Rates Of Neutropenia Research Articles

Real-world effectiveness of CPX-351 vs venetoclax and azacitidine in acute myeloid leukemia

AbstractCPX-351 and venetoclax and azacitidine (ven/aza) are both indicated as initial therapy for acute myeloid leukemia (AML) in older adults. In the absence of prospective randomized comparisons of these regimens, we used retrospective observational data to evaluate various outcomes for patients with newly diagnosed AML receiving either CPX-351 (n = 217) or ven/aza (n = 439). This study used both a nationwide electronic health record (EHR)-derived de-identified database and the University of Pennsylvania EHR. Our study includes 217 patients who received CPX-351 and 439 who received ven/aza. Paitents receiving ven/aza were older, more likely to be treated in the community, and more likely to have a diagnosis of de novo acute myeloid leukemia. Other baseline covariates were not statistically significantly different between the groups. Median overall survival (OS) for all patients was 12 months and did not differ based on therapy (13 months for CPX-351 vs 11 months for ven/aza; hazard ratio, 0.88; 95% confidence interval, 0.71-1.08; P = .22). OS was similar across multiple sensitivity analyses. Regarding safety outcomes, early mortality was similar (10% vs 13% at 60 days). However, documented infections were higher with CPX-351 as were rates of febrile neutropenia. Hospital length of stay, including any admission before the next cycle of therapy, was more than twice as long for CPX-351. In this large multicenter real-world dataset, there was no statistically significant difference in OS. Prospective randomized studies with careful attention to side effects, quality of life, and impact on transplant outcomes are needed in these populations.

Pre-phase strategy to mitigate first cycle effect in diffuse large B cell lymphoma

ContextTreatment-related toxicities in DLBCL (diffuse large B cell lymphoma) patients are higher in the initial phase of treatment (first cycle effect). Implementation of pre-phase treatment before definitive chemotherapy had been shown to alleviate some of these side-effects in a non-randomized study conducted earlier in our institute (Lakshmaiah et. al., Eur J Haematol 100:644-8, 2018).AimsThis study was aimed at validating the role of pre-phase treatment in newly diagnosed DLBCL patients.Settings and designAll newly diagnosed patients with DLBCL above the age of 18 years were evaluated for eligibility and prospectively enrolled. A single-arm prospective study was conducted at the Department of Medical Oncology, in our institute from July 2015 to December 2019.Methods and materialPatients received vincristine and prednisolone as pre-phase treatment for 7 days after which definitive chemotherapy was instituted on day 1. They were followed up for 30 days post-first cycle chemotherapy.Statistical analysis usedPaired Student’s t tests and Wilcoxon signed-ranks test were used for comparison of various clinical variables as appropriate. P value of less than 0.05 was considered significant.ResultsAmong the 180 patients who were included in study, performance status improvement was noted in significant number of patients (p < 0.001). 38.4% achieved an ECOG (Eastern Cooperative Oncology Group) performance status of 0 post-pre-phase therapy. Febrile neutropenia was observed in 12.8% in the present cohort as compared to the historical non-pre-phase cohort (34%).ConclusionsPre-phase therapy significantly improves the performance status and diminishes neutropenia rates in DLBCL patients.

Effectiveness and safety of empegfilgrastim (Extimia®, BIOCAD) in patients with lymphoproliferative diseases who receive cytotoxic therapy: results of LEGERITY, the second interim analysis of multicenter retrospective-and-prospective observational post-marketing study

Aim. To assess effectiveness and safety of Extimia BIOCAD (INN: empegfilgrastim) used to decrease the rate and duration of neutropenia, the rate of febrile neutropenia and infections that manifest in febrile neutropenia in patients with lymphoproliferative diseases who receive myelosuppressive therapy.&#x0D; Materials and methods. The paper presents the results of the second interim analysis of multicenter retrospective-and-prospective observational post-marketing study of effectiveness and safety of Extimia BIOCAD (INN: empegfilgrastim) in patients with lymphoproliferative diseases who receive cytotoxic therapy. The second stage of the interim analysis describes patient characteristics, therapy used in 221 patients with morphologically confirmed lymphoma who received one or more cycles of chemotherapy as part of LEGERITY study. The endpoints of interest included the rate of Grade 3/4 neutropenia in patients, after the first cycle of any therapy line; the rate of febrile neutropenia; the rate of Grade 3/4 infectious complications; the rate of antibacterial therapy prescriptions; and the assessment of the relative dose-intensity of received chemotherapy. Additionally, the incidence rate of all adverse drug reactions (ADRs) was assessed in patients who received at least one dose of the study drug; the incidence rate of all serious ADRs was assessed in patients who received at least one dose of the study drug; the incidence rate of Common Terminology Criteria for Adverse Events (CTCAE) 5.0 Grade 3/4 ADRs in patients who received at least one dose of the study drug; the rate of study drug discontinuations due to ADRs was also assessed.&#x0D; Results. As of the second interim analysis, LEGERITY included 221 patients with various indolent and aggressive lymphomas. Median age of the patients was 53 years (1982). A group of older patients (over 60 years of age) accounted for 34% of the study population. Patients received 1 injection of Extimia per chemotherapy cycle. Grade 3/4 neutropenia was registered in 6.7% (n=14) patients. Overall, all-grade neutropenia was reported in 21.4% (n=44) patients. Febrile neutropenia was reported in 2.9% cases. Severe infections and the use of antimicrobials were reported in no patients throughout the CT period and after each cycle of therapy. Most commonly reported adverse reactions included mild-to-moderate ossalgias (6.8%) and myalgias, back pain, and arthralgias (3.2%), that did not require pharmaceutical therapy. One (0.5%) patient had a severe adverse drug reaction a CTCAE 5.0 Grade 4 hypotension episode.&#x0D; Conclusion. Interim analysis results support high effectiveness and safety of the Russian original pegylated granulocyte colony-stimulating factor of empegfilgrastim (Extimia) in patients both with indolent and aggressive lymphomas. Real world evidence demonstrates a favourable safety and tolerability profile of empegfilgrastim in all age groups, including in the aging population. As of the moment of the interim analysis publication, the study is ongoing. Final conclusions on the safety and effectiveness of empegfilgrastim (Extimia) are to be drawn upon the study completion.

Phase 1 study of the liposomal formulation of eribulin (E7389-LF): Results from the breast cancer expansion cohort

BackgroundA liposomal formulation of eribulin, E7389-LF, may provide improved pharmacokinetics and allow increased access to tumour tissues. This expansion of a phase 1 study assessed the safety and efficacy of E7389-LF in patients with human epidermal growth factor receptor type 2-negative metastatic breast cancer. MethodsPatients received E7389-LF 2.0 mg/m2 every three weeks. Tumour assessments were conducted every six weeks by the investigator by Response Evaluation Criteria in Solid Tumours v1.1. All adverse events were monitored and recorded. Serum biomarker assessments were conducted. ResultsOf 28 patients included, 75.0% had hormone receptor-positive breast cancer (HR+ BC) and 25.0% had triple-negative breast cancer (TNBC). The most common grade ≥3 treatment-related treatment-emergent adverse events included neutropenia (67.9%), leukopenia (42.9%), thrombocytopenia (32.1%), and febrile neutropenia (25.0%). Rates of neutropenia and febrile neutropenia were lower among patients who received prophylactic pegfilgrastim. Objective response rate was 35.7% (95% confidence interval [CI]: 18.6–55.9) for all patients and 42.9% (95% CI: 21.8–66.0) for patients with HR+ BC. Median progression-free survival was 5.7 months (95% CI: 3.9–8.3). The median overall survival was 18.3 months (95% CI: 13.2–not estimable). Among the 54 biomarkers assessed, 27, including 5 of 7 vascular markers, were significantly altered by E7389-LF treatment from baseline to any time point. ConclusionE7389-LF was tolerable and favourable antitumour activity was observed, particularly in patients with HR+ BC. Prophylactic pegfilgrastim can be considered in patients at high risk for neutropenia and febrile neutropenia. Clinicaltrials.gov numberNCT03207672.

Patterns of Disease Progression and Outcome of Patients With Testicular Seminoma Who Relapse After Adjuvant or Curative Radiation Therapy

Radiation therapy is a possible treatment strategy for patients with testicular seminoma after orchiectomy in clinical stage I or II disease. Little is known about the outcome of patients who experience a relapse after radiation therapy. Data from 61 patients who relapsed after adjuvant or curative radiation therapy from 17 centers in 11 countries were collected and retrospectively analyzed. Primary outcomes were disease-free and overall survival. Secondary outcomes were time to relapse, stage at relapse, treatment for relapse, and rate of febrile neutropenia during chemotherapy for relapse. With a median follow-up of 9.9 years (95% confidence interval [CI], 7.5-10.9), we found a 5-year disease-free survival of 90% (95% CI, 79-95) and a 5-year overall survival of 98% (95% CI, 89-100). Sixty-six percent of patients had stage III disease at time of relapse and 93% of patients fell into the good prognosis group per the International Germ Cell Cancer Collaborative Group classification. The median time to relapse after radiation therapy was 15.6 months (95% CI, 12-23). Twenty-two (36%) patients relapsed more than 2 years after radiation therapy and 7 (11.5%) patients relapsed more than 5 years after radiation therapy. One-third of relapses was detected owing to patients' symptoms, whereas two-thirds of relapses were detected during routine follow-up. The majority (93%) of cases were treated with cisplatin-based chemotherapy. The rate of febrile neutropenia during chemotherapy was 35%. Five patients experienced a second relapse. At last follow-up, 55 patients (90%) were alive without disease. Only 1 patient died owing to disease progression. Cisplatin-based chemotherapy for patients with seminoma who have relapsed after treatment with radiation therapy alone leads to excellent outcomes. Patients and physicians should be aware of possible late relapses after radiation therapy.

The changing impact of cytomegalovirus among hematopoietic cell transplant recipients during the past decade: A single institutional cohort study.

With advancements in allogeneic hematopoietic cell transplantation (alloHCT), the need for cytomegalovirus (CMV) surveillance persists. We present a retrospective analysis on the impact of CMV with preemptive therapy in 1065 alloHCT patients with donor and/or recipient CMV seropositivity from 2009 to 2019. Fifty-one percent developed clinically significant CMV infection (CMV-CSI); 6.5% had CMV disease. In multivariate analysis stratified by serostatus and preparative regimen, the use of anti-thymocyte globulin (hazard ratios 2.97, 95% confidence interval 2.00-4.42, p<.001) was associated with development of CMV-CSI. Median length of stay for index hospitalization was longer in patients with CMV-CSI (27 vs. 25 days, respectively; p=.002), as were rates (32.9%vs. 17.7%; p<.001) and duration (9 d vs. 6 d; p<.001) of rehospitalization, and median total inpatient days (28 d vs. 26 d; p<.001). Patients with CMV-CSI had higher rates of neutropenia (47%vs. 20%; p<.001) and transfusion support (packed red blood cell, median 5vs. 3; p<.001; platelets, median 3vs. 3; p<.001). Preemptive therapy does not negate the impact of CMV-CSI on peri-engraftment toxicity and healthcare utilization. This cohort represents a large single center study on the impact of CMV in the preletermovir era and serves as a real-world comparator for assessing the impact of future prophylaxis.

Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design

Current standard of care for metastatic castration-sensitive prostate cancer supplements androgen deprivation therapy with either docetaxel, second-generation hormonal therapy, or radiotherapy. We aimed to evaluate the efficacy and safety of abiraterone plus prednisone, with or without radiotherapy, in addition to standard of care. We conducted an open-label, randomised, phase 3 study with a 2 × 2 factorial design (PEACE-1) at 77 hospitals across Belgium, France, Ireland, Italy, Romania, Spain, and Switzerland. Eligible patients were male, aged 18 years or older, with histologically confirmed or cytologically confirmed de novo metastatic prostate adenocarcinoma, and an Eastern Cooperative Oncology Group performance status of 0-1 (or 2 due to bone pain). Participants were randomly assigned (1:1:1:1) to standard of care (androgen deprivation therapy alone or with intravenous docetaxel 75 mg/m2 once every 3 weeks), standard of care plus radiotherapy, standard of care plus abiraterone (oral 1000 mg abiraterone once daily plus oral 5 mg prednisone twice daily), or standard of care plus radiotherapy plus abiraterone. Neither the investigators nor the patients were masked to treatment allocation. The coprimary endpoints were radiographic progression-free survival and overall survival. Abiraterone efficacy was first assessed in the overall population and then in the population who received androgen deprivation therapy with docetaxel as standard of care (population of interest). This study is ongoing and is registered with ClinicalTrials.gov, NCT01957436. Between Nov 27, 2013, and Dec 20, 2018, 1173 patients were enrolled (one patient subsequently withdrew consent for analysis of his data) and assigned to receive standard of care (n=296), standard of care plus radiotherapy (n=293), standard of care plus abiraterone (n=292), or standard of care plus radiotherapy plus abiraterone (n=291). Median follow-up was 3·5 years (IQR 2·8-4·6) for radiographic progression-free survival and 4·4 years (3·5-5·4) for overall survival. Adjusted Cox regression modelling revealed no interaction between abiraterone and radiotherapy, enabling the pooled analysis of abiraterone efficacy. In the overall population, patients assigned to receive abiraterone (n=583) had longer radiographic progression-free survival (hazard ratio [HR] 0·54, 99·9% CI 0·41-0·71; p<0·0001) and overall survival (0·82, 95·1% CI 0·69-0·98; p=0·030) than patients who did not receive abiraterone (n=589). In the androgen deprivation therapy with docetaxel population (n=355 in both with abiraterone and without abiraterone groups), the HRs were consistent (radiographic progression-free survival 0·50, 99·9% CI 0·34-0·71; p<0·0001; overall survival 0·75, 95·1% CI 0·59-0·95; p=0·017). In the androgen deprivation therapy with docetaxel population, grade 3 or worse adverse events occurred in 217 (63%) of 347 patients who received abiraterone and 181 (52%) of 350 who did not; hypertension had the largest difference in occurrence (76 [22%] patients and 45 [13%], respectively). Addition of abiraterone to androgen deprivation therapy plus docetaxel did not increase the rates of neutropenia, febrile neutropenia, fatigue, or neuropathy compared with androgen deprivation therapy plus docetaxel alone. Combining androgen deprivation therapy, docetaxel, and abiraterone in de novo metastatic castration-sensitive prostate cancer improved overall survival and radiographic progression-free survival with a modest increase in toxicity, mostly hypertension. This triplet therapy could become a standard of care for these patients. Janssen-Cilag, Ipsen, Sanofi, and the French Government.

Association between Perceived Stress and Neutropenia in Patients with Leukemia under Chemotherapy.

Background: The most prominent part of the cellular response of the immune system is driven by neutrophils. These cells tend to decline following chemotherapy in patients with leukemia. Neutropenia is an influential factor in the prognosis of cancer patients. Stress reduces white blood cells (WBCs) and neutrophils are linked to an increased risk of infectious diseases after chemotherapy. We investigated the association between neutropenia and perceived stress following chemotherapy. Materials and Methods: We performed a cross-sectional study on 60 patients with leukemia in a university hospital. Participants completed self-report measures, including the demographic data and perceived stress scale (PSS) questionnaire. We compared rates of neutropenia, as a measure of chemotherapy prognosis, 10 days after chemotherapy in different stress levels. Moreover, the number of patients with polymorphonuclear (PMN) under 1000/microliter was compared at different stress levels. Results: We found that neutropenia is directly correlated with negative stress perception and inversely correlated with positive stress perception. These effects appear more prominent in patients with PMN under 1000/microliter as the number of these patients was significantly more in groups with higher negative stress and less in groups with higher positive stress scores. Conclusion: It can be concluded that stress is correlated with neutropenia, and stress management in patients with leukemia will be accompanied by better recovery outcomes and reduced risk of infectious disease.

Real-world safety and supportive care use of second-line 5-fluorouracil-based regimens among patients with metastatic pancreatic ductal adenocarcinoma

Objective Chemotherapy-related adverse events (AEs) can negatively impact the care of patients. The prevention and management of AEs often require additional medications. This study evaluated the percentages of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) undergoing second-line therapy with 5-fluorouracil (5-FU)-based regimens that experienced AEs during treatment and received medication to manage those AEs. Methods We conducted a retrospective observational analysis utilizing the Flatiron Health database of adult patients with mPDAC who started second-line therapy between January 2016 and August 2020. The occurrence of diarrhea, fatigue, nausea and vomiting, neuropathy, and hematologic AEs including G3/G4 anemia, neutropenia, and thrombocytopenia was assessed. The use of concomitant medications including atropine and granulocyte colony stimulating factor (G-CSF) was assessed. Results Of the 825 eligible patients, 29.0% (n = 239) received FOLFIRINOX, 24.0% (n = 198) received FOLFOX, 6.8% (n = 56) received FOLFIRI, and 40.2% (n = 332) received liposomal irinotecan-based regimens. FOLFIRI and FOLFIRINOX regimens were associated with the highest rates of anemia (16.1% and 15.5%), neutropenia (19.6% and 22.6%), and thrombocytopenia (14.3% and 9.6%). The liposomal irinotecan and FOLFOX regimens were associated with lower rates of anemia (11.8% and 12.1%), neutropenia (12.4% and 14.7%), and thrombocytopenia (2.4% and 8.1%). G-CSF use was observed among 63.6%, 34.9%, 33.9%, and 44.9% of patients treated with FOLFIRINOX, FOLFOX, FOLFIRI, and liposomal irinotecan-based regimens, respectively. Diarrhea was observed among 12.5%, 4.5%, 12.5%, and 10.2% of patients who were treated with FOLFIRINOX, FOLFOX, FOLFIRI, and liposomal irinotecan-based regimens, respectively. Nausea and vomiting occurred in 14.9%, 12.6%, 10.5%, and 13.1% of patients treated with FOLFIRINOX, FOLFOX, FOLFIRI, and liposomal irinotecan-based regimens, respectively. Atropine use was higher in patients treated with FOLFIRINOX and FOLFIRI (90.8% and 94.6%, respectively) than in patients treated with liposomal irinotecan-based regimens (75.6%). Conclusions In patients with mPDAC who received second-line therapy, those who received liposomal irinotecan-based regimens had the lowest rates of anemia, neutropenia, and thrombocytopenia compared to FOLFIRI, FOLFIRINOX, and FOLFOX, while requiring a similar or lower level of medication to treat and manage those adverse events. Patients treated with FOLFIRI received the highest dose of pegfilgrastim to manage neutropenia. The results of this real-world analysis are consistent with prior evaluations of patients with mPDAC and highlight the importance of managing adverse events and associated cost implications.

Real‐world experience with venetoclax and hypomethylating agents in myelodysplastic syndromes with excess blasts

Real‐world experience with venetoclax and hypomethylating agents in myelodysplastic syndromes with excess blasts

Zanubrutinib in relapsed/refractory mantle cell lymphoma: long-term efficacy and safety results from a phase 2 study

AbstractBruton tyrosine kinase (BTK) inhibitor is an established treatment for relapsed/refractory (R/R) mantle cell lymphoma (MCL). Zanubrutinib, a highly selective BTK inhibitor, is approved for patients with MCL who have received ≥1 prior therapy. We report the long-term safety and efficacy results from the multicenter, open-label, phase 2 registration trial of zanubrutinib. Patients (n = 86) received oral zanubrutinib 160 mg twice daily. The primary endpoint was the overall response rate (ORR), assessed per Lugano 2014. After a median follow-up of 35.3 months, the ORR was 83.7%, with 77.9% achieving complete response (CR); the median duration of response was not reached. Median progression-free survival (PFS) was 33.0 months (95% confidence interval [CI], 19.4-NE). The 36-month PFS and overall survival (OS) rates were 47.6% (95% CI, 36.2-58.1) and 74.8% (95% CI, 63.7-83.0), respectively. The safety profile was largely unchanged with extended follow-up. Most common (≥20%) all-grade adverse events (AEs) were neutrophil count decreased (46.5%), upper respiratory tract infection (38.4%), rash (36.0%), white blood cell count decreased (33.7%), and platelet count decreased (32.6%); most were grade 1/2 events. Most common (≥10%) grade ≥3 AEs were neutrophil count decreased (18.6%) and pneumonia (12.8%). Rates of infection, neutropenia, and bleeding were highest in the first 6 months of therapy and decreased thereafter. No cases of atrial fibrillation/flutter, grade ≥3 cardiac AEs, second primary malignancies, or tumor lysis syndrome were reported. After extended follow-up, zanubrutinib demonstrated durable responses and a favorable safety profile in R/R MCL. The trial is registered at ClinicalTrials.gov as NCT03206970.

Guideline for the treatment of chronic lymphocytic leukaemia

Guideline for the treatment of chronic lymphocytic leukaemia

The efficacy and safety of Iodine-131-metaiodobenzylguanidine therapy in patients with neuroblastoma: a meta-analysis

ObjectiveNeuroblastoma is a common extracranial solid tumor of childhood. Recently, multiple treatments have been practiced including Iodine-131-metaiodobenzylguanidine radiation (131I-MIBG) therapy. However, the outcomes of efficacy and safety vary greatly among different studies. The aim of this meta-analysis is to evaluate the efficacy and safety of 131I-MIBG in the treatment of neuroblastoma and to provide evidence and hints for clinical decision-making.MethodsMedline, EMBASE database and the Cochrane Library were searched for relevant studies. Eligible studies utilizing 131I-MIBG in the treatment of neuroblastoma were included. The pooled outcomes (response rates, adverse events rates, survival rates) were calculated using either a random-effects model or a fixed-effects model considering of the heterogeneity.ResultsA total of 26 clinical trials including 883 patients were analyzed. The pooled rates of objective response, stable disease, progressive disease, and minor response of 131I-MIBG monotherapy were 39%, 31%, 22% and 15%, respectively. The pooled objective response rate of 131I-MIBG in combination with other therapies was 28%. The pooled 1-year survival and 5-year survival rates were 64% and 32%. The pooled occurrence rates of thrombocytopenia and neutropenia in MIBG monotherapy studies were 53% and 58%. In the studies of 131I-MIBG combined with other therapies, the pooled occurrence rates of thrombocytopenia and neutropenia were 79% and 78%.Conclusion131I-MIBG treatment alone or in combination of other therapies is effective on clinical outcomes in the treatment of neuroblastoma, individualized 131I-MIBG is recommended on a clinical basis.

Alpha-Emitter Radiopharmaceuticals and External Beam Radiotherapy: A Radiobiological Model for the Combined Treatment.

Simple SummaryThe linear–quadratic (LQ) model was adapted to 223Ra therapy using brachytherapy formalism for a mixture of radionuclides, considering the contribution of all daughter isotopes in the decay chain. The LQ model allowed us to predict the two-year overall survival and neutropenia rates with a combination of external beam radiotherapy and 223Ra treatment. The fitted model could be used to guide future optimization and personalization of combined treatments.Previously published studies combined external beam radiotherapy (EBRT) treatments with different activities of 223Ra. The data of two-year overall survival (2y-OS) and neutropenia (TOX) incidence when combining EBRT and 223Ra are not homogeneous in literature. We adapted the linear–quadratic model (LQ) to 223Ra therapy using brachytherapy formalism for a mixture of radionuclides, considering the contribution of all daughter isotopes in the decay chain. A virtual cohort of patients undergoing 223Ra therapy was derived using data from the literature. The doses delivered using 223Ra and EBRT were converted into biologically equivalent doses. Fixed-effect logistic regression models were derived for both the 2y-OS and TOX and compared with available literature. Based on the literature search, four studies were identified to have reported the 223Ra injection activity levels varying from the placebo (0) to 80 kBq/kg, associated or not with EBRT. Logistic regression models revealed a dose-dependent increase in both the 2y-OS (intercept = −1.364; slope = 0.006; p-value ≤ 0.05) and TOX (−5.035; 0.018; ≤0.05) using the EBRT schedule of 8 Gy in 1 fr. Similar results were obtained for other schedules. Discrepancies between our TOX model and those derived for EBRT combined with chemotherapy are discussed. Radiobiological models allow us to estimate dose-dependent relationships, to predict the OS and TOX following combined 223Ra + EBRT treatment, which will guide future treatment optimization.

A Pilot Randomised Controlled Trial Examining the Benefit of a Neutropenic Diet for Children Undergoing Cancer Treatment

Neutropenic diet(ND) has been hypothesized to decrease the rate of febrile neutropenia(FN) occurring post-chemotherapy for pediatric cancers. Despite widespread use, it has not shown to be of benefit by randomized controlled trials(RCT) in western countries. No RCT has been conducted in India/LMIC to evaluate its efficacy against the standard Indian diet. Forty-two(42) children, aged 3-14 y, with cancer, scheduled to receive strongly myelosuppressive chemotherapy were randomized to receive either neutropenic diet(n = 21) or standard Indian diet(n = 21) for one chemotherapeutic cycle. FN rate was recorded as the primary outcome while the focus of infection, antibiotic length, the requirement for hospital admission, adherence to diet were the secondary outcomes. The groups were similar in baseline characteristics. Twelve patients (57%) in the neutropenic diet and nine patients(43%) in the standard diet arm developed FN. Patients in ND-arm had significantly higher chance of getting neutropenic enterocolitis(NEC) (33.33% vs 4.76% p = 0.044). Mortality (14.29%vs 0%, p = 0.23) and requirement for admission (47.6%vs 19.05%, p = 0.06), was more in the ND-arm but statistically non-significant. There was no significant difference in antibiotic length. Adherence was similar in both groups (95% vs 98%). Neutropenic diet was not effective in reducing FN rate and was associated with higher rate of NEC when compared to the standard diet.

223Ra Induces Transient Functional Bone Marrow Toxicity.

223Ra is a bone-seeking, α-particle-emitting radionuclide approved for the treatment of patients with metastatic prostate cancer and is currently being tested in a variety of clinical trials for primary and metastatic cancers to bone. Clinical evaluation of 223Ra hematologic safety showed a significantly increased rate of neutropenia and thrombocytopenia in patients, hinting at myelosuppression as a side effect. Methods: In this study, we investigated the consequences of 223Ra treatment on bone marrow biology by combining flow cytometry, single-cell RNA sequencing, three-dimensional multiphoton microscopy and bone marrow transplantation analyses. Results: 223Ra accumulated in bones and induced zonal radiation damage confined to the bone interface, followed by replacement of the impaired areas with adipocyte infiltration, as monitored by 3-dimensional multiphoton microscopy ex vivo. Flow cytometry and single-cell transcriptomic analyses on bone marrow hematopoietic populations revealed transient, nonspecific 223Ra-mediated cytotoxicity on resident populations, including stem, progenitor, and mature leukocytes. This toxicity was paralleled by a significant decrease in white blood cells and platelets in peripheral blood-an effect that was overcome within 40 d after treatment. 223Ra exposure did not impair full hematopoietic reconstitution, suggesting that bone marrow function is not permanently hampered. Conclusion: Our results provide a comprehensive explanation of 223Ra reversible effects on bone marrow cells and exclude long-term myelotoxicity, supporting safety for patients.

Efficacy of Plinabulin vs Pegfilgrastim for Prevention of Docetaxel-Induced Neutropenia in Patients With Solid Tumors

Prevention of chemotherapy-induced neutropenia (CIN) and its clinical consequences is an unmet need for which plinabulin, a selective immunomodulating microtubule-binding agent, is being tested. To demonstrate noninferiority between plinabulin and pegfilgrastim for days of severe neutropenia in cycle 1 in patients with solid tumors treated with docetaxel. The Plinabulin vs Pegfilgrastim for the Prevention of Docetaxel-Induced Neutropenia in Patients With Solid Tumors (PROTECTIVE-1) double-blind phase 3 randomized clinical trial was performed in multiple centers in China, Russia, Ukraine, and the US. Participants included patients with breast, prostate, or non-small cell lung cancer treated with single-agent docetaxel chemotherapy. Data were collected from June 1, 2018, to January 31, 2019. The database was locked on February 18, 2021. Data analysis was based on intention to treat and safety and performed from October 5, 2018, to February 23, 2021. Plinabulin, 40 mg, plus placebo or pegfilgrastim, 6 mg, plus placebo. The primary end point was day of severe neutropenia in cycle 1. Additional end points included clinical consequences of CIN (febrile neutropenia, hospitalizations, infections, antibiotic use, and modifications of chemotherapy dose), patient-reported outcomes for bone pain score, markers for immune suppression (neutrophil-to-lymphocyte ratio [NLR] of >5), immature neutrophils (band, promyelocyte, and myelocyte counts >0), and safety. Among the 105 patients included in the analysis (65 [6.19%] women; median age, 59 [range, 31-81] years), the primary end point was met within a noninferiority margin of 0.65 days, with a mean difference of 0.52 days (98.52% CI, 0.40-0.65 days). Grade 4 neutropenia frequency in cycle 1 was not significantly different. Plinabulin had earlier onset of action with less grade 4 neutropenia in week 1 of cycle 1. Plinabulin had fewer adverse clinical consequences with rates of febrile neutropenia (0 of 52 vs 1 of 53 [1.9%]), infections (4 of 52 [7.7%] vs 8 of 53 [15.1%]), chemotherapy dose delay of more than 7 days (2 of 52 [3.8%] vs 3 of 53 [5.7%]), and permanent chemotherapy discontinuation (7 of 52 [13.5%] vs 14 of 53 [26.4%]). Patients receiving plinabulin had significantly less bone pain (difference, -0.67 [95% CI, -1.17 to -0.16]; P = .01) and a better immunosuppressive profile (NLR >5 at day 8, 2 of 52 [3.8%] vs 24 of 51 [46.0%]; P < .001). Plinabulin was well tolerated, with comparable safety to pegfilgrastim. Plinabulin has comparable efficacy to pegfilgrastim for the prevention of CIN, with better safety and a better immunosuppressive profile. Plinabulin's same-day dosing compared with pegfilgrastim's next-day dosing offers distinct advantages, including reducing use of health care services. ClinicalTrials.gov Identifier: NCT03102606.

Long-acting granulocyte colony-stimulating factor in primary prophylaxis of early infection in patients with newly diagnosed multiple myeloma

PurposeThis study sought to compare the efficacy of prophylactic long-acting and standard granulocyte colony-stimulating factor (G-CSF) on febrile neutropenia, early infections, and treatment delay in patients with newly diagnosed multiple myeloma (MM) receiving the therapeutic regimen of bortezomib, lenalidomide, and dexamethasone (VRd).MethodsA prospective study with 68 consecutive patients with MM was conducted in three regional hospitals. Participants were randomly treated with the VRd regimen in combination with prophylactic long-acting G-CSF (treatment group) or prophylactic standard G-CSF (control group). The primary endpoints were the incidence rates of febrile neutropenia, early infection, and treatment delays. The secondary endpoint was clinical outcomes.ResultsThirty-three patients were assigned to the treatment group, and thirty-five patients were assigned to the control group. The incidence of febrile neutropenia was 6.1% and 17.1% in the treatment and control groups, respectively (p = 0.297). However, the rates of early infection and treatment delay were markedly lower in the treatment group than in the control group (6.1% vs. 25.7% and 9.1% vs. 31.4%; p < 0.05). Notably, all early infections occurred during the first four cycles of VRd therapy, and the most common type of infection was pneumonia. No significant difference in clinical efficacy was found between the two groups. All participants achieved at least partial remission.ConclusionsProphylactic administration of domestic long-acting G-CSF markedly reduced the rates of early infection and treatment delay as compared with standard G-CSF in patients newly diagnosed with MM. Notably, all early infections occurred during the first four cycles of VRd therapy. As such, it seems appropriate to administer long-acting G-CSF with the aim of primary prophylaxis of early infection in the setting of newly diagnosed MM.

Effect of hypertensive disorders of pregnancy on peripheral venous blood cell count in preterm infants with a gestational age of 28-34 weeks.

To study the effect of hypertensive disorders of pregnancy on peripheral venous blood cell count in preterm infants with a gestational age of 28-34 weeks. A total of 227 preterm infants with a gestational age of 28-34 weeks who were admitted to the Department of Pediatrics, the First Hospital Affiliated to Kunming Medical University, from January to December 2020, and whose mothers had hypertensive disorders of pregnancy were enrolled as the study group. A total of 227 preterm infants with a gestational age of 28-34 weeks who were admitted during the same period and whose mothers did not have hypertensive disorders of pregnancy were enrolled as the control group. According to maternal blood pressure during pregnancy, the study group was divided into three subgroups: gestational hypertension (n=75), mild preeclampsia (n=81), and severe preeclampsia (n=71). According to the birth weight of the preterm infants, the study group was divided into two subgroups: small for gestational age (SGA) (n=113) and appropriate for gestational age (AGA) (n=114). Peripheral blood cell count on day 1 after birth was compared between the study and control groups, as well as between the subgroups of the study group. Compared with the control group, the study group had significantly lower white blood cell count, absolute neutrophil count, and blood platelet count (P<0.05) and significantly higher incidence rates of leucopenia and neutropenia (P<0.05). The subgroup analysis showed that the mild preeclampsia and severe preeclampsia subgroups had significantly lower white blood cell count, absolute neutrophil count, and blood platelet count than the gestational hypertension subgroup (P<0.05), and that the SGA subgroup had significantly lower white blood cell count, absolute neutrophil count, and blood platelet count than the AGA subgroup (P<0.05). Hypertensive disorders of pregnancy can affect the peripheral venous blood cell count of preterm infants, which is more significant in infants with maternal preeclampsia and SGA infants.

Human Cytomegalovirus-Specific T-Cell Reconstitution and Late-Onset Cytomegalovirus Infection in Hematopoietic Stem Cell Transplantation Recipients following Letermovir Prophylaxis

Letermovir (LTV), recently approved for the prophylaxis of human cytomegalovirus (HCMV) reactivation after hematopoietic stem cell transplantation (HSCT), has been shown to decrease the rate of infection in the first months post-transplantation. The aim of this study was to evaluate the impact of LTV prophylaxis on immune reconstitution and late-onset infection. We studied HCMV infection and HCMV-specific T cell reconstitution in 2 matched groups of HSCT recipients, those treated with LTV prophylaxis (n=30; LTV group) and those receiving preemptive therapy (n=31; PET group). We analyzed the rates of graft-versus-host disease (GVHD), neutropenia, baseline disease recurrence, and overall survival in the 2 groups. Clinically significant infections necessitating preemptive therapy showed a similar rate in the 2 groups (PET: 21 of 31 [68%]; LTV: 17 of 30 [57%]; P=.434) but occurred significantly later (after prophylaxis discontinuation) in the LTV group. There was no between-group difference in peak HCMV DNAemia level (P=.232). HCMV-specific T cell recovery was delayed by approximately 100 days in the LTV group. HCMV-specific CD4 and CD8 T cell counts were significantly lower in the LTV group at days 120 to 360 and days 90 to 120, respectively. A lower rate of chronic GVHD (P=.024) was seen in the LTV group. Time to engraftment, rate of disease relapse, and 1-year survival were not different between the 2 groups, whereas trends toward a lower rate of neutropenia (P=.124) and a higher rate of acute GVHD grade III-IV (P=.103) were observed in the LTV group. Because LTV prophylaxis delays HCMV infection and HCMV-specific immune reconstitution, immunologic and virologic monitoring should be implemented after discontinuation of prophylaxis. The potential effect of LTV prophylaxis in reducing chronic GVHD should be evaluated in prospective studies.