Double intensive consolidation chemotherapy in adult acute myeloid leukemia.

1991 ◽  
Vol 9 (8) ◽  
pp. 1432-1437 ◽  
Author(s):  
J L Harousseau ◽  
N Milpied ◽  
J Briere ◽  
B Desablens ◽  
P Y Leprise ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Cox Model ◽  
Univariate Analysis ◽  
Induction Treatment ◽  
High Dose ◽  
Consolidation Chemotherapy ◽  
Significant Difference ◽  
Wbc Count ◽  
Acute Myeloid

Of 115 adult patients with de novo acute myeloid leukemia (AML), 87 (75.5%) achieved complete remission (CR) after induction treatment with zorubicin and conventional doses of cytarabine (Ara-C). Patients under age 45 years with histocompatibility locus antigen-identical sibling underwent bone marrow transplantation (BMT). The others were treated with two courses of intensive consolidation chemotherapy (ICC): course 1 with 4 days of high-dose Ara-C and 3 days of amsacrine (m-AMSA); course 2 with carmustine (BCNU), Ara-C, cyclophosphamide, and etoposide. Forty-two patients received both planned courses, 15 received only the first, and 13 patients could only support conventional maintenance therapy. Four patients died during consolidation. With a median follow-up of 60 months, the disease-free survival (DFS) after ICC at 5 years is 40.3% (+/- 6.5%), with no statistically significant difference between patients receiving one or two courses. The DFS for the 17 transplanted patients is comparable (P = .72) and is lower for the 13 excluded patients (23% +/- 11.5%, P = .046). Age did not influence the probability of remaining in CR. In univariate analysis, three parameters had a negative impact on the 5-year DFS: a high initial WBC count (52% for patients with less than 30 x 10(9) WBC/L v 12% for patients with greater than 30 x 10(9) WBC/L, P = .01), a long delay between induction treatment and course 1 (+/- 60 days; 63% v 29%, P = .01), and a long delay between course 1 and course 2 (+/- 60 days, 61.5% v 28.5%, P = .05). In multivariate analysis (Cox model), only the WBC count remained significant. This study confirms the value of intensive postremission chemotherapy, which can be compared in AML with allogeneic or autologous BMT. It also demonstrates the prognostic value of the initial WBC count. The optimal modalities of ICC remain to be defined by further studies.

scholarly journals A randomized study of high-dose cytarabine in induction in acute myeloid leukemia [see comments]

Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 1710-1717 ◽  
Author(s):  
JF Bishop ◽  
JP Matthews ◽  
GA Young ◽  
J Szer ◽  
A Gillett ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Dose Effect ◽  
Induction Treatment ◽  
High Dose ◽  
Remission Duration ◽  
High Dose Cytarabine ◽  
Acute Myeloid

Abstract High-dose cytarabine (ara-c) may overcome cytarabine resistance in leukemic blasts. It has been used as a successful salvage and in postremission therapy but not as initial induction treatment. Patients aged 15 to 60 years, presenting with newly diagnosed acute myeloid leukemia (AML) were randomized to receive either high-dose cytarabine, 3 g/m2 12 hourly on days 1, 3, 5, and 7 for 8 doses, daunorubicin 50 mg/m2 days 1 to 3, etoposide 75 mg/m2 days 1 to 7, (HIDAC-3–7) or standard dose cytarabine 100 mg/m2 continuous intravenous infusion for 7 days with daunorubicin and etoposide at the same dose and schedule as above (7–3–7). Patients could receive a second or third induction course if complete remission (CR) was not achieved. All patients received the same postinduction consolidation therapy (5–2–5) for 2 courses. Eligible patients had no prior chemotherapy or myelodysplastic disease. Patients have been followed for a median of 4.5 years. Of 301 patients treated, complete response (CR) was achieved in 71% with HIDAC- 3–7 and 74% with 7–3–7. For patients in CR, the estimated median remission duration was 45 months with HIDAC-3–7 and 12 months with 7–3– 7 (P = .0005 univariate analysis, P = .0004 multivariate analysis). The estimated percentage of patients relapse free 5 years after achieving a CR was 49% on HIDAC-3–7 and 24% on 7–3–7. Patients in CR tended to survive longer with HIDAC-3–7 but there were no overall survival differences between the two arms. HIDAC-3–7 was associated with significantly more toxicity in induction with more leukopenia, thrombocytopenia, nausea, and vomiting and eye toxicity (all P < .001) but a similar incidence of severe central nervous system and cerebellar toxicity compared to 7–3–7. The consolidation treatment was the same in both arms but caused significantly more leukopenia and thrombocytopenia in patients previously treated with HIDAC-3–7 induction (P < .0001). We conclude that a dose-effect exists for cytarabine in AML and that HIDAC- 3–7 prolongs remission duration and disease-free survival and is tolerable when used as initial induction therapy in patients with de novo AML.

Combination of Cytarabine and Topotecan Improves Response Rate for Patients Treated for Acute Myeloid Leukemia with Persistent Disease After Frontline Induction

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2605-2605
Author(s):  
Thomas Prebet ◽  
Estelle Jean ◽  
Aurelie Autret ◽  
Aude Charbonnier ◽  
Jerome Rey ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Negative Impact ◽  
Univariate Analysis ◽  
High Dose ◽  
Significant Activity ◽  
Induction Regimen ◽  
Wbc Count ◽  
Acute Myeloid

Abstract Abstract 2605 Background: Achievement of first complete response (CR) is the objective of frontline treatment for patients treated for acute myeloid leukemia (AML). After a first course of induction chemotherapy, 30 to 40% of the patients do not achieve CR. The association of anthracyclins and intermediate dose cytarabine (IDAC) allow 50 to 60% of patients with persistent AML to achieve CR when given as early as day 14 (Lioure ASH 2006). Previous studies have shown that topotecan had a significant activity in AML patients and could be safely combined with IDAC (Kantarjian cancer 2006). We hypothesize that switching from anthracyclins to another class of topo-isomerase inhibitor for patients with persistent AML at day 14 of induction may be useful to improve tolerance and efficacy of the salvage regimen. Design: This is a retrospective single center study. Patients had (1) a diagnosis of de novo or therapy related AML excluding APL, (2) received an initial 3+7 induction regimen with 60mg/m2/d of daunorubicin, (3) had a bone marrow aspirate at day 14 with ≥5% marrow blast. We evaluated the combination of IDAC (1000mg/m2/12h day14-17) and topotecan (TA, 1.25mg/m2/d CIV day 14–17) in 31 consecutive AML and compared its results in terms of CR rate and survival with a series of 54 patients treated with IDAC (1000mg/m2/12h day14-17) + anthracyclins (AA group, daunorubicin 35 mg/m2/d day 14–15 or idarubicin 8 mg/m2/d day 14–15). Results: Pretreatment patient's characteristics were comparable between TA and AA groups including median age (48y vs 45y, p=0.34), cytogenetic risk stratification (with low/intermediate/high risk in 3/65/32% vs 2/52/46% of patients,p=0.44), median WBC count at diagnosis (11G/l vs 7 G/l), and median day 14 bone marrow blast count (21% vs 35%, p=0.23). Median follow-up was 51 months. Induction death rate (6%), neutropenia duration (38 days), thrombocytopenia duration (37 days), and frequency of microbiologically documented infections (47%) were comparable between the 2 groups. In univariate analysis, TA regimen was associated with a better CR rate (81% vs 59%, p=0.04), a better probability of overall survival (2-years estimate 66% vs 33%, p=0.03) and a better cumulative incidence of relapse (2-years estimate 38% vs 67%, p=0.002) as compared with AA. Our analysis also showed that high WBC count (more than 30G/L) and presence of adverse cytogenetics were associated with a lower frequency of CR. Adverse cytogenetics had also a negative impact on CIR and OS. The potential benefit of TA regimen was confirmed in the multivariate model for CR (HR=3.3, 95%CI [1.02–10.6], p=0.04), OS (HR=0.5, 95%CI [0.28–0.91], p=0.02), and CIR (HR=0.26, 95%CI [0.11–0.6], p=0.001). Patients in the TA group were more frequently allo-transplanted in CR1 as compared with AA (9/32 in AA group vs 17/25 in TA group, p=0.002) but survival results were confirmed if we censored patients at the time of allogeneic transplantation for CIR (p=0.002) whereas only a trend was shown for OS (p=0.057). Conclusion: This work shows that the substitution of anthracyclins by topotecan in combination with IDAC for second induction is safe and is associated with a better efficacy for AML patients with persistent leukemia after induction. The use of topotecan may be especially interesting in the context of high dose anthracyclins induction regimen in order to introduce an alternative drug in diseases selected with high resistance to chemotherapy and to limit the cumulative dose of anthracyclins administered. Disclosures: Off Label Use: RAD001.

scholarly journals A randomized study of high-dose cytarabine in induction in acute myeloid leukemia [see comments]

Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 1710-1717 ◽  
Author(s):  
JF Bishop ◽  
JP Matthews ◽  
GA Young ◽  
J Szer ◽  
A Gillett ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Dose Effect ◽  
Induction Treatment ◽  
High Dose ◽  
Remission Duration ◽  
High Dose Cytarabine ◽  
Acute Myeloid

High-dose cytarabine (ara-c) may overcome cytarabine resistance in leukemic blasts. It has been used as a successful salvage and in postremission therapy but not as initial induction treatment. Patients aged 15 to 60 years, presenting with newly diagnosed acute myeloid leukemia (AML) were randomized to receive either high-dose cytarabine, 3 g/m2 12 hourly on days 1, 3, 5, and 7 for 8 doses, daunorubicin 50 mg/m2 days 1 to 3, etoposide 75 mg/m2 days 1 to 7, (HIDAC-3–7) or standard dose cytarabine 100 mg/m2 continuous intravenous infusion for 7 days with daunorubicin and etoposide at the same dose and schedule as above (7–3–7). Patients could receive a second or third induction course if complete remission (CR) was not achieved. All patients received the same postinduction consolidation therapy (5–2–5) for 2 courses. Eligible patients had no prior chemotherapy or myelodysplastic disease. Patients have been followed for a median of 4.5 years. Of 301 patients treated, complete response (CR) was achieved in 71% with HIDAC- 3–7 and 74% with 7–3–7. For patients in CR, the estimated median remission duration was 45 months with HIDAC-3–7 and 12 months with 7–3– 7 (P = .0005 univariate analysis, P = .0004 multivariate analysis). The estimated percentage of patients relapse free 5 years after achieving a CR was 49% on HIDAC-3–7 and 24% on 7–3–7. Patients in CR tended to survive longer with HIDAC-3–7 but there were no overall survival differences between the two arms. HIDAC-3–7 was associated with significantly more toxicity in induction with more leukopenia, thrombocytopenia, nausea, and vomiting and eye toxicity (all P < .001) but a similar incidence of severe central nervous system and cerebellar toxicity compared to 7–3–7. The consolidation treatment was the same in both arms but caused significantly more leukopenia and thrombocytopenia in patients previously treated with HIDAC-3–7 induction (P < .0001). We conclude that a dose-effect exists for cytarabine in AML and that HIDAC- 3–7 prolongs remission duration and disease-free survival and is tolerable when used as initial induction therapy in patients with de novo AML.

The Use of Purine Analogues Does Not Aggravate Infectious Complications During Induction and Consolidation Therapy of Acute Myeloid Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1011-1011
Author(s):  
Marek Seweryn ◽  
Jerzy Wojnar ◽  
Dariusz Kata ◽  
Slawomira Kyrcz-Krzemien
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Infectious Complications ◽  
Induction Treatment ◽  
High Dose ◽  
Consolidation Therapy ◽  
Purine Analogues ◽  
Acute Myeloid

Abstract Abstract 1011 Poster Board I-33 Background: Addition of purine analogues to standard induction therapy of acute myeloid leukemia (AML) had previously been demonstrated to increase complete remission rate. The aim of this study was to analyze whether the use of cladribine or fludarabine during induction and consolidation increases the risk of infectious complications. Material and methods: 118 AML patients, included in two consecutive randomized trials between 1999-2006 in a single centre were analyzed. Induction therapy consisted of daunorubicin + cytarabine (DA-7, n=53) alone or in combination with cladribine or fludarabine (DAC-7 + DAF-7, n=65 ). Consolidation included one course of high-dose AraC + mitoxantrone and one course of high-dose AraC +/- purine analogues. A median age was 45(17-58) years and 48(20-60) years for patients treated with and without purine analogues, respectively. Results: The frequency of neutropenic fever as well as microbiologically documented bacterial, fungal and viral infections during induction and consolidation did not differ between two compared groups - receiving or not purine analogues. Time to infection occurrence and infection duration were similar in both study groups. During induction and both consolidation treatments significant lower values of lymphocytosis were observed in the group of patients treated with purine analogues. There was a slight tendency to increased rate of mucositis for patients treated with purine analogues (60% vs. 44.3%, p=0.07) during induction treatment, while infections affecting skin and soft tissues were significant frequent for patients treated without purine analogues (43.3% vs. 18%, p=0.03) during second consolidation treatment (high dose AraC). The usage of intravenous anti-infectious medications (antibiotics, antifungal, antiviral) and periods of hospitalization did not differ between two groups in this study. Conclusions: We conclude that the use of purine analogues, either cladribine or fludarabine along with conventional induction and consolidation therapy does not aggreviate infectious complications in adults with AML. Disclosures: No relevant conflicts of interest to declare.

Expression of CD56 Is an Independent Prognostic Factor to Predict Relapse in Acute Myeloid Leukemia with t(8;21): Results of Japan Adult Leukemia Study Group (JALSG) AML97 Protocol.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2511-2511
Author(s):  
Noriyoshi Iriyama ◽  
Yoshihiro Hatta ◽  
Jin Takeuchi ◽  
Yoshiaki Ogawa ◽  
Shigeki Ohtake ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Performance Status ◽  
Univariate Analysis ◽  
Rank Test ◽  
Hematopoietic Stem ◽  
Wbc Count ◽  
Adverse Factor ◽  
Acute Myeloid

Abstract Abstract 2511 Background: Although prognosis of acute myeloid leukemia (AML) with t(8;21) is better than other types of AML, outcome of the patients has not been satisfied. Previously, aberrant antigen expression has been reported as risk factor for AML with t(8;21). However, in the reported series, number of cases was not large enough and chemotherapy regimens were variable. We investigated the association of prognosis and several biomarkers including immunophenotype, WBC count, age, and performance status for large number of AML patients with t(8;21) uniformly treated in JALSG AML97 regimen. Patients and Methods: Seven hundred eighty-nine eligible AML patients were evaluated for the multicenter JALSG AML97 study. Adult patients with de novo AML except for APL, ages 15–64 years, were registered consecutively from 103 institutions that participated in JALSG from December 1997 to July 2001. One hundred forty-four patients with AML with t(8;21) were analyzed in this study with a median 1205 days of observation term from diagnosis. Complete remission (CR), relapse-free survival (RFS), and overall survival (OS) rates were analyzed by Fisher's exact test and log-rank test. Factors that would affect clinical outcome were analyzed by multivariate Cox proportional hazard regression model. Results: AML with t(8;21) frequently expressed CD19, CD34, and CD56 compared to other subtypes of AML. CD11b was rarely expressed. Expression of CD19 favorably affected on CR rate (96% in CD19 positive and 87% in negative patients, p<0.05). Univariate analysis showed WBC>20×109/L, CD19 negativity, and CD56 positivity were adverse factors for RFS. CD56 expression was the only independent adverse factor for RFS by multivariate analysis (73.7% in CD56 negative and 48.2% in CD56 positive patients at 3 yrs) although its expression did not affect on OS. There was no difference of age, sex, WBC count, presence or absence of Auer rod, performance status, or CD15 expression between CD56 positive and negative cases. Expression of CD19 was more common in CD56 negative patients (50% in CD56 negative and 30.6% in CD56 positive patients, p<0.05). Conclusions: We demonstrated that the expression of CD56 was a distinctive adverse factor in a large number of AML patients with t(8;21) treated with JALSG AML97 regimen. CD56 positive AML patients with t(8;21) are possible candidates for hematopoietic stem cell transplantation. Disclosures: No relevant conflicts of interest to declare.

Favourable Outcome in Infants with Acute Myeloid Leukemia Treated with the AIEOP AML 2002/01 Protocol

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3585-3585
Author(s):  
Riccardo Masetti ◽  
Martina Pigazzi ◽  
Andrea Pession ◽  
Carmelo Rizzari ◽  
Nicola Santoro ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Age Groups ◽  
The Other ◽  
Published Data ◽  
High Dose ◽  
Cns Involvement ◽  
Wbc Count ◽  
Standard Risk ◽  
Acute Myeloid

Abstract Abstract 3585 Introduction: The prognosis of paediatric patients (pts) with Acute Myeloid Leukemia (AML) has significantly improved over time not only in standard risk (SR) but also in high risk (HR) children. Pts < 1 year of age (infants) affected by AML are generally considered to be at HR. This is due to the prevalence of prognostically unfavourable clinical and cytogenetic/molecular features and to a greater vulnerability to treatment toxicities. We analyzed clinical and biological characteristics, as well as outcome of infants treated with the AIEOP AML 2002/01 protocol, comparing them to those of older children. Patients and Methods: Between 12/2002 and 06/2011, 63 infants with AML other than promyelocytic leukaemia were treated with the AIEOP AML 2002/01 protocol. Children with Down syndrome were excluded. Clinical and biological features compared to the ones of 3 different age groups (1–<2 years; 2–10 years; >10 years) are reported in Table 1. Treatment was administered according to the following risk-based stratification: pts with isolated CBF-b+ leukemia achieving complete remission (CR) after the first induction course were considered to be at Standard Risk (SR), whereas all the others were assigned to the HR group. The treatment schedule administered to infants was: 2 courses of 7-day induction therapy (idarubicin, cytarabine and etoposide: ICE 3+5+7) and 2 consolidation courses based on high-dose cytarabine (HD-Ara-c), combined with either etoposide during the first course (AVE 3+4) or mitoxantrone during the second course (HAM 3+2). After consolidation, infants were eligible to allogeneic (ALLO) HSCT in first CR from a HLA-identical relative, if available, or from alternative donors, namely unrelated donors or HLA-mismatched relatives. CR rate, early death (ED), induction failure (IF), overall survival (OS) and event free survival (EFS) of infants were calculated and compared to those of other age groups. Results: Compared to pts of other age groups, infants had significantly more CNS involvement at diagnosis (P=0.002), were assigned to the FAB M7 subtype (P=0.000) and to the HR risk group (P=0.001) (Table 1). The median white blood cell (WBC) count at diagnosis was higher in infants (P=0.028), being 71,298×103/ml (range 3,100–653,000). Comparing pts with available cytogenetic data in the different age groups, infants showed a significantly higher incidence of 11q23/MLL-rearrangements (P=0.001). The incidence by partners of 11q23/MLL-rearrangements were 10%, 7%, 1%, 4% and 14% for t(9;11), t(10;11), t(11;19), t(1;11) and other translocation partners, respectively. Infants had CR, ED and IF rates of 84%, 8% and 8%, respectively, with no statistically significant differences with other age groups. Forty-five out of 63 infants (71%) received an ALLO HSCT in first CR. With a median follow up time of 57 months (range 3–130) the 8-year probability of OS and EFS of infants were 74% and 58%, respectively, with no significant differences compared with the other age groups. Conclusions: Infants < 1 year of age at diagnosis enrolled in the AIEOP AML 2002/01 protocol presented with a significantly higher incidence of prognostically unfavourable features, like high WBC count, FAB M7 subtype, 11q23/MLL-rearrangements and CNS involvement. Despite this, a treatment strategy including a wide use of ALLO HSCT in first CR for these pts resulted in a final outcome which was not statistically different from that observed in the other age groups. Our results compare favourably with previously published data on infants with AML. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Retrospective Comparison between MEC and FLAG-Ida Regimens for Refractory or Relapsed Acute Myeloid Leukemia in Adults

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1354-1354
Author(s):  
Wellington F Silva ◽  
Lidiane Inês Da Rosa ◽  
Fernanda S Seguro ◽  
Douglas R. A. Silveira ◽  
Luciana Nardinelli ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
High Dose ◽  
Npm1 Mutation ◽  
Baseline Characteristics ◽  
One Year ◽  
Relapsed Acute Myeloid Leukemia ◽  
Acute Myeloid

Introduction: There is no consensus regarding the best salvage regimen for refractory or relapsed acute myeloid leukemia (r/rAML), with classic regimens traditionally based on high-dose cytarabine in a changeable combination with anthracyclines, purine analogs, and etoposide. Outcomes of r/rAML patients in developing countries are underreported, even though the same regimens are widely used. Methods: This is a retrospective single-center study, conducted in an academic center in Brazil. Local research ethics committee approved this analysis. All patients above 16 years of age who received MEC (mitoxantrone, etoposide and cytarabine) or FLAG-IDA (fludarabine, cytarabine, filgrastim and idarubicin) as originally reported (Amadori, S. et al. and Steinmetz, H. T. et al.) for r/rAML between December/2009 and January/2019 were included. Only patients with refractory or relapsed disease following standard upfront therapy ("7+3" regimen) were included in this analysis, being divided among refractory (less than partial response after one cycle of "7+3"), early relapsed (relapse within one year from first complete response [CR]) and late relapsed (relapse after one year of CR). Only the first salvage was considered for this study. Results: Sixty patients were included in the final analysis, with a median age of 45 years (range, 17 - 69). There were no cases of therapy-related AML. Four AML cases (7%) were secondary to myeloproliferative neoplasm (MPN) or myelodysplastic syndrome (MDS). All FLT3-ITD positive cases had an associated NPM1 mutation. Two patients had chronic human immunodeficiency virus infection and received antiretroviral therapy. Baseline characteristics of the whole cohort are summarized in Table 1. Three patients had undergone SCT in first CR and were post-SCT relapses. Twenty-eight patients received MEC and 32 received FLAG-IDA. By comparing the baseline characteristics of both groups, no difference statistically significant was found except for the indication for salvage treatment, in which there were more refractory cases in FLAG-IDA group (56 vs. 28%, p=0.029) (Table 2). Overall, 17/60 achieved CR and 12/60 CRi, with a total CR rate (CR+CRi) of 48.3% (95% confidence interval [CI], 35.4 - 61.5). Sixteen patients (27%) early died before a response assessment. By univariate analysis, only age affected the CR rate (p=0.045). No difference in CR rate was found between the two protocols (MEC 53.5 vs. FLAG-IDA 43.7%, p=0.447). Looking into this data, it can be seen that there were more refractory patients in FLAG-IDA arm (37.5 vs. 4%, p=0.02) but more patients early-died in MEC arm (35.7 vs. 18.7%, p=0.137), even though the latter was not statistically significant. After correcting the initial differences between the two groups regarding indication for salvage through a propensity score calculation, a post-matching cohort with 44 subjects was found. In this cohort, no difference in refractoriness rate could be detected (p=0.077). In the whole cohort, 17 patients proceeded to allogeneic SCT - 15 in CR/CRi and 2 with active disease, with no difference in SCT execution rate between the two groups (p=0.470). 4/17 transplanted patients were alive. Median follow-up was 48 months. Median survival for total cohort was 4 months (95% CI, 2.7 - 9.2), with a 3-year OS of 9.7% (95% CI, 4 - 23.7) and a 3-year EFS of 7.5% (95% CI, 2.5 - 22.4). In the univariate analysis for OS, age (p=0.04), FLT3 status (p&lt;0.001) and SCT procedure (p=0.002) were statistically significant. Chosen regimen did not influence OS or EFS as well as the genetic risk, colonization or time of relapse (Figure 1). In a multivariable model for EFS including age, FLT3 status and SCT procedure, only the last two indicators remained significant: FLT3-ITD mutation (Hazard ratio [HR] = 4.6 [95% CI 1.9 - 11.4], p&lt;0.001) and SCT procedure (HR = 0.43 [95% CI 0.22 - 0.82], p=0.01). Conclusion: In this analysis, there was no difference concerning the chosen regimen for r/rAML, even though a possible higher refractoriness rate could be seen in FLAG-IDA arm. High early toxicity was found, emphasizing the role of supportive care and judicious selection of patients to intensive salvage therapy in our setting. FLT3-ITD mutation and SCT remained as significant factors for survival in a multivariable analysis, which is in line with previous studies. Disclosures No relevant conflicts of interest to declare.

Bmi-1 Expression Is Useful To Design Therapy and To Predict Prognosis in Patients with Acute Myeloid Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3296-3296
Author(s):  
Moniruddin Chowdhury ◽  
Keichiro Mihara ◽  
Nanae Nakaju ◽  
Sachiko Fukumoto-Hidani ◽  
Yoshihiro Takihara ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Standard Dose ◽  
Intensive Therapy ◽  
Univariate Analysis ◽  
Granulocytic Sarcoma ◽  
High Dose ◽  
Binary Logistic Regression Model ◽  
Acute Myeloid

Abstract Since prognosis of patients with acute myeloid leukemia (AML) is highly variable even in a single subpopulation in FAB classification, it would be useful to find prognostic molecular markers for AML. Thus, we investigated Bmi-1 expression in AML cells by flow cytometry and analyzed whether it predicts prognosis in AML patients and further it is helpful to choose therapies in the modalities of treatment options, because it is known to be required for self-renewal mechanism of leukemic stem cells. Bmi-1 expression in bone marrow or peripheral blood cells was analyzed in 49 patients with AML (M0(n=5), M1(n=7), M2(n=6), M3(n=5), M4(n=8), M5(n=5), M6(n=1)), granulocytic sarcoma(n=1), MDS-AML (n=9), and secondary AML(n=2). Freshly isolated AML cells were stained with a PE-conjugated anti-CD34-antibody followed by fixation and then with anti-Bmi-1-antibody-FITC. All of patients with low Bmi-1 positivity (&lt;35%, n=11) except for de novo AML(M0) entered in complete remission (CR) with single induction chemotherapy(n=5) and accordingly had better overall survival, even though lower dose of chemotherapy (60% of standard dose) was given (n=3). Alternatively, patients with higher percentage of Bmi-1 expression in AML cells (&gt; 70%, n=19) except for AML(M3) progressed to death within two years, unless they were treated with highly intensive therapy such as high dose AraC or allogeneic stem cell transplantation (n=3). Patients with intermediate degree of Bmi-1 expression (35–60%, n=5) responded to standard intensity of chemotherapy (n=2) and are alive for more than two years. Interestingly, patients with MDS-AML (n=9) had high Bmi-1 expression (79%) and all of them have died within 20 months. Binary logistic regression model showed that significant correlation was found among survival status as dependent variable, Bmi-1, and treatment intensity as independent variable (p = 0.004). On the other hand, Univariate analysis did not reveal any relation of Bmi-1 expression to karyotype, age, WBC count, or FAB subtype. In conclusion, Bmi-1 expression could be an independent prognostic marker and useful tool to design therapy for the AML patients.

An Evaluation of Septicemia During Outpatient Consolidation Chemotherapy for Acute Myeloid Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4268-4268
Author(s):  
Lalit Saini ◽  
Mark D. Minden ◽  
Andre Schuh ◽  
Karen Yee ◽  
Aaron D Schimmer ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Infection Prophylaxis ◽  
Consolidation Chemotherapy ◽  
E Coli ◽  
Significant Difference ◽  
Ambulatory Patients ◽  
Gram Negative Organisms ◽  
Acute Myeloid

Abstract Abstract 4268 Introduction: Ambulatory chemotherapy for acute myeloid leukemia (AML) is believed to reduce exposure to nosocomial multi-drug resistant organisms and the incidence of septicemia. Materials and Methods: In this retrospective analysis we assessed the frequency of septicemia in patients receiving consolidation therapy: 256 patients received the first consolidation cycle (C1) and 217 the second consolidation cycle (C2). Patients received consolidation as inpatients or on an ambulatory basis. All ambulatory patients received infection prophylaxis with ciprofloxacin, amoxicillin and fluconazole. Results: 71 cycles of IP and 402 cycles of ambulatory consolidation chemotherapy were administered. Rates of bacteremia were higher in the IP cohort compared to the ambulatory patients (39.4% vs. 26.6%, p=0.028). IP in C1 but not C2 had significantly more septicemia then the ambulatory cohort within that cycle. Relative to C1, C2 was associated with significantly more bacteremia (p=0.03) and more Escherichia coli isolates (p=0.023) but there was no significant difference in the rates of total Gram-positive organisms (79.2% vs. 70.4%, p=0.32), total Gram-negative organisms (20.7% vs. 28.1%, p=0.32) or Streptococcus isolates (17% vs. 23.9%, p=0.34). All Streptococcus isolates in C2 were sensitive to penicillin despite amoxicillin prophylaxis whereas all E. coli strains in C2 were resistant to ciprofloxacin. Conclusions: Ambulatory consolidation chemotherapy for AML is associated with a reduced incidence of septicemia. The second consolidation cycle is associated with a higher incidence of bacteremia accounted for by increased rates of ciprofloxacin resistant E. coli and penicillin-sensitive Streptococcus. Disclosures: No relevant conflicts of interest to declare.

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