Neutropenic State Research Articles

Utility of Echocardiogram in Neutropenic Patients with Gram Positive Bacteremia: A Retrospective Study

Introduction: Hemato-oncology patients are vulnerable to bloodstream infections (BSI) due to their immunocompromised and neutropenic state, and the common use of intravascular catheters. The risk of infective endocarditis (IE) among non-neutropenic patients with gram positive bacteremia is substantial, however the risk is considered to be lower among neutropenic patients, though data is limited. We aimed to evaluate the incidence of IE among neutropenic hemato-oncology patients' cohort, and to explore the yield of echocardiogram in this specific population. Methods: A single center, retrospective study. Between 01/2007 and 12/2019, hospitalized patients in the Hematology department consisting of the hemato-oncology and bone marrow transplantation units were included, if they had positive blood cultures for specific organisms known to cause IE while neutropenic. Patient characteristics, results and timing of blood cultures and echocardiogram obtained during hospitalization were collected. Results: Two hundred seventy-four patients had positive blood cultures with pathogens known to be associated with IE. Overall, 340 isolates have been identified. After excluding 57 coagulase negative staphylococcus (CONS) isolates which were suspected as a contamination (identified in a single collection), 241 patients were included with 283 isolates. CONS were the most commonly isolates found, followed by streptococcus viridans, comprising 31.4% (89) and 24.3% (69) of isolates, respectively. Trans thoracic echocardiography (TTE) was performed in 108 (45%) patients overall, of which 14 (5.8%) had additional trans esophageal echocardiogram (TEE). Only one case of IE was diagnosed in our series, of a forty-seven-year-old female patient with a diagnosis of multiple myeloma in relapse after autologous stem cell transplantation. The patient presented with a stroke caused by septic emboli, fever and streptococcus viridans bacteremia. Lab works showed neutropenia of 0K/micl and thrombocytopenia of 8K/micl. TTE and TEE failed to demonstrate valvular pathology consistent with IE in this case. Valvular vegetations have not been identified on TTE nor on TTE in any other case as well. Conclusion In our experience, the yield of echocardiogram in hemato-oncological neutropenic patients with gram positive bacteremia is extremely low, owing to reduced probability of IE in this population, and thus could be avoided in most cases.

The need for evolution in the management of febrile neutropenia in pediatric cancer: TRIIO KIDS update.

New treatments have increased the life expectancy of pediatric patients diagnosed with malignant hematological diseases, often at the cost of protracting their immunocompromised state in the form of prolonged neutropenia. This neutropenic state favors the development of bacterial and fungal infections. Moreover, recent years have seen a series of changes in the epidemiology of fungal and Clostridium infections. These changes necessitate adaptations to the management of pediatric patients with febrile neutropenia, who are at risk of further increases in already high rates of morbidity and mortality. This article discusses the current bases for the management of febrile neutropenia and associated emerging fungal infections, as well as the epidemiology, diagnosis, and treatment of Clostridioides difficile in pediatric patients diagnosed with malignant hematological diseases.

Analysing pathogenic bacterial spectrum and drug resistance of bloodstream infection in patients with allogeneic hematopoietic stem cell transplantation

目的了解浙江省人民医院异基因造血干细胞移植（allo-HSCT）患者血流感染临床特点、病原菌谱、耐药性及危险因素。方法回顾性分析2014年10月至2019年9月浙江省人民医院血液科210例allo-HSCT患者中发生血流感染的病原学分布、耐药性、感染危险因素及转归。结果210例allo-HSCT患者中49例发生血流感染，共分离出病原菌59株，以革兰阴性菌为主（67.8％），其中以大肠埃希菌最为常见（23.7％），碳青霉烯类耐药革兰阴性菌（CRO）占42.5％；革兰阳性菌占23.7％，未发现万古霉素及利奈唑胺耐药的葡萄球菌株；真菌占8.5％。单因素分析提示血流感染影响因素有性别、移植前疾病状态、预处理方案；多因素分析显示血流感染主要与预处理方案强度有关（OR＝3.043，95％CI 1.236～7.492，P＝0.015）。49例血流感染患者中粒细胞缺乏（粒缺）血流感染占77.6％，非粒缺占22.4％；移植前活动性感染患者发生血流感染占81.0％，移植前无活动性感染患者占16.9％。生存分析结果显示，血流感染患者总生存（OS）时间短于未发生血流感染患者，CRO感染患者比无CRO感染患者OS时间短，粒缺时间>14 d患者OS时间较粒缺时间≤14 d患者短，移植前是否合并活动性感染及感染时是否处于粒缺状态与OS时间无明显相关性。结论本研究提示积极预防耐药菌血流感染、缩短粒缺时间、移植前控制感染、适合的预处理方案，能降低移植死亡率、改善预后。

Analysis of antibiotics discontinuation during bone marrow suppression in childhood, adolescent and young adult patients with febrile neutropenia.

Antibiotics have been widely and efficaciously used for febrile neutropenia in pediatric patients. However, reports are scant regarding the risk factors for recurrent fever after discontinuation of antibiotics in a neutropenic state. Here, we investigated these factors using data from our previously reported randomized study regarding meropenem and piperacillin/tazobactam for pediatric patients with febrile neutropenia. We analyzed a total of 170 febrile episodes where first line antibiotic treatment was effective and discontinued before neutrophil recovery. Recurrent fever was observed in 31 episodes (18%). The median interval from antibiotics discontinuation to recurrent fever was 5 days (0-27 days). Risk factors for recurrent fever were: incomplete remission of original disease; and high white blood cell count, neutrophil count, and C reactive protein levels at start of antibiotics. Moreover, lower neutrophil count at discontinuation of antibiotics, duration of neutropenia, and onset day of febrile neutropenia from start of neutropenia were also risk factors of recurrent fever. In multivariate analysis, neutrophil count at discontinuation of antibiotics <0.011×109/L, neutrophil count at start of antibiotics ≥0.061×109/L, febrile onset following <1 day after onset of neutropenia, and incomplete remission of original disease were independent risk factors for recurrent fever. Discontinuation of antibiotics while pediatric patients were still neutropenic was almost safe. However, physicians should note the risk factors of recurrent fever.

Mitigating Effects of 1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) on Hematopoietic Acute Radiation Syndrome after Total-Body Ionizing Irradiation in Mice.

Acute radiation syndrome (ARS) occurs as a result of partial- or whole-body, high-dose exposure to radiation in a very short period of time. Survival is dependent on the severity of the hematopoietic sub-syndrome of ARS. In this study, we investigated the mitigating effects of a lipid molecule, 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG), on the kinetics of hematopoietic cells, including absolute neutrophil count (ANC), red blood cells (RBCs) and platelet counts, in mice after gamma-ray total-body irradiation (TBI). Male and female BALB/c mice (11 weeks old) received a LD70/30 dose of TBI. PLAG significantly and dose-dependently attenuated radiation-induced mortality (P = 0.0041 for PLAG 50 mg/kg; P < 0.0001 for PLAG 250 mg/kg) and body weight loss (P < 0.0001 for PLAG 50 and 250 mg/kg) in mice. Single-fraction TBI sharply reduced ANC within 3 days postirradiation and maintained the neutropenic state (ANC < 500 cells/µl) by approximately 26.8 ± 0.8 days. However, administration of PLAG attenuated radiation-induced severe neutropenia (ANC < 100 cells/µl) by effectively delaying the mean day of its onset and decreasing its duration. PLAG also significantly mitigated radiation-induced thrombocytopenia (P < 0.0001 for PLAG 250 mg/kg) and anemia (P = 0.0023 for PLAG 250 mg/kg) by increasing mean platelet and RBC counts, as well as hemoglobin levels, in peripheral blood. Moreover, delayed administration of PLAG, even at 48 and 72 h after gamma-ray irradiation, significantly attenuated radiation-induced mortality in a time-dependent manner. When compared to olive oil and palmitic linoleic hydroxyl (PLH), only PLAG effectively attenuated radiation-induced mortality, indicating that it has a distinctive mechanism of action. Based on these preclinical observations, we concluded that PLAG has high potential as a radiation countermeasure for the improvement of survivability and the treatment of hematopoietic injury in gamma-ray-induced ARS.

Ethnic benign neutropenia: A phenomenon finds an explanation.

Ethnic benign neutropenia (ENP) is the most common form of neutropenia (NP) worldwide, if an absolute blood neutrophil count (ANC) of<1.5 G/L is used as definition. In 2009, ENP was associated with a gene variation in the ACKR1/DARC gene, the same variation that also confers the Duffy-null trait. In 2017, a novel mechanism for ENP was introduced, questioning if ENP is a true neutropenic state, when the body's total neutrophil count (TBNC) is concerned. Here, we summarize the current knowledge of ENP, asking (1) How well does the peripheral blood ANC predict the TBNC? (2) Can we improve methods for assessing TBNC? (3) Will estimates of TBNC predict infection propensity and reduce the need for further, costly workup?

BAFF-secreting neutrophils drive plasma cell responses during emergency granulopoiesis.

Prolonged infections or adjuvant usage can trigger emergency granulopoiesis (EG), leading to dysregulation in neutrophil blood counts. However, the impact of EG on T and B cell function remains largely unknown. In this study, to address this question, we used a mouse model of neutropenia and studied immune activation after adjuvant administration. The initial neutropenic state fostered an environment of increased dendritic cell activation and T cell-derived IL-17 production. Interestingly, neutropenic lysozyme 2-diphtheria toxin A mice exhibited striking EG and amplified neutrophil recruitment to the lymph nodes (LNs) that was dependent on IL-17-induced prostaglandin activity. The recruited neutrophils secreted a B cell-activating factor that highly accelerated plasma cell generation and antigen-specific antibody production. Reduction of neutrophil functions via granulocyte colony-stimulating factor neutralization significantly diminished plasma cell formation, directly linking EG with the humoral immune response. We conclude that neutrophils are capable of directly regulating T cell-dependent B cell responses in the LN.

Sepsis and neutropenia in hematological malignancies

The pre-existing inflammatory state influences the behavior of infection, a first peak of inflammation may be the risk factor during infection and predispose to a severe form of the disease [1,2]. This hypothesis is frequently accepted but has never been tested. Patients with hematological malignancies treated by chemotherapy in case of autologous stem cell transplantation (ASCT) are exposed to a neutropenic state: an abnormal low number of neutrophils. In the neutropenic patient, sepsis is more frequent than in the non-neutropenic patient. The severity of infection depends on many factors, particularly the pre-existing inflammatory state, the genetic factors, and the duration and the depth of neutropenia. In the literature, the factors involved in inflammation and infection are often confused. On the other hand, no predictive transcriptomic signature of sepsis was found. Our objective is to identify predictive genes that influence the outcomes of the infection in neutropenic patients.

Treatment of Acute Appendicitis in the Patients With Severe Neutropenia

When appendicitis occurs in neutropenic adult patients, clinicians must balance the timing and the risks of surgery. Urgent surgery may lead to high operative complications and mortality. This case report details the treatment of appendicitis in neutropenic patients with hematologic disease. Patient 1 was a 31 years old female with severe aplastic anemia and patient 2 was a 34 years old male with AML M6. Both patients' abdominal CT scan was suggestive of appendicitis. We prepared supportive care first, delayed surgery was successfully completed without acute or late complications. We suggest that, in patients in a neutropenic state, delayed elective operation is superior to urgent operation, except in the case of life-threatening complications such as peritonitis. J Med Cases. 2013;4(12):799-802 doi: https://doi.org/10.4021/jmc1286w

Pharmacokinetics of Tulathromycin in Healthy and Neutropenic Mice Challenged Intranasally with Lipopolysaccharide from Escherichia coli

Tulathromycin represents the first member of a novel subclass of macrolides, known as triamilides, approved to treat bovine and swine respiratory disease. The objectives of the present study were to assess the concentration-versus-time profile of tulathromycin in the plasma and lung tissue of healthy and neutropenic mice challenged intranasally with lipopolysaccharide (LPS) from Escherichia coli O111:B4. BALB/c mice were randomly allocated into four groups of 40 mice each: groups T-28 (tulathromycin at 28 mg/kg of body weight), T-7, T7-LPS, and T7-LPS-CP (cyclophosphamide). Mice in group T-28 were treated with tulathromycin at 28 mg/kg subcutaneously (s.c.) (time 0 h). The rest of the mice were treated with tulathromycin at 7 mg/kg s.c. (time 0 h). Animals in dose groups T-7-LPS and T7-LPS-CP received a single dose of E. coli LPS intranasally at -7 h. Mice in group T7-LPS-CP were also rendered neutropenic with cyclophosphamide (150 mg/kg intraperitoneally) prior to the administration of tulathromycin. Blood and lung tissue samples were obtained from 5 mice from each dose group at each sampling time over 144 h after the administration of tulathromycin. There were not statistical differences in lung tissue concentrations among groups T-7, T-7-LPS, and T7-LPS-CP. For all dose groups, the distribution of tulathromycin in the lungs was rapid and persisted at relatively high levels during 6 days postadministration. The concentration-versus-time profile of tulathromycin in lung tissue was not influenced by the intranasal administration of E. coli LPS. The results suggest that in mice, neutrophils may not have a positive influence on tulathromycin accumulation in lung tissue when the drug is administered during either a neutrophilic or a neutropenic state.

Evaluation of procalcitonin with liquid-phase binding assay in hematological malignancy

BackgroundTo determine procalcitonin (PCT) levels in blood, a newly analyzer based on liquid-phase binding assay (LBA) was developed (micro-total analysis system, μTAS). We evaluated analytical and clinical performance of this system in comparison with autoanalyzer based on chemiluminescence enzyme immunoassay (CLEIA), which is widely-used but takes much longer time than LBA. MethodsA total of 518 serum samples from 28 patients undergoing hematopoietic stem cell transplantation were analyzed. The correlation between the 2 methods and the comparison of the each area under the receiver operating characteristics curve (AUC) for distinguishing bacterial or fungal infections from other events were evaluated. ResultsThe minimum detection limit of serum PCT levels by LBA was 0.02ng/ml. There was an excellent correlation between the two methods in all samples (r2=0.99), the samples obtained on days of fever onset (r2=0.99), and the samples collected in neutropenic state (r2=0.99). The AUC for detection of bacterial or fungal infection on the onset of fever was not significantly different between LBA and CLEIA (0.80 by LBA and 0.82 by CLEIA, P=0.19). ConclusionsThe PCT measurement using LBA was well correlated with conventional method based on CLEIA and had enough clinical performance to detect bacterial or fungal infection in clinical setting.

A Switch in Regulatory T-Cell Memory Phenotype Is Associated with Poor Survival in Lower Risk Myleodysplastic Syndrome Patients

Abstract 1703Myleodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic diseases marked by various cytopenias including neutropenia and anemia. Hematologic improvement in response to T-cell depleting agents and immunosuppressants in a subset of MDS patients suggests that hematopoietic impairment may result from autoreactive T-cell activation. Conversely, suppression of the T-cell compartment may be permissible to the development of malignant myeloid clones. The suspicion that T-cell homeostatic balance may be disrupted in MDS has spawned numerous studies investigating mechanisms of immune suppression and autoimmune regulation. T-cell autoimmunity is regulated in part by regulatory T-cells (Tregs), which express T cell receptors (TCRs) that recognize self-antigens and function to maintain immune homeostasis. Indeed, higher numbers of Tregs have been found in higher risk MDS patients, and those MDS subtypes with higher blast percentages. However, the role of Tregs in lower risk patients is less clear, but may still represent an important component of pathogenesis in early disease.Because of the autoimmune nature of low risk MDS, we hypothesized that alterations in the Treg compartment may play a role in lower risk MDS disease progression. To address this, we analyzed Treg phenotype and numbers in MDS patients largely classified as low risk by the International Prognostic Scoring System (IPSS) and 41 age-matched controls using cell surface markers as analyzed by flow cytometry. Tregs were identified as CD3+CD4+CD25+CD127dim. The use of CD127 as a Treg marker was validated by intracellular staining with FoxP3. Naïve and memory phenotypes within the Treg compartment were analyzed using CD45RA and CD27 expression. Naïve Tregs (TregN) were characterized as CD45RA+CD27+, central memory Tregs (TregCM) as CD45RA−CD27+, and effector memory Tregs (TregEM) as CD45RA−CD27−. Two distinct subgroups of MDS patients were identified: one with elevated total numbers of Tregs, and a second with a marked shift in Treg memory phenotype away from the common TregCM phenotype and toward the rare TregEM phenotype. These two subgroups of patients were distinct from each other, and appeared to be independent of MDS WHO subtype, IPSS score, karyotype, neutropenic state, and thrombocytopenic state. MDS patients with a shift toward TregEMwere associated with anemia (p=0.0433). This association was not found in MDS patients with total increases in Treg numbers.Next, we sought to determine if there are differences in overall survival (OS) of MDS patients with either increased total numbers of Tregs or in patients with a shift toward TregEM phenotype. Patients with greater than 50 Tregs/μl did have reduced OS compared to patients with less Tregs, but this difference was not statistically significant (p=0.1387). In contrast, a highly significant difference was observed in MDS patients with a shift toward the TregEM phenotype (p=0.0200), with patients having greater than 2.5TregEM/μl displaying the worst OS (Figure 1). [Display omitted] Lastly, because an increased TregEM compartment is associated with reduced OS in MDS patients, we sought to compare the suppressive capacities of TregN, TregCM, and TregEM cells to better understand the functional consequences of Treg memory shift. CD4+ T-cells were isolated by negative selection, and then TregN, TregCM, and TregEM cells were sorted using CD45RA and CD27 expression. Conventional CD4+ responder cells were then labeled with Carboxyfluorescein succinimidyl ester (CFSE) and co-cultured with increasing ratios of each isolated Treg population. Cellular division in response to CD3/CD28 stimulation was measured 5 days later by analyzing CFSE dilution. TregCM appear to be the least suppressive, while TregN and TregEM cells were more potently suppressive. These results indicate that a shift in Treg phenotype toward TregEM may result in a more suppressive Treg compartment without obvious increases in total Treg numbers. Taken together, this data suggests that in lower risk MDS, the phenotypic makeup of the Treg compartment may be more important than total Treg numbers. In addition, this data suggests that increased TregEM cells may be a novel prognostic indicator in low risk MDS. Disclosures:Komrokji:Celgene: Honoraria, Research Funding, Speakers Bureau. List:Celgene: Consultancy.

Asacol®-induced Neutropenia Resolution Without the Use of Granulocyte Colony-stimulating Factor

We report a case of neutropenia and gram-negative septicemia in a 73-year-old male with ulcerative colitis. During the hospital course, medications were adjusted according to rare accounts of drug-induced neutropenia. While the substitution of propafenone for another antiarrhythmic brought about no change in the patient's absolute neutrophil count, the cessation of Asacol® (Warner Chilcott, Rockaway, NJ) was followed by a significant improvement in the neutropenic state. In fact, this neutrophil count continued to trend upward for months following. We thereby conclude that Asacol® carries the potential to induce neutropenia and that this reaction may be reversed in some patients solely by discontinuing the medication and without the aid of stimulating factors such as filgrastim.

Experimental study on development and lung injury in pneumonia under neutropenic condition

This study was performed to demonstrate the characteristic findings in pneumonia under neutropenic condition. The results were as follows. 1) After nebulizing Klebsiella pneumonia DT-S strains, the survival rate in the neutropenic mouse group rapidly decreased compared with that of the control group. 2) In the neutropenic state, a rapid decline of survival rate was demonstrated during the initial stage of infection. Bacteremia and endotoxemia developed earlier than in the healthy control group. 3) In neutropenic pneumonia, the neutrophil cell count in BALF was significantly lower than that in usual pneumonia. Consequently, a large number of bacteria grew in the alveolar spaces during the early period after inhalation. Neither inflammatory cell infiltration nor thickening of the alveolar wall was present; however, structural destruction of alveolar and vascular walls was found. 4) These pathological changes were also seen following intratracheal inoculation of some extracellular enzymes of Klebsiella pneumoniae DT-S into rabbit lung. However, no destruction of alveolar walls was observed after nebulizing the killed Klebsiella pneumoniae DT-S. It was suggested that the significant amount of enzymes produced by the bacteria growing in the alveoli caused tissue damage, especially in the neutropenic state. 5) Thus the typical inflammatory changes that occurred in the usual state, were not seen in neutropenic pneumonia, and a large number of bacteria grew in the alveoli. Marked tissue damage was caused by extracellular enzymes produced by bacteria. Consequently, bacteria entered the blood stream and bacteremia and endotoxemia developed. These processes observed in neutropenic pneumonia readily progressed to bacteremia of endotoxemia, which are more severe in this state.

Establishment of new severity ratings based on analysis of hospital‐acquired pneumonia

The Japanese Respiratory Society issued its first guidelines for the management of hospital-acquired pneumonia in adults in 2002. Pathological and severity ratings were investigated based on the results of a national multicenter survey of hospital-acquired pneumonia, and the new severity ratings shown below were established (Fig. II-1). Severity ratings in the 2002 guidelines were based mainly on markers that predicted the effectiveness of antimicrobial treatment. In the current revision, severity is rated using markers that predict the prognosis of patients. Five criteria were established as factors that predict prognosis: malignant tumour or immunocompromised status; decreased level of consciousness; FiO(2) >35% required to maintain SpO(2) >90%; age >or=70 years in men or >or=75 years in women; and oliguria or dehydration. Two criteria were established as factors specifying the severity of the pneumonia itself: CRP >or=200 mg/L and shadows infiltrating more than two-thirds the area of one lung on chest radiography. Patients who satisfy up to two of the five criteria above to predict prognosis are classified in the mild group (Group A) if they do not satisfy either of the two criteria specifying severity of pneumonia, or in the moderate group (Group B) if they satisfy one or both of those two criteria. Patients who satisfy three or fewer of the five criteria to predict prognosis are classified in the severe group (Group C). When the new severity ratings were applied to the results of the national multicenter survey of hospital-acquired pneumonia, the mortality rate was found to be 12.1% (101/834) in the mild group (Group A), 24.9% (69/277) in the moderate group (Group B) and 40.8% (98/240) in the severe group (Group C). Statistically-significant differences were seen between groups, and patient classification may be useful as an indicator of prognosis (Fig. II-2).

Infections in Patients With Aplastic Anemia

Infection is a major cause of death in patients with aplastic anemia (AA). There are differences between the immunocompromised state of a patient with AA and the patient who is neutropenic due to chemotherapy and this leads to a difference in the infections that they incur. Prolonged neutropenia is one of the largest risk factors for the development of infections with the invasive mycoses and bacteria. Recovery from neutropenia is directly related to survival, and supportive care plays a large role in protection while the patient is in a neutropenic state. The most common invasive mycoses include the Aspergillus species, Zygomycetes, Candida spp., and Fusarium spp. Bacterial infections that are seen in patients with AA include gram-positive coagulase-negative Staphylococcus species, Enterococcus, Staphylococus aureus, Clostridium spp., Micrococcus, alpha-hemolytic streptococci, Listeria monocytogenes, and Bacillus cereus. Gram-negative infections including gram-negative bacilli, Escherichia coli, Salmonella, Bacteroides fragilis, Klebsiella oxytoca, Klebsiella pneumonia, Aeromonas hydrophilia, Pseudomonas aeruginosa, and Vibrio vulnificus. Viral infections are much less common but include those that belong to the Herpesviridae family, community-acquired respiratory viral infection, and the viral hepatitides A, B, and C. Evidence of the parasite Strongyloides stercoralis has also been documented. This review discusses the major invasive fungal infections, bacterial pathogens, parasites, and viral infections that are found in patients with AA who are treated with immunosuppressive therapy. The specific immune impairment and current treatment parameters for each of these classes of infection will also be discussed.

Therapeutic effect of granulocyte colony-stimulating factor and cephem antibiotics against experimental infections in neutropenic mice induced by cyclophosphamide.

Effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) against severe infections in cyclophosphamide (CY)-induced neutropenic mice were investigated by its single use or by its combination with cephem antibiotics. Treatment with rhG-CSF increased the number of peripheral blood leucocytes and strikingly shortened the duration of the neutropenic state. Most of the regained population in the peripheral blood leucocytes were neutrophils. Functions of neutrophils, such as phagocytic activity, superoxide release, and expression of Mac-1 molecules, were remarkably enhanced by administration of rhG-CSF. When rhG-CSF was administered to CY-induced neutropenic mice before infection, protective effects against various kinds of bacteria were remarkable. On the other hand, such remarkable effects were not observed when rhG-CSF was administered after infections. However, even in the case of post-infectious treatment, a combination therapy of rhG-CSF with cephem antibiotics, particularly with Cefodizime (CDZM), showed a significant improvement in the survival rate and a decrease in the number of viable bacteria in the liver. These results suggest that a combination therapy of rhG-CSF with cephem antibiotics, especially with CDZM, is an efficient regime against severe infections in patients with neutropenia induced by a heavy anti-tumour chemotherapy.

Acute Sciatica: An Unusual Presentation of Extramedullary Relapse of Acute Lymphoblastic Leukemia

A 10-year-old boy who had been treated for acute lymphoblastic leukemia presented with persistent numbness of the left big toe and progressive pain of the ipsilateral lower leg. He had received allogeneic bone marrow transplantation 3 months after a testicular relapse. He was in hematologic remission at admission but as progressive swelling of his left leg continued, bone marrow relapse developed. A muscle biopsy revealed leukemic infiltrates in the surrounding muscles of the left sciatic nerve, and swelling of the nerve was found on a magnetic resonance imaging scan. His symptoms/signs subsided soon after reinduction chemotherapy. Unfortunately, he didn't survive because of a fungal sepsis that developed during the neutropenic state. This case represents a rare neurologic complication of what is currently an uncommon presentation for relapse of acute lymphoblastic leukemia, with acute sciatica and without coexisting epidural or leptomeningeal leukemia.

A Case of Fatal Multiple Cerebral Aspergillosis in a Patient with Acute Promyelocytic Leukemia during Complete Remission

Cerebral aspergillosis accounts for about 10% of all the cases of invasive aspergillosis. The brain is the only infected site in less than 10% of cases. The patients at high risk for of aspergillosis are immunocompromised patients such as those in a neutropenic state after chemotherapy, AIDS and etc. We experienced a case of cerebral aspergillosis in a patient with acute leukemia that was in complete remission. The patient visited our hospital's ER due to nasal bleeding, and then he was quickly diagnosed as having acute promyelocytic leukemia. After the first induction chemotherapy, he achieved a complete remission. Loss of consciousness developed on day 31 after chemotherapy. High signal intensity in the right temporooccipital lobe and multiple nodular lesions in both cerebral hemisphereswere observed on the brain MRI. Stereotaxic biopsy showed septate aspergillus hy phae in the brain specimen. Despite of the use of amphotericin B deoxycholate, the patient died of recurrent grand mal seizure and multiple

A Phase II Trial of Haptaplatin/5-FU and Leucovorin for Advanced Stomach Cancer

Heptaplatin (SKI-2053 R) is a new platinum analogue, with a better toxicity profile than cisplatin, and has antitumor activity even in cisplatin resistant cell lines. 5-fluoruracil (5-FU) has shown synergy with platinum compounds. This phase II trial was designed to determine the efficacy and toxicities of heptaplatin/ 5-FU (5-fluorouracil) for treating stomach cancer. Thirty-two patients with advanced, measurable gastric adenocarcinomas were enrolled in this trial. The treatment consisted of heptaplatin, 400 mg/m(2)/day (1 hour IV infusion), on day 1 and 5-FU, 800 mg/m(2)/day (12 hours IV infusion), on days 1 to 5. The cycles were repeated every 3 weeks. Of the 26 evaluable patients, 9 had partial responses and 1a complete response (overall response rate, 38%; 95% confidence interval, 19 approximately 57%). The median response duration was 23 weeks (range: 4 approximately 60 weeks). The median time to progression was 26 weeks (range: 3 approximately 68 weeks). The grades III-IV toxicities were mostly hematological toxicities: leucopenia was observed in 11 patients (35%) and thrombocytopenia 4 (13%). No definite neuropathy was observed. Grade I-II nephropathy was also noted: grade I high BUN/creatinine levels occurred in 5 patients (16%), grade II proteinuria 2 (6%), grade I proteinuria 5 (16%). Neutropenic fever developed in 5 patients (16%) and 1 died of pneumonia in a neutropenic state. This study suggests that the regimen of Heptaplatin/5-FU should be effective and have a favorable toxicity profile for the patients suffering with advanced stomach cancer.