OBJECTIVE: To screen factors affecting the prognosis of chronic myeloid leukemia (CML) patients, and construct a nomogram model for event-free survival (EFS). METHODS: To screen out meaningful variables by univariate and multivariate Cox regression analysis in CML patients, and construct a nomogram model using R software. The nomogram was validated using consistency index (C-index), receiver operating characteristic (ROC) curve, area under the ROC curve (AUC), calibration curve, decision curve analysis (DCA), and risk stratification analysis. RESULTS: This study analyzed data from 116 CML patients. Univariate and multivariate Cox regression analysis demonstrated that age, peripheral blood basophil percentage, BCR-ABL1 ^IS at 3 months, and red blood cell distribution width (RDW) were independent prognostic factors of EFS. Subsequently, a nomogram was constructed based on the above predictors. The C-index of the nomogram was 0.733(95%CI : 0.676-0.790). The AUC values for predicting 1-, 3-, and 5-year EFS rate were 0.765, 0.855, and 0.827, respectively. The results of the calibration curve and DCA curve showed that the predictive model had good consistency, as well as strong clinical utility. The patients were stratified into high-risk group and low-risk group based on the total score of the model, there was a significant difference in EFS between the two groups (P < 0.001). CONCLUSION Age, peripheral blood basophil percentage, BCR-ABL1 ^IS at 3 months, and RDW were associated with the prognosis of CML patients. The nomogram model constructed in this study can accurately predict the prognostic status of CML patients, but its widespread application still requires external and prospective validation.
Nomograms ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/mortality* ; Proportional Hazards Models ; Erythrocyte Indices ; Risk Assessment/methods* ; Fusion Proteins, bcr-abl/genetics* ; Basophils ; Leukocyte Count ; Humans

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

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

OBJECTIVETo retrospectively analyze the effects of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on childhood chronic myelogenous leukemia (CML).

METHODOf the 24 consecutive cases, 16 were boys and 8 were girls. The median age of patients was 12 (3 - 16) years old; 16 cases were in chronic phase (CP) of CML, 1 case in accelerated phase (AP) and 5 cases in blastic phase (BP). Allo-HSCT from HLA identical siblings were performed for 5 cases, HLA haplotype was performed for 14 cases and unrelated allo-HSCT for 5 cases. Twenty-four cases underwent allo-HSCT with conditioning regimen of BUCY. Prophylaxis of graft versus host disease (GVHD) included CsA + MTX plus MMF. The average follow-up was 36 months.

RESULTAll of patients were successfully engrafted. The 5-year overall survival (OS) of the 24 cases was 81%. Four patients died after allo-HSCT including 3 cases in BP from haploidentical donors and 1 case in CP from HLA identical sibling. The 5 cases who received unrelated allo-HSCT have been alive. Among the 10 cases who survived over 5 years, 3 had chronic GVHD.

CONCLUSIONChildren with CML could be treated effectively with allo-HSCT. There were no significant differences among different donors. Transplantation to children with CML should be performed as early as possible. Preparative regimen adjustment before transplantation, the transplantation of associated comorbidities and effective prevention and treatment for CML patients after prolonged graft survival of high quality have important significance.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Child, Preschool ; Cyclophosphamide ; administration & dosage ; Female ; Graft vs Host Disease ; mortality ; prevention & control ; Hematopoietic Stem Cell Transplantation ; adverse effects ; methods ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; mortality ; therapy ; Male ; Methotrexate ; administration & dosage ; Retrospective Studies ; Survival Analysis ; Transplantation Conditioning ; methods ; Transplantation, Homologous ; Treatment Outcome

OBJECTIVETo retrospectively analyze the curative effects and prognostic factors of HLA-matched sibling donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) for chronic myelogenous leukemia patients (CML).

METHODSOf the 35 CML patients, 26 were males and 9 were females, with a median age of 32 (12 - 50) years. 30 patients were in chronic phase of CML, 5 patients were in accelerated phase. Allo-HSCT from HLA identical siblings was performed for 35 patients, of whom 11 received bone marrow transplantation (BMT) and 24 peripheral blood stem cell transplantation (PBSCT). Conditioning regimens was TBI (total-body irradiation) + CY (CTX) protocol in 8 patients and BU/CY protocol in 27 patients. The average follow-up was 48 months (range 7 - 108 months).

RESULTS34 (97.1%) patients were successfully engrafted. Among them, 21 patients (60.0%) had three years disease-free (DFS) survival. The overall 5-year survival (OS) was 57.1%. Two patients (5.7%) relapsed. Transplant-related mortality occurred in 12 patients. Hemorrhagic cystitis (HC) occurred in 5 patients and HVOD was observed in 1 patient. Acute graft-versus-host disease (aGVHD) occurred in 18 patients (51.4%), among them 7 patients (20.0%) were of grade III-IV. Chronic GVHD was in 17 patients (48.5%). There was no significant difference in 3-years DFS between BMT group and PBSCT group (54.5% vs. 62.5%, P > 0.05). The 3-year disease-free survival (DFS) was 42.9% in TBI/CY group and 55.6% in BU/CY group (P > 0.05). In univariate prognostic analysis model, the DFS at 3 years is 75% and 47.4% for < or =30 years patients and >30 years patients, respectively, P < 0.05. The 3-year DFS of patients with first chronic phase is higher than patients with advanced diseases (61.3% vs. 40%, P < 0. 05). The 3-year DFS in patients of grade I - II GVHD was higher than that in patients of grade III-IV GVHD (81.8% vs. 14.3%, P < 0.05).

CONCLUSIONThe patients who had transplantation done within 1 year after diagnosis during their first chronic phase of disease and who had low-grade GVHD have better prognosis. Those patients who had III-IV acute GVHD are prone to incorporate severe infection, which was a worse prognostic factor of allo-HSCT for chronic myelogenous leukemia.

Adolescent ; Adult ; Age Factors ; Child ; Cystitis ; etiology ; Disease-Free Survival ; Female ; Follow-Up Studies ; Graft vs Host Disease ; etiology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; methods ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; mortality ; therapy ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Siblings ; Survival Rate ; Transplantation Conditioning ; Transplantation, Homologous

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 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

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

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