Behenoyl cytosine arabinoside, daunorubicin, 6-mercaptopurine, and prednisolone combination therapy for acute myelogenous leukemia in adults and prognostic factors related to remission duration and survival length.

1986 ◽  
Vol 4 (12) ◽  
pp. 1740-1747 ◽  
Author(s):  
R Ohno ◽  
Y Kato ◽  
E Nagura ◽  
T Murase ◽  
M Okumura ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Acute Myelogenous Leukemia ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Myelogenous Leukemia ◽  
Wilcoxon Test ◽  
Kaplan Meier ◽  
Acute Myelogenous ◽  
Initiation Of Therapy ◽  
Wbc Count

Fifty-one consecutive previously untreated adult patients with acute myelogenous leukemia (AML) were treated with BHAC-DMP (N4-behenoyl-I-beta-D-arabinofuranosyl-cytosine, daunorubicin, 6-mercaptopurine, and prednisolone) therapy. Forty-two patients (82.4%) achieved complete remission (CR). The Kaplan-Meier analysis revealed a probability for remaining in remission of 14% and for survival of 23% at 6 years. Pretreatment factors related to the achievement of CR, such as age, French-American-British (FAB) classification and WBC at the start of treatment, were not identified. Factors related to the CR duration and survival time of the patients who had achieved CR were first analyzed by a univariate analysis with the generalized Wilcoxon test. WBC count at the start of treatment, percent of blasts in the marrow at 1 and 2 weeks after the initiation of therapy, days required until CR, number of courses of induction therapy required until CR, and days required for the disappearance of circulating blasts were identified as statistically significant prognostic factors. When these characteristics were further analyzed by the Cox multivariate regression model, the percent of blasts in the bone marrow at 2 weeks was the most important prognostic factor with a statistical significance, and WBC count at the start of treatment and days required until CR (or number of courses required to achieve CR) were also important factors, with borderline significance.

scholarly journals Chemotherapy for acute myelogenous leukemia in children and adults: VAPA update

Blood ◽  
1983 ◽  
Vol 62 (2) ◽  
pp. 315-319 ◽  
Author(s):  
HJ Weinstein ◽  
RJ Mayer ◽  
DS Rosenthal ◽  
FS Coral ◽  
BM Camitta ◽  
...  
Keyword(s):  
Complete Remission ◽  
Maintenance Therapy ◽  
Induction Chemotherapy ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Kaplan Meier ◽  
High Incidence ◽  
Acute Myelogenous ◽  
Leukemia In Children

Abstract We designed a protocol (VAPA) that featured 14 mo of intensive postremission induction chemotherapy in an effort to improve remission durations for patients with acute myelogenous leukemia (AML). One hundred and seven patients under 50 yr of age were entered into this study. The rate of complete remission is 70%. A Kaplan-Meier analysis of patients entering remission predicts that 56% +/- 7% (+/-SE) of patients less than 18 yr and 45% +/- 9% of patients aged 18–50 yr will remain in remission at 3 yr (median follow-up is 43 mo). Patients with the monocytic subtype had a statistically significant shorter duration of remission (2-sided p less than 0.05). There was a high incidence of primary CNS relapse in children. Thirty-one of 41 patients who completed the regimen remain in remission without maintenance therapy. We conclude that the VAPA protocol continues to offer a promising approach to treatment of AML.

Does cranial irradiation reduce the risk for bone marrow relapse in acute myelogenous leukemia? Unexpected results of the Childhood Acute Myelogenous Leukemia Study BFM-87.

1993 ◽  
Vol 11 (2) ◽  
pp. 279-286 ◽  
Author(s):  
U Creutzig ◽  
J Ritter ◽  
M Zimmermann ◽  
G Schellong
Keyword(s):  
Bone Marrow ◽  
Acute Myelogenous Leukemia ◽  
Cranial Irradiation ◽  
Low Risk ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Number Of Patients ◽  
Acute Myelogenous ◽  
Wbc Count ◽  
Group B

PURPOSE One of the goals of study AMA-BFM-87 was to test prospectively in acute myelogenous leukemia (AML) patients if cranial irradiation could be replaced by late intensification therapy with high-dose cytarabine (Ara-C) and etoposide (VP-16). PATIENTS AND METHODS Patients with a low risk of CNS relapses (ie, no initial CNS disease, WBC count at diagnosis < or = 70.000/microL) were randomized for irradiation (group A, 31 patients). In 25 patients (group B), randomization was refused. As interim results showed no increase of CNS relapses in nonirradiated patients, prophylactic irradiation was discontinued after 2 1/2 years to prevent unnecessary CNS toxicity. Forty-four patients (group C) entered the study after randomization had been stopped. RESULTS In all patients with a low risk of CNS recurrences (n = 100), a significantly higher probability of relapse-free interval (pRFI) of 5 years was found in irradiated patients (pRFI = .78) compared with nonirradiated patients (pRFI = .41) (P = .007). Moreover, a slightly higher incidence of CNS relapses was observed in nonirradiated patients. Due to the small number of patients, this was not observed when randomized patients only were analyzed. In accordance with these findings, the favorable outcome of low-risk patients in the preceding study, AML-BFM-83 (pRFI > .80), could only be reproduced in study AML-BFM-87 in patients who had received cranial irradiation. CONCLUSION These results indicate that cranial irradiation should be an integral part of the treatment of all AML patients not undergoing bone marrow transplantation. Residual blasts in the CNS may escape systemic chemotherapy and lead to recurrence of the initial disease not only in the CNS, but also in the bone marrow.

Chromosome 17 Abnormalities Are Associated with Worse Overall and Relapse Free Survival in Patients with Acute Myelogenous Leukemia and Poor-Risk Cytogenetics.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1501-1501
Author(s):  
Gautam Borthakur ◽  
Constantine Tam ◽  
Hagop Kantarjian ◽  
E. Lin ◽  
Jorge Cortes ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Chromosome 17 ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Cytogenetic Abnormalities ◽  
Kaplan Meier ◽  
Variate Analysis ◽  
Acute Myelogenous

Abstract Purpose: Chromosome 17 abnormalities define a group of patients with acute myelogenous leukemia (AML) (Nahi, H. et al. Leukemia and Lymphoma2008;49:508) with poor outcomes. We analyzed the additional impact of chromosome 17 abnormalities (−17, −17p, −17q, der17) among patients with AML and cytogenetic abnormalities traditionally considered to be of adverse prognosis. Patients and Methods: 1086 patients with AML [excluding inv 16, t (8;21), t (15;17), Diploid/-y abnormality] were included in this analysis. Based on cytogenetic abnormalities patients were grouped into: −5,−7,−5and −7, complex. The following parameters were included in uni and multi-variate analysis: age, performance status, WBC, hemoglobin, platelets, marrow blast percentage, bilirubin, creatinine, albumin, LDH, chromosome 17 abnormality (yes/no). Results: Four hundred and fourteen (45%) patients achieved complete remission (CR) or CR with incomplete platelet recovery (CRp) and 267 (64.5%) patients relapsed. Two hundred seventy (24.9%) patients had abnormalities of chromosome 17. Abnormalities of chromosome 17 were associated with lower CR or CRp rate (p=0.02) and higher possibility of having cytogenetic abnormality of −5 or −7 (p&lt;0.0001). Multivariate analysis showed that patients with abnormalities of chromosome 17 had worse overall survival (OS) compared to patients without (p= 0.003)(Fig.1). Multi-variate analysis within cytogenetic subgroups showed that chromosome 17 abnormalities were associated with worse OS in patients with chromosome 5 abnormality(p=.02) (data not shown) and in those with complex cytogenetics (p=.04)(Fig.2) and not in patients with chromosome 7 (p=.17)or combined 5 and 7 abnormalities (p=.33). Similar analysis restricted to patients achieving CR/CRp after induction therapy showed that impact of chromosome 17 abnormalities on relapse free survival (RFS) mirrored their impact on OS. Conclusion: chromosome 17 abnormalities are associated with worse OS and RFS in patients with AML and adverse cytogenetics and have additional negative impact on the outcomes in certain well-known adverse cytogenetic subgroups. Figure 1: Kaplan-Meier estimates of overall survival by status of chromosome 17 Figure 1:. Kaplan-Meier estimates of overall survival by status of chromosome 17 Figure 2: Kaplan-Meier estimates of overall survival by status of chromosome 17 in subgroup of patient, complex Figure 2:. Kaplan-Meier estimates of overall survival by status of chromosome 17 in subgroup of patient, complex

scholarly journals Chemotherapy for acute myelogenous leukemia in children and adults: VAPA update

Blood ◽  
1983 ◽  
Vol 62 (2) ◽  
pp. 315-319 ◽  
Author(s):  
HJ Weinstein ◽  
RJ Mayer ◽  
DS Rosenthal ◽  
FS Coral ◽  
BM Camitta ◽  
...  
Keyword(s):  
Complete Remission ◽  
Maintenance Therapy ◽  
Induction Chemotherapy ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Kaplan Meier ◽  
High Incidence ◽  
Acute Myelogenous ◽  
Leukemia In Children

We designed a protocol (VAPA) that featured 14 mo of intensive postremission induction chemotherapy in an effort to improve remission durations for patients with acute myelogenous leukemia (AML). One hundred and seven patients under 50 yr of age were entered into this study. The rate of complete remission is 70%. A Kaplan-Meier analysis of patients entering remission predicts that 56% +/- 7% (+/-SE) of patients less than 18 yr and 45% +/- 9% of patients aged 18–50 yr will remain in remission at 3 yr (median follow-up is 43 mo). Patients with the monocytic subtype had a statistically significant shorter duration of remission (2-sided p less than 0.05). There was a high incidence of primary CNS relapse in children. Thirty-one of 41 patients who completed the regimen remain in remission without maintenance therapy. We conclude that the VAPA protocol continues to offer a promising approach to treatment of AML.

Treatment of acute myelogenous leukemia in children: results of the Italian Cooperative Study AIEOP/LAM 8204.

1987 ◽  
Vol 5 (9) ◽  
pp. 1356-1363 ◽  
Author(s):  
S Amadori ◽  
A Ceci ◽  
A Comelli ◽  
E Madon ◽  
G Masera ◽  
...  
Keyword(s):  
Acute Myelogenous Leukemia ◽  
Disease Free Survival ◽  
Myelogenous Leukemia ◽  
Free Survival ◽  
Continuation Therapy ◽  
Kaplan Meier ◽  
Acute Myelogenous ◽  
Childhood Aml ◽  
Leukocyte Counts ◽  
Cox Analysis

One hundred thirty-three children with acute myelogenous leukemia (AML) entered the multicenter Pediatric Branch of the Italian Association Against Leukemia trial AIEOP/LAM 8204 between July 1982 and May 1986. Induction therapy consisted of two courses of daunomycin (DNM) plus cytosine arabinoside (Ara-C). Those patients who achieved remission were given four courses of consolidation with DNM, 6-thioguanine (6-TG) and escalated doses of Ara-C followed by six courses of sequential continuation therapy using monthly pairs: etoposide (VP-16)/Ara-C, Ara-C/6-TG, and DNM/Ara-C. Periodic intrathecal Ara-C was used for CNS prophylaxis. One hundred seven (80%) children achieved complete remission (CR). Kaplan-Meier estimates of 3-year disease-free survival (DFS) and event-free survival (EFS) are 41% and 33%, respectively. Relapses occurred in 34 patients after 5 to 97 weeks (32 marrow; 2 marrow plus CNS). Overall, 14 patients died of complications during treatment (nine during induction; five during the postremission phase), mostly from infection. Risk factor analysis showed that induction failures occurred predominantly in children with French-American-British (FAB) M5 and in those with elevated leukocyte counts; by step-up Cox analysis, only FAB subtype was predictive of remission success. None of the variables examined was significant for predicting the duration of remission. Hyperleukocytosis was predictive of a significantly worse EFS rate. These results are encouraging and further support the use of intensive chemotherapy programs for childhood AML.

scholarly journals Improved treatment results in childhood acute myelogenous leukemia: a report of the German cooperative study AML-BFM-78

Blood ◽  
1985 ◽  
Vol 65 (2) ◽  
pp. 298-304
Author(s):  
U Creutzig ◽  
J Ritter ◽  
H Riehm ◽  
HJ Langermann ◽  
G Henze ◽  
...  
Keyword(s):  
Acute Myelogenous Leukemia ◽  
Initial Therapy ◽  
Cranial Irradiation ◽  
Myelogenous Leukemia ◽  
First Year ◽  
Cooperative Study ◽  
Table Analysis ◽  
Acute Myelogenous ◽  
Liver Enlargement ◽  
Wbc Count

One hundred fifty-one children with acute myelogenous leukemia (AML) entered the cooperative study BFM-78 between December 1978 and October 1982. The initial therapy consisted of an intensive induction and consolidation regimen over eight weeks with seven different drugs and cranial irradiation. It was followed by maintenance with thioguanine and cytosine arabinoside for two years and additional Adriamycin during the first year. One hundred nineteen (79%) patients achieved a complete remission. Thirteen (9%) children died of early hemorrhages. After a median follow-up time of 36 (12 to 57) months, 47 relapses have occurred, with CNS involvement in seven cases. The life table analysis revealed a probability for overall survival after almost five years of 45% (SD, 4%), for event-free survival 41% (SD, 4%), and for the event- free interval 52% (SD, 5%). Up to now, no relapse was seen after 2 1/2 years. Risk factor analysis showed that early fatal hemorrhages occurred predominantly in children with M5 FAB type and with initial leukocytosis. An initial high WBC count and liver enlargement were unfavorable parameters for achieving remission. No factors could be identified concerning the risk for relapse. These data indicate that the applied treatment strategy is successful in inducing complete remissions in about three fourths of children with AML and also in enhancing considerably the chances for long-term remission.

Significance of Marrow Angiogenesis Factors in Patients with Acute Myelogenous Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4424-4424
Author(s):  
Liang-In Lin ◽  
Cheng-Yeh Lee ◽  
Chung-Yi Hu ◽  
Jih-Luh Tang ◽  
Hwei-Fang Tien
Keyword(s):  
Growth Factors ◽  
Survival Time ◽  
Median Survival ◽  
Acute Myelogenous Leukemia ◽  
Median Survival Time ◽  
Myelogenous Leukemia ◽  
Enzyme Linked Immunosorbent Assay ◽  
Kaplan Meier ◽  
Acute Myelogenous ◽  
Endothelial Growth Factor

Abstract Bone marrow (BM) neoangiogenesis plays an important role in the pathogenesis of acute myelogenous leukemia (AML). Paracrine exchange of growth factors among AML blasts, endothelial cells, and other marrow compartments is believed to contribute to the pathogenesis of AML. The vascular endothelial growth factor (VEGF) and the angiopoietin (ANG) family are the two major classes of growth factors associated with angiogenesis. In the present study, BM plasma from 52 AML patients and 20 normal donors were investigated. We measured the marrow concentrations of seven molecules associated with angiogenesis, VEGF, VEGF/PlGF, VEGF-C, VEGF-D, ANG-1, ANG-2, and Tie-2, by using enzyme-linked immunosorbent assay (ELISA). Compared to normal donors, the marrow levels of VEGF/PlGF, ANG-2, and Tie-2 were increased in patients with AML (p&lt;0.005, &lt;0.0001 and &lt;0.0001, respectively). On the contrary, VEGF-C and ANG-1 levels were decreased in patients with AML (p&lt;0.0001 and &lt;0.0005, respectively). Although the values were not completely normalized, sequential study revealed that at complete remission (CR) period, VEGF/PlGF, ANG-2, and Tie-2 levels were decreased (p&lt;0.005, &lt;0.005 and =0.02, respectively), while VEGF-C increased (p=0.04). Kaplan-Meier survival curves showed that the subgroup of patients with lower Tie-2 level (29 ng/ml) had a longer median survival time than those with higher Tie-2 level (18.9 months versus 2.5 months, p&lt;0.005). In addition, subgroups of patients with higher VEGF/PlGF level (1 pg/ml) and VEGF-D level (350 pg/ml) also had a longer median survival time than those with lower levels (20.8 months versus 7.2 months, p=0.03 and 18.9 months versus 3.4 months, p=0.03, respectively). Taken together, there were significant differences in VEGF/PlGF, VEGF-C, ANG-1, ANG-2, and Tie-2 expressions between AML patients and normal donors. Expressions of VEGF/PlGF, VEGF-D, and Tie-2 might be prognostic markers in AML patients.

Rapamycin Induced Acute Myelogenous Leukemia U937 Cell Autophagy and Apoptosis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4847-4847
Author(s):  
Wenfeng Xu ◽  
Chunfu Li ◽  
Xiaoqin Feng ◽  
Yuelin He
Keyword(s):  
Survival Rate ◽  
Protein Expression ◽  
Acute Myelogenous Leukemia ◽  
U937 Cell ◽  
Statistical Significance ◽  
Myelogenous Leukemia ◽  
Control Group ◽  
U937 Cells ◽  
Rapamycin Treatment ◽  
Acute Myelogenous

Abstract Objective: To investigate the autophagy and apoptosis on acute myelogenous leukemia U937 cell induced by rapamycin. Methods: U937 cells was subcultured, and was set up blank control group (normal) and rapamycin treated groups (3 groups, 12h, 24h, 48h). The rapamycin treated groups were separately treated by 2¦ÌM concentration of rapamycin after 12h, 24h and 48h. The cell morphology of U937 cells treated by rapamycin was observed after 12h 24h and 48h. The survival rate of cells was detected by CCK-8 method. Cell apoptosis was detected by flow cytometry using Annexin V-FITC/PI double labeled. Use real-time PCR to detect the level of mRNA expression in autophagy specific protein maker LC3-¢òin different treated times by rapamycin. Rapamycin LC3 protein expression levels after treatment was detected by western blot method. Results: Visible under inverted microscope, the rapamycin treatment groups¡¯ cell number reduced gradually after cultured 12h, 24h and 48h, smaller volume, cell rupture, increase the nucleus pycnosis and cellular debris(Figure 1). With the extension of time, U937 cells survival rate is falling, compared with control group, with statistical significance(P=0.031; P<0.05). Rapamycin treatment U937 cells after 12 h, 24 h and 48 h, U937 cell apoptosis rate increased, compared with control group, with statistical significance (P=0.027; P< 0.05, Figure2). Rapamycin treatment U937 cells after 12 h, 24 h and 48 h, LC3-¢ò mRNA expression and protein expression were cut, compared with control group, with statistical significance(P=0.029; P<0.05, Figure 3). Conclusion: Rapamycin can induce autophagy and apoptosis of U937 cells. Autophagy protein LC3-¢ò in gene and protein expression level lowered, LC3-¢ò may play an important role in regulating the leukemia cell autophagy. Disclosures No relevant conflicts of interest to declare.

Acute Myelogenous Leukemia After Treatment for Malignant Germ Cell Tumors in Children

1999 ◽  
Vol 17 (10) ◽  
pp. 3226-3233 ◽  
Author(s):  
Dominik T. Schneider ◽  
Elisabeth Hilgenfeld ◽  
Dirk Schwabe ◽  
Wolfgang Behnisch ◽  
Andreas Zoubek ◽  
...  
Keyword(s):  
Germ Cell ◽  
Acute Myelogenous Leukemia ◽  
Topoisomerase Ii ◽  
Germ Cell Tumors ◽  
Myelogenous Leukemia ◽  
Cytogenetic Aberrations ◽  
Kaplan Meier ◽  
Increased Risk ◽  
Acute Myelogenous ◽  
Malignant Germ Cell Tumors

PURPOSE: To identify the long-term sequelae of therapy for malignant germ cell tumors (GCTs). PATIENTS AND METHODS: Between 1980 and 1998, 1,132 patients were prospectively enrolled onto the German nontesticular GCT studies. A total of 442 patients received chemotherapy using combinations of the drugs cisplatin, ifosfamide, etoposide, vinblastine, and bleomycin, and 174 patients were treated with a combination of chemotherapy and radiotherapy. Median follow-up duration was 38 months (range, 6 to 199 months). RESULTS: Six patients developed therapy-related acute myelogenous leukemia (t-AML). There was no t-AML among patients treated with surgery (n = 392) or radiotherapy only (n = 124). The Kaplan-Meier estimates of the cumulative incidence (at 10 years) of t-AML were 1.0% for patients treated with chemotherapy (three of 442) and 4.2% for patients treated with combined chemotherapy and radiotherapy (three of 174). Notably, four of these six patients had been treated according to a standard protocol with modest cumulative chemotherapy doses. Five patients had received less than 2 g/m2 epipodophyllotoxins, and four patients had received less than 20 g/m2 ifosfamide. Four patients presented with AML, two with myelodysplasia in transformation to AML. In five patients, cytogenetic aberrations were found, four of which were considered characteristic for t-AML. Four patients died despite antileukemic therapy. One patient is alive but suffered a relapse of his GCT, and one patient is alive and well. No secondary solid neoplasm was observed. CONCLUSION: In patients with AML after treatment for GCT, several pathogenetic mechanisms must be considered. AML might evolve from a malignant transformation of GCT components without any influence of the chemotherapy. On the other hand, the use of alkylators and topoisomerase II inhibitors is associated with an increased risk of t-AML. Future studies will show if the reduction of treatment intensity in the current protocol reduces the risk of secondary leukemia in these patients.

scholarly journals Improved treatment results in childhood acute myelogenous leukemia: a report of the German cooperative study AML-BFM-78

Blood ◽  
1985 ◽  
Vol 65 (2) ◽  
pp. 298-304 ◽  
Author(s):  
U Creutzig ◽  
J Ritter ◽  
H Riehm ◽  
HJ Langermann ◽  
G Henze ◽  
...  
Keyword(s):  
Acute Myelogenous Leukemia ◽  
Initial Therapy ◽  
Cranial Irradiation ◽  
Myelogenous Leukemia ◽  
First Year ◽  
Cooperative Study ◽  
Table Analysis ◽  
Acute Myelogenous ◽  
Liver Enlargement ◽  
Wbc Count

Abstract One hundred fifty-one children with acute myelogenous leukemia (AML) entered the cooperative study BFM-78 between December 1978 and October 1982. The initial therapy consisted of an intensive induction and consolidation regimen over eight weeks with seven different drugs and cranial irradiation. It was followed by maintenance with thioguanine and cytosine arabinoside for two years and additional Adriamycin during the first year. One hundred nineteen (79%) patients achieved a complete remission. Thirteen (9%) children died of early hemorrhages. After a median follow-up time of 36 (12 to 57) months, 47 relapses have occurred, with CNS involvement in seven cases. The life table analysis revealed a probability for overall survival after almost five years of 45% (SD, 4%), for event-free survival 41% (SD, 4%), and for the event- free interval 52% (SD, 5%). Up to now, no relapse was seen after 2 1/2 years. Risk factor analysis showed that early fatal hemorrhages occurred predominantly in children with M5 FAB type and with initial leukocytosis. An initial high WBC count and liver enlargement were unfavorable parameters for achieving remission. No factors could be identified concerning the risk for relapse. These data indicate that the applied treatment strategy is successful in inducing complete remissions in about three fourths of children with AML and also in enhancing considerably the chances for long-term remission.

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