Phase II trial of old age acute myeloid leukemia treatment by arsenic trioxide and low-dose subcutaneous cytosin arabinoside

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7075-7075
Author(s):  
A. Ghavamzadeh ◽  
S. Hashemi ◽  
K. Alimoghaddam ◽  
Z. Nasri Moghaddam ◽  
M. Shadpour ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Old Age ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Standard Treatment ◽  
Best Supportive Care ◽  
High Risk Group ◽  
Leukemia Treatment ◽  
Wbc Count ◽  
Very High

7075 Background: AML is a disease of old age, but unfortunately due to several factors standard treatment can not be delivered to these patients. Here we tried to achieve to bet possible response to these patients. Methods: Eleven old age patients selected for this trial. Patients couldn't tolerate standard treatment of AML due to old age or comorbid disorders. Treatment consist of best supportive care plus administration of low dose ARA-C (20mg/day as SQ) for 10 days each months and arsenic trioxide 10 mg/day as 2 hour iv infusion each month. Patients followed by CBC and BMA/B when peripheral blood normalized or every other month. Results: This cohort consist of 8 men and 3 women. Median age was 75 y/o (55–80). Median WBC count Hb level and platelet count at presentation were 42,860μl, 8.3g/dl and 30,500/μl, respectively. Complete remission observed in 6 and partial remission in one patient (RR = 63.6%), but remission was short live, after 6 months one patient was in CR and one in PR. After 12 months, only one patient was in PR. Median survival was 6 months and 6 patients survive more than 6 months. Two patients are alive after 12 months. Conclusions: Although prognosis of old age AML remain poor, but with this type of treatment RR is acceptable. In this very high-risk group of very old AML, combination of ATO and ARA-C possibly could improve survival. No significant financial relationships to disclose.

scholarly journals A Refined Regimen for Maximally Eliminating Early Life-Threatening Complications for Patients with High-Risk Acute Promyelocytic Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3994-3994
Author(s):  
Sanbin Wang ◽  
Lihui Peng ◽  
Lin Liu ◽  
Le Luo ◽  
Stephen Liang
Keyword(s):  
High Risk ◽  
Supportive Care ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Low Dose ◽  
Intrathecal Injection ◽  
Promyelocytic Leukemia ◽  
Severe Bleeding ◽  
Life Threatening ◽  
Wbc Count

Abstract Life-threatening complications, such as severe bleeding and/or differentiation syndrome at admission and/or along with induction treatment, among high-risk patients with acute promyelocytic leukemia (APL) are a worldwide puzzle towards the cure of the disease. Taking the rationale that high WBC count, at least in part, may cause cytokine storm related symptoms, we designed this refined regimen with low dose mitoxantrone and ATRA plus arsenic trioxide to determine the safety and efficiency of this WBC reduction, prevention of differentiation syndrome, and supportive care centered approach. In total there were 50 patients with high risk APL (WBC>10x109) from 2003-2017 were enrolled with a medium follow-up of 39 months (15-72 months). Our treatment strategy and detailed protocol are: 1) WBC reduction: it started with ATRA (25mg/m2/day) and arsenic trioxide (0.15mg/kg/day) based double induction. The advantage of decreased dose of ATRA can help to lower the happening of leukocytosis which will trigger the cytokine releasing related syndrome. Low dose mitoxantrone (3mg/m2) was added from day 2-5 plus hydroxyurea (1.5g, p.o. q6h) started from day 1. The criteria for withdrawal hydroxyurea is once both of the following standard are met: i) the WBC count has continuously decreased for three days after reached the peak value; ii) WBC < 10x109/L. 2) Prevention of Differentiation Syndrome (DS): Dexamethasone (5mg/day) was added once the diagnosis was confirmed at day 1. The criteria to taper dexamethasone are the same as to stop hydroxyurea. We require to withdraw dexamethasone within one week once start the taper process. In general, our goal is to prevent the occurrence of both leukopenia and leukocytosis and maintain the WBC count between 2-20x109. 3) Supportive care: We maintain the PLT count between 20-30x109 and fibrinogen >1.5g/L which helped to decrease the occurrence of myelo-suppression, DS and severe bleeding. 4) CNS Prophylaxis: The Intrathecal injection was given after the CR was achieved. Unless there was evidence of CNS infiltration, we gave intrathecal injection after correcting the coagulation abnormality. The consolidation began at four weeks after the end of induction. It contained four weeks of an on and off schedule of arsenic trioxide (0.15mg/kg/day), in total four cycles, and two weeks of an on and off schedule of ATRA (25mg/m2/day), in total seven cycles. A total of eight intrathecal injections were given on the first and last day of arsenic trioxide. Two death was observed through our strategy during the induction. All patients reached hCR by the end of induction. Relapse occurred in four out of 50 patients, and there was no treatment-related mortality. All the relapsed patients entered CR again after using the same protocol. Grade 3-4 adverse events were observed among 12% of all the cases. Three-year probability of overall survival (pOS) was found to be 92%. Our strategy focus of reducing WBC count sheds new light on maximally eliminating early mortality of high-risk APL patients. Disclosures No relevant conflicts of interest to declare.

Aclarubicin, Low-Dose Cytarabine Combined With G-CSF (CAG) Regimen For Patients Previously Treated Or Ineligible For Intensive Chemotherapy With Acute Myeloid Leukemia and Myelodysplastic Syndrom: A Single Center Experience

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2697-2697
Author(s):  
Koichiro Minauchi ◽  
Masato Obara ◽  
Takahide Ara ◽  
Kanako Shima ◽  
Atsushi Yasumoto ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Low Dose ◽  
Response Rate ◽  
Previous History ◽  
Intensive Chemotherapy ◽  
Intermediate Group ◽  
History Of ◽  
Wbc Count ◽  
Favorable Group

Abstract Background The incidence of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) increases with age. Intensive chemotherapy is unsuitable for older patients because of its intolerable toxicity. CAG (cytarabine, aclarubicin, and G-CSF) regimen is widely used for such elderly patients because of its relatively low toxicity mainly in Eastern Asia such as China and Japan. Several reports showed the efficacy of CAG, but their sample sizes are relatively small. Thus, we here report a retrospective, single-center analysis of 86 cases with AML and MDS treated with CAG regimen Patients and methods Patients of AML and MDS who were treated with CAG regimen at Sapporo Hokuyu hospital from 2008 to 2012 were analyzed retrospectively. To examine the efficacy of CAG, we examined response rate, overall survival (OS), event-free survival (EFS), and rate and duration of being free from transfusion. We also performed subgroup analysis on response rate, OS, and EFS by underlying diseases, chromosomal karyotypes, WBC count and LDH level. Chi-squared test was used to compare the response rate of chemotherapy between subgroups. Overall survival was defined from the time of starting chemotherapy to the time of death from any cause or to the time of last follow-up. Kaplan- Meier method was used to compare survival curves. Cox regression analysis was used to analyze differences between subgroups. Results Among 86 patients enrolled, 60 patients were with AML, and 26 were with MDS. Median age of the patients was 71 (range 17-87) years old and 57 (66.3%) patients were male. Forty-six patients had previous history of chemotherapy other than CAG, and seven had previous history of hematopoietic transplantation. Median time from diagnosis to first cycle of CAG was 169 (range 1-6104) days. Eighty-six patients received total of 136 series of CAG regimen. Each series consisted of several courses of CAG, and median number of cycles was two (range 1-6). Median follow-up duration was 276 (range 18-1718) days and 28 patients (32.6%) were alive at the last follow up. After the first series of chemotherapy, 39 patients achieved complete response (CR), 11 patients remained stable disease, and 36 patients experienced progression of disease. Overall response rate was 58.1%. CR was achieved in 30 out of 60 patients with AML (50%) and 8 out of 23 with MDS (34.8%), respectively. No significant difference of response rate was seen between the two groups (p=0.70). While 6 cases of AML and 4 cases of MDS showed partial response, 24 cases of AML and 11 cases of MDS were resistant to CAG, respectively. Half of the patients of AML were diagnosed as AML with MDS-related changes (AML with MRC). No differences of response rate were seen between AML and AML with MRC. Significant differences of CR rate were seen between three groups according to classification scheme of karyotype reported by SWOG/ECOG. In detail, CR rates were 62.9% in favorable karyotype group, 40.0% in intermediate group and 22.7% in unfavorable group, respectively (p=0.026). Favorable group was also superior on EFS compared to the other two groups (p=0.010). Median duration of OS and EFS were 349 and 457 days in favorable group, 495 and 228 days in intermediate group, 217 and 174 days in unfavorable group, respectively. Patients with normal LDH level survive significantly longer compared to patients with high LDH level (717 days vs. 296 days, p=0.004), although LDH level was not a predictive factor for CR rate (55.8% vs. 34.9%, p=0.084). Low WBC count (<3000/μl) at the time of chemotherapy also predicted longer survival time after treatment (p<0.001). Twenty-five out of 58 patients who were dependent on transfusion at the time of chemotherapy became independent from transfusion. Median duration of free from transfusion was 156 (range 35-483) days. Forty-five patients received two or more series of CAG regimen. CR rate on second or more series of the chemotherapy was 45.7%, and PR or SD was 12.5%, which were comparable to those of prior CAG treatment. Conclusions This study showed the efficacy of CAG regimen for patients with AML and MDS who were not candidate for intensive chemotherapy. CAG was first reported more than 10 years ago. But there are no prospective studies comparing this strategy with other low-dose chemotherapy, hypomethylating agents, and supportive care. To determine the place of this useful approach within the many therapeutic options for AML and MDS, prospective clinical trial is needed. Disclosures: No relevant conflicts of interest to declare.

Therapy With Demethylating Agents Significantly Improves Overall- and AML-Free Survival In Patients With MDS Classified As High-Risk By IPSS Or Very High Risk By IPSS-R and Partial Or Total Monosomy 7-Results From a German Multicenter Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2784-2784 ◽  
Author(s):  
Julie Schanz ◽  
Friederike Braulke ◽  
Katayoon Shirneshan ◽  
Kathrin Nachtkamp ◽  
Ulrich Germing ◽  
...  
Keyword(s):  
High Risk ◽  
Supportive Care ◽  
Median Time ◽  
Research Funding ◽  
Risk Group ◽  
Best Supportive Care ◽  
High Risk Group ◽  
Monosomy 7 ◽  
Free Survival ◽  
Very High

Abstract Introduction Total (-7) or partial (7q-) monosomy 7 is frequent in malignant myeloid disorders, observed in around 12% of MDS/AML and up to 40% of therapy-associated MDS/AML. Monosomy 7 is associated with poor outcome, high susceptibility to infections and poor response to chemotherapy. A therapeutic benefit for 5-azacytidine was previously described (Fenaux et al., 2009). The present study was designed to analyze clinical features, prognosis and response to different therapeutic strategies in patients with monosomy 7 in a multicentric, retrospective German cohort study. Patients and methods Currently, 231 patients with MDS/AML following MDS and monosomy 7 were included. Inclusion criteria were defined as follows: Morphologic diagnosis of MDS/AML following MDS, age ≥18 years, bone marrow blast count ≤30% and presence of -7 or 7q-. The data was assembled from centers in Düsseldorf, (n=120; 52%), Cologne (n=38; 17%), Freiburg (n=31; 13%), Göttingen (n=14; 6%), Munich (n=13; 6%), Dresden (n=11; 5%) and Mannheim (n=4; 2%). The median age in the study cohort was 67 years, 65% of patients were males. 29/231 patients (13%) were diagnosed as AML following MDS. MDS/AML was therapy-associated in 24 patients (11%). Regarding IPSS, 38 (19%) were classified as low/intermediate 1 risk and 165 (81%) as intermediate-2/high-risk. According to IPSS-R, 2 (1%) were assigned to the very-low/low risk group, 31 (16%) to the intermediate group, 52 (27%) to the high-risk group and 107 (56%) to the very high risk group. The treatment was classified as follows: Best supportive care (BSC), low-dose Chemotherapy (LDC), high-dose chemotherapy (HDC), demethylating agents (DMA; either 5-azacytidine or decitabine), and others. Results A best supportive care regimen was chosen in nearly half of the patients (49%). The remaining patients received 1-4 sequential therapies (1: 29%; 2: 11%; 3: 10%; 4: 1%). As the first line therapy, 64 patients (54%) received DMA, 24 (20%) an allo-Tx, 9 (8%) HDC, 5 (4%) LDC, and 16 (14%) were treated with other therapies. The best prognosis was observed in patients eligible for allo-Tx: The median OS in transplanted patients was 924 days as compared to 361 days (p<0.01) in patients not eligible for transplantation. In the latter cohort, patients who received DMA at any course of their disease did not differ from those receiving other therapies: The median OS was 468 days in patients treated with DMA as compared to 325 on those with alternative therapies (p not significant) and the median time to AML-transformation was 580 versus 818 days (p not significant), respectively. However, by classifying patients according to IPSS- and IPSS-R, it became obvious that patients with an IPSS high-risk or an IPSS-R very high risk showed a clear benefit from DMA: In the first group, median OS was 444 days in DMA-treated and 201 days in non-DMA-treated patients (p=0.048), in the latter group, median OS 444 days in the DMA-treated and 203 days in the non-DMA treated cohort (p=0.017). Comparable results were observed regarding AML-free survival: Median time to AML was 580 (DMA) vs. 186 (no DMA) days in IPSS high risk patients (p=0.031) and 580 (DMA) vs. 273 (no DMA) days in the IPSS-R very high risk group (p not significant). Conclusions Patients with MDS, partial or total monosomy 7 and a high risk according to IPSS or a very high risk according to IPSS-R show a pronounced benefit when treated with DMA, regarding overall- as well as AML-free survival. Further results from the ongoing data analysis will be presented in detail. The study was supported by research funding from Celgene. Disclosures: Schanz: Celgene: Research Funding. Braulke:Celgene: Research Funding. Germing:Celgene: Honoraria, Research Funding. Schmitz:Novartis: Research Funding; Celegene: Consultancy, Research Funding, Speakers Bureau. Götze:Celgene: Honoraria. Platzbecker:Celgene: Honoraria, Research Funding. Haase:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding.

scholarly journals Arsenic trioxide and low-dose cytarabine in older patients with untreated acute myeloid leukemia, excluding acute promyelocytic leukemia

Cancer ◽  
2008 ◽  
Vol 113 (9) ◽  
pp. 2504-2511 ◽  
Author(s):  
Gail J. Roboz ◽  
Ellen K. Ritchie ◽  
Tania Curcio ◽  
Juliette Provenzano ◽  
Rebecca Carlin ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Promyelocytic Leukemia ◽  
Low Dose Cytarabine ◽  
Acute Myeloid

scholarly journals Clinical Characteristics and Treatment Allocations in Patients with Myelodysplastic Syndromes and Monosomy 7: Results from an International Multicenter Study Suggest That Hypomethylating Agents Significantly Improve Overall- and AML-Free Survival in Patients Classified As Very High Risk By IPSS-R

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4656-4656 ◽  
Author(s):  
Julie Schanz ◽  
Friederike Braulke ◽  
Ghulam J. Mufti ◽  
Elena Crisà ◽  
Austin Kulasekararaj ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Research Funding ◽  
Risk Group ◽  
Best Supportive Care ◽  
High Risk Group ◽  
Study Cohort ◽  
Monosomy 7 ◽  
Free Survival ◽  
Very High

Abstract Introduction: Total (-7) or partial (7q-) monosomy 7 is the second frequent abnormality in MDS, occurring in around 12% of MDS/AML and up to 40% of therapy-associated MDS/AML. The present study was designed to analyze clinical features, prognosis and response to different therapeutic strategies in patients with -7 or del(7q) in a multicentric, retrospective cohort study. Patients and Methods: 471 patients with MDS/AML following MDS and monosomy 7 were registered and retrospectively analyzed. The median observation time was 3.6 years. Inclusion criteria were defined as follows: Morphologic diagnosis of MDS/AML following MDS, bone marrow blast count <=30% and presence of -7 or 7q- proved by chromosome banding analysis (CBA) or fluorescence in situ-hybridization (FISH). The data was coalesced from 8 centers in London (n=140; 29.7%), Duesseldorf, (n=120; 25.5%%), Goettingen (n=118; 25.1%), Cologne (n=38; 8.1%), Freiburg (n=29; 6.2%), Munich (n=13; 2.8%), Dresden (n=10; 2.1%) and Mannheim (n=3; 0.6%). The median age in the study cohort was 66 years, 63% of patients were males. MDS/AML was therapy-associated in 53 (11%). According to IPSS-R, 9 (1.9%) were assigned to the low risk group, 39 (8.3%) to the intermediate group, 81 (17.2%) to the high-risk group and 133 (28.2%) to the very high risk group. The treatment was classified as follows: Best supportive care (BSC), low-dose Chemotherapy (LDC), high-dose chemotherapy (HDC), hypomethylating agents (HMA; either 5-azacytidine or decitabine), and others (e.g. valproic acid, steroids, lenalidomide or thalidomide). Survival analyses were performed regarding overall- (OS) as well as AML-free survival (AFS) using the Kaplan-Meier method. Results: 147 patients (31.2%) showed 7q-, 313 (66.5%) -7 and 11 (2.3) patients showed both abnormalities at the first cytogenetic examination. The abnormality was detected by CBA±FISH in 440 (93.4%) and by FISH only in 31 (6.6%). In the latter cases, the CBA was either unsuccessful or showed a normal karyotype. In 182 (38.6%) patients, -7/del7q was detected as a single abnormality, 77 (16.3%) showed two abnormalities and 184 (39.1%) showed a complex karyotype involving -7/7q-. As previously described (Schanz et al., 2012), untreated patients with an isolated 7q- as compared to an isolated -7 show a better prognosis regarding OS (median: 4.0 vs. 0.7 years; p<0.01) as well as AFS (median not reached vs. 2.3 years; p=0.062). Median hemoglobin level in the study cohort was 9.3 g/dl, ANC 0.98*103/μl, platelet count 73*103/μl and the median number of bone marrow blasts was 8%. Regarding the treatment, a best supportive care regimen was chosen in 195 (41%) patients. The remaining 276 (58.6) patients received 1-5 sequential therapies (one therapy: 31.6%; more than 1 therapy: 27.0%). 81 patients received an allogeneic bone marrow transplantation (ATX). Within the group of patients treated with HMA at any time of their disease (n=167), 147 (31.2%) received 5-Azacytidine, 8 (1.7%) Decitabine and 12 (2.5%) patients were treated with both drugs. As the first line therapy, 122 patients (25.9%) received HMA, 50 (10.6%) HDC, 28 (5.9%) ATX, 28 (5.9%) 11 (2.3%) LDC, and 28 (5.9%) were treated with other therapies. Patients eligible for ATX showed a significantly better prognosis as compared to any other therapy strategy: The median OS in was 2.1 years as compared to 1.1 years in non-transplanted patients (p<0.01). In patients not eligible for ATX, treatment with HMA at any course of their disease as compared to a BSC strategy was associated with a better OS (1.4 vs. 0.8 years, p=0.014). By comparing HMA to any other therapy, the OS did not differ significantly (1.4 years in HMA vs. 1.1 years in any other, p n.s.). In patients classified as very high risk according to IPSS-R, the median OS was significantly prolonged in patients receiving HMA as compared to BSC (1.1 vs. 0.6 years, p<0.01). This was also observed for the risk of AML-transformation in this subgroup of patients: The median time to AML was 1.8 years in HMA-treated patients versus 0.6 years in BSC (p=0.012). Conclusions: To our knowledge, the study describes the largest patient cohort with MDS/AML and monosomy 7 published to date. Further data regarding the clinical characteristics of this subgroup of patients and the treatment regimes applied will be presented in detail. The study was supported by research funding from Celgene Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Schanz: Celgene: Honoraria, Research Funding, Travel grants: Celgene, Novartis, Lilly Other. Götze:Celgene Corp, Novartis Pharma: Honoraria. Nolte:Celgene, Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Travel grants Other.

scholarly journals Decitabine Improves Response Rate and Prolongs Progression Free Survival in Older Patients with Newly Diagnosed Acute Myeloid Leukemia with Monosomal Karyotype: A Subgroup Analysis of the Daco-16 Trial

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1336-1336 ◽  
Author(s):  
Agnieszka Wierzbowska ◽  
Ewa Wawrzyniak ◽  
Agnieszka Pluta ◽  
Tadeusz Robak ◽  
Grzegorz J. Mazur ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Low Dose ◽  
Response Rate ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Poor Risk ◽  
Elderly Aml ◽  
Low Dose Cytarabine

Abstract Background: Cytogenetics is one of the most important prognostic factors in acute myeloid leukemia (AML). Monosomal karyotype (MK), defined as two or more distinct autosomal monosomies or one single autosomal monosomy in the presence of at least one structural abnormality, has been identified as a new cytogenetic category associated with particularly poor prognosis (Breems, JCO, 2008). AML patients (pts) with MK+ have shorter overall survival (OS) compared to other unfavorable karyotypes, irrespective of treatment intensity. However, preliminary results from a phase II trial of decitabine (DEC) as first-line treatment for elderly AML pts demonstrated that an objective response rate (CR+PR) in MK+ pts was higher than in the MK- cases with abnormal cytogenetics. Moreover, the OS of MK+ pts was comparable to that of MK- pts (Lübbert, Haematologica, 2012). This observation might suggest a positive effect of DEC in patients with MK+ AML. Objective: To determine the effects of treatment with DEC vs low-dose cytarabine or best supportive care (BSC) as a treatment of choice (TC) on OS, progression free survival (PFS) and response rate (CR/CRp) in the subset of pts with AML MK+, who were treated in the randomized phase III DACO-16 study. A second objective is to compare the OS, PFS and CR/CRp of MK+ vs other unfavorable karyotype cases. Methods: Eligible pts were ≥65 years old with newly diagnosed, de novo or secondary AML with ≥20% bone marrow blasts, ECOG performance status 0-2, WBC count ≤40x109/L. According to study protocol pts were randomly assigned 1:1 to receive DEC 20 mg/m2 per day as a 1-hour i.v. infusion for five days every 4 weeks or TC (BSC or cytarabine 20 mg/m2 s.c. for 10 days every 4 weeks). This analysis included pts identified from the clinical database whose locally obtained cytogenetics data indicated they had MK+. Pts with poor-risk cytogenetics (Southwest Oncology Group classification) but MK- (poor-risk MK-) were used as the comparison group. Median OS (Kaplan-Meier method) and PFS were compared between decitabine vs TC treatment arms for pts MK+ and poor-risk MK-. Remission was assessed using modified IWG AML criteria (Cheson, Blood, 2003). Results: Of 480 pts in DACO-16 study, 64 (13.3%) fulfilled the criteria for MK+ and additional 99 (20.6%) had poor-risk MK- cytogenetics. In MK+ group 33 pts received DEC and 31 pts were assigned to TC. In poor-risk MK- group DEC and TC was administered to 49 and 50 pts respectively. Baseline characteristics of treatment subgroups were comparable. Outcome of MK+ and poor-risk MK- pts according to treatment arm The CR/CRp rate in MK+ pts was higher in the DEC arm compared to TC (21% vs 3%; OR=8.1; 95% CI, 0.93 to 70.04; P = 0.054). The median PFS was also improved in the DEC arm vs TC (2.6 vs 1.3 mos, HR=0.53; 95% CI, 0.31 to 0.9; P = 0.018) Fig.1. There was a trend towards longer OS by ~4 mos in the DEC arm vs TC (2.6 vs 6.3 mos; HR=0.67; 95% CI, 0.39 to 1.15; p=0.14) Fig.2. In contrast, no difference in CR/CRp rate between DEC vs TC was observed in poor-risk MK- pts (respectively 8% vs 10%; OR=0.8; 95% CI, 0.2 to 3.17; P = 1.0). Similarly, no improvement in PFS as well as OS was observed in poor-risk MK- cases treated with DEC compared to TC. Overall survival in decitabine and TC treatment arms according to cytogenetics In AML patients receiving low-dose cytarabine or BSC, patients with MK+ appeared to have a poorer outcome than pts with poor-risk MK-. The median OS was 2.6 vs 4.7 mos (HR=1.52; 95% CI, 0.91 to 2.54; p=0.11) in MK+ and poor-risk MK- pts, respectively. In contrast, in the DEC arm MK+ pts did not do worse than MK- cases with poor-risk cytogenetics. The median OS was similar: 6.3 vs 5.0 mos for MK+ and poor-risk MK- (HR=0.98; 95% CI, 0.6 to 1.58; p=0.92), respectively. Conclusions: In older patients with AML-MK+, decitabine improved CR/CRp rate and PFS compared with standard therapies. A survival analysis suggesting a benefit of about 4 months in median OS for decitabine in MK+ AML needs confirmation in further studies with larger sample size. These data might suggest decitabine overcomes the extremely poor prognosis associated with MK and may be a beneficial initial treatment as an alternative to low-dose cytarabine or best supportive care. Figure 1. PFS of patients with AML MK+ according to treatment Figure 1. PFS of patients with AML MK+ according to treatment Figure 2. OS of patients with AML MK+ according to treatment Figure 2. OS of patients with AML MK+ according to treatment Disclosures Wierzbowska: Janssen, Celgene: Consultancy. Off Label Use: Decitabine in elderly AML patients. Robak:Eisai Inc: Research Funding. Oriol:Celgene, Janssen, Amgen: Consultancy, Speakers Bureau.

scholarly journals Role of low dose cytarabine in elderly patients with acute myeloid leukemia: An experience

2015 ◽  
Vol 04 (01) ◽  
pp. 004-006 ◽  
Author(s):  
Yasir Bashir ◽  
Sajjad Geelani ◽  
Nusrat Bashir ◽  
Shabeer A. Mir ◽  
Mosin Mushtaq ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Standard Treatment ◽  
Treatment Options ◽  
Effective Treatment Option ◽  
Patient Consent ◽  
Low Dose Cytarabine ◽  
Acute Myeloid

Abstract Purpose: To highlight the acceptable results seen after use of low dose cytarabine in elderly patients of acute myeloid leukemia (AML) with comorbidities. Materials and Methods: This was a prospective study carried on 30 newly diagnosed patients of AML over 60 years of age who were unfit for standard treatment regimens. We did not use azacytidine and decitabine in our patients because these therapeutic modalities being extremely costly and our patient affordability being poor. After taking patient consent and institutional ethical clearance these patients were treated with 20 mg/m2 cytarabine subcutaneously in two divided doses 12 h apart for 4 days every week for 4 weeks which constituted a cycle before disease, re-assessment was done. A repeat cycle was administered where ever needed and after attainment of remission, we continued low dose cytarabine for 2 days/week as maintenance after complete or partial response was documented. Results: In our study, we found that around 20% of patients achieved complete remission and 30% partial remission. The remission rates were definitely influenced by counts at presentation, performance at presentation, comorbidities, underlying myelodysplastic syndrome and baseline cytogenetics. Conclusion: Low dose cytarabine is effective treatment option for elderly patients with AML when standard treatment options are not warranted.

scholarly journals MicroRNA-204 Potentiates the Sensitivity of Acute Myeloid Leukemia Cells to Arsenic Trioxide

2019 ◽  
Vol 27 (9) ◽  
pp. 1035-1042 ◽  
Author(s):  
Zhiguo Wang ◽  
Zehui Fang ◽  
Runzhang Lu ◽  
Hongli Zhao ◽  
Tiejun Gong ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Arsenic Trioxide ◽  
Myeloid Leukemia ◽  
Luciferase Activity ◽  
Cell Growth Inhibition ◽  
Apoptosis Protein ◽  
Acute Myeloid Leukemia Cells ◽  
Leukemia Treatment ◽  
Novel Target ◽  
Acute Myeloid

Although arsenic trioxide (ATO) is a well-known antileukemic drug used for acute promyelocytic leukemia treatment, the development of ATO resistance is still a big challenge. We previously reported that microRNA-204 (miR-204) was involved in the regulation of acute myeloid leukemia (AML) cell apoptosis, but its role in chemoresistance is poorly understood. In the present study, we showed that miR-204 was significantly increased in AML cells after ATO treatment. Interestingly, the increased miR-204 level that was negatively correlated with ATO induced the decrease in cell viability and baculoviral inhibition of apoptosis protein repeat-containing 6 (BIRC6) expression. Overexpression of miR-204 potentiated ATO-induced AML cell growth inhibition and apoptosis. Furthermore, miR-204 directly targets to the 3′-UTR of BIRC6. Upregulation of miR-204 decreased BIRC6 luciferase activity and expression, which subsequently enhanced the expression of p53. Restoration of BIRC6 markedly reversed the effect of miR-204 on the regulation of AML cell sensitivity to ATO. Taken together, our study demonstrates that miR-204 decreases ATO chemoresistance in AML cells at least partially via promoting BIRC6/p53-mediated apoptosis. miR-204 represents a novel target of ATO, and upregulation of miR-204 may be a useful strategy to improve the efficacy of ATO in AML treatment.

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