Episodes Of Febrile Neutropenia Research Articles

1600P The role of C-reactive protein/albumin ratio in predicting 90-day mortality in patients with febrile neutropenia

The MASCC score is widely used to predict the prognosis of febrile neutropenia after chemotherapy in cancer patients. The MASCC score does not use any laboratory data and has low sensitivity. Therefore, the search for markers to predict the prognosis of febrile neutropenia continues. Albumin(alb) and C-Reactive Protein(CRP) are acute phase reactants, besides albumin reflects nutritional status. In this study, we aimed to evaluate the effect of CRP/alb ratio on the prognosis of febrile neutropenia. The files of patients admitted with the diagnosis of febrile neutropenia between January 2018 and January 2022 were reviewed retrospectively, MASCC risk score, CRP and albumin levels at admission were collected. All patients who were followed up by the medical oncology department, received at least 1 course of chemotherapy and presented with the diagnosis of febrile neutropenia were included in the study. A total of one hundred and fifty-six (n=156) episodes of febrile neutropenia were included in the study, and 55 (35%) of these patients died within ninety days. While the 90-day mortality rate was 45% in the group of patients with MASCC <21, this rate was 26% in patients with MASCC >21 (p = 0.007). The median of the CRP/alb ratio was determined as 58 and the patients were divided into two groups according to the median value. The 90-day mortality rate was 24% in the group with a low CRP/alb ratio, and 45% in the group with a high CRP/Alb ratio (p = 0.004). In patients with a MASCC score of >21 and a CRP/alb score of <58 (n=47), the 90-day mortality rate was 21%, compared to 55% in patients with a MASCC <21 and CRP/alb >58 (p= 0.001). In conclusion, high CRP/Alb ratio worsens the prognosis of febrile neutropenia independently of other factors. The combined evaluation of MASCC risk score and CRP/Alb ratio is beneficial in predicting the prognosis of febrile neutropenia and increases the prognostic power of the MASCC risk score.

Pegfilgrastim in Supportive Care of Hodgkin Lymphoma.

Simple SummaryPegfilgrastim, the pegylated form of filgrastim (recombinant human GCSF) is widely adopted as supportive care for preventing neutropenia or febrile neutropenia episodes during chemotherapy. Neutropenia is directly cause of potentially severe infections and indirectly cause of treatment delivery delay. No guidelines address the pegfilgrastim role in the specific setting of Hodgkin lymphoma (HL). Since HL is a young-adult disease and shows mostly a very a favorable outcome after chemotherapy, treatment delay or dose reduction could potentially affect negatively the outcome. The aim of our review is to explore the current scientific literature on pegfilgratim use in HL, evaluating both observational than prospective trial. Moreover, analyzing the latter, we aim to define some practical suggestion about primary prophylaxis with pegfilgrastim in HL.Neutropenia and febrile neutropenia are common and potentially life-threating events associated with chemotherapy treatment in Hodgkin lymphoma (HL). Neutropenia-related infectious events could be an issue both for direct clinical consequences and for delay in treatment delivery, affecting final outcomes in a potentially highly curable disease. Pegfilgrastim is the pegylated form of filgrastim, the recombinant form of human G-CSF, capable of prevent and mitigate neutropenic effects of chemotherapy, when adopted as primary prophylaxis in several hematological malignancies. No updated version of major international guidelines provides clear indication on prophylaxis use of pegfilgrastim in HL to prevent febrile neutropenia episodes in HL. Moreover, to date, scarce and non-uniform clinical experiences evaluating pegfilgrastim as prophylaxis in HL are present in the literature. Herein, we propose a brief summary of the literature data about efficacy and safety of the use of pegfilgrastim as primary prophylaxis in HL during chemotherapy treatment.

Microbial blood culture patterns and antibiotic susceptibility in pediatric febrile neutropenia at Sanglah General Hospital Bali

Background: Febrile neutropenia is defined as a fever with a temperature more than or equal to 38.3°C in two measurements within 24 hours and accompanied by severe neutropenia (≤500/μL). Gram-positive bacteria have been the most common cause of febrile neutropenia in children for the previous two decades. However, the contradiction in some studies reported that gram-negative bacteria were the main pathogens causing infection. Because there are differences and shifts in the bacterial spectrum, information on the bacterial pattern and antibiotic susceptibility is critical to reaching the optimal management of febrile neutropenia patients. Methods: This observational, descriptive study was conducted in Sanglah Hospital, Bali, Indonesia, involving pediatric patients (&lt;18 years old) with febrile neutropenia. Data on antibiotic susceptibility and microbial patterns were collected retrospectively from the blood culture registry taken from febrile neutropenia patients from October 2017 to August 2020. Collected data were analyzed using the SPSS program for Windows, version 21.0. Univariate analysis was conducted, and data with a categorical scale were reported in frequency distribution and percentage, then displayed in a table and graph. Result: A total of 180 episodes of febrile neutropenia were collected from 89 patients. Among 180 blood cultures, there were found 44 (24.44%) blood cultures with positive results. A higher proportion of gram-negative organisms (33; 75%) is found compared to gram-positive organisms (11; 25%). The susceptibility rates were 100% for Azithromycin, Amoxicillin Clavulanate, Cefoperazone Sulbactam, Meropenem, Linezolid, and Doxycycline, while Cefepime, the previous empirical antibiotic, was susceptible at 79.31% isolates. Conclusion: Gram-negative bacteria were the most frequent cause of infection among febrile neutropenic patients. Although the research evidence is still weak due to the small sample size, Cefoperazone Sulbactam could be a better option to replace Cefepime as an empirical antibiotic due to its significantly higher susceptibility.

Impact of enteral immunonutrition on infectious complications and immune and inflammatory markers in cancer patients undergoing chemotherapy: A systematic review of randomised controlled trials

There is increasing awareness of the importance of nutritional support in cancer treatment including the interaction with immunity. Immunonutrition is the provision of one or more nutrients (e.g. Vitamins A, D, or E, omega-3 fatty acids, arginine and glutamine) known to modulate immune function when given at levels above those normally encountered in the diet in order to support immune system function or modulate its activity, including control of inflammation. We reviewed the role of oral or enteral immunonutrition versus standard nutrition on infection and infection-related biomarkers in adult cancer patients undergoing chemotherapy. A systematic search of oral or enteral immunonutrition versus standard nutrition in adult cancer patients during chemotherapy with or without radiotherapy or haematopoietic stem cell transplant was conducted in MEDLINE, EMBASE and CENTRAL. The search was limited to randomised controlled trials. Our primary outcome was infectious episodes or immune-related biomarkers (e.g. immune cell numbers, inflammatory markers). Secondary outcomes included incidence of malnutrition or cachexia, non-infection related adverse events (AEs), rate of remission, survival, and delays or incomplete cycles of chemotherapy. Risk of bias was assessed using ROB 2.0 and study quality was assessed using CASP for RCTs. The search yielded seven studies involving 521 patients (261 immunonutrition, 260 control) for analysis. All studies enrolled patients with solid tumours (no haematological malignancies). Studies were heterogenous for cancer type (upper gastrointestinal, head and neck, pancreatic and lung), immunonutrient composition (omega-3 fatty acids, vitamin A, E, glutamine, arginine or nucleotides), delivery route (enteral nutrition or oral nutritional supplement) and control used. Intervention period ranged from 4 to 14 weeks. No study reported absolute number of infections. Three studies reported AEs including potential infectious episodes of febrile neutropenia, pneumonitis and mucositis with oral candidiasis. Some studies report a decrease in blood concentrations of CRP and TNF-α with immunonutrition. There is currently insufficient evidence to define a role for immunonutrition on infectious episodes during chemotherapy in adult cancer patients. Further well-defined studies that account for degree of malnutrition, dose, timing and duration of immunonutrition in specific well-defined cancer groups using a standardised outcome framework are needed.

Efficacy and safety of a colostrum- and Aloe vera-based oral care protocol to prevent and treat severe oral mucositis in patients undergoing hematopoietic stem cell transplantation: a single-arm phase II study

Oral mucositis is one of the worst effects of the conditioning regimens given to patients undergoing hematopoietic stem cell transplantation. It is characterized by dry mouth, erythema, mucosal soreness, ulcers, and pain, and it may impact patient outcomes. Bovine colostrum and Aloe vera contain a wide variety of biologically active compounds that promote mucosal healing. A non-randomized phase II study was designed to assess the safety and efficacy of a combined bovine colostrum and Aloe vera oral care protocol to prevent and to treat severe oral mucositis in transplant patients. Two commercially available products were given to patients in addition to the standard protocol: Remargin Colostrum OS® mouthwash and Remargin Colostrum Gastro-Gel® taken orally. Forty-six (78.0%) patients experienced oral mucositis, 40 (67.8%) developed mild–moderate forms, and 6 (10.2%) severe ones. Comparing the study group’s outcomes with those of a homogeneous historical control group, severe oral mucositis decreased significantly (10.2% vs. 28.4%; P < 0.01), as did its duration (0.5 ± 1.9 vs. 1.5 ± 3.0 days; P < 0.01). Febrile neutropenia episodes (69.5% vs. 95.1%; P < 0.01) and duration (4.0 ± 4.7 vs. 6.2 ± 4.5 days; P < 0.01) also decreased. These findings show that the experimental protocol seems effective in preventing severe forms of oral mucositis. However, a randomized controlled trial is necessary to confirm this.

Diagnosis and Management of Febrile Neutropenia in Pediatric Oncology Patients-A Systematic Review.

Infectious diseases are associated with a high morbidity and mortality rate among pediatric cancer patients undergoing treatment or receiving a transplant. Neutropenia represents a potentially fatal complication of cancer treatment and is associated with a high risk of developing bacterial infections. Although febrile neutropenia (FN) can affect both adults and children, the latter has a higher chance of infections with an unknown origin. Prompt empiric broad-spectrum antibiotic administration is collectively considered the best therapeutic approach. This review aims to analyze the latest works from the literature regarding the therapeutic strategies, schemes, and approaches and the efficacy of these in pediatric febrile neutropenia. Following PRISMA guidelines, an advanced search on PubMed, Scopus, and Cochrane Library, using the keywords “febrile neutropenia”, “pediatric”, “cancer”, and “oncology”, was performed. A total of 197 articles were found to be eligible. After screening the abstracts and excluding unfit studies, 16 articles were analyzed. There were eight retrospective studies, five prospective studies, and two clinical trials. Altogether, these studies have described around 5000 episodes of FN. The median age of the participants was 7.6 years, and the underlying condition for most of them was acute leukemia. The infectious agent could only be determined in around one-fifth of cases, from which 90% were of bacterial origin. As such, empirical broad-spectrum antibiotics are used, with the most used treatment scheme comprising third- and fourth-generation cephalosporins and antipseudomonal penicillins. In order to improve the treatment strategies of FN episodes and to successfully de-escalate treatments toward narrower-spectrum antibiotics, hospitals and clinics should increase their efforts in identifying the underlying cause of FN episodes through blood culture urine culture and viral tests, wherever infrastructure enables it.

PB2261: LINEZOLID AS A SAFE ANTIMICROBIAL AGENT IN THROMBOCYTOPENIC PATIENTS UNDERGOING CHEMOTHERAPY FOR HEMATOLOGIC MALIGNANCIES

Background: Febrile neutropenia (FN) is a common event in patients undergoing high-dose chemotherapy (HD-CT) for hematologic malignancies. Linezolid (LZ) is the first-in-class oxazolidinone antimicrobial agent active against gram-positive bacteria, often administered during FN as treatment for hospital-acquired pneumonia, gram-positive bacteriemia and soft-skin tissue infection. LZ induced thrombocytopenia or delayed platelet recovery are adverse events of concern in patients receiving HD-CT. As of today, few data are available on the safety of LZ in this specific setting. Aims: To retrospectively analyze a cohort of thrombocytopenic patients treated with LZ for FN in a single center, evaluating bleeding risk and impact on PLT recovery time. Methods: The analysis included patients diagnosed with Acute Leukemia (AL), High Grade Lymphomas (HGL) and Multiple Myeloma (MM) treated at our institution, between 2016 and 2021, with LZ for a FN episode during induction chemotherapy or ASCT conditioning. To be enrolled, PLT count at the start of LZ therapy had to be < 50×109/L. Results: A total of 40 FN episodes treated with LZ were identified. 22 occurred during induction therapy for AL and 18 during ASCT conditioning regimens. The median PLT count at the start of LZ therapy was 19×109/L in both groups (range 5-49×109/L in the AL cohort, 5-35×109/L in the ASCT group), while the median treatment duration was 8 days in both groups (range 2-15 days in the AL cohort, 3-12 days in the ASCT cohort). Only one clinically relevant bleeding event was observed in the AL group, while 0 bleeding events were observed in the ASCT group. Resolution of infection (defined as fever resolution, normalization of CRP and blood culture negativization) after the introduction of LZ therapy was observed in 17 (77%) AL patients and 15 (83%) ASCT patients. In the AML group PLT recovery (defined as a stable PLT count ≥20×109/L without the need for PLT transfusion) was observed in 18 (81%) patients with a median time to recovery of 22 days from the start of the chemotherapeutic regimen (range 18-41). PLT recovery was observed in 10 (71%) ASCT patients with a median time to recovery of 35 days from the stem cell infusion (range 13-136). 4 out of 18 patients in the ASCT group started LZ therapy after PLT recovery, and 3 out of 18 patients in the same group died due to the infectious complication that prompted the start of LZ therapy. Median PLT recovery time was not significantly different between patients enrolled in this study and historical controls from our center (AML: median 20 days, p>0.1. ASCT: median 22.5 days, p>0.1). Summary/Conclusion: Our observations support the use of LZ in this setting, as only one relevant bleeding event was observed among the two groups, and no impact on PLT recovery time was noted after comparison with historical data. Our study suggests that LZ is a safe and effective antimicrobial therapy in patients undergoing HD-CT for hematological malignancies. This data needs to be prospectively confirmed in a larger cohort of patients in a multicenter study.

Real-world febrile neutropenia rates with same-day versus next-day pegfilgrastim after myelosuppressive chemotherapy.

Aim: To compare the incidence of febrile neutropenia (FN) after same-day versus next-day pegfilgrastim. Materials & methods: This single-institution, real-world, retrospective electronic health record-based study included patients who received chemotherapy and prophylactic same-day or next-day pegfilgrastim/pegfilgrastim-cbqv. Results: In cycle 1,117 patients received same-day pegfilgrastim and 180 patients received next-day pegfilgrastim. FN episodes in cycle 1 occurred in 6.0versus 6.7% of patients with same-day versus next-day pegfilgrastim, respectively (p=0.814). Across all cycles, 8.5and 9.4% of patients experienced ≥1 FN episode after same-day versus next-day pegfilgrastim, respectively (p=0.793). In the breast cancer patient subgroup, FN occurred 3.2% of same-day pegfilgrastim cycles versus 1.8% of next-day pegfilgrastim cycles (p=0.938). Conclusion: No significant differences were detected between same-day and next-day pegfilgrastim administration.

#32 Pediatric Febrile Neutropenia with Low Risk of Systemic Infection: When Is It Safe to Stop Antibiotics?

Abstract Background There are no standard practices about antibiotics duration in unexplained stable febrile neutropenia (FN). Absolute neutrophile count (ANC) recovery has been used clinically to represent bone marrow recovery (BMR) but data about safe ANC threshold for antibiotic cessation (AC) and discharge is still unknown. Other markers should be considered. We hypothesized that absolute monocyte count (AMC), and absolute phagocyte count (APC= ANC + AMC+ bands) are more sensitive, and an earlier safe marker of AC compared with ANC Method A retrospective review was performed for FN episodes (FNEs) at a single institution (2009 and 2016) in pediatric oncology patients. Eligible FNEs who were a febrile for 24 hours and had no documented infectious source identified at AC and did not receive chemotherapy 10 days following AC. Ten-day post-AC primary end points (recurrent fever, readmission, blood stream infection BSI, microbiology documented infection MDI, and adverse outcomes) were assessed and compared among different BMR parameters (ANC vs AMC vs APC). Secondary end point compares length of stay, antibiotics free days and cost-effectiveness among different BMR markers. Results Eligible FNEs were 391 at time of AC in 235 patients. Three groups were compared based on ANC (cells/μL) at the time of AC : &amp;lt; 200 in 102 (26%), 200-500 in 111 (28%), and &amp;gt;500 /uL in 178 (46%) with an overall ten-day recurrent fever rate 7.4% (29/391). No significant differences in primary end point outcomes rates were identified among 3 ANC groups (11.7%,, 6.3% and 5.6% respectively, P=0.06) and readmission (10%,4.5%, 4%, respectively; P=0.05)(Table 1), however, there is a trend toward unfavorable outcomes in ANC&amp;lt; 200 group compared with ANC&amp;gt;200. In subset analysis in group of ANC&amp;gt;200, favorable outcomes in (ANC&amp;gt;200 with AMC&amp;gt;100) than in the (ANC&amp;gt;200 with AMC&amp;lt;100) group. There was significant risk reduction in primary end points (75% in recurrent fever, 85% readmission, 87% in BSI, 88% in MDI and 87% in adverse events in (ANC&amp;gt;200 with AMC&amp;gt;100) compared with (ANC&amp;gt;200 with AMC&amp;lt;100/uL) group. More importantly, primary end points based on AMC&amp;gt;100 /uL as BMR for AC, regardless ANC values, showed significant favorable outcomes compared AMC&amp;lt;100 /uL. There is 80%, 88, 90%, 89%, and 93% risk reduction in end points recurrent fever, readmission BSI, MDI, and adverse outcomes respectively. Similar favorable results were seen when APC&amp;gt;300 used as threshold for AC (Table 2, 3). Median of length of stay of FN was 3 days shorter using AMC &amp;gt;100/uL for BMR compared with any threshold of ANC (P&amp;lt; 0.01) and decrease overall FN cost stay (P&amp;lt; 0.01). Conclusion Our results suggest that AMC &amp;gt; 100 /uL regardless of ANC/uL, or APC&amp;gt; 300 or ANC&amp;gt;200 with AMC&amp;gt;100/uL all are a safe thresholds for empiric AC. Further prospective studies are needed to validate AMC as accurate surrogate for AC in FN children with cancer.

Efficacy and Safety of Piperacillin-Tazobactam and Cefepime as Empirical Therapy for Febrile Neutropenic Children with Acute Lymphoblastic Leukaemia (ALL)

Background: Infection is a major clinical challenge in ALL treatment. Prompt administration of empirical antibiotic in febrile neutropenic patients has reduced the mortality. Both Cefepime or Piperacillin-Tazobactam has been used as empirical treatment.&#x0D; Objective: To compare the efficacy and safety between Piperacillin-Tazobactam with Cefepime in febrile neutropenic children with ALL.&#x0D; Materials and methods: This randomized study was conducted from August 2015 to August 2016 in BSMMU. Sixty one episodes of febrile neutropenia in children with ALL, aged 0 to18 years were included in this study. Patients were randomized into two groups. One group received Piperacilln/Tazobactam and another group received Cefepime and data of 60 febrile neutropenic episodes were analyzed.&#x0D; Results: Febrile neutropenic episodes in the Piperacillin/Tazobactam group were 28 and in Cefepime group was 32 episodes and 34(57.63%) were male and 25 (42.37%) female. Median age was 5 years and 38(62.3%) neutropenic episodes were in induction phase. Majority had fever without focus 21(35%). Microorganisms isolated in 13 (21.66%) patients and majority 6 (46.15%) had blood infection. Most of the isolated organisms were Gram negative 11(84.61%). Overall treatment success without modification in the Piperacillin/Tazobactam group was 17(60.7%) and in Cefepime group 18 (56.3%) and that comparison was not statistically significant (p= 0.732). Significant difference was also not found comparing the mean duration of fever, neutropenia and hospital stay.&#x0D; Conclusion: Both Piperacillin/Tazobactam and Cefepime were found effective and safe as an empirical therapy for febrile neutropenic children with ALL.&#x0D; BANGLADESH J CHILD HEALTH 2021; VOL 45 (2) : 83-88

Chemotherapy Induced Neutropenic Fever and Its Response to Empirical Antimicrobial Therapy

Objective: To find out the frequency of chemotherapy-induced febrile neutropenia (FN) in children diagnosed with Acute Lymphoblastic Leukemia (ALL) and its response to empirical antibiotic therapy.&#x0D; Study Design: Cross-sectional study.&#x0D; Place and Duration of Study: Department of Peadiatric Oncology, Combined Military Hospital, Rawalpindi Pakistan, from Nov 2017 to Oct 2018.&#x0D; Methodology: Newly diagnosed pediatric patients suffering from acute lymphoblastic leukemia between 1 to 15 years of age were included. All patients were treated with chemotherapy according to the United Kingdom National Randomized Trial for Children and Young adults with Acute Lymphoblastic Leukemia (UKALL) 2011 protocol. Patients with febrile neutropenic (FN) episodes were treated with empirical antimicrobial therapy as per hospital guidelines. Patients ‘response to antimicrobial therapy, blood culture results and related complications were noted.&#x0D; Results: Out of a total 77 patients, 45 (58.4%) had 69 episodes of febrile neutropenia (FN), 62 (78.5%) episodes of febrile neutropenia (FN) were started empirical treatment with first-line antibiotics (piperacillin-tazobactam and amikacin) whereas 15 (21.7%) episodes of febrile neutropenia (FN) not responding to the 1st line were shifted to second-line antibiotics (meropenem and amikacin). Mean duration of fever was 4.1 ± 2.8 days on 1st line antibiotic regimen, 2.6 ± 1 days on 2nd line antibiotics and 6.3 ± 3.3 days on combination with antifungal drug. Ten patients received antifungal therapy empirically. Efficacy of the 1st line and the 2nd line was 72.5% and 77% respectively. Staphylococcus aureus was the most frequent organism isolated from blood culture results. During the induction phase, 10 (12.9%) patients..............

Polatuzumab vedotin with dose-adjusted etoposide, cyclophosphamide, doxorubicin, and rituximab (Pola-DA-EPCH-R) for upfront treatment of aggressive B-cell non-Hodgkin lymphomas.

7546 Background: The phase 3 POLARIX trial demonstrated the superiority of polatuzumab vedotin (Pola) over vincristine in the R-CHOP regimen for large B-cell lymphomas. However, it is unknown if Pola can be safely incorporated into intensified regimens typically utilized for the highest risk histologies. To address this question, we conducted a prospective trial (NCT04231877) evaluating Pola with dose adjusted etoposide, cyclophosphamide, doxorubicin, and rituximab (Pola-DA-EPCH-R). Methods: This is a single center, open label, investigator-initiated clinical trial of 6 cycles of Pola-DA-EPCH-R in aggressive large B-cell lymphomas where DA-EPOCH-R is considered standard (eg. HGBCL, PMBCL, and select DLBCL-NOS). Pola is given at 1.8 mg/kg on day 1 without intra-patient dose escalation. All other components of the regimen including escalation of chemotherapy dosing based on neutrophil and platelet nadirs from the previous cycle are given according to Dunleavy et al NEJM 2013. The primary objective is to estimate the safety of Pola-DA-EPCH-R as measured by the rate of dose-limiting toxicities (DLTs) in the first 2 cycles with pre-specified suspension rules if the lower limit of an 80% confidence interval cannot exclude a DLT rate of &gt; 20%. Efficacy, survival, and correlative analyses will also be performed. Results: 18 patients enrolled on study and as of Feb 15, 2022, 3 patients remain on study treatment. Median age was 64 years (range 41-74). With only 3 DLTs, the study met its primary endpoint for safety. Five SAEs were observed, including one grade 5 sepsis/typhlitis (during cycle 1), 3 episodes of febrile neutropenia, and a grade 3 perforation of a colonic diverticula which required a treatment delay of 12 days before completing all expected study therapy. Other grade 3+ non-heme AEs in more than one pt. include hyperglycemia (17%), oral mucositis (17%), incidental asymptomatic pulmonary embolism (17%), abdominal pain (11%), and hypokalemia (11%). Grade 1 peripheral sensory neuropathy was uncommon (22%), no grade 2+ neuropathy was observed. One patient required a decrease in Pola dosing due to a platelet nadir at dose level 1. Among those with at least 2 cycles of treatment, 94% were able to increase chemotherapy to at least dose level 2 (Table). Post cycle 2 interim overall response rate (ORR) and complete response (CR) rate was 88% and 24%, respectively. EOT ORR and CR was 93% and 71%, respectively, with one PD. Updated data will be presented at the meeting. Conclusions: Using Pola at 1.8 mg/kg to replace vincristine in the DA-EPOCH-R regimen appears feasible and met its primary safety endpoint. These data support the further evaluation and use of this approach in histologies where the potential benefit of both an intensified regimen and Pola may be desired. Clinical trial information: NCT04231877. [Table: see text]

A phase II study of daratumumab with weekly carfilzomib, pomalidomide, and dexamethasone in relapsed and refractory multiple myeloma.

8012 Background: Daratumumab (dara), carfilzomib (K), pomalidomide (P), and dexamethasone (d) are established in relapsed multiple myeloma (MM) with activity in 3-drug combinations including: dara Kd; dara Pd; and KPd. The paradigm in relapsed/refractory disease is moving towards more intensive and well-tolerated combinations to achieve deeper and more durable responses while ensuring tolerability. Quadruplet regimens are now becoming standard in newly diagnosed MM, and we explored a 4-drug regimen in relapsed disease. Preliminary results of a phase 2 study of dara KPd with a twice/week schedule of K showed an ORR of 86% in pts with a median of 1 prior line (Jasielec et al., ASH 2020). Here we report an ongoing study of dara with weekly KPd (dara wKPd) to improve the accessibility of this regimen. Methods: This phase 2 study (NCT04176718) will enroll up to 43 pts with relapsed/refractory MM who have received at least 1 prior therapy, including both lenalidomide and a proteasome inhibitor. Prior therapy with dara, K, or P was permitted except for K and P given together as last line of therapy. Dara wKPd was given on a 28-day schedule. Dara was given according to the dara Pd schedule. An initial cohort received dara 16 mg/kg iv (with first dose split over two days); the trial was amended to dara 1800 mg sc. K 56 mg/m2 iv was given weekly on days 1, 8, 15; for C1D1, dose was 20 mg/m2. P 4 mg was given po on days 1-21. Dex 40 mg was given weekly with the dose split over two days. Treatment was until progression or unacceptable toxicity. The primary endpoints are overall response and the safety profile of dara wKPd. Secondary endpoints include PFS. Results: At time of data cutoff, 24 pts were enrolled; median age was 65 (range 42-73), and median number of prior regimens was 2 (range 1-3). All pts were refractory to their last line of therapy and had prior lenalidomide and bortezomib. Additional prior therapies included: pomalidomide (54%), carfilzomib (13%), ixazomib (46%), cyclophosphamide (4%), auto SCT (29%). High risk FISH was present (out of 24 pts): del 17p (13%); t(14;16) (8%); gain of 1q (46%). Median follow up was 8.4 months. 2 pts came off study due to neutropenia leading to delay in treatment. Grade 3-4 hematologic AEs included neutropenia (46%) and thrombocytopenia (25%). There was 1 episode of febrile neutropenia. Common non hematologic AEs (all; grade 3-4) included fatigue (42%; 0%); dyspnea (38%; 4%); increase in ALT/AST (29%; 8%); insomnia (21%; 0%); neuropathy (17%; 0%). 22 pts were evaluable for response, with an overall response rate of 95% (PR 23%, VPGR 68%, CR 5%). Median PFS at 12 months was 86.2% (95% CI, 70%-100%). Conclusions: Dara wKPd shows some of the highest response rates (95%) reported to date in relapsed/refractory MM. This likely reflects the incorporation of 4 active drugs in 1 regimen and builds on the efficacy of dara-based triplet regimens, with manageable toxicity and convenience of weekly K. Clinical trial information: NCT04176718.

The impact of COVID-19 lockdown measures on rates of febrile neutropenia in a cohort of Irish patients receiving chemotherapy.

e18784 Background: Febrile neutropenia in patients receiving chemotherapy is a life-threatening condition requiring prompt attention. This condition may also result in dose reductions, delays, or discontinuations of chemotherapy which compromise patient outcomes. This study seeks to evaluate the impact of COVID19 “lockdown” public health measures in Ireland on the incidence of febrile neutropenia in patients who were receiving cytotoxic chemotherapy regimens. Methods: All patients receiving chemotherapy at the Bon Secours Hospital Cork who were admitted with neutropenia and fever during two separate time periods were included in the study: 1st April 2018 to 31st March 2019 (“pre-pandemic year”) and 1st April 2020 to 31st March 2021 (“pandemic year”). The pandemic year selected equates to a period of heightened infection control measures in Irish society, featuring public health advice re social distancing, routine mask wearing in public and successive lockdown waves. Retrospective chart review was performed on all patients admitted to the oncology inpatient ward who had blood cultures on admission to determine the number of these patients who were neutropenic at the time of blood culture draw. Similarly, pharmacy records were accessed to determine the number of unique chemotherapy items dispensed in each year in order to establish a rate of febrile neutropenia episodes per 100 chemotherapy items dispensed for each period. The incident rate ratio was calculated using the Exact Poisson Test. Results: During the pre-pandemic year there were 57 individual admissions with febrile neutropenia compared with 32 admissions during the pandemic year. There were 4581 chemotherapy units dispensed during the pre-pandemic year compared to 4628 during the pandemic year. The rate of febrile neutropenia episodes per 100 chemotherapy units dispensed was 1.24 (95% CI 0.94, 1.61) in the pre-pandemic year and 0.69 (95% CI 0.47, 0.98) in the pandemic year. The incident rate ratio is 1.80 (95% CI 1.14, 2.87, two-sided P = 0.007). 9 of 57 (16%) admissions in the pre-pandemic year were associated with positive blood cultures compared with 4 of 32 (13%) in the pandemic year (not significant by Fisher's exact test). Conclusions: Increased precautionary infection control measures during the COVID19 pandemic public health restrictions correlated with a significant reduction in the rate of febrile neutropenia amongst patients receiving cytotoxic chemotherapy. This suggests that there may be a role for similar measures for this patient cohort in the post-pandemic period. Options which patients may consider to employ include social distancing, wearing face-coverings and restricting social contacts while at risk of neutropenia from cytotoxic chemotherapy regimens.

A prediction model for bacteremia and transfer to intensive care in pediatric and adolescent cancer patients with febrile neutropenia.

Febrile neutropenia (FN) is a common condition in children receiving chemotherapy. Our goal in this study was to develop a model for predicting blood stream infection (BSI) and transfer to intensive care (TIC) at time of presentation in pediatric cancer patients with FN. We conducted an observational cohort analysis of pediatric and adolescent cancer patients younger than 24 years admitted for fever and chemotherapy-induced neutropenia over a 7-year period. We excluded stem cell transplant recipients who developed FN after transplant and febrile non-neutropenic episodes. The primary outcome was onset of BSI, as determined by positive blood culture within 7 days of onset of FN. The secondary outcome was transfer to intensive care (TIC) within 14 days of FN onset. Predictor variables include demographics, clinical, and laboratory measures on initial presentation for FN. Data were divided into independent derivation (2009–2014) and prospective validation (2015–2016) cohorts. Prediction models were built for both outcomes using logistic regression and random forest and compared with Hakim model. Performance was assessed using area under the receiver operating characteristic curve (AUC) metrics. A total of 505 FN episodes (FNEs) were identified in 230 patients. BSI was diagnosed in 106 (21%) and TIC occurred in 56 (10.6%) episodes. The most common oncologic diagnosis with FN was acute lymphoblastic leukemia (ALL), and the highest rate of BSI was in patients with AML. Patients who had BSI had higher maximum temperature, higher rates of prior BSI and higher incidence of hypotension at time of presentation compared with patients who did not have BSI. FN patients who were transferred to the intensive care (TIC) had higher temperature and higher incidence of hypotension at presentation compared to FN patients who didn’t have TIC. We compared 3 models: (1) random forest (2) logistic regression and (3) Hakim model. The areas under the curve for BSI prediction were (0.79, 0.65, and 0.64, P < 0.05) for models 1, 2, and 3, respectively. And for TIC prediction were (0.88, 0.76, and 0.65, P < 0.05) respectively. The random forest model demonstrated higher accuracy in predicting BSI and TIC and showed a negative predictive value (NPV) of 0.91 and 0.97 for BSI and TIC respectively at the best cutoff point as determined by Youden’s Index. Likelihood ratios (LRs) (post-test probability) for RF model have potential utility of identifying low risk for BSI and TIC (0.24 and 0.12) and high-risk patients (3.5 and 6.8) respectively. Our prediction model has a very good diagnostic performance in clinical practices for both BSI and TIC in FN patients at the time of presentation. The model can be used to identify a group of individuals at low risk for BSI who may benefit from early discharge and reduced length of stay, also it can identify FN patients at high risk of complications who might benefit from more intensive therapies at presentation.

Evaluation of Using Empiric Glycopeptides in Accordance with the IDSA Guidelines in Hematologic Malignancy Patients with Febrile Neutropenia.

BackgroundThis study aimed to evaluate the effects of the appropriate use of empiric glycopeptide therapy in hematologic malignancy patients with febrile neutropenia (FN).Materials and MethodsPatients with FN who were hospitalized in our clinic and started empiric glycopeptide therapy were retrospectively analyzed. Empiric glycopeptide treatment initial indications were determined according to 7 specific criteria in the IDSA guidelines. In addition, the duration of glycopeptide use according to initial indications, causative pathogens in culture positivity, frequency of VRE infection, and the mortality rate was identified.Results87 patients were included. Of these, 102 episodes of FN were analyzed. Appropriate use of glycopeptides was observed in 98% of patients. The most common initial indication for glycopeptide was skin or soft-tissue infection, with 52% (n = 53). The mean duration of glycopeptide use was 11 (2–22) days. The time of glycopeptide use was longer in patients with catheter-related infections than in those with severe mucositis and hemodynamic instability (p = 0,041/p = 0,016). The duration of glycopeptide use was shorter in patients with consolidation therapy than in those without consolidation therapy. The mortality rate in culture-positive patients was significantly higher than in culture-negative patients (p = 0.041). At 72 h, glycopeptide therapy was discontinued in 8 of 79 FN episodes within culture-negative patients.ConclusionThis study showed that the mortality rate was higher in culture-positive patients. Additionally, glycopeptides should be discontinued early with no evidence of gram-positive infection.

Real-world challenges in the management of acute myeloid leukemia: a single-center experience from North India.

The outcome of acute myeloid leukemia (AML) in low-middle-income countries (LMIC) is dismal due to delayed clinical presentation and infection-related complications. We aimed to analyze the outcome of patients with AML and the factors associated with its prognosis. A retrospective observational study was conducted at a tertiary care university hospital in North India from January 2015 to December 2019. A total of 137 AML patients (median age 32year (3-66years) received intensive chemotherapy during study period. The median delay from diagnosis to treatment was 45days (6-177days). Among the 352 febrile neutropenia (FN) episodes analyzed, 175 (49.7%) were culture positive; Gram-negative multi-drug resistant organism (MDRO) sepsis during induction being 57.4% with 34.5% infections due to carbapenem-resistant Enterobacteriaceae (CRE) leading to a mortality rate of 14.6%. The median EFS and OS were 12.0 ± 1.57 (95% CI 8.91-15.08) and 15.0 ± 2.44 (95% CI 10.21-19.78) months respectively. Multivariable analysis revealed significant difference in median OS between favorable vs high risk AML groups (20.0 (95% CI: 12.50-27.49) vs 9.0 (95% CI: 2.99-15.01) months; p = 0.002); time from diagnosis to treatment (< 30days vs ≥ 30days; not reached vs 9.0 (95% CI: 6.81-11.18) months; p = 0.001), performance status (1 vs 2 vs 3; not reached vs 12.0 (95% CI: 10.32-13.67) vs 4.0 (95% CI:2.77-5.22); p = 0.001), and attainment of complete remission vs induction failure (not reached vs 6.0 (95% CI: 3.78-8.21); p = 0.002). Patient-related factors like delayed treatment initiation and high incidence of MDRO-associated sepsis are critical determinants of AML outcome in LMIC.

Retrospective single-center experience with OEPA/COPDAC and PET-CT based strategy for pediatric Hodgkin lymphoma in a LMIC setting

ABVD regimen for Hodgkin lymphoma (HL) is frequently used in children and young adults in low-middle income countries (LMIC). The feasibility and safety data for ‘non-ABVD’ protocols from LMIC is limited. The retrospective study was conducted in a single center in India. The Euronet PHL-C1 based protocol was administered during 2010-19. A PET-CT was performed at diagnosis and following two OEPA cycles. Radiotherapy was administered for inadequate PET response. During the 10-year period, 143 patients with HL were treated. The mean age was 7.8 ± 2.5 years. Bulky disease was observed in 82 (59%). Treatment abandonment was recorded in 13 (9.1%). The median follow-up duration was 46.4 months. An inadequate PET response was observed in 41/119 (34.4%), of which 56.1% received radiotherapy. Twelve (29.3%) patients who were supposed to receive radiotherapy received 2-cycles of COPDAC instead. Sixty-nine episodes of febrile neutropenia were observed in 54 patients. Treatment-related mortality (TRM) was observed in 7 (5.3%). The majority of episodes of febrile neutropenia (61%) and TRM (86%) occurred in the first cycle of OEPA. The 4-year event-free survival (EFS) and overall survival (OS) were 86.2 ± 3.4% and 93.5 ± 2.2%, respectively. Nine (6.3%) patients relapsed. Bulky disease lacked association with inadequate PET response (p = .800) or relapse (p = 1.000). OEPA/COPDAC regimen and response assessment by PET-CT permitted therapy reduction, including radiotherapy. Febrile neutropenia and resultant TRM (5.3%) are concerning and occurred frequently in the first cycle of OEPA. The support system for managing febrile neutropenia should be optimized for administering OEPA in LMIC.

Microbiological characterization and antimicrobial susceptibility pattern of infections associated with febrile neutropenia in pediatric hemato-oncological patients.

Febrile neutropenia (FN) is the most frequent hemato-oncological emergency, with high morbidi ty and mortality in pediatrics. The objective of the study was the microbiological characterization and antimicrobial susceptibility of infections associated with FN in pediatric hemato-oncological patients. Retrospective cohort study with patients aged between 1 month and 18 years, with onco-hematological pathology according to ICD-10 codes, hospitalized in a tertiary healthcare center in Bucaramanga, Colombia. Based on the medical records of the period 2013-2017, the episodes of FN were identified, and the isolated microorganisms and their susceptibility pattern were described. Biochemical identification and antimicrobial susceptibility testing were performed with the Dade Behring Microscan« automated system. The resistant microorganism classification was performed based on the Minimum Inhibitory Concentration (MIC) and the interpretation of the laboratory according to the cut-off points of the Clinical and Laboratory Standards Institute recommendations. Of 130 patients, 14.7% of the cultures obtained were positive. Bloods tream infection was observed in 17.5% of the episodes. The isolated microorganisms were mainly Gram-negative bacteria (75.8%). Enterobacteriaceae (EB) were the most frequent, led by Klebsiella pneumoniae, Escherichia coli, followed by Pseudomonas aeruginosa and coagulase-negative Staphylo cocci. Of the EBs, 40.5% showed resistance to Piperacillin/Tazobactam, 33.3% to Cefepime, and 8.2% to Meropenem. According to the antimicrobial resistance pattern, it was observed that 16.4% of the positive EB cultures had an extended-spectrum beta-lactamase pattern and 5% a pattern suggestive of carbapenemases. All Gram-positive cocci were sensitive to Vancomycin. In the studied patients, the predominant pathogenic microorganisms were Gram-negative ones with resistance in dices similar to those of developing countries.

Clinical Consequences and Economic Burden Associated with Febrile Neutropenia in Hospitalized Cancer Patients: A Prospective Study

Objective: Febrile neutropenia (FN) is viewed as the most decimating oncological crisis particularly inchemotherapy-incited patients. The primary objective of the study was to identify the total directexpenditure of patients during febrile neutropenia with clinical consequences and the secondary aim wasto find out the factors associated with higher cost. Materials and Method: This was a single-centered hospital-based study in the largest and only specializedcancer care centre in Bangladesh in the government sector. This prospective study was done in theinpatients’ department of the National Institute of Cancer Research and Hospital from April 2020 toJanuary 2021. The primary outcome was the out-of-pocket patient payments (adjusted by governmentsubsidy) per FN episode. Univariate analysis and multiple linear regression were conducted to identifythe factors associated with higher costs. Results and Discussions: A total of 101 patients were enrolled in the study. The mean (SD) age was33.49 (±15.79) years. Of the 101 participants, 63.4% were male. Among the patients, 13.9% died during theepisode and 86.1% recovered. Having co-morbidities and COVID-19 were associated with an increasedrisk of death. The mean cost was US$ 999.44 (±499.05) and the mean length of hospital stay was 21.98(±9.3) days. The longer hospital stay was significantly associated with higher costs. Conclusion: This study will help to ascertain the hospital cost and clinical outcome of FN whichultimately can help in policymaking strategy. J MEDICINE 2022; 23: 48-53