Chemotherapy-related Infections Research Articles

Osteosarcoma and causes of death: A report of 1520 deceased patients from the Cooperative Osteosarcoma Study Group (COSS)

PurposeMost aspects of osteosarcoma have been addressed in detail, but there is no comprehensive analysis of deceased patients and causes of death. MethodsThe database of the Cooperative Osteosarcoma Study Group COSS (1980-03/31/2021; 4475 registered high-grade central osteosarcoma patients) was searched deaths from any cause. Affected patients were analyzed for demographic and baseline variables and disease-status at the time of demise. Deaths from causes other than osteosarcoma were analyzed in detail. ResultsA total of 1520 deceased patients were identified (median age (range) at osteosarcoma diagnosis 16 (2–78) years; 908 (59.7%) male, 612 (40.3%) female; primary tumor: extremities 1263 (83.1%), trunk 208 (13.7%), craniofacial 47 (3.1%) (site unknown 2); metastases at registration: absent 1.051 (69.1%), present 466 (30.7%) (3 no data). The median time from diagnosis to death was 2.22 (0.08–32.02) years. 1286 (84.6%) patients succumbed to osteosarcoma (370 without achieving complete remission, 488 first, 428 more than one recurrences), 146 (9.6%) to other, 88 (5.8%) to unknown causes. Chemotherapy-related infections (40), secondary malignancies (39), and perioperative complications (19) were among the most frequent potentially treatment-related causes, and high-dose methotrexate (19), doxorubicin (17), and ifosfamide (15) were the drugs most commonly held responsible. Patients with unknown causes of death had an unusually long median follow-up. ConclusionThe major cause of death of patients after osteosarcoma is this malignancy, mostly from one of its multiple relapses. However, almost 10% of fatalities are due to other documented causes. Some of these deaths may be preventable with the knowledge gained from comprehensive analyses such as this.

Analysis of Risk Factors Affecting the Chemotherapy-related Infections in Patients with ALL

To analyze the risk factors affecting the chemotherapy-related infections in patients with acute lympho-blastic leukemia (ALL). The clinical data of 102 patients with ALL from January 2014 to December 2018 were collected and retrospectively studies. The risk factors of chemotherapy-related infections were analyzed by univa-riate and multivariate logistic regression. A total of 386 courses of chemotherapy were completed, out of which the infection occurred in 201 course, with the infection rate of 52.07%, identified infection number was 215 case-times, including perianal infection of 13.95% (30/215), oral infection of 13.49% (29/215), blood flow infection of 1721% (37/215), lower respiratory tract infection of 37.21% (80/215), urinary infection of 3.26% (7/215), skin infection of 3.72% (8/215), digestive and intra abdominal infection of 9.30% (20/215), and other infections of 1.86 (4/215). Totally 88 strains of pathogenic bacteria were detected, including 29 Gram-positive bacteria (32.95%), 52 Gram-negative bacteria (59.09%) and 7 fungi (7.95%). Gram-positive bacteria mainly were Staphylococcus haemolyticus and Enterococcus faecium, susceptible to tegacycline, vancomycin and linezolid; Gram-negative bacteria mainly were Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae, susceptible to tegacycline, amikacin, piperacillin/tazobactam and imipenem; Candida was the dominant fungus. Living in an ordinart ward, neutrophil defi-ciency for more than 7 days after chemotherapy and incomplete remission were independent risk factors of related infections during the induction chemotherapy in ALL inpatients, and hospitalization time also closely related with chemo-therapy-related infections in ALL inpatients (P<0.05). Neutrophil deficiency for more than 7 days after chemotherapy was an independent risk factor of chemotherapy-related infections in ALL inpatients in the consolidation chemotherapy (P<0.05). Patients with ALL are prone to chemotherapeutic-related infections, and those who lack neutrophils for more than 7 days after chemotherapy and who do not reach complete remission are more prone to infection. Living in laminar flow ward and reducing hospitalization stay can help reduce the incidence of infection.

Analysis of Risk Factors Affecting the Chemotherapy-related Infections in Patients with ALL

To analyze the risk factors affecting the chemotherapy-related infections in patients with acute lympho-blastic leukemia (ALL). The clinical data of 102 patients with ALL from January 2014 to December 2018 were collected and retrospectively studies. The risk factors of chemotherapy-related infections were analyzed by univa-riate and multivariate logistic regression. A total of 386 courses of chemotherapy were completed, out of which the infection occurred in 201 course, with the infection rate of 52.07%, identified infection number was 215 case-times, including perianal infection of 13.95% (30/215), oral infection of 13.49% (29/215), blood flow infection of 1721% (37/215), lower respiratory tract infection of 37.21% (80/215), urinary infection of 3.26% (7/215), skin infection of 3.72% (8/215), digestive and intra abdominal infection of 9.30% (20/215), and other infections of 1.86 (4/215). Totally 88 strains of pathogenic bacteria were detected, including 29 Gram-positive bacteria (32.95%), 52 Gram-negative bacteria (59.09%) and 7 fungi (7.95%). Gram-positive bacteria mainly were Staphylococcus haemolyticus and Enterococcus faecium, susceptible to tegacycline, vancomycin and linezolid; Gram-negative bacteria mainly were Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae, susceptible to tegacycline, amikacin, piperacillin/tazobactam and imipenem; Candida was the dominant fungus. Living in an ordinart ward, neutrophil defi-ciency for more than 7 days after chemotherapy and incomplete remission were independent risk factors of related infections during the induction chemotherapy in ALL inpatients, and hospitalization time also closely related with chemo-therapy-related infections in ALL inpatients (P<0.05). Neutrophil deficiency for more than 7 days after chemotherapy was an independent risk factor of chemotherapy-related infections in ALL inpatients in the consolidation chemotherapy (P<0.05). Patients with ALL are prone to chemotherapeutic-related infections, and those who lack neutrophils for more than 7 days after chemotherapy and who do not reach complete remission are more prone to infection. Living in laminar flow ward and reducing hospitalization stay can help reduce the incidence of infection.

Assessment of Antimicrobial Prescription Pattern among Paediatric Cancer Patients with Febrile Neutropenia

Febrile neutropenia (FN) is the most common haematological toxicity associated with cytotoxic chemotherapy. Individual studies are available, but national estimates on FN are required. To describe chemotherapy-induced neutropenia, its associated infection-causing organisms, and the antimicrobials prescribed, a prospective cum retrospective study was conducted for a period of 9 months, which included 50 paediatric cancer patients less than 18 years. Patients having an absolute neutrophil count (ANC) less than 1500/mm3, having body temperature of above 38.5 °C, and receiving anti-infectives as prophylaxis were included. Patient demographic details, presenting complaints, absolute neutrophil count, and laboratory findings were noted in a patient proforma. Out of the overall 584 episodes of CIN, 188 episodes (32.2%) were of febrile neutropenia. Majority of patients were boys (70%), aged between 1 and 6 years (66%), and diagnosed with acute lymphoblastic leukemia (64%). The mean ANC was 765.6 ± 235.7 × 109/l. From a total of 188 episodes of FN, in 179 episodes, patients had ANC < 500 mm3, whereas in 9 episodes, patients had ANC < 100 mm3. The predominant site of infection in these patients was bloodstream (27%), followed by urine (6%) and stool (1%). From the 51 episodes of blood culture done, the highest reported was of Staphylococcus species (49.01%). Anti-infective combinations of piperacillin/vancomycin (56%) and piperacillin/amikacin (42%) were given. Patients with positive fungal growth received Inj. amphotericin (18%) as therapy. Majority of the children undergoing chemotherapy, diagnosed with ALL, had FN. Low ANC led them susceptible to various bacterial and fungal infections. Introduction to antimicrobials and antifungals have all contributed to decreasing chemotherapy-related infections.

Risk of infection among patients with non-metastatic solid tumors or non-Hodgkin's lymphoma receiving myelosuppressive chemotherapy and antimicrobial prophylaxis in US clinical practice.

Purpose Guidelines generally do not recommend oral antimicrobials for prophylaxis against chemotherapy-related infections in patients with solid tumors. Evidence on antimicrobial prophylaxis use, and associated chemotherapy-related infection risk, in US clinical practice is limited. Methods A retrospective cohort design and data from two US private healthcare claims repositories (2008-2011) were employed. Study population included adults who received myelosuppressive chemotherapy for non-metastatic cancer of the breast, colon/rectum, or lung, or for non-Hodgkin's lymphoma. For each subject, the first chemotherapy course was characterized, and within the first course, each chemotherapy cycle and chemotherapy-related infection episode was identified. Use of prophylaxis with oral antimicrobials and colony-stimulating factors in each cycle also was identified. Results A total of 7116 (22% of all) non-metastatic breast cancer, 1833 (15%) non-metastatic colorectal cancer, 1999 (15%) non-metastatic lung cancer, and 1949 (21%) non-Hodgkin's lymphoma patients received antimicrobial prophylaxis in ≥1 cycle. Mean number of antimicrobial prophylaxis cycles during the course among these patients was typically <2, with little difference across cancers and chemotherapy regimens. Fluoroquinolones were the most commonly received class of antimicrobials, accounting for 20%-50% all antimicrobials administered. Among subjects who received first-cycle antimicrobial prophylaxis, chemotherapy-related infection risk in that cycle ranged from 3% to 6% across cancer types. Among patients who received first-cycle antimicrobial prophylaxis and developed chemotherapy-related infections, 38%-67% required inpatient care. Chemotherapy-related infection risk in subsequent cycles with antimicrobial prophylaxis was comparable. Conclusion The results of this study suggest that use of antimicrobial prophylaxis during myelosuppressive chemotherapy is far from uncommon in clinical practice. The results also suggest that an important minority of cancer chemotherapy patients receiving antimicrobial prophylaxis still develop serious infection requiring hospitalization.

Risk of Infection Among Patients with Non-Metastatic Solid Tumors or Non-Hodgkin's Lymphoma Receiving Myelosuppressive Chemotherapy and Antimicrobial Prophylaxis in US Clinical Practice

BackgroundClinical practice guidelines recommend oral antimicrobials (AMB)—principally, the fluoroquinolones—for prophylaxis against chemotherapy-related infections (CRI) in intermediate- and high-risk patients undergoing myelosuppressive chemotherapy. Available evidence on the risk of CRI among patients with non-metastatic solid tumors or non-Hodgkin's lymphoma (NHL) receiving myelosuppressive chemotherapy and AMB prophylaxis in US clinical practice is currently limited. MethodsA retrospective cohort design and data from two US private healthcare claims repositories (2008-2011) were employed. The study population included adult patients who received myelosuppressive chemotherapy for non-metastatic cancer of the breast, colon/rectum, or lung, or for NHL. For each study subject, the first qualifying chemotherapy course, and each chemotherapy cycle and episode of CRI within the course, were identified. Use of prophylaxis with oral AMB agents—including antibacterial, antifungal, and antiviral drugs—as well as colony-stimulating factors (CSF) in each cycle also was identified. CRI was ascertained based on admission to an acute-care inpatient facility with a corresponding diagnosis (1⁰ or 2⁰) or an ambulatory encounter with a corresponding diagnosis and evidence of AMB therapy. Risk of CRI was evaluated during chemotherapy cycles in which patients received AMB prophylaxis; only results for the most frequently observed regimen for each tumor type are reported herein. ResultsThe most common regimens—by tumor—were: breast cancer, docetaxel + cyclophosphamide (“TC”, 29% of 34,876); colorectal cancer, folinic acid (leucovorin) + fluorouracil + oxaliplatin (“FOLFOX”, 34% of 14,334); lung cancer, paclitaxel + carboplatin (“PC”, 25% of 17,334); and NHL, cyclophosphamide + doxorubicin + vincristine + prednisone with Rituxan (“CHOP-R”, 45% of 9,612). Across these four regimens, use of AMB prophylaxis in cycle 1 ranged from 3.5-8.6%; fluoroquinolones were the most common agents administered (range, 27.1-43.5%) (Table 1). Use of CSF prophylaxis in cycle 1 ranged from 10.4-61.2%. Among subjects who received first-cycle AMB prophylaxis, risk of CRI in that cycle ranged from 1.2-7.5%; among these subjects, 45-68% had CRI in the inpatient setting (Table 2). CRI risks in subsequent cycles with AMB prophylaxis were generally comparable. ConclusionAmong patients with non-metastatic solid tumors or NHL receiving common myelosuppressive chemotherapy and AMB prophylaxis in US clinical practice, risk of CRI ranged from 1.2-8.6% in cycles in which AMB prophylaxis was administered. [Display omitted] [Display omitted] Disclosures:Weycker:Amgen Inc.: Research Funding. Chandler:Amgen Inc.: Employment, Equity Ownership. Barron:Amgen Inc.: Employment, Equity Ownership. Xu:Amgen Inc.: Employment, Equity Ownership. Wu:Amgen Inc.: Research Funding. Girardi:Amgen Inc.: Employment, Equity Ownership. Edelsberg:Amgen Inc.: Research Funding. Lyman:Amgen Inc.: PI on a research grant to Duke University Other.

Cancer in liver transplant recipients: Management and outcomes

To investigate the management and cancer outcomes of liver transplant recipients. An audit of all liver transplant recipients from a single liver transplant center from January 1991 to March 2010. Data were obtained from case notes, cancer registry and clinical databases. 198 transplant recipients were identified and 49 (25%) were confirmed as having post-transplantation malignancies. Of these 32 (16%) patients developed skin malignancies and 17 (9%) developed post-transplant non-skin malignancies. All skin malignancies had local involvement only and none of the patients with skin malignancies developed nodal or distant metastases. All were managed with local treatment. Of those with non-cutaneous malignancies, four were managed with local therapy alone, two with immunosuppression reduction, seven with chemotherapy, including two with chemoradiotherapy, one with a targeted agent and three with supportive care only. None of the patients who were treated with chemotherapy for non-skin malignancies were able to complete the full prescribed dose of chemotherapy as a result of chemotherapy-related toxicities. Of those treated with chemotherapy one died of hepatic failure and one of chemotherapy-related infection. Liver transplant recipients are at high risk of cancer. Outcomes for liver transplant recipients with post-transplant malignancy are excellent if detected when they are amenable to local therapy alone. Outcomes are poor, with high rates of treatment-associated toxicity, in patients who require systemic therapy. Further research is required to enable the development of guidelines for the safe administration of systemic treatment in this group.

Abstract P3-08-05: Title: Copy number variation and risk of chemotherapy-related infection.

Abstract Background: Copy-number variations (CNVs) are DNA changes that result in regions of the genome being either duplicated (copy number gains) or deleted (copy number losses). CNVs have been identified in 12% of the human genome. Although CNVs do not appear to have a major role in disease susceptibility, it is known that they are involved in drug metabolism, toxicity and response. Infection is a common dose and/or treatment limiting chemotherapy-related toxicity. Infections can be a major cause of morbidity and mortality. Although a limited number of studies have investigated the association of single nucleotide polymorphisms (SNPs) with severity of infection, no studies so far have identified CNV associations with chemotherapy-related infection. In a non-oncological setting, CNVs have been noted to be associated with altered risk of certain types of infections and severe sepsis. This study aims to evaluate whether CNV are associated with the risk of chemotherapy-related infection in a genome wide association study (GWAS) of breast cancer patients recruited to clinical trials and treated with chemotherapy regimens including paclitaxel, epirubicin, cyclophosphamide, gemcitabine, 5fluorouracil and methotrexate. Method: DNA from blood and saliva samples were collected as part of the pharmacogenetics GWAS, PGSNPS. Chemotherapy-related infection was assessed using the NCI Common Toxicity Criteria (CTC). Patients (n = 1921 samples) were classified as cases (NCI CTC grades 2–4) or as controls (NCI CTC grades 0–1). The Affymetrix SNP6.0 array, which contains more than 946,000 probes for the detection of CNVs and more than 906,600 SNPs, was used as the copy number estimation platform. DNA was segmented using DNAcopy (circular binary segmentation). CNVs were called based on their median and standard deviation. Log-ratios larger than the median plus 2 times the standard deviation were considered gains and log-ratios with values smaller than 2.5 times the standard deviation were considered as losses. Only regions with a copy number alteration present in at least a 10% of the samples were considered for the analysis. Fisher's exact test was performed on each of these regions and the variable ‘infection’. 2-side p-values were obtained and adjusted using Benjamin-Hochberg correction. Results: One CNV region (frequency of gain 0.16) showed an association with increased risk of infection (Odds Ratio=1.79, 95% Confidence Interval [1.34–2.40], P = 6.37 × 10−5). Five other CNV regions demonstrated copy number gains and three CNV regions showed copy number losses that were associated with an increased risk of infection (P = 10−4). All regions had a frequency of gain or loss &amp;gt; 0.10 and were therefore not rare variants. Conclusion: These data suggest that CNVs may play a role in increased risk of chemotherapy-related toxicity. The most significant CNVs associated with infection are currently undergoing validation using an independent cohort of adjuvant breast cancer patients with similar exposure to chemotherapy and comparable documentation of chemotherapy-related infection. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-08-05.

M-ficolin in children with cancer

Objectives M-ficolin (ficolin-1) is a complement-activating pattern-recognition molecule structurally related to mannan-binding lectin. It is produced by monocytes and neutrophils, and is found in serum. Its biological role is largely unknown. We assessed M-ficolin concentration in serum from pediatric cancer patients. The aim of this study was to explore association of M-ficolin with clinical and hematological parameters, and to investigate whether the risk of chemotherapy-related infections was related to M-ficolin concentrations in serum. Methods M-ficolin was measured by time-resolved immunofluorometric assay in serum taken at cancer diagnosis and was correlated with peripheral blood counts and bone marrow examinations performed at the same time. Results Median M-ficolin concentration in 94 children with cancer was 1.6 μg/mL (interquartile range, 0.57–2.7; range, 0.055–25.8), and was not different from age-matched controls (median, 1.7 μg/mL; p = 0.92). M-ficolin was strongly associated with absolute counts of neutrophils (Spearman's rho, 0.45; 95%-CI, 0.26–0.65; p < 0.001), monocytes (0.34; 0.12–0.55; p < 0.001), and thus phagocytes (0.42; 0.20–0.63; p < 0.001) in peripheral blood. Similarly, M-ficolin correlated strongly with neutrophils (0.36; 0.14–0.59; p = 0.002) and phagocytes (0.31; 0.08–0.54; p = 0.009) in bone marrow. Low serum M-ficolin (≤0.5 μg/mL) was not associated with an increased incidence of fever in neutropenia during chemotherapy (multivariate Poisson rate ratio, 1.04; 95%-CI, 0.68–1.60; p = 0.85). Conclusions The concentration of M-ficolin in serum from children with cancer was strongly associated with neutrophil and monocyte counts in blood and bone marrow. These results suggest that M-ficolin concentrations in serum reflect the pool of phagocytes.

H-ficolin serum concentration and susceptibility to fever and neutropenia in paediatric cancer patients

H-ficolin (Hakata antigen, ficolin-3) activates the lectin pathway of complement similar to mannose-binding lectin. However, its impact on susceptibility to infection is currently unknown. This study investigated whether the serum concentration of H-ficolin at diagnosis is associated with fever and neutropenia (FN) in paediatric cancer patients. H-ficolin was measured by time-resolved immunofluorometric assay in serum taken at cancer diagnosis from 94 children treated with chemotherapy. The association of FN episodes with H-ficolin serum concentration was analysed by multivariate Poisson regression. Median concentration of H-ficolin in serum was 26 mg/l (range 6-83). Seven (7%) children had low H-ficolin (< 14 mg/l). During a cumulative chemotherapy exposure time of 82 years, 177 FN episodes were recorded, 35 (20%) of them with bacteraemia. Children with low H-ficolin had a significantly increased risk to develop FN [relative risk (RR) 2.24; 95% confidence interval (CI) 1.38-3.65; P = 0.004], resulting in prolonged duration of hospitalization and of intravenous anti-microbial therapy. Bacteraemia occurred more frequently in children with low H-ficolin (RR 2.82; CI 1.02-7.76; P = 0.045). In conclusion, low concentration of H-ficolin was associated with an increased risk of FN, particularly FN with bacteraemia, in children treated with chemotherapy for cancer. Low H-ficolin thus represents a novel risk factor for chemotherapy-related infections.

Deficiency of Mannose-Binding Lectin-Associated Serine Protease-2 Associated With Increased Risk of Fever and Neutropenia in Pediatric Cancer Patients

Mannose-binding lectin-associated serine protease-2 (MASP-2) is an essential component of the lectin pathway of complement activation. MASP-2 deficiency is common because of genetic polymorphisms, but its impact on susceptibility to infection is largely unknown. The aim of the present study was to determine whether children with cancer and MASP-2 deficiency develop more frequent or more severe episodes of fever and severe chemotherapy-induced neutropenia (FN). Serum MASP-2 was measured by enzyme-linked immunosorbent assay at the time of diagnosis in children treated with chemotherapy for cancer. Association of FN episodes with MASP-2 concentration was analyzed using Poisson regression accounting for chemotherapy intensity and duration. Median MASP-2 in 94 children was 527 ng/mL (interquartile range, 367-686). Nine (10%) children had MASP-2 deficiency (<200 ng/mL). During a cumulative chemotherapy exposure time of 82 years, 177 FN episodes were recorded. MASP-2 deficient children had a significantly increased risk of developing FN (multivariate risk ratio, 2.08; 95% confidence interval, 1.31-3.21; P = 0.002), translating into significantly prolonged cumulative duration of hospitalization and of intravenous antimicrobial therapy. They experienced significantly more episodes of FN without a microbiologically defined etiology, and there was a trend toward more frequent episodes of FN with bacteremia. In this study, MASP-2 deficiency was associated with an increased risk of FN in children treated with chemotherapy for cancer. MASP-2 deficiency represents a novel risk factor for chemotherapy-related infections.

Effects of G-CSF and GM-CSF on Chemotherapy-Related Mortality and Infection

Cytokine supportive care with the colony-stimulating factors G-CSF (granulocyte colony–stimulating factor) or GM-CSF (granulocyte-macrophage colony–stimulating factor) is used widely for patients who are undergoing chemotherapy or stem-cell transplantation. Shorter duration of neutropenia and lower infection rates have been reported with CSF use, but the effect of CSFs on rates of serious infection and overall mortality has been unclear because of the small size of individual studies. Researchers evaluated all-cause and infection-related mortality rates in a comprehensive meta-analysis of randomized controlled trials in which G-CSF or GM-CSF was compared with placebo or no CSF treatment in chemotherapy or stem-cell–transplantation patients. Studies were …

Chemotherapy‐related infections in patients with multiple myeloma: associations with mannan‐binding lectin genotypes

To study a possible association between mannan-binding lectin genotypes and severe infections in patients with multiple myeloma receiving moderate strength induction chemotherapy. Chemotherapy-related infections were identified retrospectively using clinical records and database files. Mannan-binding lectin genotypes were identified with polymerase chain reaction on stored samples of stem cells or formalin-fixed paraffin-embedded bone marrow biopsies. We included 138 myeloma patients. In five patients, data were incomplete, and 133 patients were analysed. Eighty-eight patients were homozygous for wild-type MBL2 (AA) and forty-five patients were heterozygous or homozygous for variant genotypes (AO/OO). A total of 390 chemotherapy cycles were reviewed. Common Toxicity Criteria grades 3 and 4 infections in general were seen in relation to 104 cycles and were not more common in patient with variant MBL2 (P = 0.90). Septicaemia was seen after 10% of chemotherapy cycles in AA patients vs. 15% in AO/OO patients (P = 0.15). In multi-variate analyses, we found indication of a reduced risk of septicaemia in AA patients [OR 0.27 (0.08-0.90), P = 0.03], after first chemotherapy cycle, but reduction of the risk including all cycles was not significant. A similar trend was seen for grades 3 and 4 infections in general. During induction chemotherapy in patients with multiple myeloma, a general protective effect of wild-type MBL2 against chemotherapy-related infections was not apparent in this study. However, we found indications of a reduced occurrence of septicaemia in patients with wild-type compared with variant MBL2. Further studies in larger cohorts of patients are relevant.

Neulasta (pegfilgrastim): a once-per-cycle option for the management of chemotherapy-induced neutropenia

Neutropenia is a significant hematologic complication induced by cytotoxic chemotherapy. The clinical consequences of chemotherapy-induced neutropenia are often severe and can be potentially life-threatening. Patients who develop febrile neutropenia often need to be hospitalized, reducing their quality of life and increasing costs. Neutropenia can also compromise the ability to deliver chemotherapy at the full dose and on schedule. To help prevent the occurrence of neutropenia, patients with a high risk of developing chemotherapy-related infections may be given prophylactic colony-stimulating factors. Filgrastim is a recombinant human granulocyte colony-stimulating factor that has been widely used (in over 3 million patients) for over 12 years in the management of neutropenia. Pegfilgrastim is an approved, long-acting, next generation of granulocyte colony-stimulating factor that has similar clinical benefits to filgrastim but has novel pharmacokinetic properties. Pegfilgrastim shows at least comparable safety and efficacy to filgrastim, with the added benefit of simplified once-per-chemotherapy-cycle dosing. In addition, two randomized, controlled pivotal trials have shown that a single dose of pegfilgrastim given once per cycle led to a lower observed incidence of febrile neutropenia following myelosuppressive chemotherapy, compared with daily injections of filgrastim. Clinical trials are currently expanding the clinical experience with pegfilgrastim in a variety of solid tumors and hematologic malignancies. In addition to prevention of chemotherapy-induced neutropenia in 21- and 28-day regimens, future studies are examining the suitability of pegfilgrastim in dose-dense therapy and other cancer settings.

No strong relationship between mannan binding lectin or plasma ficolins and chemotherapy-related infections.

Chemotherapy causes neutropenia and an increased susceptibility to infection. Recent reports indicate that mannan-binding lectin (MBL) insufficiency is associated with an increased duration of febrile neutropenia and incidence of serious infections following chemotherapy for haematological malignancies. We aimed to confirm or refute this finding and to extend the investigation to the plasma ficolins, P35 (L-ficolin) and the Hakata antigen (H-ficolin). MBL, L-ficolin and H-ficolin were measured in 128 patients with haematological malignancies treated by chemotherapy alone or combined with bone marrow transplantation. Protein concentrations were related to clinical data retrieved from medical records. MBL concentrations were elevated compared with healthy controls in patients who received chemotherapy, while L-ficolin concentrations were decreased and H-ficolin levels were unchanged. There was no correlation between MBL, L-ficolin or H-ficolin concentration and febrile neutropenia expressed as the proportion of neutropenic periods in which patients experienced fever, and there was no relation between abnormally low (deficiency) levels of MBL, L-ficolin or H-ficolin and febrile neutropenia so expressed. Patients with MBL < or =0.1 microg/ml had significantly more major infections than no infections within the follow-up period (P<0.05), but overall most patients had signs or symptoms of minor infections irrespective of MBL concentration. Neither L-ficolin nor H-ficolin deficiencies were associated with infections individually, in combination or in combination with MBL deficiency. MBL, L-ficolin and H-ficolin, independently or in combination, did not have a major influence on susceptibility to infection in these patients rendered neutropenic by chemotherapy. These results cast doubt on the potential value of MBL replacement therapy in this clinical context.

188 Chemotherapy-related infections in myelodysplastic syndromes (MDS) and acute myeloid leukemia secondary to MDS (sAML). A study of 27 patients

188 Chemotherapy-related infections in myelodysplastic syndromes (MDS) and acute myeloid leukemia secondary to MDS (sAML). A study of 27 patients