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 w...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.展开更多
ATYPICAL chronic myeloid leukaemia （aCML）, which shows both myeloproliferative and mye- Iodysplastic features, is a type of myeloprolif- erative/myelodysplastic disease as defined bythe World Health Organisation （...ATYPICAL chronic myeloid leukaemia （aCML）, which shows both myeloproliferative and mye- Iodysplastic features, is a type of myeloprolif- erative/myelodysplastic disease as defined bythe World Health Organisation （WHO） classification of the myeloid neoplasms. Because of the presence of neutrophilic leukocytosis, aCML may resemble chronic myeIogenous leukemia （CML）. However, in contrast with CML, aCML does not have the Philadelphia chromosome or the bcr/abl fusion gene.展开更多
Rationale:Chronic myeloid leukaemia is a myeloproliferative disorder due to clonal hyperproliferation of myeloid cells within the bone marrow.It can present both pro-and anti-thrombotic states.CML has different presen...Rationale:Chronic myeloid leukaemia is a myeloproliferative disorder due to clonal hyperproliferation of myeloid cells within the bone marrow.It can present both pro-and anti-thrombotic states.CML has different presentations within the gastrointestinal tract.Patient’s concern:A 40-year-old non-diabetic and non-hypertensive male complained of abdominal pain with nausea and emesis for 1 day.Besides,he had a history of abdominal distension and fever for 1 day.Diagnosis:Acute small bowel gangrene due to chronic myeloid leukaemia.Intervention:A limited resection of small intestine with ileostomy and mucus fistula.Outcome:After 3 months following surgery the patient underwent stoma closure.The patient was followed up for more than 3 years postoperatively.During the follow-up,the patient was asymptomatic without any recurrence of the disease.Lesson:Chronic myeloid leukaemia should be considered as one of the causes for small intestine gangrene when there is increased leukocyte count,splenomegaly without evidence of atherosclerotic occlusion or systemic emboli from the heart.展开更多
OBJECTIVE To study the mechanism of IFN on CML.METHODS Samples of 15 CML patients and 10 healthy controlswere studied. The flow cytometry was performed to identifycirculating pDCs. The concentration of IFN-α in serum...OBJECTIVE To study the mechanism of IFN on CML.METHODS Samples of 15 CML patients and 10 healthy controlswere studied. The flow cytometry was performed to identifycirculating pDCs. The concentration of IFN-α in serum and that inthe supernatant of peripheral blood mononuclear cells (PBMCs)cultured after stimulation with CpG ODN2216 were examinedboth in CML patients and in the healthy controlsRESULTS There was significant reduction in the numberof circulating pDCs, serum concentration of IFN-α and thecapacity of IFN-α producing PBMCs in CML patients comparedwith those in healthy control individuals (P < 0.001). After theactive treatment with IFN-α and hydroxyurea, the quantity andfunction of pDCs were increased in stabilized patients, especiallythe function of pDCs in 2 patients achieving major cytogeneticresponse (MCR). The proportion and function of pDCs and theserum levels of IFN were inversely correlated with both WBC andage of the patients with CML, and positively correlated with thestate of the illness.CONCLUSION CML patients had a reduced number anddysfunction of circulating pDCs. The active treatment with IFN inCML patients may be related to the restoration of pDCs.展开更多
Background: Treatment for Chronic Myeloid Leukaemia (CML) is mainly imatinib mesylate (IM) from original-brand, Glivec? or generic-type homologs, Imatib?. Materials and Methods: A collection of 149 CML patients was tr...Background: Treatment for Chronic Myeloid Leukaemia (CML) is mainly imatinib mesylate (IM) from original-brand, Glivec? or generic-type homologs, Imatib?. Materials and Methods: A collection of 149 CML patients was treated over a period of 6 years at Hiwa hospital. These patients were clustered into three groups: Group A was treated with Imatib for more than one year. All survivors of group A patients were switched to Glivec, classified as group B. Group C received only Glivec after June 2011. Imatib and Glivec are administered at doses 400-, 600- and 800-mg according to the CML stage. Results: Among group A patients, 68 (60%) were in complete haematological response (CHR), 32 (28.3%) developed acceleration and 13 (11.5%) patients were deceased. After switching to Glivec (group B), 69 (69%) patients remained in CHR, 10 (10%) patients weredeceased and 21 (21%) patients remained in acceleration. Of the 36 patients in group C, 33 (91.7%) were in CHR, 1 (2.8%) were in acceleration and 2 (5.5%) deceased. Those patients with CHR were tested randomly for BCR/ABL by FISH, and only 1/25 (4%) patients were found with complete cytogenetic response (CCyR) in group A, while 31/42 (73.8%) and 13/17 (76.5%) have CCyR in group B and C, respectively. Conclusions: Our results demonstrate a less cytogenetic response to treatment in patients of CML, who received the Imatib therapy, while a significant cytogenetic remission was found in patients with CHR after they switched to Glivec.展开更多
Background: This document includes recommendations and guidelines issued by a group of Mexican researchers and specialists gathered in the First National Colloquium for the Diagnosis and Management of Chronic Myeloid ...Background: This document includes recommendations and guidelines issued by a group of Mexican researchers and specialists gathered in the First National Colloquium for the Diagnosis and Management of Chronic Myeloid Leukaemia (CML) by initiative of Instituto Nacional de Cancerología and with the support of the Leukaemia Department of the MD Anderson Cancer Center. Mexico lacks of updated information taken from its own reality on the diagnosis and treatment of CML and other haematological disorders;besides, there are no national guidelines. Aim: To publish a consensus document with guidelines for the management of CML adjusted to the national environment and overall characteristics. Method: The participants answered a DELPHI questionnaire about the overall aspects of the disease, aiming to target controversial topics, discuss them in the colloquium, and to agree on the best ones. After those meetings, a final document was drawn up. Results: The group presents recommendations for definition, diagnosis, prognosis, monitoring, and treatment of CML in Mexico. Conclusions: Having consensus guidelines for the clinical management of CML in our country will enable the consensual practice of Mexican specialists regarding the clinical approach to CML, as well as optimize the resources which allow the rational planning of the medical care strategies.展开更多
Priapism is a painful and prolonged erection occurring without any sexual stimulation and not resulting in ejaculation. It most often occurs in patients with sickle cell disease. We report here the case of acute recur...Priapism is a painful and prolonged erection occurring without any sexual stimulation and not resulting in ejaculation. It most often occurs in patients with sickle cell disease. We report here the case of acute recurrent priapism revealing inaugural mode of CML in a 22-year-old patient with no particular pathological history. The study of the onco-hematological karyotype revealed a karyotype with 46 chromosomes with a clonal chromosomal anomaly: The t (9;22) “Philadelphia chromosome”. The evolution was favorable under imatinib.展开更多
OBJECTIVE To investigate the effects of survivin antisense oligodeoxy-nucleotid (ASODN) on proliferation and apoptosis in the chronic myeloid leukemia cell line K562. METHODS Different concentrations of an antisense o...OBJECTIVE To investigate the effects of survivin antisense oligodeoxy-nucleotid (ASODN) on proliferation and apoptosis in the chronic myeloid leukemia cell line K562. METHODS Different concentrations of an antisense oligodeoxy-nucleotid and control sequence (scrambled ODN) targeting the survivin gene were transferred into K562 by a lipofectin reagent. The MTT assay was used to measure the growth inhibitory rate, IC50, and to observe the cytotoxicity of survivin ASODN in the K562 cells. The morphologic changes in the nucleus and the apoptotic rate were observed by Hoechst33342/PI staining. Caspase-3 activity was evaluated by a kinase activity assay. The changes of survivin protein expression after transfection were detected by Western blots. RESULTS Eight hours after transfection, fluorescence in the K562 cells was well distributed. Treatment of the cells for 44 h with different concentrations of survivin ASODN produced a IC50 of 800 nmol/L. The growth inhibitory rate with 200, 400, 600 and 1000 nmol/L of survivin ASODN was 15.8±1.6%, 23.8±5.9%, 37.1±5.6% and 77.3±2.5% respectively. After 36 h of of survivin ASODN treatment, distinct morphologic changes characteristic of cell apoptosis such as karyopyknosis and conglomeration were observed by Hoechst33342/PI staining. Caspase-3 activity increased significantly after treatment of the cells with different concentrations of survivin ASODN(P<0.01)and following treatment with 800 nmol/L survivin ASODN, survivin expression decreased significantly. CONCLUSION Survivin ASODN exerts an anti-cancer effect by inducing apoptosis in K562 leukaemia cells. Up-regulated expression of caspase-3 may play a role in this process.展开更多
Although the advent of tyrosine kinase inhibitors(TKIs)has dramatically improved the survival of patients with chronic myeloid leukaemia(CML),acquired drug resistance and TKI-insensitive leukaemic stem cells(LSCs)rema...Although the advent of tyrosine kinase inhibitors(TKIs)has dramatically improved the survival of patients with chronic myeloid leukaemia(CML),acquired drug resistance and TKI-insensitive leukaemic stem cells(LSCs)remain major obstacles to a CML cure.In recent years,the reprogramming of mitochondrial metabolism has emerged as a hallmark of cancers,including CML,and in turn may be exploited for therapeutic purposes.Here,we investigated the effects of several drugs on the mitochondrial function of the CML cell line K562 and found that 5-aminoimidazole-4-carboxamide ribotide(AICAR)and decitabine could effectively increase the ATP content and mitochondrial biogenesis.In addition,these two drugs induced cell cycle arrest and a decrease in colony-forming capacity and promoted K562 cell differentiation.Moreover,we demonstrated that treatment with AICAR or decitabine enhanced the sensitivity o f K562 cells to imatinib,as evidenced by a combination treatment assay.Altogether,our findings indicate that TKIs combined with mitochondrial regulation may provide a therapeutic strategy for the treatment of CML.展开更多
文摘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.
文摘ATYPICAL chronic myeloid leukaemia （aCML）, which shows both myeloproliferative and mye- Iodysplastic features, is a type of myeloprolif- erative/myelodysplastic disease as defined bythe World Health Organisation （WHO） classification of the myeloid neoplasms. Because of the presence of neutrophilic leukocytosis, aCML may resemble chronic myeIogenous leukemia （CML）. However, in contrast with CML, aCML does not have the Philadelphia chromosome or the bcr/abl fusion gene.
文摘Rationale:Chronic myeloid leukaemia is a myeloproliferative disorder due to clonal hyperproliferation of myeloid cells within the bone marrow.It can present both pro-and anti-thrombotic states.CML has different presentations within the gastrointestinal tract.Patient’s concern:A 40-year-old non-diabetic and non-hypertensive male complained of abdominal pain with nausea and emesis for 1 day.Besides,he had a history of abdominal distension and fever for 1 day.Diagnosis:Acute small bowel gangrene due to chronic myeloid leukaemia.Intervention:A limited resection of small intestine with ileostomy and mucus fistula.Outcome:After 3 months following surgery the patient underwent stoma closure.The patient was followed up for more than 3 years postoperatively.During the follow-up,the patient was asymptomatic without any recurrence of the disease.Lesson:Chronic myeloid leukaemia should be considered as one of the causes for small intestine gangrene when there is increased leukocyte count,splenomegaly without evidence of atherosclerotic occlusion or systemic emboli from the heart.
基金supported by a grant from the Science and Technology Planning Project of Gansu Province,China(No.2005LZ0627).
文摘OBJECTIVE To study the mechanism of IFN on CML.METHODS Samples of 15 CML patients and 10 healthy controlswere studied. The flow cytometry was performed to identifycirculating pDCs. The concentration of IFN-α in serum and that inthe supernatant of peripheral blood mononuclear cells (PBMCs)cultured after stimulation with CpG ODN2216 were examinedboth in CML patients and in the healthy controlsRESULTS There was significant reduction in the numberof circulating pDCs, serum concentration of IFN-α and thecapacity of IFN-α producing PBMCs in CML patients comparedwith those in healthy control individuals (P < 0.001). After theactive treatment with IFN-α and hydroxyurea, the quantity andfunction of pDCs were increased in stabilized patients, especiallythe function of pDCs in 2 patients achieving major cytogeneticresponse (MCR). The proportion and function of pDCs and theserum levels of IFN were inversely correlated with both WBC andage of the patients with CML, and positively correlated with thestate of the illness.CONCLUSION CML patients had a reduced number anddysfunction of circulating pDCs. The active treatment with IFN inCML patients may be related to the restoration of pDCs.
文摘Background: Treatment for Chronic Myeloid Leukaemia (CML) is mainly imatinib mesylate (IM) from original-brand, Glivec? or generic-type homologs, Imatib?. Materials and Methods: A collection of 149 CML patients was treated over a period of 6 years at Hiwa hospital. These patients were clustered into three groups: Group A was treated with Imatib for more than one year. All survivors of group A patients were switched to Glivec, classified as group B. Group C received only Glivec after June 2011. Imatib and Glivec are administered at doses 400-, 600- and 800-mg according to the CML stage. Results: Among group A patients, 68 (60%) were in complete haematological response (CHR), 32 (28.3%) developed acceleration and 13 (11.5%) patients were deceased. After switching to Glivec (group B), 69 (69%) patients remained in CHR, 10 (10%) patients weredeceased and 21 (21%) patients remained in acceleration. Of the 36 patients in group C, 33 (91.7%) were in CHR, 1 (2.8%) were in acceleration and 2 (5.5%) deceased. Those patients with CHR were tested randomly for BCR/ABL by FISH, and only 1/25 (4%) patients were found with complete cytogenetic response (CCyR) in group A, while 31/42 (73.8%) and 13/17 (76.5%) have CCyR in group B and C, respectively. Conclusions: Our results demonstrate a less cytogenetic response to treatment in patients of CML, who received the Imatib therapy, while a significant cytogenetic remission was found in patients with CHR after they switched to Glivec.
文摘Background: This document includes recommendations and guidelines issued by a group of Mexican researchers and specialists gathered in the First National Colloquium for the Diagnosis and Management of Chronic Myeloid Leukaemia (CML) by initiative of Instituto Nacional de Cancerología and with the support of the Leukaemia Department of the MD Anderson Cancer Center. Mexico lacks of updated information taken from its own reality on the diagnosis and treatment of CML and other haematological disorders;besides, there are no national guidelines. Aim: To publish a consensus document with guidelines for the management of CML adjusted to the national environment and overall characteristics. Method: The participants answered a DELPHI questionnaire about the overall aspects of the disease, aiming to target controversial topics, discuss them in the colloquium, and to agree on the best ones. After those meetings, a final document was drawn up. Results: The group presents recommendations for definition, diagnosis, prognosis, monitoring, and treatment of CML in Mexico. Conclusions: Having consensus guidelines for the clinical management of CML in our country will enable the consensual practice of Mexican specialists regarding the clinical approach to CML, as well as optimize the resources which allow the rational planning of the medical care strategies.
文摘Priapism is a painful and prolonged erection occurring without any sexual stimulation and not resulting in ejaculation. It most often occurs in patients with sickle cell disease. We report here the case of acute recurrent priapism revealing inaugural mode of CML in a 22-year-old patient with no particular pathological history. The study of the onco-hematological karyotype revealed a karyotype with 46 chromosomes with a clonal chromosomal anomaly: The t (9;22) “Philadelphia chromosome”. The evolution was favorable under imatinib.
文摘OBJECTIVE To investigate the effects of survivin antisense oligodeoxy-nucleotid (ASODN) on proliferation and apoptosis in the chronic myeloid leukemia cell line K562. METHODS Different concentrations of an antisense oligodeoxy-nucleotid and control sequence (scrambled ODN) targeting the survivin gene were transferred into K562 by a lipofectin reagent. The MTT assay was used to measure the growth inhibitory rate, IC50, and to observe the cytotoxicity of survivin ASODN in the K562 cells. The morphologic changes in the nucleus and the apoptotic rate were observed by Hoechst33342/PI staining. Caspase-3 activity was evaluated by a kinase activity assay. The changes of survivin protein expression after transfection were detected by Western blots. RESULTS Eight hours after transfection, fluorescence in the K562 cells was well distributed. Treatment of the cells for 44 h with different concentrations of survivin ASODN produced a IC50 of 800 nmol/L. The growth inhibitory rate with 200, 400, 600 and 1000 nmol/L of survivin ASODN was 15.8±1.6%, 23.8±5.9%, 37.1±5.6% and 77.3±2.5% respectively. After 36 h of of survivin ASODN treatment, distinct morphologic changes characteristic of cell apoptosis such as karyopyknosis and conglomeration were observed by Hoechst33342/PI staining. Caspase-3 activity increased significantly after treatment of the cells with different concentrations of survivin ASODN(P<0.01)and following treatment with 800 nmol/L survivin ASODN, survivin expression decreased significantly. CONCLUSION Survivin ASODN exerts an anti-cancer effect by inducing apoptosis in K562 leukaemia cells. Up-regulated expression of caspase-3 may play a role in this process.
文摘Although the advent of tyrosine kinase inhibitors(TKIs)has dramatically improved the survival of patients with chronic myeloid leukaemia(CML),acquired drug resistance and TKI-insensitive leukaemic stem cells(LSCs)remain major obstacles to a CML cure.In recent years,the reprogramming of mitochondrial metabolism has emerged as a hallmark of cancers,including CML,and in turn may be exploited for therapeutic purposes.Here,we investigated the effects of several drugs on the mitochondrial function of the CML cell line K562 and found that 5-aminoimidazole-4-carboxamide ribotide(AICAR)and decitabine could effectively increase the ATP content and mitochondrial biogenesis.In addition,these two drugs induced cell cycle arrest and a decrease in colony-forming capacity and promoted K562 cell differentiation.Moreover,we demonstrated that treatment with AICAR or decitabine enhanced the sensitivity o f K562 cells to imatinib,as evidenced by a combination treatment assay.Altogether,our findings indicate that TKIs combined with mitochondrial regulation may provide a therapeutic strategy for the treatment of CML.
