The strategy change of targeting iron homeostasis for leukemia therapy: from iron chelation to iron overload as a therapeutic strategy to induce ferroptosis / 白血病·淋巴瘤

Iron, an indispensable element for life, is involved in all kinds of vital physiological activities. Due to its potential toxicity, the body has a strict regulation mechanism of iron metabolism to maintain the "iron homeostasis". Dysregulation of iron metabolism and subsequent accumulation of excess iron are closely associated with the development and progression of leukemia. Specifically, due to the pro-oxidative nature of iron and its damaging effects on DNA, excess iron promotes the progression of leukemia; on the other hand, leukemia cells need to obtain more iron than normal cells to maintain rapid growth and proliferation, which is known as "iron addiction". Iron chelators can remove iron in leukemia cells and induce differentiation and apoptosis of leukemia cells. However, "iron addiction" makes leukemia cells more susceptible to iron overload, and is more sensitive to a new form of iron-catalyzed cell death which was named ferroptosis. According to the different needs of leukemia cells and normal cells for iron, the method of selectively killing leukemia cells through iron overload may become a new strategy for leukemia treatment. This paper reviews the strategy of targeting iron homeostasis for leukemia therapy.

Clinical characteristics and prognosis analysis of children with acute lymphoblastic leukemia and TP53 mutation / 白血病·淋巴瘤

Objective:To investigate the clinical characteristics and efficacy of children with acute lymphoblastic leukemia (ALL) and TP53 mutation, and to explore the relationship between TP53 mutation and the prognosis of children with ALL.Methods:The clinical data of 141 children with newly diagnosed ALL from November 2016 to December 2019 in Fujian Medical University Union Hospital were collected, and the whole-exome gene assay was performed in bone marrow samples of the children by using next-generation sequencing technology. The clinical characteristics of children with TP53 mutation were retrospectively analyzed, and the Kaplan-Meier method was used to compare the overall survival (OS) and event-free survival (EFS) of children with or without TP53 mutation.Results:Among the 141 children with newly diagnosed ALL, TP53 mutations were detected in 5 children (3.5%), all of which were B-precursor acute lymphoblastic leukemia (B-ALL). No TP53 mutation was detected in T-cell acute lymphoblastic leukemia (T-ALL) children, and TP53 mutation accounted for 4.0% (5/126) of B-ALL children. The types of TP53 mutation were all single nucleotide variants. Five ALL children with TP53 mutation were male, with a median age of 60 months (16- 156 months). At the time of onset, all children had anemia and elevated lactate dehydrogenase, and 4 children had subcutaneous hemorrhage and hyperuricemia. The immunophenotypes of all children were precursor B-cell type, and 4 children had myeloid antigen expression. Among 4 ALL children with TP53 mutation who received standard treatment, 2 cases relapsed, and the recurrence time was 8.9 months and 12.1 months, respectively. The expected 15-month EFS rate and OS rate of ALL children with TP53 mutation were lower than those of ALL children without TP53 mutation (37.5% vs. 97.7%, χ2 = 29.90, P < 0.001; 37.5% vs.98.3%, χ2 = 24.90, P < 0.001). Conclusions:ALL children with TP53 mutation are more commonly found in male and B-cell type, with high early recurrence rate and poor efficacy. TP53 mutation may become a necessary supplement for prognostic assessment.

Progress of chronic myeloid leukemia / 白血病·淋巴瘤

In the tyrosine kinase inhibitor (TKI) therapy era, patients with chronic myeloid leukemia (CML) have embarked on the trend of "chronic disease management". With the advent of 4 generations TKI drugs, there remain unmet needs for optimal CML treatment, such as treatment-free remission and disease recurrence after discontinuation. This article reviews the research progress of CML at the 63rd American Society of Hematology annual meeting.

Progress of disease transformation and drug discontinuation in chronic myeloid leukemia / 白血病·淋巴瘤

Since the identification of BCR-ABL fusion gene and the advent of targeted tyrosine kinase inhibitors (TKI), patients with chronic myeloid leukemia (CML) have been "walking" on the path of chronic disease for around twenty years. In recent years, the second - and third -generation TKI have provided further protection for the long-term survival of CML patients. However, TKI discontinuation and the prognostic situation of a small number of patients with TKI resistance or carrying poor prognostic genes are still hot issues in CML-related researches. This article reviews the research progress of CML at the 62nd American Society of Hematology Annual Meeting.

Primary central nervous system anaplastic lymphoma kinase-positive anaplastic large cell lymphoma in children: report of one case and review of literature / 白血病·淋巴瘤

Objective:To investigate the clinical features and prognosis of primary central nervous system (CNS) anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) in children.Methods:The clinical data of a child with primary CNS ALK-positive ALCL in Fujian Medical University Union Hospital were retrospectively analyzed, and the relevant literature was reviewed.Results:The child went to other hospitals with headache and fever as the main symptoms. Head magnetic resonance imaging showed a right cerebellar mass, and there was no evidence of lymphoma infiltration outside the CNS before surgery. Later, cerebellar tumor resection was performed. After the surgery, through pathological examination, the child was diagnosed as ALK-positive ALCL, but did not receive chemotherapy in time. The child transferred to Fujian Medical University Union Hospital on the 27th day after surgery, and the tumor had spread to bone marrow, testis, vertebrae, etc., and the peripheral blood NPM-ALK fusion gene was positive. The child received 2 courses of chemotherapy and achieved complete remission, but eventually died of chemotherapy complications.Conclusions:Primary CNS ALK-positive ALCL is rare and easy to be misdiagnosed. The disease progresses quickly, and the overall prognosis is poor. Timely biopsy for diagnosis and early comprehensive treatment based on chemotherapy may improve the prognosis of patients.

Clinical observation of azacitidine combined with CAG regimen in reinduction treatment of pediatric relapsed/refractory acute myeloid leukemia / 白血病·淋巴瘤

Objective:To investigate the efficacy and safety of azacitidine combined with CAG (cytarabine + aclacinomycin + granulocyte colony-stimulating factor) regimen in reinduction treatment of pediatric relapsed/refractory acute myeloid leukemia (AML) patients.Methods:The clinical data of 3 pediatric patients with relapsed/refractory AML treated with azacitidine combined with CAG regimen reinduction in Fujian Medical University Union Hospital between November 2018 and October 2019 were retrospectively analyzed, and the efficacy, prognosis and adverse reactions were also analyzed.Results:Among 3 patients, 2 cases were relapsed AML (relapse time began 18 months and 8 months after treatment started, respectively), and 1 case was refractory AML (cannot achieve complete remission after 2 courses of standard chemotherapy). After 2 courses of azacitidine combined with CAG regimen reinduction, 2 cases achieved complete remission, and 1 case achieved partial remission. And then they all underwent hematopoietic stem cell transplantation (HSCT) and had leukemia-free survival after 16-21 months follow-up (time from the first azacitidine combined with CAG reinduction). Except for hematological adverse reactions and infection, azacitidine did not increase other adverse effects.Conclusions:Azacitidine combined with CAG regimen in reinduction treatment of pediatric relapsed/refractory AML has a higher remission rate and safety, and patients undergoing timely bridging HSCT may have a good prognosis.

Treatment and diagnosis progress of chronic myeloid leukemia / 白血病·淋巴瘤

The identification of BCR-ABL fusion gene and the advent of tyrosine kinase inhibitors (TKI) targeting this mutation have promoted the landmark progress of diagnosis and treatment in chronic myeloid leukemia (CML), and have dramatically changed the treatment management and disease prognosis for CML patients. Most of the western countries hold a view that CML is cut and dried, but the situation is not the same in developing countries. Currently, more attention is paid to the discontinuation of TKI. In addition, deep challenges remain in the low- and middle-income countries. This paper reviews the treatment progress of CML and challenges in low-and middle-income countries reported at the 61st American Society of Hematology Annual Meeting.

Four-year follow-up of patients with imatinib-resistant or intolerant chronic myeloid leukemia receiving dasatinib: efficacy and safety / 医学前沿

Dasatinib is a highly effective second-generation tyrosine kinase inhibitor used to treat chronic myeloid leukemia (CML). In 2007, a pivotal phase-2 study of dasatinib as second-line treatment was initiated in 140 Chinese CML patients. This report from the 4-year follow-up revealed that 73% of 59 patients in chronic phase (CML-CP) and 32% of 25 patients in accelerated phase (CML-AP) remained under treatment. The initial dosage of dasatinib for CML-CP and CML-AP patients were 100 mg once daily and 70 mg twice daily (total = 140 mg/ day), respectively. The cumulative major cytogenetic response (MCyR) rate among patients with CML-CP was 66.1% (versus 50.8% at 18 months), and the median time to MCyR was 12.7 weeks. All CML-CP patients who achieved MCyR after a 4-year follow-up also achieved a complete cytogenetic response. The cumulative complete hematological response (CHR) rate among patients with CML-AP was 64% (16/25), with three CML-AP patients achieving CHR between 18 months and 4 years of follow-up; the median time to CHR was 16.4 weeks. The adverse event (AE) profile of dasatinib at 4 years was similar to that at 6 and 18 months. The most frequently reported AEs (any grade) included pleural effusion, headache, and myelosuppression. These long-term follow-up data continue to support dasatinib as a second-line treatment for Chinese patients with CML.

Clinical risk score for invasive fungal diseases in patients with hematological malignancies undergoing chemotherapy: China Assessment of Antifungal Therapy in Hematological Diseases (CAESAR) study / 医学前沿

Invasive fungal disease (IFD) is a major infectious complication in patients with hematological malignancies. In this study, we examined 4889 courses of chemotherapy in patients with hematological diseases to establish a training dataset (n = 3500) by simple random sampling to develop a weighted risk score for proven or probable IFD through multivariate regression, which included the following variables: male patients, induction chemotherapy for newly diagnosed or relapsed disease, neutropenia, neutropenia longer than 10 days, hypoalbuminemia, central-venous catheter, and history of IFD. The patients were classified into three groups, which had low (0-10, ~1.2%), intermediate (11-15, 6.4%), and high risk ( > 15, 17.5%) of IFD. In the validation set (n = 1389), the IFD incidences of the groups were ~1.4%, 5.0%, and 21.4%. In addition, we demonstrated that antifungal prophylaxis offered no benefits in low-risk patients, whereas benefits were documented in intermediate (2.1% vs. 6.6%, P = 0.007) and high-risk patients (8.4% vs. 23.3%, P = 0.007). To make the risk score applicable for clinical settings, a pre-chemo risk score that deleted all unpredictable factors before chemotherapy was established, and it confirmed that anti-fungal prophylaxis was beneficial in patients with intermediate and high risk of IFD. In conclusion, an objective, weighted risk score for IFD was developed, and it may be useful in guiding antifungal prophylaxis.

Clinical effect and safety of dasatinib combined with Chinese Children's Leukemia Group-acute lymphoblastic leukemia 2008 protocol in treatment of childhood Philadelphia chromosome-positive acute lymphoblastic leukemia / 白血病·淋巴瘤

Objective@#To investigate the clinical effect and safety of dasatinib combined with Chinese Children's Leukemia Group-acute lymphoblastic leukemia (CCLG-ALL) 2008 protocol in treatment of childhood Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL).@*Methods@#The clinical data of 22 patients with Ph+ ALL who were newly diagnosed at the age of less than 15 years old in Fujian Medical University Union Hospital from January 2014 to December 2018 were retrospectively analyzed. All patients were treated with dasatinib combined with CCLG-ALL2008 protocol (high-risk group). The patients were assigned to two groups according to different starting times of oral dasatinib: the dasatinib-induced group (starting from day 15 of induction chemotherapy) and the dasatinib-consolidated group (starting with early consolidated chemotherapy). The early treatment response and 5-year event-free survival (EFS) rate were compared between the two groups.@*Results@#The differences of clinical characteristics and early efficacy of chemotherapy before treatment of dasatinib between the two groups were not statistically significant (both P > 0.05). The complete remission (CR) rate on day 33 of induction chemotherapy was higher in the dasatinib-induced group than that in the dasatinib-consolidated group [100% (10/10) vs. 75% (9/12)], but the difference was not statistically significant (χ 2= 2.895, P= 0.221). The rate of minimal residual disease (MRD) turned negative (<0.01%) on day 33 of induction chemotherapy in the dasatinib-induced group was significantly higher than that in the dasatinib-consolidated group [70% (7/10) vs. 17% (2/12)], and the difference was statistically significant (χ 2= 6.418, P= 0.027). The 3-year EFS rate was higher in the dasatinib-induced group than that in the dasatinib-consolidated group (88.9% vs. 63.5%), but the difference was not statistically significant (P= 0.163). The incidence of grade 3-4 infection in the dashatinib-induced group was lower than that in the dasatinib-consolidated group, and the difference was statistically significant [60% (6/10) vs. 100% (12/12), P= 0.029]. the other grade 3-4 adverse reactions related to the chemotherapy drugs mainly included hematological toxicity, diarrhea, abnormal liver function, edema and pleural effusion, but there was no significant difference between the two groups (all P > 0.05).@*Conclusions@#Dasatinib combined with CCLG-ALL2008 protocol in the treatment of children with Ph+ ALL has good efficacy and safety. Furthermore, the early use of dasatinib on day 15 of induction chemotherapy can enable patients to achieve deeper remission earlier and improve long-term efficacy.

Clinical and biological features of mixed﹣phenotype acute leukemia: an analysis of 24 cases / 白血病·淋巴瘤

Objective To investigate the clinical and biological features of patients with mixed﹣phenotype acute leukemia (MPAL). Methods The clinical data of 24 de novo adult patients with MPAL who were admitted to Fujian Medical University Union Hospital from January 2012 to October 2018 were retrospectively analyzed. These patients were diagnosed according to the World Health Organization (WHO) 2016 criteria. The clinical and biological characteristics of the patients were analyzed by morphological and cytochemical staining, immunophenotyping, cytogenetics and molecular biology. Results Of the 24 patients, 16 were male and 8 were female, and the median age of the patients at diagnosis was 27 years old (5-66 years old). The average blasts of bone marrow were (57.41 ±23.20)% . Thirteen cases (54.2% ) were diagnosed as MPAL morphologically, while 5 cases (20.8% ) were diagnosed as acute myeloid leukemia (AML), 5 cases (20.8%) were diagnosed as acute lymphoblastic leukemia (ALL) and 1 case (4.2%) was inconclusive. Eighteen patients (75.0%) co﹣expressed B﹣lymphoid and myeloid markers, while 5 patients (20.8%) with T﹣lymphoid and myeloid markers and 1 patient (4.2%) with B﹣lymphoid and T﹣lymphoid markers, respectively. The positive rate [median (range)] of CD38, HLA﹣DR and CD34 was 90.5% (0.1%-99.7%), 90.1% (1.1%-98.8% ) and 81.3% (0.1%-97.8%), respectively. Eighteen cases underwent chromosome examination, of which 5 cases carried with t(9;22)(q34;q11), 3 cases with t(v;11q23.3), 2 cases with complex karyotypes, and 2 cases with t(9;22)(q34;q11) and complex karyotypes, respectively. Twenty﹣one cases underwent genetic examination, of which 6 cases were positive for BCR﹣ABL, 3 cases were positive for MLL, 1 case was positive for MLL and BCR﹣ABL, 1 case was positive for BCR﹣ABL and TP53, and 1 case was positive for PHF6 and ASXL1 respectively. Of the 24 patients, 7 refused chemotherapy and 17 received induction chemotherapy. Of the patients receiving chemotherapy, 9 cases achieved complete remission (CR), 1 case was partial remission (PR), and 7 cases were not relieved (NR). In 11 patients treated by ALL﹣type induction regimen and 6 patients treated by ALL and AML﹣type induction regimen, 8 cases and 1 case achieved CR, the difference in CR rate was statistically significant (P<0.05). In 6 patients with Philadelphia chromosome (Ph) positive and 11 patients with Ph negative, 1 case and 8 cases achieved CR, the difference in CR rate was statistically significant (P<0.05). The median follow﹣up time was 5.5 months (0-36 months). The 3﹣year overall survival (OS) rate was 17.5% and the median OS time was 6 months. The 3﹣year OS rates in the allogeneic hematopoietic stem cell transplantation and non﹣transplanted groups were 75.2% and 0, respectively, and the median OS time was not reached and 4 months (P< 0.05). Conclusions MPAL is rare, it mostly co﹣expresses lymphoid and myeloid antigens and shows a much higher incidence of CD34, CD38 and HLA﹣DR. MPAL is often associated with Ph positive and complex karyotypes. MPAL has a low remission rate and poor prognosis, and a reasonable and effective treatment plan should be further explored.

Clinical features and prognosis of children with hematological malignancies after chemotherapy with Stenotrophomonas maltophilia blood stream infection / 白血病·淋巴瘤

Objective To investigate the clinical features and prognosis of children with hematological malignancies after chemotherapy accompanied with Stenotrophomonas maltophilia blood stream infection (BSI). Methods The clinical data and antimicrobial susceptibility test of 25 hospitalized children with hematological malignancies who were diagnosed as Stenotrophomonas maltophilia BSI in the Department Pediatric Hematology of Fujian Medical University Union Hospital from January 2013 to May 2018 were analyzed retrospectively. Results A total of 25 children, including 18 males and 7 females with the median age 4 (1-11) years old were diagnosed as hematological malignancies and all received chemotherapy. The frequent risk factors of Stenotrophomonas maltophilia BSI in children with hematological malignancies included prior carbapenem antibiotic for more than 1 week (80％, 20/25), and neutropenia for more than 1 week (68％,17/25) and indwelling central venous catheter (48％, 12/25). Clinically, the main manifestations included neutropenia with fever after chemotherapy; however, anti-pseudomonas cephalosporin/carbicillin antibiotic combined with vancomycin and anti-fungal therapies were ineffective. Drug susceptibility test showed that all strains were sensitive to compound sulfamethoxazole, levofloxacin and minocycline. Before blood culture report, 3 patients died of septic shock, pulmonary hemorrhage and respiratory failure; after blood culture report, the treatment regimens were adjusted to compound sulfamethoxazole combined with cefoperazone sodium and sulbactam sodium (200-260 mg·kg-1·d-1) or levofloxacin anti-infective. Finally, 18 patient was cured, 2 patients died of the bad efficacy of underlying diseases, and 2 patients died of pulmonary hemorrhage. The overall fatality rate was 28％ (7/25) and the related mortality rate caused by Stenotrophomonas maltophilia BSI was 20％ (5/25). Conclusion Stenotrophomonas maltophilia BSI in children with hematological malignancies after chemotherapy has a high fatality rate, and better basic disease control and appropriate antibacterial therapy are the key to improve the prognosis.

Hodgkin lymphoma in children: clinical analyses of 20 cases / 白血病·淋巴瘤

Objective To summarize the long-term outcomes and safety of childhood Hodgkin lymphoma (HL) with protocol ABVD. Methods The clinical data of 20 children with HL admitted to the Union Hospital of Fujian Medical University from July 2010 to June 2017 were retrospectively analyzed. Among the 20 children with HL, 15 were male and 5 were female. The median age of initial diagnosis was 6.5 years old (3-12 years old). The pathological types were as follow: 1 case was nodular lymphocyte-predominant HL (NLPHL) and 19 cases were classical HL (cHL), including 9 cases of mixed cell type, 9 cases of nodular sclerosis type and 1 case of lymphocyte rich type. Basing on Ann Arbor staging system, 1 patient was evaluated as stage Ⅰ, 4 patients were stage Ⅱ, 10 patients were stage Ⅲ, and 5 patients were stage Ⅳ. There were 3 patients in the low-risk group, 7 patients in the intermediate-risk group, and 10 patients in the high-risk group. There were 9 patients with B symptoms. All patients were treated with the ABVD regimen. Results All the 20 patients completed all chemotherapy courses. After 2 courses, the effective rate was 100％(20/20), including 12 cases of complete remission (CR) and 8 cases of partial remission (PR). After the treatment, 19 cases achieved CR, and at the end of the 6 courses, the evaluation showed that 1 case had residual lesions. Follow-up to February 2018, clinical symptoms of 18 cases achieved CR, 2 cases relapsed (all high-risk group); the median follow-up time was 42 months (10.1-87.9 months), the overall survival rate was 100 ％ (20/20), the estimated 5-year rate of freedom from treatment failure (FFTF) was (89.1 ±7.3) ％.Conclusions According to the risk stratification, ABVD regimen has good safety and long-term efficacy for children with cHL. Even the patients in low-risk or intermediate-risk group do not achieve CR after 2 courses and do not receive radiotherapy, the prognosis of them is still good.

Clinical features and prognosis of primary intestinal B-cell lymphoma: analyses of 50 cases / 白血病·淋巴瘤

Objective To investigate the clinical characteristics and prognostic factors for patients with primary intestinal B-cell lymphoma. Methods The clinical data of 50 patients with primary intestinal B-cell lymphoma in Fujian Medical University Union Hospital from January 2004 to December 2013 were retrospectively analyzed. An analysis was also conducted in their clinical characteristics and related prognostic factors. Results A total of 50 patients included 35 males and 15 females with the median age of 58 years old (16-79 years old). The clinical symptoms were abdominal pain or abdominal distension [70 % (35/50)]. The common origins were small intestine and ileocecus, and the most common pathological type was diffuse large B-cell lymphoma (DLBCL) [54 % (27/50)]. The median survival time of 43 cases was 49.4 months. The 1-year, 3-year and 5-year overall survival (OS) rates were 79.1 %, 72.1 %, 58.1 %, respectively. Univariate analysis indicated that hemoglobin levels, albumin levels, lactic dehydrogenase (LDH), the maximum diameter of mass, international prognostic index (IPI) score, Lugano stage, and Eastern Cooperative Oncology Group (ECOG) score were the affecting factors of OS. Multivariate analysis showed that IPI score ≥ 2 was an independent risk factor for the prognosis of intestinal B-cell lymphoma ( OR＝ 6.766, 95 % CI 1.853-24.702, P＝ 0.004). The efficacy analysis showed that 5-year cumulative OS rate of R-CHOP like treatment group was better than that of CHOP like treatment group (91.7 % vs. 44.7 %, P ＝0.048). Conclusion IPI score can be used as an important indicator for clinical treatment and prognosis evaluation of primary intestinal B-cell lymphoma. Some patients with primary intestinal B-cell lymphoma can benefit from rituximab.

Disseminated aspergillosis in children with leukemia after chemotherapy: report of three cases and review of literature / 白血病·淋巴瘤

Objective To investigate the clinical features,diagnosis,treatment and prognosis of disseminated aspergillosis in children with leukemia after chemotherapy.Methods The clinical features and treatment of 3 leukemia children after chemotherapy complicated with disseminated aspergillosis were retrospectively analyzed.Results The underlying diseases of all recruited cases were leukemia,which occurred many high-risk predisposing factors for invasive fungal diseases.The major clinical features of disseminated aspergillosis in children with leukemia were prolonged and antibiotics uncontrollable fever,subcutaneous solid nodules,nodules or cavities in pulmonary CT,spread low density lesions in hepatosplenic and kidney in abdominal MR(T2 weighted)and positive serum aspergillus galactomannan(GM).The diagnosis of invasive fungal disease was proven by histopathologic examination.Amphotericin B lipid complex was selected in antifungal therapy for 2 patients and the course of treatment was more than 4 weeks.Moreover,chemotherapy was advised for the 2 patients when clinical manifestations of disseminated aspergillosis improved significantly,neutrophil counts recovered and images did not deteriorate.The patients received voriconazole treatment with follow-up from 6 months to 12 months,and then disseminated aspergillosis was cured up to the standard.1 case received complete remission and was still alive until follow-up period,1 case was died of leukemia relapse because of suspension demand from the family members,and the other 1 case was died of no response or serious adverse drug reactions,uncontrolled infection,and leukemia relapse because of long-term chemotherapy suspension.Conclusions Patients with leukemia after chemotherapy may present with the following manifestations,including fever,subcutaneous solid nodules,pulmonary nodules or cavities,spread low density lesions in hepatosplenic and kidney and serum aspergillus GM antigen positive,which may indicate disseminated aspergillosis.The improvement of prognosis depends on effective and adequate antifungal treatment and chemotherapy for leukemia at the right time.

Disseminated aspergillosis in children with leukemia after chemotherapy: report of three cases and review of literature / 白血病·淋巴瘤

Objective To investigate the clinical features,diagnosis,treatment and prognosis of disseminated aspergillosis in children with leukemia after chemotherapy.Methods The clinical features and treatment of 3 leukemia children after chemotherapy complicated with disseminated aspergillosis were retrospectively analyzed.Results The underlying diseases of all recruited cases were leukemia,which occurred many high-risk predisposing factors for invasive fungal diseases.The major clinical features of disseminated aspergillosis in children with leukemia were prolonged and antibiotics uncontrollable fever,subcutaneous solid nodules,nodules or cavities in pulmonary CT,spread low density lesions in hepatosplenic and kidney in abdominal MR(T2 weighted)and positive serum aspergillus galactomannan(GM).The diagnosis of invasive fungal disease was proven by histopathologic examination.Amphotericin B lipid complex was selected in antifungal therapy for 2 patients and the course of treatment was more than 4 weeks.Moreover,chemotherapy was advised for the 2 patients when clinical manifestations of disseminated aspergillosis improved significantly,neutrophil counts recovered and images did not deteriorate.The patients received voriconazole treatment with follow-up from 6 months to 12 months,and then disseminated aspergillosis was cured up to the standard.1 case received complete remission and was still alive until follow-up period,1 case was died of leukemia relapse because of suspension demand from the family members,and the other 1 case was died of no response or serious adverse drug reactions,uncontrolled infection,and leukemia relapse because of long-term chemotherapy suspension.Conclusions Patients with leukemia after chemotherapy may present with the following manifestations,including fever,subcutaneous solid nodules,pulmonary nodules or cavities,spread low density lesions in hepatosplenic and kidney and serum aspergillus GM antigen positive,which may indicate disseminated aspergillosis.The improvement of prognosis depends on effective and adequate antifungal treatment and chemotherapy for leukemia at the right time.

Efficacy and safety of IA regimen containing different doses of idarubicin in de-novo acute myeloid leukemia for adult patients / 中华血液学杂志

Objective@#To investigate the efficacy and safety of IA regimen which contains idarubicin (IDA) 8 mg/m2, 10 mg/m2 or 12 mg/m2 as induction chemotherapy for adult patients with de-novo acute myeloid leukemia (AML) .@*Methods@#A total of 1 215 newly diagnosed adult AML patients, ranging from May 2011 to March 2015 in the First Affiliated Hospital of Soochow University and other 36 clinical blood centers in China were enrolled in the multicenter, single-blind, non-randomized, clinical controlled study. To compare the response rate of complete remission (CR) , adverse events between different dose idarubicin combined with cytarabine (100 mg/m2) as induction chemotherapy in newly diagnosed patients of adult AML.@*Results@#Of 1 207 evaluable AML patients were assigned to this analysis of CR rate. The CR rates of IDA 8 mg/m2 group, IDA 10 mg/m2 group and IDA 12 mg/m2 group were 73.6% (215/292) , 84.1% (662/787) and 86.7% (111/128) , respectively (P<0.001) . After adjusted for age, blast ratio of bone marrow, FAB classification and risk stratification, the odds ratios (95% CI) of IDA 10 mg/m2 group and IDA 12 mg/m2 group were 0.49 (0.34-0.70) and 0.36 (0.18-0.71) , as compared with the IDA 8 mg/m2 group (P<0.001, P=0.003) . In the intermediate and favorable groups, CR rates was 76.5% (163/213) , 86.9% (506/582) and 86.1% (68/79) in different doses of IDA (P=0.007) . Interestingly, IA regimen with IDA 10 mg/m2 was the only beneficial factor affecting CR in this group after adjusted for age, blast ratio of bone marrow and FAB classification[OR=0.47 (95% CI 0.31-0.71) , P<0.001]. CR rates in adverse group was 50.0% (18/36) , 60.6% (43/71) and 81.8% (18/22) respectively (P=0.089) . However, the odds ratios (95% CI) of IDA 12 mg/m2 when compared with the IDA 8 mg/m2 was 0.22 (0.06-0.80) , after adjusted for age, blast ratio of bone marrow and FAB classification. The median time (days) of neutrophil count less than 0.5×109/L in IDA 8 mg/m2 group, IDA 10 mg/m2 group and IDA 12 mg/m2 group were 14 (11-18) , 15 (11-20) and 18 (14-22) , respectively (P=0.012) and of platelet count lower than 20×109/L were 14 (7-17) , 15 (11-20) and 17 (15-21) , respectively (P=0.001) . The incidences of lung infection in the three groups were 9.8%, 13.5% and 25.2%, respectively (P<0.001) .@*Conclusions@#For young adult patients (aged 18-60 years) with AML in China, intensifying induction therapy with idarubicin 10 mg/m2 is clinically superior to IDA 8 mg/m2 and IDA 12 mg/m2 in favorable intermediate AML subgroup. However, idarubicin 12 mg/m2 is more suitable to adverse AML subgroup.

Distribution and drug resistance of pathogens of blood stream infection in patients with hematological malignancies after chemotherapy / 中华血液学杂志

Objective@#To investigate the distribution and resistance of pathogens isolated from blood cultures in patients with hematological malignancies after chemotherapy in Union Hospital of Fujian Medical University so as to understand the real situation of blood stream infection (BSI) and provide the basis for rational use of antibiotics in clinic.@*Methods@#The data of 657 strains isolated from blood culture specimens of patients with hematological malignancies from January 2013 to December 2016 were collected analyzed.@*Results@#A total of 657 cases of blood culture positive bacterial strains were included in the study, involving 410 cases (62.4%) with single Gram-negative bacteria (G- bacteria) , 163 cases (24.8%) with single Gram-positive bacteria (G+ bacteria) , 50 cases (7.6%) with single fungi. The most common 5 isolates in blood culture were Klebsiella pneumoniae (17.5%) , Escherichia coli (17.2%) , Coagulase negative staphylococci (CNS) (14.9%) , Pseudomonas aeruginosa (14.2%) and Staphylococcus aureus (3.5%) . The extended-spectrum beta-lactamase (ESBL) production rates of Klebsiella pneumoniae and Escherichia coli were 25.2% and 55.8%, respectively. ESBL producing strains were almost more resistant than non-ESBL producing strains. The resistance rates of Enterobacteriaceae to carbapenems, piperacillin/tazobactam and tigecycline were lower than 14.0%. The resistance rates of Pseudomonas aeruginosa to a variety of drugs were lower than 12.0%. Tigecycline-resistant Acinetobacter baumannii bacteria were not detected, and the resistance rates of Acinetobacter baumannii to cefixime and cefotaxime were 7.1%. Methicillin-resistant strains in CNS (MRCNS) and in Staphylococcus aureus (MRSA) accounted for 84.7% and 43.5%, respectively. Vancomycin, linezolid and tigecycline-resistant G+ bacteria were not detected.@*Conclusion@#The pathogens isolated from blood culture were widely distributed. Most of them were G- bacteria, and the resistance to antibiotics was quite common. Furhermore, vancomycin, linezolid and tigecycline can be chosen empirically to treat patiens who ar suspected to have G+ bacterial BSI.

Clinical analysis of intravenous itraconazole in different antifungal strategies for hematologic diseases patients with invasive fungal disease / 白血病·淋巴瘤

Objective To investigate the efficacy and safety of intravenous itraconazole in different antifungal strategies for hematologic diseases patients with invasive fungal disease. Methods The efficacy and safety of intravenous itraconazole injection in the treatment of 160 hematologic diseases patients with invasive fungal disease, including the related factors were retrospectively analysed. Results The total efficacy rate of itraconazole was 58.12 %(93/160). The response rates in therapy for undefined patients without any evidence of patients, diagnostic-driven therapy for possible IFD patients, targeted therapy for proven IFD patients were 65.82 %(52/79), 53.57 %(30/56) and 44.00 %(11/25), respectively (P=0.054). The incidence rate of itraconazole-related adverse effect was 8.13 % (13/160), and the main adverse reaction was liver impairment. Multiple-factor analysis showed that the efficacy of itraconazole for the treatment of hematologic diseases patients with invasive fungal disease was not associated with age, medical history, agranulocytosis, and initial treatment. Conclusion Itraconazole itraconazole is effective and safe in the treatment of fungal therapy for patients with hematologic diseases.

A prospective, multi-centre clinical trial to evaluate the early clinical efficacy and safety of a generic imatinib in treating patients with chronic phase of chronic myelogenous leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the early hematologic, cytogenetic and molecular responses in newly diagnosed patients with chronic myelogenous leukemia in chronic phase（CML-CP）and initially treated with a generic imatinib（Xinwei）, manufactured by Jiansu Hansoh Pharmaceutical Group Co., Ltd.</p><p><b>METHODS</b>107 newly diagnosed patients of CML-CP, whose ages were above 18- year- old and who had never received any tyrosine kinase inhibitor（TKI）were treated with Xinwei 400 mg QD. The hematologic, cytogenetic and molecular responses were assessed at 3- and 6-month, and adverse effects were evaluated throughout the study.</p><p><b>RESULTS</b>107 patients were treated with Xinwei for at least 3 months, 54 of them were treated for 6 months or more. At 3- month, the complete hematologic responses（CHR）rate were 98.1%（105/107）; 47/57（82.5%） patients achieved major cytogenetic response（MCyR）, and 20/57 （35.1%） patients complete cytogenetic response（CCyR）; BCR- ABLIS was ≤10% in 77/106 patients （72.6%）, 11 of them（10.4%）achieved major molecular response（MMR, BCR-ABLIS was ≤0.1%）. At 6-month, the CHR rate was 100%（54/54）; 28/39 patients（71.8%）achieved CCyR; BCR-ABLIS was ≤1% in 37/54 patients （68.5% ）, 18 of them （33.3% ） achieved MMR. The grade Ⅲ leukopenia, thrombocytopenia and anemia rates were 19.5%, 23.0% and 13.8%, respectively. No grade Ⅳ hematologic toxicity occurred. The common non- hematologic toxicities were edema（74.7%）, nausea（48.3%）, bone pain（42.5%）, rash（36.8%）, diarrhea（34.5%）, fever（23.0%）, cramp（11.5%）and impaired liver function （3.4%）. No patient experienced grade Ⅳ non- hematologic toxicity. No adverse effects related death occurred.</p><p><b>CONCLUSION</b>Our results revealed the excellent early haematology, cytogenetic and molecular responses and safety of Xinwei in treating patients with CML-CP.</p>