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1.
Qual Life Res ; 24(12): 2895-906, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26205768

ABSTRACT

PURPOSE: To describe the health-related quality of life (HRQoL) of an unselected population of patients with chronic lymphocytic leukaemia (CLL) including untreated patients. METHODS: HRQoL was measured by the EORTC QLQ-C30 including the CLL16 module, EQ-5D, and VAS in an observational study over multiple years. All HRQoL measurements per patient were connected and analysed using area under the curve analysis over the entire study duration. The total patient group was compared with the general population, and three groups of CLL patients were described separately, i.e. patients without any active treatment ("watch and wait"), chlorambucil treatment only, and patients with other treatment(s). RESULTS: HRQoL in the total group of CLL patients was compromised when compared with age- and gender-matched norm scores of the general population. CLL patients scored statistically worse on the VAS and utility score of the EQ-5D, all functioning scales of the EORTC QLQ-C30, and the symptoms of fatigue, dyspnoea, sleeping disturbance, appetite loss, and financial difficulties. In untreated patients, the HRQoL was slightly reduced. In all treatment stages, HRQoL was compromised considerably. Patients treated with chlorambucil only scored worse on the EORTC QLQ-C30 than patients who were treated with other treatments with regard to emotional functioning, cognitive functioning, bruises, uncomfortable stomach, and apathy. CONCLUSIONS: CLL patients differ most from the general population on role functioning, fatigue, concerns about future health, and having not enough energy. Once treatment is indicated, HRQoL becomes considerably compromised. This applies to all treatments, including chlorambucil, which is considered to be a mild treatment.


Subject(s)
Health Status , Leukemia, Lymphocytic, Chronic, B-Cell/psychology , Quality of Life , Adult , Aged , Chlorambucil/adverse effects , Chlorambucil/therapeutic use , Dyspnea/psychology , Fatigue/psychology , Female , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Longitudinal Studies , Male , Middle Aged , Netherlands , Sleep Wake Disorders/psychology , Surveys and Questionnaires
2.
Leuk Res ; 38(1): 84-90, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24268350

ABSTRACT

We performed a comprehensive cost calculation identifying the main cost drivers of treatment of chronic lymphocytic leukaemia in daily practice. In our observational study 160 patient charts were reviewed repeatedly to assess the treatment strategies from diagnosis till the study end. Ninety-seven patients (61%) received ≥1 treatment lines during an average follow-up time of 6.4 years. The average total costs per patient were €41,417 (€539 per month). The costs varied considerably between treatment groups and between treatment lines. Although patients were treated with expensive chemo(immuno-)therapy, the main cost driver was inpatient days for other reasons than administration of chemo(immuno-)therapy.


Subject(s)
Diagnostic Tests, Routine/economics , Drug Therapy/economics , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Stem Cell Transplantation/economics , Adult , Aged , Aged, 80 and over , Cost-Benefit Analysis , Costs and Cost Analysis , Diagnostic Tests, Routine/methods , Drug Therapy/methods , Female , Humans , Male , Middle Aged , Netherlands , Stem Cell Transplantation/methods
3.
Leukemia ; 25(11): 1697-703, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21647160

ABSTRACT

Event-free survival (EFS) at 5 years in pediatric acute lymphoblastic leukemia (ALL) is >80%. Outcome in adult ALL is still unsatisfactory, which is due to less cumulative dosing of chemotherapy and less strict adherence to timing of successive cycles. In the present phase II trial, we evaluated a pediatric regimen in adult patients with ALL under the age of 40. Treatment was according to the pediatric FRALLE approach for high-risk ALL patients and characterized by increased dosages of asparaginase, steroids, methotrexate and vincristin. However, allogeneic stem cell transplantation was offered to standard risk patients with a sibling donor and to all high-risk patients in contrast to the pediatric protocol. Feasibility was defined by achieving complete remission (CR) and completion of treatment within a strict timeframe in at least 60% of patients. In all, 54 patients were included with a median age of 26. CR was achieved in 49 patients (91%), of whom 33 completed treatment as scheduled (61%). Side effects primarily consisted of infections and occurred in 40% of patients. With a median follow-up of 32 months, EFS estimated 66% at 24 months and overall survival 72%. These data show that a dose-intensive pediatric regimen is feasible in adult ALL patients up to the age of 40.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Marrow Transplantation , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/surgery , Adolescent , Adult , Combined Modality Therapy , Feasibility Studies , Female , Humans , Male , Middle Aged , Remission Induction , Young Adult
4.
Ann Hematol ; 86(2): 117-25, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17031690

ABSTRACT

A prospective randomized phase III study was performed to evaluate whether intensified cytarabine would induce a higher response rate and longer event-free interval as compared to low-dose cytarabine in chronic myeloid leukemia (CML). One hundred and eighteen patients with CML in early chronic phase entered the study. Twenty-eight out of 32 patients assigned to group A received two cycles of a combination of intensified cytarabine and idarubicin followed by interferon alfa (IFN-alpha) maintenance, 28 patients in group B received standard treatment by a combination of low-dose cytarabine and IFN-alpha. Forty-nine patients with a human leukocyte antigen-identical sibling donor proceeded to allogeneic stem cell transplantation (allo-SCT) and nine patients were excluded from the analysis. Hematological response was observed in 97% of the patients in group A vs 86% of the patients in group B during the first year of treatment. In group A, 16 patients (50%) achieved a major cytogenetic response, which compared to seven patients (25%) with a major cytogenetic response in group B. With a median follow-up of 58 months (range 34-76), event-free survival was not significantly different between arms A and B. The estimated 5-year survival rate was 56% in the intensified arm and 77% in the low-dose arm (P = 0.05). Recipients of allo-SCT showed a 5-year estimated survival rate of 55%. Although intensified cytarabine induced a higher initial percentage of major and complete cytogenetic responses, responses were not sustained by IFN-alpha maintenance therapy.


Subject(s)
Cytarabine/therapeutic use , Interferon-alpha/therapeutic use , Leukemia, Myeloid, Chronic-Phase/drug therapy , Leukemia, Myeloid, Chronic-Phase/pathology , Adolescent , Adult , Aged , Cytarabine/administration & dosage , Cytogenetics , Disease-Free Survival , Dose-Response Relationship, Drug , Drug Therapy, Combination , Female , Humans , Interferon-alpha/adverse effects , Leukemia, Myeloid, Chronic-Phase/genetics , Leukemia, Myeloid, Chronic-Phase/surgery , Male , Middle Aged , Stem Cell Transplantation , Survival Rate , Transplantation, Homologous
5.
Cancer Invest ; 24(5): 479-83, 2006.
Article in English | MEDLINE | ID: mdl-16939955

ABSTRACT

PURPOSE: Cancer patients treated with cytostatic drugs often develop oral mucositis, considered to be a mucosal injury in which various cytokines, such as interleukin 8 (IL-8), may play a role. Plasma IL-8 is a systemic inflammatory response parameter. This study investigated whether oral mucositis affects plasma IL-8 levels in febrile neutropenic cancer patients. PATIENTS AND METHODS: Patients (n = 57) who were hospitalized with chemotherapy-induced neutropenic fever were scored for oral mucositis on the second day of hospitalization according to a validated oral mucositis assessment scale (OMAS) and WHO toxicity grading. Patients (n = 20) with a clinical sepsis or local bacterial infection were excluded from this evaluation. The remaining 37 patients were divided in groups with and without oral mucositis. RESULTS: The difference in plasma IL-8 level between patients with and without mucositis was not significant (P = 0.7). Similarly no difference was observed in the degree and duration of granulocytopenia. CONCLUSION: These results indicate that low-grade oral mucositis is not related to the systemic plasma IL-8 level in febrile neutropenic cancer patients without a clinical sepsis or local bacterial infection.


Subject(s)
Antineoplastic Agents/adverse effects , Fever/blood , Inflammation Mediators/blood , Interleukin-8/blood , Neutropenia/blood , Stomatitis/blood , Adolescent , Adult , Child , Child, Preschool , Female , Fever/chemically induced , Humans , Male , Middle Aged , Neoplasms/drug therapy , Neoplasms/immunology , Neutropenia/chemically induced , Severity of Illness Index , Stomatitis/chemically induced , Stomatitis/pathology
6.
Eur J Cancer ; 39(17): 2495-8, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14602135

ABSTRACT

Cancer patients treated with chemotherapy are susceptible to bacterial infections. When an adult patient presents with febrile neutropenia, standard diagnostic care includes physical examination, laboratory diagnostics, chest X-ray (CXR) and sinus radiography. However, the yield of routine radiography in the diagnostic evaluation of ambulatory adult febrile neutropenic patients with normal findings at their physical examination is questionable. Two CXRs and one sinus X-ray were obtained in 109 and 106 febrile neutropenic episodes after chemotherapy in ambulatory adult patients who had no clinical signs suggesting pulmonary infection or sinusitis. We found that in only two of 109 (1.8%; 95% Confidence Interval (CI): 0.3-5.8%) febrile neutropenic episodes without clinical signs of new pulmonary disease, the CXR showed a consolidation suggesting pneumonia. In addition, in five of 88 (5.7%; 95% CI: 2.2-12.0%) febrile episodes in asymptomatic patients, sinus X-ray suggested sinusitis. In none of these seven episodes was a change of antibiotic therapy necessary. In the absence of clinical signs indicating pneumonia or sinusitis, the yield of CXR and sinus radiography in ambulatory adult cancer patients presenting with febrile neutropenia is minimal; CXR and sinus radiography should no longer be performed on a routine basis.


Subject(s)
Bacterial Infections/diagnostic imaging , Fever/diagnostic imaging , Neoplasms/complications , Neutropenia/diagnostic imaging , Adolescent , Adult , Aged , Antineoplastic Agents/adverse effects , Female , Humans , Male , Middle Aged , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Neutropenia/chemically induced , Radiography
7.
Clin Diagn Lab Immunol ; 10(4): 558-63, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12853386

ABSTRACT

Cancer patients who are leukopenic due to chemotherapy are susceptible to bacterial infections. Normally, clinical conditions during bacterial infections are caused by pathogen-associated molecular patterns, which are components that bind to Toll-like receptor (TLR) 2 (TLR-2) and TLR-4 on leukocytes, resulting in the production of inflammatory cytokines. The mechanism of this inflammatory response in cancer patients with diminished numbers of leukocytes is not completely clear. The levels of interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha measured in the circulation of leukopenic cancer patients are lower than those measured in that of nonleukopenic patients during bacterial infections, whereas plasma interleukin 8 (IL-8) levels show distinct identical increases during bacterial infections in both leukopenic and nonleukopenic patients. Normally, these cytokines are mainly secreted by leukocytes. In cancer patients with bacterial infections and a diminished number of leukocytes, other sources of IL-8 production, such as endothelial cells, might be expected. Endothelial cells instead of leukocytes become the most important producers of IL-8 during bacterial infections in patients with chemotherapy-induced leukopenia through TLR-2 and TLR-4 signaling. Whole blood samples from six cancer patients were stimulated with lipopolysaccharide (LPS), and then IL-8 concentrations in supernatants were measured. Further, human umbilical vein endothelial cells (HUVECs) were incubated with sera from leukopenic cancer patients with or without bacterial infections, and then IL-8 concentrations in supernatants were measured (n = 6). In addition, the same HUVEC experiment was performed with the addition of neutralizing antibodies against TLR-2 and TLR-4. During leukopenia (<10(9) cells/liter), LPS stimulation of whole blood did not result in an increase in IL-8 levels. However, when endothelial cells were incubated with sera from leukopenic cancer patients during bacterial infections, a three- to eightfold increase in IL-8 production was found, compared to the IL-8 production found after incubation with sera from patients without signs of infections. This increase did not reflect a higher level of IL-8 already present in the sera. Further, we demonstrated that IL-8 production induced in endothelial cells by sera from patients with documented gram-negative infections could be reduced significantly by up to 40% when the cells were incubated with neutralizing antibodies against TLR-4 (P = 0.028). The addition of TLR-2 antibodies slightly enhanced the reduction of IL-8 production. These results suggest that during bacterial infections in cancer patients with markedly diminished numbers of leukocytes, endothelial cells become important producers of IL-8 through TLR-4 signaling and, to a lesser extent, TLR-2 signaling.


Subject(s)
Bacterial Infections/metabolism , Endothelium, Vascular/metabolism , Interleukin-8/biosynthesis , Leukopenia/complications , Membrane Glycoproteins/physiology , Neoplasms/complications , Receptors, Cell Surface/physiology , Adult , Antineoplastic Agents/adverse effects , Bacterial Infections/etiology , Blood Physiological Phenomena , Cells, Cultured/drug effects , Cells, Cultured/metabolism , Child , Culture Media/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Hematologic Neoplasms/blood , Hematologic Neoplasms/complications , Humans , Interleukin-8/blood , Interleukin-8/genetics , Leukopenia/chemically induced , Lipopolysaccharides/pharmacology , Membrane Glycoproteins/antagonists & inhibitors , Neoplasms/blood , Prospective Studies , Receptors, Cell Surface/antagonists & inhibitors , Toll-Like Receptor 2 , Toll-Like Receptor 4 , Toll-Like Receptors , Tumor Necrosis Factor-alpha/analysis , Tumor Necrosis Factor-alpha/biosynthesis
8.
Crit Rev Oncol Hematol ; 44(2): 163-74, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12413633

ABSTRACT

Cancer patients treated with chemotherapy are susceptible to bacterial infections. Therefore, all neutropenic cancer patients with fever receive standard therapy consisting of broad-spectrum antibiotics and hospitalization. However, febrile neutropenia in cancer patients is often due to other causes than bacterial infections. Therefore, standard therapy should be re-evaluated and new treatment strategies for patients with variable risk for bacterial infection should be considered. This paper reviews the changing spectrum of microorganisms and resistance of microorganisms to antibiotics in infection during neutropenia and discusses new strategies for the selection of patients with low-risk for bacterial infection using clinical and biochemical parameters such as acute phase proteins and cytokines. These low-risk patients may be treated with alternative therapies such as oral antibiotics, early discharge from the hospital or outpatient treatment.


Subject(s)
Fever/etiology , Neoplasms/complications , Neutropenia/chemically induced , Antineoplastic Agents/adverse effects , Cytokines/immunology , Fever/drug therapy , Humans , Immunity/genetics , Immunity/physiology , Neoplasms/diagnosis , Neoplasms/drug therapy , Neutropenia/drug therapy , Opportunistic Infections/chemically induced , Opportunistic Infections/drug therapy , Opportunistic Infections/microbiology , Risk Assessment
9.
Neth J Med ; 60(6): 256-9, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12365470

ABSTRACT

A 54-year-old patient with myelofibrosis developed paresis of the legs, and bladder dysfunction due to extramedullary haematopoiesis in the spinal channel. He was given palliative radiotherapy but died shortly afterwards. Although rare, the possibility of extramedullary haematopoiesis in the central nervous system should be considered when neurological symptoms appear in a patient with myelofibrosis, because good palliation is possible with timely radiotherapy.


Subject(s)
Hematopoiesis, Extramedullary , Primary Myelofibrosis/physiopathology , Humans , Male , Middle Aged , Palliative Care , Paraplegia/etiology , Primary Myelofibrosis/radiotherapy , Urinary Bladder, Neurogenic/etiology
11.
Hematology ; 6(4): 231-40, 2001.
Article in English | MEDLINE | ID: mdl-27414842

ABSTRACT

Although 6-mercaptopurine (6-MP) is frequently used in the treatment of acute myeloid leukaemia (AML), its effect on disease progression has not been studied systematically. In a small retrospective analysis, we found that 6-MP could induce marked haematological improvement in a considerable number of AML patients who were not treated with intensive remission induction courses. Due to the inherent limitations of retrospective analyses, we then investigated prospectively in 51 consecutive patients over a 3-year period in a single centre, to what extent, oral 6-MP 250 mg twice a week could be beneficial to AML patients who were not-or no longer-eligible for intensive chemotherapy. Clinical response was scored according to changes in blood cell counts and dependency on blood transfusions. Thirteen patients (25%) were considered responders since they showed an increased platelet count from the first month after initiation of 6-MP onwards and they became independent of blood transfusions after 3 months. This effect lasted for 13 (range 7-30+) months. Median overall survival of this subgroup was 16.5 (6-33+) months. Ten patients (20%) had a shorter or incomplete response and a survival of 12 (6-30) months. Seven patients were lost to follow-up. Twenty-one (41%) failed to respond and survived for 4 (1.5-17) months. The response seemed not to be affected by previous chemotherapy, history of myelodysplasia, or karyotype abnormalities, but high leukocyte count initially was unfavourable. 6-MP thus can induce marked improvement of blood cell counts in a considerable proportion of AML patients who are not eligible for intensive chemotherapy, leading to good quality of life and a significant prolongation of survival.

14.
Leukemia ; 13(8): 1207-13, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10450748

ABSTRACT

The purpose of this study was to determine the safety and efficacy of filgrastim as an adjunct to induction and consolidation chemotherapy in poor risk patients with myelodysplastic syndrome (MDS). Filgrastim was given both during and after chemotherapy with the objective to accelerate hematopoietic repopulation and enhance the efficacy of chemotherapy. In a prospective randomized multicentre phase II trial, a total of 64 patients with poor risk primary MDS were randomized to receive either granulocyte colony-stimulating factor (G-CSF, filgrastim, AMGEN, Breda, The Netherlands) 5 microg/kg/day subcutaneously or no G-CSF in addition to daunomycin (30 mg/m2/days 1, 2 and 3 intravenous bolus) and cytarabine (200 mg/m2 days 1-7, continuous infusion). The overall complete response rate was 63%: 73% for patients receiving filgrastim as compared to 52% in the standard arm (P = 0.08). Overall survival at 2 years was estimated at 29% for patients assigned to the filgrastim arm and 16% for control patients (P = 0.22). The median time for recovery of granulocytes towards 1.0 x 10(9)/l post-chemotherapy was 23 days in the filgrastim-treated patients vs 35 days in the standard arm (P = 0.015). There were no differences in time of platelet recovery, length of hospital stay, duration of antibiotic use or infectious complications between the two treatment groups. However the earlier recovery of neutrophils in the filgrastim group was associated with a reduced interval of 9 days between the induction and consolidation cycle. In patients with poor risk MDS the use of filgrastim during and after induction therapy results in a significantly reduced neutrophil recovery time. Further study may be warranted to see if the apparent trend of the improved response to chemotherapy in combination with filgrastim can be confirmed in greater number of patients and to assess the effect of the addition of filgrastim on survival.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cytarabine/administration & dosage , Daunorubicin/administration & dosage , Granulocyte Colony-Stimulating Factor/administration & dosage , Hematopoiesis/drug effects , Myelodysplastic Syndromes/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Female , Filgrastim , Granulocyte Colony-Stimulating Factor/adverse effects , Humans , Infusions, Intravenous , Male , Middle Aged , Myelodysplastic Syndromes/pathology , Myelodysplastic Syndromes/physiopathology , Prognosis , Recombinant Proteins , Remission Induction
15.
Bone Marrow Transplant ; 23(12): 1279-82, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10414916

ABSTRACT

The clinical use of autologous marrow transplantation in acute myeloid leukemia (AML) has been hampered by the inability to collect adequate numbers of cells after remission induction chemotherapy and the notably delayed hematopoietic regeneration following autograft reinfusion. Here we present a study in which the feasibility of mobilizing stem cells was investigated in newly diagnosed AML. Among 96 AML patients, 76 patients (79%) entered complete remission. Mobilization was undertaken with low dose and high dose schedules of G-CSF in 63 patients, and 54 patients (87%) were leukapheresed. A median of 2.0 x 10(6) CD34+ cells/kg (range 0.1-72.0) was obtained in a median of three leukaphereses following a low dose G-CSF schedule (150 microg/m2) during an average of 20 days. Higher dose regimens of G-CSF (450 microg/m2 and 600 microg/m2) given during an average of 11 days resulted in 28 patients in a yield of 3.6 x 10(6) CD34+ cells/kg (range 0-60.3) also obtained following three leukaphereses. The low dose and high dose schedules of G-CSF permitted the collection of 2 x 10(6) CD34-positive cells in 46% and 79% of cases respectively (P = 0.01). Twenty-eight patients were transplanted with a peripheral blood stem cell (PBSC) graft and hemopoietic repopulation was compared with the results of a previous study with autologous bone marrow. Recovery of granulocytes (>0.5 x 10(9)/l, 17 vs 37 days) and platelets (>20 x 10(9)/l; 26 vs 96 days) was significantly faster after peripheral stem cell transplantation compared to autologous bone marrow transplantation. These results demonstrate the feasibility of PBSCT in the majority of cases with AML and the potential advantage of this approach with respect to hemopoietic recovery.


Subject(s)
Bone Marrow Transplantation , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid/therapy , Acute Disease , Adolescent , Adult , Aged , Antigens, CD34 , Antineoplastic Agents, Alkylating/therapeutic use , Busulfan/therapeutic use , Cyclophosphamide/therapeutic use , Female , Granulocyte Colony-Stimulating Factor/therapeutic use , Hematopoietic Stem Cell Mobilization , Humans , Male , Middle Aged , Transplantation Conditioning , Transplantation, Autologous
16.
J Clin Oncol ; 15(12): 3496-506, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9396403

ABSTRACT

PURPOSE: The hematopoietic growth factors (HGFs) introduced into induction chemotherapy (CT) of acute myeloid leukemia (AML) might be of benefit to treatment outcome by at least two mechanisms. HGFs given on days simultaneously with CT might sensitize the leukemic cells and enhance their susceptibility to CT. HGFs applied after CT might hasten hematopoietic recovery and reduce morbidity or mortality. MATERIALS AND METHODS: We set out to evaluate the use of granulocyte-macrophage colony-stimulating factor (GM-CSF; 5 microg/kg) in a prospective randomized study of factorial design (yes or no GM-CSF during CT, and yes or no GM-CSF after CT) in patients aged 15 to 60 years (mean, 42) with newly diagnosed AML. GM-CSF was applied as follows: during CT only (+/-, n = 64 assessable patients), GM-CSF during and following CT (+/+, n = 66), no GM-CSF (-/-, n = 63), or GM-CSF after CT only (-/+, n = 60). RESULTS: The complete response (CR) rate was 77%. At a median follow-up time of 42 months, probabilities of overall survival (OS) and disease-free survival (DFS) at 3 years were 38% and 37% in all patients. CR rates, OS, and DFS did not differ between the treatment groups (intention-to-treat analysis). Neutrophil recovery (1.0 x 10(9)/L) and monocyte recovery were significantly faster in patients who received GM-CSF after CT (26 days v 30 days; neutrophils, P < .001; monocytes, P < .005). Platelet regeneration, transfusion requirements, use of antibiotics, frequency of infections, and duration of hospitalization did not vary as a function of any of the therapeutic GM-CSF modalities. More frequent side effects (eg, fever and fluid retention) were noted in GM-CSF-treated patients predominantly related to the use of GM-CSF during CT. CONCLUSION: Priming of AML cells to the cytotoxic effects of CT by the use of GM-CSF during CT or accelerating myeloid recovery by the use of GM-CSF after CT does not significantly improve treatment outcome of young and middle-aged adults with newly diagnosed AML.


Subject(s)
Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage , Leukemia, Myeloid/drug therapy , Acute Disease , Adolescent , Adult , Blood Cell Count , Disease-Free Survival , Evaluation Studies as Topic , Female , Granulocyte-Macrophage Colony-Stimulating Factor/adverse effects , Humans , Male , Middle Aged , Remission Induction , Time Factors , Treatment Outcome
17.
Eur J Clin Microbiol Infect Dis ; 16(5): 364-8, 1997 May.
Article in English | MEDLINE | ID: mdl-9228476

ABSTRACT

The tolerance of aerosolised amphotericin B as prophylaxis against invasive pulmonary aspergillosis was investigated in 61 granulocytopenic periods in 42 patients treated for a haematologic malignancy. Each patient was to receive amphotericin B in doses escalating to 10 mg three times daily (t.i.d.), but only 20 (48%) patients managed to complete the scheduled regimen. One patient tolerated the full dose initially, but had to discontinue treatment when dyspnea developed as a result of pneumonia and acute respiratory distress. Another 22 patients (52%) experienced side effects, including eight (19%) who reported mild coughing and dyspnea but who tolerated the full dose and three (7%) patients whose dose was reduced to 5 mg t.i.d. Another six (14%) patients could tolerate only 5 mg t.i.d., and five (12%) others stopped treatment because of intolerance. Elderly patients (p < 0.05) and those with a history of chronic pulmonary obstructive disease (p = 0.09) were more likely to develop side effects during inhalation. Twelve (28%) patients developed proven of possible invasive fungal infections, but no correlation was established between infection and the total amount of amphotericin B inhaled. Inhalation of aerosolised amphotericin B is poorly tolerated and does not appear useful in preventing invasive pulmonary aspergillosis in granulocytopenic patients.


Subject(s)
Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Aspergillosis/prevention & control , Fungemia/prevention & control , Hematologic Neoplasms/complications , Lung Diseases, Fungal/prevention & control , Administration, Inhalation , Adolescent , Adult , Aged , Agranulocytosis/complications , Agranulocytosis/immunology , Amphotericin B/adverse effects , Antifungal Agents/adverse effects , Aspergillosis/etiology , Chi-Square Distribution , Confidence Intervals , Dose-Response Relationship, Drug , Female , Fungemia/etiology , Hematologic Neoplasms/immunology , Humans , Lung Diseases, Fungal/etiology , Male , Middle Aged , Treatment Outcome
18.
Br J Haematol ; 86(2): 415-7, 1994 Feb.
Article in English | MEDLINE | ID: mdl-7515269

ABSTRACT

Two patients with a myeloid malignancy in whom Sweet's syndrome (acute febrile neutrophilic dermatosis) was diagnosed, are described. They suffered from fever and showed cutaneous lesions, with infiltration of the skin by mature neutrophils without signs of vasculitis. In one of them the clonal origin of the infiltrating neutrophils could be demonstrated by in situ hybridization. In this patient an association with the use of recombinant human granulocyte-colony stimulating factor was suspected. In the other patient, Sweet's syndrome was the initial symptom of haematological disease. Inadequate wound healing after surgical procedures led to the diagnosis.


Subject(s)
Anemia, Refractory, with Excess of Blasts/complications , Leukemia, Myeloid, Acute/complications , Sweet Syndrome/etiology , Adolescent , Anemia, Refractory, with Excess of Blasts/genetics , Chromosome Aberrations , Granulocyte Colony-Stimulating Factor/adverse effects , Humans , Leukemia, Myeloid, Acute/genetics , Male , Middle Aged , Recombinant Proteins/pharmacology , Sweet Syndrome/genetics
19.
Scand J Infect Dis ; 26(5): 585-95, 1994.
Article in English | MEDLINE | ID: mdl-7855556

ABSTRACT

143 aplastic episodes with fever in 91 haematological patients with granulocytopenia were treated empirically in a randomized prospective study using either imipenem (Imi) or a combination of tobramycin and cefuroxime (T/C). Response after 72 h was significantly better in patients receiving Imi (44/75 vs 27/68, p < 0.05). This was seen especially in patients with bacteriologically proven infections where the isolated staphylococci and streptococci were more susceptible to Imi. In both groups, patients who failed to respond to the initial antibiotic therapy were given vancomycin and aztreonam (V/A). The response rate after another 72 h, measured using the same criteria as after the first 72 h, did not differ statistically between the groups. One patient in each study group died from the bacterial infection, both from Gram-positive bacteraemia. Duration of fever was significantly shorter in the Imi group (4 days vs 7 days, p < 0.04). Serum peak and trough concentrations of the antibiotics were comparable. Both regimens were well tolerated. Our results show that monotherapy with imipenem is superior to the combination of tobramycin and cefuroxime during the first 72 h of therapy and can be safely administered to neutropenic patients with predominantly Gram-positive infections. A combination of vancomycin and aztreonam, given when initial imipenem treatment has failed, was effective in only a few patients. Adjuvant glycopeptide therapy from the outset in the treatment of febrile granulocytopenic patients did not seem worthwhile.


Subject(s)
Agranulocytosis/etiology , Drug Therapy, Combination/therapeutic use , Fever of Unknown Origin/etiology , Gram-Positive Bacterial Infections/drug therapy , Imipenem/therapeutic use , Adolescent , Adult , Aged , Agranulocytosis/drug therapy , Aztreonam/administration & dosage , Aztreonam/therapeutic use , Cefuroxime/administration & dosage , Cefuroxime/therapeutic use , Drug Therapy, Combination/administration & dosage , Female , Fever of Unknown Origin/drug therapy , Gram-Positive Bacterial Infections/complications , Humans , Imipenem/administration & dosage , Male , Microbial Sensitivity Tests , Middle Aged , Prospective Studies , Tobramycin/administration & dosage , Tobramycin/therapeutic use , Treatment Failure , Vancomycin/administration & dosage , Vancomycin/therapeutic use
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