scholarly journals Comorbidity is an independent predictor of complete remission in elderly patients receiving induction chemotherapy for acute myeloid leukemia

Cancer ◽  
2007 ◽  
Vol 109 (7) ◽  
pp. 1376-1383 ◽  
Author(s):  
Anne Etienne ◽  
Benjamin Esterni ◽  
Aude Charbonnier ◽  
Marie-Joëlle Mozziconacci ◽  
Christine Arnoulet ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Elderly Patients ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Independent Predictor ◽  
Acute Myeloid

Impact of Time Between Induction Chemotherapy and Complete Remission on Survival Outcomes in Patients With Acute Myeloid Leukemia

2019 ◽  
Vol 19 (11) ◽  
pp. 729-734 ◽  
Author(s):  
Rafiye Ciftciler ◽  
Haluk Demiroglu ◽  
Ibrahim Celalettin Haznedaroglu ◽  
Nilgun Sayınalp ◽  
Salih Aksu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Survival Outcomes ◽  
Acute Myeloid

Early Allogeneic Hematopoietic Cell Transplantation during Induction Chemotherapy in High-Risk Acute Myeloid Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2299-2299 ◽  
Author(s):  
Gerhard Ehninger ◽  
Uwe Platzbecker ◽  
Christian Thiede ◽  
Thomas Illmer ◽  
Ulrich S. Schuler ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Complete Remission ◽  
Cell Transplantation ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Minor Response ◽  
Cytogenetic Aberrations ◽  
Acute Myeloid

Objectives: In patients with acute myeloid leukemia and high-risk cytogenetic aberrations or minor response to the first cycle of induction chemotherapy (IC) the probability of achieving a sustained complete remission is low. Thus early treatment intensification may be warranted in order to achieve long-term disease control. We performed a prospective trial to evaluate whether reduced-intensity conditioning followed by allogeneic hematopoietic stem cell transplantation (HSCT) from related or unrelated donors can be performed during the aplastic phase of IC in patients with poor-risk AML. Methods: Seventeen patients (n=17) aged between 17 and 63 years (median 45) with acute myeloid leukemia and high-risk cytogenetic aberrations (n=14, complex, inv3 or t(3;3), t(3;5), −7 or del 7q, +8) or more than 10 % marrow blasts on day 15 after the first cycle of IC (n=3) were included so far. During aplasia a median of thirteen days (range 7–35) after the first (n=8) or second (n=9) cycle of IC patients received 5 x 30 mg/m2 fludarabine i.v. combined with either 8 mg/kg busulfan p.o. (n=4) or 150 mg/m2 melphalan iv. (n=13) followed by allogeneic G-CSF mobilized peripheral blood stem cells (PBSC, n=16) or bone marrow (n=1) from related (n=7) or unrelated (n=10) donors. Nine out of seventeen patients were not in complete remission before conditioning therapy was started. Patients with unrelated grafts received antithymocyte globulin (4 x 10 mg/kg ATG Fresenius). GvHD prophylaxis was performed with cyclosporine A (CSP). Results: All patients engrafted (ANC > 0.5 Gpt/l on day 11, range 8–19, platelets > 50 Gpt/l day 15, range 11–32) and went into remission. Acute GvHD grade II-IV occurred in 8 patients and extensive chronic GvHD was documented in 5 patients with a follow-up of > 100 days. Two patients died while being in remission from infectious complications associated with acute (n=1) or chronic (n=1) GvHD and two patients died during relapse eight and twelve months after PBSC. With a median follow-up of 15 months (range 1–65) thirteen out of seventeen patients (76 %) are alive and in remission. Conclusion: Early allogeneic HSCT as part of primary induction therapy seems to be an effective strategy in AML patients with either poor risk karyotype or minor response to the first induction cycle.

Molecular Minimal Residual Disease After Induction Is Related to ABC Proteins' Activity and Associated with Survival in 26 Patients with NPM1 Mutated Acute Myeloid Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4909-4909
Author(s):  
Pierre Hirsch ◽  
Ruoping Tang ◽  
Christophe Marzac ◽  
Fanny Fava ◽  
Jean-Yves Perrot ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Induction Chemotherapy ◽  
Cytogenetic Analysis ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Abc Proteins ◽  
Minimal Residual ◽  
Acute Myeloid

Abstract Abstract 4909 Background: A major issue in the treatment of acute myeloid leukemia (AML) is resistance to chemotherapeutic drugs. The role of ABC proteins, and specially ABCB1 (PgP/mdr1), in this resistance has been well established, and higher ABC proteins' activity, assessed with functional tests, has been associated with poorer complete remission rates and poorer overall prognosis (Marzac et al, Haematologica, 2011). Furthermore, the evaluation of molecular minimal residual disease (MRD), using mutated nucleophosmin (NPM1)expression quantification has been related to patients' global prognosis (Krönke et al, J. Clin. Oncol., 2011), and to response to treatments. In this study, we evaluate the impact of ABC proteins' activity on MRD after one course of induction chemotherapy, in 26 patients with NPM1 mutated AML. Material and methods: We retrospectively identified 26 AML patients with NPM1 mutation treated in our center and with MRD data. MRD was evaluated as the ratio of NPM1 mutated allele and total NPM1, using PCR DNA quantification and the delta delta Ct method. MRD was measured at the time of diagnosis and after one course of anthracycline-based induction chemotherapy. ABC proteins' activity was evaluated at the time of diagnosis using JC1 +/− cyclosporine A assay (Legrand et al, Blood, 2001). Correlations between ABC proteins' activity and the level of post induction MRD were evaluated with the Mann-Whitney test. Survival was evaluated using the Cox model. For all analyses, P values were considered significant when lower than 0. 05. Results: Median age at diagnosis was 53 years old. Twenty-two patients had normal cytogenetic analysis at diagnosis, and the other 4 patients had intermediate prognosis cytogenetic analysis. Nine patients harboured FLT3-ITD mutation. Median ABC proteins' activity was 0. 11 (0 – 0. 77). After one course of induction chemotherapy, 3 patients did not reach cytological complete remission. In 17 patients MRD level after induction therapy was inferior to 1 %, in 11 patients MRD was inferior to 0. 1 % and in 7 patients MRD was inferior to 0. 01 %. Overall, higher MRD level after induction (defined by MRD level higher than 0. 1 %) was associated with poorer prognosis for disease free survival (HR= 4. 25 [95% CI 1. 049–17. 27]; p=0. 04), and for overall survival HR=11. 25 [95% CI 1. 22–103. 23]; p=0. 03). Higher ABC proteins' activity was associated with higher MRD levels post induction, and patients who did not reach MRD level lower than 0. 1 % had significantly higher ABC proteins' activity than other patients (p=0. 008). ABC proteins' activity was also associated with overall survival in our patients (p=0. 04). Conclusion: Higher ABC proteins' activity is associated with higher MRD levels after one course of induction chemotherapy in 26 NPM1 mutated AML patients, and is also associated with poorer overall survival. The poorer prognosis associated with high ABC proteins' activity in AML seems to be in part related to direct resistance to chemotherapy. These data should be confirmed in larger studies. Disclosures: No relevant conflicts of interest to declare.

Increased angiogenesis in the bone marrow of patients with acute myeloid leukemia

Blood ◽  
2000 ◽  
Vol 95 (8) ◽  
pp. 2637-2644 ◽  
Author(s):  
Teresa Padró ◽  
Sandra Ruiz ◽  
Ralf Bieker ◽  
Horst Bürger ◽  
Martin Steins ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Induction Chemotherapy ◽  
Microvessel Density ◽  
Myeloid Leukemia ◽  
Remission Induction ◽  
Bone Marrow Biopsies ◽  
Acute Myeloid

The importance of angiogenesis for the progressive growth and viability of solid tumors is well established. In contrast, only few data are available for hematologic neoplasms. To investigate the role of angiogenesis in acute myeloid leukemia (AML), bone marrow biopsies from 62 adults with newly diagnosed, untreated AML (day 0) were evaluated. Further studies were done after the completion of remission induction chemotherapy (day 16 of induction chemotherapy, n = 21; complete remission, n = 20). Microvessels were scored in at least 3 areas (×500 field, 0.126 mm2) of the highest microvessel density in representative sections of each bone marrow specimen using immunohistochemistry for von Willebrand factor and thrombomodulin. Microvessel counts were significantly higher in patients with AML (n = 62) compared with control patients (n = 22): median (interquartile range) 24.0 (21.0-27.8)/×500 field vs 11.2 (10.0-12.0)/×500 field, respectively (P < .001). On day 16 of induction chemotherapy, microvessel density was reduced by 60% (44-66) (P < .001) in hypoplastic marrows without residual blasts, in contrast to only 17% (0-37) reduction in hypoplastic marrows with ≥ 5% residual blasts (P < .001 for the difference between both groups). Bone marrow biopsies taken at the time of complete remission displayed a microvessel density in the same range as the controls. In conclusion, there is evidence of increased microvessel density in the bone marrow of patients with AML, which supports the hypothesis of an important role of angiogenesis in AML. Furthermore, these findings suggest that antiangiogenic therapy might constitute a novel strategy for the treatment of AML.

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.>

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

Nonanthracycline Induction Chemotherapy (T-FLAG) for Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4356-4356
Author(s):  
Amit Mahipal ◽  
Emmanuel C. Besa ◽  
Anne Marie Valorie-Oberlie ◽  
Isaac Matthias ◽  
Adam Thode
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Progression Free Survival ◽  
Free Survival ◽  
Related Mortality ◽  
Acute Myeloid

Abstract Abstract 4356 Introduction: Prognosis of elderly patients (age>60 years) with acute myeloid leukemia (AML) is poor as compared to younger patients with a higher incidence of cardiac co-morbidities. With standard induction therapy, complete remission (CR) is achieved in 35% to 50% of elderly patients. However, the induction anthracycline containing chemotherapy related mortality is in this population has been reported to be approximately 30%. We attempted to decrease this by replacing the anthracycline with topotecan. Alternative therapies are needed that are less toxic but equally efficacious. In a phase I/II trial of the combination of topotecan, fludarabine, cytarabine and G-CSF (T-FLAG) in elderly AML and MDS, there was 50% CR and 15% treatment related deaths. In this study, we report patients >60 years of age treated with T-FLAG as an initial therapy for AML at our institute. Methods: We retrospectively reviewed the charts of elderly patients with AML treated with T-FLAG at our institution. Elderly patients were defined as more than 60 years of age. IRB approval was obtained for the study. All patients received topotecan 2mg/m2, fludarabine 30 mg/m2, and cytarabine 2000 mg/m2 all given over 30 min from day 1 to day 4 and G-CSF 400 μ g/m2/day from the day 5 to neutrophil counts recovery. International working group criteria was used to assess responses. All statistical analysis was done using SAS statistical software. Descriptive statistics were used. Progression free survival was defined from the time of diagnosis to progression, death or last follow up, whichever comes first. Overall survival and progression free survival was calculated using Kaplan and Meier method. Results: Thirteen elderly patients were treated with T-FLAG. The median age of diagnosis was 73 years (Range: 60–86 years). There were 10 male and 3 female patients. Ten (77%) patients had complex cytogenetics. Cardiomyopathy (EF <50%) or elevated liver function tests precluding anthracycline use was present in 54% of the patients. Response rate was 69% with 7 (54%) patients achieving CR and 2 (15%) patients achieving partial remission. Out of 10 patients with abnormal cytogenetics at baseline, 7 (70%) patients had cytogenetic CR. Eleven (85%) patients were alive at day 30. Median progression free survival and overall survival was 36 weeks and 54 weeks respectively. The median time for the recovery of neutrophil counts (>500/μ L) was 22 days (Range: 10–47 days). Conclusions: In this study of unfavorable risk group elderly patients, T-FLAG induction chemotherapy results in comparable remission rates with low induction chemotherapy related mortality. It may be an alternative regimen for elderly patients with complex cytogenetics or patients who cannot tolerate anthracyclines. More studies are needed to confirm these results. This however, may be useful to bridge patients to transplant or maintenance demethylating agents to improve survival. Disclosures: No relevant conflicts of interest to declare.

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