Prognostic significance of marked leukocytosis in hospitalized patients

Study objective:To identify the prognostic significance of marked neutrophilic leukocytosis (MNL), defined as white blood cell (WBC) count of ≥25,000/μL and ≥80% mature neutrophils by differential count, in hospitalized patients. Design:A central laboratory computer identified all consecutive patients with MNL in a one-month period. After exclusion of outpatients, neonates, and patients with bematologic malignancies or incomplete records, the remaining patients were studied and followed until discharge or death. Setting:Inpatient services of a 988-bed tertiary care teaching hospital. Patients:72 inpatients with MNL. Interventions:None. Measurements and main results:Associated conditions and hospital mortality were recorded. Potentially confounding or contributing variables, including age, sex, intensive care unit stay, infection, acidosis, uremia, malignancy, hemorrhage, surgery or invasive procedure, peak WBC count, and duration of MNL, were examined by multivariate analysis with mortality as the outcome variable. Overall hospital mortality was 29% in study patients. A higher peak WBC count (p=0.0046), increasing age (p=0.0058), MNL duration of > one day (p=0.025), and lack of associated invasive procedures (p=0.04) were jointly significant in the prediction of mortality in MNL patients. Conclusions:The results confirm the impression of poor outcome associated with MNL and validate the use of MNL data in indices of severity of illness and as a prognostic marker for hospitalized patients regardless of underlying disease.     

Leukocytosis due to adrenal metastases from malignant melanoma: reversal after bilateral adrenalectomy with long-term survival

Leukocytosis has been noted in association with many non-hematologic malignancies in the absence of concurrent infection or metastatic involvement of bone marrow. We report a case of sustained, neutrophilic leukocytosis in a patient with disseminated malignant melanoma which reversed after bilateral adrenalectomy for adrenal metastases.     

Comparison of bone marrow histology in early chronic granulocytic leukemia and in leukemoid reaction

A retrospective study was performed on bone marrow biopsies of 50 untreated patients with leukemoid reactions (LR) and 50 untreated patients with early chronic granulocytic leukemia (CGL). A comparison was made between hematopoietic and adipose tissues, bone and its cells, as well as other stromal components in these two disorders. Histologic and histomorphometric analyses revealed significant differences in trabecular structure, in localization of fat cells, in numbers of sinusoids, capillaries and various stromal elements. No significant differences between LR and CGL were detected in the quantity of erythro- and granulocytopoiesis and of megakaryocytes, but these were smaller in CGL than in LR. This histologic and histomorphometric evaluation demonstrates that certain histologic features may serve as valuable aids in distinguishing LR from CGL.     

肝肉瘤样癌伴类白血病反应1例报告

1病例资料患者男性,65岁,因“上腹部疼痛3 d”于2017年10月7日入本院。既往史:糖尿病病史5年,口服二甲双胍,控制情况不详。否认肝炎、结核等传染病病史,无吸烟饮酒嗜好,无家族遗传病史。入院查体:腹部平软,上腹部有压痛伴肌卫,无反跳痛,肝脾肋下未及,无移动性浊音,双下肢无浮肿。     

A case of chronic neutrophilic leukemia with original chromosomal abnormalities

We report a new case of the unusual myeloproliferative syndrome chronic neutrophilic leukemia (CNL) that met all the criteria generally required for the diagnosis of this entity. The patient presented abnormalities in platelet function not previously reported that may explain the bleeding tendency observed in these patients. The study of neutrophil function suggested also defective mobility and intracellular bactericidal activity. The chromosomal study revealed original abnormalities consisting of multiple chromosomal ruptures and figures. The disease was controlled with busulfan. After 20 months, the patient died of sepsis. An autopsy was performed confirming the diagnosis and ruling out the existence of a cause of a leukemoid reaction, such as cancer or granulomatous disease.     

Elevated Granulocyte Colony-Stimulating Factor, Non-Infectious Leukocytosis and Fevers in a Patient with Multiple Myeloma

Background: We report the case of a 56-year-old male with multiple myeloma in whom recurrent fevers and leukocytosis delayed potentially effective chemotherapy due to concern for active infection. Design and measurements: A thorough infectious workup, including CT and PET scans, was negative. The patient was eventually found to have an elevated serum granulocyte colony-stimulating factor (G-CSF) of 113 pg/ml (normal range 0.0 – 39.1 pg/ml), which was likely the cause of his persistent leukocytosis and fevers. Multiagent chemotherapy was initiated, and the fevers resolved in the next 4 days. Results: Leukocyte concentrations trended down after initiation of chemotherapy, but it is uncertain how much of the decline was attributable to immunosuppression. Conclusion: We report this well-documented case to demonstrate that G-CSF production should be considered as a cause of unexplained fever and leukocytosis in patients with multiple myeloma to prevent inappropriate and delayed definitive diagnosis and treatment.     

Citrullination of CXCL8 increases this chemokine’s ability to mobilize neutrophils into the blood circulation

Background

During the first line defense of an infected host, circulating neutrophils invade the inflamed tissue, whereas mature neutrophils from the bone marrow pool migrate into the blood circulation and from there reinforce tissue infiltration. The CXC chemokine CXCL8, also know as interleukin-8, is a potent attractant of neutrophils. Recently, we discovered a new natural post-translational modification of CXCL8, i.e. the deimination of arginine into citrulline by peptidylarginine deiminases.

Design and Methods

The ability to provoke leukocytosis was assessed by intravenous administration of citrullinated CXCL8 in rabbits. Adsorption of citrullinated CXCL8 to the Duffy antigen/receptor for chemokines on human or rabbit erythrocytes was evaluated using a competitive binding assay. Finally, surface expression of adhesion molecules was studied after stimulating neutrophils with citrullinated CXCL8.

Results

Citrullination of CXCL8 significantly increased this chemokine’s ability to recruit neutrophils into the blood circulation. In addition, the competitive binding properties of CXCL8 for the Duffy antigen/receptor for chemokines were impaired upon citrullination. Since the Duffy antigen/receptor for chemokines is an important scavenging receptor for CXCL8 in the blood stream, citrullination may delay CXCL8 clearance from the circulation. Furthermore, the shedding of CD62L (L-selectin) and the upregulation of CD11b (β₂-integrin) protein expression on CXCL8-induced neutrophils were improved by deimination of CXCL8, possibly contributing to the neutrophil egress from the bone marrow. Conversely, surface expression of CD15, the neutrophilic ligand of endothelial selectins, was equally well upregulated by intact and citrullinated CXCL8.

Conclusions

These data show that citrullination of CXCL8 enhances leukocytosis, possibly through impaired chemokine clearance from the blood circulation and prolonged presentation to the bone marrow.     

Leukocytosis in obese individuals: possible link in patients with unexplained persistent neutrophilia

BACKGROUND: Recently, it was shown that fat tissue produces and releases inflammatory cytokines, and that obesity may be regarded as a state of low-grade inflammation. In this regard, we aimed to establish an association between obesity and persistent leukocytosis. PATIENTS AND METHODS: We present clinical observations of obese subjects primarily referred for further evaluation of leukocytosis without a cause and validated the link between leukocytosis and elevated body mass index (BMI) in a cross-sectional study. RESULTS: During 1999-2005, 327 patients were referred for further investigation because of persistent leukocytosis. Of these, 15.3% were asymptomatic obese, mostly females, with mild persistent neutrophilia accompanied by elevated acute-phase reactants. After careful evaluation, no recognized cause for leukocytosis was found other than the fact that the patients were obese. During a mean follow-up of 45.6 months, the leukocytosis and the elevated acute-phase reactants persisted and no new causes for leukocytosis were evident. Furthermore, in a cross-sectional analysis of 3716 non-smoker subjects, 62 were found to have leukocytosis. Compared with the population with a normal white blood count range, these subjects with leukocytosis had higher BMI, serum C-reactive protein (CRP) levels, waist circumference, and neutrophil and platelet count (all P < 0.0005). After logistic regression analysis, only BMI was shown to be associated with leukocytosis (P < 0.0005). CONCLUSIONS: Obesity is recognized as a possible cause for reactive leukocytosis. Awareness of this 'obesity-associated leukocytosis' may help the clinician to avoid more extensive and unnecessary diagnostic work-up, particularly in similar obese subjects.     

Pancreatic carcinoma associated with marked eosinophilia: a case report

A case of pancreatic carcinoma associated with marked eosinophilia is reported. A 71-yr-old man was admitted to hospital because of melena and abdominal pain. The systematic examinations revealed pancreatic adenocarcinoma with multiple metastases (rectum, lung and brain). The leukocyte count was gradually increased and reached up to 81.7 X 10(9)/l, of which 54% consisted of eosinophils. Colony-stimulating factor (CSF) was detected both in the patient's serum and in the tumor extracts by a normal human bone marrow culture system. The colonies which were stimulated with patient's serum largely consisted of granulocyte, granulocyte/macrophage and eosinophil types. These results suggest that blood leukocytosis and eosinophilia were due to a high concentration of plasma CSF, which was probably produced by the tumor cells.     

Esophageal carcinoma with high serum parathyroid hormone-related protein (PTHrP) level

We report two patients with esophageal carcinoma with high levels of serum parathyroid hormone-related protein (PTHrP). Patient 1 was a 66-year-old man in whom the serum calcium level was also high, and patient 2 was an 81-year-old woman. The serum PTHrP level was 411 pM (normal range, 13.8–55.3 pM) in patient 1 and 94.5 pM in patient 2 (in whom the serum granulocyte colony-stimulating factor level was also high). We demonstrated PTHrP immunohistologically in esophageal carcinoma cells in both patients. After admission, patient 1 died of pneumonia on the 17th day of hospitalization (the 48th day after he had had an episode of frequent hiccuping) and patient 2 died of acute circulatory failure on the 12th day of hospitalization (the 25th day after she had vomited after a meal). Neither of these patients died of cancer. Pneumonia in patient 1 was believed to be due to weakened body defenses, while the acute circulatory failure in patient 2 was due to emaciation. Since esophageal carcinoma with humoral hypercalcemia of malignancy and leukocytosis is characterized by rapid progression and metastasis, early diagnosis and treatment are mandatory. Received: December 10, 1998 / Accepted: February 26, 1999     

To early distinguish neonatal transient leukemoid proliferation from congenital leukemia by in vitro cell growth

Summary To differentiate neonatal transient leukemoid proliferation from congenital leukemia at an early stage is often difficult. Bone marrow culture is found to be helpful in this aspect. A normal in vitro growth pattern suggests transient leukemoid proliferation, while an abnormal growth pattern indicates congenital leukemia. A neonate who manifested with pictures mimicking acute myeloblastic leukemia (M₁), had a karyotype of 46, XY/46, XY, i(21 q). However, the in vitro growth pattern was normal and so only supportive treatment was given. All the leukemoid manifestations disappeared several months later and he is now a healthy 2 year old boy remaining in complete remission. A second neonate who also displayed features of acute myeloblastic leukemia (M₂), had a karyotype of 46, XY/47, XY, +21 and abnormal in vitro growth pattern. This neonate died at 18 days of age.     

进展性缺血性卒中的危险因素分析

目的：探讨进展性缺血性卒中的危险因素，为其预防提供依据。方法：回顾性分析2002年8月-20004年8月收治的166例进展性缺血性卒中病例，并以同期住院的65例非进展性缺血性卒中患者作为对照组。对两组患者的年龄、性别、血脂水平、血纤维蛋白原水平、血糖水平、发热、白细胞增多、平均动脉压、糖尿病史和CT早期梗死征象进行比较。结果：进展组患者的糖尿病史（P〈0．05）、CT早期梗死征象（P〈0.05）、发热（P〈0．01）和白细胞增多（P〈0．001）的比例显著较高，血糖（P〈0．05）和纤维蛋白原（P〈0．05）水平明显高于对照组；多变量logistic回归分析表明，糖尿病史（P=0．029）、发热（P=0.0146）、白细胞增多（P=0．005）和CT早期梗死征象（P=0．0027）是缺血性卒中早期病情加重的独立预测因素。结论：糖尿病史、发热、白细胞增多和CT早期梗死征象是进展性缺血性卒中的独立危险因素。     

A High Level of Colony-Stimulating Activity in a Lung Cancer Patient with Extensive Leucocytosis,and the Establishment of a CSA Producing Cell Line (KONT)

Colony-stimulating activity (CSA) was demonstrated in materials taken from a patient suffering from lung cancer associated with excessive leucocytosis. CSA was detected not only in his urine, serum and pleural effusion but also in the supernatant of cell cultures originating from the effusion. The excessive leukocytosis of the patient might be due to a CSA producing tumor. A cell line (KONT) originating from the CSA producing tumor has been maintained for 4 years and shown to produce mouse- and human-CSA.     

Initial performance evaluation of the UniCel® DxH 800 Coulter® cellular analysis system

The Beckman Coulter UniCel^® DxH 800 is a hematology analyzer incorporating new electronic and mechanical design with advanced algorithm technology to perform CBC, white blood cell (WBC) differential, nucleated red blood cell (NRBC), and reticulocyte analysis. Evaluation of this instrument was performed in our 800‐bed tertiary care hospital and specifically centered upon the correlation of WBC, NRBC, and platelet (PLT) enumeration when compared to a predicate analyzer, the Coulter^® LH 780, and flow cytometry (FCM) reference methods. Of particular interest were those samples with morphologically confirmed interference and extreme leukocytosis (evaluated with respect to red blood cell parameter correction). The sample set (n = 272) consisted of morphologically normal and hematologically abnormal patients. Correlation of the WBC, PLT, and NRBC showed r² values of 0.994, 0.985, and 0.910 for the DxH 800 vs. FCM, respectively. The presence of interfering particles did not affect the accuracy of the DxH 800 with respect to WBC counts. The DxH 800 showed accurate PLT and NRBC counts in the clinically significant low range when compared to FCM. Compared to the LH 780, flagging rates were significantly reduced (NRBC flag), or equivalent (WBC, PLT flag) on the DxH 800. The DxH 800 demonstrated higher sensitivity and specificity for PLTs and NRBCs and achieved a lower NRBC false negative rate compared to the LH 780. The UniCel^® DxH 800 represents a significant improvement to previous impedance analyzers in accurately detecting the presence of NRBCs at counts >1/100 WBC. Furthermore, it provides accurate PLT and WBC counts in the presence of interference and improved NRBC flagging efficiency when compared to the LH 780. Correction of red blood cell parameters is appropriate and accurate in cases of extreme leukocytosis.     

Granulocyte colony‐stimulating factor‐producing lung cancer and acute respiratory distress syndrome

Granulocyte colony‐stimulating factor (G‐CSF)‐producing lung cancers are known to cause extreme leukocytosis. However, acute respiratory distress syndrome (ARDS) caused by G‐CSF‐producing lung cancer is extremely rare. We present a case of G‐CSF‐producing lung cancer with marked leukocytosis, which rapidly led to severe ARDS after the patient developed pneumonia. The present case suggests that extreme leukocytosis may easily lead to ARDS, triggered by infection. Thus, G‐CSF‐producing lung cancer with marked leukocytosis should be carefully monitored before surgery and during treatment.     

Poor survival in t(8;21)(q22;q22)-associated acute myeloid leukaemia with leukocytosis

Abstract: Twenty-nine consecutive cases with a t(8;21)(q22;q22) in the bone marrow (BM) karyotype were retrospectively studied concerning clinical, morphological and cytogenetic data. All had been diagnosed as acute myeloid leukaemia (AML), 27 FAB subtype M2 and two M1, comprising 5% of all cytogenetically analysed AML during 18 yr. Auer rods were the most consistent t(8;21)-associated morphological finding and were demonstrated in 92% of the reviewed BM specimens, whereas BM eosinophilia was seen in only 24%. The median age was 53 yr, and 30% of the patients were >60 yr old. Twenty-four patients had received induction chemotherapy; 22 of these (91%) entered a complete remission (CR). The median survival time in treated patients was 18 months. Leukocytosis at diagnosis (>20×10⁹/l) was significantly (p=0.01) associated with shorter survival time. All four children are still in first CR after 9–80 months. Seven cases (25%) developed granulocytic sarcomas, discovered either at diagnosis (n=4) or at first relapse (n = 3). Secondary chromosome abnormalities were found in 62% of the cases, most often loss of a sex chromosome. The presence of such secondary aberrations did not correlate with any morphological or clinical characteristics, including survival. This first Scandinavian study of AML with t(8;21) corroborates the previous findings that these AMLs are characterized by distinct morphological features, a high frequency of CR and a striking tendency to develop extramedullary leukaemic manifestations. Leukocytosis at diagnosis indicates a less favourable prognosis.     

Constitutive production of granulocyte colony-stimulating factor and interleukin-6 by a human lung cancer cell line, KSNY: gene amplification and increased mRNA stability.

A human lung squamous cell carcinoma cell line designated KSNY was established from a patient suffering from marked neutrophilia and polyclonal hyper-gamma-globulinemia. In our previous report, we demonstrated colony-stimulating activities in the culture supernatant of this cell line. To determine the exact molecules for the activities, we investigated the gene expression of various cytokines in KSNY cells and showed the mRNA expression of both granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6). We also detected substantial amounts of G-CSF and IL-6 in the culture supernatant with sensitive enzyme-linked immunosorbent assays (ELISA). The amplification of the gene locus for G-CSF, but not for IL-6 was shown by Southern blot analysis. Furthermore, we also showed that the mRNAs for G-CSF and IL-6 were relatively stable in KSNY cells. These findings are thought to be related to the constitutive production of the cytokines in KSNY cells.     

A new myeloproliferative syndrome

We report here two cases of a previously undescribed myeloprollferative disorder. Both were young adult males who presented with generalized lymphadenopathy, splenomegaly, leukocytosis, polycythemia, and persistent thrombocytopenia. The leukocyte alkaline phosphatase (LAP) score was low in both cases, and the bone marrow was hypercellular without dysplasia or fibrosis, but lacked the Philadelphia chromosome, BCR gene rearrangement, or other karyotypic abnormalities. The clinical course was indolent in each case. One patient died from an unusual ‘blast crisis’ after 12 years, while the second patient remains in a complete hematologic remission on hydroxyurea and alpha interferon 4 years from diagnosis. Interestingly, changes in therapy in this patient have consistently resulted in precise and concerted fluctuations in his blood counts, with the red and white cells cycling together and the platelets and mean corpuscular volume (MCV) changing concomitantly but in the opposite direction. This unique myeloproliferative disorder is distinguishable from all previously described forms of chronic myeloid leukemia and other myeloproliferative syndromes. ©1995 Wiley-Liss, Inc.