Impact of CRi on the Outcome of Elderly Patients with Acute Myeloid Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4384-4384 ◽  
Author(s):  
Anne Etienne ◽  
Aude Charbonnier ◽  
Thomas Prebet ◽  
Diane Coso ◽  
Anne-Marie Stoppa ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
New Drugs ◽  
Response Criteria ◽  
Remission Induction ◽  
Remission Duration ◽  
Acute Myeloid

Abstract New international recommendations of response for treatment of acute myeloid leukemia (AML) include morphologic complete remission with incomplete blood count recovery (CRi). This response criteria was defined following evaluation of new drugs used for the treatment of AML in first relapse (Sievers et al., JCO2001;19:3244–3254). The objective of our study was to determine the outcome of elderly patients with newly diagnosed AML achieving CRi. Between 1995 and 2006, 240 patients aged 65 years or older with previously untreated acute non promyelocytic leukemia received a conventional anthracycline and cytarabine induction chemotherapy at a single institution. Median age was 71 years (range, 65–85). One hundred and nineteen patients achieved a complete response (CR) (50%), 15 patients achieved CRi (6%), 69 patients had persisting leukemia (29%), and 37 died during remission induction therapy (15%). Patients who reached a CR or CRi after 1 or 2 cycles of induction chemotherapy proceeded to consolidation. Only 9 patients in CRi received this consolidation chemotherapy course (60%) and none had intensification (intermediate-dose cytarabine and/or autologous stem cell transplantation) whereas for patients achieving CR, 88% (n=104) and 69% (n=82) had consolidation and intensification, respectively (p=0,01 and p=0,03). The median overall survival (OS) was respectively 9 and 18 months for patients in CRi and CR (p=0,08). OS was significantly lower for patients in CRi younger than 70 years (5 versus 17 months for CR, p=0,02). By landmark analysis, there was no difference in OS between patients in CRi and a group of 67 patients with induction failure surviving at less 40 days (p=0,14). Disease-free survival (DFS) and remission duration were not significantly different between patients in CRi and CR overall (5 and 8 months, and 5 and 7 months, respectively), but we found a difference for patients younger than 70 years (p=0,004 and p=0,009 for DFS and remission duration, respectively). There was significantly more multilineage dysplasia in patients achieving CRi (8 versus 33, p=0,009) and platelet count at diagnosis were lower (44 G/L versus 82 G/L). Cytogenetic did not differ between the two groups. Our results show that the outcome of elderly patients who achieved CRi is inferior to patients in CR, especially for patients younger than 70 years. Although this response criteria seems to indicate activity, we were not able to found a difference with patients who did not achieve CR. This result will be revaluated in a larger study. Our data also suggest that patients with CRi have different initial disease characteristics. Figure Figure

Priming with Granulocyte Colony-Stimulating Factor (G-CSF) Has No Impact on Treatment Outcome but Impairs Mobilization of Peripheral Blood Stem Cells (PBSC) in Elderly Patients with Acute Myeloid Leukemia: Results of a Randomized Oligocenter Trial.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 867-867
Author(s):  
Gesine Bug ◽  
Steffen Koschmieder ◽  
S. Wiebe ◽  
Gerd Heil ◽  
Carla Delfs ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Treatment Outcome ◽  
Elderly Patients ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Secondary Aml ◽  
Remission Duration ◽  
Cd34 Cells ◽  
Acute Myeloid

Abstract Treatment of elderly patients with acute myeloid leukemia (AML) is characterized by a low complete remission (CR) rate of less than 50% and short remission duration with a median disease-free survival (DFS) of less than one year (Rowe et al., Blood 2004). Sensitization of leukemic cells with growth factors may enhance the efficacy of chemotherapy in AML patients. Aims of this randomized prospective, oligocenter study were 1) to assess whether induction chemotherapy given simultaneously with and followed by G-CSF (G-CSFpriming) was superior to G-CSF following induction (G-CSFpost) with regard to CR rate and DFS in pts aged older than 60 yrs with previously untreated de novo and secondary AML and 2) to examine the feasibility of an early consolidation therapy followed by autologous stem cell transplantation (ASCT) as late consolidation. Between 01/00 and 04/04, a total of 116 eligible patients (median age 67 yrs) were randomly assigned to receive G-CSFpriming (n=57) or G-CSFpost (n=59) during two remission-induction cycles consisting of idarubicin, cytarabine and etoposide (IdAV) with daily application of 5μg/kg G-CSF (Neupogen®, Amgen). Pts achieving a CR received early consolidation using fludarabine, cytarabine, idarubicin, G-CSF (mini-FlagIda) and PBSC harvest, followed by ASCT. Pts lacking PBSC due to mobilization failure were optionally treated with a second cycle of mini-FlagIda. After induction chemotherapy, 74 out of 116 pts (63.8%) achieved CR. Response was not significantly different in the G-CSFpost vs. G-CSFpriming group (67.8 vs. 59.6%), nor was recovery of neutrophils. Of 74 complete responders, 44 have relapsed and 3 died in CR. Median remission duration was 15.2 and 14.7 months in the G-CSFpost and G-CSFpriming group, resp. Median DFS was 16.5 months and the probability of DFS at 4 yrs 21.2%, with no significant difference between the treatment groups and a median follow-up of 22 months at the time of this interim analysis. Mini-FlagIda consolidation was administered to 51 out of 74 CR patients (68.9%). The number of circulating CD34+ cells was monitored in 43 patients. The probability of mobilizing at least 1x106/kg CD34+ cells was significantly lower in the G-CSFpriming compared to the G-CSFpost group with 29.4% (5/17 pts) and 59.2% (16/26 pts), resp (p<0.05). ASCT was performed in 10 pts resulting in a significantly better 4-yr DFS (55%) compared to 10 pts treated with a second course of mini-FlagIda (22%, p<0.05). The major reason for not being autografted in spite of efficient collecting of CD34+ cells was early relapse. Conclusion: In elderly pts with de novo or secondary AML, G-CSF priming did not enhance the antileukemic efficacy of induction chemotherapy and had no significant impact on overall treatment outcome compared with G-CSF administered after induction. As ASCT proved to be an effective consolidation modality for CR patients mobilizing sufficient amounts of CD34+ cells, the detrimental effect of G-CSF priming on the collection of PBSC is clinically relevant.>

Postremission treatment of elderly patients with acute myeloid leukemia in first complete remission after intensive induction chemotherapy:results of the multicenter randomized Acute Leukemia French Association (ALFA) 9803 trial

Blood ◽  
2007 ◽  
Vol 109 (12) ◽  
pp. 5129-5135 ◽  
Author(s):  
Claude Gardin ◽  
Pascal Turlure ◽  
Thierry Fagot ◽  
Xavier Thomas ◽  
Christine Terre ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Elderly Patients ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Remission Induction ◽  
Intensive Chemotherapy ◽  
Transfusion Requirements ◽  
Acute Myeloid

Abstract In elderly patients with acute myeloid leukemia (AML) treated intensively, no best postremission strategy has emerged yet. This clinical trial enrolled 416 patients with AML aged 65 years or older who were considered eligible for standard intensive chemotherapy, with a first randomization comparing idarubicin with daunorubicin for all treatment sequences. After induction, an ambulatory postremission strategy based on 6 consolidation cycles administered monthly in outpatients was randomly compared with an intensive strategy with a single intensive consolidation course similar to induction. Complete remission (CR) rate was 57% with 10% induction deaths, and estimated overall survival was 27% at 2 years and 12% at 4 years, without notable differences between anthracycline arms. Among the 236 patients who reached CR, 164 (69%) were randomized for the postremission comparison. In these patients, the multivariate odds ratio in favor of the ambulatory arm was 1.51 for disease-free survival (P =.05) and 1.59 for overall survival from CR (P =.04). Despite repeated courses of chemotherapy associated with a longer time under treatment, the ambulatory arm was associated with significantly shorter rehospitalization duration and lower red blood cell unit and platelet transfusion requirements than observed in the intensive arm. In conclusion, more prolonged ambulatory treatment should be preferred to intensive chemotherapy as postremission therapy in elderly patients with AML reaching CR after standard intensive remission induction.

scholarly journals The Expression Changes of CX3CL1 and Interlukin-6 Genes During Remission Induction Therapy in Patients With Acute Myeloid Leukemia

2021 ◽  
Vol 10 ◽  
pp. e2288
Author(s):  
Mahdiyar Iravani Saadi ◽  
Mani Ramzi ◽  
Aliasghar Karimi ◽  
Maryam Owjfard ◽  
Mahmoud Torkamani ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Hematologic Malignancy ◽  
Quantitative Polymerase Chain Reaction ◽  
Remission Induction ◽  
Response To Chemotherapy ◽  
Before And After ◽  
Acute Myeloid

Background: Acute Myeloid Leukemia syndrome (AML) is a hematologic malignancy which is due to clonal extensive proliferation of leukemic precursor cells and is rapidly fatal unless treated or response to chemotherapy. Cytogenetic findings have important role in prognosis and categorization of AML. The aim of this study was to investigate the expression changes in CX3CL1 and Interlukin-6 (IL-6) genes before and after chemotherapy as remission induction therapy in AML patients. Materials and Methods: In this study 69 patients (36 males, 33 female) with AML was selected from tertiary medical heath center. A quantitative polymerase chain reaction (PCR) was done for mRNA expression of CX3CL1 and IL-6genes before and after induction chemotherapy. To obtain expression changes in CX3CL1 and IL-6genes, we used 2-ΔΔCT method. Results: The expression of CX3CL1 and IL-6 was significantly increased after induction chemotherapy. Also, the ΔCt mean of CX3CL1 and IL-6 mRNA was not significant between AML subtype groups. Conclusion: In conclusion, as we showed that chemotherapy significantly increase the expression of CX3CL1 and IL-6 which can be used as a prognostic factor of AML.

scholarly journals Target Therapy in Acute Myeloid Leukemia

2020 ◽  
Author(s):  
Vasko Graklanov
Keyword(s):  
Clinical Trials ◽  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Acute Leukemia ◽  
Mechanism Of Action ◽  
Myeloid Leukemia ◽  
Target Therapy ◽  
New Drugs ◽  
Cytotoxic Treatment ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is the most common form of acute leukemia in elderly patients. Over the past four decades the basic therapeutic armamentarium was the standard cytotoxic treatment. The new insights in understanding the pathogenesis of AML was the momentum that revolutionized the treatment landscape in AML. The last five years unprecedented growth has been seen in the number of target therapy drugs for the treatment of AML. These new drugs did not just have a clinical benefit as single agents but also have improved AML patient outcomes if combined with conventional cytotoxic therapy. Here, we review recent advances in target-based therapy for patients with AML focusing on their mechanism of action and the results from already published clinical trials.

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.

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