Complete Blood Count Monitoring Research Articles

Sepsis-induced Pancytopenia in an Adolescent Girl with Thyroid Storm: A Case Report.

Thyroid storm is a rare but life-threatening condition mainly triggered by infection and abrupt discontinuation of antithyroid drug therapy for Graves' disease. Pancytopenia is a rare adverse reaction to antithyroid drugs. We present a 13-year-old girl with thyroid storm and pancytopenia with symptoms similar to those of methimazole-induced pancytopenia. Although in this context the use of methimazole is still under debate, due to multiple normal complete blood counts monitored during fever, sepsis-induced pancytopenia with thyroid storm was considered, and methimazole treatment combined with methylprednisolone and meropenem was able to resolve both pancytopenia and thyroid storm. During the period of infection and antithyroid drug therapy, close monitoring of complete blood count may help differentiate the aetiology of pancytopenia. This is the first paediatric case report that outlines the use of methimazole in the management of thyroid storm with pancytopenia.

A chronic EBV infection causing persistent facial erythema multiforme and a retrospective literature review: A case report

Epstein-Barr virus (EBV) infection is associated with a variety of diseases and can involve multiple organs and systems, with complex and nonspecific clinical manifestations that are easily misdiagnosed. Chronic EBV infection with persistent erythema multiforme (EM) on the cheek as the main manifestation is very rare and has been reported rarely. This article reports a case of an adolescent female with chronic EBV infection who presented with chronic symmetrical erythema lesions on the face for 4 years, exacerbated with photophobia, lacrimation, Henoch-Schonlein purpura (HSP)-like rash, decline in granulocyte and erythrocyte lineages, hematuria, and proteinuria for 1 week. The disease was initially misdiagnosed as systemic lupus erythematosus (SLE) and later confirmed as chronic EBV infection by skin biopsy. In the case, EBV infection not only caused chronic facial EM, but also induced acute HSP and purpura nephritis (hematuria and proteinuria type). The child was treated with 1 week of glucocorticosteroids in adequate doses combined with acyclovir antiviral therapy and 3 sessions of hemoperfusion. After discharge, she took prednisone acetate (15 mg twice a day) orally for 1 month and then discontinued. She was discharged with her rash relieved and normal blood routine test and urine routine test. After 13 months of long-term follow-up, her facial erythema and hyperpigmentation became lighter, and there was no new rash on the whole body, and no abnormality in continuous monitoring of complete blood count and urine test. This case suggests the need to be alert for chronic EBV infection in adolescent females with chronic facial EM rash and multiple organs and systems injury, in addition to connective tissue diseases such as SLE.

Baseline predictors of hematological toxicity in patients with advanced cancer treated with ATR inhibitors in phase I/II clinical trials.

3111 Background: Ongoing trials are exploring ATR inhibitors (ATRi) in genomically selected contexts. However, myelosuppression, particularly anemia, has limited the therapeutic window of this class of drugs. We sought to discover clinical biomarkers predicting severe hematological toxicity from ATRi. Methods: We retrospectively analyzed clinical parameters and peripheral blood cell indices retrieved from complete blood count (CBC) reports of patients (pts) pre- and during treatment with an oral ATRi on phase I/II trials at our center. Pts received ATRi monotherapy or in combination with a PD1 inhibitor (PD1i) or a PARP inhibitor (ATRi+PARPi) in dose-escalation and expansion cohorts, which included ATRi at potentially toxic doses. Results: 37553 indices from 2209 CBC reports of 141 pts treated with an ATRi from 10/2017 to 1/2022 were analyzed. 132 (93.6%) pts received ATRi +/- PD1i; 9 (6.4%) pts received ATRi+PARPi. The incidences of ≥ grade (G) 3 anemia, neutropenia and thrombocytopenia were 47.5%, 31.9% and 11.4%. 73/141 (51.8%) pts received red cell transfusion. Baseline risk factors predicting ≥G3 anemia on univariate analysis included: lower median (med) hematocrit (Hct) (hazard ratio (HR) (95% confidence interval) = 3.05 (1.82, 5.13) ≤med vs > med; p < 0.0001), hemoglobin (Hb) (HR = 2.74 (1.64,4.57) ≤med vs > med; p = 0.0001), mean corpuscular Hb concentration (HR = 1.85 (1.11,3.10) ≤med vs > med; p = 0.019); and higher median immature reticulocyte fraction (HR = 0.43 (0.25,0.71) ≤med vs > med; p = 0.0012), reticulocyte count (ct) (HR = 0.59 (0.35,0.97) ≤med vs > med; p = 0.037) and red cell distribution width (RDW) (HR = 0.54 (0.33,0.88) ≤med vs > med; p = 0.015). On multivariate analysis, lower median Hct (HR = 3.76 (2.15, 6.6) ≤med vs > med; p < 0.0001), higher immature granulocyte ct (HR = 1.71 (1.30, 2.25) per 1 fold increase; p = 0.0001), higher RDW (HR = 7.83 (1.70, 36.03) per 1 fold increase; p = 0.0082) and higher ATRi starting dose (HR = 1.40 (1.05, 1.86) per 1 fold increase; p = 0.022) significantly predicted ≥G3 anemia risk. Baseline risk factors for ≥G3 neutropenia on univariate analysis included: lower median absolute neutrophil ct (ANC) (HR = 2.26 (1.18, 4.33) ≤med vs > med; p = 0.015) or white blood cell ct (WBC) (HR = 2.73 (1.40, 5.33) ≤med vs > med; p = 0.0032). On multivariate analysis, lower median WBC (HR = 2.85 (1.45, 5.59) ≤med vs > med; p = 0.0024) was associated with higher risk of neutropenia, while ATRi+PARPi increased risk of neutropenia (ANC < 0.75) (HR = 4.15 (1.40, 12.3); p = 0.01) and thrombocytopenia (HR = 3.90 (1.47, 10.4); p = 0.0064). Conclusions: ≥G3 anemia was frequent in pts receiving ATRi. At baseline, lower median Hct and higher RDW predict severe anemia, while lower WBC predicts neutropenia from ATRi. ATRi+PARPi has increased risk of neutropenia and thrombocytopenia vs ATRi +/- PD1i. These indices may inform patient selection and CBC monitoring for future ATRi trials.

Real-world treatment patterns of palbociclib and blood count monitoring in patients with advanced breast cancer in Japan.

Aim: To reveal the treatment patterns of palbociclib and complete blood count (CBC) monitoring in a Japanese real-world setting. Materials & methods: Deidentified data of patients with advanced breast cancer who received palbociclib from 2017 to 2020 were examinedfrom a Japanese claims database. Results & conclusion: We identified 1074 patients. Palbociclib was commonly prescribed as second- or later-line treatment in 2017/2018; thereafter its first-line treatment increased. Regardless of treatment lines, fulvestrant was most commonly prescribed in combination with palbociclib (57-66% in the first-third-line), and this finding differed from that in the USA. Most patients initiated palbociclib at 125mg/day; however, over a half of patients reduced doses within the first 8weeks. Although CBC was regularly monitored, some patients did not undergo blood tests. Early dose reduction and CBC monitoring should be performed cautiously to minimize safety concern and prevent early treatment discontinuation.

Safety profile of onasemnogene abeparvovec in children with spinal muscular atrophy

Goal. To evaluate the safety profile of onasemnogene abeparvovec (Zolgensma®) gene therapy in children with spinal muscular atrophy (SMA) in real clinical practice. Materials and methods. The study included 30 SMA children who underwent gene replacement therapy with onasemnogene abeparvovec (Zolgensma®) from December 2020 to December 2021 at the Center for Pediatric Psychoneurology. All children had a diagnosis of SMA confirmed by molecular genetic methods, with no more than 3 copies of the SMN2 gene and the absence of antibodies to the adeno-associated virus serotype 9. The safety profile was assessed by monitoring the clinical and laboratory data of the patients after administration of onasemnogene abeparvovec. Clinical events included all changes in the child’s condition that could be associated with the administration of the drug (hyperthermia, decreased appetite, nausea, vomiting, stool disorders). Laboratory assessment included monitoring of complete blood count, biochemical blood tests, blood coagulation indices. The degree of laboratory changes was estimated according to common terminology criteria for adverse events (CTCAE version 5.0). Results. The safety profile of the drug Zolgensma® was studied in 30 children aged from 3 to 39 months, with a weight of 5.2 kg to 14.2 kg. Twenty-eight (93.3%) children had at least one clinical event associated with the administration of the drug. Hyperthermia was observed in 24 (80%) children, nausea and vomiting in 18 (60%) children, decreased appetite in 20 (66.7%) children, stool changes in 4 (13.3%) children. Monitoring of laboratory indices revealed thrombocytopenia and monocytosis in twenty-two (73.3%) children and neutropenia in twelve (40%) children in the general blood test. An increase in the level of transaminases was noted in all children, the CTCAE grade 1 was detected in fifteen (50%) children, the CTCAE grade 2 in 7 (23.3%) children, CTCAE grade 3 in 6 (20%) children, CTCAE grade 4 in 2 (6.7%) children. Children with CTCAE grade 3 required correction of the prednisone dose up 2 mg/kg per day for 2-4 weeks. Two children with CTCAE grade 4 required pulse therapy with methylprednisolone at a dose of 30 mg/kg per day. Regardless of the level of transaminases, no change in the level of total and direct bilirubin was observed in any case. A decrease in prothrombin time was observed in 14 (46.6%) children. An increase in the level of troponin I was detected in four (13.3%) children. In all cases of serious adverse events, according to laboratory indices, the clinical condition of the children remained stable. The average duration of prednisone intake was 17.8 ± 6.6 weeks. Conclusion. The safety profile of the drug onasemnogene abeparvovec (Zolgensma®) in real clinical practice in children with SMA is presented.

Ocrelizumab associated late-onset neutropenia in the patient with multiple sclerosis: Case report and literature review

Introduction. Ocrelizumab is a recombinant humanized monoclonal antibody that selectively depletes CD20-expressing B cells, which is approved for the treatment of the relapsing and primary progressive multiple sclerosis (MS). It is extremely rarely associated with late-onset neutropenia (LON), as an adverse event. Case outline. We describe a case, from the Treatment Registry of the Clinic of Neurology, University Clinical Center of Serbia, Belgrade, of a transient, asymptomatic LON detected in a naive relapsing?remitting MS patient, six-months after treatment with ocrelizumab. Conclusion. Having in mind all the presently available data, which indicate that rarely occurring LON on ocrelizumab is asymptomatic and transient in the majority of cases, we assume that it may be suggested that only in patients with complaints suggesting the presence of possible infection, additional complete blood count monitoring should be mandatory, exclusively at that moment, apart from the precisely defined regular follow-up.

Association of serum prostate-specific antigen with Complete Blood Counts in patients with prostatic cancer

Background: Prostate cancer is the second most common cancer and one of the most leadingcauses of death in men worldwide. The prostate-specific antigen (PSA) as a screening methodshowed that there has been a slight decrease in prostate cancer mortality. Effective biomarkers inscreening and diagnosis would be beneficial for avoiding unnecessary operations. The predictive andprognostic value of complete blood count (CBC) has been manifested by recent studies. We aimed todetermine the association of serum PSA with Complete blood counts in patients with prostate cancer.Method: The present study included 100 subjects, 50 patients diagnosed with new prostate cancerand 50 patients with prostate cancer. All the was undertaken in the central diagnostic laboratory atVIMS and RC. Blood samples were collected from all the subjects after taken permission from theinstitutional ethics committee and consent form. The haemoglobin, RBCs, MCV, MCHC, RDW will beanalysed by using laboratory standard methods (Beckman coulter LH-780) and The serum PSAlevels are estimated by commercially available kits based on enzyme-linked immunosorbent assay(ELISA). Results: In the present study found significantly elevated levels of a prostate specificantigen in both groups of prostatic cancer patients. The reduced levels of hemoglobin, red bloodcells, platelets, neutrophils were observed in prostatic cancer patients when compared to newlydiagnosed prostate cancer patients. The PSA levels were negatively correlated with total bloodcounts. Conclusion: This study suggests that the elevated levels of prostate specific antigen wereuseful for diagnosis and prognosis of prostatic cancers, along with the monitoring of complete bloodcount may be useful for the treatment of patients with prostatic cancers.

Effects of filgrastim versus pegfilgrastim on outcomes of DA-R-EPOCH for non-Hodgkin's lymphoma.

Our study aimed to compare the median and average last dose level reached with DA-R-EPOCH, which includes the chemotherapy agents etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab, in patients using filgrastim versus pegfilgrastim as febrile neutropenia primary prophylaxis. A retrospective, single-center chart review from January 1, 2014, to September 30, 2019, at The University of Kansas Health System identified patients > 18 years old who received at least four cycles of DA-R-EPOCH in an inpatient or outpatient setting for any subtype of lymphoma along with at least one dose of filgrastim or pegfilgrastim. Data was collected to compare dosing levels reached, appropriate discontinuation of daily filgrastim when ANC > 5000 cells/mm3, completion of at least twice weekly complete blood count (CBC) monitoring after chemotherapy administration, the incidence of infections, FN, hospitalizations from infections or FN, and bone pain. We hypothesized that patients receiving pegfilgrastim will achieve similar median and average dose levels of DA-EPOCH, event-free survival rates, overall response rates, completion of at least twice weekly CBC monitoring, and incidence of infections, FN, hospitalizations for infections or FN, and bone pain compared to patients receiving filgrastim. The use of pegfilgrastim as a supportive care agent resulted in similar efficacy and safety outcomes compared to filgrastim with DA-R-EPOCH in terms of dose intensity levels and incidence of infections, FN, and bone pain.

Meropenem-induced pancytopenia in a preterm neonate: a case report

BackgroundA post-marketing surveillance study has reported an association between meropenem use and the incidence of hematologic abnormalities, including leukopenia, thrombocytopenia, hemolysis, and neutropenia, but the precise incidence in neonates is unknown. Here, we report meropenem-induced pancytopenia in a preterm neonate.Case presentationA preterm newborn Pakistani received intravenous meropenem 40 mg/kg every 8 hours to treat Klebsiella pneumoniae in blood cultures and suspected meningitis. The baby developed severe thrombocytopenia, with a platelet count of 22 × 103 cells/mm3, low hemoglobin level of 9.7 g/dl, and low absolute neutrophil count (ANC) of 816 cells/mm3 on days 3, 14, and 17 of meropenem therapy, respectively. Based on the blood culture and institutional guidelines, meropenem treatment was continued with monitoring and supportive care for a total of 19 days. After discontinuation of meropenem, the baby was monitored continuously for hematological changes, and low counts persisted for 3 days. ANC improved to > 1500 cells/mm3 on the fourth day, and the platelet count reached > 150 × 103 cells/mm3 for the first time on the seventh day of meropenem discontinuation. All subsequent complete blood count (CBC) reports showed improving trends. The baby was discharged on the 48th day of life (DOL), with follow-up monitoring of CBC. The baby was kept on iron supplements, and hemoglobin level of 11.2 g/dl was observed on the 59th DOL.ConclusionNeonatal pancytopenia may lead to serious health complications; therefore, clinicians and pharmacists need to vigilantly monitor CBC in this vulnerable population, even when administering meropenem in septic doses for the recommended duration.

Continuous Pre-Dose Assessment of Laboratory Parameters Is Not Required for Multiple Myeloma Patients Receiving Lenalidomide, Bortezomib, and Dexamethasone (RVD)

Background Lenalidomide, bortezomib, and dexamethasone (RVD) is a standard front-line regimen for both transplant eligible and ineligible multiple myeloma (MM) patients. Based on original APEX study data, which reported development of thrombocytopenia, anemia, and neutropenia in 35%, 26%, and 19%, respectively, complete blood counts before every administration of bortezomib has been recommended. Although an injection of bortezomib takes only 3-5 seconds, waiting for the results of a complete blood count (CBC), with or without a comprehensive metabolic panel (CMP), can add approximately an hour to the visit. This can be cumbersome for patients, who are usually older adults, and it can also present a financial burden for patients, payers, and institutions. Methods The primary objective of this study was to identify patients who can receive RVD safely without repeat labs prior to each bortezomib injection. Secondary objectives included evaluation of costs and appointment visit times. Eighty-nine patients were identified in an institutional review board- approved descriptive, retrospective, medical chart review of patients with MM aged ≥ 18 years who received ≥3 cycles of RVD treatment from January 1, 2016 to January 31, 2020. Sixty-eight patients (76%) received bortezomib on a weekly schedule and twenty-one patients (24%) received bortezomib on a twice weekly schedule. Seventy-four patients (83%) were newly diagnosed and fifteen patients were relapsed/refractory when they began treatment with RVD. Results Thrombocytopenia On day 1 of each cycle (starting cycle 2), 100% of patients had a platelet (PLT) count ≥75,000 cells/µL (Table 1 and 2). Less than 10% of patients developed grade ≥ 2 thrombocytopenia, including 2% and 0% with grade 3 and 4 events, respectively. No patients had treatment delays or interventions for any grade of thrombocytopenia. Only one patient (1.6%) had platelets less than 50,000 cells/µL on day 15 of cycle 2. In cycles 3 and 4, 100% of patients had platelets greater than 50,000 cells/µL on each treatment day. Neutropenia The majority of patients had an absolute neutrophil count (ANC) ≥ 1,000 cells/µL at the beginning of each cycle: 94%, 100%, and 100% in cycles 2-4, respectively. Of the patients with absolute neutrophils ≥ 1,000 cells/µL on the first day of cycles 2-4, more than 93% of the patients had absolute neutrophils ≥ 1,000 cells/µL on subsequent days of cycles 2-4 (Table 3 and 4). Grade 3 and 4 neutropenia was observed in 6.7% and 1.1% of patients, respectively. Only two patients (2.9%) had treatment delays. Filgrastim was administered for 3 incidences of grade 3 neutropenia and 1 incidence of grade 4 neutropenia. One patient (1.4%) had a dose reduction in lenalidomide due to grade 3 neutropenia. We did not observe any significant impact of either once a week or twice a week regimens on changes in platelet or absolute neutrophil counts. Serum Creatinine and Total Bilirubin No significant trends occurred in serum creatinine or total bilirubin. The average serum creatinine and total bilirubin for both cohorts was ≤ 1.2 mg/dL throughout the study for cycles 1-4. Wait Time and Costs Implications We evaluated the time saved and expense reduction by checking labs only on day 1 of each cycle and identified an average time saving of 3 to 4.5 hours and financial savings of $1,542 per cycle for each patient. Conclusion This study demonstrates that beyond the first cycle, patients with platelets ≥ 75,000 cells/µL and absolute neutrophils ≥ 1,000 cells/µL on the first day of a cycle do not need labs prior to each administration of bortezomib (while on RVD regimen). Furthermore, a CMP does not need to be obtained prior to each dose of bortezomib, unless otherwise indicated, since no significant trends occurred in serum creatinine or total bilirubin in our study. Decreased monitoring of CBCs and reducing the number of labs needed during each cycle will improve resource utilization, save money, and save time for patients and health care providers. These cytopenias were typically cyclic and transient. Prescribing information for bortezomib and lenalidomide recommend monitoring compete blood counts and platelets at several intervals and neither medication package inserts give guidance on how frequent serum creatinine and total bilirubin should be monitored. With so many recommendations for monitoring, the frequency of obtaining labs is often left at the discretion of the provider. Disclosures Munshi: BMS: Consultancy; OncoPep: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; C4: Current equity holder in private company; Janssen: Consultancy; Adaptive: Consultancy; Legend: Consultancy; Amgen: Consultancy; AbbVie: Consultancy; Karyopharm: Consultancy; Takeda: Consultancy.

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Response to the Time

Abstract P5-14-13: Real-world dosing and CBC monitoring in patients with metastatic breast cancer during palbociclib plus letrozole therapy

Abstract Background: Palbociclib in combination with letrozole (P+L) was the first cyclin-dependent-kinase 4/6 inhibitor approved in the U.S for treatment of metastatic breast cancer (mBC). Per the U.S. label, the recommended starting dose for Palbociclib (P) is 125 mg and patients should have complete blood count (CBC) monitoring prior to the start of treatment, at the beginning of each cycle, on day 15 of the first 2 cycles, and as clinically indicated. We sought to evaluate adherence to these FDA label in patients receiving P+L as initial endocrine-based therapy. Methods: Adult post-menopausal women with metastatic HR+/HER2- breast cancer who initiated P+L on or after 02/03/2015 were randomly identified by providers in the Cardinal Health Oncology Provider Extended Network (OPEN), which includes over 7,000 US oncologists/hematologists. Providers who were part of OPEN who responded to an initial feasibility request (survey) indicating an interest to participate in the study and treating the patients of interest were invited to participate. Providers were asked to randomly select eligible patients treated with P+L who were initiated on first-line P+L at least 3 months following their first treatment of any patient with P+L. Providers were asked to indicate that the patient had been randomly selected from among all eligible patients and were able to enter up to 10 total patients. All data were abstracted by the patient's treating provider in an electronic case report form (eCRF). Providers abstracted data related to patient characteristics, dosing, and frequency of CBC monitoring in the 30 days prior to and during the first 2 cycles of therapy of randomly selected patients from the time of initiation of P+L through Feb 2019 (or end of follow up/death). Providers completed data validation by re-entering select data from randomly selected patients (10% of the total sample) and for patients which were flagged for quality control review by Cardinal Health clinical research staff and data analytics team members when the results were inconsistent or deviated from the population averages. Results: Thirty-one providers submitted 202 eCRFs, of which 193 were eligible (9 patients removed with non-verifiable data). Demographics: mean age was 65.0 y/o (SD = 10.5), 74.6% white, 38.6% commercially insured. Clinical characteristics: 65.8% de novo metastatic, 51.3% visceral disease at initiation of P+L, 25.4% bone only disease, 10.4% ECOG-PS ≥2. Median follow-up from P+L initiation was 15.4 months, 45.6% of patients had discontinued P+L at data cut-off. Overall, 86.0%, 13.5%, and 0.5% of patients initiated treatment of P at the 125 mg, 100 mg, and 75mg dose, respectively. Dose reductions were reported in 17.1% of patients. CBC testing was conducted prior to P+L initiation in 99.0% of patients; median number of CBC tests during cycle 1 was 2.0; 37% of patients had only one CBC test. In cycle 2, median number of CBC tests was 1.5 and 46.5% of patients had only one CBC test. Conclusions: Physicians were generally compliant with the Palbociclib package insert recommendations for dosing and monitoring during the first cycle, less so for monitoring during the second cycle in women with HR+/HER2- mBC. Funding: Pfizer Inc. Citation Format: Jonathan Kish, Talia Miller, Damion Nero, Djibril Liassou, Xianchen Liu, Lynn McRoy, Bruce Feinberg, Lin Zhan, Jeffrey Trocio. Real-world dosing and CBC monitoring in patients with metastatic breast cancer during palbociclib plus letrozole therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-13.

2646. Incidence of Myelosuppression Related to Valganciclovir Prophylaxis in Solid-Organ Transplant Recipients at High Risk of CMV Disease

BackgroundValganciclovir (VGCV) prophylaxis in solid-organ transplant patients (SOT) is limited by myelotoxicity. We aimed to analyze the impact of VGCV prophylaxis on myelotoxicity and risk factors for its occurrence.MethodsRetrospective single-center cohort study of adult CMV-seronegative recipients transplanted between July 2005 and November 2017. CMV D+/R− recipients received 3 to 6 months of VGCV prophylaxis whereas CMV D-/R- received no VGCV. Definitions: leukopenia < 3.5 × 109/L, significant neutropenia < 1.0 × 109/L and significant thrombocytopenia < 50 × 109/L.ResultsA total of 363 SOT recipients were included, 169 (47%) CMV D+/R− and 194 (53%) CMV D−/R−, with a mean age of 49.5 years and 275 (76%) males; types of organ transplant: 133 (37%) liver, 181 (50%) kidney, 37 (10%) simultaneous kidney-pancreas and 12 (3%) other. Although there was no difference in the incidence of significant neutropenia or thrombocytopenia per transplant type, leukopenia in the first year was more common in liver transplant patients (P < 0.001). New onset leukopenia post-SOT, significant neutropenia (Figure 1) and significant thrombocytopenia in the first year were more common in patients receiving VGCV: 116 D+/R− (69%) vs. 52 D−/R− (31%), P < 0.001; 86 (91%) vs. 9 (9%), P < 0.001; 8 (80%) vs. 2 (20%), P = 0.050; respectively. G-CSF was used more frequently in patients receiving prophylaxis (60% CMV D+/R− vs. 10% CMV D−/R−, P < 0.001). Significant neutropenia had no impact on long-term mortality adjusted by age and transplant type (HR 1.1, 95% CI 0.6–2.1, P = 0.709). Significant neutropenia led to decrease immunosuppression in 90% of patients (vs. 46%, P < 0.001) and was associated with increased risk of rejection (HR 8.5, P < 0.001). In multivariate analysis for significant neutropenia in the first year, VGCV prophylaxis was the only predictor of this outcome after adjusting for confounders (HR 15.1, 95% CI 7.5–30.1, P < 0.001).ConclusionVGCV prophylaxis increased the risk of significant neutropenia by 15-fold post-SOT. No other clinical variables were useful to predict this complication. Therefore, complete blood count monitoring is still needed for all SOT recipients receiving VGCV prophylaxis. Disclosures All authors: No reported disclosures.

The clinical utility of laboratory monitoring during isotretinoin therapy for acne and changes to monitoring practices over time

As a result of concerns about hypertriglyceridemia, liver enzyme abnormalities, and leukopenia during isotretinoin therapy for acne, patients are often monitored closely with routine laboratory assessments, although the value of this practice has been questioned. We conducted a cohort study of patients receiving isotretinoin for acne between January 1, 2008, and June 30, 2017, using the OptumInsights Electronic Health Record Database (Optum, Eden Prairie, MN) to evaluate the frequency of laboratory abnormalities. Poisson regression was used to evaluate for changes to the frequency of routine laboratory monitoring over time. Among 1863 patients treated with isotretinoin, grade 3 or greater triglyceride and liver function testing abnormalities were noted in fewer than 1% and 0.5% of patients screened, respectively. No grade 3 or greater cholesterol or complete blood count abnormalities were observed. There were no meaningful changes in the frequency of laboratory monitoring over time. Limitations include that we are unable to evaluate the clinical notes to understand the exact clinical decision making when clinicians encountered abnormal laboratory values. Although laboratory abnormalities are rare and often do not influence management, frequent laboratory monitoring remains a common practice. There are opportunities to improve the quality of care among patients being treated with isotretinoin for acne by reducing the frequency of lipid and liver function monitoring and by eliminating complete blood count monitoring.

Real-World Experience of Palbociclib-Induced Adverse Events and Compliance With Complete Blood Count Monitoring in Women With Hormone Receptor–Positive/HER2-Negative Metastatic Breast Cancer

BackgroundThe cyclin-dependent kinase 4/6 inhibitor palbociclib has emerged as a novel therapeutic agent in metastatic breast cancer. Neutropenia is commonly observed, and thus stringent treatment guidelines regarding complete blood count (CBC) monitoring have been developed. The aim of this study was to provide a real-world experience of the toxicities associated with palbociclib therapy and to evaluate compliance with CBC monitoring. Patients and MethodsWe performed a retrospective single-center audit of hormone receptor–positive metastatic breast cancer patients treated with palbociclib over a 6-month period in an Irish tertiary referral hospital. ResultsA total of 64 patients were included in the analysis. Palbociclib was most commonly used in combination with letrozole (n = 40). A total of 28 patients (44%; 95% confidence interval, 31.2-56.2) had treatment deferrals due to neutropenia, with a median time to first deferral of 4 weeks. Fifteen patients (23%; 95% confidence interval, 15.4-37.7) required dose adjustments; however, there was no association with an increased risk of progressive disease (P = .56). Only 3 patients discontinued treatment as a result of poor tolerance. Adverse events were as expected; however, 7 venous thromboembolic events were reported. ConclusionCompliance was good with existing CBC monitoring guidelines. We observed an 11% incidence of venous thromboembolic events, a significant increase from 2% reported in the PALOMA-3 trial. Further studies are recommended to determine if prophylactic anticoagulation may benefit these patients.

Evaluating the Effect of the Changes in FDA Guidelines for Clozapine Monitoring.

Concerns exist that clozapine is underutilized in the management of treatment-resistant schizophrenia. Although a 2015 change in the US Food and Drug Administration (FDA) monitoring recommendations lowered the threshold of the absolute neutrophil count for treatment interruption from 1,500/μL to 1,000/μL and removed white blood cell count thresholds from the monitoring algorithm, the implications of this policy change on clozapine interruptions remain unknown. We analyzed outpatient prescribing records for antipsychotic medications in the Veterans Integrated Service Network 7 (VISN 7) database between 1999 and 2012 to assess the potential impact of the recent changes in FDA neutropenia monitoring recommendations on clozapine treatment discontinuation. We evaluated results of complete blood count monitoring to compare percentages of patients who developed or would have developed ≥ 1 hematologic event under the previous and current FDA guidelines in the first year following initiation of clozapine. From a cohort of 14,620 patients with schizophrenia (ICD-9-295.x), 246 patients received clozapine treatment (1.7%). No agranulocytosis was observed during the study period. Under the former recommendations, 5 patients in the clozapine initiation cohort (n = 160, 3.1%; 95% CI, 0.43-5.83) qualified for treatment interruption during the first year of clozapine treatment, while only 1 patient (0.6%) qualified under the current recommendations. Under the former recommendations, hematologic events occurred at a similar rate for individuals taking and not taking clozapine. While clozapine remains an underused medication, the new FDA monitoring guidelines are likely to substantially reduce the percentage of patients who meet criteria for clozapine-associated hematologic events requiring treatment interruption. This decrease may reduce the clinical burden of managing patients on clozapine and therefore increase the number of individuals treated with this uniquely effective medication. However, prospective studies of individuals treated under the new guidelines are needed to fully assess safety of the FDA's change.

Outpatient Parenteral Antimicrobial Therapy (OPAT) Practices at a Veterans Affairs Hospital: Potential for Pharmacist Impact

BackgroundThe Infectious Diseases Society of America (IDSA) OPAT Practice Guidelines and Handbook recommend multidisciplinary team involvement as a key element to the success of OPAT. Studies have demonstrated that OPAT pharmacist oversight can improve monitoring of intravenous (IV) antibiotics and achieve clinical cure in 77% of patients. Pharmacists at the Veterans Affairs Palo Alto Health Care System are currently not routinely involved with the management of OPAT patients.MethodsA retrospective analysis was performed to determine the rate of adherence to IDSA recommendations on antibiotic laboratory and clinical monitoring in veterans discharged with OPAT between July 1, 2015 and June 30, 2016. Secondary outcomes assessed were rates of clinical cure, treatment failure, readmission, and OPAT complications. Data was analyzed using descriptive statistics.ResultsOf 83 patients evaluated, 91 IV antibiotics were administered and 70 patients completed OPAT. The most common infections were osteomyelitis (n = 33, 40%), bacteremia (n = 13, 13%), and skin and soft-tissue infection (n = 9, 11%). Cephalosporins (n = 41, 45%) were most commonly used, followed by vancomycin (n = 18, 20%) and penicillins (n = 12, 13%). Appropriate monitoring of complete blood count, basic metabolic panel, and liver function occurred 45%, 45%, and 25% of the time, respectively, based on IDSA guidance. An increase in treatment failure was observed when less than 25% of weekly lab monitoring was conducted. Twenty-six patients (31%) met the IDSA recommendation for follow-up visits within 7–14 days of discharge and 51 patients (61%) received follow-up visits upon OPAT completion. Clinical cure was achieved in 52 patients (63%). There were more 90-day readmissions related to infection, adverse drug reactions, catheter-related complications, and C. difficile infections reported in the treatment failure group compared with the clinical cure group.ConclusionIn most cases, IDSA recommendations on OPAT management were not appropriately followed and lack of monitoring was associated with treatment failure. Fewer patients achieved clinical cure compared with rates documented in the literature, strongly suggesting the need for an OPAT pharmacist to achieve optimal monitoring and follow-up.Disclosures All authors: No reported disclosures.

Cutting costs and standardizing care: Once‐per‐cycle complete blood count monitoring may be safe for patients undergoing platinum‐based chemotherapy

The aim of this study was to evaluate whether frequency of complete blood count (CBC) testing during chemotherapy for gynecologic cancer impacts hospital admissions or rates of neutropenic fever. A retrospective cohort study was performed at a single academic institution. Patients undergoing platinum-based chemotherapy for endometrial or ovarian cancer from January 2010 to December 2014 were identified from a clinical database. Patients receiving dose-dense chemotherapy or on a clinical trial were excluded. Electronic chart review collected demographic and clinical characteristics. The primary outcome was the rate of febrile neutropenia or hospital admission. A total of 174 patients were identified, 63 (36%) with endometrial and 111 (64%) with ovarian cancer. Fifty-four percent of patients received multiple CBC per cycle compared with 46% who only had one CBC per cycle. The majority of patients were treated with a platinum-based doublet (85%). Dose reductions, addition of granulocyte colony stimulating factor, and rates of grade 3 or 4 anemia and neutropenia were significantly associated with more frequent testing. There was no difference in rates of neutropenic fever (5.3 vs 3.8%, P = 0.45) or hospital admission (22.3 vs 21.3%, P = 0.86) for multiple versus single CBC monitoring. More frequent laboratory testing detected more cases of grade 3 or 4 hematopoietic toxicities and was associated with more interventions. There were no differences in number of hospitalizations or cases of neutropenic fever by frequency of laboratory testing, suggesting that it may be appropriate to decrease routine laboratory tests for select patients.

Safety and Efficacy of Enoxaparin Prophylaxis in Adults Receiving Peg-Asparaginase Containing Induction Regimens for Acute Lymphoblastic Leukemia (ALL)

Background:Peg-asparaginasecan cause dysregulationof pro-coagulant and anti-coagulant proteins, resulting in a significant risk of venous thromboembolism(VTE) in ALL, particularly in adults undergoing induction chemotherapy. In late 2014, we adopted a policy at our institution to use prophylactic dose ofenoxaparin 40 mg daily for up to 3 weeks following the administration of peg-asparaginase. Patients are also to undergo monitoring of complete blood count, and coagulation parameters including fibrinogen and anti-thrombin. Enoxaparin may be held if patients develop severe thrombocytopenia (platelet count <30,000/µL). Cryoprecipitate is given if fibrinogen drops below 100 mg/dl. In the present study, we aim to analyze primarily the safety, and secondarily the efficacy ofenoxaparin prophylaxis in this setting and highlight the changes in coagulation parameters following peg-asparaginase use during induction therapy.Methods:This is a single-center study of17 consecutive adult patients (>18 years old) treated for ALL with peg-asparaginasecontaining induction regimen before and after the establishment of institutional policy to useenoxaparinprophylaxis. Patients were identified from hospital research database. The diagnoses were verified. Medical records were reviewed for the occurrence of any clinically relevant bleeding and VTE within 3 months of receiving peg-asparaginase. Levels of coagulation parameters, whenever available, were collected at baseline and at weekly intervals for up to 4 weeks after receiving peg-asparaginase. The risk of bleeding and VTE among patients receivingenoxaparinwas compared to those who did not receiveenoxaparin. Fisher exact test was used for testing the association of categorical variable, and binomial exact test was used for computing confidence intervals. T-test or nonparametric test was used for comparing the continuous variables depending on whether or not the data were normally distributed.Results:The patient population consisted of 59% females. Mean age was 35 years. Histology consisted of Pre-B ALL in 76%, pre-T ALL in 18% and mixed lineage leukemia in 6%. 88% percent received pediatric-type chemoregimenand intramuscular peg-asparaginase; the most common doses of peg-asparaginaseincluded 2000 mg/m2 (41%) and 2500 mg/m2 (35%). Duration ofenoxaparin prophylaxis was 21 days in 66.7% and 7 days in 33.3%. Average changes in coagulation parameters at baseline and at weekly intervals following the use of peg-asparaginase therapy are highlighted in figures 1 and 2. The drop inantithrombin and fibrinogen levels was the highest during the first two weeks after the administration of peg-asparaginase. 41% of patients required cryoprecipitate (median 15 units, range 5-35 units over 4 weeks). No patients, including theenoxaparin group, had any clinically relevant bleeding event. The risk of VTE was 18% (95% confidence 4-43%); 2 out of 3 VTE events were cerebral venous thrombosis. No VTE occurred in theenoxaparin prophylaxis group (n=9), whereas 37% of patients (3 out of 8 patients), who did not receiveenoxaparin, developed VTE.Enoxaparin prophylaxis was associated with a trend towards a lower risk of VTE, however, the difference was not statistically significant (p=0.08).Conclusion:Within the limits of this study, in adult ALL patients receiving peg-asparaginase, the use of daily prophylactic dose ofenoxaparinmay not be associated with an increased risk of clinically relevant bleeding, and may have a potential to lower the risk of VTE. Patients receivingenoxaparin, however, should be carefully monitored for the need of platelet transfusion and cryoprecipitate supplementation. The difference in the risk of VTE was not statistically significant, which may be, in part, due to a small sample size.Antithrombindepletion may also contribute to a reduction in the efficacy ofenoxaparin. Larger prospective studies should be performed to validate the preliminary findings. [Display omitted] [Display omitted] DisclosuresArmitage:Spectrum Pharmaceuticals: Consultancy; Roche: Consultancy; Conatus - IDMC: Consultancy; GlaxoSmithKline IDMC: Consultancy; ZiopharmOncology: Consultancy; Tesaro bio Inc: Membership on an entity's Board of Directors or advisory committees. Lunning:Genentech: Consultancy; AbbVie: Consultancy; Bristol-Myer-Squibb: Consultancy; Juno: Consultancy; Spectrum: Consultancy; Pharmacyclics: Consultancy; Celgene: Consultancy; Gilead: Consultancy; TG Therapeutics: Consultancy.

Linezolid Induced Twice Pure Red Cell Aplasia in a Patient with Central Nervous System Infection after Allogeneic Stem Cell Transplantation.

Linezolid (LZD), severed as the first oxazolidinone antibiotic, was active against multidrug-resistant gram-positive strains. LZD can induce thrombocytopenia, anemia and leukocytopenia. Currently, reports on pure red cell aplasia (PRCA) cases induced by LZD are relatively rare (4-7). In this paper, we reported a patient with PRCA twice induced by LZD. A 37-year-old man was diagnosed with myelodysplatic syndrome (MDS) and underwent allo-HSCT from an unrelated donor with ABO blood type and leukocyte antigen (HLA)-matching. After HSCT for 2 years, the patient suffered from refractory fever and headache. He was first treated with empirical antifungal agent and antibiotics for central nervous system (CNS) infection, but then changed to LZD therapy for little effect. Twenty-eight days after LZD treatment, the symptom improved significantly but the hemoglobin declined to 70 g/L and the reticulocyte level was only 0.23%. The LZD therapy was stopped and the fever and headache symptoms reoccurred 1 week latter. Then, erythropoietin (EPO) and halved dosage of LZD were used for treatment. The CNS infection and the anemia symptom relieved gradually and the level of hemoglobin and reticulocyte declined again. After blood transfusion, the half dose of LZD was sustained without anaemia recovery. In summary, patients with anemia, myelosuppressants history or potential abnormal proliferation of T cells may suffer PRCA with long term LZD treatment. The monitoring of complete blood count and reticulocyte count were necessary during LZD therapy. If the clinical condition permits, LZD dosage reduction and blood transfusion should be considered.