OBJECTIVE: To investigate the efficacy, prognosis and safety of decitabine combined with low-dose CAG regimen in the treatment of elderly patients with acute myeloid leukemia （AML）. METHODS: The clinical data of 40 elderly patients with relapsed/refractory AML （69-85 years old） admitted to our hospital from January 2014 to August 2016 were analyzed retrospectively. 40 patients were divided into combination therapy group and CAG group according to different treatment methods. 20 patients of the combination therepy group were treated with decitabine combined with low-dose CAG （decitabine, 15 mg/m, d 1; aclarithromycin, 10 mg/m, d 3-6; Cytidine, 10 mg/m, d 1-14; recombinant human granulocyte macrophage colony-stimulating factor （G-CSF） for injection, 200 μg/（m·d）, d 1-14）. 20 patients of CAG group were treated by the standard CAG protocol （acralmycin 20 mg/m, d 1-4; cytarabine for injection, 15 mg/m, d 1-14; G-CSF 400 μg/（m·d）, d 1-14）. One course of treatment lasted for 2 weeks, after 2 courses of continuous medication, the complete remission rate （CR）, overall remission rate （ORR）, overall survival （OS）, 1-year survival rate, hemoglobin, white blood cells, platelets improvement, and incidence of adverse reactions were compared. RESULTS: In combination therapy group the CR was 55.00% （11/20）, OR was 85.00% （17/20）, but in the CAG group CR was 30.00% （6/20）, and OR was 50.00% （10/20）. Till to February 2018, out of 40 patients 17 survived, 20 died, and 3 failed to be followed-up. The median follow-up time was 12 （2 to 35） months; the median survival time in the comtination therapy group was 13 （2-35） months, and the 1-year OS rate was 70.00%, and the median survival time of the CAG group was 10 （2-31） months, and the 1-year OS rate was 50.00%, without staistical significance between the 2 groups （P>0.05）. After treatment, the WBC and Plt counts in the combination therapy group were higher than those in the CAG group, but the Hb level was lower than that in the CAG group with statistically significant difference （P<0.05）. In the combination therapy group, the incidence of lung infection, nausea and vomiting was higher than that of the CAG group （65.00% vs 25.00%, 50.00% vs 20.00%）, with statistically significant difference （P<0.05）. CONCLUSION Decitabine combined with low-dose CAG regimen is effective for the treatment of relapsed/refractory AML in the elderly. Compared with the standard CAG regimen, the long-term efficacy of this regimen is not different significantly, but its adverse reactions are increase, thus the preventive treatment should be given in time.
Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; Cytarabine ; administration & dosage ; Decitabine ; administration & dosage ; Granulocyte Colony-Stimulating Factor ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Prognosis ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To investigate the complications and clinical outcome of children with acute myeloid leukemia (AML) undergoing mitoxantrone-cytarabine-etoposide (MAE) induction therapy. METHODS: A total of 170 children with AML were given MAE induction therapy, and the complications and remission rate were analyzed after treatment. RESULTS: The male/female ratio was 1.33:1 and the mean age was 7.4 years (range 1-15 years). Leukocyte count at diagnosis was 29.52×10/L [range (0.77-351)×10/L]. Of all children, 2 had M0-AML, 24 had M2-AML, 2 had M4-AML, 48 had M5-AML, 3 had M6-AML, 7 had M7-AML, 69 had AML with t(8;21)(q22;q22), and 15 had AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22). The most common complication was infection (158/170, 92.9%). Among these 158 patients, 22 (13.9%) had agranulocytosis with pyrexia (with no definite focus of infection), and 136 (86.1%) had definite focus of infection (including bloodstream infection). Other complications included non-infectious diarrhea, bleeding, and drug-induced hepatitis. Treatment-related mortality was observed in 10 children, among whom 8 had severe infection, 1 had multiple organ failure, and 1 had respiratory failure. Remission rate was evaluated for 156 children and the results showed a complete remission rate of 85.3%, a partial remission rate of 4.5%, and a non-remission rate of 10.3%. CONCLUSIONS Induction therapy with the MAE regimen helps to achieve a good remission rate in children with AML after one course of treatment. Infection is the main complication and a major cause of treatment-related mortality.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Child, Preschool ; Cytarabine ; Drug Administration Schedule ; Etoposide ; Female ; Humans ; Infant ; Leukemia, Myeloid, Acute ; drug therapy ; Male ; Mitoxantrone ; Remission Induction

Conventional combination therapies have not resulted in considerable progress in the treatment of acute myeloid leukemia (AML). Elderly patients with AML and poor risk factors have grave prognosis. Midostaurin has been recently approved for the treatment of FLT-3-mutated AML. Venetoclax, a BCL-2 inhibitor, has been approved for the treatment of relapsed and/or refractory chronic lymphoid leukemia. Clinical trials on applying venetoclax in combination with cytarabine and other agents to treat various hematological malignancies are currently underway. Here, we present a case of a male patient with poor performance status and who developed AML following allogeneic hematopoietic stem cell transplant for high-risk myelodysplasia. The patient with high risk AML achieved complete response to the combined treatment regimen of low-dose cytarabine and venetoclax. Furthermore, we reviewed current clinical trials on the use of venetoclax for hematological malignancies.
Aged ; Bridged Bicyclo Compounds, Heterocyclic ; administration & dosage ; Combined Modality Therapy ; Cytarabine ; administration & dosage ; Fatal Outcome ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; genetics ; Male ; Recurrence ; Remission Induction ; Sulfonamides ; administration & dosage

To investigate the clinical efficacy and toxicities for the NAPD regimen (vinorelbine, cytarabine, cisplatin, and dexamethasone) in the treatment of recurrent refractory diffuse large B-cell lymphoma.
 Methods: A total of 30 patients identified with recurrent refractory diffuse large B-cell lymphoma were enrolled in this retrospective study. The curative efficacy of NAPD regimen was evaluated after 2 consecutive cycles. The toxicities and adverse reaction were evaluated after 1 cycle. The objective response rate (ORR), overall survival (OS), progress free survival (PFS), and the rates of 1, 2, and 4-year OS and PFS were analyzed. The prognosis was evaluated with univariate analysis.
 Results: The ORR was 56.7% and clinical benefit rate (CBR) was 83.3% after 2 cycles. Five patients achieved complete remission, 12 achieved partial remission, and 8 achieved stable disease. The median OS was 22 (1.5-140) months. The 1, 2, and 4-year OS rates were 59.1%, 48.2%, and 40.2%, respectively. The median PFS was 14 (1.5-140) months. The 1, 2 and 4-year PFS rates were 56.3%, 42.2%, and 31.7%, respectively. The main adverse reaction was myelosuppression. Three patients suffered from grade III-IV leukopenia and 1 thrombocytopenia. Grade I-II gastrointestinal toxicity was 20%. No heart, liver, and kidney damages at grade III-IV were observed.
 Conclusion: The NAPD regimen is effective and its toxicity is well tolerated for the treatment of recurrent refractory diffuse large B-cell lymphoma. It is a salvage chemotherapy regimen worth to be verified.
Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Cisplatin ; administration & dosage ; Cytarabine ; administration & dosage ; Dexamethasone ; administration & dosage ; Humans ; Induction Chemotherapy ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; mortality ; Neoplasm Recurrence, Local ; drug therapy ; mortality ; Retrospective Studies ; Salvage Therapy ; methods ; Treatment Outcome ; Vinblastine ; administration & dosage ; analogs & derivatives ; Vinorelbine

Objective: To explore outcomes in adult with de novo acute myeloid leukemia (AML) received IA10 (10 mg/m(2) d1-3 idarubicin plus cytarabine 100 mg/m(2) d1-7) regimen as induction chemotherapy. Methods: From January 2008 to February 2016, data of consecutive newly-diagnosed AML (non-M(3)) adults treated with IA10 who achieved morphologic leukemia-free state (MLFS) but not accepted allogeneic hematopoietic stem cell transplantation (allo-HSCT) were assessed retrospectively. Results: A total of 198 patients were included in this study with 96 (48.5%) male and a median age of 42 years old (range, 18-62 years old). Using the SWOG cytogenetic classification, 45 (22.7%), 104 (52.5%), 24 (12.1%) and 25 (12.6%) patients belonged to favorable, intermediate, unfavorable and unknown categories, respectively. 6 (3.0%) patients had monosomal karyotype, and 28 (14.1%) positive FLT3-ITD mutation. A complete remission (CR, defined as MLFS with ANC ≥ 1×10(9)/L and PLT ≥ 100×10(9)/L) achieved in 168 (84.8%) patients, a CRp (defined as MLFS with incomplete PLT recovery) in 16 (8.1%) and a CRi (defined as MLFS with incomplete ANC and PLT recovery) in 14 (7.1%). With a median follow-up period of 15 months (range, 1 to 70 months) in survivors, the probabilities of cumulative incident of relapse (CIR), disease free survival (DFS) and overall survival (OS) rates at 2-year were 45.2%, 46.9% and 62.9%, respectively; the median durations of relapse, DFS and OS were 34, 20 and 37 months respectively. At the time of achieving first MLFS, multivariate analyses showed that positive FLT3-ITD mutation and CRi were common adverse factors affecting CIR, DFS and OS; unfavorable-risk of SWOG criteria was an adverse factor affecting CIR and DFS; monosomal karyotype was associated with shorter OS. After first consolidation therapy, FLT3-ITD mutation positive and unfavorable-risk of SWOG criteria had negatively impact on CIR, DFS and OS; peripheral blasts ≥ 0.50 and positive MRD (defined as RQ-PCR WT1 mRNA ≥ 0.6% or any level of abnormal blast population detected by flow cytometry) after first consolidation therapy were common adverse factors affecting CIR and DFS; CRi was an adverse factor affecting DFS and OS. Conclusions: In adult with de novo AML received IA10 regimen as induction regimen, unfavorable molecular markers or cytogenetics at diagnosis and CRi independently predicted poor outcome. In addition, a higher percentage of peripheral blasts, monosomal karyotype and positive MRD after first consolidation therapy had negatively impact on outcomes.
Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Cytarabine/administration & dosage* ; Disease-Free Survival ; Female ; Humans ; Idarubicin/administration & dosage* ; Induction Chemotherapy ; Leukemia, Myeloid, Acute/drug therapy* ; Male ; Middle Aged ; Prognosis ; Remission Induction ; Retrospective Studies ; Young Adult

Objective: To probe the feasibility of decitabine (DAC) combined with micro-transplantation as consolidation treatment for older patients with acute myeloid leukemia (AML). Methods: Between November 2012 and September 2015, 37 consecutive patients with AML ≥60 years of age were analyzed. Of them, 19 patients received consolidation therapy with DAC followed by micro-transplantation (microtransplant group). Another 18 ones (chemo group) were treated with DAC plus priming regimen as consolidation chemotherapy in the same period. Results: There were no significant differences in terms of age, WBC count, and disease status of onset between the microtransplant and chemo groups (P>0.05). The two regimens were well tolerated. There was no difference of CTC grade 3-4 nonhematologic toxicities between the microtransplant and chemo groups (36.8% vs 27.8%, χ(2)=0.347, P=0.728). The median recovery durations for neutrophil and platelet in the microtransplant group were similar to those in the chemo group (12 vs 13 days, z=1.599, P=0.110; 14 vs 12 days, z=-1.314, P=0.189, respectively). No graft-versus-host disease was observed in the microtransplant group. The 2-year leukemia-free survival and overall survival were better in microtransplant group (50.7% and 54.9%, respectively) than in chemo group (24.3% and 30.0%, respectively) (P=0.047 and P=0.071, respectively). Conclusion: DAC combined with micro-transplantation as a consolidation regimen may be a safe and promising option for older patients with AML.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Consolidation Chemotherapy ; Cytarabine ; Decitabine/administration & dosage* ; Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Middle Aged ; Treatment Outcome

Objective: To evaluate the clinical efficacy and safety of decitabine in combination with lower-dose CAG regimen (G-CSF, cytarabine and aclarubicin; D-CAG regimen) in the treatment of myelodysplastic syndromes with excess blasts (MDS-EB) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), compared to standard CAG regimen. Methods: A total of 42 patients with newly diagnosed MDS-EB and AML-MRC from May 2011 to March 2017 were included in the retrospective study. 21 cases were initially treated with G-CSF for priming, in combination with cytarabine of 10 mg/m(2) q12h for 14 days and aclarubicin of 20 mg/d for 4 days (CAG regimen) and the other 21 cases were initially treated with decitabine of 20 mg/m(2) for 5 days and lower-dose CAG regimen (cytarabine of 10 mg/m(2) q12h for 7 days, aclarubicin of 10 mg/d for 4 days, and G-CSF for priming (D-CAG regimen). After two cycles of induction chemotherapy, the patients who obtained complete remission(CR) received consolidation chemotherapy or hematopoietic stem cell transplantation (HSCT). Results: Among a total of 42 patients, the median age was 52.5 years (18-65 years) and 64.3% of them were male. Baseline characteristics of patients between D-CAG group and CAG group showed no significant differences. The CR for patients in D-CAG group was 81.0% (17/21), compared to 52.4% (11/21) in CAG group after 2 cycles of therapy (χ(2)=3.857, P=0.050). The overall response rate (ORR) for patients in D-CAG group and CAG group was 85.7% (18/21) and 76.2% (15/21) respectively, without significant difference (χ(2)=1.273, P=0.259). By December 2017, the median follow-up of D-CAG group and CAG group was 13(6-32) months and 15(2-36) months respectively. Finally, 10 patients in D-CAG group and 7 patients in CAG group received HSCT respectively. Except patients receiving HSCT, the median leukemia-free survival (LFS) time for patients in D-CAG group and CAG group was 18.0 (95%CI 6.6-29.4) months and 11.0 (95%CI 0-23.9) months respectively. Probabilities of 12 months LFS for D-CAG group and CAG group were (63.6±14.5)% and (50.0±13.4)% respectively, without difference (χ(2)=0.049, P=0.824). Except patients receiving HSCT, there were 2 deaths in D-CAG group and 7 deaths in CAG group respectively. The cumulative probabilities of 12 months OS for non-HSCT patients in D-CAG group and CAG group were (90.9±8.7)% and (61.5±13.5)% respectively, without significant difference (χ(2)=1.840, P=0.175). The incidences of side effects between D-CAG group and CAG group did not show significant differences (P=0.479), and the main side effects included cytopenias, pneumonia, infections of skin and soft tissues, neutropenic patients with fever, liver dysfunction. Conclusion: The decitabine in combination with lower-dose CAG regimen improved CR for patients with MDS-EB and AML-MRC, and was a promising choice.
Aclarubicin ; Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Cytarabine/administration & dosage* ; Decitabine/administration & dosage* ; Female ; Granulocyte Colony-Stimulating Factor/administration & dosage* ; Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Male ; Middle Aged ; Myelodysplastic Syndromes/drug therapy* ; Remission Induction ; Retrospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVETo evaluate the efficacy and adverse effects of low dose thalidomide (TD) combined with modified VCMP (vincristine+cyclophosphamide+melphalan+prednisone) (TD+mVCMP) and VAD (vincristine+doxorubicin+dexamethsone) (TD+VAD) regimens for treating aged patients with MM.

METHODSA total of 47 patients with newly diagnosed MM were enrolled in this study. Among them 27 cases were treated with TD+mVCMP regimen (TD+mVCMP group), 20 cases were treated with TD+VAD regimen (TD+VAD group). The dose of TD in 2 groups all was 100 mg/d. Each patient received 4 or more courses of treatment.

RESULTSOut of 27 cases in TD+mVCMP group, 9 cases achieved complete remission (CR), 5 cases-very good partial remission (VGPR), 6 cases-partial remission (PR); among 20 cases in TD+VAD group, 3 cases achieved CR, 3 cases achieved VGPR, 4 cases achieved PR. The total effective rate in 2 group was 74.1% and 50% respectively, there was statistical difference between 2 groups (P<0.05). The differences of Hb level, plasmocytic ratio of bone marrow and M protein level in 2 groups before and after treatment were significant (P<0.05). The 5 years survival rate of patients in TD+mVCMP and TD+VAD group was 72.8% and 66.9% respectively, there was no statistical difference (P>0.05). The incidence of adverse reactions including caxdiac toxicity, severe leucopenia and thrombocytopenia in TD+mVCMP group was lower than that in TD+VAD group.

CONCLUSIONLow dose TD combined with modified VCMP regimen for treatment of newly diagnosed aged patients with MM is safe and effective, which may be used as the first line treatment regimen for population in aged MM patients.

Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Cyclophosphamide ; administration & dosage ; therapeutic use ; Cytarabine ; administration & dosage ; therapeutic use ; Dexamethasone ; administration & dosage ; therapeutic use ; Humans ; Melphalan ; administration & dosage ; therapeutic use ; Multiple Myeloma ; drug therapy ; Prednisone ; administration & dosage ; therapeutic use ; Remission Induction ; Survival Rate ; Thalidomide ; administration & dosage ; therapeutic use ; Thrombocytopenia ; Vincristine ; administration & dosage ; therapeutic use

Leukemia is a type of malignant tumors of hematopoietic system with the abnormal increased immature leukemia cells showing metastasis and invasion ability. Liver is one of the main targets of the leukemia cells spread to, where they may continue to proliferate and differentiate and cause liver function damage, even liver failure. Our previous studies showed that Angelica polysscharides (APS), the main effective components in Angelica sinensis of Chinese traditional medicine, was able to inhibit the proliferation and induced differentiation of the leukemia cells, however, its effect on the liver during the treatment remains elucidated. In the present study, the human leukemia NOD/SCID mouse model were established by implantation human leukemia K562 cells line, then the leukemia mouse were treated with APS, Ara-c or APS + Ara-c respectively by peritoneal injection for 14 days, to explore the effect and mechanism of the chemicals on the mouse liver. Compared to the human leukemia NOD/SCID mouse model group with the treatments of APS, Ara-c and APS + Ara-c, We found that severe liver damage and pathological changes of the liver were able to alleviate: First, the number of white blood cells in the peripheral blood was significantly lower and with less transplanted K562 leukemia cells; Second, liver function damage was alleviated as liver function tests showed that alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBiL) were significantly reduced, while the albumin (Alb) was notably increased; Third, liver antioxidant ability was improved as the activities of the antioxidant enzymes glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were significantly increased, and the contents of GSH and malonaldehyde (MDA) were decreased significantly in the liver; Fourth, the inflammation of the liver was relieved as the level of IL-1beta and IL-6, the inflammatory cytokines, were decreased significantly in the liver. Fifth, liver index was increased as the pathological observation showed that leukemia cells with diffused infiltration into the liver lobules were significantly reduced and with a remarkable increase of apoptotic positive cell rate by TUNEL test. Furthermore, the APS + Ara-c combined administration showed an even more significant positive effect. In conclusion, the APS, Ara-c therapy reduced the accumulation of leukemia cells within the liver, reduced the liver function damage and levels of inflammatory factors, improved antioxidant capacity of the liver tissue and thus alleviate the pathological changes of the liver. Moreover, the APS + Ara-c combination therapy may have an additive effect.
Angelica ; chemistry ; Animals ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Cell Line, Tumor ; Cytarabine ; administration & dosage ; Humans ; K562 Cells ; Leukemia ; drug therapy ; Liver ; drug effects ; Male ; Mice ; Mice, SCID ; Polysaccharides ; administration & dosage

This study was purposed to compare the clinical efficacy and adverse reactions of low-dose decitabine combined with CAG regimen (aclarubicin, Ara-C, and G-CSF) and CAG regimen alone in intermediate to high-risk myelodysplastic syndromes (MDS), and evaluate the validity and efficacy of the former regimen as new treatment method of intermediate to high-risk myelodysplastic syndromes. A total of 12 patients with intermediate (IR) to high-risk (HR) MDS treated by low-dose decitabine combined with CAG regimen and 10 patients with IR to HR MDS treated by CAG regimen alone were evaluated after treatment of 1 cycle and at least after 2 cycles. The complete remission (CR) after 1 cycle, overall remission rate (ORR), progression free survival (PFS) and overall survival (OS) between them were analyzed. The results showed that 9 patients treated by low-dose decitabine combined with CAG regimen achieved complete remission after 1 cycle, 2 patients achieved partial remission, 1 patient did not show reaction. The complete remission rate was 75.0% and overall response rate was 91.7%. The median time of disease free survival was 9 months (0-27 months). The median overall survival time was 16 months (3-28 months). 4 patients suffered from pulmonary infection after treatment and then were all cured after treatment with anti-infective therapy. The 5 patients treated by CAG regimen alone achieved complete remission,3 patients achieved partial remission, 2 patients showed non-reaction. The complete remission rate was 50.0% and overall response rate was 80.0%. The median time of disease free survival was 6 months(0-18 months). The median overall survival time was 13 months(3-31 months), 4 patients suffered from pulmonary infection, 1 patient suffered from enteric infection and 1 patient suffered from Escherichia coli septicemia after treatment, all of them becomed better after active treatment. Two groups of patients all had no serious adverse reactions, All patients could tolerate, no severe complication-related death occurred in them. The statistical analysis indicated that the patients treated with low-dose decitabine combined with CAG regimen had longer progression free survival time than those treated with CAG regimen alone, and had longer overall survival time but did not have statistically significant. It is concluded that low-dose decitabine combined with CAG regimen has better clinical efficacy for patients with intermediate to high-risk MDS and did not increase risk for them. It is worth to apply in clinic.
Aclarubicin ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Azacitidine ; administration & dosage ; analogs & derivatives ; Cytarabine ; therapeutic use ; Disease-Free Survival ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Myelodysplastic Syndromes ; drug therapy ; Remission Induction ; Treatment Outcome