics of TFDP or CC-TFDP were comparable to their originating plasma, making future clinical studies appropriate.

Higher Grade Cytokine Release Syndrome Is a Predictive Factor for Gvhd in Haploidentical Stem Cell Transplantation with Peripheral Blood Cell

Background:Early Cytokine Release Syndrome (CRS) is a common complication following haploidentical stem cell transplantation (Haplo-HSCT) induced by the proliferation of alloreactive T-Cells. CRS is occurring more frequently in patients receiving peripheral blood stem cells (PBSC) comparatively to bone marrow transplant, however its impact on outcome, notably graft versus host disease (GVHD) remain unclear. The main objective was to evaluate the impact of severity of CRS on the risk of GVHD.Patients and Methods:This retrospective single-center study included patients who had received a first haplo-HSCT for hematological malignancies, with PBSC as graft source. All patients received either a reduced-intensity conditioning (RIC) based on thiotepa (5mg/kg), busulfan (260 mg/m²) and fludarabine (120 mg/m²) [TBF], or a non-myeloablative conditioning (NMAC) based on fludarabine (150 mg/m²), cyclophosphamide (29 mg/kg) and 2 Gy TBI [CyFluTBI]. GVHD prophylaxis was based on PT-Cy 50 mg/kg (day+3 and +4) and cyclosporine A plus mycophenolate mofetil starting at day+5. All patients were given GSCF from day+5 to neutrophil recovery.Results:241 consecutive patients were analyzed. One hundred patients (54%) had myeloid malignancies, and 111 (46%) had lymphoid malignancies. Most patients had intermediate or low risk DRI (n = 180, 75%) and HCT-CI was ≥ 3 for 159 patients (66%). Using ASTCT consensus criteria, 226 patients (94%) developed CRS, including 183 grade 1 and 43 grade ≥ 2. Transplantation and patient characteristics were not significantly different between patients with CRS grade 0-1 vs. ≥ 2, except for age. Indeed, patients with CRS grade ≥ 2 were significantly older than patients with CRS grade 0-1 (median 65 vs 60 yo respectively, p = 0.01).Patients with grade ≥ 2CRS had significantly higher cumulative incidence of day-100 grade II-IV acute GVHD (grade 0-1 vs. ≥ 2 : 28% and 44%, p = 0.028) and 4-year moderate to severe chronic GVHD (grade 0-1 vs. ≥ 2 : 16% and 30%, p = 0.024) compared to patients with grade 0-1 CRS (Figure 1). No difference in the cumulative incidence of relapse was observed between CRS groups (grade 0-1 vs. ≥ 2 : 22% and 21%, p = 0.802).By multivariate analysis, CRS grade ≥ 2 was the only factor associated with grade II-IV acute GVHD (HR = 1.99; 95%CI = [1.17-3.39], p = 0.011). CRS grade ≥ 2 was significantly associated with a higher risk of moderate to severe chronic GVHD (HR = 2.67; 95%CI = [1.36-5.21], p = 0.004) and poorer GVHD- and relapse-free survival (GRFS) (HR = 1.78 ; 95%CI = [1.19-2.67], p = 0.005). Progression free survival, overall survival and non-relapse mortality were not influenced by the severity of CRS.Conclusion:In the context of PBSC haplo-HSCT, the occurrence of grade ≥ 2 CRS following graft infusion is significantly associated with an increased risk of both acute and chronic GVHD. This may improve the early identification of patients with high risk of GVHD for whom specific enhanced GVHD prophylaxis should be investigated. [Display omitted] DisclosuresChabannon: Sanofi SA: Other: Travel Support, Research Funding, Speakers Bureau; Bellicum Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Novartis: Speakers Bureau; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Terumo BCT: Speakers Bureau; Miltenyi Biotech: Research Funding; Fresenius Kabi: Research Funding; EBMT: Membership on an entity's Board of Directors or advisory committees. Blaise: Jazz Pharmaceuticals: Honoraria.

Randomized Controlled Trial of the Efficacy and Safety of Deferiprone: Subgroup Analysis of Pediatric Patients in Iron-Overloaded Patients with Sickle Cell Disease and Other Anemias

Randomized Controlled Trial of the Efficacy and Safety of Deferiprone: Subgroup Analysis of Pediatric Patients in Iron-Overloaded Patients with Sickle Cell Disease and Other Anemias

Improved GvHD-Free, Relapse-Free Survival (GRFS) with Post-Transplant Cyclophosphamide and Tacrolimus for GvHD Prevention in Older Adults Undergoing Allogeneic Hematopoietic Cell Transplantation

INTRODUCTIONThe continuous refinement of transplant techniques has lead to a reduction of transplant-related toxicity resulting on an increasing number of allogeneic hematopoietic cell transplantation (alloHCT) performed in older patients. Since 2014, post-transplant cyclophosphamide (PTCy) with tacrolimus (PTCy-TK), alone, has been progressively implemented at our Institution as GvHD prophylaxis for related, matched and mismatched unrelated donor transplantation (MRD, MUD, MMUD). The experience has proved that the use of this prophylaxis induces effective GvHD prevention without increased relapsed rates (Pedraza et al, 2021).Secondary to the encouraging results obtained from the use of PTCy-TK at our Institution, and considering that older patients with hematological disorders are a group of patients with higher risk to develop transplant-related toxicity, this study compares, as far as we know, the results provided by the use of PTCy-TK with conventional GVHD prophylaxis in a consecutive cohort of patients older than 50 years.METHODSBetween January 2014 and June 2020, 147 adults with hematological malignancies and > 50 years underwent alloHCT either from MRD or UD at our Institution. Seventy-two (48.9%) patients received PTCy 50 mg/kg/day IV on day +3 and +4, followed by TK, initiated at a dose of 0.03/kg/24h IV on day +5 and titrated to achieve a therapeutic level of 5-15mg/mL. Other GvHD prophylaxes combined calcineurine inhibitors combined with methotrexate, mycophenolate mofetil, or sirolimus, and anti-thymocyte globulin was added especially when MMUD were selected. Data were collected retrospectively and updated in June 2021. Overall survival (OS) and GvHD-Free/Relapsed free survival (GRFS) were considered the main outcome variables, and the cumulative incidence of GvHD was calculated accounting relapse and dead as competing events. In order to analyze the independent impact of PTCy-TK prophylaxis on OS and GRFS, a multivariate Cox regression analysis was performed including GvHD prophylaxis, Disease Risk Index, and transplant year (dichotomized with a cut-off in 2017, given the marked increase of PTCy-TK after this year) as explanatory variables together with other variables with prognostic value in the univariate analysis.RESULTSBaseline characteristics of patients classified according to the GvHD prophylaxis are reported in Figure 1. The two cohorts of patients according to GvHD prophylaxis are well balanced. Peripheral blood was the predominant stem cell source in the vast majority (97%). Of note, 53 out of 72 patients receiving PTCy-TK were transplanted between July 2017 and December 2020. And UD was used in more than 90% of PTCy-TK alloHCT, compared to 44% of alloHCT with other prophylaxes.The median of days for neutrophil (20 vs 16, p<0.01) and platelet (19 vs 11, p<0.01) engraftment were higher for patients receiving PTCy-TK, while the differences between the incidences of viral reactivations and infections were not statistically significant between the two groups. The cumulative incidence of grade II-IV aGvHD (day +100: 21.9% vs 21.5%, p=0.88) and grade III-IV aGvHD (day +100: 9.2% vs 9.3%, p=0.88) were comparable between both cohorts, but the use of PTCY-TK resulted on a significant reduction on the incidence of moderate/severe cGvHD (1-y: 9% vs 31.5%, p<0.01) (Figure 1).OS (1-y: 72.1% vs 66.7%, HR 0.98; p=0.91), NRM (1-y: 18.1% vs 13.3%, HR 1.20; p=0.63), and relapse rates (1-y: 18.1% vs 22.9%, HR 0.86, P=0.65) were similar in both groups (PTCy-TK and other GvHD prophylaxis, respectively). However, PTCy-TK significantly resulted into an improved GRFS (1-y: 52.6% vs 30.7%, HR 1.68, p=0.01). A multivariate analysis confirmed the independent favorable impact of PTCy-TK prophylaxis on GRFS (HR 0.58, p=0.01), but not on OS (Figure 1).CONCLUSIONSPTCy-TK, alone, is an effective GVHD prophylaxis for alloHCT when related and UD are selected. The use of this innovative combination provides superior GRFS than the use of conventional GvHD prophylaxis in older adults undergoing alloHCT, with comparable transplant-related mortality and relapse rates. GRFS is a composite endpoint considered a surrogate outcome of health-related quality of life, and the improvement of this parameter is remarkable in PTCy-TK alloHCT, especially for older patients. [Display omitted] DisclosuresLozano: Grifols: Honoraria; Terumo BCT: Honoraria, Research Funding; Macopharma: Research Funding. Rosinol: Janssen, Celgene, Amgen and Takeda: Honoraria. Esteve: Novartis: Consultancy, Research Funding; Abbvie: Consultancy; Astellas: Consultancy; Jazz: Consultancy; Novartis: Research Funding; Pfizer: Consultancy; Bristol Myers Squibb/Celgene: Consultancy.

ERN-EuroBloodNet European Registry of Patients Affected by Red Blood Cell Disorders and COVID-19

ERN-EuroBloodNet European Registry of Patients Affected by Red Blood Cell Disorders and COVID-19

Polyclonality Strongly Correlates with Biological Outcomes and Is Significantly Increased Following Improvements to the Phase 1/2 HGB-206 Protocol and Manufacturing of LentiGlobin for Sickle Cell Disease (SCD; bb1111) Gene Therapy (GT)

Polyclonality Strongly Correlates with Biological Outcomes and Is Significantly Increased Following Improvements to the Phase 1/2 HGB-206 Protocol and Manufacturing of LentiGlobin for Sickle Cell Disease (SCD; bb1111) Gene Therapy (GT)

Single Needle Option: An Alternative to Dual-Needle Access in Erythrocytapheresis in Patients with Sickle Cell Disease

Background: Erythrocytapheresis or red cell exchange (RCE) is an invaluable treatment option for patients with complications related sickle cell disease, including acute stroke, stroke prevention, acute chest syndrome, and recurrent pain crisis. The procedure entails the removal of each patient's red blood cells containing the abnormal sickle hemoglobin and replacing them with normal red blood cells carrying non-sickled hemoglobin. Adequate vascular access is essential for erythrocytapheresis to allow for high flow rates and various forms of access are used including peripheral veins and central venous access devices. Our center typically uses a single vortex port (Angiodynamics, Walnut Creek, CA) with placement of a peripheral IV at time of procedure in order to maintain a circuit for exchange. Using peripheral access reliably becomes particularly difficult in young patients and those that require multiple access over time due to scaring. To ensure a successful procedure in patients with poor peripheral access, a single-needle (SN) option for TPE (SN-TPE) that is available on Spectra Optia (Terumo BCT, Lakewood, CO) was used. The single-needle procedure utilizes intermittent, rather than continuous, flow, and thus requires extra procedure run time. One discontinuous cycle consists of “exchanging red cells,” which is the drawing of blood and removal of the red cells, and “adjusting the volume in the reservoir,” which is the returning of blood. These cycles continue until the procedure is complete. This procedure allows us to continue RCE in a select number of patients with poor vascular access.Methods: We evaluated our institutional experience on patients treated using single-needle RCE. In addition, information regarding each RCE session was collected including duration of procedure and inlet flow rate.Results: An average of 45 RCE procedures are performed each month. Patients are scheduled every 3 to 8 weeks, with an average of every 4-5 week frequency. We started the Single Needle option in July of 2019 on 3 patients: one adult aged patient and 2 pediatric patients. By the end of 2019 we had perform a total of 27 SN procedures. In 2020, we performed a total of 112 SN procedures, average of 9 procedures each month. As of the first 6 months of 2021, we have completed 35 SN procedures, averages 6 a month.In patients undergoing single needle exchange we were able to increase inlet flow rates from an average of 30-50ml/min to 60-80ml/min. This decreased the duration of run times from 120-198 min to 77- 119 min. Pre and post hemoglobin S% was comparable between dual and single exchange patients and there was no change in the interval between RCE sessions. Conclusion: With our increasing experience with single-needle RCE, our findings suggest that RCE can be successfully completed using the single-needle option with no impact on pre- and post-exchange hemoglobin S% levels. There was a reduction in the total length of procedure due to ability to maintain higher inlet rates and decreased time to obtain access for RCE. The single needle option also improved patient satisfaction due to more reliable access and negating need for peripheral IV access. DisclosuresMunson: Terumo Medical Corporation: Consultancy, Honoraria, Speakers Bureau. Raj: Forma therapeutics: Consultancy; Terumo Medical Corporation: Honoraria, Speakers Bureau; Global biotherapeutics: Speakers Bureau.

Safety of Anti-NKG2A Blocking Antibody Monalizumab As Maintenance Therapy after Allogeneic Hematopoietic Stem Cell Transplantation: A Phase I Study

BackgroundFollowing allogeneic hematopoietic stem cell transplantation (Allo-HSCT), the phenotype and function of circulating NK Cells are altered; notably NK cells display an immature (CD56-bright/KIR -/CD57 -/NKG2A +) phenotype and a low cytotoxic activity. Since NK cells have demonstrated anti-leukemic activity in the context of Allo-HCT while less prone to induce GVHD than T cells, we hypothesized that NKG2A inhibition using the checkpoint inhibitor monalizumab (humanized IgG4 blocking monoclonal antibody) could improve NK cell mediated graft-versus-tumor effect, without triggering graft-versus-host disease. We thus performed the first clinical trial evaluating the safety of monalizumab as a prophylactic treatment after Allo-HSCT (NCT02921685).MethodThe objective was to determine the maximal tolerated dose (MTD) of a single infusion of monalizumab administered on day+75 or thereafter following Allo-HSCT. Inclusion criteria were: 1) adult patients who underwent first Allo-HSCT for hematological malignancy; 2) no prior history of GVHD, 3) reduced toxicity conditioning regimen, 4) ATG or PT-Cy based GVHD prophylaxis, and 5) GVHD prophylaxis with cyclosporine A ongoing at the time of monalizumab infusion.Four dose levels were investigated in this dose escalation study (0.04, 0.1, 0.3, and 1.0 mg/kg). Dose limiting toxicities (DLT) were defined by the occurrence of any grade 3 to 4 monalizumab-related adverse event within 28 days after infusion, including grade 3 to 4 acute GVHD and moderate to severe chronic GVHD. In case of DLT, a Bayesian continuous reassessment model (CRM) was used to predict the maximal tolerated dose (MTD) after each series of 3 patients treated at a given dose level. It was planned to treat 18 patients. Beyond clinical safety, blood samples were collected for NK and T cell immunomonitoring and receptor saturation assay.ResultsFifteen patients received monalizumab at a median time of 83 days (range: 75-103) after Allo-HSCT (3 at 0.04 mg/kg, 3 at 0.1 mg/kg, 3 at 0.3 mg/kg, and 6 at 1 mg/kg). Patients were transplanted for hematological diseases (9 AML, 3 MDS, 1 lymphoma, 1 CLL and 1 myelofibrosis), from a matched sibling (n=8), matched unrelated (n=6) or haploidentical donor (n=1).No DLT was observed during the dose escalation process or among the 6 patients treated at the highest dose level, justifying study early termination after 15 patients. Two patients developed transient low grade GVHD that spontaneously resolved without treatment (1 grade I acute GVHD on day+8 and 1 mild chronic GVHD on day+118). Systemic steroid requiring GVHD occurred in 3 patients (20%): 1 severe overlap GVHD (day+42, CR after treatment), 1 severe chronic GVHD (day+80, death from GVHD) and 1 late severe chronic GVHD after cyclosporine tapering for mixed chimerism (day+149, complete remission [CR] after treatment). No disease recurrence was observed, except for one patient with myelofibrosis who relapsed 3 years after monalizumab infusion. At a median follow up of 22 months (3-48) after monalizumab infusion, 13 out of 15 patients are in CR from their underlining malignancy without GVHD and immunosuppressive treatment at last contact.At the dose of 1 mg/kg, receptor saturation assays (RSA) showed persistent binding of monalizumab on peripheral blood NK cells. Indeed, more than 90% of NKG2A-positive NK cells were positive for monalizumab detection (Anti-IgG4-PE) until at least 14 weeks post treatment.ConclusionsMonalizumab can be safely administered after Allo-HSCT, with prolonged persistence on circulating NK cells. In the absence of DLT, MTD was not reached. Future trials will aim at measuring the clinical efficacy of monalizumab in this context, alone or in combination therapy. Disclosuresboyer Chammard: Innate Pharma: Current Employment. Chabannon: Sanofi SA: Other: Travel Support, Research Funding, Speakers Bureau; Bellicum Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Novartis: Speakers Bureau; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Terumo BCT: Speakers Bureau; Miltenyi Biotech: Research Funding; Fresenius Kabi: Research Funding; EBMT: Membership on an entity's Board of Directors or advisory committees. Vey: Amgen: Honoraria; BMS: Honoraria; BIOKINESIS: Consultancy, Research Funding; NOVARTIS: Consultancy, Honoraria, Research Funding; SERVIER: Consultancy; JAZZ PHARMACEUTICALS: Honoraria; JANSSEN: Consultancy. Olive: ImCheck Therapeutics: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Alderaan Biotechnology: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Emergence Therapeutics: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees. Blaise: Jazz Pharmaceuticals: Honoraria.

Validation of Different Prognostic Scores in Allogeneic Hematopoietic Cell Transplantation in the Post-Transplant Cyclophosphamide Era

INTRODUCTIONThe use of post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GvHD) prophylaxis has decreased the rates of this complication, resulting on an improvement of transplant-related toxicity and survival. Secondary to its efficacy, the use of PTCy has been almost universally integrated for allogeneic hematopoietic cell transplantation (alloHCT), independently of the selected donor source.Clinical decisions in alloHCT are supported by the use of prognostic scores for outcome prediction. However, capability of prediction by diverse scores can vary depending on their features and on the composition of the study cohort. Additionally, the continuous innovation on alloHCT techniques and practices leads to an ongoing need to update risk indices aimed at improving risk stratification of patients undergoing alloHCT. This study explores the predictive capacity of different prognostic scores routinely used in alloHCT, in a contemporaneous cohort of adults undergoing peripheral blood (PB) alloHCT using PTCy-based GvHD prophylaxis.METHODSBetween 2014 and 2020, 230 consecutive adults with hematological malignancies underwent PB-alloHCT with PTCy-based GvHD prophylaxis at our Institution. Data related to Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI), Karnosfky Performance Status (KPS), Disease Risk Index (DRI), European Bone Marrow Transplantation (EBMT) score, and Endothelial Activation and Stress Index (EASIX) were collected retrospectively. Complete information was available for 216 patients. Overall survival (OS) was considered the main outcome variable. Patients were grouped into two risk groups based on the optimal cut-off value for each score. In the case of EASIX, 1.578 was the most discriminating cut-off for OS. The score discrimination for OS was measured independently for each index using the receiver operating characteristic curve (AUC) calculated using receiver operating characteristic (ROC) curves, and determined at different time-points after alloHCT.RESULTSOf the 216 patients included, the median age was 52 years (range: 18-70), acute myeloid leukemia (36.1%) was the most prevalent baseline diagnosis, 42.1% of adults underwent reduced-intensity conditioning alloHCT, 69.4% received grafts from unrelated donors, and 23.0% from haploidentical donors. With a median follow-up of 22.6 months, 24.1% patients relapsed, and 2-y OS and non-relapse mortality were 67.3% and 19.9%.DRI, HCT-CI, KPS, and EASIX successfully grouped patients into higher and lower risk strata, supporting their use for risk classification. HCT-CI [(score>3 (vs 0-3): HR 2.02, p<0.01], DRI [High - Very High risk (vs Low - Int): HR 2.08, p<0.01], and EASIX [>1.578 (vs ≤ 1.578): HR 1.73, p<0.02], maintained an optimal discrimination capacity during the entire post-transplant follow-up (median AUC ranges > 55%).DRI was the most accurate prognostic index during the entire post-transplant period (median AUC ranges > 60%). KPS score was found to be a useful predictor of mortality up to the first year after alloHCT and with the highest prognostic accuracy at 3 months (AUC 67.09%). HCT-CI score was found to present a better discrimination capacity once elapsed 6 months after alloHCT and with a peak of prediction capacity at 2 years (AUC 60.3%). EASIX, when measured at the pre-transplant evaluation, demonstrated to have acceptable predictive ability during the entire post-transplant period (median AUC > 55%), and with a peak of prediction at 3 months (AUC 62.6%). The EBMT score had the lowest predictive capacity in our analysis (Figure 1). CONCLUSIONThis study validates, for the first time, the risk stratification capacity for OS of DRI, HCT-CI, KPS, and EASIX in PB-alloHCT with PCTy-based prophylaxis. Interestingly, the prediction accuracy of the prognostic scores differed depending on the time-period. This result can be taken into consideration to enhance the applicability of these scores and refine the clinical decisions taken based on the information provided from their use in routine clinical practice. [Display omitted] DisclosuresLozano: Terumo BCT: Honoraria, Research Funding; Macopharma: Research Funding; Grifols: Honoraria. Rosinol: Janssen, Celgene, Amgen and Takeda: Honoraria. Esteve: Novartis: Consultancy, Research Funding; Astellas: Consultancy; Jazz: Consultancy; Pfizer: Consultancy; Novartis: Research Funding; Abbvie: Consultancy; Bristol Myers Squibb/Celgene: Consultancy.

Apheresis Products from Patients with Multiple Myeloma Treated with G-CSF Are a Suitable Source of T Cells for the Production of BCMA-Targeting CAR-T Cells

Background:Autologous chimeric antigen receptor-T (CAR-T) cells that target BCMA (BCMA-CARs) have emerged as a promising treatment for multiple myeloma (MM). Current clinical protocols dictate that BCMA-CAR therapy is only used after patients have repeatedly relapsed. However, at this stage, the immunosuppressive nature of advanced MM and/or side-effects of the previous therapies cause T cell dysfunction and an unfavourable phenotype, such as exhaustion, senescence and loss of early memory cells.An alternative and convenient pool of ‘fitter’ T cells are apheresis products that are routinely collected to obtain progenitor cells for autologous stem cell transplantation (ASCT), an intervention that is often carried out early in MM treatment. However, to mobilise the progenitor cells, patients are treated with G-CSF, which could have negative effects on T cells such as reduce proliferation, impair CD8 + T cell function and induce regulatory T cell (Treg) expansion. Whether this has an effect on the BCMA-CARs generated from these T cells, however, is unknown. Therefore, we aimed to establish whether G-CSF treatment had detrimental effects on T cell phenotype, and moreover, to ascertain whether BCMA-CARs that are generated from these T cells were impaired compared to those produced from T cells prior to G-CSF infusion.Methods:T cells were isolated from the blood of 9 patients with MM before and after 4 days of subcutaneous G-CSF administration (PRE G-CSF and POST G-CSF, respectively) prior to peripheral blood CD34 + cell harvesting for an ASCT as consolidation after first-line induction treatment. Following stimulation with anti-CD3/anti-CD28 beads and IL-2, T cells were transduced with ARI2h, an anti-BCMA CAR produced at our institution that is currently being explored in a clinical trial for relapsed/refractory MM (NCT04309981). Freshly-isolated T cells or expanded ARI2h cells were analysed by flow cytometry for markers of cell identity, activation, dysfunction and memory, or alternatively, challenged with an MM cell line (ARP-1 or U266) and then tested for cytokine production and cytotoxic ability. In addition, PRE and POST G-CSF ARI2h CARs were injected into ARP-1 tumour-bearing mice to assess their in vivo function.Results:Firstly, the phenotype of PRE G-CSF and POST G-CSF T cells, before CAR production, was analysed to identify effects of G-CSF treatment. Interestingly, there were fewer POST G-CSF CD8 + T cells with a stem cell memory (CCR7 +CD45RA +CD95 +) phenotype, but the proportion of naïve (CCR7 +CD45RA +CD95 -) cells and other memory populations was not significantly different. Moreover, POST G-CSF T cells had a lower CD4:CD8 ratio, but did not contain more senescent-like cells or display evidence of pre-activation or increased expression of exhaustion markers. Due to the known effect of G-CSF on CD4 + Treg expansion, the percentage of Tregs was also compared between the PRE G-CSF and POST G-CSF samples, but no difference was observed.Following T-cell activation and CAR transduction, comparable transduction efficiencies and proliferation rates were obtained. Likewise, the in vitro function of PRE G-CSF and POST G-CSF ARI2h cells, as determined by assessing their cytotoxic response to MM cell lines and ability to produce effector molecules such as granzyme B, was similar. To test the in vivo function of ARI2h CAR-T cells expanded from PRE G-CSF and POST G-CSF samples, they were injected into a murine xenograft model of advanced MM. Mice administered with both PRE and POST G-CSF ARI2h cells survived longer than those given untransduced T cells (p=0.015 and p=0.039, respectively), but there was no difference in the longevity of mice between the PRE G-CSF and POST G-CSF groups (p=0.990) (Figure 1). The similarity of the in vitro and in vivo function of PRE and POST G-CSF ARI2h cells was reflected in the phenotype of the CAR-T cells after ex vivo expansion, with cells from both groups displaying equal levels of activation, exhaustion, and importantly for CAR-T cell activity, memory/effector phenotype.Conclusions:The in vitro and in vivo functions of ARI2h CAR-T cells when generated from either PRE G-CSF or POST G-CSF samples were comparable, despite G-CSF administration decreasing the CD8 + stem cell memory pool. Overall, we conclude that T cells from apheresis products, performed to collect G-CSF-mobilised peripheral blood progenitor cells for ASCT, are suitable for BCMA-CAR manufacture. [Display omitted] DisclosuresLozano: Grifols: Honoraria; Terumo BCT: Honoraria, Research Funding; Macopharma: Research Funding. Fernandez de Larrea: BMS: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Takeda: Honoraria, Research Funding; GSK: Honoraria; Sanofi: Consultancy; Janssen: Consultancy, Honoraria, Research Funding.

Are you finishing strong in cell therapy manufacturing? Tackling your final fill and finish challenges with automation

Dalip SethiManager, Senior Scientist at Terumo BCTDalip Sethi, is the Director of Scientific Affairs, and currently serves as Scientific and Clinical Development Lead for the cell therapy technologies portfolio at Terumo BCT. Prior to that, Dalip was engaged in the development of technologies and methods for use in cell therapy applications. He has authored multiple scientific publications, and is co-inventor on several patents.Annie CunninghamLaboratory Scientist, Terumo BCTAnnie Cunningham, is a Laboratory Scientist at Terumo BCT, were she is leading projects on the quantum cell expansion system, and the FINIA fill and finish system. Annie spent most of her career in the biotechnology industry, before shifting focus into immunotherapy, and contributing to the development of the CAR T program. She continued her research into the human immune system at the University of Colorado.

Total platelet donation count and donation frequency are determinants of plateletpheresis-associated lymphopenia.

Plateletpheresis using a leukocyte reduction system (LRS) traps donor WBCs in the LRS chamber, which may lead to lymphopenia, especially in frequent plateletpheresis donors. It seems plausible that this might cause adverse effects. However, current knowledge about potential confounders and donor health impacts is incomplete. Recent platelet donors and donations collected at University Hospital Regensburg from 2016 to 2019 using the Terumo BCT Trima Accel LRS system were retrospectively analyzed and compared with historical platelet donors and donations collected mainly with Fresenius Kabi Amicus non-LRS system from 2010 to 2013. Additionally, recent donors were prospectively surveyed using a health-related topics questionnaire. Analysis of 819 recent donors with 11,254 blood counts and 1464 questionnaires and 1011 historical donors with 12,848 blood counts revealed that increased annual platelet donation frequencies were associated with decreased lymphocyte counts in both groups. Median lymphocyte counts in recent donors with no versus ≥24 previous annual donations declined from 2.0 to 1.2 × 103 /μL (p < 2.2 × 10-16 ), and those in historical donors with no versus ≥24 previous annual donations decreased from 2.0 to 1.5 × 103 /μL (p=6 × 10-4 ), respectively. The questionnaire results showed that donation frequency and lymphopenia were not associated with upper respiratory tract infection (URTI) incidence or duration, but platelet donors who concomitantly donated granulocytes had significantly shorter URTI durations than those who did not (p=.008). This study confirmed that plateletpheresis-associated lymphopenia occurs in LRS and to a lesser degree in non-LRS platelet donors, but revealed no evidence of a negative impact on donor health.

Blood Cell Exchange in Sickle Cell Disease

Background and Objectives: Red cell exchange (RCE) is a type of therapeutic apheresis procedure aimed at removing the deformed red blood cells of a patient and replacing them with those obtained from healthy donors. It is a commonly used but yet underutilized procedure for the treatment of hemoglobinopathies such as sickle cell disease (SCD) (acute or chronic), and other diseases and conditions such as ABO-incompatible hematopoietic stem cell transplantation, severe erythrocytosis, hereditary hemochromatosis, severe infection with intra-erythrocytic parasites such as malaria, babesiosis or cases of a drug overdose, poisoning and to perform envenomation. The objective of the study is to study and understand the efficacy of RCE in the management of patients in various clinical scenarios. Methods: This is a retrospective study carried out at a tertiary care hospital in North India over a period of 4 years (2016–2020). All the RCE were performed on Spectra Optia apheresis (System 1 P0 4552 (Terumo BCT, Lakewood, CO, USA) which comes with a built-in software (Version 11) for performing RCE. Results: A total of 8 exchanges were performed in five patients. Three of these patients had undergone the procedure twice. Two out of the five patients were found to be antibody screen positive. Corresponding antigen-negative units of packed red cells were issued for these patients. The targeted and final fraction of red cell remaining values which were kept at ≤30% was achieved in all cases. Conclusion: RCE is a safe and effective therapeutic treatment modality for patients of SCD. It is a simple and relatively safe treatment modality that provides immediate relief in acute complications and also prevents the risk of long-term complications such as iron overload and iron-induced organ damage.

The Epidemiology of Platelet Transfusions: An Analysis of Platelet Use at 12 U.S. Hospitals

Background: Platelet transfusions in the United States are increasing in sharp contrast to the marked decrease in red cell and plasma use. Understanding the epidemiology and clinical practice for patients requiring platelet transfusions, particularly in the non-oncologic setting, is needed to identify clinical needs or significant change in practice. Such information can be used to focus the design of evidence based studies to assess platelet transfusion practice and efficacy to areas of high clinical need.Methods: Patient demographics, laboratory and clinical data were extracted from 2013 - 2015 from blood bank information systems and medical records from 12 REDS-III hospitals (both academic and community) located in four states across the U.S. A patient encounter was defined as any inpatient admission or outpatient visit documented with a unique visit date and discharge date. A transfusion episode was defined as all platelets transfused within an 8 hour interval beginning with the first platelet dose transfused within any encounter. Pre-platelet counts are defined as the nearest count up to 24 hours prior to the first transfusion for inpatients, and up to 48 hours before for outpatients. Post-platelet counts are defined as the first count up to 24 hours after completing the last transfusion for inpatients, and up to 48 hours after for outpatients.Results: A total of 122,298 platelet doses were issued for transfusion: 74,721 (61%) were apheresis platelets; 47,577 (39%) were pooled whole blood derived platelets; 103,759 (85%) were for inpatients, 18,539 (15%) were for outpatients. For inpatient transfusions 54% were issued to the General Ward, 29% to ICU, 12% to OR, 3% to ER. One platelet dose was issued per episode 78% of the time, 2 doses in 17%, 3 doses in 3%, and 4 doses in 1%. ABO donor-recipient identical platelets were transfused 37% of the time. For selected ABO mis-matched transfusions, type O platelets were given to non-type O patients 8%, and non-type O platelets to type O patients 19% of the time. Cardiovascular, Hematology-Oncology and Gastrointestinal were the most common broad diagnostic categories for encounters. The top three primary ICD 9-10 codes for each of these categories were: Cardiovascular: coronary atherosclerosis of the native coronary artery, aortic valve disorder and intracerebral hemorrhage; Hematology-Oncology: acute myeloid leukemia without achieving remission, neutropenia NOS, and multiple myeloma with achieving remission; Gastrointestinal: alcohol cirrhosis of the liver, cirrhosis of the liver NOS and hepatic encephalopathy.For inpatients a platelet count between >20,000/µL and 50,000/µL was the most common pre-transfusion count (28% of all episodes) with similar results for general ward (29%) and ICU patients (35%). In the ED and OR a platelet count >100,000/µL was most common - found in 38% and 37% of all episodes. For outpatient transfusions a count of >10,000/µL to 20,000/µL was most common (25%). For inpatients post-platelet count increment ranged from a median of 12,000/µL to 23,000/µL with progressively larger increments seen with progressively higher starting counts (Table 1). For outpatients post-platelet count increments ranged from 21,000/µL to 27,000/µL (Table 1).Conclusion: The REDS-III data base provides a wealth of information to assess platelet transfusion therapy in the U.S. Transfusion of more than 1 dose of platelets per episode is uncommon. Transfusion of ABO mismatched platelets is a common practice. Cardiovascular and Hematology -Oncology patients are prominent users of platelet products. General Ward and ICU dominate the location for platelet transfusion therapy and have similar transfusion practice patterns. The common pre-transfusion platelet count of 20,000-50,000/µL is surprising (as this exceeds evidence based recommendations for prophylactic transfusions in hematology-oncology patients) with reasons unclear. Platelet count increments were also surprisingly low. These findings, particularly the high pre-transfusion platelet count, the poor platelet increments and the high number ABO mis-matched transfusions, highlight differences in real world versus controlled studies and provide epidemiologic and laboratory data to develop future research to improve platelet transfusion practice. [Display omitted] DisclosuresNess:Terumo BCT: Consultancy.

Outcomes of Immunosuppressive Therapy for Pediatric Aplastic Anemia: A North American Pediatric Aplastic Anemia Consortium (NAPAAC) Study

Immunosuppressive therapy (IST) is effective treatment for severe aplastic anemia (SAA); however data on the quality of that survival for pediatric patients are limited. To investigate the clinical features and outcomes of children with SAA treated with IST, NAPAAC conducted a retrospective study of patients aged 1 to 20 years (yrs) treated with IST at 25 member institutions between 1/1/2002 and 6/30/2014 with a minimum of 24 months (mos) of follow-up.A total of 314 patients were treated with IST for SAA defined as a hypocellular marrow with at least two cytopenias: 1) absolute neutrophil count <500/uL, 2) platelet count <20,000/uL, and/or 3) hemoglobin <8 g/dL. The median age at diagnosis was 9.7 yrs and 51.6% were male. Patients were racially diverse with 58.3% white (15.9% overall Latino ethnicity), 16.6% Black, 7.3% Asian, and 17.8% mixed/other. A history of hepatitis was reported in 43 (13.7%) patients. Mean red cell volume (MCV) was elevated ≥100 fL in 54 of 272 pts (19.9%), median 89.1fL. Absolute lymphocyte count was <1,000/uL in 110 of 260 pts (42.3%). Lymphocyte telomere length was <1st percentile for age in 6 of 92 pts (6.5%). A granulocyte PNH clone was detectable in 55 of 140 pts (39.3%), all with a small clone size (75th quartile 0.12%).IST regimens included: horse ATG and cyclosporine (hATG/CSA; n=263), horse ATG/ tacrolimus (n=15), rabbit ATG/CSA (n=14), rabbit ATG/tacrolimus (n=1), cyclophosphamide (n=19) and sequential horse/rabbit ATG (n=2). Median time from diagnosis to IST was 24 days, with 168 (54.2%) treated within 4 weeks (wks).Response to IST was defined as follows: •Complete Response (CR): Hgb ≥ 10 g/dl, ANC ≥1,000/uL, Plts ≥100,000/uL•Very Good Partial Response (VGPR): Hgb ≥ 8 g/dl, ANC ≥ 500/uL, Plts ≥ 50,000/uL•Partial Response (PR): Hgb ≥ 8 g/dl, ANC ≥ 500/uL, Plts ≥ 20,000/uL•No Response (NR): Hgb < 8 g/dl, ANC < 500/uL, Plts < 20K/uLPatients receiving PRBCs within 6 wks, platelets or G- or GM-CSF within 2 wks of a timed endpoint were deemed to have no response.At a median follow-up of 61.5 mos post IST, 30 of 314 pts (9.6%) had died. Best response at any time after IST of 301 evaluable patients was CR (192; 61.1%), VGPR (25; 8%), PR (10; 3.2%) and NR (74; 23.6%). The median time to best response was 6 mos (range 3-48 mos), and did not differ with time between diagnosis and IST. Of the 227 pts with a CR, VGPR or PR at any time, 47 (20.7%) ultimately died or required additional therapy (IST and/or HSCT). Overall survival was 98% at 6 mos, 95% (95% CI: 92-97) at 24 mos, and 93% (95% CI: 90-96) at 60 mos. Survival did not differ between patients treated <4 vs ≥4 wks from diagnosis (p=0.533) with 24 mos estimate of 96% vs 94%. Survival without a subsequent therapy was 84% (95% CI: 80-88) at 6 mos, 68% (95% CI: 63-73) at 24 mos, and 58% (95% CI: 52-64) at 60 mos. Of the 261 evaluable pts treated with hATG/CSA, 21 pts (8.1%) died, overall survival was 94% (95% CI: 91-97) and one-third required at least one additional therapy.Cytogenetics were available at diagnosis for 271 of 314 (86.3%) pts, and 8 (3%) had clonal abnormalities. Of 171 patients with cytogenetics after IST, 13 (7.6%) additional patients developed clonal abnormalities at a median time of 28.5 mos (range: 4.3-143 mos). Monosomy 7, del 7q, and del 13q were the most common abnormalities. Only 4 patients with clonal abnormalities developed MDS, with one each progressing to ALL and AML. The other two patients received a HSCT soon after the MDS diagnosis. There was no significant association between hepatitis, cytogenetic abnormalities, short telomeres, or PNH clone at diagnosis with response to IST.In conclusion, we report a large multicenter retrospective analysis of ethnically diverse North American IST treated pediatric SAA patients. Acquisition of clonal abnormalities and progression to MDS/leukemia was rare. Outcomes included 69.1% of pts with a CR or VGPR and overall survival of 93%. Among the 314 patients, event-free survival was 58% at 60 mos with 130 (41%) having died or required subsequent therapies. Unexpectedly, neither clonal abnormalities at diagnosis or time between diagnosis and IST affected response. Clinical and laboratory features associated with survival, quality, and durability of response to IST are currently being ascertained. These data support the need for new approaches to treatment of pediatric SAA. DisclosuresRogers:Terumo BCT: Consultancy; Pfizer: Research Funding. Rothman:Agios Pharmaceuticals: Honoraria; Pfizer: Consultancy. Thompson:Celgene: Consultancy, Research Funding; Baxalta: Research Funding; Novartis: Consultancy, Research Funding; bluebird bio: Consultancy, Research Funding. Glader:Agios Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Huang:Baxter: Research Funding; Biogen: Research Funding; Bio Products Laboratory: Other: Study investigator; Novartis: Other: support to attend meeting. Shimamura:TransCellular Therapeutics: Other: Spouse is majority shareholder .

Platelets Feeding Bacteria with Lactate during Room Temperature Storage: Mitigated By Refrigeration

Introduction: Platelet transfusion related sepsis is a serious concern limiting platelet storage time to 5 days. Room temperature (RT) storage of platelets increases the risk of bacterial growth and necessitates implementation of bacterial contamination monitoring. Cold storage of platelets represents an attractive alternative for improving platelet safety. In this study, we assessed bacterial growth in platelets stored either at room temperature (22oC) or refrigerated (4oC).Methods: Apheresis platelets in plasma (PLT) were obtained from healthy donors using the Terumo Trima Accel Automated Blood Collection System (Terumo BCT). Platelet poor plasma (PPP) was obtained from PLT aliquots centrifuged twice at 2,500 x g for 5 min. In some experiments aliquots of PPP were supplemented with 5 to 20 mM lactic acid. Aliquots of PLT or PPP were transferred to pH SAFE minibags (Blood Cell Storage, Inc) and inoculated with Acinetobacter baumannii strains Ci77 or Ci79, Escherichia coli, Pseudomonas aeruginosa, or PBS (uninfected control). Minibag aliquots stored at RT were agitated using an orbital shaker set to 60 rpm while refrigerated aliquots were stored under static conditions. Bacterial growth was monitored daily through dilution plating. Lactate levels in PLT aliquots were assessed by iSTAT (Abbott) using CG4+ test cartridges. Platelet activation and aggregation were assessed on days 0, 1, 3, and 5 by flow cytometry and Multiplate platelet aggregometry respectively.Results: Growth of A. baumannii progressed exponentially over the first 3 days post-collection in PLT aliquots stored at RT. However, growth was significantly (p < 0.05) reduced in PPP units. Growth of E. coli and P. aeruginosa, both of which are capable of utilizing glucose present in the anticoagulant used, grew at significantly faster rates and did not seem to be dependent on metabolically active PLTs. Lactate levels were assessed in PLT units and found to mirror growth of A. baumannii . Furthermore, addition of ≥ 15 mM lactic acid to RT stored PPP restored A. baumannii growth. Although lactate levels did not appear to contribute to growth of E. coli, lactate levels began to decrease in PLT units contaminated with the bacterium at a rapid rate after day 3. Lactate levels in units contaminated with P. aeruginosa increased throughout the observation window. Bacterial growth remained static throughout under all treatment conditions stored refrigerated and lactate levels were reduced. PLT also appeared to retain function throughout cold storage irrespective of bacterial contamination while RT storage resulted in a decrease in aggregation over time which was exacerbated by bacterial contamination.Conclusions: Bacterial growth remained static throughout under cold storage. Additionally, PLT lactate production was increased at RT and correlated with increased growth of A. baumannii . Growth of E. coli and P. aerugionsa appeared to proceed independently of lactate production or metabolically active PLTs. However, E. coli did appear to utilize lactate as a carbon source at later time points. These data demonstrate that bacterial growth can be controlled through refrigeration without loss of function and RT stored platelets may potentiate growth of certain bacterial strains through accelerated metabolism relative to cold storage. DisclosuresNo relevant conflicts of interest to declare.

Eyelid myotonia and face stiffness in skeletal muscle sodium channelopathy

Title Eyelid myotonia and face stiffness in skeletal muscle sodium channelopathy&#x0D; Video Legend Video 1. Notice the delayed relaxation of the eyelids after forced eye closure (eyelid myotonia). Also, notice the full facial hair to prevent facial muscle stiffening exacerbation with cold weather.&#x0D; AuthorsSrijan Adhikari, MBBS, Jeffrey Statland, MD, Constantine Farmakidis, MD&#x0D; Authors information:&#x0D; Srijan Adhikari, MBBS, ORCID ID: 0000-0001-9653-3079, University of Kansas Medical Center, Department of Neurology, Kansas City, Kansas, USAJeffrey Statland, MD, ORCID ID: 0000-0003-0790-5315 University of Kansas Medical Center, Department of Neurology, Kansas City, Kansas, USAConstantine Farmakidis, MD, ORCID ID: 0000-0002-4688-9224, University of Kansas Medical Center, Department of Neurology, Kansas City, Kansas, USA&#x0D; Corresponding Author &#x0D; Srijan Adhikari, MBBS,Department of Neurology,University of Kansas Medical Center,3901 Rainbow Boulevard., MS 2012,Kansas City, KS 66160sadhikari@kumc.edu&#x0D; Author Conflict of Interests &#x0D; Dr Adhikari has nothing to disclose.Dr. Statland reports grants from NIH, grants from MDA, grants from FSHD Society, grants from Friends of FSH Research, personal fees from Dyne, personal fees from Fulcrum, personal fees from Avidity, personal fees from MT Pharma, personal fees from Acceleron, personal fees from Sarepta, personal fees from Strongbridge, outside the submitted work. Dr. Farmakidis reports personal fees from Argnex, personal fees from Momenta, personal fees from Terumo BCT, outside the submitted work.

Variable response to therapeutic plasma exchange in pediatric anti-NMDA receptor encephalitis.

Anti-NMDA receptor encephalitis in an acute form generally presents with abnormal movements and psychiatric symptoms. Therapeutic plasma exchange has been considered to be one of the first line treatment options. This report highlights the role of plasma exchange in anti-NMDA receptor encephalitis in pediatric patients. This is a retrospective analysis of four cases of a severe form of encephalitis due to anti-NMDA receptor antibody. All these four patients were evaluated for clinical and laboratory profile before plasma exchange. Plasma exchange was performed with Cobe Spectra Version 7.0(Terumo BCT, USA), and 5% albumin and fresh frozen plasma were used as replacement fluid. A total of 20 procedures (range: 2-8/patient) were performed on four patients on an alternate day basis. Slow recovery and long-term hospitalization (range: 25-70 days) was observed in all these patients and may be due to delayed initiation of plasma exchange. One patient was lost in follow up while another one had fatal consequences after one month of discharge from the hospital. Early diagnosis and timely initiation of therapeutic plasma exchange along with immunosuppressive therapy hasten the recovery, duration of hospitalization and yield a better outcome.