A Homoharringtonine-Based Protocol Is Superior to Daunorubicin and Idarubicin-Based Protocols in Elderly Patients with Newly-Diagnosed Acute Myeloid Leukemia with Comparable Effects and Low Toxicities: Experience in a Chinese Center.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1946-1946
Author(s):  
Jianmin Wang ◽  
Shuqing Lü ◽  
Jianmin Yang ◽  
Xianmin Song ◽  
Li Chen ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Early Death ◽  
Newly Diagnosed ◽  
Survival Times ◽  
Free Survival ◽  
Elderly Aml ◽  
Acute Myeloid

Abstract Homoharringtonine (HHT) is a plant alkaloid which has been used in China for the treatment of acute myeloid leukemia (AML) and chronic myeloid leukemia for over 30 years. We present here a retrospective analysis designed to compare the efficacy and toxicity of HHT with daunorubicin (DNR) and idarubicin for the treatment of AML in elderly patients. Fifty-three patients over 60 years with newly diagnosed non-M3 AML between January 1998 and December 2007 were treated with cytarabine (Ara-c, 100mg/m2/day for 7 days) in combination with HHT (2mg/m2/day for 7 days; HA group; n=19), or DNR (40mg/m2/d for 3 days; DA group; n=16), or idarubicin (8mg/m2/d for 3 days; IDA group; n=18). In the HA group, 42.1% (8/19) of patients achieved complete remission (CR), 26.3% (5/19) of patients had partial remission (PR). In the DA group, the CR and PR rates were each 18.8% (3/16). In the IDA group, 55.5% (10/18) of patients achieved CR, 5.9% (1/18) patients had PR. The CR and OR rates were not significantly different between the three groups. However, whereas in the IDA and DA groups the early death rate within one month after chemotherapy was 33.3% (6/18) and 23.5% (4/16) respectively, there was no early death in the HA group. The estimated OS (overall survival) times were 23.2±7.9 months, 7.6 ±2.1 months, 14.0±3.4 months in HA, DA, and IDA groups (HA versus DA, P = 0.048; HA versus IDA, P = 0.678). The estimated mean disease-free survival (DFS) time of those patients who achieved CR in the HA group (44.3±17.3) were also significantly higher than those in the DA group (7.8±2.7; P = 0.047), and comparable with those in the IDA group (18.0±4.2; P = 0.598). In summary, the response to HA induction therapy was at least equal to that of DA and IDA induction, with relatively mild extramedullary toxicity and lower myocardial toxicity. So HHT is a particularly suitable candidate for the treatment of elderly AML patients.

scholarly journals Prognostic significance of serum ferritin levels on initial diagnosis in patients with acute myeloid leukemia

2021 ◽  
Vol 2 (4) ◽  
pp. 362-370
Author(s):  
Dejan Dudok ◽  
Marijana Virijević
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Serum Ferritin ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Early Death ◽  
Induction Phase ◽  
Free Survival ◽  
Disease Free ◽  
Acute Myeloid

Introduction/Aim: Acute myeloid leukemia (AML) is a heterogenous malignant disease whose course and outcome are influenced by a number of prognostic factors. Serum ferritin (SF) is often elevated in oncology patients, and it has been shown that it strongly influences an unfavorable outcome in various malignancies. The aim of this study is to assess the effect of high SF values on overall survival and disease-free survival, as well as to assess the correlation of SF values with other prognostic markers, such as clinical and laboratory parameters. Methods: Retrospective analysis included 108 patients diagnosed with AML at the Clinic for Hematology of the Clinical Center of Serbia (CCS), in Belgrade, in the period 2017 - 2019. Patients with acute promyelocytic leukemia, acute mixed lineage leukemia, secondary AML and patients treated with palliative therapy were excluded from the study. Patients were grouped based on the SF cutoff value of 800 µg/L. Results: Patients with higher SF values had a significantly higher incidence of early death (p = 0.020), sepsis in the induction phase of therapy (p < 0.010), and significantly lower initial hemoglobin levels (p = 0.040), as compared to patients with lower SF values. SF at diagnosis appeared to be a significant independent predictive factor of overall survival (p = 0.019) and of disease-free survival (p = 0.040). Conclusion: Our study showed a significant association of high SF values with sepsis in induction, early death, mean hemoglobin, overall survival, and disease-free survival. Identification of SF as an independent prognostic factor and a potential target site of the action of new drugs could contribute to a better prognosis of AML patients.

scholarly journals Decitabine Versus Intensive Chemotherapy for Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2713-2713 ◽  
Author(s):  
Eun-Ji Choi ◽  
Je-Hwan Lee ◽  
Han-Seung Park ◽  
Jung-Hee Lee ◽  
Miee Seol ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Myeloid Leukemia ◽  
Treatment Options ◽  
Induction Treatment ◽  
Intensive Chemotherapy ◽  
Newly Diagnosed ◽  
Monosomy 7 ◽  
Elderly Aml ◽  
Acute Myeloid

Abstract Background Elderly patients with acute myeloid leukemia (AML) has generally poor prognosis prognosis in accordance with their unfavorable clinical and biologic features. Hypomethylating agents have shown potential in the treatment of AML as well as myelodysplastic syndrome (MDS). In this retrospective study, we compared the outcomes of elderly AML patients according to induction treatment options: decitabine versus intensive chemotherapy. We also tried to identify specific subsets of patients who are most likely to benefit from decitabine or intensive chemotherapy. Methods This study included elderly patients aged 65 years or older who received induction treatment with decitabine or intensive chemotherapy for newly diagnosed AML at a single institute. The endpoints for this study were overall survival (OS), response, and event-free survival (EFS). Response included complete remission (CR), CR with incomplete hematologic recovery (CRi), and CR with partial hematologic recovery (CRh). Results A total of 107 patients, decitabine for 75 and intensive chemotherapy for 32, were analyzed. Decitabine was given as 20 mg/m2/day for 5 days every 4 weeks. Median 5 courses (range, 1-43) were delivered to the patients and 16 patients were still on decitabine treatment at the time of analysis. Intensive chemotherapy regimens included cytarabine plus daunoruribin (n=21) or idarubicin (n=10), and hyper-CVAD (n=1): 25 patients received one course and 7 received two courses for induction treatment. The rate for CR + CRi + CRh (CRR) was 38.6% (39 of 101 assessable patients). With a median follow-up duration of 14.8 months (95% confidence interval [CI], 12.0-22.8) among surviving patients, 79 patients died and 22 relapsed. The median OS and EFS were 12.3 months (95% CI, 10.0-14.7) and 4.1 months (95% CI, 2.5-5.7), respectively. Decitabine showed lower CRR (26.1% vs. 65.6, P<0.001) with similar EFS (median 3.4 vs. 6.1 months, P=.338) and OS (median 11.0 vs. 14.8 months, P=.124) compared to intensive chemotherapy (Figure 1). Multivariate analysis demonstrated that induction treatment option, peripheral blood (PB) blast percentage, and leukemia type (secondary vs. de novo) were independent risk factors for CRR. A presence of FLT3-ITD mutation, complex karyotype, and higher PB blast percentage were independently associated with shorter OS. Subgroup analysis for OS showed that intensive chemotherapy was superior to decitabine in patients with FLT3-ITD mutation (median 9.5 vs. 2.6 months, P=.025) and poor cytogenetic risk (10.8 vs. 6.1 months, P=.027), but decitabine showed tendency towards a longer OS compared to intensive chemotherapy in those with monosomy 7 or del(7q) (11.7 vs. 3.3 months, P=.093; Figure 2). Conclusion Decitabine showed similar OS to intensive chemotherapy despite of lower response rate in elderly AML patients. Clinical outcomes of specific subgroups seemed to be different according to induction treatment options. Further studies are warranted for selection of optimal treatment options for elderly AML patients. Disclosures No relevant conflicts of interest to declare.

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.

Prospective Randomized Comparison of Idarubicin and High-Dose Daunorubicin in Induction Chemotherapy for Newly Diagnosed Acute Myeloid Leukemia

2017 ◽  
Vol 35 (24) ◽  
pp. 2754-2763 ◽  
Author(s):  
Je-Hwan Lee ◽  
Hawk Kim ◽  
Young-Don Joo ◽  
Won-Sik Lee ◽  
Sung Hwa Bae ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Phase Iii ◽  
High Dose ◽  
Newly Diagnosed ◽  
Survival Times ◽  
Event Free Survival ◽  
Free Survival ◽  
Acute Myeloid

Purpose We compared two induction regimens, idarubicin (12 mg/m2/d for 3 days) versus high-dose daunorubicin (90 mg/m2/d for 3 days), in young adults with newly diagnosed acute myeloid leukemia (AML). Patients and Methods A total of 299 patients (149 randomly assigned to cytarabine plus idarubicin [AI] and 150 assigned to cytarabine plus high-dose daunorubicin [AD]) were analyzed. All patients received cytarabine (200 mg/m2/d for 7 days). Results Complete remission (CR) was induced in 232 patients (77.6%), with no difference in CR rates between the AI and AD arms (80.5% v 74.7%, respectively; P = .224). At a median follow-up time of 34.9 months, survival and relapse rates did not differ between the AI and AD arms (4-year overall survival, 51.1% v 54.7%, respectively; P = .756; cumulative incidence of relapse, 35.2% v 25.1%, respectively; P = .194; event-free survival, 45.5% v 50.8%, respectively; P = .772). Toxicity profiles were also similar in the two arms. Interestingly, overall and event-free survival times of patients with FLT3 internal tandem duplication (ITD) mutation were significantly different (AI v AD: median overall survival, 15.5 months v not reached, respectively; P = .030; event-free survival, 11.9 months v not reached, respectively; P = .028). Conclusion This phase III trial comparing idarubicin with high-dose daunorubicin did not find significant differences in CR rates, relapse, and survival. Significant interaction between the treatment arm and the FLT3-ITD mutation was found, and high-dose daunorubicin was more effective than idarubicin in patients with FLT3-ITD mutation.

Intensively timed induction therapy followed by autologous or allogeneic bone marrow transplantation for children with acute myeloid leukemia or myelodysplastic syndrome: a Childrens Cancer Group pilot study.

1993 ◽  
Vol 11 (8) ◽  
pp. 1448-1457 ◽  
Author(s):  
W G Woods ◽  
N Kobrinsky ◽  
J Buckley ◽  
S Neudorf ◽  
J Sanders ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Cancer Group ◽  
Acute Myeloid

PURPOSE Childrens Cancer Group (CCG) protocol 2861 was designed to test the feasibility of aggressively timed induction therapy followed by autologous or allogeneic bone marrow transplantation (BMT) as the sole postremission therapy for newly diagnosed children with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). PATIENTS AND METHODS Between April 1988 and October 1989, 142 patients were eligible for study. All patients entered received a timing-intensive five-drug induction of dexamethasone, cytarabine (Ara-C), thioguanine, etoposide, and daunorubicin (DCTER) over 4 days with a second cycle administered after 6 days of rest, irrespective of hematologic status at that time. Most patients subsequently received a second two-cycle induction course. Those who achieved remission were eligible for bone marrow ablative therapy with busulfan and cyclophosphamide, followed by 4-hydroperoxy-cyclophosphamide (4-HC)-purged autologous or allogeneic BMT rescue. RESULTS One hundred eight (76%) patients achieved remission: 19 (13%) died of complications of the leukemia and/or chemotherapy, and 15 (11%) failed to achieve remission. Seventy-four patients subsequently underwent BMT with either autologous (n = 58) or allogeneic (n = 16) rescue. For patients who received autologous rescue with 4-HC-purged grafts, the actuarial disease-free survival (DFS) rate at 3 years from the day of transplant is 51%, compared with 55% for patients who received allogeneic grafts (P = .92). At 3 years, the overall actuarial survival rate for all 142 patients entered on this study is 45%, with an event-free survival (EFS) rate of 37%. Adverse prognostic factors for outcome included an elevated WBC count or the presence of CNS leukemia at the time of AML diagnosis. CONCLUSION Results suggest that aggressively timed induction therapy followed by marrow ablation and BMT rescue with either autologous or allogeneic grafts for children with newly diagnosed AML or MDS is both feasible and effective.

scholarly journals A novel nutritional index “simplified CONUT” and the disease risk index independently stratify prognosis of elderly patients with acute myeloid leukemia

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hajime Senjo ◽  
Masahiro Onozawa ◽  
Daisuke Hidaka ◽  
Shota Yokoyama ◽  
Satoshi Yamamoto ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Nutritional Status ◽  
Risk Stratification ◽  
Elderly Patients ◽  
Myeloid Leukemia ◽  
The Elderly ◽  
Genetic Alterations ◽  
Newly Diagnosed ◽  
Hematopoietic Stem ◽  
Acute Myeloid

Abstract Elderly patients aged 65 or older with acute myeloid leukemia (AML) have poor prognosis. The risk stratification based on genetic alteration has been proposed in national comprehensive cancer network (NCCN) guideline but its efficacy was not well verified especially in real world elderly patients. The nutritional status assessment using controlling nutritional status (CONUT) score is a prognostic biomarker in elderly patients with solid tumors but was not examined in elderly AML patients. We performed prospective analysis of genetic alterations of 174 patients aged 65 or older with newly diagnosed AML treated without hematopoietic stem cell transplantation (HSCT) and developed simplified CONUT (sCONUT) score by eliminating total lymphocyte count from the items to adapt AML patients. In this cohort, both the NCCN 2017 risk group and sCONUT score successfully stratified the overall survival (OS) of the elderly patients. A multivariable analysis demonstrated that adverse group in NCCN 2017 and high sCONUT score were independently associated with poor 2-year OS. Both risk stratification based on NCCN 2017 and sCONUT score predict prognosis in the elderly patients with newly diagnosed AML.

Clinical relevance of P-glycoprotein expression in de novo acute myeloid leukemia

Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 1997-2004 ◽  
Author(s):  
G Del Poeta ◽  
R Stasi ◽  
G Aronica ◽  
A Venditti ◽  
MC Cox ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Normal Karyotype ◽  
Free Survival ◽  
Negative Phenotype ◽  
Acute Myeloid

Abstract Cytofluorimetric detection of the multidrug resistance (MDR)-associated membrane protein (P-170) was performed at the time of diagnosis in 158 patients with acute myeloid leukemia using the C219 monoclonal antibody (MoAb). In 108 of these cases the JSB1 MoAb was also tested. An improved histogram subtraction analysis, based on curve fitting and statistical test was applied to distinguish antigen-positive from antigen-negative cells. A marker was considered positive when more than 20% of the cells were stained. At onset, P-170 was detected in 43% of cases with C219 and in 73% of cases with JSB1. There was a strict correlation between C219 and JSB1 positivity, as all C219+ cases were also positive for JSB1 MoAb (P < .001). No relationship was found between sex, age, organomegaly, and MDR phenotype. Significant correlation was found between CD7 and both C219 and JSB1 expression (P < .001 and .001, respectively). C219-negative phenotype was more often associated with a normal karyotype (24 of 55 with P = .030). Rhodamine 123 (Rh123) staining and flow cytometry analysis showed a significantly decreased mean fluorescence in 51 C219+ and 38 JSB1+ patients compared to 42 MDR negative ones (P < .001). The rate of first complete remission (CR) differed both between C219+ and C219- cases and between JSB+ and JSB- ones (30.9% v 71.1% and 35.4% v 93.1%, respectively, P < .001). Of the 21 C219+ patients who had yielded a first CR, 19 (90.4%) relapsed, compared with 28 of 64 (43.7%) C219- patients (P < .001). Of the 28 JSB1+ patients in first CR, 17 (60.7%) relapsed relative to 8 (29.6%) of 27 JSBI- ones (P = .021). A higher rate of relapses among MDR+ compared with MDR- patients was observed both for C219 and JSB1 MoAbs taken separately (C219 80% v 44%; JSB1 52% v 27%), with no relationship to age. The survival rates (Kaplan-Meyer method) were significantly shorter both in C219+ patients and in JSB1+ cases (P < .001). Disease-free survival curves followed this same trend. The combination (C219- JSB1+) identified a subset of patients with an intermediate outcome compared to C219 positive cases. The prognostic value of both markers (C219 and JSB1) was confirmed in multivariate analysis. These results suggest that the assessment of MDR phenotype by flow cytometry may be an important predictor of treatment outcome.

Low Platelet Counts at Diagnosis Predict Better Survival for Patients with Intermediate-Risk Acute Myeloid Leukemia

2019 ◽  
Vol 143 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Yimin Zhang ◽  
Haihui Gu ◽  
Qi Chen ◽  
Ying Zhang ◽  
Hui Cheng ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Negative Impact ◽  
Disease Free Survival ◽  
Intermediate Risk ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Risk Patients ◽  
Immature Cells ◽  
Acute Myeloid

Background: Aggressive growth of primitive and immature cells in the bone marrow results in reductions in megakaryocyte and platelet (PLT) counts, leading to thrombocytopenia in acute myeloid leukemia (AML). However, not all AML patients show thrombocytopenia at the time of diagnosis, and the association of PLT count with patient survival is largely unknown. Methods: A retrospective study was performed to determine PLT counts at diagnosis in the peripheral blood in 291 newly diagnosed AML patients and assess the association of PLT counts with the overall survival (OS) and disease-free survival (DFS) of these patients. Results: Low PLT counts (≤40 × 109/L) were associated with better outcomes for the whole cohort (5-year OS, 55.1 ± 3.8 vs. 35.3 ± 3.5%, p < 0.001; 5-year DFS, 49.1 ± 3.8 vs. 25.7 ± 4.0%, p < 0.001) and intermediate-risk patients (5-year OS, 64.5 ± 5.4 vs. 41.0 ± 4.8%, p < 0.001; 5-year DFS, 60.8 ± 5.6 vs. 28.6 ± 5.6%, p < 0.001). Moreover, low PLT counts were related to deeper molecular remission. Low PLT counts correlated with better survival of intermediate-risk AML patients treated with chemotherapy only. Allogeneic hematopoietic stem cell transplantation attenuated the negative impact of high PLT counts on the survival of intermediate-risk patients. Furthermore, univariate and multivariate analyses demonstrated that PLT count at diagnosis was an independent prognostic factor for intermediate-risk AML. Conclusion: PLT count at diagnosis predicts survival for patients with intermediate-risk AML.

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