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Severe Neutropenia (severe + neutropenia)
Selected AbstractsPulmonary complications in chronic lymphocytic leukemiaCANCER, Issue 9 2003Shahid Ahmed M.D. Abstract BACKGROUND Although pulmonary complications account for significant morbidity and mortality in patients with chronic lymphocytic leukemia (CLL), to the authors' knowledge there are sparse data available in published literature. The authors evaluated pulmonary complications in patients with CLL and identified prognostic variables that predict hospital mortality in these patients. METHODS Clinical data were analyzed retrospectively from patients with CLL who required hospitalization for a respiratory illness at a tertiary care institution from January 1993 to December 2001. A logistic regression analysis with a backward elimination procedure was carried out to determine prognostic variables that predict hospital mortality. RESULTS There were 110 patients who were admitted on 142 occasions with a pulmonary complication. The median age was 75 years (range, 43,97 years), and the male:female ratio was 1.7:1.0. Among 142 admissions, 68% were high risk according to the Rai criteria, 68% of patients admitted had received prior therapy for CLL, and 35% had received treatment within 3 months of admission. The most common pulmonary complications were pneumonias (75%), malignant pleural effusion/and or lung infiltrate due to CLL (9%), pulmonary leukostasis (4%), Richter transformation or nonsmall cell lung carcinoma (3%), and upper airway obstruction (2%). Forty-four of 110 patients (40%) died. In multivariate analysis, admission absolute neutrophil counts , 0.5 × 109/L (odds ratio, 4.6; 95% confidence interval [95% CI], 1.3,16.6) and blood urea nitrogen (BUN) levels , 20 mg/dL (odds ratio, 3.0; 95% CI, 1.1,8.3) were correlated significantly with mortality. CONCLUSIONS Pneumonia was the major pulmonary complication in hospitalized patients with CLL. Severe neutropenia and high BUN levels were correlated significantly with increased mortality. Cancer 2003. © 2003 American Cancer Society. [source] Oxford experience with neoadjuvant chemotherapy and surgical resection for esophageal adenocarcinomas and squamous cell tumorsDISEASES OF THE ESOPHAGUS, Issue 3 2008P. M. Safranek SUMMARY., The Medical Research Council trial for oesophageal cancer (OEO2) trial demonstrated a clear survival benefit from neoadjuvant chemotherapy in resectable esophageal carcinoma. Since February 2000 it has been our practice to offer this chemotherapy regime to patients with T2 and T3 or T1N1 tumors. We analyzed prospectively collected data of patients who received neoadjuvant chemotherapy prior to esophageal resection under the care of a single surgeon. Complications of treatment and overall outcomes were evaluated. A total of 194 patients had cisplatin and 5-fluorouracil prior to esophageal resection. Six patients (5.7%) had progressive disease and were inoperable (discovered in four at surgery). During chemotherapy one patient died and one perforated (operated immediately). Complications including severe neutropenia, coronary artery spasm, renal impairment and pulmonary edema led to the premature cessation of chemotherapy in 12 patients (6.2%). A total of 182 patients with a median age of 63 (range 30,80), 41 squamous and 141 adenocarcinomas underwent surgery. Operations were 91 left thoracoabdominal (50%), 45 radical transhiatal (25%), 40 Ivor-Lewis (22%) and six stage three (3%), and 78.6% had microscopically complete (R0) resections. Median survival was 28 months with 77.3% surviving for 1 year and 57.7% for 2 year. In hospital mortality was 5.5% and anastomotic leak rate 7.7%. A radical surgical approach to the primary tumor in combination with OEO2 neoadjuvant chemotherapy has led to a high R0 resection rate and good survival with acceptable morbidity and mortality. [source] Invasive pulmonary aspergillosis resulting in respiratory failure during neutrophil recovery from postchemotherapy neutropenia in three patients with acute leukaemiaJOURNAL OF INTERNAL MEDICINE, Issue 2 2002T. Takuma Abstract.,Takuma T, Okada K, Uchida Y, Yamagata A, Sawae Y (Kyushu University Graduate School of Sciences, Fukuoka, Japan; University of California, CA, USA; and Shin-kokura Hospital, Fukuoka, Japan). Invasive pulmonary aspergillosis resulting in respiratory failure during neutrophil recovery from postchemotherapy neutropenia in three patients with acute leukaemia (Case Report). J Intern Med 2002; 252: 173,177. Respiratory failure is a severe complication of invasive pulmonary aspergillosis (IPA). Its pathogenesis is not well understood. We herein describe three cases of subacute respiratory failure that occurred during the recovery phase of neutropenia following induction chemotherapy for acute leukaemia with IPA. In each case, severe neutropenia (19,85 days), high-grade fever, severe anaemia, the use of granulocyte-colony-stimulating factor and increasing infusion volume were noted. As the neutrophil count was recovering, the shadows on the chest X-ray expanded with progressing hypoxia. We should pay attention to the respiratory failure during the recovery phase of neutropenia in patients with IPA. [source] Clinicopathologic presentations of dermatomycoses in cancer patientsJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 8 2008P Quatresooz Abstract Many of the skin fungal infections in cancer patients may look similar to those infections in non-cancer patients. However, in some cases, they become more extensive and even life threatening. Prolonged and severe neutropenia is the main risk factor for the dramatic issue of fungal infections. The dermatomycoses in cancer patients can be classified in four broad groups: primary superficial dermatophytoses, primary superficial yeast infections, opportunistic mold infections with distinct potential for dissemination and secondary cutaneous manifestations of fungaemia. Occasionally, more than one fungus are found inside a given skin lesion. A special condition is represented by the mycotic colonization of mucosal squamous cell carcinomas. Angio-invasion by fungi accounts for the frequency of disseminated infections prevailing in immunocompromised cancer patients. In case of skin involvement, the dermatologist may assist by recognizing subtle semiological signs and performing biopsies for swift histological examination, molecular biology and/or culture. [source] Unrelated cord blood transplantation in children with severe congenital neutropeniaPEDIATRIC TRANSPLANTATION, Issue 6 2009M. Akif Yesilipek Abstract:, SCN is an inherited hematological disorder with severe neutropenia and recurrent infections. Although there are some reports that recombinant rhG-CSF improves clinical outcome, allogeneic HSCT appears to be the only curative treatment for these patients. We report here two children with SCN successfully treated by CBT from unrelated donors. They were refractory to rhG-CSF treatment and have no identical family donor. Bu + CY were given as conditioning. Case 1 and Case 2 received 6/6 and 5/6 HLA-matched unrelated umbilical cord blood, respectively. The number of infused nucleated cells was 6, 18 × 107/kg and CD34+ cell number was 3, 74 × 105/kg in Case 1. Those cell numbers were 8, 8 × 107/kg and 5, 34 × 105/kg for Case 2, respectively. Neutrophil/platelet engraftments were 45/49 days in Case 1 and 24/36 days in Case 2. Grade II cutaneous acute GVHD was seen in Case 2 that was treated successfully with prednisolone. Both patients are well with normal hematological findings and full donor chimerism for post-transplant 20 and 24 months, respectively. We conclude that UCB can be considered as a safe source of stem cell in patients with SCN who need urgent HSCT. [source] Efficacy and safety of rituximab in adults' warm antibody autoimmune haemolytic anemia: Retrospective analysis of 27 cases,AMERICAN JOURNAL OF HEMATOLOGY, Issue 3 2009Guillaume Bussone To better assess the efficacy and safety of rituximab in adults' warm antibody autoimmune hemolytic anemia (wAIHA), we conducted a retrospective study including 27 adults (mean age 49.7 ± 21 years) with either primary (n = 17) or secondary (n = 10) wAIHA. On average, the patients received 2.1 ± 1.4 treatment lines before rituximab and six had undergone splenectomy. Five patients were resistant to corticosteroids, 16 had a corticosteroid-dependent wAIHA and six had relapsed after an initial remission. Overall, 25/27 (93%) patients achieved an initial response from rituximab (eight complete responses and 17 partial responses). During a mean follow-up of 20.9 months after rituximab, five of the responders relapsed, three of whom were successfully retreated with rituximab. Two mild infusion-related-reactions occurred, one patient had a rituximab-related severe neutropenia and one case of pneumocystis jiroveci pneumonia occurred in a severely immunocompromized patient. In conclusion, rituximab seems highly effective and relatively safe in adults with steroid-resistant or steroid-dependent wAIHA. Am. J. Hematol. 2009. © 2008 Wiley-Liss, Inc. [source] The low frequency of defective TPMT alleles in Turkish population: A study on pediatric patients with acute lymphoblastic leukemia,AMERICAN JOURNAL OF HEMATOLOGY, Issue 10 2007Tugba Boyunegmez Tumer 6-Mercaptopurine (6MP) is an essential anticancer drug used in the treatment of childhood acute lymphoblastic leukemia (ALL). Thiopurine methyltransferase (TPMT) polymorphisms are the major determinants of interindividual differences in the severe toxicity or efficacy of 6MP. Four variant alleles, TPMT*2, TPMT*3A, TPMT*3B, and TPMT*3C, are responsible over the 80% of low or undetectable enzyme activity. The frequencies of these variants were investigated among 106 children with ALL in Turkish population. TPMT*3A and TPMT*3C were the only deficiency alleles detected in Turkish population with an allele frequency of 0.9% for both. While *3C allele frequency in Turkish population was found to be very similar to Asian and other Caucasian populations, *3A allele frequency was significantly (P < 0.05) lower. So far, studies showed that the genetic polymorphisms of other drug metabolizing enzymes like CYP2E1, CYP1A1, GSTM1/ T1 in Turkish population were similar to Caucasian populations. However, we found that the distribution of TPMT polymorphisms in Turkish population was significantly lower than those in other Caucasians like British, French, and Italian whereas the distributions of TPMT variants were found to be very similar to Kazak population which is also Caucasian in ethnic origin. In this study, the clinical histories of the patients in the sample population were also examined, retrospectively. The patients with heterozygous or homozygous mutant genotypes had developed severe neutropenia and infection during 6MP therapy. The study provides the first data on the frequency of common TPMT variants in the Turkish population, based on analysis of pediatric patients with ALL. Am. J. Hematol. 82:906,910, 2007. © 2007 Wiley-Liss, Inc. [source] Predictors of Toxicity and Toxicity Profile of Adjuvant Chemotherapy in Elderly Breast Cancer PatientsTHE BREAST JOURNAL, Issue 4 2009Praveen Garg MD Abstract:, Women older than 70 years have been underrepresented in breast cancer adjuvant chemotherapy trials due to concerns about toxicity, safety and tolerance of chemotherapy. The aim of our study was to assess the tolerance of chemotherapy in older women with breast cancer and determine patterns of toxicity including the impact of age, chemotherapy regimen, functional status and comorbid conditions on this toxicity. We retrospectively reviewed the charts of early stage (stages 1 and 2) breast cancer patients older than 70 years from 1998 to 2004. A total of 62 patients, with mean age of 74.3 years, were identified. Chemotherapy was completed in 89% patients. Overall 79% completed chemotherapy without any significant side-effects, dose reductions, or breaks during chemotherapy. Using logistic regression model increasing age was not associated with early termination of chemotherapy (p = 0.19, OR: 0.868, 95% CI: 0.7,1.076). However, increasing age, lower functional status, and higher comorbidity index scores were associated with reduction in dose and breaks in chemotherapy. None of the patients who received pegfilgrastim prophylactically developed high-grade neutropenia. Our study suggests that adjuvant chemotherapy is safe in elderly patients. Older patients with good functional status and low comorbidity index scores tolerate chemotherapy as well as the younger patients. Prophylactic use of pegfilgrastim may reduce occurrence of severe neutropenia and related toxicity such as febrile neutropenia in the elderly patient. [source] Clinical scale ex vivo manufacture of neutrophils from hematopoietic progenitor cellsBIOTECHNOLOGY & BIOENGINEERING, Issue 4 2009Nicholas E. Timmins Abstract Dose-intensive chemotherapy results in an obligatory period of severe neutropenia during which patients are at high risk of infection. While patient support with donor neutrophils is possible, this option is restricted due to donor availability and logistic complications. To overcome these problems, we explored the possibility of large scale ex vivo manufacture of neutrophils from hematopoietic progenitor cells (HPC). CD34+ HPC isolated from umbilical cord blood (UCB) and mobilized peripheral blood (mPB) were expanded in serum-free medium supplemented with stem cell factor, granulocyte colony stimulating factor, and a thrombopoietin peptide mimetic. After 15 days of cultivation a 5,800-fold expansion in cell number was achieved for UCB, and up to 4,000-fold for mPB, comprising 40% and 60% mature neutrophils respectively. Ex vivo expanded neutrophils exhibited respiratory burst activity similar to that for donor neutrophils, and were capable of killing Candida albicans in vitro. These yields correspond to a more than 10-fold improvement over current methods, and are sufficient for the production of multiple neutrophil transfusion doses per HPC donation. To enable clinical scale manufacture, we adapted our protocol for use in a wave-type bioreactor at a volume of 10,L. This is the first demonstration of a large scale bioprocess suitable for routine manufacture of a mature blood cell product from HPC, and could enable prophylactic neutrophil support for chemotherapy patients. Biotechnol. Bioeng. 2009; 104: 832,840 © 2009 Wiley Periodicals, Inc. [source] Delayed-onset neutropenia associated with rituximab therapyBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2003Kritika Chaiwatanatorn Summary. The characteristics of severe neutropenia with a delayed onset following administration of rituximab have been evaluated in 53 consecutively treated patients. All but one patient received rituximab for the treatment of non-Hodgkin's lymphoma. Eight episodes of grade 4 neutropenia were detected between 1 and 5 months after rituximab, when administered alone on five occasions, and on three occasions in combination with chemotherapy, where neutrophil counts had recovered prior to the development of neutropenia. In three episodes, the patients presented with sepsis. Development of neutropenia did not correlate with either the presence of detectable disease or the administration of further treatment. Neutropenia was associated with selective depletion of neutrophil precursors in all but one episode, where it was associated with generalized bone marrow hypoplasia. All episodes developed after a period of either normal or mildly depressed neutrophil counts following treatment with rituximab, and persisted for between several days and several months, before undergoing spontaneous recovery in four instances, and after administration of filgrastim in the remainder. Episodes of neutropenia were associated with disordered immune status manifested by lymphopenia and hypogammaglobulinaemia, raising the possibility that either disturbance of the balance of lymphocyte subsets or an immune dyscrasia induced by rituximab resulted in the development of this type of neutropenia. [source] Cost effectiveness of pharmacogenetic testing for uridine diphosphate glucuronosyltransferase 1A1 before irinotecan administration for metastatic colorectal cancer,CANCER, Issue 17 2009Heather Taffet Gold PhD Abstract BACKGROUND: The objective of this study was to examine the cost effectiveness of using a pharmacogenetic test for uridine diphosphate glycosyltransferase 1A1*28 (UGT1A1*28) variant homozygosity before administering irinotecan to patients with metastatic colorectal cancer. METHODS: A decision-analytic model from the Medicare payer perspective followed hypothetical patients who were treated with combined 5-fluorouracil, leucovorin, and irinotecan. Under usual care, patients received a full dose of irinotecan. With genetic testing, irinotecan dosage was reduced 25% in homozygotes with the UGT1A1*28 variant allele. Test performance, chemotherapy toxicity, and quality-of-life weights were derived from clinical literature and product labels, and costs were derived from 2007 Medicare fee schedules. Chemotherapy efficacy after dose reduction, adverse event risk, and other parameters were varied in 1-way and probabilistic sensitivity analyses. The authors also calculated the value of investing in further studies of chemotherapy efficacy after homozygote dose reductions. RESULTS: Pretreatment genetic testing costs less ($272 savings per patient tested) and yields slightly improved quality-adjusted life expectancy (0.1 quality-adjusted day per patient tested; approximately 2 quality-adjusted hours). Results depended on treatment efficacy but not adverse event risk assumptions. The results indicated that testing would avoid 84 cases of severe neutropenia, including 4.4 deaths. At a threshold of $100,000 per quality-adjusted life year, the therapeutic efficacy of irinotecan in homozygotes after dose reduction had to be ,98.4% of full-dose efficacy for genetic testing to remain preferred. Future studies to determine whether this efficacy level can be achieved have an economic value of $22 million. CONCLUSIONS: The current results indicated that pharmacogenetic testing for UGT1A1*28 variant homozygosity may be cost effective, but only if irinotecan dose reduction in homozygotes does not reduce efficacy. Future studies to evaluate reduced-dose efficacy in homozygotes should be considered. Cancer 2009. © 2009 American Cancer Society. [source] Emesis predicts bacteremia in immunocompromised children with central venous catheters and fever,CANCER, Issue 14 2009Matthew W. Richardson MD Abstract BACKGROUND: The objective of this study was to determine whether vomiting at presentation of a febrile illness in immunocompromised children with central venous catheters (CVCs) predicts bacteremia. METHODS: A chart review was conducted of children who were admitted to the hospital with a diagnosis of cancer or aplastic anemia, fever, and a CVC. Data were collected on the presence or absence of vomiting, catheter type, presence or absence of severe neutropenia, C-reactive protein (Crp) value, and culture results. RESULTS: There were 143 admissions for fever among 48 children. Among 35 admissions with emesis, 19 included bacteremia; whereas, among 107 admissions without emesis, 19 included bacteremia (P < .001). There was a 5-fold greater risk of bacteremia in children with children without vomiting (odds ratio, 5.50; 95% confidence interval, 2.20-13.67). Gram-negative organisms were more likely to be associated with vomiting than Gram-positive organisms (P = .008). Children with severe neutropenia did not have a significantly higher rate of bacteremia than children who had neutrophil counts >500 cells/mm3. Other factors that were associated with higher rates of bacteremia were underlying diagnosis and catheter type. CONCLUSIONS: Immunocompromised children with a CVC and a fever who presented with vomiting were more likely to have bacteremia than similar children who presented without vomiting. Gram-negative organisms were more likely to be associated with emesis than Gram-positive organisms. The absence of severe neutropenia was not associated with a decreased likelihood of bacteremia. These findings may be useful in identifying children who are at high risk for bacteremia and in determining initial, empiric therapy. Cancer 2009. © 2009 American Cancer Society. [source] Role of UGT1A1*6, UGT1A1*28 and ABCG2 c.421C>A polymorphisms in irinotecan-induced neutropenia in Asian cancer patientsCANCER SCIENCE, Issue 9 2007Srinivasa Rao Jada The objectives of the present study were (i) to study the pharmacogenetics of UGT1A1*6, UGT1A1*28 and ABCG2 c.421C>A in three distinct healthy Asian populations (Chinese, Malays and Indians), and (ii) to investigate the polygenic influence of these polymorphic variants in irinotecan-induced neutropenia in Asian cancer patients. Pharmacokinetic and pharmacogenetic analyses were done after administration of irinotecan as a 90-min intravenous infusion of 375 mg/m2 once every 3 weeks (n = 45). Genotypic,phenotypic correlates showed a non-significant influence of UGT1A1*28 and ABCG2 c.421C>A polymorphisms on the pharmacokinetics of SN-38 (P > 0.05), as well as severity of neutropenia (P > 0.05). Significantly higher exposure levels to SN-38 (P = 0.018), lower relative extent of glucuronidation (REG; P = 0.006) and higher biliary index (BI; P = 0.003) were found in cancer patients homozygous for the UGT1A1*6 allele compared with patients harboring the reference genotype. The mean absolute neutrophil count (ANC) was 85% lower and the prevalence of grade 4 neutropenia (ANC , 500/µL) was 27% in patients homozygous for UGT1A1*6 compared with the reference group. Furthermore, the presence of the UGT1A1*6 allele was associated with an approximately 3-fold increased risk of developing severe grade 4 neutropenia compared with patients harboring the reference genotype. These exploratory findings suggest that homozygosity for UGT1A1*6 allele may be associated with altered SN-38 disposition and may increase the risk of severe neutropenia in Asian cancer patients, particularly in the Chinese cancer patients who comprised 80% (n = 36) of the patient population in the present study. (Cancer Sci 2007; 98: 1461,1467) [source] Thalidomide for the Treatment of Refractory Multiple Myeloma: Association of Plasma Concentrations of Thalidomide and Angiogenic Growth Factors with Clinical OutcomeCANCER SCIENCE, Issue 9 2002Tsunayuki Kakimoto Recent reports showed that thalidomide has anti-angiogenic activity and is effective for the treatment of refractory multiple myeloma (MM). We examined the relationship between the clinical efficacy and adverse effects of thalidomide and the plasma concentrations of this drug as well as angiogenic growth factors in refractory MM. Ten out of twenty-four evaluable patients (42%) showed more than 25% reduction of M-protein, and eight (33%) achieved more than 50% reduction. These changes were associated with restoration of anemia and recovery of normal immunoglobulin level. Somnolence and headache, constipation, peripheral neuropathy and skin rash were frequently observed, but were well tolerated. However, grade 2,4 severe neutropenia was also observed in nine cases. These adverse effects other than neutropenia occurred more frequently in the patients with higher plasma concentrations of thalidomide (,2.0 ,g/ml at 12 h after the last administration) and were readily alleviated by dose reduction. In contrast, neutropenia developed regardless of the plasma concentration. Plasma concentrations of angiogenic growth factors were frequently elevated before treatment. After thalidomide treatment, these growth factor levels tend to decrease to near-normal ranges in responders but were still high in most non-responders. After thalidomide treatment, plasma vascular endothelial growth factor (VEGF) level was significantly reduced in responders (P=0.025), but not in non-responders (P=0.37). Reduction of plasma VEGF level might be an important indicator for anti-myeloma effect of thalidomide. [source] Induction therapy by anti-thymocyte globulin (rabbit) in renal transplantation: a 1-yr follow-up of safety and efficacyCLINICAL TRANSPLANTATION, Issue 6 2003Matthias Büchler Abstract: Background: Two hundred and forty cadaveric renal transplant recipients given anti-thymocyte globulin (Thymoglobulin®) as induction immunotherapy were followed up prospectively to review safety and efficacy. Methods: The median number of infusions was 10 [2,21] with a cumulative dose of 8.8 mg/kg [2.0,23.2 mg/kg]. During the fortnight following transplantation, 231 patients (96%) received a calcineurin inhibitor; all patients were given steroids and azathioprine or mycophenolate mofetil. At 1 yr, 60% of patients were on tripletherapy, 38% on bitherapy, and 2% on monotherapy; 20% had discontinued steroids. Results: Tolerance was excellent with no cases of anaphylaxis. The commonest adverse event was fever (55%). Eighteen patients developed serum sickness on median day 11 [10,14]. Seven patients had thrombocytopenia; six patients had severe neutropenia. All of these adverse events recovered spontaneously. The overall incidence of delayed graft function was 24%. At 1 yr patient and graft survival were 98 and 95%, respectively, and creatinine was 135 ± 43 ,mol/L. Clinically suspected and biopsy-proven acute rejection were observed in 65 patients (27%) and 34 patients (14%), respectively. There were 62 non-cytomegalovirus (CMV) infections (two fatal) and 81 episodes of CMV infections. Eight malignancies were reported; two possibly related to immunosuppression. Conclusions: These results demonstrate that anti-thymocyte globulin has a safety profile with good tolerability and excellent efficacy. [source] | |||||||||||||||||||||||||