Nadir Phase Research Articles

Predicting chemotherapy-induced thrombotoxicity by NARX neural networks and transfer learning

BackgroundThrombocytopenia is a common side effect of cytotoxic chemotherapies, which is often dose-limiting. Predicting an individual’s risk is of high clinical importance, as otherwise, a small subgroup of patients limits dosages for the overall population for safety reasons.MethodsWe aim to predict individual platelet dynamics using non-linear auto-regressive networks with exogenous inputs (NARX). We consider different architectures of the NARX networks, namely feed-forward networks (FNN) and gated recurrent units (GRU). To cope with the relative sparsity of individual patient data, we employ transfer learning (TL) approaches based on a semi-mechanistic model of hematotoxicity. We use a large data set of patients with high-grade non-Hodgkin’s lymphoma to learn the respective models on an individual scale and to compare prediction performances with that of the semi-mechanistic model.ResultsOf the examined network models, the NARX with GRU architecture performs best. In comparison to the semi-mechanistic model, the network model can result in a substantial improvement of prediction accuracy for patients with irregular dynamics, given well-spaced measurements. TL improves individual prediction performances.ConclusionNARX networks can be utilized to predict an individual’s thrombotoxic response to cytotoxic chemotherapy treatment. For reasonable model learning, we recommend at least three well-spaced measurements per cycle: at baseline, during the nadir phase and during the recovery phase. We aim at generalizing our approach to other treatment scenarios and blood lineages in the future.

IP-10 and complement activation as friend or foe in COVID-19.

IntroductionThe Innate immune system senses danger signals of COVID-19 infection and produce an orchestration of cellular, complement and cytokines cascades. These led to the approach using immunosuppressive agents. It is intriguing whether certain biomarkers can aid the proper administration of such drugs.MethodsPlasma specimens of 58 COVID-19 patients with differing severity, from very mild illness (group A), mild (group B), moderate (group C), and severe/critical illness (group D) were assayed for cyto-chemokines and terminal complement complex (SC5b-9) during the course of diseases. None received anti-IL-6 therapy, there was no mortality in this cohort.ResultsIP-10 and RANTES levels were dominant cytokines. IP-10 levels increased significantly in all groups when compared between pre-nadir and nadir phases (group A, p =0.428; group B =0.034; group C =0.159; group D <0.001) and in groups B and D when compared between nadir and recovery phases (p <0.001). RANTES levels were elevated in all groups across all phases with no significant differences. SC5b-9 levels increased significantly as compared to healthy controls [pre-nadir- group A versus healthy, p =0.122; group B-D versus healthy, p =0.021); nadir-group A versus healthy, p =0.003; group B-D versus healthy, p <0.001; recovery phase (p <0.001)] but not between groups A and B-D at pre-nadir (p=0.606).ConclusionThe absence of significant pro-inflammatory responses and early elevation of IP-10 levels and complement activation may be favorable and necessary for viral elimination in COVID-19 patients. Expression of distinct cyto-chemokines during each clinical phase may be useful for guiding proper therapeutic interventions on alleviating thrombo-inflammation responses to COVID-19 infection.

COVID-19 Vaccination in Cancer Patients: A Review Article.

Coronavirus disease 2019 (COVID-19) infection is caused by severe acute respiratory syndrome coronavirus 2. Adults with cancer are immunocompromised due to several causes including cancer itself and immunosuppressive therapy. Thus, cancer patients are more susceptible to develop COVID-19 infection. As COVID-19 vaccines became available, patients with cancer would benefit from receiving the vaccine. This article aims to review the recent evidences and recommendations about COVID-19 vaccination in cancer patients.Current guidelines recommend that patients with cancer should have the priority to receive the vaccine given their immunocompromised state. The timing of administration varies depending on cancer type and treatment. Generally, the vaccine should be given before starting the chemotherapy if possible or in between chemotherapy cycles and away from nadir phase. For other cancer treatments, it is recommended to give the vaccine when there is evidence of blood count recovery. In general, induction therapy and treatment for newly diagnosed patients should not be delayed for the vaccination purpose. It is noteworthy to mention that cancer patients especially those with hematologic malignancies might have absented or attenuated response to the vaccine due to their pathophysiological status.On the other hand, the current vaccine guidelines have been criticized for lacking evidence on some important topics that need to be addressed. Firstly, some vaccines have been granted an emergency use authorization, prior to the usual comprehensive safety and efficacy evaluation process. Secondly, specific populations including cancer patients were excluded from the approval trials for safety reasons. Finally, some recommendations regarding the COVID-19 vaccines are extrapolated from other vaccines studies. Further studies are required to fill these gaps and observational studies that include cancer patients are warranted to have a better understanding of the safety and efficacy of the vaccines in cancer patients.

Safety and Functional Studies of Ex Vivo Generated Megakaryocytic Progenitors/Platelets in a Myeloablative Non-Human Primate Model

The ex vivo induction of megakaryocytes/platelets of hematopoietic stem cells represent an effective treatment for thrombocytopenia. We have previously reported a clinically feasible "two-stage culture system" for expanding CD34+ cells and producing megakaryocytes/platelets. With this culture system one cord-blood unit (2 × 106 - 5 × 106 CD34+ cells) yields sufficient megakaryocytes/platelets for treating up to 85 patients (with an average weight of 70 kg and infusion cell number 5.45 × 106 cells/kg). The induced human megakaryocytic cells were capable of producing functional platelets in xenotransplantation mouse model.Here, we further tested the safety and feasibility of ex vivo generated megakaryocytic progenitors/platelets in a myeloablative non-human primate model. Mobilized peripheral blood CD34+ cells of cynomolgus monkeys (Macaca fascicularis) wereisolated after daily administration of G-CSF (100 μg/kg/day) and SCF (50 μg/kg/day) for five days. Expansion and subsequent differentiation of CD34+ cells and megakaryocytic progenitor cells were performed in a modified IMDM basal medium supplemented with various cytokine combinations including stem cell factor, Flt-3 ligand, thrombopoietin, interleukin 3, StemRegenin 1, interleukin 6 for 8 days. The expansion and differentiation processes were closely monitored by flow cytometry for expression of cell surface markers. In vitro morphological identification and CFU assays were carried out for monkey megakaryocytic progenitors. Furthermore, safety and efficacy of induced megakaryocytic progenitor cells were evaluated in vivo by using a thrombocytopenia model of monkeys. Briefly, cynomolgus monkeys were administered with carboplatin at a dose of 8 mg/kg/day on days 1, 2 and 3. On day 7 after the first carboplatin injection, the experimental group monkeys were infused with megakaryocytic progenitor cells (4.6±1.2 × 106/kg ) labeled with anti-monkey IgG-microbead-FITC conjugates. Negative control group was treated with normal saline. Peripheral blood and bone marrow from the tested animals were obtained for analyzing cell differentiation at various times. In vivo bleeding time was recorded to assess the matured platelet function, which was the time length of the bleeding to stop by making a cut in the forearm of the monkeys.After culturing for 8 days, total cells were expanded up to 13.65±3.79-fold. Analysis of the percentage of component cells further showed that CD34+, CD41+, and CD34+/CD41+ megakaryocytic progenitor cells were 46.8%±3.2%, 22.9%±4.6%, and 20.3%±2.8%, respectively. Induced megakaryocytic cells were morphologically distinguishable as they were much larger than CD34+ cells with apparent lobular nuclei. CFU analysis revealed that they increased 12±4.3-fold on day 8 as compared with day 1. In the experimental group, platelet count nadir occurred on day 14 or 15 with 40% of normal value and completely recovered to the normal value on day 26. On the other hand, the nadir of the platelet count in the control group occurred on day 19 or 20 with 20% of normal value and recovered to the normal on day 32. During the nadir phase (from days 14 to 20), the in vivo bleeding time of experimental group was considered normal (6-7.5 minutes) relative to untreated normal monkey values (range 5-7 minutes), whereas it was longer (~8.5 minutes) in control group. Likewise, the nadir of white blood cell (WBC) count (with 45% of the normal value) occurred on day 17, which completely recovered on day 22 for the monkeys infused with induced megakaryocytic progenitors/ platelets. On the other hand, the nadir of WBC count of the control group was 35% of normal value on day 19, which recovered to the normal on day 36. Fifteen days after infusion, flow cytometry and fluorescent microscope analyses showed that about 1% of fluorescent cells remained in bone marrow, indicating successful engraftment of CD34+ stem/progenitor cells in the infused cell preparation. The infused monkeys have survived with no apparent abnormalities for more than one year.Combined, our results strongly suggest that functional human megakaryocytes/platelets can be produced in a large-scale from CD34+ cells for potential clinical application. More importantly, induced non-human primate megakaryocytic progenitors/platelets can be safely administrated to myelosuppressive monkeys, contributing to platelet recovery and early engraftment. DisclosuresQin:Biopharmagen. corp: Employment. Ren:Biopharmagen corp: Employment. Jiang:Biopharmagen.corp: Employment.

Metabolomic Model For Chronic Gvhd Diagnosis

IntroductionMetabolomics is an essential tool for Translational Medicine, with a holistic non targeted approach, which provides information from the metabolic profile that can be used as a potential biomarker for a certain feature. The identification of biomarker profiles can be translated into simplified tests for the early diagnosis of diseases such as graft-versus-host disease (GVHD). AimTo evaluate the feasibility of a diagnostic protocol for chronic GVHD (cGVHD) based on the metabolic profile of blood serum from patients (pts) submitted to hematopoietic stem cell transplantation (HSCT). MethodologyThe study included a prospective, nested cohort of 41 adult pts who had undergone first full-match allogeneic HSCT at Hospital de Cl'nicas/ University of Campinas between August, 2011-January, 2013 and had signed the Consent Form. Blood serum samples were prospectively collected on the day of hospitalization (D-8), day of transplantation (D0), NADIR phase (D+10) and D+100 post-HSCT. The Nuclear Magnetic Resonance (NMR)-based metabolomic experiments were performed at the Brazilian Biosciences National Laboratory (LNBio/CNPEM). Samples were previously filtered on a 3 kDa cut off filter, diluted 3X on 100 mM phosphate buffer pH 7.4, referenced with 10% D2O and 0.5 mM DSS (4,4-dimethyl-4-silapentane-1-sulfonic acid) for further absolute quantification of metabolites. The acquisition of 1D spectra was performed on a Agilent/Varian INOVA spectrometer operating at 1H resonance frequency of 600MHz. The spectra processing, identification and quantification of metabolites were performed by using the application package Chenomx NMR Suite and the target profiling approach (Chenomx, Inc). Samples from pts who developed chronic GVHD, at anytime, were marked as “cGVHD group”, and those who did not develop chronic GVHD, “cGVHD-free group” . Blood samples from pts who died up to 200 days after HSCT and did not develop chronic GVHD were excluded from the analysis, as were also all samples from pts whose sample collection was lacking at least in one period. T-tests (p<0.05) were applied at each sampling time in order to select metabolites and perform Principal Component Analysis (PCA), hierarchical clustering and calculate Receiver Operating Characteristic (ROC) curve for cGVHD diagnosis model using the software Pirouette¨ 4.0 (Infometrix, Inc) and the web tools MetaboAnalyst 2.0 and ROCCET. ResultsMedian age was 41(18-69) years old and 61% were male. 18/41(44%) pts matched the inclusion criteria for the study. 6/18 (33%) pts had undergone cGVHD therapy. Seventy-three metabolites were identified and quantified in the blood serum samples. 8 metabolites were selected by T-test application at each studied time (2 metabolites from D-8, 2 from D0, 3 from D+10 and 1 from D+100). Using the selected metabolites the PCA showed clear separation between pts from “cGVHD” and “cGVHD-free” groups as well as hierarchical clustering (Fig. 1), confirmed by ROC analysis as a high sensitivity and specificity model for cGVHD diagnosis (AUC 0.99 and CI 0.93-1.00) (Fig. 2). [Display omitted] [Display omitted] ConclusionMetabolic differences were found in both studied groups. These differences may be used as a biomarker profile for cGVHD diagnosis up 100 days post-HSCT. Our results demonstrated that the statistical model using combined prospective time-series analysis is a powerful metabolomic model for early cGVHD diagnosis. Disclosures:Alborghetti:Sao Paulo Research Foundation: Research Funding. da Silva:Coordination for the Improvement of Higher Education Personnel (CAPES): Research Funding.

Abstract 1843: Surgical and chemotherapy influence on circulating developmental microRNA miR17-92 and long term survival in breast and ovarian cancer patients.

Abstract Background Breast cancer (BrCa) is treated with surgery (SUR), radiation (RAD) and or chemotherapy (CTx) based on stage at diagnosis. Over 75% of women are diagnosed with ovarian cancer (OvCa) are diagnosed at stage III and treated with debulking SUR and CTx. Only 1/5 of OvCa are cured of their disease with SUR followed by CTx. In stage III BrCa 40% are long term survivors after SUR, CTx &amp; RAD. There are no markers to quantify the contribution of each therapeutic intervention to the overall success in cancer patients. Patterns of circulating miRs may explain the role of SUR and CTx in ovarian/breast cancer cure. MiRs-17-92 have essential roles in embryonal and immune system development. MiR-17-92 cluster is deleted in 20% of ovarian cancers. Aims We set out to identify changes microRNA patterns in plasma obtained before and after surgery for breast/ovarian cancer and during chemotherapy that correlated with the patients’ long-term outcomes. Methods Between 2004 and 2011 we investigated patterns of plasma miRNAs collected before, after surgery, during and after chemotherapy in 50 patients presenting for surgery for ovarian cancer 18 breast cancer patients and 11 age and race-matched normal controls. We also collected blood at ovarian cancer relapse and tumor and benign ovary for miRNA analysis. 2-sample t-test was used for all 2-sample comparison and ANOVA followed by Benjamin-Hochberg method for multiple testing to limit the false discovery rate (FDR) at the 5% level. All tests were 2-tailed and results with a p&amp;lt;0.05 were considered statistically significant. Results Fifty patients were operated for EOC mean age at surgery 65 (range 51-78), 11 race matched women controls - mean age of 58 (range 25-67). Four patients were cured, 21 patients died within 36 month of their diagnosis and 21 patients who survived long term not cured but continue to receive chemotherapy. 18 brCa patients were ER/PR/Her2- W(5), B(5) and ER/PR+ W(5) B(3). MiR-19a was pre-op in patients with short over all survival (p&amp;lt; 0.003). CTx increased miR-19a 38-fold compared to the pre-SUR levels (p&amp;lt;0.0002). CTx up-ed MiR-19b 38 fold (p&amp;lt;0.003). MiR-92 low in pre-SUR plasma increased 17-fold during CTx (p&amp;lt;0.003). MiR-25 low in pre-SUR plasma and increased 47-fold during CTx (p&amp;lt;0.002). Changes in miR-17-92 cluster were the most dramatic in patients with OvCa treated with SUR and CTx. Post-SUR miRs from 17-92 cluster increased post-SUR in BrCa. High pre-SUR miR17-92 pre-SUR &amp; during CTx forecast good outcome. Conclusions During CTx, levels of miR-17-92 change dramatically compared to the pre-surgical levels. Shifts in microRNAs from the cluster 17-92 observed in the nadir phase of adjuvant chemotherapy for ovarian cancer patients correlate with long term outcomes. Breast and ovarian cancer patients with higher circulating miR-17-92 levels in pre-surgical plasma levels had better long-term survival. Citation Format: Iuliana Shapira, Annette Lee, Michaela Oswald, Janaki Parameswaran, Keith Sultan, Daniel Budman. Surgical and chemotherapy influence on circulating developmental microRNA miR17-92 and long term survival in breast and ovarian cancer patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1843. doi:10.1158/1538-7445.AM2013-1843

Predictive value of hematological and phenotypical parameters on postchemotherapy leukocyte recovery

Grade IV chemotherapy toxicity is defined as absolute neutrophil count <500/microL. The nadir is considered as the lowest neutrophil number following chemotherapy, and generally is not expected before the 7th day from the start of chemotherapy. The usual prophylactic dose of rHu-G-CSF (Filgrastim) is 300 microg/day, starting 24-48 h after chemotherapy until hematological recovery. However, individual patient response is largely variable, so that rHu-G-CSF doses can be different. The aim of this study was to verify if peripheral blood automated flow cytochemistry and flow cytometry analysis may be helpful in predicting the individual response and saving rHu-G-CSF. During Grade IV neutropenia, blood counts from 30 cancer patients were analyzed daily by ADVIA 120 automated flow cytochemistry analyzer and by Facscalibur flow cytometer till the nadir. "Large unstained cells" (LUCs), myeloperoxidase index (MPXI), blasts, and various cell subpopulations in the peripheral blood were studied. At nadir rHu-G-CSF was started and 81 chemotherapy cycles were analyzed. Cycles were stratified according to their number and to two dose-levels of rHuG-CSF needed to recovery (300-600 vs. 900-1200 microg) and analyzed in relation to mean values of MPXI and mean absolute number of LUCs in the nadir phase. The linear regressions of LUCs % over time in relation to two dose-levels of rHu-G-CSF and uni-multivariate analysis of lymphocyte subpopulations, CD34(+) cells, MPXI, and blasts were also performed. In the nadir phase, the increase of MPXI above the upper limit of normality (>10; median 27.7), characterized a slow hematological recovery. MPXI levels were directly related to the cycle number and inversely related to the absolute number of LUCs and CD34(+)/CD45(+) cells. A faster hematological recovery was associated with a higher LUC increase per day (0.56% vs. 0.25%), higher blast (median 36.7/microL vs. 19.5/microL) and CD34(+)/CD45(+) cell (median 2.2/microL vs. 0.82/microL) counts. Our study showed that some biological indicators such as MPXI, LUCs, blasts, and CD34(+)/CD45(+) cells may be of clinical relevance in predicting individual hematological response to rHu-G-CSF. Special attention should be paid when nadir MPXI exceeds the upper limit of normality because the hematological recovery may be delayed.

The nociceptin/orphanin FQ antagonist UFP-101 differentially modulates the glucocorticoid response to restraint stress in rats during the peak and nadir phases of the hypothalamo–pituitary–adrenal axis circadian rhythm

The involvement of nociceptin (N/OFQ) and the nociceptin/orphanin FQ peptide (NOP) receptor in behavior associated with stress and anxiety has been established but their role in the regulation of the hypothalamo–pituitary–adrenal (HPA) axis under conditions of stress has not been fully investigated. We used the selective NOP receptor antagonist UFP-101 to examine the contribution of endogenous N/OFQ to HPA axis control under conditions of restraint stress in the morning and the evening. We found that in the morning during the HPA axis circadian nadir rats exposed to restraint stress in both the presence and absence of UFP-101 exhibited significantly elevated plasma corticosterone at 30 min post-i.c.v. injection compared to the home cage control group. Additionally, rats treated with UFP-101 and exposed to restraint had significantly elevated corticosterone levels at 60 min post-i.c.v. injection compared to all other treatment groups. Interestingly, while there was a significant increase in the expression of CRF mRNA in the paraventricular nucleus (PVN) of rats exposed to restraint stress only, there was no comparable increase in those co-treated with UFP-101. There was no change in the expression of AVP or POMC mRNA in any of the treatment groups. In contrast, when carried out in the evening we observed significantly elevated plasma corticosterone in the vehicle-treated restraint group only at 30 min post-i.c.v. injection. There was no significant difference between the UFP-101-treated restraint group and either of the home cage control groups or the vehicle-treated restraint group. Additionally, in contrast to the morning study, UFP-101 did not prolong glucocorticoid release at the 60 min time-point. These results demonstrate for the first time a differential effect of UFP-101 on restraint stress-induced HPA axis activity characterized by significant prolongation of stress-induced activity in the morning but no significant effect on the response to restraint in the evening.

Fatal Fulminant Clostridium difficile Colitis during CHOP Therapy for Lymphoma: An Autopsy Case

Although Clostridium difficile colitis is a common problem during chemotherapy, fulminant expression is rarely observed. Here, we describe a 68-year-old woman who developed fatal colitis due to Clostridium difficile infection. The patient was treated with CHOP therapy for relapsed lymphoma. In the nadir phase, she developed severe bloody diarrhea with a high fever and died within 12 hours after the beginning of symptoms. Clostridium difficile was identified in her stool and an autopsy showed hemorrhagic necrosis on the whole colon and rectum. This case demonstrates the substantial incidence of an unexpected feature with Clostridium difficile infection even with popular chemotherapy.

A simple technique to determine thrombopoiesis level using immature platelet fraction (IPF)

Immature platelet fraction (IPF) has been measured by fully automated analyzer (XE-2100) as reticulated platelet (RP) which is reflected with thrombopoiesis in bone marrow. IPF value in the healthy volunteers was 3.3% (1.0–10.3) and upper 95% confidential interval (95% CI) of IPF was determined as 7.7%. IPF was significantly high in the patients with idiopathic thrombocytopenic purpura (ITP; 17.4%, 1.2–53.2%) and recovery phase of post-chemotherapy, and significantly low in nadir phase of post-chemotherapy, and within normal range in the patients with ITP in complete remission (CR) and with aplastic anemia (AA). Total count of IPF was significantly low in patients with ITP, AA or post-chemotherapy. Mean platelet volume (MPV) was significantly high in only patients with ITP. IPF 7.7% is best point for highest sensitivity (86.8%) and specificity (92.6%) in diagnosis of ITP and recovery phase of post-chemotherapy. In receiver operating characteristic curve for diagnosis of ITP and recovery phase of post-chemotherapy, IPF was significantly more useful than MPV. These results show that IPF reflects the pathology of thrombocytopenic disorders, and that measurement of IPF is useful for the differential diagnosis and analysis of platelet kinetics.

Model analysis of the contrasting effects of GM-CSF and G-CSF treatment on peripheral blood neutrophils observed in three patients with childhood-onset cyclic neutropenia.

Human cyclic neutropenia (CN) is a rare haematological disorder characterized by regular fluctuation in the serial count of blood neutrophils. The oscillations occur at subnormal levels with a stable 3-week period. To reduce the risk of serious infections during the severe neutropenic nadir phases (< 0.25 x 10(9) neutrophils/l) patients are usually treated with recombinant growth factors. Compared with G-CSF, which has been shown to enhance the amplitudes substantially, the response to GM-CSF is poor: neutrophil numbers are not amplified, the cycles remain unchanged or are dampened. However, two cases with a modest neutrophil increase have been reported in the literature. In a recently published clinical study the different effects of GM-CSF and G-CSF application have been investigated in the same patients. Based on a mathematical model of CN we previously proposed, the detailed neutrophil data measured in this study are analysed by simulation. The contrasting clinical results can be quantitatively explained by the model concept of regulatory control together with possible individual feedback defects, i.e. abnormally reduced mitotic responsiveness of granulopoietic progenitor cells to GM-CSF and G-CSF.

A Flexible Model for Human Circadian Rhythms

Many hormones and other physiological processes vary in a circadian pattern. Although a sine/cosine function can be used to model these patterns, this functional form is not appropriate when there is asymmetry between the peak and nadir phases. In this paper we describe a semiparametric periodic spline function that can be fit to circadian rhythms. The model includes both phase and amplitude so that the time and the magnitude of the peak or nadir can be estimated. We also describe tests of fit for components in the model. Data from an experiment to study immunological responses in humans are used to demonstrate the methods.

Plasma lysozyme in drug-induced and spontaneous cyclic neutropenia.

Summary. In order to evaluate how well the plasma lysozyme concentration reflects changes in the neutrophil status in a non‐steady state system, six patients, treated with bone‐marrow depressing agents, were followed with neutrophil counts and plasma lysozyme determinations. In all patients, plasma lysozyme rather accurately mirrored changes in the neutrophil counts. The minimum change in neutrophil counts detectable by sequential studies of plasma lysozyme concentration was about 1000 neutrophils per μl blood, corresponding to a change in the granulocyte turnover rate of 30 × 107 neutrophils per kg per day. No time lag was found between changes in the neutrophil counts and plasma lysozyme concentrations, which suggests that the life span of the neutrophilic granulocytes in the tissues is less than 24 hr. In the neutrophil nadir phases the plasma lysozyme concentration was consistently higher than expected from the neutrophil counts. This was probably to a large extent due to ‘background’ lysozyme from non‐neutrophilic sources, but might in addition suggest a reduced life span in the neutropenic phases.Similar investigations were carried out in two patients with spontaneous cyclic neutropenia. Whereas in these patients little variation of plasma lysozyme with the neutrophil phases could be demonstrated, plasma lysozyme was constantly higher than the concentrations found in the patients with drug‐induced neutropenia at similar neutrophil levels. This suggests a reduced neutrophil life span in the patients with cyclic neutropenia, especially in the nadir phases. Kinetic studies of blood neutrophils with DF32P labelling in one of the patients with cyclic neutropenia showed a slightly reduced blood half‐disappearance time in the zenith phase and a greatly reduced half‐disappearance time in the nadir phase.