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.

Assessment of Patients Fitness at Diagnosis in Elderly Acute Myeloid Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4012-4012
Author(s):  
Semra Aydin ◽  
Ernesta Audisio ◽  
Stefano D'Ardia ◽  
Bernardino Allione ◽  
Barbara Nicolino ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Board Of Directors ◽  
Myeloid Leukemia ◽  
Intensive Chemotherapy ◽  
Advisory Committees ◽  
Perfect Agreement ◽  
Medical Board ◽  
Acute Myeloid

Abstract Background:Acute myeloid leukemia (AML) is a disease which predominantly affects patients with a median age at diagnosis over 65 years. The elderly population is highly heterogeneous and assessment strategies are needed to define the frailty profile. To date, evaluation of disease-related and patients specific factors in the context of clinic decision making has been largely subjective. Concerning AML therapy, several studies demonstrated improved survival for older patients receiving intensive induction chemotherapy compared to those receiving supportive care alone. Defining this subset of patients who are eligible or "fit" for intensive chemotherapy involves a great deal of subjectivity. Criteria yet have to be standardized across or within institutions. Aim:Aim of this study was to investigate the validity of four scores for assessment of patient fitness at diagnosis in parallel to physician evaluation. Further patient outcome according the respective evaluation was compared. Methods: In a single hematology center a total of 85 clinically and molecularly well characterized consecutive elderly (>60 years) patients with newly diagnosed AML were treated from 2012 to 2015 according to age, performance status and co-morbidities. Therapy response was defined according to ELN criteria. Therapy intensity decision was based on an initial haematologist evaluation followed by discussion of the patient case in an interdisciplinary board. Independently from the medical board, in parallel the local geriatric G8 screening tool, consisting of seven items from the Mini Nutritional Assessment (MNA) questionnaire and age, the HCT-CI comorbidity score as well as the AML scores proposed by the German Acute Myeloid Leukemia Cooperative Group, predicting probability of complete remission (CR) and early death (ED) were performed. Overall survival from diagnosis was compared between groups using the Cox model. Results:A total of 42 (49,4%) patients were evaluated "fit" by the medical board and treated by intensive chemotherapy ("7+3" regimen), whereas 4 patients (4,7%) underwent semi-intensive with hypomethylating agents and 39 patients (45,8%) received palliative therapy (low dose Cytarabine or Hydroxyurea). Twenty-six patients (30,6%) achieved a complete remission after induction chemotherapy, could follow consolidation chemotherapy and six of them underwent allogeneic hematopoietic stem cell transplantation. Fourty-four (51,8%) were non responders and 15 patients (17,6%) died during the first cycle. Overall, the median survival time was 6,7 months (95% CI 3,7-9,5). Primary physician care evaluation was able to define in a statistically significant manner a "fit" from an "unfit" patient. Median survival time from the "fit" patients was 10 moths (95%CI 5-not reached) compared to the "unfit" evaluated patients with 3,4 months (95%CI 1,4-5), p<0.001 with a HR (95%CI) of 3,18 (1,81 to 5,59). Parallel evaluation of patients unfitness according the proposed cut-point of the G8 (≤14), AML for CR (<40) and AML for ED (≥30) scores discriminated significantly patients survival with HRs equal to 3.03 (p<0,001), 2.11 (p=0,007) and 2.83 (p<0.001), respectively. The agreement between the frailty scores and physician evaluation on the prediction of fitness classification was analyzed by calculating the Cohens' Kappa. In this approach a Kappa level of 1,0 denotes perfect agreement. The agreement of was moderate for HCT-CI score and AML score for CR (0.47 and 0.46, respectively). The agreement was fair for G8 and AML score for ED (0.27 and 0.33, respectively). Summary/Conclusion: In conclusion, in the present AML cohort the applied frailty scores at diagnosis correlated significantly with the median overall survival. Since no perfect agreement was found respect to physician for fitness classification, frailty scores can help to improve the prognosis prediction. These results may encourage a following multi-centre analysis in order to increase the statistic power of the performed analysis. Disclosures Vitolo: Roche: Membership on an entity's Board of Directors or advisory committees, Other: Honoraria for lectures; Gilead: Other: Honoraria for lectures; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Honoraria for lectures; Takeda: Other: Honoraria for lectures.

scholarly journals Long-term survival after intensive chemotherapy or hypomethylating agents in AML patients aged 70 years and older: a large patient data set study from European registries

Leukemia ◽  
2021 ◽  
Author(s):  
Christian Récher ◽  
Christoph Röllig ◽  
Emilie Bérard ◽  
Sarah Bertoli ◽  
Pierre-Yves Dumas ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Intensive Chemotherapy ◽  
Hypomethylating Agents ◽  
Term Survival ◽  
Acute Myeloid

AbstractThe outcome of acute myeloid leukemia patients aged 70 years or older is poor. Defining the best treatment option remains controversial especially when choosing between intensive chemotherapy and hypomethylating agents. We set up a multicentric European database collecting data of 3 700 newly diagnosed acute myeloid leukemia patients ≥70 years. The primary objective was to compare overall survival in patients selected for intensive chemotherapy (n = 1199) or hypomethylating agents (n = 1073). With a median follow-up of 49.5 months, the median overall survival was 10.9 (95% CI: 9.7–11.6) and 9.2 months (95% CI: 8.3–10.2) with chemotherapy and hypomethylating agents, respectively. Complete remission or complete remission with incomplete hematologic recovery was 56.1% and 19.7% with chemotherapy and hypomethylating agents, respectively (P < 0.0001). Treatment effect on overall survival was time-dependent. The Royston and Parmar model showed that patients treated with hypomethylating agents had a significantly lower risk of death before 1.5 months of follow-up; no significant difference between 1.5 and 4.0 months, whereas patients treated with intensive chemotherapy had a significantly better overall survival from four months after start of therapy. This study shows that intensive chemotherapy remains a valuable option associated with a better long-term survival in older AML patients.

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

European Development of Clofarabine as Treatment for Older Patients With Acute Myeloid Leukemia Considered Unsuitable for Intensive Chemotherapy

2010 ◽  
Vol 28 (14) ◽  
pp. 2389-2395 ◽  
Author(s):  
Alan K. Burnett ◽  
Nigel H. Russell ◽  
Jonathan Kell ◽  
Michael Dennis ◽  
Donald Milligan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Performance Status ◽  
Poor Performance Status ◽  
Intensive Chemotherapy ◽  
Phase Ii Studies ◽  
Acute Myeloid

Purpose Treatment options for older patients with acute myeloid leukemia (AML) who are not considered suitable for intensive chemotherapy are limited. We assessed the second-generation purine nucleoside analog, clofarabine, in two similar phase II studies in this group of patients. Patients and Methods Two consecutive studies, UWCM-001 and BIOV-121, recruited untreated older patients with AML to receive up to four or six 5-day courses of clofarabine. Patients in UWCM-001 were either older than 70 years or 60 to 69 years of age with poor performance status (WHO > 2) or with cardiac comorbidity. Patients in BIOV-121 were ≥ 65 years of age and deemed unsuitable for intensive chemotherapy. Results A total of 106 patients were treated in the two monotherapy studies. Median age was 71 years (range, 60 to 84 years), 30% had adverse-risk cytogenetics, and 36% had a WHO performance score ≥ 2. Forty-eight percent had a complete response (32% complete remission, 16% complete remission with incomplete peripheral blood count recovery), and 18% died within 30 days. Interestingly, response and overall survival were not inferior in the adverse cytogenetic risk group. The safety profile of clofarabine in these elderly patients with AML who were unsuitable for intensive chemotherapy was manageable and typical of a cytotoxic agent in patients with acute leukemia. Patients had similar prognostic characteristics to matched patients treated with low-dose cytarabine in the United Kingdom AML14 trial, but had significantly superior response and overall survival. Conclusion Clofarabine is active and generally well tolerated in this patient group. It is worthy of further evaluation in comparative trials and might be of particular use in patients with adverse cytogenetics.

scholarly journals Conventional chemotherapy for acute myeloid leukemia: a Brazilian experience

2000 ◽  
Vol 118 (6) ◽  
pp. 173-178 ◽  
Author(s):  
Kátia Borgia Barbosa Pagnano ◽  
Fabiola Traina ◽  
Tatiana Takahashi ◽  
Gislaine Borba Oliveira ◽  
Marta Soares Rossini ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Disease Free Survival ◽  
Conventional Chemotherapy ◽  
Free Survival ◽  
Disease Free ◽  
Acute Myeloid

CONTEXT: Young patients affected by acute myeloid leukemia (AML) achieve complete remission (CR) using conventional chemotherapy in about 55-85%. However, 30% of patients fail to achieve CR and the remission duration is often only about 12 months. More intensive treatment after CR seems to be necessary in order to maintain CR and obtain a definitive cure. In Brazil, few reports have been published on this important subject. OBJECTIVE: The aim of this study was to describe a Brazilian experience in the treatment of "de novo" acute myeloid leukemia (AML) in younger adult patients (age < 60 years). DESIGN: Retrospective analysis. SETTING: University Hospital, Hematology and Hemotherapy Center, State University of Campinas, Brazil. PARTICIPANTS: Newly diagnosed cases of "de novo" AML in the period from January 1994 to December 1998 were evaluated retrospectively, in relation to response to treatment, overall survival (OS) and disease free survival (DFS). Cases with acute promyelocytic leukemia (APL) were also included in this analysis. RESULTS: On the basis of an intention to treat, 78 cases of AML, including 17 cases of APL, were evaluated. The overall median follow-up was 272 days. The complete remission (CR) rate was 63.6% in the AML group (excluding APL) and 78% in the APL group. The 5-year estimated disease-free survival (DFS) was 80% for the APL group and 34% for the AML group (P = 0.02). The 5-year estimated overall survival (OS) was 52% for the APL group and 20.5% for the AML group, respectively (P = NS). Relapse was observed in 12/39 (30.7%) patients with AML and 1/11 (9%) with APL. CONCLUSIONS: These results are similar to those reported in the literature. However, relapse and mortality rates remain high, and a search for more aggressive strategies in order to prevent relapse is recommended.

scholarly journals Combination of dasatinib with chemotherapy in previously untreated core binding factor acute myeloid leukemia: CALGB 10801

2020 ◽  
Vol 4 (4) ◽  
pp. 696-705 ◽  
Author(s):  
Guido Marcucci ◽  
Susan Geyer ◽  
Kristina Laumann ◽  
Weiqiang Zhao ◽  
Donna Bucci ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Core Binding Factor ◽  
Free Survival ◽  
Binding Factor ◽  
Disease Free ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) with either t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22) is referred to as core binding factor (CBF) AML. Although categorized as favorable risk, long-term survival for these patients is only ∼50% to 60%. Mutated (mut) or overexpressed KIT, a gene encoding a receptor tyrosine kinase, has been found almost exclusively in CBF AML and may increase the risk of disease relapse. We tested the safety and clinical activity of dasatinib, a multi-kinase inhibitor, in combination with chemotherapy. Sixty-one adult patients with AML and CBF fusion transcripts (RUNX1/RUNX1T1 or CBFB/MYH11) were enrolled on Cancer and Leukemia Group B (CALGB) 10801. Patients received cytarabine/daunorubicin induction on days 1 to 7 and oral dasatinib 100 mg/d on days 8 to 21. Upon achieving complete remission, patients received consolidation with high-dose cytarabine followed by dasatinib 100 mg/d on days 6 to 26 for 4 courses, followed by dasatinib 100 mg/d for 12 months. Fifteen (25%) patients were older (aged ≥60 years); 67% were CBFB/MYH11–positive, and 19% harbored KITmut. There were no unexpected or dose-limiting toxicities. Fifty-five (90%) patients achieved complete remission. With a median follow-up of 45 months, only 16% have relapsed. The 3-year disease-free survival and overall survival rates were 75% and 77% (79% and 85% for younger patients [aged &lt;60 years], and 60% and 51% for older patients). Patients with KITmut had comparable outcome to those with wild-type KIT (3-year rates: disease-free survival, 67% vs 75%; overall survival, 73% vs 76%), thereby raising the question of whether dasatinib may overcome the negative impact of these genetic lesions. CALGB 10801 was registered at www.clinicaltrials.gov as #NCT01238211.

High ROBO3 expression predicts poor survival in non-M3 acute myeloid leukemia

2021 ◽  
pp. 153537022098824
Author(s):  
Zhimei Cai ◽  
Jifeng Wei ◽  
Ze Chen ◽  
Haiqing Wang
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Signaling Pathway ◽  
Myeloid Leukemia ◽  
Remission Induction ◽  
Intensive Chemotherapy ◽  
Event Free Survival ◽  
Free Survival ◽  
Receptor Proteins ◽  
Acute Myeloid

Roundabout guidance receptor proteins are crucial components of the SLIT/ROBO signaling pathway. This pathway is important for the nervous system and in embryonic development. Recently, increasing evidence has shown that roundabout guidance receptor proteins and the SLIT/ROBO signaling pathway also participate in tumorigenesis. Here, by analyzing transcriptome data from the TCGA and GEO databases, we found that ROBO3 is highly expressed in non-M3 acute myeloid leukemia. High ROBO3 expression was associated with increased age at diagnosis and poorer risk classification (both P <  0.01). Patients with high ROBO3 expression had higher rates of TP53 and RUNX1 mutations (both P <  0.05). Significantly worse overall survival and event-free survival were observed in high ROBO3 expression patients compared with low ROBO3 expression patients (OS: P =  0.004; EFS: P= 0.012). High ROBO3 expression was also associated with poorer overall survival and event-free survival in a subgroup of patients who received intensive chemotherapy (OS: P =  0.024; EFS: P =  0.040). Moreover, multivariate analysis indicated that high ROBO3 expression was an independent risk factor for poor overall survival in non-M3 acute myeloid leukemia patients who are younger than 60 and received intensive chemotherapy during remission induction. Bioinformatics analysis by Kyoto Encyclopedia of Genes and Genomes and Gene Ontology revealed that high ROBO3 expression significantly altered cell adhesion and extracellular matrix-related pathways (adjusted P <  0.05). Taken together, the data demonstrate that ROBO3 is upregulated in non-M3 acute myeloid leukemia and may be a potent biomarker of inferior prognosis.

Addition of Androgens Improves Survival in Elderly Patients With Acute Myeloid Leukemia: A GOELAMS Study

2017 ◽  
Vol 35 (4) ◽  
pp. 387-393 ◽  
Author(s):  
Arnaud Pigneux ◽  
Marie C. Béné ◽  
Philippe Guardiola ◽  
Christian Recher ◽  
Jean-Francois Hamel ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Maintenance Therapy ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Event Free Survival ◽  
Free Survival ◽  
Disease Free ◽  
Acute Myeloid

Purpose Elderly patients with acute myeloid leukemia (AML) have a poor prognosis, and innovative maintenance therapy could improve their outcomes. Androgens, used in the treatment of aplastic anemia, have been reported to block proliferation of and initiate differentiation in AML cells. We report the results of a multicenter, phase III, randomized open-label trial exploring the benefit of adding androgens to maintenance therapy in patients 60 years of age or older. Patients and Methods A total of 330 patients with AML de novo or secondary to chemotherapy or radiotherapy were enrolled in the study. Induction therapy included idarubicin 8 mg/m2 on days 1 to 5, cytarabine 100 mg/m2 on days 1 to 7, and lomustine 200 mg/m2 on day 1. Patients in complete remission or partial remission received six reinduction courses, alternating idarubicin 8 mg/m2 on day 1, cytarabine 100 mg/m2 on days 1 to 5, and a regimen of methotrexate and mercaptopurine. Patients were randomly assigned to receive norethandrolone 10 or 20 mg/day, according to body weight, or no norethandrolone for a 2-year maintenance therapy regimen. The primary end point was disease-free survival by intention to treat. Secondary end points were event-free survival, overall survival, and safety. This trial was registered at www.ClinicalTrials.gov identifier NCT00700544. Results Random assignment allotted 165 patients to each arm; arm A received norethandrolone, and arm B did not receive norethandrolone. Complete remission or partial remission was achieved in 247 patients (76%). The Schoenfeld time-dependent model showed that norethandrolone significantly improved survival for patients still in remission at 1 year after induction. In arms A and B, respectively, 5-year disease-free survival was 31.2% and 16.2%, event-free survival was 21.5% and 12.9%, and overall survival was 26.3% and 17.2%. Norethandrolone improved outcomes irrelevant to all prognosis factors. Only patients with baseline leukocytes > 30 × 109/L did not benefit from norethandrolone. Conclusion This study demonstrates that maintenance therapy with norethandrolone significantly improves survival in elderly patients with AML without increasing toxicity.

Selection of Elderly Acute Myeloid Leukemia Patients for Intensive Chemotherapy: Effectiveness of Intensive Chemotherapy and Subgroup Analysis

2014 ◽  
Vol 133 (3) ◽  
pp. 300-309 ◽  
Author(s):  
Dae Sik Kim ◽  
Ka Won Kang ◽  
Eun Sang Yu ◽  
Hong Jun Kim ◽  
Jung Sun Kim ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Subgroup Analysis ◽  
Myeloid Leukemia ◽  
Treatment Guideline ◽  
Definitive Treatment ◽  
Intensive Chemotherapy ◽  
Elderly Aml ◽  
Acute Myeloid

Background: Despite the advances in acute myeloid leukemia (AML) treatment, the prognosis of elderly patients remains poor and no definitive treatment guideline has been established. In the present study, we aimed to evaluate the effectiveness of intensive chemotherapy in elderly AML patients and to determine which subgroup of patients would be most responsive to the therapy. Methods: We retrospectively analyzed 84 elderly patients: 35, 19, and 30 patients were administered intensive chemotherapy, low-dose chemotherapy, and supportive care, respectively. Results: Among those who received intensive chemotherapy, there were 17 cases of remission after induction chemotherapy; treatment-related mortality was 22.9%. The median overall survival was 7.9 months. Multivariate analysis indicated that the significant prognostic factors for overall survival were performance status, fever before treatment, platelet count, blast count, cytogenetic risk category, and intensive chemotherapy. Subgroup analysis showed that intensive chemotherapy was markedly effective in the relatively younger patients (65-70 years) and those with de novo AML, better-to-intermediate cytogenetic risk, no fever before treatment, high albumin levels, and high lactate dehydrogenase levels. Conclusions: Elderly AML patients had better outcomes with intensive chemotherapy than with low-intensity chemotherapy. Thus, appropriate subgroup selection for intensive chemotherapy is likely to improve therapeutic outcome. © 2014 S. Karger AG, Basel

Improved Outcomes of Low-Dose Cytarabine Regimen By Increased Dose and Duration of Cytarabine in Combination with Oral Etoposide for Elderly Acute Myeloid Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1338-1338
Author(s):  
Seung-Hwan Shin ◽  
Seung-Ah Yahng ◽  
Jae-Ho Yoon ◽  
Byung-Sik Cho ◽  
Hee-Je Kim ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Oral Etoposide ◽  
Intensive Chemotherapy ◽  
Platelet Recovery ◽  
Low Dose Cytarabine ◽  
Acute Myeloid

Abstract Background: For elderly patients unfit for intensive chemotherapy in acute myeloid leukemia (AML), low-dose cytarabine (LDAC; 20 mg SQ BID for 10 days) still remains to be the standard treatment, despite its unsatisfactory complete response (CR) rate of 18% and median overall survival (OS) of < 6 months (Burnett, 2007). Recently, there have been huge efforts to develop more effective and less-toxic therapies, such as decitabine, azacitidine, clofarabine, or gemtuzumab ozogamicin, but their benefits were not concrete, even though they were compared to the classical LDAC. To improve outcomes of the classical LDAC, we modified it by giving a higher dose of cytarabine for an extended duration in combination with oral etoposide. Herein, we present the results. Methods: Between 2002 and 2014, 93 consecutive older (≥ 60 years) patients with AML, who were unfit for intensive chemotherapy, received 1st cycle of modified LDAC (mLDAC) regimen consisting of cytarabine (20 mg/m2 SQ BID) and oral etoposide (50 mg PO BID) for 14 days. Thereafter, they received additional subsequent cycles (for a maximum of 7 cycles) for 10 days every 6 to 8 weeks. We retrospectively analyzed their overall response (OR), disease-free survival (DFS), and overall survival (OS) rates. In this analysis, OR was defined as CR plus CR with incomplete platelet recovery (CRp) or blood count recovery (CRi). Results: The median age of patients in our cohort, including 69 (74.2%) with poor performance status (ECOG ≥ 2), 15 (16.1%) with AML with myelodysplastic-related changes or secondary AML, and 13 (14.0%) with poor cytogenetic risk, was 68 years (range, 60-83). The median number of mLDAC regimen cycles which they received was 2 (range, 1-8). Clinically relevant toxicities of grade III-IV including nausea/vomiting, diarrhea, hyperbilirubinemia and neutropenic fever were observed in 4 (4.3%) patients, 6 (6.5%), 3 (3.2%), and 42 (45.2%), respectively, which were comparable with those of classical LDAC (Burnett, 2007). The early mortality rates at 30 and 60 days were 11.8% and 15.0%, respectively. The OR was observed in 45 (48.4%) patients, including 34 (36.6%) CR, 7 (7.5%) CRp, and 4 (4.3%) CRi, within two cycles of mLDAC. With median follow-up duration of 26.1 months, the median DFS and OS were 6.2 and 15.8 months, respectively. For patients who achieved OR, they were 14.5 and 36.9 months, respectively. The OR of patients who had poor cytogenetic risk was not significantly different compared to others (57.1%, 46.2%, and 38.5% for favorable, intermediate, and poor cytogenetics, respectively; P=0.50). However, they showed significantly shorter median DFS (9.8, 6.6, and 5.1 months, respectively; P=0.01) and OS (NR, 1.4, and 5.1 months, respectively; P=0.01) with significantly shorter OR duration (30.6, 19.1, and 8.6 months, respectively; P=0.01). Between 2009 and 2014, among 17 patients treated with hypomethylating agents (HMA; 14 decitabine and 3 azacitidine), 1 CR and 3 partial response were achieved with a median survival of 5.5 months, and 5 patients after HMA treatment failure received subsequent mLDAC, and 3 achieved additional CR (n=2) and CRp (n=1). Conclusions: These results suggest that the outcomes of classical LDAC in elderly patients with AML can be improved by modifying it, with improved response and survival rates without increasing toxicities, even in patients with poor cytogenetics. Additionally, mLDAC could induce clinical responses in patients with HMA failure. Our mLDAC regimen may become another therapeutic option with emerging novel agents for elderly patients with AML, and these should be confirmed by large randomized trials. Disclosures No relevant conflicts of interest to declare.

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