The aim of study was to evaluate the clinical efficacy and toxicity of fludarabine combined with cytarabine (FA) regimen in the treatment of patients with refractory and/or relapsed acute myeloid leukemia (AML). Nineteen cases with refractory/relapsed AML were treated with FA regimen in which fludarabine phosphate 25 mg/(m(2) x d), d1-5; cytarabine (Ara-C) 2 g/(m(2) x d), d1-5. Another 20 cases were treated with salvage chemotherapy (MAE regimen: mitoxantrone, Ara-C and etoposide or DAE regimen: daunorubicin, Ara-C and etoposide). All patients received at least 2 cycles chemotherapy. The results showed that 9 patients (47%) in FA regimen group achieved complete remission (CR), 8 cases (42%) obtained partial remission (PR), the clinical efficacy was superior to that of the MAE or DAE regimens (p < 0.05). Major toxicity of FA regimen was myelosuppression. Grade IV hematologic toxicity occurred in all patients received FA regimen. Nonhematologic complications consisted of gastrointestinal side effects, mucositis, liver toxicity, which were mild to moderate and could be alleviated with supportive therapy. In conclusion, FA regimen is an effective regimen for treatment of refractory and relapsed AML.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cytarabine ; administration & dosage ; Female ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Male ; Middle Aged ; Recurrence ; Vidarabine ; administration & dosage ; analogs & derivatives

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cytarabine ; therapeutic use ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Leukemia, Myeloid, Acute ; pathology ; therapy ; Vidarabine ; analogs & derivatives ; therapeutic use

OBJECTIVETo observe the clinical safety and efficacy of decitabine in patients of acute myeloid leukemia and myelodysplastic syndromes (MDS/AML).

METHODSTotally 79 patients with MDS/AML were divided into three groups: (1)Treated with decitabine alone (20 mg/m² for 5 days). (2) Combination of decitabine with half dose CAG chemotherapy (Acla 20 mg qod×3 d, Ara-C 10 mg/m² q12 h×7 d, G-CSF 300 μg/d, the dose of G-CSF adjust to the amount of blood routine). (3)Combination of decitabine with CAG chemotherapy (Acla 20 mg qod×4 d, Ara-C 10 mg/m² q12 h×14 d, G-CSF 300 μg/d, the dose of G-CSF adjust to the amount of blood routine). We observed complete remission (CR) rate, overall response rate (ORR) and overall survival (OS) of the three groups; meanwhile, we analyzed the factors relevant to decitabine efficacy and the prognosis.

RESULTSORR in the three groups were 53.3%, 56.5% and 69.2% respectively, with no statistically significant differences (P>0.05). Due to the last follow-up at 2014.04.01, 20 patients still survived, 45 died, 14 were lost to follow-up. The 5-year cumulative survival rate of 79 patients was 25.3%, the 2-year survival were of the three groups were 34.8%, 24.8 and 29.2% respectively with no statistically significant differences (P>0.05). Adverse events of infection and bleeding were mainly caused by decitabine. Grade 3 to 4 hematological toxicities were observed in 72 cases with the average time for the lack of granulocytes as 14.8 days. 59 patients experienced infectious events, including grade 3 or 4 infections in 14 cases, grade 1 or 2 infections in 45 cases. There were no statistically significant differences (P>0.05) among the three groups in terms of infection rates, bleeding rates, duration of neutrophenia, mean MAP transfusion and mean platelet transfusion. 79 patients were safely through bone marrow suppression by anti-infective and supportive treatment without treatment-related deaths.

CONCLUSIONTreating MDS/AML with decitabine alone, in combination with half or one course CAG regimen produced high efficacy. ORR of the combination of decitabine with one course CAG regimen was relatively higher. Three groups of patients were all well tolerated.

Aclarubicin ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Azacitidine ; analogs & derivatives ; Cytarabine ; Granulocyte Colony-Stimulating Factor ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Myelodysplastic Syndromes ; drug therapy

OBJECTIVETo investigate the safety and efficacy of decitabine combined with CAG regimen in the treat-ment of newly diagnosed elderly patients with acute myeloid leukemia(AML).

METHODSFourty-nine patients with newly diagnosed acute myeloid leukemia (except M3) who were admitted to our hospital were selected. All the patients were older than 50 years old, and allogeneic hematopoietic stem cell transplantation could not be performed for various reasons. Decitabine-based chemotherapy regimens were used during induction therapy including single decitabine therapy(DAC), decitabine combined with CAG regimen(DAC-CAG) and decitabine combined with HAAG regimen(DAC-HAAG). Most of patients continued to use the original treatment after complete remission, while others were given the standard "3+7" regimen chemotherapy. A total of 2-4 courses of treatment was conducted in the majority of patients.

RESULTSAll of the 49 patients completed the induction therapy, in which 26 cases achieved complete remission(CR), 7 cases achieved partial remission(PR) and no response(NR) existed in 16 cases. The complete remission and the overall response rate(ORR) were 53% and 67% respectively. The overall response rate of DAC group, DAC-CAG group and DAC-HAAG group were 17%, 77% and 63% respectively. 14 patients were infected and 1 patients died of pulmonary infection during the induction therapy. The median number of suspended red blood cells and platelet infused were 9 units and 69 units respectively. Neutrophil recovery time was 15.1 days while the platelet recovery time was 20.1 days during the induction therapy. The mean follow-up time was 21 months. Overall survival(OS) was 75% at 6 months, 30% at 1 year, and 26% at 2 year, while disease-free survival(DFS) was 83% at 3 months, 54% at 1 year, and 47% at 2 year. The induction therapy could reach CR that was an independent prognostic factor, however, the initial white blood cell count, platelet count, age, chemotherapy regimen, prognostic stratification and whether complical by pnenmonia during chemotherapy were not independent prognostic factors.

CONCLUSIONThe induction efficacy of decitabine combined with chemotherapy is superior to that of decitabine alone. The outcome of induction chemotherapy is an independent prognostic factor, however, the high white blood cell count, poor karyotype, complications and AML with myelodysplasia-related changes do not affect long-term survival. DAC-CAG regimen is effective and have relatively few adverse reactions in AML. It is suitable for the patients who are ineligible for conventional chemotherapy.

Aged ; Antineoplastic Combined Chemotherapy Protocols ; Azacitidine ; analogs & derivatives ; Cytarabine ; Decitabine ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute ; Middle Aged ; Remission Induction ; Treatment Outcome

We report a case of reversible encephalopathy syndrome in a 16-year-old girl with acute myelogenous leukemia (AML), who is undergoing during consolidation chemotherapy composed of BH-AC (N4-behenoyl-1-beta-D-arabinofuranosyl cytosine) and idarubicin. On the 6th day of chemotherapy, she was in a drowsy state following generalized tonic clonic seizure lasting 20 minutes. MR images revealed extensive cortical and subcortical white matter brain edema. Alertness returned over the 24 hr following by the discontinuation of BH-AC and intravenous administration of diphenylhydantoin, although she complained of intermittent headaches and visual disturbance. She gradually recovered from these symptoms during subsequent 7 days. Previously noted abnormal signal intensities have nearly disappreared on follow-up MRI obtained on the 22nd day after the first seizure. She was discharged without any neurologic sequela. This case suggests that BH-AC, a derivative of cytosine arabinoside (1-beta-D-arabinofuranosylcytosine) could be a cause of reversible encephalopathy syndrome.
Adolescence ; Antineoplastic Agents/therapeutic use ; Antineoplastic Agents/adverse effects* ; Brain/radiography ; Case Report ; Cytarabine/therapeutic use ; Cytarabine/analogs & derivatives* ; Cytarabine/adverse effects ; Female ; Human ; Leukemia, Myelocytic, Acute/drug therapy ; Leukemia, Myelocytic, Acute/complications* ; Magnetic Resonance Imaging ; Seizures/radiography* ; Seizures/chemically induced

OBJECTIVETo explore the clinical efficacy and adverse effects of GHA(G-CSF+homoharringtonin+cytarabine C) and new combined priming chemotherapeutic regimens(GHAA/GHTA) with high efficacy and low toxicity for treatment of relapsed and refractory acute myeloid leukemia(AML) and myelodysplastic syndrome(MDS), and to analyze the relation of above-mentioned regimens with the expression of co-stimuolating molecule B7.1.

METHODSStandard GHA regimen consisting of G-CSF: 100 µg/(m2·d) subcutaneous injection, d 0-14; homoharringtonine: 1.0 mg/(m2·d) intravenous drip, d 1-14; Ara-C: 7.5-10 mg/(m2·d) subcutaneous injection, q12h, d 1-14. Other regimens as GHAA/GHTA were combined respectively with aclarubicin 20 mg d 1-7, or pirarubicin 20 mg d 1-7. 74 patients with refractory AML and 46 patients with MDS received these priming chemotherapy. The clinical efficacy and toxicity of above-mentioned priming chemotherapy were compared with 56 patients received routine chemotherapy (MA/TAE) respectively. And the expression of costimulatory molecule B7.1 on leukemia cells in patients of different subtypes was also detected by immunofluoressence and its relationship with clinical efficiency was explored.

RESULTS(1) for AML patients treated with priming chemotherapy, the total remission was 67.56% (CR 54.05%, PR 13.51%), which was much higher than that of patients received routine chemotherapy (P<0.05). The CR rate of AML-M2 and AML-M5 group (65.51%, 61.90% respectively) was much higher than that of AML other subtypes (P<0.05), and the longest remission period lasted for 4 years; (2) for MDS patients treated with priming chemotherapy, the total remission was 60.87% (CR 45.65%, PR 15.22%), which was also significantly higher than that of patients received routine chemotherapy (P<0.05); (3) in comparison with patients received standard GHA priming regimen, the remission rate of combined priming chemotherapy GHAA/GHTA was significantly higher both in patients with AML (85.18%) and MDS (81.25%); (4) side effects after chemotheropy, including granulocyte deficiency, thrombocytopenia and anemia etc, lasted for 7-14 days; the severe infection rate was 1%, there were no severe bleeding, digest effect and damage of function in heart, liver and kidney. The therapy-related mortality was zero. Compared with routine chemotherapy, priming chemotherapy proved significantly safe and effective (P<0.05); (5) the expression rate of costimulatory molecule B7.1 showed large variance between AML and MDS, it was higher in AML-M2/AML-M5 and lower in AML of other subtypes (P<0.05). In the same case, B7.1 expression was positive correlated with efficiency of priming chemotherapy.

CONCLUSIONGHA priming chemotherapy, as well as other combination regimens GHAA/GHTA, are well-tolerated, effective regimens for refractory AML and advanced MDS, without severe side effects and therapy-related mortality. Especially the new regimens GHAA/GHTA has better efficacy, which are proved more efficient than conventional GHA. Efficiency of priming chemotherapy is positive correlated with B7.1 expression, its mechanism will be further explored.

Aclarubicin ; analogs & derivatives ; Antineoplastic Combined Chemotherapy Protocols ; B7-1 Antigen ; Cohort Studies ; Cytarabine ; Doxorubicin ; analogs & derivatives ; Granulocyte Colony-Stimulating Factor ; Granulocytes ; Harringtonines ; Humans ; Leukemia, Myeloid, Acute ; Myelodysplastic Syndromes ; Recurrence ; Thrombocytopenia

OBJECTIVETo investigate the therapeutic efficacy and side effects of treating patients with myelodysplastic syndrome-RAEB (MDS-RAEB) and with refractory acute myeloid leukemia (AML) by using decitabine combined with CAG regimen.

METHODSClinical data of 21 patients with MDS-RAEB or refractory AML from July 2011 to July 2014 were analyzed retrospectively. Among 21 patients there were 4 cases of MDS-RAEB and 17 cases of refractory AML; 12 cases were beyond 60 years old; 13 cases had high-risk karyotypes. All the patients received decitabine combined with CAG regimen consisting of decitabine 20 mg/(m(2) · d), d 1-5; aclarubicin 10 mg/d, d 6-13; cytarabine 20 mg/d, d 6-19; G-CSF 300 µg/d, d 6-19.

RESULTSAfter 1 cycle of treatment with DCAG regimen, the outcome of 21 patients showed that 8 cases achieved complete remission (42.1%), 8 cases achieved partial remission (42.1%), 2 cases achieved hematologic improvement, 1 cases achieved non-remission and 2 cases died; and the 1 year overall survival rate was 67.5%. The outcome of 12 patients beyond 60 years old showed that 6 cases achieved complete renission (60%, 6/10), and the 1 year overall survival rate was 62.5%. The outcome of 13 patients with high-risk karytype showed that 6 cases achieved complete renission (54.5%, 6/11), and the 1 year overall survival rate was 61.5%. The main adverse event was myelosuppression, and non-hematological toxicity included liver dysfunction and gastrointestinal tract reaction.

CONCLUSIONDecitabine combined with CAG regimen is effective and safe for treatment of MDS-RAEB and refractory AML patients, which can prolong lives of patiens with refractory hematological diseases.

Aclarubicin ; analogs & derivatives ; Antineoplastic Combined Chemotherapy Protocols ; Azacitidine ; analogs & derivatives ; Cytarabine ; Granulocyte Colony-Stimulating Factor ; Humans ; Karyotype ; Leukemia, Myeloid, Acute ; Myelodysplastic Syndromes ; Pancytopenia ; Recurrence ; Remission Induction ; Retrospective Studies ; Survival Rate ; Treatment Outcome

Sapacitabine is an orally bioavailable prodrug of the nucleoside analog 2'-C-cyano-2'-deoxy-1-β-D-arabino-pentofuranosylcytosine (CNDAC). Both the prodrug and active metabolite are in clinical trials for hematologic malignancies and/or solid tumors. CNDAC has a unique mechanism of action: after incorporation into DNA, it induces single-strand breaks (SSBs) that are converted into double-strand breaks (DSBs) when cells go through a second S phase. In our previous studies, we demonstrated that CNDAC-induced SSBs can be repaired by the transcription-coupled nucleotide excision repair pathway, whereas lethal DSBs are mainly repaired through homologous recombination. In the current work, we used clonogenic assays to compare the DNA damage repair mechanism of CNDAC with two other deoxycytidine analogs: cytarabine, which is used in hematologic malignacies, and gemcitabine, which shows activity in solid tumors. Deficiency in two Rad51 paralogs, Rad51D and XRCC3, greatly sensitized cells to CNDAC, but not to cytarabine or gemcitabine, indicating that homologous recombination is not a major mechanism for repairing damage caused by the latter two analogs. This study further suggests clinical activity and application of sapacitabine that is distinct from that of cytarabine or gemcitabine.
Animals ; Antimetabolites, Antineoplastic ; pharmacology ; Arabinonucleosides ; pharmacology ; CHO Cells ; Cricetinae ; Cricetulus ; Cytarabine ; analogs & derivatives ; pharmacology ; Cytosine ; analogs & derivatives ; pharmacology ; DNA Breaks, Double-Stranded ; drug effects ; DNA Repair ; drug effects ; DNA-Binding Proteins ; deficiency ; Deoxycytidine ; analogs & derivatives ; pharmacology ; Homologous Recombination ; genetics ; Inhibitory Concentration 50 ; Prodrugs

This study was aimed to explore the effect and feasibility of reduced conditioning intensity allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed ETO positive acute myeloid leukemia (AML) patients. Fifteen cases of relapsed AML received the reducing conditioning intensity allo-HSCT from January 2011 to January 2013 in Beijing Military Command General Hospital. All patients were high-risk type of relapsed or refractory AML, including 10 males and 5 females, aged from 16 to 48 years old with mean age of 32.5 years. Ten cases are HLA-identical matching and other 5 cases are HLA-haploidentical.donors received granulocyte colony-stimulating factor (G-CSF) to mobilize the peripheral blood stem cell for transplantation. Conditioning regimen was fludarabine combined with busulfex, cytarabine and cyclophosphamide. The preventive donor's peripheral blood stem cell infusion were performed after 3 months of transplantation, and the toxicity, GVHD and disease-free survival were observed in patients after transplantation. The results showed that all patients achieved hematopoietic reconstitution, the average time of neutrophils ≥ 0.5 × 10⁹/L and platelets ≥ 20 × 10⁹/L were 15.5 d and 16.8 d respectively. Implantation was confirmed by the evidence of 100% donor hematopoiesis. Follow-up to June 2014, with a median follow-up duration of 27.5 months (18-54 months), GVHD occurred in 8 cases of all patients, one died of complication, the other 4 cases died of relapse and the other three patients remained in disease-free survival. The disease-free survival rate of 2-year was 66.7%,the longest disease-free survival time was up to 54 months. It is concluded that the reduced conditioning intensity allo-HSCT is the effective and safe method for relapsed AML with ETO-positive, and it may be chosen as a treatment method for relapsed ETO positive AML patients.
Adolescent ; Adult ; Allografts ; Cytarabine ; Disease-Free Survival ; Erythropoietin ; analysis ; Female ; Granulocyte Colony-Stimulating Factor ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; therapy ; Male ; Middle Aged ; Transplantation Conditioning ; Vidarabine ; analogs & derivatives ; Young Adult

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