Median Absolute Neutrophil Count Research Articles

Safety and Efficacy of Splenic Irradiation for Non-Hodgkin Lymphoma

Background: Splenic infiltration and associated splenomegaly is a challenging complication of non-Hodgkin lymphoma (NHL). The choice between splenectomy and splenic radiation (RT) is controversial, with little data to provide guidance in NHL. We aim to assess the tolerability and efficacy of splenic RT in NHL. Methods: We reviewed NHL patients treated from 2002 to 2021 with RT to the spleen alone. Splenomegaly was defined as vertical length >13cm. Splenic volume was obtained by manual contouring in MIM PACS 6.9.7 on the baseline pre-RT CT scan and the CT scan at best splenic response post-RT. PET response was evaluated by Lugano criteria. Adverse events (AEs) were retrospectively graded by clinicians using CTCAE v5.0. Cell counts were collected at baseline pre-RT and through 90 days post-RT completion; cell counts were censored at initiation of cytotoxic chemo post-RT if received. Significance was assessed with the Kruskal Wallis test. Results: 21 patients (11 diffuse large B-cell lymphoma (DLBCL), 5 marginal zone lymphoma (MZL), 4 mantle cell lymphoma (MCL), 1 follicular lymphoma) were identified with 23 courses of splenic RT. Median age was 75 (42-94); median KPS was 80 (50-90). Most patients (57%) had splenic only disease. Median splenic height pre-RT was 13.6 cm (6.4-26.6); 13 patients (57%) had baseline splenomegaly. Median splenic volume was 682cc (104-3355). 11 patients (48%) were symptomatic pre-RT (most frequently with pain: n=7, dyspnea: n=4, or nausea: n=4). 91% had any cytopenia before RT with median baseline absolute neutrophil count (ANC) 2.3 (0.2-10.6), hemoglobin 9.8 (7.1-13.8), and platelets 93 (9-221). RT was performed with definitive (n=11) or palliative (n=9) intent, or as bridging to chimeric antigen receptor T cells (n=3). Median dose was 30Gy for DLBCL (10.8-45), and 4Gy for MCL/MZL/FL (0.6-20); 10 patients received ≥20Gy. RT was well tolerated with 43% of courses without AEs and 57% with G1-2 AEs. AEs with frequency >10% were G1 fatigue (n=6), G1 anorexia (n=5), G1 nausea (n=5), G1 diarrhea (n=4), and G2 fatigue (n=4). There were no G3-4 AEs. One patient died from respiratory failure secondary to fungal pneumonia which was not felt to be attributable to splenic RT. Median nadirs in the 19 patients with cell count data: ANC 1.6 (0.2-3.8), hemoglobin 10.1 (6-13.4), platelets 70 (6-182) with 8, 6, and 15 median days from RT start to nadir (Table 1). ANC and platelets were disproportionately affected (median reduction: 26% and 28% for ANC and platelets, respectively vs. 5% for hemoglobin; p=0.006). There were no significant differences in reductions in ANC, platelets, or hemoglobin by RT dose (≥20Gy vs. <20Gy; p>0.1). In 3 patients (14%) cytopenias completely normalized post-RT. In most patients, cell counts normalized to pre-RT baseline (see Table 1). 4/13 symptomatic patients (31%) experienced complete relief. Median reduction in splenic volume was 34% (0-90%) with no significant difference in cytoreduction between low and high dose RT groups (median 27% reduction in <20Gy and 46% in ≥20Gy; p=0.2), see Figure 1. Overall response rate (ORR) by PET was 85% (35% complete response, 50% partial response, 10% stable disease, 5% progressive disease). With a median follow up of 12mo, median duration of radiographic response was 8mo (0.5-103) with more durable response at ≥20Gy (median 35 vs. 4mo, p=0.01). Conclusion: Splenic RT was well tolerated and had a high ORR of 85%. Radiographic response was more durable at doses ≥20Gy. Larger sample sizes with homogenous histology are needed to further evaluate the impact of dose on cell counts, clinical toxicity, and symptomatic relief. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A Prospective, Randomized Trial Examining the Use of G-CSF Versus No G-CSF in Patients Post-Autologous Transplantation

Contemporary, prospective data regarding the impact of granulocyte-colony stimulating factor (G-CSF) on outcomes after autologous hematopoietic stem cell transplantation (Auto-HSCT) in an era when stem cell grafts are more qualitatively robust are limited. Recent retrospective analyses have not supported a beneficial effect of post-transplantation G-CSF use on major outcomes after Auto-HSCT leading to strategies to delay or eliminate the use of G-CSF altogether in this context. To test the hypothesis that the infusion of consistently higher doses of stem cells (defined as ≥4 × 106/kg) in Auto-HSCT will obviate the need for post-transplantation G-CSF. If so, the impact of withholding G-CSF will be noninferior to the use of G-CSF in terms of length of stay (LOS). The specific objectives were to conduct a prospective, randomized clinical trial primarily examining the impact of post-transplantation G-CSF on LOS, and secondarily on engraftment, infectious complications, antibiotic usage, and incidence of engraftment syndrome after Auto-HSCT in patients receiving versus not receiving G-CSF after Auto-HSCT. Patients with multiple myeloma or non-Hodgkin lymphoma (NHL) who underwent Pegfilgrastim plus Plerixafor-primed stem cell collection followed by Auto-HSCT were randomized to the G-CSF group (receive G-CSF starting at day 3 after Auto-HSCT) or the no G-CSF group (G-CSF withheld after Auto-HSCT). Seventy patients per arm were planned to demonstrate the primary endpoint of noninferiority in LOS between the G-CSF and the no G-CSF groups. Patient outcomes in the two groups were followed up and compared after Auto-HSCT, and an interim analysis for futility was planned when accrual reached 50%.The primary finding of this study was that despite only a 2-day longer median absolute neutrophil count (ANC) recovery in the no G-CSF arm (median 11 versus 13 days; P = .001), LOS was 4 days longer in patients not treated with G-CSF (median 11 days versus 15 days; P = .001). G-CSF use was associated with more robust incremental daily increases in ANC once recovered (P = .001), fewer days of febrile neutropenia (P = .001), and fewer days on antibiotics (P = .001), potentially contributing to this disproportionate finding. Inferiority in LOS in the no G-CSF group was demonstrated on the interim analysis, and the study was closed at the half-way point. There were no significant group differences in platelet recovery, documented infections, hospital readmissions, or overall survival at 1 year. Engraftment syndrome occurred in 54.3% of patients and was not related to G-CSF use. These results suggest that the increased LOS associated with the omission of G-CSF is largely due to concerns regarding the potential for infection in patients without a stable, recovered ANC in a hospital setting. Engraftment syndrome represented a significant source of febrile neutropenia further contributing to patient safety concerns and requires strategies to decrease its incidence. Infectious complications and death were not affected by the omission of G-CSF supporting a carefully monitored outpatient approach to Auto-HSCT in which white blood cell growth factor is eliminated or given as needed for documented infection.© 2023 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Childhood aplastic anaemia with paroxysmal nocturnal haemoglobinuria clones: A retrospective single-centre study in South Africa.

BackgroundParoxysmal nocturnal haemoglobinuria (PNH) clones in children are rare but commonly associated with aplastic anaemia (AA) and myelodysplasia.ObjectiveThis study aimed to determine the prevalence of PNH clones in paediatric patients with idiopathic AA, identify differences in clinical and laboratory features and outcomes, and determine the impact of clone size on clinical presentation.MethodsPatients with confirmed idiopathic AA who were tested for PNH between September 2013 and January 2018 at the Inkosi Albert Luthuli Central Hospital, Durban, KwaZulu-Natal, South Africa, were included. PNH clones were detected in neutrophils and monocytes by flow cytometry using fluorescent aerolysin, CD24, CD66b and CD14.ResultsTwenty-nine children with AA were identified and 11 were excluded. Ten patients (10/18, 55.6%) had PNH clones ranging from 0.11% to 24%. Compared to the PNH-negative group, these children were older (median: 10 years vs 4 years, p = 0.02) and had significantly lower total white cell counts (median 1.7 × 109/L vs 3.2 × 109/L; p = 0.04). There was no difference in median absolute neutrophil count or haemoglobin concentration. Four patients in each group received immunosuppressive therapy (IST). At six months, all four patients with PNH clones had responded, compared to one in the PNH-negative group.ConclusionMore than half of children with AA had a PNH clone. The size of the clone did not impact clinical severity; however, IST use may positively impact prognosis. We recommend early initiation of IST in patients with AA to avoid delays associated with human leukocyte antigen typing.

Abstract P015: Characterization and prognostic impact of DC-HIL in advanced colorectal cancer

Abstract Introduction: DC-HIL is the T cell-inhibitory receptor that is expressed by exponentially expanding CD14+HLA-DRno/low myeloid-derived suppressor cells (MDSC) and critically mediates the immunosuppressive function. We previously reported that this DC-HIL expression is associated with colorectal cancer (CRC) progression. The purpose of this investigation was to determine the correlation of DC-HIL-expressing MDSC subpopulation in blood with clinical outcomes in advanced CRC. Methods: Patients with metastatic CRC (n = 63) were analyzed by flow cytometry for DC-HIL or PDL1 expression on blood CD14+HLA-DRno/low MDSC. A retrospective chart review was performed to obtain data on demographics, tumor, and clinical characteristics including tumor laterality, histology, mutational and microsatellite stability status, stage, metastatic sites, CEA level, and white blood cell count, and differential and treatment outcomes including response to therapy and survival. Baseline characteristics were compared using the two-tailed Student's t-test, ANOVA test, or Pearson correlation test as appropriate. Survival analysis was estimated using the Kaplan-Meier method and Cox regression model, and groups were compared using the log-rank test. Results: Median age at diagnosis was 56 years (range 30-78) and patients were predominantly male (59%) and white (76%). Forty pts had left-sided tumors (63%), the majority had moderately differentiated adenocarcinoma (66%) and stage IV colorectal cancer at diagnosis (68%). At the time of DC-HIL collection, 95% of pts had stage IV disease. Most (95%) pts had microsatellite stable disease, 24% of pts had a KRAS mutation and 22% had a BRAF mutation, 69% of patients underwent surgical resection of the primary malignancy or metastatic site or both. Median CEA level was 40 ng/ml, median white blood cell (WBC) count was 5.9 × 109, median absolute monocyte count (AMC) was 0.64 × 109, median absolute neutrophil count (ANC) was 3.6 × 109, median monocyte to lymphocyte ratio (M/L) was 0.53 and median neutrophil to lymphocyte ratio (N/L) was 2.7. Most pts (90%) received FOLFOX chemotherapy as first-line and 84% of pts received an anti-VEGF agent throughout the course of their treatment. Median CD14+/PBMC for pts was 14.4, median %MDSC/PBMC was 7.0, median %DC-HIL+/MDSC was 66, median %DC-HIL+/MDSC/PBMC was 4.1 and median sDC-HIL was 20.0 ng/ml. Our results showed that there was a statically significant correlation between % MDSC/PBMC, %DCHIL+MDSC/PBMC, and the monocyte/lymphocyte (M/L) ratio with p=0.047 and p=0.03 respectively. There was no statistically significant correlation between DCHIL+/MDSC levels and response to therapy, time-to-next therapy (p=0.11), or overall survival (p=0.67). Conclusion: DC-HIL+ MDSC is positively correlated with M/L ratio, a possible prognostic marker in CRC patients. DC-HIL correlates poorly with other clinical outcomes; chemotherapy response, time-to-next therapy, or overall survival. Citation Format: Jude Khatib, Jin-Sung Chung, Sarah Reddy, Nivan Chowattukunnel, Allante Milsap, Yasin Goksu, Kiyoshi Ariizumi, Syed Kazmi. Characterization and prognostic impact of DC-HIL in advanced colorectal cancer [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr P015.

A Multi-Center Retrospective Study of Polatuzumab for Patients with Large B-Cell Lymphoma Relapsed after Standard of Care CAR T-Cell Therapy

A Multi-Center Retrospective Study of Polatuzumab for Patients with Large B-Cell Lymphoma Relapsed after Standard of Care CAR T-Cell Therapy

Clinical Characteristics of Severe Acute Chest Syndrome in Children with Sickle Cell Disease

Background: Acute chest syndrome (ACS) is a form of acute lung injury that is a leading cause of morbidity and mortality in children and adults with sickle cell disease (SCD). Despite advances in health maintenance and disease-modifying therapies for SCD, ACS remains a common and often severe complication. There is still limited understanding of why some patients suffer more severe ACS episodes. Few studies have specifically investigated clinical parameters associated with severe ACS in the pediatric population. The purpose of this study is to determine the association between hematologic and radiologic clinical findings and severe ACS in children and adolescents with SCD.Methods: We conducted a single-institution retrospective chart review of 120 pediatric patients with HbSS or HbSβ 0 thalassemia and at least one documented episode of ACS, and then further classified patients by their most severe ACS event. We extracted laboratory and radiologic data to compare clinical findings. Infections reported in patient encounters were verified by documented viral PCR and blood cultures. Continuous variables were analyzed using Welch's t-test; categorical variables were analyzed using Fisher's exact test.Results: Eighty patients in the moderate ACS group were excluded for this analysis. Twenty patients (median age 5.6 years, SD 4.20) had mild ACS defined by no supplemental oxygen requirement, only one segmental or lobar infiltrate on chest radiography, and transfusion of less than 3 units (or 15 cc/kg) of red blood cells. Twenty patients (median age 7.6 years, SD 4.01) had severe ACS characterized by acute respiratory failure requiring mechanical (invasive or non-invasive) ventilation and/or exchange transfusion. Median length of stay for patients with severe ACS was longer than for the mild cohort (mean: 8 days vs 2 days, p <0.001). The median absolute neutrophil count (ANC) was significantly higher in the severe ACS cohort (19.8 x 10 3µL vs. 9.4 x 10 3 µL, p = 0.004). The median platelet count nadir was significantly lower in the severe ACS group compared to the mild group (165 x 10 3 µL vs. 309 x 10 3 µL, p <0.001). Review of radiologic data showed that the median number of lobes affected in the severe ACS group were 3, compared to 1 lobe in the mild group (p <0.001). Approximately 65% of patients with mild ACS had left-sided disease (p = 0.18), while 85% of patients with severe ACS had bilateral disease (p = 0.002). The risk of pleural effusions was also significantly increased with severe ACS [OR 76.00 (95% CI 9.235-825.6), p <0.001]. When we analyzed infection at time of ACS, the proportion of laboratory-confirmed viral infections were twice as high in the mild ACS cohort (41.2%), compared to the severe ACS cohort (20.0%, p = 0.279). There were no bloodstream bacterial infections found in either cohort.Conclusion: Severe ACS in children is a clinically distinct phenotype associated with longer length of stay, higher ANC and lower platelet nadir counts during active ACS, increased involvement of 3 or more lung lobes, and presence of pleural effusions. A lower proportion of confirmed viral infections were found in the severe ACS cohort compared to mild ACS patients, although did not reach statistical significance. Future prospective studies investigating the utility of these specific laboratory and radiographic parameters as components of an ACS severity prediction score are warranted. DisclosuresTubman: Forma Pharmaceuticals: Consultancy; Novartis Pharmaceuticals: Honoraria, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Perkin Elmer: Honoraria. Fasipe: Emmaus: Consultancy; Bluebird Bio: Consultancy; Global Blood Therapeutics: Consultancy, Other: Grant Review Committee ; Novartis: Consultancy; Pfizer: Research Funding.

A Phase I Study of the Combination of Venetoclax and Azacitidine in Relapse/Refractory Higher Risk Myelodysplastic Syndrome (MDS)

A Phase I Study of the Combination of Venetoclax and Azacitidine in Relapse/Refractory Higher Risk Myelodysplastic Syndrome (MDS)

Increased Frequency of Mutations in the Gene Responsible for Familial Mediterranean Fever (MEFV) in a Cohort of Patients with Chronic Idiopathic Neutropenia

▪Introduction-Aim: Chronic idiopathic neutropenia (CIN) is a neutrophil disorder characterized by the prolonged and unexplained reduction in the number of peripheral blood (PB) absolute neutrophil counts (ANC). The underlying pathogenesis in CIN implicates the production of proinflammatory cytokines by activated lymphocytes and monocytes that induce excessive apoptotic death of the bone marrow (BM) granulocytic progenitor cells. Clonal hematopoiesis identified by next generation sequencing (NGS) of myeloid genes is found in 11% of CIN patients conferring an increased risk for MDS/AML transformation whereas the non-clonal patients display usually a benign course. The basis for the immune cell activation and proinflammatory cytokine production in CIN remains obscure. Based on previously reported data showing increased frequency of mutations of the MEFV gene encoding pyrin in patients with idiopathic inflammatory conditions other than typical Familial Mediterranean Fever (FMF), we sought to investigate the common MEFV mutations in a cohort of well characterized CIN patients.Patients-Methods: We have studied 50 patients fulfilling the previously reported diagnostic criteria of CIN (median ANC 1.5x10 9/L, range 0.2-1.7 x10 9/L), 44 females and 6 males with a median age of 56 years (range 25-87 years) and a long-follow-up (median 132 months, range 8-336 months) in the Department of Hematology of the University Hospital of Heraklion, Crete, Greece. Nonisotopic RNase cleavage assay (NIRCA) analysis was used as first screening method to detect MEFV exons 10 and 2 mutations in DNA extracted from PB or BM samples from CIN patients, confirmed by direct NGS analysis. These sequences contain the main disease-related mutations and polymorphisms.Results: Genetics alterations of MEFV were detected in 22 out of 50 CIN patients (44%). Pathogenic mutations (variants associated with typical or “atypical” FMF phenotype in Greek population) were identified in 10/50 CIN patients (20%). The 20% frequency of MEFV mutations in exon 10 and/or exon 2 in CIN patients is significantly higher compared to the carrier rate of common MEFV mutations in the healthy Greek population (0.7%) according to our previously reported data (P<0.0001, Fisher's exact test). NGS analysis confirmed the mutational pattern of NIRCA and specifically showed: (a) one patient with heterozygous I720M (ATC>ATG; Ile>Met), two patients with heterozygous A744S (GCC>TCC; Ala>Ser) and one with homozygosity, one patient with heterozygous M694V (ATG>GTG; Met>Val), one with heterozygous K695R (AAG>AGG; Lys>Arg) and one with heterozygous M680I (ATG>ATC; Met>Ile), all in exon 10, and (b) four patients with homozygous R202Q mutation in exon 2 (one patient with homozygous A744S co-mutation in exon 10) and two patients with R202Q heterozygosity combined with heterozygosity of I720M and A744S of exons 10, respectively. None of the patients displayed any symptoms/signs of FMF or other systemic inflammatory disease. No statistically significant differences were identified between MEFV mutated and non-mutated CIN patients in the severity of neutropenia or in lymphocyte, monocyte, hemoglobin and platelet counts. A significant difference was identified between the two patient groups in serum IgG (1440±264 vs 1133±245 mg/dl; P = 0.0023, Mann-Whitney test) but not IgA or IgM levels.Discussion: This study reports for the first time that 20% of unselected, consecutive patients with CIN carry mutations of the MEFV gene without clinical manifestations of FMF. Whether these patients represent atypical cases of FMF or the identified MEFV genetic alterations have a pathogenetic/modifying effect in the inflammatory responses associated with CIN is an open/novel field of research. As a first step we are currently investigating the neutrophil autophagic status, IL-1β production and the neutrophil extracellular trap (NET) formation in CIN patients with mutations in MEFV to clarify their potential effect in the immune deregulation known to characterize CIN. DisclosuresNo relevant conflicts of interest to declare.

Bendamustine Is a Safe and Effective Regimen for Lymphodepletion before Tisagenlecleucel in Patients with Large B-Cell Lymphomas

Bendamustine Is a Safe and Effective Regimen for Lymphodepletion before Tisagenlecleucel in Patients with Large B-Cell Lymphomas

Incidence, Risk Factors and Outcomes of Pancytopenia Following Chimeric Antigen Receptor (CAR)-T Cell Therapy in Relapsed Refractory Diffuse Large B Cell Lymphoma

Introduction: CD19 directed CAR-T cell therapy has changed treatment paradigm of relapse refractory diffuse large B cell lymphoma (DLBCL). It is associated with certain unique toxicities including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), B-cell aplasia and hypogammaglobulinemia. However, the information on hematologic toxicity including neutropenia, thrombocytopenia and anemia is limited.Methods: We retrospectively evaluated patients who received CAR-T cell therapy for relapsed refractory DLBCL to estimate incidence, risk factors and outcomes of hematological toxicity especially pancytopenia. We also evaluated the impact of prophylactic G-CSF administration on incidence and duration of neutropenia, and infectious complications.Results: Between April 2018 and December 2020, 30 adult patients received CAR-T cell therapy (AxiCel=22, TisaCel=8). Median age of the population was 57 years (range, 23-81). Median time from diagnosis to CAR-T cell therapy was 674 days. Four patients each had double expressor and double hit subtypes. Seventy percent patients had extra-nodal disease, 60% of patients received three or more lines of therapy, 27% of patients received prior autologous stem cell transplant (autoSCT), and 23% patients received bridging therapy. All patients received Fludarabine and Cyclophosphamide (Flu/Cy) as a lymphodepleting therapy. CRS and ICANS were noted in 83% and 37% patients, respectively. One-year progression-free and overall survival were 49.76% and 85.91%, respectively.After CAR-T cell therapy, 93% (28/30) patients developed neutropenia with 17 (57%) experiencing absolute neutrophil count (ANC) <100/mm3, 9 (30%) developing ANC 100-500/mm3, and two (7%) with ANC 500-1000/mm3. Median ANC nadir was zero (range, 0-2800/mm3). The median time to ANC <1500/mm3, ANC <1000/mm3, ANC <500/mm3 and ANC <100/mm3 was 1 day, 2 days, 4 days, and 7 days post-CAR-T cell therapy, respectively. At day+30, the cumulative incidences of ANC <1500/mm3, ANC <500/mm3, ANC <100/mm3 were 93.3%, 90%, and 56.7%, respectively. The median duration of ANC <1500/mm3, ANC <500/mm3, and ANC <100/mm3 was 24 days, 6 days, and 3 days, respectively. At day +30, 3.7% of patients had persistent neutropenia with ANC <500/mm3, whereas 23.21% of patients experienced mild neutropenia (ANC <1500/mm3) at day +80 following CAR-T cell therapy. Nineteen patients received prophylactic G-CSF and 11 patients did not. No difference in infectious complications, and ICU admission was noted between both groups.Following CAR-T cell therapy, 86% (26/30) patients developed thrombocytopenia with two (7%) experiencing platelets <10,000/µL, 12 (40%) developing platelets 10,000-50,000/µL, and 12 (40%) with platelets 50,000-150,000/µL. Median platelet nadir was 57,000/µL (range, 2000-194,000). The median time to platelets <150,000/µL, <50,000/µL, and <10,000/µL was 1 day, 6 days, and 20 days post-CAR-T cell therapy, respectively. At day+30, the cumulative incidences of platelets <150,000/µL, platelets <50,000/µL, and platelets <10,000/µL were 83.3%, 40%, and 6.67%, respectively. The median duration of platelets <50,000/µL was 28.5 days and <150,000/µL was 192 days. At day +30, 50% of patients had persistent thrombocytopenia with platelets <50,000/µL, and 80.77% of patients had thrombocytopenia with platelets <150,000/µL. Sixty-one percent patients still experienced platelets <150,000/µL at day +80 following CAR-T cell therapy.Univariable analyses revealed that high dose of CAR-T cell was associated with decreased incidence of neutropenia (HR, 0.63; p=0.02), while absence of extra-nodal disease was associated with increased incidence of neutropenia (HR, 3.19; p=0.02). Moreover, patients with prior autoSCT had a lower likelihood of resolution of neutropenia (HR, 0.33; p=0.03), and those with multiple prior therapies had a lower likelihood of resolution of thrombocytopenia (HR, 0.36; p=0.002).Conclusion: Our study shows that a proportion of patients experienced prolonged hematological toxicity, and prior autoSCT and multiple lines of therapy were identified as risk factors. Prophylactic G-CSF did not appear to have any benefit on the prevention of neutropenia or infectious complications. [Display omitted] DisclosuresDeol: Kite, a Gilead Company: Consultancy. Modi: Genentech: Research Funding; Seagen: Membership on an entity's Board of Directors or advisory committees; MorphoSys: Membership on an entity's Board of Directors or advisory committees.

Patterns of leukocyte recovery predict infectious complications after CD19 CAR-T cell therapy in a real-world setting.

Adoptive immunotherapy using CD19-targeted Chimeric antigen receptor T cells (CAR-T) has revolutionized the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Data is limited on the propensity of infections and lymphohematopoietic reconstitution after Day 30 (D30) following CAR-T cell therapy. In this study, we evaluated the prevalence and nature of infectious complications in an expanded cohort of DLBCL patients treated with CD19 CAR-T therapy and its association with the dynamics of leukocyte subpopulation reconstitution post-CAR-T cell therapy. We conducted a retrospective study including 19 patients who received axicabtagene ciloleucel and investigated associations between cytopenia and infectious complications after D30. Nineteen patients were included, consisting of 42% Hispanic, 32% Caucasian, 21% African-American, and 5% Asian subjects. Post-D30 of CAR-T infusion, 47% patients (n=9) developed an infection and 53% (n=10) remained infection-free. The most common infection type observed was viral (7 patients) followed by bacterial (5 patients) and fungal (3 patients). Of 25 total infectious events, 56% were grade 1 or 2 and 44% were grade 3 with 10 being viral in etiology. To determine the kinetics of lymphohematopoietic reconstitution and its association with infection risk, we evaluated the relationship between cytopenias and rates of infection after D30. Notably, compared to non-infection group, infection group had a higher median absolute lymphocyte count (ALC) (1,000/µL vs. 600/µL, P<0.05), a lower median absolute neutrophil count (ANC)/ALC ratio (1.6 vs. 3.1, P<0.05) and a lower median AMC/ALC at D30 (0.37 vs. 1.67, P<0.05). In addition, we observed that only 22% of patients had recovered ANC >1,500/µL in the infection group as opposed to 70% in the non-infection group at D90 (P<0.05). Fifty-eight percent of the patients (11/19) with relapsed refractory DLBCL achieved a complete response with a median follow-up of 233 days (7.7 months). Although CAR-T cell therapy is highly effective, infectious complications remain an important cause of morbidity and mortality. Low ANC/ALC and AMC/ALC ratios at D30 are potential novel predictors of infection and can be considered in future prophylactic strategies.

Pre-treatment Neutropenia in Children and Adolescents with Autoimmune Hyperthyroidism

Objective:Neutropenia can occur in untreated autoimmune hyperthyroidism (AIH) or in association with treatment with the anti-thyroid drug, methimazole (MMI). Starting MMI in children and adolescents with AIH and pre-existing neutropenia could thus be worrisome. The aim was to describe the prevalence of neutropenia in pediatric AIH, prior to antithyroid drug therapy and to assess the effect of antithyroid drugs on neutrophil count.Methods:Patients with AIH attending a pediatric endocrinology clinic were retrospectively reviewed. Absolute neutrophil count (ANC) data at presentation and during anti-thyroid treatment for up to 24 weeks was collected. AIH was defined as elevated free thyroxine (fT4) or free tri-iodothyronine (fT3), suppressed thyroid stimulating hormone, and positive thyroid autoantibodies. Neutropenia was defined as ANC <1500 cells/μL.Results:Thirty-one patients (71% female) were included with a median interquartile range (IQR) age of 14.71 (11.89-17.10) years. Neither fT4 nor fT3 levels correlated with ANC at presentation (rs=0.22, p=0.24 and rs=0.13, p=0.54, respectively). 26/31 (84%) had normal baseline ANC. None developed neutropenia with thionamides. 5/31 (16%) had baseline neutropenia (median ANC 1,200/μL; IQR 874-1200). Four of these five started MMI at diagnosis while one was started on propranolol only but MMI was started one week later. All five normalized ANC within 24 weeks.Conclusion:In this cohort, 16% of AIH patients had neutropenia at presentation, but this resolved in the short term and did not worsen with thionamides. Thionamides may be used with caution in these patients with close monitoring of blood counts.

Clinical Characteristics and Predictive Factors of Invasive Fungal Disease in Pediatric Oncology Patients with Febrile Neutropenia in a Country with Limited Resources.

BackgroundThe most common complication among pediatric oncology patients is febrile neutropenia (FN). Invasive fungal disease (IFD) is suspected when fever persists >4–7 days after empirical antibiotics. Its clinical characteristics and predictive factors associated with IFD among pediatric oncology patients with FN were thus explored.MethodsPediatric oncology patients with FN between January 1, 2012 and December 31, 2016 were enrolled in this study. Clinical characteristics, including laboratory investigations, treatment modalities, and final outcomes of IFD were retrospectively reviewed and analyzed.ResultsIn all, 73 patients with 180 episodes of confirmed diagnosis of FN were studied. Median age at diagnosis was 6.2 years, with equal sex distribution. The most common diagnosis was acute lymphoblastic leukemia (n=91, 51%), followed by acute myeloid leukemia (n=47, 26%), Burkitt’s lymphoma (n=7, 4%) and neuroblastoma (n=7, 4%). Median absolute neutrophil count at FN diagnosis was 0 (0–806) cells/mm3. IFD was diagnosed for 25 (14%) episodes. Mortality rates for FN and IFD were 4% and 20%, respectively. Respiratory compromise, oxygen requirement, hypotension, prolonged hospitalization, duration of fever and neutropenia, bacteremia, bacteriuria, funguria, abnormal liver-function results, and prolonged broad-spectrum antibiotic administration were factors associated with IFD (P<0.05). Prolonged duration between initiation of fever and antifungal administration for nearly 10 days was an independent factor in prediction of IFD occurrence (P=0.014).ConclusionRespiratory compromise, oxygen requirement, hypotension, prolonged hospitalization, duration of fever and neutropenia, bacteremia, bacteriuria, funguria, abnormal liver-function results and prolonged broad-spectrum antibiotic administration were factors associated with IFD. Duration between initiation of fever and antifungal administration of nearly 10 days were considered a risk factors of IFD among patients with FN.IRB Reference NumberIRBRTA 825/2560.

Predictors for Recurrent 30-Day Unplanned Readmissions in Patients with Hematologic Malignancies

BackgroundNewly diagnosed hospitalized patients (pts) with hematologic malignancies (HM) frequently have high symptom burden, often need prolonged courses of highly myelosuppressive chemotherapy and consequent protracted transfusion support- factors that predispose these pts to unplanned readmissions (UR). Given the paucity of data on risk factors associated with repeated UR in HM pts, we first analyzed the baseline characteristics of pts with one or more 30-day UR and then evaluated factors that predicted for additional 30-day UR following the first 30-day UR event.MethodsAdult (≥ 18 years) HM pts treated at Cleveland Clinic between January 2011-February 2016 were included in the study. Thirty-day UR was defined as hospitalization within 30 days of index admission for any reason other than planned chemotherapy. A readmission event served as an index admission for the subsequent readmission. Bone marrow transplant pts were excluded. HM included acute leukemias, myelodysplastic syndromes (MDS) and aggressive lymphomas (Diffuse Large B-Cell Lymphoma, Burkitt's). Demographics (age, race, sex, highest education attained, median income, payer status), clinical characteristics (HM type, symptoms at index admission/readmission, disease status, body mass index at discharge, absolute neutrophil count (ANC) at discharge/readmission, and discharge on intravenous antibiotics or narcotics), hospitalization (reason for readmission, length of stay (LOS) at index admission/readmission), and discharge characteristics (discharged to and readmitted from) were collected. Data were analyzed using Fisher's exact test chi-square tests, and t-tests for univariable analyses; and logistic regression for multivariable analyses. Recursive partitioning was used to find cut points for continuous factors.ResultsA total of 259 thirty-day UR were observed in 157 pts - 107 had a single 30-day UR, while 50 (32%) had > 2 UR. The majority of pts were males (59%), with a median age of 66 years (yrs, interquartile range (IQR) 48-75). Acute myeloid leukemia was the most common HM diagnosis (44%) and 50% had relapsed or refractory disease. Pt median income was $51,700 and 86% (IQR, 80-90%) had greater than a high school education, using census tract based data (Table 1). By payer source, 49% of pts were covered by Medicare, 12% by Medicaid, and 36% by private insurance. Discharges following UR were to: home (50%), home with home health (32%), nursing facility (15%) and hospice (3%). Of the discharges after UR, 10% were discharged on intravenous antibiotics, 44% on opioids and 48% on psychotropic drugs. Neutropenic fever with or without a confirmed source was the primary diagnosis (61%) for 30-day UR and 59% had symptoms at presentation. Median ANC at discharge from an UR was 870/mL (IQR 190-3570) and was 940/mL (IQR, 100-3700) at the time of readmission. The median LOS during 30-day UR was 5 days (IQR 3-10) and the median interval from prior discharge to readmission was 11 days (IQR 5-19). The majority of 30-day UR originated from outpatient clinic, emergency department, or pt's home (46%) followed by a non-health care facility (27%) and outside hospital transfers (22%). Table 1 shows univariable analysis of factors significantly associated with 30-day UR. In multivariate analysis, factors that independently predicted for subsequent 30-day UR included pts with the following characteristics - ANC <2000/mL at last discharge (OR 7.5, P=.0002), constitutional symptoms (fevers/chills/sweats/severe fatigue at index admission presentation) (OR 5.84, P=.002), gastrointestinal symptoms (OR 5.11, P=.009), if pt was transferred from an outside facility (OR 3.26, P=.005), febrile neutropenia as reason for index admission (OR 3.18, P=.0001), relapsed/refractory disease (OR 2.94, P=.009), and higher education (OR 2.08, P=.01).ConclusionOur findings suggest directing UR reduction strategies to optimize symptom control (constitutional and gastrointestinal) prior to discharge and design specific measures for the cohort with relapsed/refractory disease who might further benefit with individualized care from a multidisciplinary care team, and closer ambulatory follow up. Increased risk of additional 30-day UR with education may reflect better understanding of care complexities resulting in a lower threshold for seeking care with a change in medical condition, or possibly a surrogate for better health care access. [Display omitted] DisclosuresGerds:Incyte: Consultancy; CTI BioPharma: Consultancy. Advani:Takeda/ Millenium: Research Funding; Pfizer: Consultancy. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees.

Monoclonal Antibody Utilization Characteritics in Patients with Multiple Myeloma

Background: Monoclonal antibodies (MoAb) including daratumumab (Dara) and elotuzumab (Elo) are important additions to multiple myeloma (MM) therapeutics and have become cornerstones of patients with relapsed and/or refractory disease (RRMM). While large clinical trial data define their efficacy and safety, real-world experience to help understand their true utilization and serve as guidelines for community practice are lacking.Methods: Data on the utilization of Dara and Elo for treatment of MM including patient and disease characteristics, infusion attributes, supportive medication use and adverse event profile were collected and analyzed using descriptive statistics. Baseline laboratory data including median absolute lymphocyte count (ALC), eosinophil count (AEC), neutrophil count (ANC) and immunoglobulin level (Ig) were documented and their correlation with infusion-related reactions (IRRs) was explored using Wilcoxon rank sum test.Results: Ninety-one consecutive patients with MM treated using Dara (n=78) or Elo (n=13) not on clinical trials between 1/1/16 and 12/31/16 at Mayo Clinic in Florida (MCF; n=30) or Arizona (MCA; n=61) were included. A total of 1036 infusions of Dara (Median: 12 per patient; Range: 1-38) and 210 of Elo (Median: 18 per patient; Range: 3-29) were administered over 12 months. Study cohort included 56 males (61.5%) with median age 63 years (range: 37-81) and majority (83.5%) of Caucasian race. Treatment regimes of MoAb alone or with immunomodulatory drug (IMiD) and/or proteasome inhibitor (PI) are shown in Figure 1. Prior lines of therapy were >3 in 52.7%, 3 in 13.2%, 2 in 19.8%,1 in 12.1% and in 1 case each Dara and Elo were given in first line of therapy. Majority of patients who received Dara (60.3%) had >3 prior lines of therapy while majority who received Elo (53.8%) had 1 prior line of therapy for MM. Pre-treatment blood sample for type/screen was sent in 67% patients. Any grade hematologic (heme) adverse events (AE) were seen in 66 (84.6%) patients with Dara and 6 (46.2%) patients with Elo, while non-heme AEs were seen in 64 (82.1%) patients with Dara and 11 (84.6%) patients with Elo. Actual MoAb administration took an average 2 hours lesser (Range: -3 to +6 hours for Dara and -1 to +5 hours for Elo) than scheduled with median 2 hours lesser for both the drugs. In 2 cases first Dara infusion was given in divided dose over 2 days. Most common premedications prior to first MoAb infusion included acetaminophen (90.1% cases), diphenhydramine (86.8% cases) and methylprednisone (78% cases) with dexamethasone, famotidine, prochlorperazine and ondansetron used less frequently. Number of patients without any premedications use changed from 9.9% before infusion 1 to 94.5% before infusion 29 of any MoAb, showing a sharp decrease in the use of premedications in subsequent dose infusions of MoAbs. IRRs were seen in 39 (42.9%) patients with first MoAb infusion with respiratory IRRs (bronchospasm, cough, dyspnea, nasal congestion, throat irritation, wheezing) seen in 35 (38.5%) and non-respiratory IRRs (chills, nausea, hypertension, tachycardia, pruritus, bradycardia, emesis) in 16 (17.6%) patients. No patients had any higher than grade 2 IRRs. Majority of the IRRs (91.3%) were observed during the first MoAb infusion, none of the patient's required discontinuation of MoAb treatment as a result of IRRs, with a significant decrease in IRR incidence during second (3.3%) and subsequent (5.4%) infusions. In 10 cases (9 for Dara and 1 for Elo) premedication regimen was modified after first infusion. MoAb AEs seen in ≥10% cases across various regimens included neutropenia (51.6%), lymphopenia (42.9%), thrombocytopenia (33%), anemia (18.7%), fatigue (40.7%), diarrhea (22%), pneumonia (22%), cough (18.7%), fever (18.7%) and nausea (12.1%). Median baseline labs included ALC 0.95 K/mm3, ANC 2.22 K/mm3 and AEC 0.07 K/mm3. There was no association seen between median baseline ALC, ANC or AEC and the risk of any IRRs, respiratory or non-respiratory.Conclusions: We present a comprehensive analysis of real-world experience regarding the utilization of novel MoAb agents for the treatment of MM. Although the role of MoAbs in MM therapeutics is evolving, these data help understand their true utilization and identify how resources may be best employed to optimize their benefit for patients. [Display omitted] DisclosuresAilawadhi:Novartis: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Pharmacyclics: Research Funding; Amgen: Consultancy, Honoraria. Sher:LAM Therapeutics, Inc: Research Funding. Fonseca:Bayer: Consultancy; Takeda: Consultancy; Jansen: Consultancy; Celgene Corporation: Consultancy, Research Funding; AMGEN: Consultancy; Bristol-Myers Squibb: Consultancy; Mayo Clinic & Dr Fonseca: Patents & Royalties: Prognostication of myeloma via FISH, ~$2000/year; Merck: Consultancy; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy; Novartis: Consultancy; Pharmacyclics: Consultancy.

Neutropenia Following Intravenous Immunoglobulin Therapy in Adult Patients with Immune Thrombocytopenic Purpura

BackgroundImmune thrombocytopenic purpura (ITP) is an autoimmune disease in which anti-platelet antibodies accelerate the destruction of platelets. Traditional therapies such as steroid therapy, intravenous immunoglobulin (IVIG) therapy, and splenectomy generally reduce the peripheral destruction of platelets. However, they may cause significant side effects. In particular, it has been recently reported that neutropenia sometimes develops in children as an adverse effect after IVIG administration. On the other hand, there is no previous report on neutropenia developing as a complication of IVIG therapy in adult patients with ITP. The aim of this study was to further investigate the incidence and course of neutropenia following IVIG therapy in adults with ITP.MethodsWe performed a retrospective chart review of 88 ITP patients who had received IVIG to manage severe thrombocytopenia between January 2006 and March 2016 at Pusan National University Hospital in Korea. Inclusion criteria were the following: age ≥ 18 years, ITP diagnosis according to the American Society of Hematology guidelines (platelet count of less than 100 × 109/L in the absence of other causes or disorders that may be associated with thrombocytopenia). Exclusion criteria included other diseases known to be associated with ITP, such as human immunodeficiency virus or hepatitis C virus infection, lympho-proliferative disorders, thyroid or liver disease, and definite systemic lupus erythematosus. Patients included in this study had a complete and differential blood count performed before and after the IVIG treatment. Patients were treated according to a standard protocol, consisting of IVIG administration (1 g/kg per day for two days).ResultsThe baseline characteristics of patients are shown in Table 1. Among 88 patients, 24 (27.3%) were male, and 64 (72.7%) were female. The median ages were 45 years in the group that developed neutropenia and 41 years in the group that did not develop neutropenia. The groups were comparable in age, sex distribution, initial white blood cell (WBC) count, and absolute neutrophil count (ANC). Neutropenia developed in 43 patients (48.9%) after IVIG treatment. In patients with a decrease in WBC count and ANC compared to baseline, median WBC count decreased from 6,280/μL to 4,530/μL after IVIG therapy, and median ANC decreased from 3,840/μL to 2,840/μL after IVIG therapy. Only two patients in this study developed a post-treatment ANC of less than 1,000/μL, and only one patient developed neutropenic fever, which subsided soon without any treatment. The neutropenia induced by IVIG had resolved spontaneously after several days, and the mean recovery time was 8.72 days after the completion of the IVIG treatment (Table 1, Figure 1 and 2). Including the present case, we identified previous reports of neutropenia developing as a complication of IVIG therapy in the English literature (Table 2). The majority of reports of neutropenia following IVIG therapy are pediatric patients with ITP. There were two reports on the incidence of neutropenia induced IVIG in adults except for pediatric patients with ITP. Matsuda M et al. reported neutropenia induced by high-dose IVIG in adult patients with neuro-immunologic disorders. And Lemos S et al. reported acute neutropenia in patients with primary antibody-deficiencies, after receiving IVIG. However, as mentioned earlier, there has been no reports of neutropenia following IVIG therapy in adult patients with ITP. Therefore, this study is the first report of neutropenia after IVIG therapy in adult patients with ITP. Although further studies are required in order to clarify the precise mechanism of neutropenia following IVIG treatment, this would be the important report of neutropenia following IVIG therapy in adult patients with ITP.ConclusionsThe results of this study suggest that IVIG may cause neutropenia commonly in adults with ITP, and it seems to be transient and self-limited. This study is meaningful as the first report that not only pediatric ITP patients may develop neutropenia post IVIG administration, but also adult patients suffering ITP. Therefore, an awareness of this common association of neutropenia following IVIG treatment in adult patients with ITP is likely to aid physicians in caring for these patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Only SF3B1 mutation involving K700E independently predicts overall survival in myelodysplastic syndromes.

SF3B1 mutations (SF3B1mut ) in myelodysplastic syndromes (MDS) frequently involve codon K700E and have a favorable prognosis. The prognostic effect of non-K700E SF3B1mut is uncertain. The authors analyzed the clinicopathological features and outcomes of a single-institution series of 94 treatment-naive SF3B1mut MDS patients (18%) and 415 treatment-naive SF3B1wt MDS patients and explored the differences between K700E and non-K700E SF3B1mut MDS. Fifty-five patients (59%) carried K700E. Recurrent non-K700E mutations (39 [41%]) included R625, H662, and K666. Compared with SF3B1mut K700E patients, non-K700E patients had a lower median absolute neutrophil count (1.8 vs 2.4; P = .005) and were frequently "high" according to the Revised International Prognostic Scoring System (19% vs 4%; P = .031). Non-K700E MDS was associated frequently with RUNX1 (26% vs 7%; P = .012) and exclusively with BCOR, IDH2, and SRSF2 mutations. A splicing analysis showed the differential distribution of alternatively spliced events and gene expression profiles between K700 and non-K700E MDS patients. The majority (at least 80%) of SF3B1mut K700E, SF3B1mut non-K700E, and SF3B1wt patients were treated with hypomethylating agents. Over a median follow-up of 16 months, SF3B1mut had superior overall survival (OS) in comparison with SF3B1wt in all MDS patients (not reached vs 25.2 months; P = .0003), in patients with low-grade MDS, and in patients with myelodysplastic syndromes with ring sideroblasts (MDS-RS). Compared with SF3B1wt , SF3B1mut K700E had superior outcomes in all MDS (median OS, 25 months vs not reached; P = .0001), in low-grade MDS (median OS, 41.3 months vs not reached; P = .0015), and in MDS-RS (median OS, 22.3 months vs not reached; P = .0001), but no significant difference was seen between non-K700E and SF3B1wt MDS. By multivariable analysis, the absence of SF3B1mut K700E mutations was independently associated with the prognosis. This study highlights the importance of the SF3B1 mutation subtype in MDS risk assessment. Myelodysplastic syndromes (MDS) with SF3B1 mutations are regarded as having a favorable prognosis by both the World Health Organization and the International Working Group for the Prognosis of Myelodysplastic Syndromes. However, this article shows that only MDS patients with SF3B1 K700E mutations have a favorable prognosis (and not MDS patients with SF3B1 mutations involving other codons). This has important implications for refining future MDS subclassification and risk assessment criteria.

Efficacy of Rabbit Anti-Thymocyte Globulin (ATG) Compared to Horse ATG In Severe Aplastic Anemia

AbstractAbstract 2236Intense immunosuppression therapy (IST) using a combination of ATG and cyclosporine A (CsA) produces responses in 60–70% of patients (pts) with severe aplastic anemia (sAA). Until recently, horse ATG (hATG, ATGAM) has been the primary preparation used upfront for sAA. Relapsed or refractory pts may be treated with rabbit ATG (rATG, Thymoglobulin) a second course of IST. However, only limited efficacy data are available for rATG used as initial therapy in sAA. For both ATG preparations, recognition of the biomarkers and clinical parameters predictive of response has been a major focus of research in AA. A significant minority of patients remains refractory to IST and these patients may benefit from an early application of alternative therapeutic approaches such as bone marrow transplantation.We performed a phase II study of rATG/CsA combination (3.5 mg/kg/day × 5 days followed by CsA, dosing based on blood levels) as first line therapy for sAA. We then compared these pts to historical controls who received hATG (40 mg/kg/day × 4 days/CsA) as an initial therapy. sAA was defined according to well established criteria (cellularity <30%, with at least 2 of the following: absolute neutrophil count (ANC) <0.5 × 109/l, absolute reticulocyte count (ARC) <60 × 109/l, platelet count < 20 × 109/l. Responses (as previously defined by Rosenfeld, 2003) were assessed at 3, 6 and 12 months, as were early death rates and overall survival. Immunologic parameters that could potentially predict responses were also assessed.A total of 22 patients with sAA treated initially with rATG (770 days median f/u) were compared to 67 control pts (1165 days median follow-up) who received hATG as initial IST. There were no significant differences in most hematologic characteristics prior to IST administration: age (55 vs 49, p=.34), platelets (14K vs. 14K, p=.35), median ANC (0.60 vs. 0.60, p=.99), median ALC (1.46 vs. 1.42, p=.81), presence of PNH clone >1% (11 versus 21, p=.45) and presence of HLA-DR15 (9 vs. 21 p=1.00), median absolute reticulocyte count (0.020 vs. 0.028, p=.09). Response was similar for pts treated with rATG compared to hATG at 3, 6 and 12 months: 41% vs. 52% (p=.15), 50% vs. 59% (p=.62) and 54% vs 59% (p=.66), respectively. The number of early deaths also did not differ between the ATG preparations, with 2 (9%) for rATG and 6(9%) for hATG (p=.98). Similarly, no difference in overall survival was observed (log rank test p=0.32). Both groups also showed similar relapse rates (14% vs 16%, p=.81) in the observation interval. We then performed a retrospective analysis of patients who received a second course of different ATG preparations (i.e. rATG after hATG and hATG after rATG). 18/67 (26%) patients initially treated with hATG had second treatment with rATG and 6/22 (27%) patients who initially received rATG were retreated hATG. There was no statistically significant difference of response at 12 months between these groups at 50% vs. 56% (p=.88). As rATG and hATG had similar baseline and response characteristics, we performed a combined analysis of all 89 patients for predictor of response at 6 months. The presence of a PNH clone and a higher reticulocyte count were the only variables found to be independent prognostic factors for response (p=.004 and .009, respectively). Similarly, multivariable models (cox proportion hazards) showed that age (p=.003), ALC (p=.02), and ANC (p=.03) were found to be independent predictors for survival. At 5 years, pts with >2 poor prognostic features (i.e. higher age, lower ANC and ALC) had a 16% survival rate compared to 67% for patients with <2 poor prognostic features (p=.001). We also analyzed cytokine gene polymorphisms, particularly TGF-β codons 10/25 and IFN-γ. Our analysis did not show any significant association between a specific genotype and response or survival. Analysis of TCR V beta repertoire by flow cytometry prior to initiation of IST revealed that patients with an expanded CD4 T cell clone were more likely to respond at 3 months to ATG (12/15, 80%) than those without (19/40, 47%, p=.037) indicating that CD4 TCR V beta skewing may be a marker of immune-mediated disease. Conclusion:Our study demonstrates that rATG shows a comparable efficacy to hATG for upfront treatment as well as salvage of sAA in a relapsed and refractory setting. Disclosures:Kalaycio: Genzyme: Speakers Bureau; Genetech: Speakers Bureau; Cephalon: Speakers Bureau. Maciejewski: Genzyme: Research Funding.

Diagnosis and management of acute appendicitis in 21 pediatric hematology and oncology patients at a tertiary care cancer center

Acute appendicitis is a rare gastrointestinal complication of anti-cancer chemotherapy and hematopoietic stem cell transplantation. Among a cohort of 2341 hemato-oncologic patients at a pediatric tertiary care cancer center, we identified 21 patients (0.9%) with 23 episodes of acute appendicitis, based on pathological imaging of the appendix and clinical findings. Median age at diagnosis was 10.21 years. Types of underlying disease included acute leukemias (n = 15), solid tumors (n = 4), and aplastic anemia (n = 2). Clinical symptoms seen in > 1 case were recorded for all 23 episodes as follows: abdominal pain, n = 22; abdominal tenderness, n = 4; fever, n = 7; nausea, n = 2; emesis; n = 2; diarrhea, n = 5; and constipation, n = 2. Median leukocyte count at diagnosis was 0.5 × 109/L, with a median of 0.1 × 109/L for the absolute neutrophil count (ANC). All patients received broad-spectrum antibiotics and 18/23 (78%) patients underwent uneventful appendectomy after a median of 5 days and with a median ANC of 0.7 × 109/L. Median duration until continuation of chemotherapy was 17 days for the 20 cases of appendicitis occurring during the patients’ disease course. Overall, 5/21 (19%) patients died including one related to the appendicitis itself which progressed to a typhlitis and was due to a fungal infection. The other fatalities were transplant- (n = 2) and leukemia-related (n = 2). Acute appendicitis is a rare and usually not life-threatening event in pediatric hemato-oncologic patients, which, if managed by prompt administration of broad-spectrum antibiotics (and antimycotics), can be safely followed by an elective (delayed) appendectomy, even before complete recovery of the neutrophils is achieved.

Incidence and predictive risk factors of neutropenic sepsis in post-chemotherapy febrile patients in emergency department: A single-center retrospective longitudinal study

Introduction: Neutropenic sepsis is an emergency sequela in post-chemotherapy fever. Its definition comprises of spectrums of diseases with variable quoted mortality. This study aims to evaluate the incidence of “modified” neutropenic sepsis, with a more stringent definition employed. Predictive risk factors toward occurrence of “modified” neutropenic sepsis among Chinese patients would also be explored. Methods: A single-center retrospective longitudinal study was conducted in a medium-sized regional hospital in Hong Kong. All patients with diagnoses of post-chemotherapy fever fulfilling the inclusion and exclusion criteria were recruited. Baseline characteristics and outcome variables of each case subject were collected. Six potential predictive risk factors were chosen for further analysis. Case subjects were followed up for the inpatient progress and outcomes. Relative risks of each risk factor to “modified” neutropenic sepsis were calculated. Results: A total of 135 case subjects were recruited. Five developed “modified” neutropenic sepsis, that is, incidence 3.70% (95% confidence interval = 1.59%–8.38%). Only background hematological malignancy was found to be significantly associated with the outcome of “modified” neutropenic sepsis (Relative Risk [RR] 13.2, 95% confidence interval = 1.56–115.70, p = 0.010), with an incidence of 12.9% (95% confidence interval = 5.14%–28.85%). Hematological malignancy was also found to be significantly associated with lower median absolute neutrophil counts (0.95 × 109/L vs 2.3 × 109/L, p = 0.005) and longer median hospital stay (8 days vs 6 days, p &lt; 0.001). Conclusion: Incidence of “modified” neutropenic sepsis is low. Hematological malignancy is associated with significantly higher rate of “modified” neutropenic sepsis.