scholarly journals Analyzing How Elderly Acute Myeloid Leukemia Patients Are Treated, an Institutional Experience

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5849-5849
Author(s):  
Christopher Allen Willner ◽  
Mohammad Muhsin Chisti ◽  
Michaela Soriano ◽  
James Huang
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Data Analysis ◽  
Induction Therapy ◽  
Acute Myelogenous Leukemia ◽  
Myeloid Leukemia ◽  
Myelogenous Leukemia ◽  
Elderly Populations ◽  
Acute Myelogenous ◽  
Acute Myeloid

Rationale: Treatment of acute myelogenous leukemia (AML) remains a challenge in elderly populations, those with comorbid conditions, and patients with poor performance status indices. The optimal choice for induction therapy as well as further agent selection is unclear, and current guidelines recommend enrollment in a controlled clinical trial. Methods: Institutional cases of AML via an electronic medical record query performed in November 2017 containing cases of AML in patients 65 years of age or greater from 01/01/2000 to 06/21/2017 were extracted. Instances of acute myelogenous leukemia were identified by ICD codes. Age, gender, induction therapy, cytogenetics, molecular analyses, and overall survival were collected. Results: A total of 61 cases of AML in patients aged 65 or greater were identified, with those having incomplete data being excluded from analysis. The mean age of included patients was 78.9 years of age, 35 were male and 26 were female. 60 confirmed deaths were recorded. 26 patients received conventional 7+3 (42.6%), 22 received a hypomethylating agent (HMA) (31.1%), 16 (26.2%) did not receive treatment. Conclusion: Our institutional data showed overall survival was significantly longer when treated with 7+3, 354 days (95% CI [93, 614]), vs. 61 days (95% CI [15, 107]). Similarly, OS was significantly longer when treated with HMA, 303 days (95% CI [23, 583]). Risk of death, accordingly, was as follows: 7+3 HR .347 (.179-.672), HMA HR .348 (.173-.703). Our institutional mortality data reasonably reflected SEER data analysis reported by Medeiros et al concerning untreated patients, but trended toward a greater OS for those treated with 7+3 or HMA. Registry data, as well as our institutional data, demonstrate a survival benefit to intensive chemotherapy and palliative chemotherapy, while controlled trials have not shown this benefit consistently in elderly populations. Practices regarding induction therapy vary greatly between institutions. Determination of which elderly patients to treat with intensive therapy remains difficult. References: Almeida AM, Ramos F. Acute myeloid leukemia in the older adults. Leuk Res Rep. 2016;6:1-7. Eleni LD, Nicholas ZC, Alexandros S. Challenges in treating older patients with acute myeloid leukemia. J Oncol. 2010;2010:943823. Medeiros BC, Satram-hoang S, Hurst D, Hoang KQ, Momin F, Reyes C. Big data analysis of treatment patterns and outcomes among elderly acute myeloid leukemia patients in the United States. Ann Hematol. 2015;94(7):1127-38. Disclosures Chisti: Eli Lilly: Speakers Bureau; Medscape: Honoraria; UpToDate: Honoraria.

Results of High Dose Chemotherapy and Autologous Stem Cell Transplantation in Patients with Acute Myeloid Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5438-5438
Author(s):  
Kenneth A. Ault ◽  
Delvyn Caedren Case ◽  
Marjorie A. Boyd ◽  
Thomas J. Ervin ◽  
Frederick Aronson ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Acute Myelogenous Leukemia ◽  
Myeloid Leukemia ◽  
Medical Center ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Transplant Program ◽  
Maine Medical ◽  
Acute Myelogenous ◽  
Acute Myeloid

Abstract 43 patients with acute myeloid leukemia have undergone transplantation at our institution over the past 14 years. Patient selection criteria included age less than 70 years, creatinine less than 2mg/ml, no active infection, cardiac ejection fraction >40%, DLCO > 50% of predicted and no other co-morbid conditions that would jeopardize survival. 39 patients were in first remission, 4 were in second or higher remission. 3 patients had favorable cytogenetics, 40 had intermediate or unfavorable cytogenetics. After achieving remission for at least 30 days, patients were consolidated with Etoposide and AraC, followed by G-CSF. Hematopoietic stem cells were collected when the WBC rebounded to at least 10,000/μl. The target dose of CD34 positive cells was 5×106/kg. The minimum dose given was 2.3 × 106/kg). High dose therapy consisted of Busulfan 1mg/kg and Etoposide 60mg/kg. The average age at transplantation was 42 years (range 20 to 61). Days of neutropenia (AGC<500/μl) ranged from 2 to 10 (average 5.2). The median length of follow up is 4.0 years. Kaplan-Meier progression-free survival is 38% at 5 years and 35% at 10 years. Currently 26 patients are alive, and 23 are free from progression. Overall survival is 60%. Maine Medical Center Autologous HPC Transplant Program Acute Myelogenous Leukemia Maine Medical Center Autologous HPC Transplant Program Acute Myelogenous Leukemia

Targeted Intravenous Busulfan and Fludarabine Allogeneic Transplantation Conditioning in Acute Myeloid Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2290-2290
Author(s):  
Joseph A. Pidala ◽  
Jongphil Kim ◽  
Claudio Anasetti ◽  
Melissa Alsina ◽  
Ernesto Ayala ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Large Series ◽  
Myelogenous Leukemia ◽  
Secondary Aml ◽  
Relapsed Disease ◽  
Acute Myeloid

Abstract Abstract 2290 Poster Board II-267 Reduced and intermediate intensity conditioning with allogeneic hematopoietic cell transplantation (HCT) offers promise to effectively control hematologic malignancies, while limiting treatment related toxicity and mortality (TRM). We aimed to examine the efficacy of IV targeted Busulfan and Fludarabine (IV-Bu/Flu) in a large series of adults with exclusively acute myelogenous leukemia (AML). One hundred adults (median age 48) with AML (CR1 49, CR2 25, REL1 8, REL2 1, PIF 16, untreated 1) were treated with Busulfan 130-145 mg/m2/day for four days with pharmacokinetic targeting on the final two days to achieve an area under the curve (AUC) of 5300 (+/-10%) μmol*min/L/day and Fludarabine 40mg/m2/day for 4 days, followed by transplantation of G-CSF mobilized peripheral blood stem cells (PBSC) (N=98) or unstimulated bone marrow (BM) (N=2) from allogeneic donors (MRD 38, MUD 38, MMUD 24). Acute GVHD prophylaxis consisted of tacrolimus/methotrexate (N = 77), tacrolimus/mycophenolate mofetil (N = 22), or tacrolimus/sirolimus (N = 1). Median time to neutrophil and platelet engraftment was 16 and 12 days, respectively. Non-relapse mortality was 3% at 100 days, and 15% by 1 year. The cumulative incidence of relapse was 41%. Overall survival (OS) was 59% (95% CI: 48.1 – 67.5) at 1 year, and 42% (95% CI: 30.8-53.3) at 4 years. OS at 4 years for primary AML in CR1, secondary AML in CR1, CR2, and PIF were 52.9%, 40.1%, 41.2%, and 57.5% respectively; none with relapsed disease survived to 4 years (log-rank p = 0.0014). Progression-free survival (PFS) was 53% (95% CI: 42.8 – 62.2) at 1 year, and 32.3% (95% CI: 21.8 – 43.2) at 4 years. PFS at 4 years for primary AML in CR1, secondary AML in CR1, CR2, and PIF were 44.1%, 33.4%, 33.9%, and 33.1%, respectively, while none with relapsed disease at transplant reached this endpoint (p = 0.0264). On multivariable modeling, remission status at HCT (relapsed disease HR 14.85 (95% CI: 2.12 - 104.2), p = 0.007), moderate/severe cGVHD (HR 0.281, 95% CI: 0.10 - 0.76; p = 0.013), and day 90 bone marrow (BM) chimerism ≥ 90% (HR 0.245, 95% CI: 0.08 - 0.79; p = 0.018) predicted overall survival, and day 90 BM chimerism ≥ 90% (HR of 0.18 (95% CI: 0.08 - 0.45), p = 0.0002) predicted PFS. The following were not significantly related with OS or PFS: age, cytogenetics, donor relation, number of induction cycles, aGVHD prophylaxis regimen, maximum aGVHD grade, WBC at diagnosis, time in first CR, or % BM blasts prior to transplant. Day 90 BM chimerism and cGVHD were significantly related with relapse. Maximum grade of aGVHD predicted non-relapse mortality. These data support the low TRM and efficacy of IV-Bu/Flu in a large series of exclusively AML patients, and demonstrate the impact of day 90 bone marrow chimerism as an important prognostic factor. Further efforts to mitigate relapse risk after HCT are warranted, particularly in those with advanced disease at time of transplant. Disclosures: Off Label Use: IV busulfan and fludarabine for the treatment of acute myeloid leukemia. Alsina:Ortho Biotech: Research Funding, Speakers Bureau; Millenium: Research Funding, Speakers Bureau. Field:PDL BioPharma: Research Funding. Fernandez:Otsuka: Honoraria.

Daunorubicine, Cytarabine and Cladribine (DAC) Vs Daunorubicine and Cytarabine (DA) Induction Treatment in Elderly Acute Myeloid Leukemia (AML) Patients – Results of the Prospective, Multicenter, Randomized Trial of the Polish Adult Leukemia Group (PALG)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3602-3602
Author(s):  
Agnieszka Pluta ◽  
Tadeusz Robak ◽  
Agata Wrzesien-Kus ◽  
Bozena Katarzyna Budziszewska ◽  
Kazimierz Sulek ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Treatment Option ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Performance Status ◽  
Hematological Toxicity ◽  
Proportional Hazard ◽  
Newly Diagnosed ◽  
Acute Myeloid

Abstract Abstract 3602 Background: AML in elderly patients is associated with very poor prognosis. The best treatment option for this group of patients is not established, yet. The intensity of treatment depends on performance status and comorbidities. The previous PALG AML study showed that addition of cladribine (2CdA) to conventional induction therapy; especially in patients above 40 yrs, is associated with better outcome (Ho3owiecki 2004). Based on this observation we designed a study addressed to newly diagnosed AML patients above 60 yrs old, who were fit enough to intensive treatment. Aim: To verify whether addition of 2CdA has an impact to clinical outcome in newly diagnosed AML patients older than 60 years old. Methods: From October 2004 to November 2011, 178 patients from 16 hematological PALG centers were randomly assigned to DA induction therapy consisting of daunorubicine (DNR) 45mg/m2, intravenously (iv), day 1–3 and cytarabine (AraC) 100 mg/m2, iv, day 1–7 (DA) or DA with addition of 2CdA 5mg/m2, iv, day 1–5 (DAC). Patients, who achieved complete remission (CR), received one course of consolidation with mitoxantron 6mg/m2 iv day1–2 and AraC 100mg/m2 iv day 1–5, followed by six cycles of maintenance consisting of (DNR 30mg/m2 iv day 1–2 with AraC 100mg/m2 sc day 1–5 and tioguanine 100mg/m2, p.o., twice day, day 1–5 with AraC 100mg/m2 s.c. day 1–5, alternately). Response criteria were determined according to revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia (Chesson 2003). Statistical analysis: Pairwise comparisons between patient characteristics were performed by the Mann-Whitney U-test for continuous variables and by χ2-statistics or Fisher's exact test for categorical variable. The Kaplan-Meier estimates of survival were calculated and compared using the log-rank test. For multivariate analysis, the Cox proportional hazard regression model was applied. P values < 0.05 were considered significant. Results: 88 pts with median age 66 yrs (range 60–79 yrs) were randomized to DA and 90 pts with median age 64 yrs (range 60–79 yrs) was enrolled to DAC schema. The both groups were comparable in terms of age, sex, performance status, white blood cell count, hemoglobin level, platelets count, tumor burden parameters, cytogenetic, between the both groups. The overall CR rate was 38%. In DA and DAC groups CR was achieved in 33% and 43% pts, respectively (p=0.12). However, in patients under 65 yrs the trend towards higher CR rate in DAC arm than DA group was observed (47% vs. 29%, p=0.09). In pts above 65 yrs the CR rate was comparable (39% vs. 38%, p=0.8). The efficacy and hematological toxicity in DA and DAC groups was similar (Table 1). Also no statistical significant differences in non-hematological toxicity were observed (data not shown). Early deaths in DA and DAC did not differ significantly. Median overall survival (OS) in DA and DAC arm was also similar in both groups (Table 1). In proportional hazard Cox analysis only age under 65yo, CR achievement and WBC above 100G/L were important for better OS (p=0.02, p<0.001 and p=0.09). The presence of dysplastic changes, karyotype, LDH, number of bone marrow blasts did not influenced OS. Conclusions: Our data suggest that prolonged overall survival can be achieved in elderly AML patients mainly till 65yrs. Intensive therapy, especially in patients older than 65yrs, may be associated with high number of complications what results withdrawing from intensive treatment protocol. Hematological and non-hematological toxicity of DA and DAC schema is comparable, however higher CR rate in DAC group in patient till 65yrs may suggest, that addition of 2CdA to DA does not increase toxicity and may be a treatment option in this patient population. Disclosures: Wiktor-Jedrzejczak: Janssen-Cilag: Consultancy; Amgen: Consultancy; Novartis: Consultancy, Speakers Bureau; Pfizer: Consultancy; Bayer: Consultancy; Genopharm: Speakers Bureau; Celgene: Speakers Bureau; Genzyme: Speakers Bureau; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Addition of Lomustine to Idarubicin and Cytarabine Improves the Outcome of Elderly Patients With De Novo Acute Myeloid Leukemia: A Report From the GOELAMS

2010 ◽  
Vol 28 (18) ◽  
pp. 3028-3034 ◽  
Author(s):  
Arnaud Pigneux ◽  
Jean-Luc Harousseau ◽  
Francis Witz ◽  
Mathieu Sauvezie ◽  
Marie-Christine Bene ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Elderly Patients ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Group I ◽  
Acute Myeloid

Purpose No significant improvement in treatment outcome has been seen in elderly patients with acute myeloid leukemia (AML) over the past 20 years. This retrospective analysis investigated the prognostic factors for complete remission (CR) and survival in older patients with AML. Patients and Methods The study involved 847 patients older than 60 years enrolled onto three trials carried out in France between 1995 and 2005. Induction therapy consisted of idarubicin (8 mg/m2, days 1 through 5) and cytarabine (100 mg/m2, days 1 through 7; group I, 339 patients) or the same drugs plus lomustine (200 mg/m2 orally on day 1; group II, 508 patients). Consolidation therapy consisted of anthracycline and cytarabine courses at lower doses, preceded or not by a first course of intermediate-dose cytarabine. Results The rate of CR was significantly higher in patients in group II compared with group I (68% v 58%; P = .002). The rate of toxic death was similar in the two groups. In multivariate analysis, two prognostic factors were linked to CR: nonadverse cytogenetic (P < .003) and addition of lomustine to induction chemotherapy (P = .002). Median overall survival was significantly improved in patients treated with lomustine (median and SE, 12.7 ± 2.2 months v 8.7 ± 2.7 months; P = .004). In multivariate analysis, five prognostic factors positively affected overall survival: addition of lomustine (P = .002), age ≤ 69 years (P < .001), Eastern Cooperative Oncology Group performance status lower than 2 (P = .002), French-American-British subgroup 1/2 (P = .02), and nonadverse cytogenetic (P < .001). Conclusion Lomustine improves the rate of CR and survival in elderly patients with de novo AML when added to standard induction therapy.

Geriatric Assessment Predicts Overall Survival Among Older Adults Receiving Induction Chemotherapy for Acute Myelogenous Leukemia.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1535-1535 ◽  
Author(s):  
Heidi D. Klepin ◽  
Janet A. Tooze ◽  
Ann M. Geiger ◽  
Stephen Kritchevsky ◽  
Jeff Williamson ◽  
...  
Keyword(s):  
Older Adults ◽  
Overall Survival ◽  
Activities Of Daily Living ◽  
Grip Strength ◽  
Geriatric Assessment ◽  
Induction Therapy ◽  
Acute Myelogenous Leukemia ◽  
Daily Living ◽  
Myelogenous Leukemia ◽  
Acute Myelogenous

Abstract Abstract 1535 Background: Acute myelogenous leukemia (AML) is a disease which largely affects older adults, for whom optimal therapy is unclear. Evidence-based strategies to identify those older adults who may tolerate and benefit from standard therapies are lacking. Objective: Evaluate the predictive value of bedside geriatric assessment (GA) on overall survival (OS) for older adults receiving induction therapy for AML. Methods: Ongoing prospective study of patients ≥60 years of age with newly diagnosed AML and planned induction chemotherapy admitted to Wake Forest University. Bedside GA was performed during inpatient work-up for AML. GA measures included the Modified Mini-Mental Status Exam (3MS), Center for Epidemiologic Studies Depression Scale (CES-D), Distress thermometer, Pepper Assessment Tool for Disability ([PAT-D], includes self- reported activities of daily living (ADL), instrumental activities of daily living (IADL), and mobility questions), Short Physical Performance Battery ([SPPB], includes timed 4-meter walk, chair stands, standing balance), and grip strength. Cox proportional hazards models were fit for each GA measure as a predictor of OS, controlling for age, gender, Eastern Cooperative Oncology Group (ECOG) score, Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) score, and cytogenetic risk group. The median follow-up was 4.7 months. Results: Among 53 consecutive patients the mean age was 69 (SD 11.5) years, 59.3% were female, and 46.3% had significant comorbidity (HCT-CI score >1). The majority had intermediate (72.6%) or poor risk (23.6%) cytogenetics. Approximately two thirds (64.7%) received standard induction therapy with anthracycline, cytarabine ± etoposide. Mean baseline GA scores included: 3MS 82.4 (SD 9.6), CES-D 13.5 (SD 11.3), Distress 4.2 (SD 3.3), PAT-D 1.6 (SD 0.6), SPPB 6.4 (SD 4.2), grip strength 32.0 kilograms (SD 8.5). In adjusted analyses, better performance on the cognitive screen (3MS) was associated with improved OS (HR 0.94, 95% CI 0.89–0.99). There was a trend towards worse OS among individuals who screened positive for depression at baseline (CES-D>16) (HR 2.3, 95% CI 0.75–6.80) and among those with a slower gait speed (< 1 meter/second) (HR 5.9, 95% CI 0.80–45.3). Additional baseline GA measures were not associated with OS in this analysis. Conclusions: Geriatric assessment measures may independently predict OS among older adults receiving induction therapy for AML. If validated in future studies, these screening measures may improve risk stratification and inform interventions to improve outcomes for older adults with AML. Supported by the American Society of Hematology Scholar Award, Atlantic Philanthropies, the John A. Hartford Foundation, ASP, and the WFU Pepper Center (P30 AG-021332). Disclosures: No relevant conflicts of interest to declare.

scholarly journals The expression of PTEN and INPP4B and their clinical significance in patients with acute myeloid leukemia

2019 ◽  
Vol 17 ◽  
pp. 205873921985740
Author(s):  
Haobin Song ◽  
Yuanda Zhang ◽  
Yan Liu ◽  
Haiyan Hu ◽  
Qing Zhao ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Quantitative Polymerase Chain Reaction ◽  
Myelogenous Leukemia ◽  
Control Group ◽  
Inositol Polyphosphate ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Acute Myelogenous ◽  
Acute Myeloid

This study investigates the expression of phosphatase and tensin homolog (PTEN) and Inositol polyphosphate 4-phosphatase type II (INPP4B) in children with acute myeloid leukemia. The levels of PTEN and INPP4B in bone marrow, from 95 acute myelogenous leukemia (AML) patients and 84 controls, respectively, were assessed by immunohistochemistry, quantitative polymerase chain reaction (qPCR), and Western blot. The prognosis was followed up and investigated and the correlation analysis was made. We found that the expression levels of PTEN and INPP4B were significantly lower in the AML group than those in the control group ( P < 0.05). The survival time was lower in PTEN and INPP4B negative children relative to PTEN and INPP4B positive children ( P < 0.05). In AML patients, INPP4B and PTEN expression was positively correlated (r = 0.552, P = 0.000). In conclusion, the levels of INPP4B and PTEN were reduced significantly and correlated positively in AML patients accompanying with abnormal karyotypes. The current investigation of INPP4B and PTEN could give new insight into targeted therapy for AML.

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