In order to find an appropriate model suitable for a multistate survival experiment, 634 patients with chronic myeloid leukaemia (CML) were selected to illustrate the method of analysis. After transplantation, there were 4 possible situations for a patient: disease free, relapse but still alive, death before relapse, and death after relapse. The last 3 events were considered as treatment failure. The results showed that the risk of death before relapse was higher than that of the relapse, especially in the first year after transplantation with competing-risk method. The result of patients with relapse time less than 12 months was much poor by the Kaplan-Meier method. And the multistate survival models were developed, which were detailed and informative based on the analysis of competing risks and Kaplan-Meier analysis. With the multistate survival models, a further analysis on conditional probability was made for patients who were disease free and still alive at month 12 after transplantation. It was concluded that it was possible for an individual patient to predict the 4 possible probabilities at any time. Also the prognoses for relapse either death or not and death either before or after relapse may be given. Furthermore, the conditional probabilities for patients who were disease free and still alive in a given time after transplantation can be predicted.
Bone Marrow Transplantation ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*mortality ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/surgery ; Models, Statistical ; Probability ; Survival Analysis

Pneumonia, along with graft-versus-host disease, is a major cause of morbidity and mortality in patients receiving bone marrow transplantation. The community respiratory virus infections have been found to be large causes of pneumonia. Upper respiratory infection with Parainfluenza virus can progress to severe lower respiratory diseases in bone marrow transplant recipients, of which clinical findings are similar to those of pneumonia by exotic opportunistic pathogens. We report a patient with chronic myelogenous leukemia who had suffered a community-acquired pneumonia by Parainfluenza virus type 3 after bone marrow transplantation.
Bone Marrow Transplantation* ; Bone Marrow* ; Graft vs Host Disease ; Humans ; Leukemia ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Mortality ; Parainfluenza Virus 3, Human* ; Paramyxoviridae Infections* ; Pneumonia* ; Transplantation

Typhlitis is a life threatening necrotizing enterocolitis of the cecum, ascending colon and terminal ileum seen in severely neutropenic patients, however its pathogenesis is not identified up to this time.The incidence of typhlitis in leukemic patient is 10~12%, estimated by postmortem examination, and 46% in induction chemotherapy of leukemia. Recently, entity incidence is more high due to increasing challenges to high dose chemotherapy in solid tumors.We experienced four cases of typhlitis, one was developed in the circumstance of neutropenia induced by induction chemotherapy for acute myelocytic leukemia and others in neutropnia due to primary diseases without chemotherapy, ig, chronic myelocytic leukemia, acute lymphocytic leukemia, myelodysplastic syndrome.All cases were treated with high dose broad spectrum antibiotics in early phase of disease and its outcome was good, so that, early diagnosis of typhlitis is essential, then prompt treatment with high dose antibiotics and intravenous fluid before onset of transmural necrosis is associated with lower morbidity and mortality than surgical resection.
Anti-Bacterial Agents ; Autopsy ; Cecum ; Colon, Ascending ; Drug Therapy ; Early Diagnosis ; Enterocolitis, Necrotizing ; Humans ; Ileum ; Incidence ; Induction Chemotherapy ; Leukemia ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Leukemia, Myeloid, Acute ; Mortality ; Necrosis ; Neutropenia ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Typhlitis*

Leukemia cutis (LC) is defined as a neoplastic leukocytic infiltration of the skin. Few clinical studies are available on recent trends of LC in Korea. The purpose of this study was to analyze the clinical features and prognosis of LC in Korea and to compare findings with previous studies. We performed a retrospective study of 75 patients with LC and evaluated the patients' age and sex, clinical features and skin lesion distribution according to the type of leukemia, interval between the diagnosis of leukemia and the development of LC, and prognosis. The male to female ratio was 2:1, and the mean age at diagnosis was 37.6 yr. The most common cutaneous lesions were nodules. The most commonly affected site was the extremities in acute myelocytic leukemia and chronic myelocytic leukemia except for acute lymphocytic leukemia. Compared with previous studies, there was an increasing tendency in the proportion of males and nodular lesions, and LC most often occurred in the extremities. The prognosis of LC was still poor within 1 yr, which was similar to the results of previous studies. These results suggest that there is a difference in the clinical characteristics and predilection sites according to type of leukemia.
Adult ; Extremities/pathology ; Female ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*diagnosis/mortality/pathology ; Leukemia, Myeloid, Acute/*diagnosis/mortality/pathology ; *Leukemic Infiltration ; Male ; Neoplasm Staging ; Retrospective Studies ; Skin/*pathology

BACKGROUND: Invasive fungal infection (IFI) is an important cause of morbidity and mortality in patients with hematologic malignancy. Patients with IFI who fail to standard therapy have poor prognoses. We investigated the efficacy and safety of caspofungin (CAS) in Korean adults with hematologic diseases and IFI who did not respond to the conventional antifungal therapy. MATERIALS AND METHODS: Patients with IFI refractory or intolerant to standard antifungal therapy received CAS 50 mg IV daily after 70 mg loading dose on day 1. Efficacy and safety of CAS were assessed in patients who received more than one dose. Favorable response [complete (CR) or partial (PR)] was defined as significant improvement of all clinical symptoms, signs, and radiologic abnormalities. RESULTS: From Feb. 2004 to Feb. 2005, 55 patients who met the inclusion criteria were enrolled. There were 32 male and 23 female patients with mean age of 38.2 years (range, 16-65). Underlying diseases were acute leukemia (33 cases), myelodysplastic syndrome (12 cases), chronic myelogenous leukemia (3 cases), and other hematologic diseases (7 cases). Thirty-six patients were receiving chemotherapy and 13 patients were under hematopoietic stem cell transplantation (HSCT). The number of proven, probable, possible, and indeterminate IFI cases was 1, 5, 47, and 2, respectively. Conventional amphotericin B, intravenous itraconazole, and liposomal amphotericin B were administered for average of 14.9 days prior to administering CAS. Mean duration of CAS therapy was 12.8 days (range, 1-45). Twenty-three patients (41.8%) showed favorable responses (CR:PR=8:15) at the end of CAS therapy. Chemotherapy group, neutropenic state, remitted state of underlying disease, and no steroid therapy were significant prognostic factors for favorable response. Eight (14.5%) patients developed drug-related adverse events such as fever, skin eruption, and hepatic dysfunction which were reversible after discontinuation of CAS. Drug-related nephrotoxicity was not observed. CONCLUSION: On the basis of our investigation, CAS was effective and safe as a salvage therapy of refractory IFI or as an alternative for patients intolerant to standard antifungal agents.
Adult ; Amphotericin B ; Antifungal Agents ; Drug Therapy ; Female ; Fever ; Hematologic Diseases* ; Hematologic Neoplasms ; Hematopoietic Stem Cell Transplantation ; Humans ; Itraconazole ; Leukemia ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Male ; Mortality ; Myelodysplastic Syndromes ; Prognosis ; Salvage Therapy* ; Skin

BACKGROUND: Invasive fungal infection (IFI) is an important cause of morbidity and mortality in patients with hematologic malignancy. Patients with IFI who fail to standard therapy have poor prognoses. We investigated the efficacy and safety of caspofungin (CAS) in Korean adults with hematologic diseases and IFI who did not respond to the conventional antifungal therapy. MATERIALS AND METHODS: Patients with IFI refractory or intolerant to standard antifungal therapy received CAS 50 mg IV daily after 70 mg loading dose on day 1. Efficacy and safety of CAS were assessed in patients who received more than one dose. Favorable response [complete (CR) or partial (PR)] was defined as significant improvement of all clinical symptoms, signs, and radiologic abnormalities. RESULTS: From Feb. 2004 to Feb. 2005, 55 patients who met the inclusion criteria were enrolled. There were 32 male and 23 female patients with mean age of 38.2 years (range, 16-65). Underlying diseases were acute leukemia (33 cases), myelodysplastic syndrome (12 cases), chronic myelogenous leukemia (3 cases), and other hematologic diseases (7 cases). Thirty-six patients were receiving chemotherapy and 13 patients were under hematopoietic stem cell transplantation (HSCT). The number of proven, probable, possible, and indeterminate IFI cases was 1, 5, 47, and 2, respectively. Conventional amphotericin B, intravenous itraconazole, and liposomal amphotericin B were administered for average of 14.9 days prior to administering CAS. Mean duration of CAS therapy was 12.8 days (range, 1-45). Twenty-three patients (41.8%) showed favorable responses (CR:PR=8:15) at the end of CAS therapy. Chemotherapy group, neutropenic state, remitted state of underlying disease, and no steroid therapy were significant prognostic factors for favorable response. Eight (14.5%) patients developed drug-related adverse events such as fever, skin eruption, and hepatic dysfunction which were reversible after discontinuation of CAS. Drug-related nephrotoxicity was not observed. CONCLUSION: On the basis of our investigation, CAS was effective and safe as a salvage therapy of refractory IFI or as an alternative for patients intolerant to standard antifungal agents.
Adult ; Amphotericin B ; Antifungal Agents ; Drug Therapy ; Female ; Fever ; Hematologic Diseases* ; Hematologic Neoplasms ; Hematopoietic Stem Cell Transplantation ; Humans ; Itraconazole ; Leukemia ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Male ; Mortality ; Myelodysplastic Syndromes ; Prognosis ; Salvage Therapy* ; Skin

OBJECTIVETo determine the frequency of the derivative 9 [der(9)] deletion among chronic myeloid leukemia (CML) patients with classic and variant Ph translocations, and assess the correlation between this deletion and clinical prognosis.

METHODSCytogenetic analysis of bone marrow cells was performed by direct method and/or 24 h culture method. RHG banding was used for karyotype analysis. Dual-color and dual-fusion DNA probe was used to perform FISH for investigating the deletion of der(9) in Ph+ CML patients.

RESULTSCytogenetics studies showed typical Ph translocation in 76/105 and variant Ph translocation in 29/105 cases. Interphase-FISH studies showed deletion of der(9) in 12 (15.8%) of 76 patients with classic Ph translocation and in 4 (13.7%) of 29 patients with variant translocation. The frequency of deletion was similar in classic and variant translocations (P > 0.05). When the deletion was seen in the patient, it was present in all the Ph+ metaphases and nuclei. In 3 patients there were mixed cell populations with either 5'-abl or 3'-bcr deletion and all the 3 patients had both 5'-abl and 3'-bcr deletion. The median survival time of patients with deletion was significantly shorter than those without deletion (34 months vs 76 months; P < 0.05).

CONCLUSIONDeletion of der(9) is seen in about 1/6 of Ph+ CML patients in our study on Chinese CML patients, Ph+ CML patients with the deletion have shorter median survival time than those without it, indicating that it is a poor prognostic index.

Adolescent ; Adult ; Aged ; Child ; Chromosome Deletion ; Chromosomes, Human, Pair 9 ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; diagnosis ; genetics ; mortality ; Male ; Middle Aged ; Philadelphia Chromosome ; Prognosis ; Survival Rate ; Translocation, Genetic ; Young Adult

This study was aimed to analyze the prognostic factors of the patients with chronic myeloid leukemia (CML). Survival curve and survival rate of 204 patients with CML were estimated with Kaplan-Meier method and Logrank respectively. Univariate and multivariate analysis of prognostic factors carried out by Cox's regression model. The Sokal and Hasford score were used to discriminate the relative risk of Hu and IFN group. The results showed that among the 204 patients, the median survival time was 50 (32-65) months, and 5 year survival rate was 32.3% (95% CI, 23.7%-42.6%). The median survival times of IFN and Hu group were 56 (41-67) and 41 (19-56) months, and 5 year survival rates were 45.4% (95% CI, 37.5%-54.2%) and 26.8% (95% CI, 21.6%-33.3%) (P < 0.001) respectively. From the Cox stepwise regression model, Ph chromosome negative, high LDH, low Hct, percentage of peripheral blood basophils > or = 10%, marrow blasts + promyelocytes > or = 10% and presence of nucleated RBCs was associated with poor prognosis, and the treatment also played an important role in CML. According to the Sokal score, the high, intermediate and low risk rates of Hu group were 72.9%, 21.5% and 5.6%, the median survival time reached 34 (23-49) months, 43 (32-58) and 50 (38-62) months respectively; while censored by the Hasford score, the high, intermediate and low risk rates of IFN group were 17.6%, 25.1% and 57.3% respectively, the median survival time was 44 (33-57), 56 (45-70) and 66 (52-76) months respectively. It is concluded that Ph chromosome, concentration of LDH, percentage of Hct, peripheral blood basophils, marrow blasts, promyelocytes, presence of nucleated RBCs and treatment are the most important prognostic factors for CML. The Sokal score can not discriminate the relative risk of Hu group well, while the Hasford score can discriminate the relative risk of IFN group.
Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Female ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; mortality ; Middle Aged ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Risk Assessment ; methods ; Survival Rate ; Treatment Outcome

OBJECTIVETo investigate the therapeutic efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with chronic myelogenous leukemia (CML), and to analyze the possible prognostic factors.

METHODSThe clinical data of 20 children with CML who had received allo-HSCT was analyzed retrospectively to investigate possible prognostic factors, including age, sex, interval between diagnosis and transplantation, HLA matching between donors and recipients, illness status on transplantation and acute and chronic graft-versus-host disease (GVHD).

RESULTSAt the end of follow-up, 13 of the 20 treated children had disease-free survival (DFS) and the rest (7 cases) died. Four died of severe acute GVHD, two of chronic GVHD and its complications, and one of relapse after transplantation. The three-year DFS was (64.6±1.1%). As shown by the univariate analysis, age was the most important prognostic factor in children with CML who had received allo-HSCT (P<0.05), and in children over 10 years, the prognosis was poor. No other of the above factors had a significant impact on prognosis (P>0.05). The multivariate logistic regression analysis also confirmed age as the only prognostic factor (P<0.01). Severe acute and/or chronic GVHD was the most important cause of patient death. 10/10 HLA-matched donors could improve the transplantation outcome.

CONCLUSIONSAllo-HSCT is an effective treatment for children with CML. To improve the prognosis and treatment outcome, children with CML aged over 10 years should receive allo-HSCT as early as possible. 10/10 HLA-matched donors are preferred in allo-HSCT and GVHD should be prevented.

Adolescent ; Child ; Child, Preschool ; Female ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Histocompatibility Testing ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; mortality ; surgery ; Logistic Models ; Male ; Retrospective Studies ; Transplantation, Homologous

BACKGROUND: Cytomegalovirus (CMV) infection causes the greatest morbidity and mortality after stem cell transplantation (SCT), and in many western studies, CMV infection develops in approximately 70 to 80% of patients treated with allogeneic bone marrow transplantation (BMT). There have been no reports regarding the prevalence and clinical features of CMV infection and disease in patients receiving SCT in Korea. Therefore, we investigated the frequency and clinical characteristics of CMV infection in 53 cases of SCT. METHODS: Underlying diseases were acute myelocytic leukemia (n=21), acute lymphocytic leukemia (n=14), chronic myelocytic leukemia (n=4), severe aplastic anemia (n=13) and non- Hodgkin lymphoma (n=1). Pre-transplant serostatus of donors and recipients was all positive for CMV infection. For screening test of CMV detection, CMV antigen assay or shell vial culture was done. CMV infection was defined as CMV antigenemia or recovery of CMV in culture or positive CMV PCR, and CMV disease was diagnosed when patients had symptoms and signs of specific organs with CMV infection. RESULTS: 1) The incidence of CMV infection was 18.9% (10/53) in all transplant recipients. No significant difference of rate of infection and disease between allogeneic BMT and autologous peripheral blood stem cell transplantation was observed. 2) Five of 10 patients with CMV infection had asymptomatic CMV infection, and the other 5 patients developed overt CMV disease. 3) There was no difference of incidence of CMV infection according to age, type of SCT and use of total body irradiation. But, patients with acute graft-versus-host disease (GVHD) had significantly higher incidence of CMV infection than those without acute GVHD in allogeneic BMT (33.3 vs. 7.4%; P=0.04). 4) CMV antigen assay was evaluated as the most sensitive method for the detection of CMV (83.3%), whereas CMV culture showed the lowest sensitivity (37.5%). CONCLUSIONS: The lower incidence of CMV infection of patients with SCT in our study than that of other western countries may be associated with low incidence of acute GVHD.
Anemia, Aplastic ; Bone Marrow Transplantation ; Cytomegalovirus Infections* ; Cytomegalovirus* ; Graft vs Host Disease ; Hodgkin Disease ; Humans ; Incidence ; Korea ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Leukemia, Myeloid, Acute ; Mass Screening ; Mortality ; Peripheral Blood Stem Cell Transplantation ; Polymerase Chain Reaction ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prevalence ; Stem Cell Transplantation* ; Stem Cells* ; Tissue Donors ; Transplantation ; Whole-Body Irradiation