OBJECTIVE: To investigate the efficacy and safety of colistin sulfate in the treatment of hematonosis patients infected by multidrug-resistant (MDR) gram-negative bacteria (GNB), and discuss the possible factors that affect the efficacy of colistin sulfate. METHODS: The clinical data of 85 hematologic patients infected with MDR GNB in the Soochow Hopes Hematonosis Hospital from April 2022 to November 2022 were collected and divided into clinically effective group with 71 cases and ineffective group with 14 cases according to the therapeutic efficacy of colistin sulfate. The age, gender, type of hematologic disease, status of hematopoietic stem cell transplantation, infection sites, type of pathogen, timing of administration, daily dose and duration of colistin sulfate, and combination with other antibacterial agents of patients in two groups were compared. Logistic regression was used to analyze on the meaningful variables to study the influencing factors of colistin sulfate. The adverse reactions of colistin sulfate were also evaluated. RESULTS: There were no significant differences in age, gender, type of hematologic disease, hematopoietic stem cell transplantation status, infection sites and pathogen type between the effective group and the ineffective group (P>0.05). Compared with the medication time more than 7 days, meropenem used within 7 days in the clinical effective group, and timely replacement with colistin sulfate could obtain better efficacy, the difference was statistically significant (P=0.018). The duration of tigacycline before colistin sulfate did not affect the efficacy, and there was no significant difference in efficacy between the effective and ineffective groups. The therapeutic effect of colistin sulfate at daily dose of 500 000 U q8h was better than that of 500 000 U q12h, the difference was statistically significant (P=0.035). The time of colistin sulfate use in the clinically effective group was longer than that in the ineffective group, which had a statistical difference (P=0.003). Compared with the clinical ineffective group, the efficacy of combination regimens with colistin sulfate was better than that of colistin sulfate monotherapy, and the difference was statistically significant (P=0.013). Multivariate logistic regression analysis was performed on the indicators with statistical differences in the two groups of patients, which suggested that the use time of colistin sulfate (B: 2.358; OR: 10.573; CI: 1.567-71.361; P=0.015) and the combination of colistin sulfate (B: 1.720; OR: 5.586; CI: 1.210-25.787; P=0.028) were influential factors in the efficacy of colistin sulfate. During the treatment, the incidence of nephrotoxicity, hepatotoxicity and peripheral neurotoxicity were 5.9%, 1.2% and 1.2%, respectively. CONCLUSION The use of colistin sulfate improves the clinical efficacy of MDR GNB infections in hematological patients, and the timing of colistin sulfate administration and the combination of drugs are independent factors affecting its clinical efficacy, and the safety during treatment is high.
Humans ; Colistin/adverse effects* ; Anti-Bacterial Agents/therapeutic use* ; Meropenem/adverse effects* ; Treatment Outcome ; Gram-Negative Bacteria ; Hematologic Diseases

PURPOSE: To identify prognostic factors for the outcomes of empirical antifungal therapy, we performed a multicenter, prospective, observational study in immunocompromised patients with hematological malignancies. MATERIALS AND METHODS: Three hundred seventy-six patients (median age of 48) who had neutropenic fever and who received intravenous (IV) itraconazole as an empirical antifungal therapy for 3 or more days were analyzed. The patients with possible or probable categories of invasive fungal disease (IFD) were enrolled. RESULTS: The overall success rate was 51.3% (196/376). Age >50 years, underlying lung disease (co-morbidity), poor performance status [Eastern Cooperative Oncology Group (ECOG) > or =2], radiologic evidence of IFD, longer duration of baseline neutropenic fever (> or =4 days), no antifungal prophylaxis or prophylactic use of antifungal agents other than itraconazole, and high tumor burden were associated with decreased success rate in univariate analysis. In multivariate analysis, age >50 years (p=0.009) and poor ECOG performance status (p=0.005) were significantly associated with poor outcomes of empirical antifungal therapy. Twenty-two patients (5.9%) discontinued itraconazole therapy due to toxicity. CONCLUSION: We concluded that empirical antifungal therapy with IV itraconazole in immunocompromised patients is effective and safe. Additionally, age over 50 years and poor performance status were poor prognostic factors for the outcomes of empirical antifungal therapy with IV itraconazole.
Antifungal Agents/adverse effects/*therapeutic use ; Female ; Hematologic Neoplasms ; Humans ; Immunocompromised Host ; Itraconazole/adverse effects/*therapeutic use ; Male ; Middle Aged ; Prospective Studies ; Republic of Korea

OBJECTIVETo analyze the duration of preventive filgrastim administration as support for chemotherapy and its affecting factors.

METHODSSingle institutional data from a phase Ⅱ clinical trial and a phase Ⅲ clinical trial of pegylated filgrastim were combined. In the two randomized cross-over trials, patients with previously untreated cancer received two cycles of chemotherapy of the same regimen. In the study group, the patients received a single subcutaneous injection of 100 μg/kg pegylated filgrastim, and in the control group, they received daily subcutaneous injections of 5 μg/kg filgrastim.

RESULTSIn 53 chemotherapy cycles, the median duration of filgrastim administration was (9.57±2.10)d. 83.0% (44/53) of them received filgrastim for 7-11 days. Patients with baseline absolute neutrophil count of <4×10(9)/L or body mass index less than 22 received a longer filgrastim prophylaxis(P<0.05). RESULTS of multivariate analysis showed that the baseline absolute neutrophil count is associated with the time of filgrastim administration(P=0.019). The most common adverse event of rhG-CSF was skeletal pain, generally mild and no treatment-related death occurred.

CONCLUSIONSThe median duration of filgrastim support for chemotherapy was 10 days. Patients with lower baseline neutrophil count require a longer filgrastim prophylaxis.

TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01285219.

Antineoplastic Agents ; adverse effects ; Cross-Over Studies ; Filgrastim ; adverse effects ; therapeutic use ; Hematologic Agents ; adverse effects ; therapeutic use ; Humans ; Induction Chemotherapy ; Injections, Subcutaneous ; Multivariate Analysis ; Neoplasms ; drug therapy ; Neutropenia ; chemically induced ; prevention & control ; Time Factors

TNF-alpha mediated apoptosis of the hematopoietic cells has been thought to contribute to the ineffective hematopoiesis observed in myelodysplastic syndrome (MDS). The combination of pentoxifylline (P) and ciprofloxacin (C) has been shown to reduce the serum levels of TNF-alpha, and an earlier trial of P and C with dexamethasone (D) provided good palliation for patients with MDS. The purpose of this study is to assess the hematologic response to PCD therapy for patients suffering with MDS. 21 of 25 patients who completed at least of 12 weeks of treatment were evaluable for the treatment efficacy. At baseline, the patient's median age was 60 yr (range: 18-75 yr). The diagnoses according to WHO classification included: RA (n=5), RCMD (n=10), RARS (n=1), RCMD/RS (n=1), RAEB (3), and CMML (n=1). 11 patients (52%) had at least single lineage response. 3 patients (11%) showed improvement of triple lineage cytopenia. There were no differences in the response rates between the FAB subtypes. The median time to response was 4 weeks (range: 2-12 weeks), and it is interesting that 9 of 11 patients who had a response remained without relapse for a median of 177 days (range: 78-634 days). These preliminary results indicate that anti-cytokine therapy with PCD is an effective and well tolerated palliative treatment for patients with MDS.
Adolescent ; Adult ; Aged ; Anti-Infective Agents/adverse effects/therapeutic use ; Anti-Inflammatory Agents/adverse effects/therapeutic use ; Apoptosis/*drug effects ; Ciprofloxacin/adverse effects/therapeutic use ; Comparative Study ; Dexamethasone/adverse effects/therapeutic use ; Drug Therapy, Combination ; Erythrocyte Count ; Female ; Hematologic Agents/adverse effects/therapeutic use ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes/*blood/drug therapy ; Nausea/chemically induced ; Pentoxifylline/adverse effects/therapeutic use ; Platelet Count ; Time Factors ; Treatment Outcome ; Tumor Necrosis Factor-alpha/*metabolism

BACKGROUNDInvasive fungal infection (IFI) is a common and fatal complication in neutropenic patients with hematological malignancy. Empirical antifungal therapy is widely used in practice due to the difficulty of pathogens determination and illness of the hosts. The aim of this study was to evaluate the efficacy and safety of itraconazole as empirical antifungal therapy for persistent fever in neutropenic patients with hematologic malignancies.

METHODSTwo hundred and seventy-four patients with hematologic malignancies who had suspected fungal infections were enrolled in 18 centers across China between April 2008 and April 2009. Empirical antifungal therapy with intravenous itraconazole 200 mg twice daily was given for the first two days, followed by 200 mg once daily for the next 12 days. Oral itraconazole solution was sequential for follow-up therapy if necessary. Five composite end points were evaluated for the response, which was more restrictive and adopted for the first time in such study in China.

RESULTSThe intent-to-treat analysis included data from 274 patients (full analysis set, FAS), of whom 248 were included as the per-protocol population (PPS). As the composite end point of five indices was concerned, the overall response rate was 43.4%. Seperately, defervescence was achieved in 90% of patients in which 55.5% occured during neutropenia. The mean time to defervescence was 2.71 days. Absence of breakthrough IFI during drug administration or within the first 7 days after study completion was observed in 71.5% of patients. Fifty-five point five percent patients with IFI at baseline was successfully treated. Ninety point five percent patients survived for at least 7 days after completing the study. PPS analysis revealed that the duration of neutropenia ≥ 10 days was a statistically significant negative predictor for the response. The withdrawal rate due to drug-related toxicity or lack of efficacy was 11.0%. The incidence of adverse events was 22.6%, in which 11.6% was study drug related. The most frequent adverse events were mild to moderate liver toxicity.

CONCLUSIONItraconazole shows desirable efficacy and safety as empirical antifungal therapy for febrile neutropenic patients with hematologic malignancies.

Adolescent ; Adult ; Aged ; Antifungal Agents ; adverse effects ; therapeutic use ; Female ; Hematologic Neoplasms ; drug therapy ; microbiology ; Humans ; Itraconazole ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Neutropenia ; drug therapy ; microbiology ; Treatment Outcome ; Young Adult

We assessed the success rate of empirical antifungal therapy with itraconazole and evaluated risk factors for predicting the failure of empirical antifungal therapy. A multicenter, prospective, observational study was performed in patients with hematological malignancies who had neutropenic fever and received empirical antifungal therapy with itraconazole at 22 centers. A total of 391 patients who had abnormal findings on chest imaging tests (31.0%) or a positive result of enzyme immunoassay for serum galactomannan (17.6%) showed a 56.5% overall success rate. Positive galactomannan tests before the initiation of the empirical antifungal therapy (P=0.026, hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.10-4.69) and abnormal findings on the chest imaging tests before initiation of the empirical antifungal therapy (P=0.022, HR, 2.03; 95% CI, 1.11-3.71) were significantly associated with poor outcomes for the empirical antifungal therapy. Eight patients (2.0%) had premature discontinuation of itraconazole therapy due to toxicity. It is suggested that positive galactomannan tests and abnormal findings on the chest imaging tests at the time of initiation of the empirical antifungal therapy are risk factors for predicting the failure of the empirical antifungal therapy with itraconazole. (Clinical Trial Registration on National Cancer Institute website, NCT01060462)
14-alpha Demethylase Inhibitors/adverse effects/therapeutic use ; Adolescent ; Adult ; Aged ; Antifungal Agents/adverse effects/*therapeutic use ; Aspergillosis/complications/*drug therapy ; Candidiasis/complications/*drug therapy ; Coccidioidomycosis/complications/drug therapy ; Febrile Neutropenia/complications/drug therapy ; Female ; Hematologic Neoplasms/complications/drug therapy/*microbiology ; Humans ; Itraconazole/adverse effects/*therapeutic use ; Male ; Mannans/blood ; Middle Aged ; Prospective Studies ; Treatment Outcome ; Young Adult

This study was to investigate the relationship between Clostridium difficile associated diarrhea (CDAD) and intestinal microecosystem in patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) and to clarify clinical characteristics of intestinal microecosystem disorder. Clostridium difficile (CD) was isolated and identified by enzyme-linked-immunosorbent assay using clostridium difficile Premier toxins A&B Kit and anaerobic culture in 44 cases with diarrhea. Fecal flora (bifidobacteria, lactobacillus, bacteroides, peptostreptococcus, Clostridium perfringens, enterobacteriaceae, enterococcus, and yeasts) of patients were quantitatively and qualitatively analyzed by Mitsuoka's methods. The results showed that CDAD occurred after using antibiotic or chemotherapy. Clostridium difficile was detected in 12 patients with diarrhea (positive rate was 27.27%). There was marked changes of intestinal microecosystem when patients suffered from CDAD. The number of lactobacillus, bifidobacteria, bacteroides, enterobacteriaceae and so on decreased significantly. It was effective to treat CDAD with vancomycin, metronidazole and probiotic, but the recurrence rate was 16.67%. In conclusion, CDAD complicated by allo-HSCT is related to change of intestinal microecosystem. While treating CDAD with the sensitive antibiotic, the intestinal flora of patients should be supported actively. This treatment contributes to improving disease status and reducing diarrhea recurrence.
Adolescent ; Adult ; Anti-Bacterial Agents ; adverse effects ; therapeutic use ; Child ; Clostridium Infections ; microbiology ; Clostridium difficile ; growth & development ; Diarrhea ; microbiology ; Female ; Hematologic Neoplasms ; therapy ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Male ; Middle Aged ; Young Adult

BACKGROUND/AIMS: The financial burden of caring for iron-related complications (IRCs) is an emerging medical problem in Korea, as in Western countries. We produced a preliminary estimate of the costs of treating patients for IRCs. METHODS: The medical records of patients who had received multiple transfusions were reviewed. Newly developed cardiomyopathy, heart failure, diabetes mellitus, liver cirrhosis, and liver cancer were defined as IRCs. The costs of laboratory studies, medication, oxygenation, intervention, and education were calculated using working criteria we defined. Costs that had a definite causal relationship with IRCs were included to produce as accurate an estimate as possible. RESULTS: Between 2002 and 2006, 650 patients with hematologic diseases, including 358 with acute leukemia, 102 with lymphoma, 58 with myelodysplastic syndrome or myeloproliferative disease, 46 with multiple myeloma, and 31 with chronic leukemia, received more than 10 units of red blood cells. Nine patients developed IRCs. The primary diagnoses of eight patients were aplastic anemia and that of one patient was chronic lymphocytic leukemia. Two patients who had diabetes were excluded because one was treated at another hospital and the other was diagnosed as oxymetholone-induced diabetes. Of the seven patients included, liver cirrhosis developed in two, heart failure in four, and diabetes mellitus in three. Some of them had two diagnoses. The total cost attributed to IRCs for the seven patients was 47,388,241 KRW (approximately 50,000 USD). CONCLUSIONS: The medical costs of IRCs are considerable, and more effective iron-chelating therapy is necessary to save medical resources and improve patient care. More in the way of comprehensive health and economic studies of IRCs are needed to allow both clinicians and health-policy makers to make better decisions.
Adult ; Costs and Cost Analysis/methods ; Erythrocyte Transfusion/adverse effects ; Female ; Health Care Costs/*statistics & numerical data ; Hematologic Diseases/therapy ; Humans ; Iron/blood ; Iron Chelating Agents/*economics/therapeutic use ; Iron Overload/*economics/etiology/*therapy ; Korea ; Male ; Middle Aged ; Retrospective Studies

Propylthiouracil (PTU) is known to be a potential cause of antineutrophil cytoplasmic antibody (ANCA) positive small vessel vasculitis, resulting in glomerulonephritis and diffuse alveolar hemorrhage (DAH). Herein, we describe a 25-year-old pregnant woman who developed a perinulcear ANCA (p-ANCA) and myeloperoxidase ANCA (MPO-ANCA) positive DAH during PTU therapy. The patient improved after corticosteroid therapy and discontinuation of the PTU. Methimazole was prescribed in spite of the risk of recurrence of DAH because of the pregnancy. The patient is currently free from pulmonary problems. Our case shows that the alternative agent, methimazole, can be used to treat hyperthyroidism in a pregnant patient with PTU associated DAH.
Tomography, X-Ray Computed ; *Pulmonary Alveoli ; Propylthiouracil/*adverse effects/therapeutic use ; *Pregnancy Complications, Hematologic ; Pregnancy ; Hyperthyroidism/blood/complications/*drug therapy ; Humans ; Hemoptysis/*chemically induced/diagnosis/immunology ; Female ; Diagnosis, Differential ; Bronchoscopy ; Antithyroid Agents/*adverse effects/therapeutic use ; Antibodies, Antineutrophil Cytoplasmic/*blood ; Adult

This study evaluated the toxicity profiles of temozolomide in the treatment of malignant glioma as either concurrent or adjuvant chemotherapy. We retrospectively reviewed the medical records of 300 malignant glioma patients treated with temozolomide in two medical institutions in Korea between 2004 and 2010. Two hundred nine patients experienced a total of 618 toxicities during temozolomide therapy. A total of 84.8% of the 618 toxicities were Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or 2, while 15.2% were grade 3 or 4. Among the hematologic toxicities, thrombocytopenia (13.7%), anemia (11.0%), and AST/ALT increases (7.0%) were common. Among the non-hematologic toxicities, nausea (44.3%), vomiting (37.0%), and anorexia (14.3%) were the three most common toxicities. There was no mortality due to temozolomide. Although temozolomide showed many types of toxicities, the majority of the toxicities were tolerable and of lower grade. Gastrointestinal troubles are the most common toxicities in Korean patients treated with temozolomide.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anorexia/etiology ; Antineoplastic Agents, Alkylating/adverse effects/*therapeutic use ; Brain Neoplasms/*drug therapy/pathology/radiotherapy ; Dacarbazine/adverse effects/*analogs & derivatives/therapeutic use/toxicity ; Female ; Glioma/*drug therapy/pathology/radiotherapy ; Hematologic Diseases/etiology ; Humans ; Male ; Middle Aged ; Nausea/drug therapy/etiology ; Neoplasm Staging ; Republic of Korea ; Retrospective Studies ; Severity of Illness Index ; Sex Factors ; Vomiting/drug therapy/etiology ; Young Adult