The broad dissemination of next-generation sequencing capability has increased recognition of clonal hematopoiesis in various clinical settings. In hematologically normal individuals, somatic mutations may occur at an increasing frequency with age in genes that are also commonly mutated in overt myeloid malignancies such as AML and MDS (e.g., DNMT3A, TET2, and ASXL1). This is referred to as clonal hematopoiesis of indeterminate potential (CHIP) and is a benign state; however, it carries a risk of progression to hematologic malignancy as well as mortality primarily because of increased cardiovascular events. In clinical settings, clonal hematopoiesis may be observed in cytopenic patients who do not otherwise meet the criteria for hematologic malignancy, a condition referred to as clonal cytopenias of undetermined significance (CCUS). Distinguishing CCUS from overt MDS or other myeloid neoplasms can be challenging because of the overlapping mutational landscape observed in these conditions. Genetic features that could be diagnostically helpful in making this distinction include the number and biological function of mutated genes as well as the observed variant allele frequency. A working knowledge of clonal hematopoiesis is essential for the diagnosis and clinical management of patients with hematologic conditions. This review describes the key characteristics of clonal hematopoiesis with particular focus on implications for differential diagnosis in patients with CHIP, idiopathic cytopenia, CCUS, and myeloid malignancy.
Diagnosis ; Diagnosis, Differential ; Gene Frequency ; Hematologic Neoplasms ; Hematopoiesis ; Humans ; Mortality

PURPOSE: Fungal infections are an important cause of morbidity and mortality in patients with hematologic malignancies. The therapy of choice in documented or suspected invasive fungal infections has been intravenous Amphotericin B (AmB). Adverse effects such as fever, chils, thrombophlebitis, nausea or vomiting are common. A more serious adverse effect is potential renal impairment. As AmB administration mixed with Intralipid (AmB/Intralipid) was reported to decrease AmB toxicity without a concomitant loss of antifungal efficacy, we studied the efficacy and side effects of long-term administration of AmB/Intralipid in leukemic children with invasive fungal diseases. METHODS: AmB/Intralipid was administered in seven leukemic children (male, 3; female, 4) who had invasive fungal infections between July 1994 and March 1997. RESULTS: AmB/Intralipid was administered at a mean concentration of 1.45mg/kg/day for a mean of 58.1 days with cumulative dose of 3.01g. Excluding 2 patients who succumbed to the underlying leukemia, 4 out of 5 remaining patients remained free of both fungal infection and leukemia. Chills associated with AmB/Intralipid were found 13 times in 4 patients. One patient could not continue the administration because of the chills on the 45th day of AmB/Intralipid. Renal and hepatic impairment greater than Grade II toxicity was found in each case, respectively. The other 6 patients showed mild elevation from the baseline, but remained within the normal limits. CONCLUSION: Long-term, high-dose AmB/Intralipid therapy can be safely and effectively used in immunocompromised children with invasive fungal infections.
Amphotericin B* ; Child* ; Chills ; Female ; Fever ; Hematologic Neoplasms ; Humans ; Leukemia ; Mortality ; Nausea ; Thrombophlebitis ; Vomiting

Multiple myeloma is a hematologic neoplasm with a unique and characteristic manifestation. This condition is responsible for 10% of hematologic malignancies, and thus represents 1% of all cases of cancer in the US. In Korea, unlike in Western society, myeloma has classically been relatively rare, due in part to racial differences. However, the incidence of this disease in Korea has increased steadily over the last 25 years. During this period, both the incidence of and mortality due to myeloma increased by up to 30-fold. Currently, incidence rate and mortality rate exceed 1.0/100,000. Possible reasons for this increase include better detection, as well as an actual increase, probably attributable to contributing factors, including pollution, exposure to chemicals, and socioeconomic change, all of which are related to rapid industrialization. Aging is another important factor contributing to this perceived increase. With the advent of targeted therapy, Korean myeloma study group was organized under the auspice of Korean society of hematology. In addition, Korean myeloma registry was established recently. In this study, epidemiological changes in the incidence and mortality of multiple myeloma in Korea are assessed and compared with the situations of the US and Japan. This article also claims the need for multicenter clinical trials as well as activation of basic researches in myeloma.
Aging ; Epidemiologic Studies ; Epidemiology ; Hematologic Neoplasms ; Hematology ; Incidence ; Japan ; Korea* ; Mortality ; Multiple Myeloma* ; Prevalence ; Industrial Development

BACKGROUND: Invasive pulmonary aspergillosis, a frequent fungal infection in immunocompromised patients, is known to have a poor prognosis despite the use of antifungal therapy in leukemic patients. We studied the outcome of surgical resection of invasive pulmonary aspergillosis where bleeding tendency, localized recurrence of infection, and incidence could be reduced. MATERIAL AND METHOD: We retrospectively reviewed 14 patients with a hematological malignancy where invasive pulmonary aspergillosis was diagnosed during the 10 years between 1998 and 2007. From the medical records, we reviewed the type and treatment of the hematological malignancy, including the diagnostic methods of invasive pulmonary aspergillosis, the preoperative hematological conditions and their management, and the surgical methods and records. We also analyzed the development of postoperative complications and patient mortality, the recurrence of postoperative invasive pulmonary aspergillosis, and if the patients had a bone marrow transplant. RESULT: Fourteen patients with invasive pulmonary aspergillosis and a hematological malignancy underwent a pulmonary lobectomy. One patient had a complication of bronchopleural fistula, but there were no other serious complications such as bleeding or wound infection, and none of the patients died postoperatively. CONCLUSION: We have shown that pulmonary lobectomy is a safe and effective therapy for invasive pulmonary aspergillosis in patients with hematological malignancies that allow further treatment of the hematological malignancy.
Bone Marrow ; Fistula ; Hematologic Diseases ; Hematologic Neoplasms* ; Hemorrhage ; Humans ; Immunocompromised Host ; Incidence ; Invasive Pulmonary Aspergillosis* ; Medical Records ; Mortality ; Postoperative Complications ; Prognosis ; Pulmonary Aspergillosis ; Recurrence ; Retrospective Studies ; Wound Infection

BACKGROUND: Clostridium difficile infection (CDI) is a nosocomial condition prevalent in patients with hematological disorders. We aimed to identify the risk factors associated with the development of CDI and assess the mortality rate at 15 and 30 days among hematologic patients admitted to a tertiary care center. METHODS: We conducted a retrospective case-control study from January 2010 to December 2015. Forty-two patients with hematologic malignancy and CDI, and 84 with hematologic disease and without history of CDI were included in the case and control groups, respectively. RESULTS: Univariate analysis revealed that episodes of febrile eutropenia [odds ratio (OR), 5.5; 95% confidence interval (CI), 2.3–12.9; P<0.001], admission to intensive care unit (OR, 3.8; 95% CI, 1.4–10.2; P=0.009), gastrointestinal surgery (OR, 1.2; 95% CI, 1.1–1.4; P<0.001), use of therapeutic (OR, 6.4; 95% CI, 2.5–15.9; P<0.001) and prophylactic antibiotics (OR, 4.2; 95% CI, 1.6–10.7; P=0.003) in the last 3 months, and >1 hospitalization (OR, 5.6; 95% CI, 2.5–12.6; P<0.001) were significant risk factors. Multivariate analysis showed that use of therapeutic antibiotics in the last 3 months (OR, 6.3; 95% CI, 2.1–18.8; P=0.001) and >1 hospitalization (OR, 4.3; 95% CI, 1.7–11.0; P=0.002) were independent risk factors. Three (7.1%) and 6 (14.2%) case patients died at 15 and 30 days, respectively. CONCLUSION: The risk factors for developing CDI were exposure to therapeutic antibiotics and previous hospitalization. Hematological patients who developed CDI had higher early mortality rates, suggesting that new approaches for prevention and treatment are needed.
Anti-Bacterial Agents ; Case-Control Studies ; Clostridium difficile ; Clostridium ; Hematologic Diseases ; Hematologic Neoplasms ; Hospitalization ; Humans ; Intensive Care Units ; Mortality ; Multivariate Analysis ; Retrospective Studies ; Risk Factors ; Tertiary Care Centers

PURPOSE: The purpose of this study was to determine whether light alcohol drinking increases the risk of cancer by using a meta-analysis of cohort studies because the newly revised 2015 European Code against Cancer fourth edition on alcohol and cancer was based on critical flaws in the interpretation and citation of the previous meta-analyses. MATERIALS AND METHODS: PubMed and EMBASE were searched in April, 2016. Two authors independently reviewed and selected cohort studies on the association between very light (≤ 0.5 drink/day), light (≤ 1 drink/day), or moderate drinking (1-2 drinks/day) and the risk of cancer incidence and mortality. A pooled relative riskwith its 95% confidence intervalwas calculated by a random-effects meta-analysis. Main outcome measures were cancer incidence and mortality. RESULTS: A total of 60 cohort studies from 135 articles were included in the final analysis. Very light drinking or light drinking was not associated with the incidence of most cancers except for female breast cancer in women and male colorectal cancer. Conversely, light drinking was associated with a decreased incidence of both female and male lung cancer significantly and both female and male thyroid cancer marginally significantly. Moderate drinking significantly increased the incidence of male colorectal cancer and female breast cancer,whereas it decreased the incidence of both female and male hematologic malignancy. CONCLUSION: We found that very light or light alcohol drinking was not associated with the risk of most of the common cancers except for the mild increase in the incidence of breast cancer in women and colorectal cancer in men.
Alcohol Drinking* ; Alcohols ; Breast ; Breast Neoplasms ; Cohort Studies* ; Colorectal Neoplasms ; Drinking ; Female ; Hematologic Neoplasms ; Humans ; Incidence ; Lung Neoplasms ; Male ; Mortality ; Outcome Assessment (Health Care) ; Thyroid Neoplasms

No abstract available.
Cohort Studies ; Female ; Hematologic Neoplasms/mortality ; Humans ; Male ; *Occupational Health ; Research/trends ; Retrospective Studies ; *Semiconductors ; Volatile Organic Compounds/toxicity

PURPOSE: Infection is a major complication in patients with malignant disease. This study was performed to identify the causes and the etiologic agents of febrile infections and to characterize the clinical courses including the response to antimicrobial agents inpediatric cancer patients. METHODS: This study reviewed 274 febrile episodes occurring in 163 children with neoplastic disease which were indentified prospectively at Seoul National University Children's Hospital from January, 1991 to June, 1993. Neutropenia was defined as [granulocyte+band from] < or = 500mm(3). Each febrile episode was classified as a microbiologically documented infection(MDI), a clinically documented infection(CDI), and a probale infection(PI). The responses to initial antimicrobial atents were categorized into improvement, temporary improvement, failure, and not evaluable according to period to defervescence. RESULTS: Seventy seven percent of the febrile epidodes developed in neutropenic state. MDI were 98(36%), CDI 92(34%), and PI 84(30%) episodes. Bacteria were isolated in 75%, viruses in 13% and fungi in 11% of MDI. Fifty two episodes(19% of all) were associated with a bacteremia, and focal infections were indentified in 63% of bacteremia. The most frequent organisms causing MDI were E. coli(22%), K. pneumoniae(15%), S.epidermidis(7%). The great majority of infections other than bacteremia ocurred in the lung(32%), oral cavity(17%), skin and soft tissue(13%), and urinary tract(11%). The frequency of antimicrobial resistance of causative organisms was high. The responses to initial antimicrobial agents were improvement in 49%, temporary improvement in 13%, and failure in 38%. Patients with bacteremia responded less well than those with other categories. Mortality was 7% of total episodes. All of the fatal cases occurred in neutropenia and all but one had hematologic malignancies. CONCLUSIONS: This study documents the etiology and the type of infections and the responses to antimicrobial therapy in children with neoplastic diseases. The changes of causative agents and antimicrobial resistance should be considered in therapeutic strategies of cancer infection.
Anti-Infective Agents ; Bacteremia ; Bacteria ; Child* ; Focal Infection ; Fungi ; Hematologic Neoplasms ; Humans ; Mortality ; Neutropenia ; Prospective Studies ; Seoul ; Skin

The mortality rate of the invasive pulmonary aspergillosis to be able to developed during chemotherapy induced myleosuppressionin is high in hematologic malignancy patients despite antifungal treatment. Effective antifungal treatment combined with operation can decrease the mortaligy rate of the invasive pulmonary aspergillosis. Recently, we experienced the successful management of the two cases of invasive pulmonary aspergillosis in acute lymphoblastic leukemia through effective antifungal treatment and surgical resection. We report this cases with review of literature.
Drug Therapy ; Hematologic Neoplasms ; Hematology ; Humans ; Invasive Pulmonary Aspergillosis* ; Mortality ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Pulmonary Aspergillosis

BACKGROUND: Vancomycin resistant enterococcal (VRE) bacteremia is increasing among patients with hematologic malignancies. Our study was to determine the clinical characteristics, risk factors for mortality, and effect of adequate antimicrobial therapy on outcome in patients with hematologic malignancies who developed VRE bacteremia. MATERIALS AND METHODS: we retrospectively reviewed episodes of VRE bacteremia in 90 patients with hematologic malignancices from January 1997 to December 2006. Adequate antimicrobial therapy was defined as the use of linezolid or quinupristin/dalfopristin, initiated within 72 hours of initial positive blood culture and continuing for at least 48 hours. Outcome was evaluated at 14 and 28 days after onset of bacteremia. RESULTS: The overall 14-day and 28-day mortality rates were 44.4% (40/90) and 54.4% (49/90) respectively. Failure of neutrophil recovery (odds ratio [OR], 40.29; 95% confidence interval [CI], 6.22 to 260.72; P< or =0.001) and increased APACHE II score (OR, 1.30; 95% CI, 1.07 to 1.58; P=0.008) were independent risk factors for 14-day as well as for 28-day mortality. To specifically examine the effects of adequate antimicrobial therapy, we performed a separate analysis of the 14-day mortality, after excluding 6 patients who died within 48 hours of bacteremia onset. Multivariate analysis showed that failure of neutrophil recovery (OR, 42.10; 95% CI, 5.77 to 307.00; P< or =0.001) and increased APACHE II score (OR, 1.25; 95% CI, 1.02 to 1.53; P=0.026) were still independently associated with mortality. Adequate antimicrobial therapy, however, did not have a protective effect (OR, 1.91; 95% CI, 0.50 to 7,22; P= 0.338). Of the 65 patients with monomicrobial bacteremia, 30 (46.2%) received adequate antimicrobial therapy and 35 (53.8%) did not: their 14-day mortality rates were 40.0% (12/30) and 42.9% (15/35), respectively (P=0.816). CONCLUSION: In conclusion, severity of underlying illness was associated with mortality. Adequacy of antimicrobial therapy did not improve survival, this may be due to low virulence of enterococci and severity of underlying disease.
APACHE ; Bacteremia* ; Enterococcus ; Hematologic Neoplasms ; Hematology* ; Humans ; Linezolid ; Mortality* ; Multivariate Analysis ; Neutrophils ; Retrospective Studies ; Risk Factors* ; Vancomycin ; Virulence