1702. Assessing the Safety and Efficacy of Valganciclovir Dosing for Cytomegalovirus Prophylaxis in Solid Organ Transplant Recipients on Hemodialysis

Background Valganciclovir is the standard of care used for the prevention of Cytomegalovirus (CMV) infections among solid organ transplant (SOT) recipients. Currently there is minimal guidance for prophylaxis in SOT recipients undergoing intermittent hemodialysis (IHD). At Mount Sinai Hospital (MSH), the current practice for CMV prophylaxis in SOT recipients on IHD is valganciclovir 450 mg every other day (Q48H) or three-times weekly (TIW). This study aims to evaluate the safety and effectiveness of these dosing regimens in SOT recipients on IHD. Methods A single-center, retrospective chart review study was conducted among all MSH SOT recipients on valganciclovir 450 mg Q48H or TIW for CMV prophylaxis and undergoing IHD for at least 30 days. The primary study outcome was the safety of using these valganciclovir doses determined by the incidence of leukopenia, thrombocytopenia, and the administration of growth colony stimulating factor (GCSF). The secondary outcome were the incidences of CMV viremia and CMV disease while on prophylaxis. Results Eighteen transplant encounters satisfied the inclusion and exclusion criteria. The majority were liver (7, 38.9%) and kidney (5, 27.8%) transplants. Thirteen (72.2%) recipients were on valganciclovir 450 mg Q48H dosing, while 5 (27.8%) were on valganciclovir 450 mg TIW dosing. Both the mean platelet count nadir (131 ± 93 vs 161 ± 115) and mean white blood cell count nadir (3.4 ± 2.5 vs 5.1 ± 3.8) were lower in the Q48H regimen. Four patients (22.2%) in the Q48H regimen group required GCSF vs none (0.0%) in the TIW regimen. No patient had a detectable CMV viral load while on either prophylactic dose. Two (11.1%) CMV high risk patients on the every other day dosing regimen and one (5.6%) CMV moderate risk patient on the three times weekly regimen developed CMV viremia about 2-3 months after their prophylaxis was stopped. Table 1. Baseline Demographics. Table 2. Primary Outcomes Table 3. Secondary Outcomes Conclusion Valganciclovir 450 mg TIW may be safer than and as efficacious as Q48H dosing for prophylaxis in SOT recipients on chronic IHD. This data supports the use of three times weekly dosing as standardized practice at MSH, however more data is necessary to determine a conclusive result. Disclosures All Authors: No reported disclosures

Progressive multifocal leukoencephalopathy on dimethyl fumarate with preserved lymphocyte count but deep T-cells exhaustion

Background: Progressive multifocal leukoencephalopathy (PML) among multiple sclerosis (MS) patients receiving dimethyl fumarate (DMF) is associated with iatrogenic lymphopenia, predominating on CD8+ T-cells. Objectives and Methods: We report an unusual case of DMF-related PML in a 66-year-old MS patient with preserved lymphocyte count (nadir: 810/mm3) and normal CD8+ T-cells count. Results: A massive overexpression of the inhibitory receptor Programmed Cell Death 1 (PD-1) on CD8+ and memory effector T-cells together with an impaired anti-JC virus (JCV) specific T-cells response were found, compatible with exhaustion. Following DMF withdrawal, PML progressively regressed, PD-1 was downregulated, and a functional anti-JCV response was established. Conclusion: T-cells exhaustion may favor PML onset on DMF independently of lymphocyte count.

P0248HEPARIN-INDUCED THROMBOCYTOPENIA (HIT): A POSSIBLE CAUSE OF VENOUS THROMBOEMBOLISM IN ACTIVE SYSTEMIC VASCULITIS

Background and Aims Increased incidence of venous thromboembolism in active phase of vasculitis has been found by several authors. Examining large cohorts of patients, the underlying mechanisms still remain unclear. Patients with active vasculitis are not rarely exposed to heparin mainly because of dialysis, plasmafiltration or ECMO. In the high inflammatory context of active vasculitis, as in major surgery, heparin exposure could promote the formation of anti-PF4/heparin antibodies and induce HIT. Method Description of cases with active vasculitis and HIT observed in our cohort of ANCA-associated vasculitis patients from 1994 to 2019. Review of cases reported in the literature. Results We observed 18 patients with systemic vasculitis and HIT (10 M and 8 F, median age: 69.5 yo). Fourteen had ANCA antibodies, one patient had both ANCA and anti-GBM antibodies (double positive), two had positive anti-GBM antibodies, one had negative ANCA and anti-GBM antibodies. Among 15 patients with positive ANCAs, 13 had anti-MPO antibodies and 2 anti-PR3 antibodies (Fig. 1). All patients were exposed to heparin, 10 because of plasmafiltration and dialysis, 8 for dialysis alone. Mean platelet count nadir was 76100/mm3 (range 23000-197000/mm3). In all patients PF4–heparin antibody immunoassay was strongly positive (optical density >1 in 13 patients). The most frequent manifestations were thrombocytopenia and repeated clotting of the extracorporeal circuit and dialyzer with thrombosis of the hemodialysis catheter (6/18 patients). Four patients developed deep vein thrombosis almost invariably in the site of the hemodialysis catheter. Pulmonary embolism was observed in only one patient (Fig. 2). To our knowledge, only 11 cases of HIT in patients with vasculitis have been reported in literature (Table I). Detailed data are available for 7 patients (6 M and 1 F, median age 69.6 yo). Three patients had anti-PR3 antibodies, 2 anti-MPO antibodies, 1 both ANCA anti-MPO and anti-GBM antibodies (double positive), 1 only anti-GBM antibodies. Mean platelet count nadir was 45625/mm3 (range 17000-131000/mm3). Three out of 11 patients developed repeated clotting of the extracorporeal circuit and dialyzer, 2 patients had deep vein thrombosis in the site of the hemodialysis catheter, and one patient had also leukopenia and subarachnoid hemorrhage. Six patients were asymptomatic and developed only thrombocytopenia. Conclusion When patients with active systemic vasculitis develop venous thromboembolism and thrombocytopenia after exposure to heparin, or repeated coagulation of the extracorporeal circuit and dialyzer or plasma-filter, HIT should be included in the possible differential diagnosis, and Platelet factor 4–heparin antibody tests should be performed.

White Blood Cell Count Nadir and Duration of Aplasia Do Not Associate with Treatment Outcome in Adult Patients with Acute Myeloid Leukemia Undergoing Intensive Chemotherapy

<b><i>Introduction:</i></b> Adult patients with acute myeloid leukemia (AML) are usually treated with intensive chemotherapy, leading to prolonged bone marrow aplasia. It is usually assumed that a short duration of aplasia could be a surrogate marker of poor therapeutic efficacy in clearing bone marrow blasts, especially in older patients. No studies have evaluated the usefulness of such a surrogate marker in younger AML patients treated with intensive chemotherapy. <b><i>Materials and Methods:</i></b> In the present study, we retrospectively assessed the role of white blood cell (WBC) count nadir and duration of aplasia in 68 patients with AML treated with intensive chemotherapy and potentially candidate to stem cell transplantation. <b><i>Results:</i></b> The median (interquartile range) bone marrow aplasia was 25 days, and the mean WBC count nadir from chemotherapy start was at day +12, whereas the median neutrophil recovery occurred at day +24. No significant differences were found between responders and nonresponders for mean aplasia duration (25 vs. 26 days, <i>p</i> value = 0.76), mean WBC count nadir (12 vs. 12 days, <i>p</i> value = 0.86), and median neutrophil recovery (24 vs. 24, <i>p</i> value = 0.67). <b><i>Discussion:</i></b> The present study evaluated the potential prognostic role of WBC count nadir and duration of aplasia, demonstrating that they are not associated with treatment outcomes in adult patients with AML treated with intensive chemotherapy. Therefore, a short duration of aplasia seems not linked to poor therapeutic efficacy in clearing bone marrow blasts. Our findings, although needing validation in larger and more homogeneous cohorts, may offer helpful clues in the management of aplasia of AML patients.

The impact of proton beam therapy on blood cell count nadir during neoadjuvant chemoradiation therapy for esophageal cancer.

137 Background: To analyze the blood cell count nadir, particularly grade 4 hematologic toxicities, in patients with esophageal cancer who were treated with neoadjuvant chemoradiation (nCRT) with either Proton Beam Therapy (PBT) or Intensity Modulated Radiation Therapy (IMRT) in a propensity-matched pair analysis. Methods: Esophageal cancer patients (n = 480) treated from 2005-2016 with nCRT with (n = 167) or without (n = 313) induction chemotherapy (ICT) were analyzed. White blood cell, neutrophil, lymphocyte and platelet counts nadir during ICT and CRT were obtained, and graded according to the CTCAE v.4.0. Univariate and multivariable logistic regression models to identify factors associated with increased risk of grade 4 lymphopenia were fitted. By propensity score matching, 136 PBT cases and 136 propensity score matched IMRT controls were selected for comparison. Results: In the entire study cohort during CRT (n = 480), 2 (0.4%), 1 (0.2%), 159 (33%), and 2 (0.4%) patients experienced grade 4 leukopenia, neutropenia, lymphopenia and thrombocytopenia, respectively. This is not seen in patients who received ICT (n = 167), as only 0 (0%), 2 (1.2%), 1 (0.6%) and 0 (0%) patients experienced grade 4 leukopenia, neutropenia, lymphopenia and thrombocytopenia during the ICT phase. Multivariable analyses identified older age (p = 0.0139), larger planning tumor volume (PTV) (p = 0.0213), distal vs upper/mid tumor location (borderline significance, p = 0.0779) and IMRT vs PBT (p < 0.0001) as factors associated with increased risk of grade 4 lymphopenia during CRT. Among the 272 propensity-matched patients treated with either PBT or IMRT, 24 (17.6 %) and 55 (40.4 %) patients experienced grade 4 lymphopenia, respectively (p < 0.001). Grade 4 lymphopenia correlates with poorer survival (p = 0.0587), lower progression free survival (p = 0.0384) and distant metastatic recurrence (p = 0.0185). Conclusions: The use of PBT may be an important modifying factor in altering the incidence of grade 4 lymphopenia during CRT in esophageal cancer. The dosimetric factors that can modulate this risk is a subject of continued investigation.