pirarubicin and Leukemia--Myeloid--Acute

To compare the efficacy and toxicity of the chemotherapeutic regimen containing pirarubicin and mitoxantrone on the treatment of relapsed or refractory acute myeloid leukemia (AML) in adults.. In this open prospective multicentre study, we randomly assigned patients with relapsed or refractory AML to receive TAE regimen (pirarubicin+cytarabine+etoposide) versus MAE regimen (mitoxantrone + cytarabine + etoposide). The efficacy and toxicity were compared between the two groups.. 56 patients entered this clinical trial. The complete remission (CR) rate on TAE arm was 79.0% versus 55.6% on MAE arm with the overall response (OR) rates of 86.8% versus 88.9%, respectively. The CR was higher on TAE arm (P=0.035) but with no significant difference between the two groups regarding the overall response (OR) rate. The regimens were well tolerated in both groups. Hematologic and non-hematologic toxicity were similar except relatively lower the mean dosage of G-CSF, red blood cells and platelets transfusion on TAE arm. No significant differences were seen between the two groups regarding the overall survival and relapse free survival rates.. TAE regimen might be an effective salvage therapy in patients with relapsed or refractory AML.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Dactinomycin; Doxorubicin; Etoposide; Granulocyte Colony-Stimulating Factor; Humans; Leukemia, Myeloid, Acute; Methotrexate; Prospective Studies; Recurrence; Remission Induction

The aim of the JCCLSG AML 9805 Down study was to evaluate the effect of continuous and high-dose cytarabine combined chemotherapy on the survival outcome of acute myeloid leukemia (AML) with Down syndrome (DS).. From May 1998 to December 2006, DS patients with newly diagnosed AML were enrolled. Remission induction therapy consisted of two courses of pirarubicin, vincristine, and continuous-dose cytarabine (AVC1). The patients who achieved complete remission (CR) after two courses of AVC1 were subsequently treated with mitoxantrone and continuous-dose cytarabine (MC), etoposide and high-dose cytarabine (EC) and pirarubicin, vincristine, and continuous-dose cytarabine (AVC2).. Twenty-four patients were enrolled. All patients were younger than 4 years and diagnosed as having acute megakaryoblastic leukemia. Twenty-one patients achieved CR. Three patients died during remission induction therapy due to serious infection. No toxic deaths were observed during remission. All but one patient maintained CR without serious complications. The 5-year overall and event-free survivals were 87.5%  ± 6.8% and 83.1%  ± 7.7%, respectively.. Continuous and high-dose cytarabine combined chemotherapy with reduced intensity would be effective in DS children with AML.

Topics: Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Cytarabine; Disease-Free Survival; Down Syndrome; Doxorubicin; Female; Humans; Infant; Infant, Newborn; Japan; Leukemia, Myeloid, Acute; Male; Mitoxantrone; Survival Rate; Vincristine

Chemotherapy regimen containing anthracyclines has been used as the standard treatment for acute myeloid leukemia (AML). This study was to compare the efficacy and toxicity of the chemotherapy regimen containing perarubicin (THP) with that containing mitoxantrone (MIT) for young patients with newly diagnosed AML.. A total of 129 patients with newly diagnosed AML, aged 16 to 60 years olds, were assigned for induction chemotherapy containing one to two courses with standard-dose cytarabine (Ara-C) and an anthracycline antibiotic, THP or MIT. When complete remission was achieved after induction therapy, the patients received two courses of consolidation therapy identical to the induction regimen. From then, the patients were alternately given four courses of consolidation therapy consisting of Ara-C/THP or Ara-C/MIT every three weeks. Maintenance treatment continued for three years when patients were in continuous complete remission (CCR).. Twenty-six out of 42 patients (61.90%) receiving THP therapy, and 48 out of 73 patients (65.75%) treated by MIT achieved CR (P>0.05). Nine (34.61%) and 11 (22.92%) out of CR patients treated by THP and MIT, respectively, relapsed within one year (P=0.28). Moreover, the incidences of toxicities, such as infection, nausea/vomiting and cardiac events, were similar in these two groups (P>0.05) except for alopecie, which was 26.19% in the THP group compared to 42.47% in the MIT group (P<0.01).. Regimen containing THP plus Ara-C can be used for young adults with newly diagnosed AML for remission induction, but it is not superior to the regimen with MIT. Consolidation chemotherapy with THP or MIT is feasible for young adults with AML after CR.

Topics: Adolescent; Adult; Agranulocytosis; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Doxorubicin; Female; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Mitoxantrone; Nausea; Recurrence; Remission Induction; Young Adult

This study analyzed data on 35 infants with acute myeloid leukemia (AML) who were treated with intensive chemotherapy between 1995 and 1998 in Japan. The incidence of boys, younger age (< 6 months old), and hyperleukocytosis at onset was high in patients with the M4/M5 subtype (n = 23) in the French-American-British classification, compared with the non-M4/M5 subtype (n = 12). Thirteen (56%) and 16 (70%) patients with the M4/M5 subtype also showed 11q23 translocations and MLL gene rearrangements, respectively, whereas only one patient with the non-M4/M5 subtype had this rearrangement. All 35 patients were treated with the ANLL91 protocol consisting of etoposide, high-dose cytarabine, and anthracyclines. Overall survival and the event-free survival (EFS) rates at 3 years of all patients were 76% (95% confidence interval [CI], 61.3%-90.7%) and 72% (95% CI, 56.4%-87.9%), respectively. EFS showed no significant difference between 2 subgroups divided by age, gender, presence of the MLL gene rearrangements, and white blood cell count at onset; EFS in patients with the M4/M5 subtype tended to be better than those with the non-M4/M5 subtype. Although all 6 patients who underwent allogeneic stem cell transplantation (SCT) have been in complete remission, no benefit of SCT was confirmed. These findings suggest that the intensive chemotherapy with the ANLL91 protocol might have been responsible for the observed good outcome of infant AML, even without SCT. The presence of the MLL gene rearrangements or the age at onset had no impact on the outcome of infant AML.

Topics: Aclarubicin; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chromosomes, Human, Pair 11; Cytarabine; Disease-Free Survival; DNA-Binding Proteins; Doxorubicin; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Histone-Lysine N-Methyltransferase; Humans; Immunophenotyping; Infant; Leukemia, Myeloid, Acute; Male; Mitoxantrone; Myeloid-Lymphoid Leukemia Protein; Prognosis; Proto-Oncogenes; Remission Induction; Survival Rate; Transcription Factors; Translocation, Genetic; Treatment Outcome; Vincristine

Treatment results were evaluated in 45 children with acute myeloblastic leukemia (AML) treated on the ANLL-9205 protocol of the Children's Cancer Leukemia Study Group (CCLSG, Japan). In this protocol, terarubicin (THP-ADR), vincristine and continuous infusion of cytosine arabinoside (Ara C) were applied for remission induction therapy (AVC), and VP16+ high dose Ara C were used sequentially for 32 or 48 weeks. Eleven patients received stem cell transplantation. Thirty-eight out of the 43 eligible patients (88.4%) achieved complete remission, and the overall 3-year event-free survival (EFS) was 55.6% (S.E.,10%). This favorable response was attributed mainly to the high induction rate of patients with the M5, M7 FAB subtypes and higher WBC counts (> or = 10 x 10(9)/L). There was no difference in the 3-year EFS of these patients who discontinued treatment between 32 weeks and 48 weeks. Serious toxicities were not observed in this study. These findings suggest that the ANLL-9205 protocol is an effective and safe treatment regimen for childhood AML. When comparing the treatment period of 32 or 48 weeks, the difference was not statistically significant.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Child; Child, Preschool; Combined Modality Therapy; Cytarabine; Disease-Free Survival; Doxorubicin; Drug Administration Schedule; Etoposide; Female; Humans; Infant; Leukemia, Myeloid, Acute; Male; Prognosis; Remission Induction; Risk Factors; Vincristine

Eighty-four previously treated adult patients with acute leukemia and malignant lymphoma were treated with (2"R)-4'-O-tetrahydropyranyladriamycin (THP). THP (10-55 mg/m2) was administered by i.v. bolus injection daily for acute leukemia, and according to three different schedules for malignant lymphoma: daily, weekly or once every 3-4 weeks. Complete and partial remission (CR and PR) were achieved by 1 (5%) and 3 of 19 patients with acute myelogenous leukemia and by 2 (13%) and 3 of 15 patients with acute lymphoblastic leukemia, respectively. All CRs were in the groups receiving 25 mg/m2 THP daily. CR and PR were achieved by 6 (14%) and 8 of 42 patients with non-Hodgkin lymphoma (NHL) and by 4 (50%) and 2 of 8 patients with Hodgkin's disease (HD), respectively. No particular sensitivity was found among the subtypes of NHL and HD. Response (CR + PR) was noted in 10 (40%) of 25 patients treated every 3-4 weeks, in 1 (17%) of 6 treated weekly, and in 9 (47%) of 19 treated daily. The major side effects were myelosuppression and gastrointestinal toxicities. Alopecia was observed in only 10 (12%) patients. ECG abnormalities were observed in 7 (10%) patients, all of whom had previously been treated with other anthracyclines. No severe cardiotoxicity was observed.

Topics: Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Clinical Trials as Topic; Doxorubicin; Drug Administration Schedule; Electrocardiography; Female; Heart; Hodgkin Disease; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphoma; Lymphoma, Non-Hodgkin; Male; Middle Aged; Naphthacenes

Topics: Aclarubicin; Adolescent; Adult; Aged; Antimetabolites, Antineoplastic; Clinical Trials as Topic; Cytarabine; Doxorubicin; Drug Evaluation; Humans; Infusions, Parenteral; Leukemia, Myeloid, Acute; Lymphoma; Middle Aged; Naphthacenes

Dysregulated Yes-associated protein 1 (YAP1) is closely associated with cancer progression and chemo-resistance. We aim to explore the role of YAP1/Hippo pathway in regulating doxorubicin (ADM)-resistance in acute myeloid leukemia (AML).. In this study, we established two ADM-resistant cell lines (THP-1/ADM and K562/ ADM). Then, cell viability and apoptosis were detected by MTT assay and FCM assay, respectively. Real-time PCR was performed to examine the expression of genes in the AML/ADM cells and the clinic BM samples. The levels of all related proteins were examined by Western blot.. We found that the YAP1 and its downstream target genes, including EGFR, SOX2, and OCT4, were associated with ADM resistance, evidenced by the increased expression in ADMresistant AML/ADM cells and clinical BM specimens. Additionally, YAP1 ablation enhanced the promoting effects of ADM treatment on cell death in AML/ADM cells. Conversely, YAP1 increased ADM-a resistance in the original ADM-sensitive AML cells. These results may provide important new insights into understanding the role of YAP1 in regulating AML resistance by affecting CSCs characteristics.. In summary, we evidenced that the dysregulated YAP1/Hippo pathway influenced ADM resistance in AML. YAP1 might be a novel biomarker for the treatment of drug resistance in AML.

Topics: Doxorubicin; Drug Resistance, Neoplasm; Hippo Signaling Pathway; Humans; Leukemia, Myeloid, Acute; Transcription Factors

To 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.. Standard 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.. (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.. GHA 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.

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

Topics: Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Cytarabine; Disease-Free Survival; Down Syndrome; Doxorubicin; Female; Humans; Infant; Infant, Newborn; Japan; Leukemia, Myeloid, Acute; Male; Mitoxantrone; Survival Rate; Vincristine

To evaluate the therapeutic effects of chemotherapeutic regimen containing pirarubicin (THP) on the treatment of high-risk or refractory and relapsed acute leukemia (AL) in adults.. Forty patients with high-risk or refractory and relapsed AL, 26 males and 14 females, aged 33 (14-63) received treatment regimens with THP: TA regimen [THP + cytosine-arabinoside (Ara-C)] for acute myeloid leukemia (AML) and TAOP regimen [THP + Ara-C + vincristine (VCR) + prednisone (Pred)] for acute lymphocytic leukemia (ALL) or biphenotype-AL. Forty matched patients received mitoxantron (MIT) + Ara-C for AML or MIT + Ara-C + VCR + Pred for ALL and biphenotype AL as controls. The therapeutic effects were observed.. The complete remission (CR) rate was 47.5% vs 45% (P > 0.05), partial response (PR) rate was 25% vs 20% (P > 0.05), and overall response (OR) rate was 72.5% vs 65% (P > 0.05) in the treatment group and control group. The continuous CR time was 528 days in the treatment group, significantly longer than in the control group (463 days, P < 0.05). Marrow suppression was more serious in the treatment group. The patients in the treatment group had higher incidence of infections (P < 0.05). The time with sustained recovery of platelet number was 13.9 days in the treatment group, significantly longer than in the control group (P < 0.05).. Regimens with THP are more effective on treatment of high-risk or refractory and relapsed AL in adults, however, with more serious marrow suppression and higher incidence of infection.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Doxorubicin; Female; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Vincristine

To evaluate the therapeutic effects of chemotherapeutic regimen with pirarubicin in the management of adult high-risk acute leukemia.. Twenty-nine high-risk acute leukemia patients were selected as the treatment group and another 29 patients with similar pretreatment conditions as the control group. In the treatment group, 18 patients had acute non-lymphocytic leukemia (ANLL), and 8 had acute lymphocytic leukemia (ALL) and 3 had mixed leukemia, all received treatment regimens with pirarubicin+cytarabine, vincristine+pirarubicin+prednisone, Vincristine+pirarubicin+L-asparaginase (L)+prednisone or pirarubicin+cytarabine+vincristine+prednisone. Routine therapeutic regimens were adopted in the management of the control.. In ANLL patients, the overall remission rate was significantly higher in the treatment group than in the control group (77.78% vs 44.44%, P=0.031). Patients in the treatment group had greater marrow suppression and higher incidence of infections than the control group (P=0.012).. Regimens with pirarubicin is more effective than the routine regimens in the management of patients with high-risk ANLL and produce greater but tolerable marrow suppression.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Female; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Microspectrofluorometry allows the analysis of fluorescent molecules such as anthracyclines in the nucleus of isolated living cells. Using this technique, we confirmed that the amount of doxorubicin or THP-doxorubicin incorporated into the nucleus was related to the resistant or sensitive character of K562 cells. It was then extended to the study of fresh leukemic cells and kinetic studies were performed allowing the calculation of the retention rate (RR) of anthracycline (THP-doxorubicin) into the cell nucleus. A reproducibility study confirmed the accuracy of the method. Blast cells collected in patients with acute myeloid (n = 22) or lymphoid (n = 8) leukemia, at diagnosis (n = 26), or in relapse (n = 4) have been studied. RR varied from 8 to 98% independently of the type of leukemia or the clinical status. RR did not correlate either with P-glycoprotein or with CD34 expression although this latter result should be confirmed on a higher number of subjects. Among 18 patients presenting with AML at diagnosis, 14 have been treated with intensive chemotherapy including anthracyclines; the only one who had resistant disease had the lowest RR value. In conclusion, the results obtained here show that microspectrofluorometry allows the performance of kinetic studies on fresh leukemic cells in order to quantify chemo-resistance phenomena related to drug transport.

Topics: Biological Transport; Cell Compartmentation; Cell Nucleus; Doxorubicin; Drug Resistance; Humans; In Vitro Techniques; Leukemia, Myeloid, Acute; Microscopy, Confocal; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Spectrometry, Fluorescence; Tumor Cells, Cultured

A 25 year-old woman diagnosed as acute myelocytic leukemia (M0) suffered a fourth relapse in February 1992 at which time she already had anthracycline-induced cardiac dysfunction. Although remission was induced by low dose cytosine arabinoside and etoposide combined with pirarubicin, she developed acute heart failure followed by extreme elevation of transaminases level and DIC. Abdominal echography and CT revealed small round lesions in the liver. We diagnosed this episode as ischemic hepatitis because of the following clinical findings; serological markers of virus hepatitis were negative, hypotension and reduced blood flow to the liver were seen, and both transaminases and LDH were markedly elevated. Dobutamin and oxygen inhalation were started, her liver function returned to almost normal levels 8 days later.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cardiomyopathies; Cytarabine; Doxorubicin; Etoposide; Female; Hepatitis; Humans; Ischemia; Leukemia, Myeloid, Acute; Liver; Remission Induction

Three patients, diagnosed as acute promyelocytic leukemia and disseminated intravascular coagulation (DIC), were treated with THP-ADM in combination with heparin and intensive platelet transfusion. Two of the three patients achieved complete remission. The remaining one patient also responded favorably to the therapy and achieved marrow aplasia, and significant improvement of coagulopathy was observed after chemotherapy. However, he suddenly died of intractable congestive cardiac disturbance ten days after the completion of THP-ADM induction therapy. The mechanism of this unique delayed anthracycline-associated cardiotoxicity was discussed.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine Monophosphate; Disseminated Intravascular Coagulation; Doxorubicin; Heparin; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged

Topics: Adolescent; Adult; Doxorubicin; Drug Evaluation; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Middle Aged