Duration Of Neutropenia Research Articles

Prognostic Impact of Neutropenia Recovery and G-CSF Use in Onco-Hematological Neutropenic Patients Admitted to Intensive Care Unit for Acute Respiratory Failure: A Retrospective, Real World Analysis.

The effect of neutropenia and theuse of granulocyte colony-stimulating factor (G-CSF) in critically ill patients with cancer are controversial, notably in those with lung injury. Neutropenia recovery can be associated with an acute respiratory failure (ARF) requiring intensive care unit (ICU) admission, especially when G-CSF is administered. In a single-center retrospective study, we evaluated (1) the effect of neutropenia recovery on the 90-day mortality and (2) the impact of G-CSF use on the outcome of patients with cancer and neutropenia with ARF admitted to the ICU. Among 1098 screened patients, 152 were neutropenic at ICU admission. The 90-day mortality was 44.7%. Factors independently associated with the 90-day mortality were invasive mechanical ventilation, ground-glass opacities and nodules on computed tomography scans, a disease in progression and the Simplified Acute Physiology Score (SAPS II) at ICU admission. The lack of neutropenia recovery during the ICU stay was associated with the 90-day mortality. Using G-CSF had no effect on the 90-day mortality or the neutropenia duration, but the PaO2:FiO2 ratio was significantly lower after neutropenia recovery in patients who received G-CSF. Thus, respiratory deterioration can occur in the neutropenia recovery period, potentially exacerbated by G-CSF. Our study suggests that neutropenia recovery was associated with survival in critically ill patients with cancer and neutropenia with ARF admitted to ICU, and the G-CSF could worsen the respiratory parameters.

Real world comparison of filgrastim to filgrastim-sndz in patients with chemotherapy-induced neutropenia.

There exists some apprehension by prescribers, healthcare providers, and other stakeholders regarding the real-world safety and effectiveness of biosimilars. While some of the apprehension is likely due to clinician knowledge gaps in the biosimilarity exercise, additional data (including those generated from the real-world) regarding safety and efficacy could reduce a clinician's perception of biosimilar uncertainty and can potentially increase biosimilar acceptance and uptake. The published literature is lacking regarding the real-world impact on healthcare costs and clinical outcomes when a single healthcare institution converts from filgrastim to filgrastim-sndz as its short-acting Granulocyte Colony Stimulating Factor (GCSF), especially within diverse populations and indications not explicitly studied through the registration trials. Specifically, both filgrastim and filgrastim-sndz possess FDA-approved indications within patients with hematologic malignancies receiving high-dose chemotherapy and in those undergoing bone marrow transplantation. As a biosimilar to filgrastim, the FDA did not require prospective, randomized controlled trials to obtain these indications for filgrastim-sndz. The purpose of this study is to describe real-world healthcare resource costs, utilization patterns, and clinical outcomes in patients with hematologic malignancies who received filgrastim-sndz or filgrastim to support neutrophil recovery following chemotherapy (i.e., induction or consolidation) or a bone marrow transplant (BMT) at Yale New Haven Hospital (YNHH). A total of 148 patients were identified and met the following criteria: at least 18 years old, Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, absence of fever or infection, newly diagnosed acute myeloid leukemia or newly post-bone marrow transplant and received filgrastim-sndz (Zarxio®) or reference filgrastim (Neupogen®). Healthcare resource utilization outcomes were compared between biosimilar and reference filgrastim using descriptive statistics. There were no major differences between either cohort, including duration of hospitalization, the number of overall emergency room visits and additional hospital admissions with a primary diagnosis of febrile neutropenia or neutropenia within 30 days post-discharge from initial hospital admission, time to neutrophil recovery following GCSF support, and the incidence and duration of both fever and febrile neutropenia. The total cost based on treatment of all patients in each arm differed significantly with filgrastim-sndz being the most cost-effective choice. filgrastim-sndz significantly reduced healthcare utilization costs compared to reference filgrastim with similar effect on absolute neutrophil count, incidence of fever, and febrile neutropenia.

Clinical effect of prophylactic pegfilgrastim in patients with newly diagnosed acute lymphoblastic leukemia who receive intensive chemotherapy.

Using granulocyte colony-stimulating factor (G-CSF) after completing chemotherapy reduces the duration of neutropenia and infections. However, the efficacy and safety of prophylactic pegfilgrastim in acute lymphoblastic leukemia (ALL) patients have not yet been evaluated after intensive cytotoxic chemotherapy compared to the daily G-CSF. This study aimed to evaluate the efficacy of pegfilgrastim for ALL patients who received intensive chemotherapy compared with a short-acting G-CSF. Clinical data of 145 patients treated with hyper-CVAD, modified VPDL/VPD, or KALLA 1406/1407 regimen were retrospectively evaluated. Pegfilgrastim or the short-acting G-CSF was selected according to the clinician's discretion. Patients not receiving pegfilgrastim were treated with the short-acting G-CSF. The median age of enrolled patients was 45years. Sixty newly diagnosed ALL patients were treated with hyper-CVAD regimen, while KALLA and VPDL regimens were administered to 39 and 46 patients, respectively. Among the 60 patients treated with hyper-CVAD, 20 patients received pegfilgrastim. Patients who received pegfilgrastim had a significantly shorter duration of neutropenia and hospitalization and reduced incidence of severe infections compared to patients receiving the short-acting G-CSF. Consistent results were also confirmed in an analysis targeting only patients who achieved remission during hyper-CVAD induction therapy. There was no significant difference in neutrophil recovery ability and hospitalization duration when the daily short-acting G-CSF was used prophylactically after completing hyper-CVAD, KALLA, and VPDL regimens as induction therapy. Using pegfilgrastim after hyper-CVAD therapy was more effective than the short-acting G-CSF in terms of infection, neutropenia recovery, and hospitalization in patients with newly diagnosed ALL.

The impact of delayed versus early administration of granulocyte colony-stimulating factor following autologous hematopoietic stem cell transplantation on transplantation outcome.

Granulocyte colony-stimulating factor (G-CSF) is routinely administered after autologous hematopoietic stem cell transplantation (auto-HSCT) to decrease the duration of neutropenia and diminish the incidence of febrile neutropenia. Nevertheless, the most advantageous timeframe for administering G-CSF in the transplantation setting remains elusive. We conducted a cross-sectional study of 200 patients diagnosed with hematological malignancies who underwent auto-HSCT between July 2017 and January 2022. Patients were divided into two groups of 100 individuals based on the timing of G-CSF administration after auto-HSCT. In the first group, G-CSF was administered on post-transplantation day +1, while in the second group, G-CSF was administered on post-transplantation day +5. Patient demographics and clinical outcomes, including time to neutrophil engraftment, time to platelet engraftment, length of hospital stay, duration of fever, and incidence of bacterial and fungal bloodstream infections, were compared between the two groups. We identified a significantly shorter platelet engraftment time in the day +5 group than in the day +1 group (P<0.001), though the groups were similar regarding neutrophil engraftment time. The total number of G-CSF injections differed significantly according to the administration schedule. The number of red blood cells and length of hospital stay was greater in the day +1 group (all P<0.001). The incidence of bacterial and fungal bloodstream infections and duration of fever did not differ between the groups. Delayed administration of G-CSF on day +5 is as effective as early administration and can positively influence platelet engraftment, transfusion support, and hospitalization time.

Incidence, duration, and severity of neutropenia in adults with B-cell acute lymphoblastic leukemia receiving blinatumomab consolidation

Blinatumomab is a CD3 × CD19 antibody approved for adults with B-cell acute lymphoblastic leukemia (B-ALL). Blinatumomab is not considered myelosuppressive, but significant neutropenia has been seen in practice. We reviewed 95 patients with B-ALL who received blinatumomab at Dana-Farber Cancer Institute between 2015 and 2024. Of these, 71 patients were treated in morphologic remission with absolute neutrophil count (ANC) ≥1 × 109/L, for which 41% experienced grade ≥3 neutropenia and 13% developed ANC <0.1 × 109/L during blinatumomab. Neutropenia occurred more frequently during cycle 2 than cycle 1, and neutropenia did not necessarily portend worse neutropenia in later cycles. Multivariable analysis did not identify concurrent tyrosine kinase inhibitor use as a significant covariate for neutropenia. The nine patients who experienced ANC <0.1 × 109/L did not develop serious infections and received supportive care. Neutropenia occurs frequently and may be severe in patients with B-ALL who receive blinatumomab during remission, but complications appear manageable.

Predicting Neutropenic Sepsis in Patients with Hematologic Malignancy: A Retrospective Case-Control Study.

Neutropenic sepsis (NS) is one of the leading causes of death among patients with hematologic malignancies. Identifying its predictive factors is fundamental for early detection. Few studies have evaluated the predictive factors in relation to microbial infection confirmation, which is clinically important for initiating sepsis treatment. This study aimed to determine whether selected biomarkers (i.e., body temperature, C-reactive protein, albumin, procalcitonin), treatment-related characteristics (i.e., diagnosis, duration of neutropenia, treatment modality), and infection-related characteristics (i.e., infection source, causative organisms) can predict NS in patients with hematologic malignancies. We also aimed to identify the optimal predictive cutoff points for these parameters. This retrospective case-control study used the data from a total of 163 patients (58 in the sepsis group and 105 in the non-sepsis group). We collected data with reference to the day of specimen collection, with which microbial infection was confirmed. Multiple logistic regression was used to determine predictive risk factors and the area under the curve (AUC) of the receiver operating characteristic for the optimal predictive cutoff points. The independent predictors of NS were average body temperature during a fever episode and procalcitonin level. The odds for NS rose by 9.97 times with every 1°C rise in average body temperature (95% confidence interval, CI [1.33, 75.05]) and by 2.09 times with every 1 ng/mL rise in the procalcitonin level (95% CI [1.08, 4.04]). Average body temperature (AUC = 0.77, 95% CI [0.68, 0.87]) and procalcitonin levels (AUC = 0.71, 95% CI [0.59, 0.84]) have fair accuracy for predicting NS, with the optimal cutoff points of 37.9°C and 0.55 ng/mL, respectively. This study found that average body temperature during a fever episode and procalcitonin are useful in predicting NS. Thus, nurses should carefully monitor body temperature and procalcitonin levels in patients with hematologic malignancies to detect the onset of NS.

Forty years of human G-CSF: A short history in time.

Human G-CSF was identified in 1984 at Memorial Sloan-Kettering Cancer Centre, New York. Based on these findings, recombinant G-CSF was developed by Amgen, Thousand Oaks. In 1987, clinical trials began using recombinant G-CSF in cancer patients following chemotherapy to reduce the duration of neutropenia and in patients with congenital neutropenia (CN) to increase the number of neutrophils. It has changed the quality of life for many cancer patients and saved the lives of many patients with (CN).

Factors associated with the duration of neutropenia in acute leukemia patients receiving chemotherapy at Prof. Dr. I.G.N.G. Ngoerah Hospital

Introduction:Acute leukemia patients undergoing chemotherapy often experience febrile neutropenia. Neutropenia is defined as a neutrophil count &lt; 500 cells/mm³. The duration of neutropenia, defined as the number of days a patient experiences a neutropenia episode, is categorized into more than 7 days (prolonged neutropenia) and less than or equal to 7 days (non-prolonged neutropenia). Methods: This cross-sectional study included a sample of 78 acute leukemia patients receiving chemotherapy at Prof Dr IGNG Ngoerah Hospital in Denpasar, observed over 4 months. Factors evaluated in relation to the duration of neutropenia included type of acute leukemia, age, gender, nutritional status, LDH levels, leukocyte levels, use of GCSF, chemotherapy, and comorbidities. Genetic factors, molecular subtypes, race, antibiotic use, and variations in chemotherapy regimens were not included in this study. Results: Out of the 78 patients, 25 (32.1%) experienced prolonged neutropenia, while 53 (67.9%) experienced neutropenia lasting less than 7 days. There was a relationship between the duration of neutropenia and comorbidities, but it was not statistically significant (p = 0.091; OR = 2.956, 95% CI: 0.841-10.397). GCSF therapy also showed a relationship but was not statistically significant (p = 0.998; OR = 364864349.738, 95% CI: 0.000). Induction chemotherapy had a significant relationship with the duration of neutropenia (p = 0.000; OR = 11.264, 95% CI: 3.121-40.646). Conclusion: Chemotherapy is currently the best treatment for acute leukemia patients, but prolonged hospitalization due to extended neutropenia duration can reduce the quality of life.

Evaluate the Efficacy of Myeloablative Conditioning Regimens for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myelogenous Leukemia at BTH, Vietnam.

Background: Busulfan plus cyclophosphamide (Bu/Cy) is considered one of the classical myeloablative conditioning regimens. However, its toxicity can significantly increase mortality rates. To reduce both acute and long-term complications after hematopoietic stem cell transplantation (HSCT), newer conditioning regimens are being investigated. The purposes of this study were to assess the efficacy and safety of busulfan plus cyclophosphamide (Bu/Cy) and busulfan plus fludarabine (Bu/Flu) conditioning regimen for allogeneic HSCT (allo-HSCT) in acute myelogenous leukemia (AML). Materials and Methods: We conducted a single-center, retrospective analysis of AML, both adults and children, who underwent either Bu/Cy or Bu/Flu conditioning regimen for allo-HSCT and received peripheral blood stem cell transplants from HLA-matched donors. Results: From 2005 - 2019, 49 AML patients receiving Bu/Cy and 21 receiving Bu/Flu were identified, meeting inclusion criteria. The two groups showed no significant differences in age, gender, disease status pre-transplant, the median time to neutrophil and platelet engraftment. Bu/Flu patients had a shorter duration of neutropenia (median 7 days vs 10 days, p = 0.001) and shorter duration of thrombocytopenia (median 10 days vs 15 days, p = 0.016) than Bu/Cy. No difference was observed in disease-free survival (DFS) and overall survival (OS) between the two groups. Both univariate and multivariate analyses showed that age, disease status pre-transplant, and chronic graft-versus-host disease (GvHD) are related to worse DFS and OS. Conclusion : With similar efficacy to Bu/Cy but faster neutrophil and platelet recovery time, Bu/Flu is suitable as a pre-HSCT conditioning regimen for patients with AML.

Invasive fungal rhinosinusitis: current evidence and research opportunities.

To summarize the evidence surrounding diagnosis, treatment, prognosis, and surveillance of patients with acute invasive fungal sinusitis (AIFS) and discuss future research needs. New risk factors for AIFS such as COVID have been identified, and a new prognostic staging system has been developed. Most patients who develop AIFS are immunocompromised, with the majority having a history of diabetes or a hematologic malignancy. Unfortunately, there are not any highly sensitive and specific diagnostic tools. Therefore, a combination of signs and symptoms, imaging, endoscopy, biopsy, and labs should be used to diagnosis AIFS. Although surgery and systemic antifungals are known to improve outcomes, there is limited data on time to intervention, duration of antifungals, and surveillance patterns. There is also limited information on factors that can predict outcomes in AIFS patients. However, sensory/perceptual changes, prolonged neutropenia duration, and comorbidity burden may be associated with a poor prognosis.

Effectiveness and safety of empegfilgrastim (Extimia®) in patients with solid tumors receiving cytotoxic therapy: final results of the DEFENDOR study

Aim. To evaluate the effectiveness and safety of Extimia® (empegfilgrastim, JSC "BIOCAD") in reducing the frequency, duration of neutropenia, the incidence of febrile neutropenia (FN) and infections caused by FN in patients with solid tumors receiving myelosuppressive therapy. Materials and methods. The paper presents the final results of a multicenter prospective observational post-marketing study of the safety and effectiveness of Extimia® (empegfilgrastim) in patients with solid tumors receiving cytotoxic therapy. For the primary prevention of FN, all patients received empegfilgrastim at 7.5 mg subcutaneously once per course of chemotherapy (CT) 24 hours after the end of CT administration. The primary endpoint included an assessment of the relative dose-intensity (RDI) of the CT courses administered. The endpoints of interest included the assessment of the RDI of CT courses by nosology and CT regimen, the frequency of dose-limiting neutropenia, and the incidence of all adverse events (AEs) in patients who received at least one dose of the study medication, including serious AEs. Results. From February 2021 to December 2022, 3218 patients with various malignancies were included in 41 study centers of the Russian Fede- ration. Of these, 3217 (99.97%) patients received at least one dose of the study drug, and 2663 (82.8%) patients were included in the RDI evaluation population according to the study protocol. The mean age in this group was 56.9 (18–84) years. RDI ≥85% was achieved in 2,415 (90.7%) patients. The mean RDI was 96.2%, with a median of 100%. FN risk factors were present in 1216 (45.7%) patients, with age ≥65 years being the most common risk factor at 761/2663 (28.6%). It should be noted that in patients younger than 65 years, the RDI was 91.5%, and in elderly patients (≥65 years) 88.7%. Dose-limiting neutropenia was reported in 19 (0.7%) patients. There were 74 cases of grade 3–4 AEs (according to CTCAE v.5) in 59 (1.8%) patients. The most common were neutropenia, anemia, and diarrhea in 19 (0.7%), 7 (0.2%), and 6 (0.2%) patients, respectively. Serious AEs were reported in 17 patients (0.5%). Conclusion. Primary prophylaxis of FN with long-acting granulocyte colony-stimulating factor empegfilgrastim effectively maintains RDI in various nosological and therapeutic groups of patients with different CT regimens in real-world clinical practice.

Predictors of severe hematotoxicity after CAR T-cell therapy.

7024 Background: The EHA/EBMT immune effector cell-associated hematotoxicity (ICAHT) grading system characterizes hematotoxicity after CAR T-cell therapy based on depth and duration of neutropenia (Rejeski et al, Blood, 2023). We evaluated pre- and post-infusion factors associated with grade 3-4 ICAHT and developed a predictive model in 602 patients with hematologic malignancies undergoing CAR T-cell therapy at Fred Hutch Cancer Center. Methods: Grading of early hematotoxicity (day-0-30 after CAR T-cell cell infusion) was automated using the heatwaveR package. Associations with 50 patient, disease-related, and laboratory factors, and grade 3-4 ICAHT were modeled using univariate and multivariable logistic regression. Results: The most common disease types were aggressive non-Hodgkin lymphoma (NHL; n = 293; 49%), indolent NHL (n = 150; 25%), and acute lymphoblastic leukemia (ALL; n = 94; 16%). The most common CAR T-cell products were the investigational CD19 CAR T-cell product JCAR014 (n = 197; 33%), axicabtagene ciloleucel (n = 129; 21%), and lisocabtagene maraleucel (n = 73; 12%). Incidences of early ICAHT grades 1, 2, 3, and 4 were 319 (53%), 96 (16%), 60 (10%), and 35 (6%) patients, respectively. Baseline patient factors associated with grade 3-4 ICAHT included ALL (reference: aggressive NHL, OR = 4.18, 95% CI, 2.41-7.26, p &lt; 0.001) , Hispanic or Latino ethnicity (OR = 2.17, 95% CI, 1.07-4.20, p = 0.025), and lower age (OR = 1.03, 95% CI, 1.02-1.05, p &lt; 0.001). Pre-lymphodepletion (LD) laboratory factors associated with grade 3-4 ICAHT in univariate analyses included lower ANC (OR = 6.67 per log10 cells/μL, 95% CI, 4.0-11.1, p &lt; 0.001), LDH (OR = 8.70per log10U/L, 95% CI, 4.03-19.4, p &lt; 0.001), CRP (OR = 3.18 per log10mg/L, 95% CI, 2.06-5.07, p &lt; 0.001), and ferritin (OR = 6.07 per log10mg/L, 95% CI, 3.65-10.6, p &lt; 0.001). Peak CRP (OR = 15.6, 95% CI, 7.27-36.4, p &lt; 0.001), peak ferritin (OR = 7.41, 95% CI, 5.02-11.3, p &lt; 0.001), peak CRS grade (OR = 2.01, 95% CI, 1.59-2.56, p &lt; 0.001), and peak ICANS grade (OR = 1.51, 95% CI, 1.29-1.77, p &lt; 0.001) after CAR T-cell infusion were also strongly associated with grade 3-4 ICAHT. A multivariable model using restricted cubic splines and including disease type, pre-LD ANC, pre-LD LDH, peak CRP, peak ferritin, and CRS grade demonstrated high discrimination to predict grade 3-4 ICAHT (C-index = 0.89). Internal validation using bootstrapping showed near-perfect calibration without overfitting. Sensitivity and specificity based on the Youden criteria was 74% and 90%, respectively. The sensitivity and specificity of the CAR-HEMATOTOX score in predicting grade 3-4 ICAHT was 93% and 30%, respectively. Conclusions: We identified pre- and post-infusion predictors of grade 3-4 ICAHT and internally validated a multivariable logistic regression model including disease-type, pre-LD ANC, pre-LD LDH, peak CRP, peak ferritin, and CRS grade. We plan to further evaluate our model in an external cohort.

Retrospective study on the correlation between MASCC score and the evolution of febrile neutropenia for patients with solid cancer.

e13570 Retrospective study on the correlation between MASCC score and the evolution of febrile neutropenia for patients with solid cancer. Background: The Multinational Association for Supportive Care in Cancer (MASCC) score is used to risk-stratify outpatients with febrile neutropenia. Currently, data on the use of the MASCC score are based on studies with a small number of patients. Our primary aim was to determine whether a MASCC score ≥ 21 identifies patients with solid tumors who would evolve without complications. Methods: We conducted a retrospective cohort study of patients admitted with febrile neutropenia and solid cancer at Sherbrooke University Hospital from 2011 to 2022. We collected patients' demographics, type of cancer, current chemotherapy regimen, whether patients were candidates for outpatient treatment, MASCC score, duration of IV antibiotic therapy, complications (intensive care unit admission, hypotension, hypoxemia, acute kidney failure, bacteriemia (persistent or developing after 48h of IV antibiotics) and escalation in antimicrobial regimen after hospital admission), and inpatient deaths. We used chi-square analysis and multivariate analysis to determine factors other than MASCC that predict complications. Results: A total of 290 febrile neutropenia patients with solid tumors were identified. 93 patients had a MASCC score &lt;21 and 196 were identified as low risk (MASCC score ≥ 21). The preliminary results showed that the MASCC score had a specificity of 58,3% [95% CI 48,4%-67,8%], a sensibility of 83,0% [95% CI 76,7%-88,1%], a positive predictive value of 77,0% [95% CI 72,7%-80,9%] and a negative predictive value of 67,0 [95% CI 58,7%-74,4%] to identify complications. A low risk MASCC score showed statistically significative reduction in duration of neutropenia, IV antibiotics, fever and length of hospitalisation. Conclusions: The MASCC score did not demonstrate high enough accuracy to precisely identify patients which would have evolved without complications. However, a low-risk score identified by using the MASCC score was found to have strong association with reduction of duration of hospitalisation burden. Furter data will be collected to increase the strength of the study.

Comparison of prophylactic effects for chemotherapy-induced neutropenia between same-day vs next-day administration of pegteograstim in chemotherapy regimen composed of day 1 intensive myelosuppressive agent: A randomized phase III trial (CONCISE, KCSG PC22-11).

TPS12149 Background: Administration of peg-GCSF 24 to 72 hours after chemotherapy is usually recommended. Next-day administration (after 24 hours) resulted in fewer duration of Gr4 chemotherapy-induced neutropenia (CIN) and decreased severity of CIN than same-day (within 4 hours). However, patients sometimes receive same-day Peg-GCSF for the sake of convenience. In addition, a few prior studies showed that the same-day method is comparable or superior to the next-day in preventing CIN, especially in regimens that include day 1 myelosuppressive agents. Thus, we aim to test hypothesis that same-day administration of pegteograstim, a new formulation of peg-GCSF, is non-inferior to next-day administration in terms of Gr4 CIN duration. Methods: This study is a randomized, multicenter, open-label, investigator-initiated phase 3 study. Patients with adjuvant/neoadjuvant or 1st palliative chemotherapy comprising intensively myleosuppressive agents on day 1 (mFOLFIRINOX, ECb, EP, FOLFIRI, and FOLFOX) are enrolled. The patients are assigned to the same-day arm or the next-day arm in a 1:1 ratio. Randomizations are stratified according to number of CIN risk (1 vs ≥2), setting (perioperative vs palliative), and interval (2- vs 3-week). In the same-day, pegteograstim 6 mg is SC injected within 4 hrs after chemotherapy, while 24-36 hrs in the next-day. CBC test is performed daily from day 5 to 9 during the cycle 1. From cycle 2 to 4, treatments are performed in accordance with general practice, including checking for febrile neutropenia (FN), dose intensity, and safety. The primary endpoint is duration of Gr4 CIN (during cycle 1), and secondary endpoints include incidence of Gr 3-4 CIN (cycle 1), severity of CIN (cycle 1), time to recovery ANC 1000/㎕ (cycle 1), incidence of FN, CIN-related dose delay, and dose intensity. In order to verify non-inferiority of 0.6 days of Gr4 CIN duration, we estimated a significance level of 5%, power of 80%, and drop-out rate of 15%. This results in the need for a total of 160 patients, 80 in each arm. We are currently recruiting patients (since Nov 2022). Clinical trial information: KCT0007694 .

Efficacy and safety of mecapegfilgrastim in preventing neutropenia during concurrent chemoradiotherapy.

e24119 Background: Current guidelines recommend prophylactic use of granulocyte colony-stimulating factor (G-CSF) to reduce the incidence, duration, and severity of chemotherapy-induced neutropenia. We evaluated the efficacy and safety of mecapegfilgrastim, a long-acting G-CSF, in preventing neutropenia for solid tumor patients during concurrent chemoradiotherapy (CCRT). Methods: In this multicenter, open-label, randomized controlled trial, patients with lung, esophageal, or cervical cancers, and an ECOG performance status of 0-2 were randomized 1:1 to the study or control group. Both groups received standard CCRT with two 21-day cycles of taxanes and platinum-based chemotherapy. In the study group, mecapegfilgrastim 6 mg was administered 24 hours after chemotherapy for each cycle, whereas the control group received no prophylaxis for neutropenia. Short-acting G-CSF was administered if neutrophil counts fell below 2.0×10^9/L. Treatment-emergent adverse events (TEAEs) were monitored for 2 cycles and graded per CTCAE v5.0. The primary endpoint was the incidence of grade 3/4 neutropenia during CCRT. Results: From Apr 2022 to Dec 2023, 97 patients were enrolled: 48 in the study group and 49 in the control group. The median age was 59 years (range 51-71) in the study group and 60 years (range 34-71) in the control group. Baseline characteristics were balanced between two groups. Eleven patients (22.9%) in the study group experienced grade 3/4 neutropenia, compared to 27 (55.1%) in the control group (nominal p= 0.002). Three patients (6.3%) in the study group and 2 (4.1%) in the control group developed febrile neutropenia (FN). For 18 lung cancer patients, none of the study group experienced grade 3/4 neutropenia, while 2 patients (25.0%) in the control group did. FN was not reported in either group. Among 40 esophageal cancer patients , grade 3/4 neutropenia was observed in 4 patients (21.1%) of the study group, compared to 12 (57.1%) of the control group, with one case of FN in each group. For 39 gynecological cancer patients, grade 3/4 neutropenia occurred in 7 patients (36.8%) in the study group and 13 (65.0%) in the control group. Two patients of the study group and 1 of the control group developed FN. Short-acting G-CSF was required in 18 patients (37.5%) of the study group and 33 (67.4%) of the control group. TEAEs were reported in 27 patients (56.3%) of the study group and 41 (83.7%) of the control group. Notably, grade ≥3 TEAEs were reported in 21 patients (43.8%) of the study group and 30 (61.2%) of the control group, maily including hematologic toxicities like neutropenia, thrombocytopenia, and lymphocytopenia. Serious TEAEs were reported in 1 patient (2.1%) of the study group and 2 (4.1%) of the control group. One patient (2.1%) in the study group discontinued treatment due to TEAEs. Conclusions: Prophylaxis with mecapegfilgrastim reduced the incidence of grade 3/4 neutropenia during CCRT, with good safety. Clinical trial information: ChiCTR2200058551.

Overexposure to venetoclax is associated with prolonged-duration of neutropenia during venetoclax and azacitidine therapy in Japanese patients with acute myeloid leukemia.

An observational study was conducted to evaluate the pharmacokinetics of venetoclax and its impact on the efficacy and safety for Japanese patients with acute myeloid leukemia (AML) treated with venetoclax and azacitidine therapy. The association between the plasma concentration, after the first cycle of azacitidine and venetoclax therapy, and the efficacy and safety was evaluated in 33 patients with untreated or relapsed/refractory AML. Full dose of venetoclax was administered to all patients. Venetoclax treatment was 28day long in 82% of patients; the relative dose intensity of azacitidine was 82%. Trough concentration was significantly higher among patients with complete remission (CR) and CR with incomplete hematologic recovery (CRi) than those with the morphologic leukemia-free state and partial remission, and no response groups (P = 0.01). Median duration of grade 3 neutropenia was 28 days (range 8-46 days). Area under the concentration-time curve (AUC0-24) was significantly higher among patients with protracted grade 3 neutropenia (≥ 28 days) than those with a shorter duration (< 28 days) (P = 0.03); multivariate analysis revealed that a higher AUC0-24 was a significant predictor of a longer duration of neutropenia (odds ratio 54.3, P = 0.007). Plasma concentrations of venetoclax were variable in Japanese patients with AML. Higher plasma concentrations were associated with CR/CRi and protracted grade 3 neutropenia. Therefore, it is essential to adjust the duration of venetoclax administration based on individual pharmacokinetic data to limit total drug exposure, reduce severe neutropenia, and achieve higher efficacy.

Prolonged cytopenias after immune effector cell therapy and lymphodepletion in patients with leukemia, lymphoma and solid tumors

Background aimsThe success of chimeric antigen receptor (CAR) T-cell therapy in treating B-cell malignancies has led to the evaluation of CAR T-cells targeting a variety of other malignancies. Although the efficacy of CAR T-cells is enhanced when administered post-lymphodepleting chemotherapy, this can trigger bone marrow suppression and sustained cytopenia after CD19.CAR T-cell therapy. Additionally, systemic inflammation associated with CAR T-cell activity may contribute to myelosuppression. Cytopenias, such as neutropenia and thrombocytopenia, elevate the risk of severe infections and bleeding, respectively. However, data on the incidence of prolonged cytopenias after immune effector therapy in the solid tumor context remain limited. ObjectiveWe compared the incidence of prolonged cytopenias after immune effector therapy including genetically modified T-cells, virus-specific T-cells (VSTs) and NKT-cells, as well non-gene-modified VSTs for leukemia, lymphoma, and solid tumors (ST) to identify associated risk factors. MethodsA retrospective analysis was conducted of 112 pediatric and adult patients with relapsed and/or refractory cancers who received lymphodepleting chemotherapy followed by immune effector therapy. Patients treated with 13 distinct immune effector cell therapies through 11 single-center clinical trials and 2 commercial products over a 6-year period were categorized into 3 types of malignancies: leukemia, lymphoma and ST. We obtained baseline patient characteristics and adverse events data for each participant, and tracked neutrophil and platelet counts following lymphodepletion. ResultsOf 112 patients, 104 (92.9%) experienced cytopenias and 88 (79%) experienced severe cytopenias. Patients with leukemia experienced significantly longer durations of severe neutropenia (median duration of 14 days) compared with patients with lymphoma (7 days) or ST (11 days) (P = 0.002). Patients with leukemia also had a higher incidence of severe thrombocytopenia (74.1%), compared with lymphoma (46%, P = 0.03) and ST (14.3%, P < 0.0001). Prolonged cytopenias were significantly associated with disease type (63% of patients with leukemia, 44% of patients with lymphoma, and 22.9% of patients with ST, P = 0.006), prior hematopoietic stem cell transplant (HSCT) (66.7% with prior HSCT versus 38.3% without prior HSCT, P = 0.039), and development of immune effector cell-associated neurotoxicity syndrome (ICANS) (75% with ICANS versus 38% without ICANS, P = 0.027). There was no significant association between prolonged cytopenias and cytokine release syndrome. ConclusionsImmune effector recipients often experience significant cytopenias due to marrow suppression following lymphodepletion regardless of disease, but prolonged severe cytopenias are significantly less common after treatment of patients with lymphoma and solid tumors.

Growth Factor in the Setting of CAR T-Cell Therapy: To Use or Not to Use

Patients undergoing chimeric antigen receptor (CAR) T-cell therapy may experience side effects including cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome (ICANS), neutropenia, and infection. Growth factor has historically been used to treat neutropenia; however, its role in CAR T-cell therapy is not well explained. Existing data on the safety and efficacy of growth factor are conflicting. The purpose of this integrative review was to explore the safety and efficacy of growth factor in adult patients with hematologic malignancies undergoing CAR T-cell therapy. A literature review was conducted using PubMed, Cumulative Index to Nursing &amp; Allied Health (CINAHL), and Scopus databases. A total of 2,635 articles were retrieved. Four studies were included that looked at the use of growth factor in the CAR T-cell setting. Safety outcomes evaluated included CRS, ICANS, neutropenic fever and/or infection, and neutropenia duration. Efficacy outcomes evaluated included CAR T-cell expansion and treatment response. The literature suggests that growth factor may not increase CRS prevalence, but may lead to an increased grade of CRS, namely grade 2. Growth factor administration does not have any association with ICANS toxicity, CAR T-cell expansion, or treatment response. Its use may not necessarily lead to decreased infection rates but may shorten the duration of neutropenia. Practice implications for providers working with this unique patient population include using growth factor early in the course of CAR T-cell therapy as treatment to shorten the duration of neutropenia rather than infection prophylaxis.

Comparison between a single dose of PEG G-CSF and multiple doses of non-PEG G-CSF: a systematic review and meta-analysis from Clinical Practice Guidelines for the use of G-CSF 2022.

Granulocyte colony-stimulating factor (G-CSF) is widely used for the primary prophylaxis of febrile neutropenia (FN). Two types of G-CSF are available in Japan, namely G-CSF chemically bound to polyethylene glycol (PEG G-CSF), which provides long-lasting effects with a single dose, and non-polyethylene glycol-bound G-CSF (non-PEG G-CSF), which must be sequentially administrated for several days. This current study investigated the utility of these treatments for the primary prophylaxis of FN through a systematic review of the literature. A detailed literature search for related studies was performed using PubMed, Ichushi-Web, and the Cochrane Library. Data were independently extracted and assessed by two reviewers. A qualitative analysis or meta-analysis was conducted to evaluate six outcomes. Through the first and second screenings, 23 and 18 articles were extracted for qualitative synthesis and meta-analysis, respectively. The incidence of FN was significantly lower in the PEG G-CSF group than in the non-PEG G-CSF group with a strong quality/certainty of evidence. The differences in other outcomes, such as overall survival, infection-related mortality, the duration of neutropenia (less than 500/μL), quality of life, and pain, were not apparent. A single dose of PEG G-CSF is strongly recommended over multiple-dose non-PEG G-CSF therapy for the primary prophylaxis of FN.

Development and validation of an automated computational approach to grade immune effector cell-associated hematotoxicity.

Hematologic toxicity frequently complicates chimeric antigen receptor (CAR) T-cell therapy, resulting in significant morbidity and mortality. In an effort to standardize reporting, the European Hematology Association (EHA) and European Society of Blood and Marrow Transplantation (EBMT) devised the immune effector cell-associated hematotoxicity (ICAHT) grading system, distinguishing between early (day 0-30) and late (after day +30) events based on neutropenia depth and duration. However, manual implementation of ICAHT grading criteria is time-consuming and susceptible to subjectivity and error. To address these challenges, we introduce a novel computational approach, utilizing the R programming language, to automate early and late ICAHT grading. Given the complexities of early ICAHT grading, we benchmarked our approach both manually and computationally in two independent cohorts totaling 1251 patients. Our computational approach offers significant implications by streamlining grading processes, reducing manual time and effort, and promoting standardization across varied clinical settings. We provide this tool to the scientific community alongside a comprehensive implementation guide, fostering its widespread adoption and enhancing reporting consistency for ICAHT.