Results of the Hyper-CVAD Regimen in Elderly Acute Lymphocytic Leukemia (ALL)

Abstract Background. Understanding the causes of failure in older patients with ALL may help improve treatment strategies for this age group. Study Aims. To define the causes of death in older (age ≥60 years) patients with ALL during induction and consolidation-maintenance with the dose intensive Hyper-CVAD regimen, and compare their outcome to those of older patients treated previously with less intensive regimens, and to those of younger patients treated with Hyper-CVAD. Study Groups. 122 older patients treated with Hyper-CVAD were compared with 34 older patients treated with less intensive regimens, and 409 younger patients treated with Hyper-CVAD. Results. The outcome in older patients on Hyper-CVAD, older patients on other regimens, and younger patients on Hyper-CVAD are shown in the Table. Conclusion. Intensifying the chemotherapy in older patients with ALL reduced the incidence of leukemia resistance but increased the incidence of death in CR from myelosuppression-associated infections. The overall benefit: risk was favorable. Identifying novel low-intensity agents/regimens for older patients with ALL may improve the results. Parameter Older; Hyper CVAD Older; Other Younger; Hyper CVAD P value Most deaths during induction and in CR were related to infections Number 122 34 409 % CR 84 59 92 <0.001 % Induction mortality 10 12 2 NS for older % Resistance 5 27 2 <0.001 % Death in CR 34 15 7 <0.001 % Relapse 40 80 48 0.004 % 5-year survival 20 9 48 <0.001

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Clinical Characteristics and Outcome of Young Chronic Lymphocytic Leukemia Patients: A Single Institution Study of 204 Cases

Blood ◽

10.1182/blood.v94.2.448 ◽

1999 ◽

Vol 94 (2) ◽

pp. 448-454 ◽

Cited By ~ 147

Author(s):

Francesca R. Mauro ◽

Robert Foa ◽

Diana Giannarelli ◽

Iole Cordone ◽

Sabrina Crescenzi ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Clinical Features ◽

Median Survival ◽

Survival Probability ◽

Older Patients ◽

Lymphocytic Leukemia ◽

Second Primary ◽

Age Group ◽

Single Institution ◽

Younger Patients

Abstract A retrospective analysis on chronic lymphocytic leukemia (CLL) patients ≤55 years observed at a single institution was performed with the purpose of characterizing the clinical features and outcome of young CLL and of identifying patients with different prognostic features. Over the period from 1984 to 1994, 1,011 CLL patients (204 [20%] ≤55 years of age and 807 [80%] >55 years of age) were observed. At diagnosis, younger and older patients displayed a similar distribution of clinical features, except for a significantly higher male/female ratio in younger patients (2.85 v 1.29;P < .0001). Both groups showed an elevated rate of second primary cancers (8.3% v 10.7%), whereas the occurrence of Richter’s syndrome was significantly higher in younger patients (5.9% v 1.2%; P < .00001). Younger and older patients showed a similar overall median survival probability (10 years) but were characterized by a different distribution of causes of deaths: CLL unrelated deaths and second primary malignancies predominated in the older age group, whereas the direct effects of leukemia were prevalent in the younger age group. Although younger and older patients displayed a similar survival, the evaluation of the relative survival rates showed that the disease had a greater adverse effect on the expected survival probability of the younger population. Multivariate analysis showed that for young CLL patients only dynamic parameters, such as lymphocyte doubling time and other signs of active disease, were the independent factors that significantly influenced survival probability (P = .00001). A prolonged clinico-hematologic follow-up allowed us to identify two subsets of young CLL patients with a different prognostic outcome: a group of patients (40%) with long-lasting stable disease without treatment and an actuarial survival probability of 94% at 12 years from diagnosis and another group (60%) with progressive disease and a median survival probability of 5 years after therapy. For the latter patients, the therapeutic effect of innovative therapies with curative intents needs to be investigated in prospective, comparative clinical trials.

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Clinical Characteristics and Outcome of Young Chronic Lymphocytic Leukemia Patients: A Single Institution Study of 204 Cases

Blood ◽

10.1182/blood.v94.2.448.414k13_448_454 ◽

1999 ◽

Vol 94 (2) ◽

pp. 448-454

Author(s):

Francesca R. Mauro ◽

Robert Foa ◽

Diana Giannarelli ◽

Iole Cordone ◽

Sabrina Crescenzi ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Clinical Features ◽

Median Survival ◽

Survival Probability ◽

Older Patients ◽

Lymphocytic Leukemia ◽

Second Primary ◽

Age Group ◽

Single Institution ◽

Younger Patients

A retrospective analysis on chronic lymphocytic leukemia (CLL) patients ≤55 years observed at a single institution was performed with the purpose of characterizing the clinical features and outcome of young CLL and of identifying patients with different prognostic features. Over the period from 1984 to 1994, 1,011 CLL patients (204 [20%] ≤55 years of age and 807 [80%] >55 years of age) were observed. At diagnosis, younger and older patients displayed a similar distribution of clinical features, except for a significantly higher male/female ratio in younger patients (2.85 v 1.29;P < .0001). Both groups showed an elevated rate of second primary cancers (8.3% v 10.7%), whereas the occurrence of Richter’s syndrome was significantly higher in younger patients (5.9% v 1.2%; P < .00001). Younger and older patients showed a similar overall median survival probability (10 years) but were characterized by a different distribution of causes of deaths: CLL unrelated deaths and second primary malignancies predominated in the older age group, whereas the direct effects of leukemia were prevalent in the younger age group. Although younger and older patients displayed a similar survival, the evaluation of the relative survival rates showed that the disease had a greater adverse effect on the expected survival probability of the younger population. Multivariate analysis showed that for young CLL patients only dynamic parameters, such as lymphocyte doubling time and other signs of active disease, were the independent factors that significantly influenced survival probability (P = .00001). A prolonged clinico-hematologic follow-up allowed us to identify two subsets of young CLL patients with a different prognostic outcome: a group of patients (40%) with long-lasting stable disease without treatment and an actuarial survival probability of 94% at 12 years from diagnosis and another group (60%) with progressive disease and a median survival probability of 5 years after therapy. For the latter patients, the therapeutic effect of innovative therapies with curative intents needs to be investigated in prospective, comparative clinical trials.

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Abstract 17469: Comparing the Effect of CRT Implantation on Quality of Life in Older Patients Compared With Younger Patients: Systematic Review and Meta-Analysis

Circulation ◽

10.1161/circ.142.suppl_3.17469 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Praveen Ponnamreddy ◽

Saeed Juggan ◽

Lauren Gilstrap

Keyword(s):

Quality Of Life ◽

Older Patients ◽

Meta Analysis ◽

Nyha Class ◽

Age Group ◽

Walk Test ◽

Younger Patients ◽

Six Minute Walk Test ◽

Minute Walk

Background: CRT had been accepted as standard of care for patients with HFrEF who qualify for the therapy. The pivotal CRT trials enrolled patients significantly younger than the typical HFrEF patients seen in the community. Benefits of CRT in older HFrEF patients is largely unknown. We sought to evaluate the change in quality of life in older patients undergoing CRT in comparison to younger patients. Hypothesis: CRT implantation is associated with comparable improvements in quality of life in younger patients (age <70) and older patients (age 70 and above). Methods: PubMed, The Cochrane Library, Scopus, and Web of Science were queried for comparative effectiveness studies of CRT in older HFrEF patients. We gathered data for Quality of life measurements including improvement in NYHA class, MLHFQ, Six minute walk test. MLHFQ, Six minute walk test data was analyzed qualitatively as data was insufficient to impute Standard deviation for mean change. Changes in NYHA class was analyzed quantitatively. Random effects meta-analysis of improvement in NYHA class and relative risk (RR) is reported along with estimates of heterogeneity Results: Seven studies [n=2494 for younger group and n=1035 for older group] were included in changes in NYHA class meta-analysis. Older age group patients had similar improvement in NYHA class compared to younger age group patients. Relative risk 0.99 with 95%CI 0.93-1.06 (figure). Five studies reported Baseline and follow up MLHFQ scores for both the groups. All the five studies reported improvements in MLHFQ in both the groups. Three studies reported change in six minute walk test in meters before and after CRT implantation. All the studies reported improvement in six minute walk test both in younger and older group. Conclusions: People older than 70 years of age with heart failure with reduced ejection fraction who qualify for CRT derive similar benefits with improvement in quality of life compared to patients aged less than 70 years of age.

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Systemic Therapy for Elderly Patients with Gastrointestinal Cancer

Clinical Medicine Insights Oncology ◽

10.4137/cmo.s6983 ◽

2011 ◽

Vol 5 ◽

pp. CMO.S6983 ◽

Cited By ~ 1

Author(s):

Joleen M. Hubbard ◽

Axel Grothey ◽

Daniel J. Sargent

Keyword(s):

Clinical Trials ◽

Elderly Patients ◽

Systemic Therapy ◽

Survival Benefit ◽

Older Patients ◽

The Elderly ◽

Age Group ◽

Gastrointestinal Cancers ◽

Younger Patients ◽

Multiple Trials

The majority of patients with gastrointestinal cancers are over the age of 65. This age group comprises the minority of the patients enrolled in clinical trials, and it is unknown whether older patients achieve similar results as younger patients in terms of survival benefit and tolerability. In addition, there are few studies specifically designed for patients over 65 years. Subset analyses of individual trials and studies using pooled patient data from multiple trials provide some understanding on outcomes in older patients with gastrointestinal cancers. This article reviews the evidence on chemotherapeutic regimens in the elderly with colorectal, pancreatic, and gastroesophageal cancers, and discusses a practical approach to provide the best outcomes for older patients.

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Cancer in older patients

Reviews in Clinical Gerontology ◽

10.1017/s0959259803001035 ◽

2003 ◽

Vol 13 (3) ◽

pp. 203-213 ◽

Cited By ~ 5

Author(s):

N Beechey-Newman ◽

D Kulkarni

Keyword(s):

Life Expectancy ◽

Old Age ◽

Older Patients ◽

Causes Of Death ◽

Late Life ◽

General Context ◽

Age Group ◽

Men And Women ◽

Very High

As the number of people living to reach old age increases, so the proportion of cancers presenting in this age group increases to an even greater degree. Although 70% of all cancers in men and women occur over the age of 65 and in the over-75s, who are perhaps more appropriately classified as ‘elderly’, the figures are still very high (46% of all cancers occur in women over 75 and 35% in men over 75). As a consequence, cancer is rapidly becoming a problem of late life, and the management of patients in old age is an important part of general oncology. The magnitude of the overlap between old age and cancer is increasing because of improved life expectancy, more sensitive methods of diagnosing cancer and the biological fact that most cancers occur more commonly with increasing age. It is interesting, however, to put these figures into a more general context by examining the different causes of death in older patients by decade.

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Age distribution of tumor gene expression in patients with stage II/III colon cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.552 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 552-552

Author(s):

Howard S. Hochster ◽

Anna Lau ◽

Michelle Turner ◽

Christy Ann Russell

Keyword(s):

Gene Expression ◽

Colon Cancer ◽

Older Patients ◽

Clinical Laboratory ◽

Stage Ii ◽

Age Group ◽

Younger Patients ◽

Incidence And Mortality ◽

Tumor Gene Expression ◽

Tumor Gene

552 Background: Colorectal cancer (CRC) incidence and mortality have been rising in the US among adults <55 y. Younger patients with CRC are more likely than older patients to receive postoperative systemic chemotherapy, despite lack of consensus on the prognostic value of age in this disease. CRC diagnosed in younger patients may be biologically different from that in older patients, but characteristics are unknown. Thus, we examined whether age-specific differences were measurable by tumor gene expression using the 12-gene Oncotype DX Colon Recurrence Score (RS) test (Genomic Health, Inc. [GHI]; Redwood City, CA). The Colon RS test is validated to predict risk of recurrence in patients with stage II/III colon cancer. Methods: We analyzed Colon RS test results and single-gene results for the 12 genes by age group (age <40, 40-54, 55-64, and ≥65) using data from the GHI clinical laboratory dated 1/2010 to 7/2017. Results: As of 7/2017, 21,925 Colon RS reports have been delivered. Median age was 63 y; 50% were male. About 23% of patients were <55 y (Table). Mean (SD) RS result was 25 (11). Colon RS result distributions were similar by age group (Table). Expression of individual tumor genes measured in the Colon RS test were also similar by age group (data to be presented). Conclusions: The etiology of the increase in both incidence and mortality from CRC in adults <55 y is poorly understood. Our findings suggest that colon cancer in younger patients is not biologically different from that in older patients, as measured by the Colon RS test in a large cohort referred for testing. As shown by this test in the GHI clinical laboratory experience, most patients with stage II/III colon cancer have low-risk disease, including patients <55 years. Our findings support a biology-driven approach to disease management of patients with stage II/III colon cancer regardless of age. This well-validated genomic assay may identify a group of younger patients for whom adjuvant chemotherapy might represent overtreatment. [Table: see text]

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Older Age Is An Independent Risk Factor in AML

Blood ◽

10.1182/blood.v112.11.555.555 ◽

2008 ◽

Vol 112 (11) ◽

pp. 555-555

Author(s):

Thomas Buchner ◽

Wolfgang E. Berdel ◽

Claudia Haferlach ◽

Susanne Schnittger ◽

Torsten Haferlach ◽

...

Keyword(s):

Risk Factors ◽

Older Patients ◽

Normal Karyotype ◽

Older Age ◽

Age Group ◽

Risk Profiles ◽

Mutation Status ◽

Younger Patients ◽

Age Related ◽

Younger Age

Abstract Among the entire patients with AML the majority is 60 years of age or older. In present German multicenter AML Cooperative Group (AMLCG) trial the proportion of these older patients amounts to 54% of all 2734 patients enrolled and receiving intensive chemotherapy. While older age AML is increasingly recognized as a main challenge the therapeutic outcome unlike that in younger patients has remained constantly poor. Thus, the patients of ≥ 60y show an overall survival (OS) of 13% and a relapse rate (RR) of 82% at 5y versus 40% and 52% in younger patients. Age related differences in treatment and in risk profiles are commonly used to explain the differences in outcome. In the AMLCG 99 trial including 2734 patients 16 to 85 (median 61) years of age we investigated factors determining the disease biology and outcome. For induction treatment patients received standard dose TAD and high-dose AraC 3 (age < 60y) and 1 (≥ 60y) g/m² × 6/mitoxantrone (HAM) or randomly HAM-HAM, for consolidation TAD, and for maintenance monthly reduced TAD randomized (in patients < 60y) against autologous SCT. When compared with patients younger than 60y older patients had more frequent secondary AML (29% vs 17%, p< 0.0001), unfavorable cytogenetics (29% vs 23%, p= 0.0004), less frequent favorable cytogenetics (4% vs 12%, p< 0.0001), and NPM1mut/FLT3-ITDneg status (26% vs 34%, p< 0.009) in those with normal karyotype, and overall even lower median WBC (7.360 vs 12.600/μl, p< 0.0001) and LDH (340 vs 413 U/l, p< 0.0001). A multivariate analysis identified independent risk factors determining therapeutic endpoints such as CR rate, OS, RR, and RFS. With similar results across all endpoints, risk factors for OS were age ≥ 60y (HR 1.96, 95% CI 1.75–2.17), AML secondary to MDS or cytotoxic treatment (1.28, 1.14–1.45), unfavorable karyotype (2.17, 1.92– 2.44), WBC > 20×10³/μl (1.15, 1.02– 1.30), LDH > 700U/L (1.32, 1.15– 1.52), favorable karyotype (0.49, 0.38– 0.63) and female gender (0.90, 0.81– 0.99). In the 891 patients with normal karyotype and complete mutation status risk factors for OS were age ≥ 60y (2.00, 1.64– 2.44), and NPM1mut/FLT3-ITDneg (0.39, 0.30– 0.49). Risk factors for RR overall were age ≥ 60y (2.04, 1.75– 2.38), unfavorable karyotype (2.08, 1.47– 2.13), LDH (1.41, 1.16– 1.72) and favorable karyotype (0.40, 0.29– 0.56). In patients with normal karyotype and complete mutation status risk factors for RR were age ≥ 60y (2.00, 1.56– 2.63), and NPM1mut/FLT3-ITDneg (0.32, 0.23– 0.43). Testing the role of older age in favorable subgroups, the 198 patients with CBF leukemia show an OS at 5 years of 27.5 (95% CI 12.0– 43.0) % in the older versus 69.4 (60.7– 78.2) % in the younger age group, and a RR of 56.6 (35.7– 77.3) % versus 25.0 (15.6– 34.4) %. Comparatively, the 264 patients with a normal karyotype and NPM1mut/FLT3-ITDneg show an OS of 37.1 (26.6– 47.5) % in the older versus 71.9 (63.4– 80.4) % in the younger age group, and a RR of 61.0 (47.8– 74.2) % versus 23.0 (14.0– 32.0) %. There was no influence by randomized treatment variables on any therapeutic endpoint. Conclusion: Considering the prognostic spectrum of all major historic or genetic subgroups older age maintains its dominant role not explained by age related differences in risk profiles. Even within CBF leukemias and sole NPM1 mutation as the best prognostic categories older age predicts for markedly shorter OS and higher RR. Thus, understanding older age AML requires further genetic and epigenetic work.

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Age-Related Differences in Disease Characteristics and Clinical Outcomes in Polycythemia Vera

Blood ◽

10.1182/blood.v118.21.1758.1758 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1758-1758

Author(s):

Brady L Stein ◽

Jerry L. Spivak ◽

Alison R. Moliterno

Keyword(s):

Older Patients ◽

Disease Duration ◽

Vascular Complications ◽

Jak2 V617f ◽

Vascular Complication ◽

Group Differences ◽

Age Group ◽

Leukemic Transformation ◽

Younger Patients ◽

History Of

Abstract Abstract 1758 Introduction: Advanced age is an important prognostic indicator in Polycythemia Vera (PV), since this variable influences thrombosis risk as well as myelofibrotic and leukemic transformation. Whether younger patients are at less risk for these complications is unknown, but longer disease duration may offer more opportunity to experience these cardinal complications. To address this question, we retrospectively analyzed 134 PV patients, comparing those diagnosed before age 45 (N=70), to those diagnosed after age 65 (N=64), from the Johns Hopkins Center for Myeloproliferative Disorders. Methods: The parent cohort consisted of 223 PV patients; those diagnosed between the ages of 46 and 64 were excluded. Clinical and demographic variables were ascertained at the last intake visit, including disease duration, spleen size, blood counts, JAK2 V617F allele burden as well as a history of vascular complications, myelofibrotic and leukemic transformation. The Mann-Whitney Rank Sum test was used to test age group differences for continuous variables; testing for age group differences in proportions was performed using the z test, or Fisher's exact test. Results: PV in the young significantly differed from PV in the old with respect to gender (83% women in young vs. 55% in the old, p=0.001), and median disease duration at last follow-up (8 years in the young vs. 4 years in the old; p=<0.001). The proportion of patients with a Myeloproliferative Neoplasm (MPN) family history did not differ between younger and older patients (13% vs. 9%; p=0.80), nor did a history of antecedent ET (21.4 vs. 21.9%). Both groups were predominantly JAK2 V617F-positive (98.6 and 98.4%), but the younger group had a significantly lower median JAK2 V617F allele burden (52% vs. 66%; p=0.03). The younger and older cohorts did not differ with respect to hydroxyurea use (36% vs. 45%; p=0.19), but younger patients were more likely to have received interferon (17% vs. 3.3%; p=0.04), and marginally less likely to take aspirin (32% vs. 50%; p=0.05). The proportion with splenomegaly was greater in the younger cohort (50% vs. 25.8%, p=0.007), but the leukocyte count was significantly lower when compared to the older cohort (9.2 × 109/L vs. 14.3 × 109/L; p=0.001). The proportion of patients with a vascular complication did not differ between the younger and older cohorts (30.4% vs. 30.2%, p=0.99); however, 6 patients in the younger cohort had multiple events. Overall, a dependence between age group and the type of vascular complication was identified (p=0.009); venous events were more common in younger patients vs. older patients (19/29 (65.5%) vs. 4/19 (21%); p=0.0025), the majority of which involved the abdominal venous system (11 vs. 2 events). Acute coronary syndromes (5 events vs. 1 event) and transient ischemic attacks (8 events vs. 3 events) were more common in the older cohort. The proportion developing post-PV myelofibrosis, usually marked by the onset of anemia, was also similar by age group (14.3% (young) vs. 8%; p=0.28), but the median time to transformation was longer in the young (17 years vs. 4 years; p=0.04). AML transformation occurred in 1 young cohort patient, at 28 years from diagnosis, and in 4 older cohort patients, at a median of 6 years from diagnosis. There were 6 deaths (8.6%) in the younger cohort (1 AML, 1 CNS hemorrhage, 3 considered to be disease-related, 1 unknown), and 6 deaths (9.4%) in the older cohort (3 AML, 2 unknown, 1 renal failure). Conclusion: In conclusion, in one of the larger retrospective studies of PV patients diagnosed before age 45, this group was predominantly female and had a comparable history of vascular complications, though events more frequently involved the abdominal venous system compared to patients diagnosed after age 65. The proportion with myelofibrotic transformation was similar in the two groups, but occurred after a longer disease course in the younger cohort. Leukemic transformation was rare, and of comparable proportions, but contributed to more deaths in the older age group. Thus, younger patients do not appear to be protected from cardinal MPN complications, possibly due to a longer disease duration, which offers more opportunity for time-dependent complications. If disease-modifying effects of pegylated interferon and JAK-inhibitors are identified, then these agents might also be considered in young PV patients to offset time-dependent MPN complications. Disclosures: No relevant conflicts of interest to declare.

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Treatment of older patients with chronic lymphocytic leukemia: key questions and current answers

Hematology ◽

10.1182/asheducation-2013.1.158 ◽

2013 ◽

Vol 2013 (1) ◽

pp. 158-167 ◽

Cited By ~ 34

Author(s):

Tait Shanafelt

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Life Expectancy ◽

Elderly Patients ◽

Older Patients ◽

Age At Onset ◽

Lymphocytic Leukemia ◽

Newly Diagnosed ◽

Organ Function ◽

Younger Patients ◽

Key Questions

AbstractDespite the advanced age at onset, chronic lymphocytic leukemia (CLL) shortens the life expectancy of the majority of newly diagnosed patients. The management of elderly patients with CLL is more complex than that of younger patients due to the greater frequency of comorbidities and functional impairment as well as reduced organ function. Many of the recent advances in the care of CLL patients (prognostication, more intense combination therapy regimens) are of unclear relevance for elderly patients. This review addresses 5 key questions in the management of elderly patients with CLL: (1) why is classifying the “fitness” of CLL patients necessary; (2) what criteria should be used to classify patient fitness; (3) when should elderly patients be treated; (4) how should therapy be selected for elderly patients; and (5) which therapy is best (for this patient)?

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Satz-Mogel Short Form of WAIS with Older Psychiatric Patients

Psychological Reports ◽

10.2466/pr0.1984.55.3.895 ◽

1984 ◽

Vol 55 (3) ◽

pp. 895-898 ◽

Cited By ~ 3

Author(s):

Lee A. Hyer ◽

Blaze Harkey

Keyword(s):

Older Patients ◽

Short Form ◽

Psychiatric Patients ◽

Age Group ◽

Adult Intelligence Scale ◽

Intelligence Scale ◽

Younger Patients ◽

Wechsler Adult Intelligence Scale ◽

Wechsler Adult Intelligence ◽

Pearson Correlations

The Satz-Mogel short form of the Wechsler Adult Intelligence Scale was evaluated for use with older psychiatric inpatients. 57 older patients (— 55 yr.) and 50 younger patients (< 40 yr.) were administered the WAIS. The original WAIS was rescored according to the Satz-Mogel format. Pearson correlations between these two methods within each age group were high for each subtest as well as the Verbal, Performance, and Full Scale IQs. Analyses, however, detected significant differences within each age group on some of the Performance subtests. These findings suggest that the Satz-Mogel is an appropriate instrument for use with older psychiatric patients.

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