Period Of Leukopenia Research Articles

Risk factors associated with Clostridium difficile infection after kidney and pancreas transplantation

Clostridium difficile infection (CDI) is a common cause of nosocomial antibiotic-associated diarrhea with an increased incidence reported in solid organ transplant recipients. We sought to determine if kidney and/or pancreas transplant recipients possess unique risk factors for CDI. Between January 2009 and February 2011, 942 kidney and 56 pancreas transplants were performed at the 2 centers. Of these, 28 recipients (kidney, n=24; pancreas, n=4) developed CDI. Cases were matched to controls (n=56) in a 1:2 ratio. Those with CDI were mostly male patients (82% vs. 48%, P=0.003), deceased-donor organ recipients (86% vs. 64%, P=0.045), more likely to have leukopenia (18% vs. 4%, P=0.038), and had undergone a gastrointestinal procedure within 3months preceding CDI diagnosis (18% vs. 4%, P=0.038). Cases had higher cumulative and restricted antimicrobial exposure in days (37±79 vs. 8±12, P=0.009 and 27±69 vs. 7±10, P=0.032). Cephalosporin use was more common among cases (43% vs. 16%, P=0.008). Careful antimicrobial selection and assurance of optimal treatment duration in the kidney and pancreas transplant population is prudent. Clinicians should have a heightened awareness of CDI risk particularly during periods of leukopenia and in the setting of gastrointestinal procedures.

Granulocyte Colony-Stimulating Factor Therapy Is Associated With a Reduced Incidence of Acute Rejection Episodes or Allograft Vasculopathy in Heart Transplant Recipients

BackgroundWe evaluated the potential effects of granulocyte colony-simulating factor (G- CSF) on the incidence of rejection and allograft vasculopathy in heart transplant recipients. MethodsOf 247 patients undergoing heart transplantation from 2000 to 2007, 52 (21%) developed leukopenia (white blood cell [WBC] <2.5 × 109cells/L) in the absence of active infection, rejection, or malignancy. In 24 (46%) patients a clinical decision was made to treat the leukopenia with G-CSF (G-CSF group), and 28 (54%) Patients received no G-CSF (non-GCSF group). Patients followed up for 1 year after the period of leukopenia were assessed for allograft vasculopathy and acute rejection incidence. ResultsAt baseline, the G-CSF group and the non-GCSF group did not differ in age, gender, race, heart failure etiology, creatinine, left ventricular ejection fraction (LVEF) or immunosupressive regimen. During 1-year follow-up there were no deaths in the G-CSF group, and 1 death in the non-GCSF group (P = .34). The incidence of rejection or progressive allograft vasculopathy was lower in the G-CSF group when compared with the non-GCSF group (2 [8%] vs 15 [53%]; P < .01). Multivariate analysis identified both prior rejection episodes and G-CSF therapy as factors associated with the combined end-point of rejection or progressive allograft vasculopathy (odds ratio [OR] = 7.89 [1.67–37.2] and OR = 0.09 [0.02–0.52], respectively). ConclusionsG-CSF therapy appears to be associated with a decreased incidence of acute rejection episodes or allograft vasculopathy in heart transplant recipients, suggesting a potential immunomodulatory effect of G-CSF.

Acquired pulmonary alveolar proteinosis after umbilical cord blood transplantation for acute myeloid leukemia

Pulmonary alveolar proteinosis (PAP) is a heterogeneous disease that occasionally develops with hematological malignancy. However, PAP in association with hematopoietic stem cell transplantation is quite rare. Here we present the first report of a patient who developed PAP after cord blood transplantation (CBT). A 45-year-old female with AML underwent unrelated CBT. On day +2 after CBT she developed congestive heart failure with diffuse alveolar infiltrates in the bilateral lungs. Despite treatment, the alveolar infiltrates further increased with progression of multiple organ failure (MOF). She died from MOF before hematopoietic recovery on day +27. Post-mortem study revealed that massive amorphous materials positive for periodic acid-Schiff stain filled in the pulmonary alveoli. These findings led to a diagnosis of PAP. The bone marrow was hypocellular without the leukemic cells. The impaired immunity during the period of leukopenia as well as the impaired clearance of surfactant proteins might contribute to the development of PAP.

Infectious complications in children with acute lymphoblastic leukemia and T-cell lymphoma – a rationale for tailored supportive care

Infections still remain a major cause of therapy-associated morbidity and death in patients with malignant diseases. To further lower the risk of serious and long-lasting infections by additional supportive measures, detailed information on the frequency and characteristic features of infections is needed. Therefore, patient data from 112 children with acute lymphoblastic leukemia and T-cell lymphoma who were treated according to the COALL-05-92 protocol in our department were analyzed for differences in the frequency and origin of febrile episodes in relation to age, immunological type of leukemia, treatment in group assessed as being at high or low risk of relapse, actual occurrence of relapse, and course of chemotherapy. At the time of diagnosis, low-risk patients more commonly presented with febrile episodes than high-risk patients. In total, patients developed a fever in 313 (24%) of 1,307 evaluated chemotherapy cycles. Febrile episodes were associated with microbiologically or clinically documented infections in 60% of all cases, while in 40% the fever was of unknown origin. Gram-positive pathogens had a markedly higher incidence than gram-negative or fungal ones. The incidence of febrile episodes during therapy appeared to be correlated with certain chemotherapeutic drug combinations. The highest rate was found after high-dose cytarabine and asparaginase causing a long period of leukopenia. However, after other chemotherapy courses with a similar duration of leukopenia the incidence of febrile episodes was significantly lower, suggesting that specific interactions of different chemotherapeutic agents with the immune response might be an important factor in development of infections. Individual factors might also account for an increased incidence of infections, since the number of high-risk patients with recurrent infections was significantly higher than expected on the basis of statistical evaluation. In conclusion, our findings suggest that the risk of infections during chemotherapy may not only be influenced by leukopenia, but that drug-specific effects of the various chemotherapeutic agents and individual factors may also be important contributory factors. These observations must be further expanded in prospective studies so that new tailored supportive care protocols can be elaborated.

WR-2,721: Enhanced chemoprotection by increasing cyclophosphamide activation with phenobarbitol

In the animal model, WR-2721 protects the bone marrow against the cytotoxicity of cyclophosphamide (CYC) and nitrogen mustard (NH 2) by factors of 1.5–2.4 and 3.2–4.6, respectively. NH 2 is rapidly metabolized within minutes, while CYC is activated slowly over hours by the hepatic mixed function oxidases. The prolonged half-life of CYC may account for the reduced chemoprotection as compared to NH 2. Phenobarbitol (PB) pretreatment significantly shortens the half-life of CYC in man and in the rat model. Thus, pretreatment with PB, by inducing hepatic microsomal enzymes, may enhance chemoprotection with WR-2721. Experiments were performed to determine: (1) The effect of PB pretreatment on the clearance of WR-2721; (2) Whether WR-2721 protects against CYC myelotoxicity measured by daily leukocyte counts; (3) Whether PB increases chemoprotection with WR-2721 and CYC. Female Fisher rats were pretreated with daily PB 40 mg/kg intraperitoneally (ip) for four days prior to the administration of 100 mg/kg CYC ip with and without WR-2721 200 mg/kg ip. Controls received saline ip in place of PB on the same schedule. CYC levels and alkylating activity were measured at 15, 30, 60, and 180 minutes after CYC. Serum and tissue levels of WR-2721 were assayed by radiolabel technique. Following CYC, daily WBC were obtained for 10 days at which point all counts had returned to baseline. The mean WBC during the period of leukopenia was 1091 /mm 3 with CYC alone; 2587/ mm 3 with WR-2721 + CYC; 1436/mm 3 with PB + CYC; and 3493/ mm 3 with PB + WR-2721 + CYC. PB may increase the acute toxicity of WR-2721 as judged by hypothermic response. PB had minimal effects on serum and tissue levels of WR-2721. PB appears to enhance WR-2721's chemoprotection against myelosuppression from CYC by hastening marrow recovery and decreasing the extent of leukopenia.

Efficacy of granulocyte transfusions in the control of systemic candidiasis in the leukopenic host

An experimental canine model was designed to evaluate the effect of granulocyte transfusions on systemic infection with Candida albicans in the granulocytopenic host. Each of a pair of dogs was rendered granulocytopenic with a single intravenous (i.v.) dose of cyclophosphamide (50 mg/kg body weight) and challenged with 10(6) Candida albicans organisms administered i.v. when granulocyte counts were less than or equal to 500/mm3. Granulocytes procured by leukofiltration were infused into six experimental dogs 1, 24, 48, and 72 hr after challenge with Candida. An average of 13 +/- 1.3 X 10(9) granulocytes were administered per infusion, producing an average 1-hr increment of 588 +/- 146 granulocytes/mm3 over the pretransfusion granulocyte count. Experimental and control dogs were killed 96 hr after challenge and organs examined grossly and by quantitative culture techniques to measure the extent of infection. All animals receiving granulocyte transfusions had significantly less tissue infection than nontransfused controls (p less than 0.05). It was concluded that granulocyte transfusions are effective in reducing the severity of infection by Candida albicans during periods of leukopenia.

Efficacy of Granulocyte Transfusions in the Control of Systemic Candidiasis in the Leukopenic Host

An experimental canine model was designed to evaluate the effect of granulocyte transfusions on systemic infection with Candida albicans in the granulocytopenic host. Each of a pair of dogs was rendered granulocytopenic with a single intravenous (i.v.) dose of cyclophosphamide (50 mg/kg body weight) and challenged with 10(6) Candida albicans organisms administered i.v. when granulocyte counts were less than or equal to 500/mm3. Granulocytes procured by leukofiltration were infused into six experimental dogs 1, 24, 48, and 72 hr after challenge with Candida. An average of 13 +/- 1.3 X 10(9) granulocytes were administered per infusion, producing an average 1-hr increment of 588 +/- 146 granulocytes/mm3 over the pretransfusion granulocyte count. Experimental and control dogs were killed 96 hr after challenge and organs examined grossly and by quantitative culture techniques to measure the extent of infection. All animals receiving granulocyte transfusions had significantly less tissue infection than nontransfused controls (p less than 0.05). It was concluded that granulocyte transfusions are effective in reducing the severity of infection by Candida albicans during periods of leukopenia.

LEUKOPENIA, BONE PAIN, AND BONE NECROSIS IN PATIENTS WITH ACUTE LEUKEMIA: A CLINICOPATHOLOGIC COMPLEX.

Article1 April 1965Leukopenia, Bone Pain, and Bone Necrosis in Patients with Acute LeukemiaA Clinicopathologic ComplexBOYD A. NIES, M.D., DONALD W. KUNDEL, M.D., LOUIS B. THOMAS, M.D., EMIL J FREIREICH, M.D.BOYD A. NIES, M.D.Search for more papers by this author, DONALD W. KUNDEL, M.D.Search for more papers by this author, LOUIS B. THOMAS, M.D.Search for more papers by this author, EMIL J FREIREICH, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-62-4-698 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptSeveral recent studies have demonstrated the occurrence of bone necrosis in acute leukemia (1-4). Kundel, Brecher, Bodey, and Brittin (1) recently have studied a group of patients with acute lymphocytic leukemia and increased bone marrow reticulin, in which six patients were also found to have bone and marrow necrosis. Their results suggested that the clinical course of this group was characterized by bone pain, long periods of leukopenia, and poor response to therapy. Bone necrosis was found to occur much more frequently in acute lymphocytic leukemia than in acute myelogenous leukemia.In order to determine if the above suggested features...

Long-term intraoral findings in humans after exposure to total-body irradiation from sudden radioactive fallout. I. Five year postdetonation studies

The intraoral clinical findings obtained in March 1959 on Marshallese natives 5 yr after exposure to total-body irradiation from sudden, significant quantities of radioactive fallout are described. This fallout was precipitated on Rongerik atoll, Rongelap atoll, Ailingnae, and Uterik in the Marshall Islands after detonation of a 15-Mt thermonuclear test device at the Bikini Proving Grounds in February 1954. As a result, 239 Marshallese were accidentally exposed to total-body irradiation ranging from 14 to 175 r. Examinations disclosed similar degrees of caries activity in irradiated and nonirradiated children. Although the prevalence of periodontal disease was practically identical in both the irradiated and nonirradiated groups, the extent of periodontal destruction was greater in the irradiated Rongelapese. This difference may or may not be related to factors such as leukopenia and lower tissue resistance and the presence of preexisting periodontal disease. Children born of irradiated parents, including those children in utero at the time of initial exposure, and irradiated children 6 to 18 yr old, showed no evidence of any morphologic effects on oral tissues from total-body irradiation when compared with the nonirradiated control groups. No evidence of intraoral neoplasm was noted; however, one 42-yr- old irradiated Rongelap man had a smallmore » leukoplakic-like lesion on the gingiva. No clear relation of radintion exposure in the Rongelap people to the higher levels of periodontal destruction in this group is suggested. Because of the generally substandard levels of oral hygiene among the Marshallese, it is likely that the disease was prevalent at the time of their radiation exposure. However, the period of leukopenia after this group's exposure might have enhanced the progress of periodontal disease, although they showed no evidence of increased infection, oral or otherwise, or bleeding tendency during the period of leukopenia and thrombocytopenia. (BBB)« less

The effect of penicillin on the blood system

In response to milk injection or to stomach inflation leukocytosis develops in cats following a short period of leukopenia. There is also a shif, of the leukocytic formula with an increase of the number of band forms without any rise in the number of eosinophilic elements. Preliminary administration of penicillin, injection of foreign protein (milk) or the stimulation of the gastric mechanoceptors caused a pronounced eosinophilia disappearing in 9–10 days after discontinuing the administration of this antibiotic. Thus, penicillin causes a condition of sensitization in which the usual leukocytic reactions to humoral and the reflex stimulations are distorted and acquire the character of eosinophilia.