Hee Je Kim

Risk factors for acute respiratory distress syndrome during neutropenia recovery in patients with hematologic malignancies.

IntroductionNeutropenia recovery may be associated with deterioration in oxygenation and exacerbation of pre-existing pulmonary disease. However, risk factors for acute respiratory distress syndrome (ARDS) during neutropenia recovery in patients with hematologic malignancies have not been studied.MethodsWe studied critically ill patients with hematologic malignancies with the dual objectives of describing patients with ARDS during neutropenia recovery and identifying risk factors for ARDS during neutropenia recovery. A cohort of consecutive neutropenic patients with hematologic malignancies who were admitted to the intensive care unit (ICU) was studied. During a 6-year period, 71 patients recovered from neutropenia, of whom 38 (53.5%) developed ARDS during recovery.ResultsCompared with non-ARDS patients, patients who experienced ARDS during neutropenia recovery were more likely to have pneumonia, be admitted to the ICU for respiratory failure, and receive mechanical ventilator therapy. The in-ICU mortality was significantly different between the two groups (86.8% versus 51.5%, respectively, for patients who developed ARDS during neutropenia recovery versus those who did not during neutropenia recovery). In multivariate analysis, only occurrence of pneumonia during the neutropenic episode was associated with a marked increase in the risk of ARDS (odds ratio, 4.76).ConclusionsPatients with hematologic malignancies complicated by pneumonia during neutropenia are at increased risk for ARDS during neutropenia recovery.

Prognostic factors in critically ill patients with hematologic malignancies admitted to the intensive care unit.

OBJECTIVEnDespite an improvement in the prognosis of patients with hematologic malignancies, the mortality of such patients transferred to the intensive care unit (ICU) is high. This study determined the predictors of mortality in a cohort of critically ill patients with hematologic malignancies admitted to the ICU.nnnMETHODSnWe studied 227 critically ill patients with hematologic malignancies who were admitted to the ICU between April 2009 and December 2011. A cohort of consecutive patients with hematologic malignancies was reviewed retrospectively to identify clinically useful prognostic factors.nnnRESULTSnThe ICU mortality rate was 84.1%, and the in-hospital mortality rate was 89.9%. The ICU mortality was significantly higher in patients with acute leukemia than in those with other malignancies. A significant difference between survivors and nonsurvivors was found in neutropenia and its recovery during the ICU stay, presence of cardiac dysfunction, the need for an invasive mechanical ventilator, use of inotropic/vasopressor agents, platelet count, aspartate transaminase level, pH, and Acute Physiology And Chronic Health Evaluation II score. In the multivariate analysis, acute leukemia, need for invasive mechanical ventilator, use of inotropic/vasopressor agents, and Acute Physiology And Chronic Health Evaluation II scores were independently associated with a worse outcome in patients with hematologic malignancies admitted to the ICU.nnnCONCLUSIONnHigher mortality in patients with hematologic malignancies admitted to the ICU is associated with more severe illness, as reflected by higher organ failure scores or respiratory or hemodynamic instability. Mortality is higher in patients with acute leukemia as compared with other hematologic malignancies.

Selective bowel decontamination for the prevention of infection in acute myelogenous leukemia: a prospective randomized trial.

Background Infection is still a frequent cause of morbidity and mortality in acute myelogenous leukemia (AML) patients receiving chemotherapy. Recently the main cause of infection has changed from gram-negative to gram-positive bacteria and the resistance to antibiotics has increased. This study aimed to access the effectiveness of antimicrobial prophylaxis (AP) with orally absorbable antibiotics. Methods Ninety-five AML patients receiving chemotherapy at Catholic Hemopoietic Stem Cell Transplantation Center from March 1999 to July 1999 were randomly divided into the AP group (250 mg ciprofloxacin twice a day, 150 mg roxithromycin twice a day, 50 mg fluconazole once a day) and the control group for a prospective analysis. Results The incidence of fever was 82.6% in the AP group and 91.6% in the control group (p = 0. 15). Though classification and sites of infections showed no difference between the two groups, the catheter associated infection occurred more frequently in the AP group in significance. The time interval between initiation of chemotherapy and onset of fever, white blood cell (WBC) count at the onset of fever, duration of leukopenia (WBC <1,000/mm3), duration of systemic antibiotic therapy, mortality due to infection and hospitalization period from the data starting chemotherapy showed no differences between the two groups. Infections due to gram negative bacteria decreased to 33.3% in the AP group (vs. 92% in the control group), but infections due to gram positive bacteria increased to 66.7% (vs. 8% in the control group). Gram negative bacteria showed 100% resistance to ciprofloxacin in the AP group and gram-positive bacteria showed 90–100% resistance to erythromycin, regardless of the presence of AP. Conclusion The AP could not reduce the occurrence of infection or infection associated death in AML patients receiving chemotherapy. On considering increased gram-positive infection and resistance to fluoroquinolone and macroiide, routine prescription of AP should be reconsidered. Further studies that assess the effectiveness of AP in other malignancies, aplastic anemia and bone marrow transplantation are required.

Allogeneic bone marrow transplantation for chronic myeloid leukemia: a retrospective study of busulfan–cytoxan versus total body irradiation–cytoxan as preparative regimen in Koreans

From January 1990 to December 1997, 53 Korean patients with chronic myeloid leukemia (CML) receiving bone marrow transplantation (BMT) from human leucocyte antigen (HLA)‐identical sibling donors conditioned with either busulfan and cyclophosphamide (BU/CY regimen) or total body irradiation and cyclophosphamide (TBI/CY regimen) were compared retrospectively. u2028 Transplantation‐related mortality was 19% in BU/CY and 12% in TBI/CY, and early death (<100 d) occurred in 3 patients conditioned with BU/CY. Grade II–IV acute graft‐versus‐host disease (GVHD) was 9% of BU/CY and 52% of TBI/CY patients. Overall incidence of chronic GVHD was 50% of BU/CY and 52% of TBI/CY patients. In patients with chronic phase, 5‐yr overall survival was 73% in the BU/CY group compared with 87% in the TBI/CY group (p=NS), and overall disease‐free survival was 75% in the BU/CY group and 59% in the TBI/CY group (p=NS). So far, with a median follow‐up of 45 months, 11 patients have relapsed; three relapses occurred after BU/CY and 8 after TBI/CY. The actuarial 5‐yr relapse rate was 15% after BU/CY, 34% after TBI/CY (p=0.46). For patients transplanted in chronic phase within 1 yr after diagnosis, there was a clear trend for a lower relapse rate in the BU/CY group (5‐yr relapse rate 0%) compared with the TBI/CY group (5‐yr relapse rate 30%). u2028 The BU/CY group had similar BMT‐related toxicity and similar overall survival and showed a clear trend of low relapse compared with the TBI/CY group. Therefore, BU/CY is an acceptable alternative for patients with CML during HLA‐identical sibling allogeneic BMT.

The Outcome of Unrelated Hematopoietic Stem Cell Transplants with Total Body Irradiation (800 cGy) and Cyclophosphamide (120 mg/kg) in Adult Patients with Acquired Severe Aplastic Anemia

To verify the feasibility of 800 cGy of total body irradiation (TBI) with 120 mg/kg of cyclophosphamide (TBI-800/Cy-120) as a conditioning regimen for unrelated stem cell transplantation (u-SCT) in adult patients with severe aplastic anemia, we analyzed 50 consecutive patients who underwent u-SCT, including 26 patients from our previous pilot study. Seventeen patients received transplants from mismatched donors via high-resolution DNA typing (8 of 8). Thirty-eight patients received bone marrow and 12 peripheral blood stem cells (PBSCs). Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and short-course methotrexate. All patients achieved engraftment, and the median days of neutrophil and platelet recovery were 13 days and 20 days, respectively. The 5-year estimated overall survival was 88.0%. The cumulative incidences of acute grade II-IV GVHD (aGVHD) and chronic GVHD (cGVHD) were 46.0% and 50.3%, respectively. Only an HLA-mismatched donor was associated with the occurrence of aGVHD on multivariate analyses, whereas prior aGVHD and the use of PBSCs were associated with the occurrence of cGVHD on univariate analyses. In conclusion, the excellent outcomes of u-SCT with TBI-800/Cy-120 suggest that u-SCT may be applicable to patients with severe aplastic anemia even without prior treatment with immunosuppressive therapy, which will require testing in prospective trials in the future.

Bacteremic cellulitis caused by non-O1, non-O139 Vibrio cholerae in a patient following hematopoietic stem cell transplantation.

Bacteremic cellulitis caused by non-O1, non-O139 Vibrio cholerae in a patient following hematopoietic stem cell transplantation

Reduced antibody formation after influenza vaccination in patients with neuromyelitis optica spectrum disorder treated with rituximab

Vaccination against infection becomes important in patients with neuromyelitis optica spectrum disorder (NMOSD) because they are at an increased risk of infection due to long‐term immunosuppressive therapy. However, it is unclear whether NMOSD patients under immunosuppression therapy show proper antibody formation after vaccination. Thus the antibody formation after influenza A (H1N1) vaccination in patients with NMOSD receiving rituximab was evaluated.

DNMT3A R882 Mutation with FLT3-ITD Positivity Is an Extremely Poor Prognostic Factor in Patients with Normal-Karyotype Acute Myeloid Leukemia after Allogeneic Hematopoietic Cell Transplantation

The prognostic relevance of epigenetic modifying genes (DNMT3A, TET2, and IDH1/2) in patients with acute myeloid leukemia (AML) has been investigated extensively. However, the prognostic implications of these mutations after allogeneic hematopoietic cell transplantation (HCT) have not been evaluated comprehensively in patients with normal-karyotype (NK)-AML. A total of 115 patients who received allogeneic HCT for NK-AML were retrospectively evaluated for the FLT3-ITD, NPM1, CEBPA, DNMT3A, TET2, IDH1/2, WT1, NRAS, ASXL2, FAT1, DNAH11, and GATA2 mutations in diagnostic samples and analyzed for long-term outcomes after allogeneic HCT. The prevalence rates for the mutations were as follows: FLT3-ITD positivity (FLT3-ITD(pos)) (32.2%), NPM1 mutation (43.5%), CEBPA mutation (double) (24.6%), DNMT3A mutation (DNMT3A(mut)) (31.3%), DNMT3A R882(mut) (18.3%), TET2 mutation (8.7%), and IDH1/2 mutation (16.5%). The 5-year overall survival (OS) and event-free survival (EFS) rates were 57.3% and 58.1%, respectively. A multivariate analysis revealed that FLT3-ITD(pos) (hazard ratio, [HR], 2.23; Pxa0=xa0.006) and DNMT3A R882(mut) (HR, 2.74; Pxa0=xa0.002) were unfavorable prognostic factors for OS. In addition, both mutations were significant risk factors for EFS and relapse. People with DNMT3A R882(mut) accompanied by FLT3-ITD(pos) had worse OS and EFS, and higher relapse rates than those with the other mutations, which were confirmed in a propensity score 1:2 matching analysis. These results suggest that DNMT3A R882(mut), particularly when accompanied by FLT3-ITD(pos), is a significant prognostic factor for inferior transplantation survival outcome by increasing relapse risk, even after allogeneic HCT.

JAK2 V617F mutation in myelodysplastic syndrome, myelodysplastic syndrome/myeloproliferative neoplasm, unclassifiable, refractory anemia with ring sideroblasts with thrombocytosis, and acute myeloid leukemia

Background The JAK2 V617F mutation has been noted in the cases of polycythemia vera, essential thrombocythemia, and primary myelofibrosis patients. This mutation occurs less frequently in acute myeloid leukemia (AML) and other hematologic diseases, such as myelodysplastic syndrome (MDS); myelodysplatic syndrome/myeloproliferative neoplasm, unclassifiable (MDS/MPN-U); and refractory anemia with ring sideroblasts with thrombocytosis (RARS-T). Methods Patients diagnosed with hematologic diseases other than MPN who visited Seoul St Marys Hospital from January 2007 to February 2010 were selected. A total of 43 patients were enrolled in this study: 12 MDS, 9 MDS/MPN-U, 7 RARS-T, and 15 AML patients. The diseases were diagnosed according to the 2008 WHO classification criteria. Data obtained from JAK2 V617F mutation analysis and cytogenetic study as well as complete blood count and clinical data were analyzed. Results Of the 43 patients, 6 (13.9%) harbored the JAK2 V617F mutation. The incidence of the JAK2 V617F mutation in each patient group was as follows: 8.3% (1/12), MDS; 22.2% (2/9), MDS/MPN-U; 14.3% (1/7), RARS-T; and 13.3%, (2/15) AML. The platelet count was higher than 450×109/L in 3 of the 6 patients (50%) harboring the JAK2 V617F mutation, and it was in the normal range in the remaining 3 patients. Among the 6 patients, 1 MDS and 1 MDS/MPN-U patients had the 46,XX,del(20)(q11.2) karyotype. Conclusion The JAK2 V617F mutation is associated with an increased platelet count in MDS, MDS/MPN-U, RARS-T, and AML patients. Cytogenetic abnormalities of del(20)(q11.2) occurred in 1/3 of patients with the JAK2 V617F mutation but further studies are required to confirm this association.

Adverse prognostic effect of homozygous TET2 mutation on the relapse risk of acute myeloid leukemia in patients of normal karyotype.

Mutation in ten-eleven-translocation oncogene family member 2 ( TET2 ) has been extensively investigated in the context of several hematologic malignancies and occurs in 7%–23% of patients with acute myeloid leukemia (AML).[1][1]–[4][2] TET2 acts to demethylate DNA, and TET2 mutations are