Review article
Comorbidity and geriatric assessment for older patients with hematologic malignancies: A review of the evidence

https://doi.org/10.1016/j.jgo.2011.11.004Get rights and content

Abstract

The majority of hematologic malignancies occur in patients aged more than 65 years. Such patients have very variable health status, comorbidity levels, and geriatric syndrome prevalence. It is important to identify who would be a candidate for standard treatment schemes, and who would be a candidate for modified therapeutic approaches. Accurate assessment of patient fitness and comorbidities is key when planning therapy for this group as such factors will affect prognosis. In this paper, we review the published literature on a comprehensive geriatric assessment and comorbidity measurements in patients with hematologic malignancies and their correlation with outcomes. Our review identified the Charlson score and the Cumulative Illness Rating Scale-Geriatric as the most frequently used comorbidity instruments in the general setting, and the Hematopoietic Cell Transplantation-Comorbidity Index in the transplant setting. For the geriatric assessments, the most commonly used scheme combines age, comorbidity, Activities of Daily Living, and the presence of geriatric syndromes. Correlations with overall survival and treatment tolerance are fairly consistently demonstrated. Some tentative thresholds are apparent but remain to be firmly confirmed. Future trials should integrate these assessments as correlates or stratification tools in order to build on the early results already available.

Introduction

The majority of patients with hematologic malignancies are over the age of 65. In the US, the median age at diagnosis is 65 years for chronic myelogenous leukemia (CML), 67 years for acute myelogenous leukemia (AML) and non-Hodgkin's lymphoma (NHL), 69 years for multiple myeloma, and 72 years for chronic lymphocytic leukemia (CLL). Hodgkin's disease remains diagnosed mostly in young people, with a median age of 38 years. Acute lymphoblastic leukemia (ALL) has a bimodal distribution with an incidence peak in early childhood and another one in the elderly (http://seer.cancer.gov/). Older patients have a significant amount of comorbidity, functional decline, and geriatric syndromes that might impact the treatment selection and outcome of their hematologic malignancy. Whereas healthy older patients can receive treatment similar to younger ones for most hematologic malignancies, at the cost of some increased toxicity, patients with a heavy comorbidity burden have more limited benefits and increased toxicity and might benefit from alternate treatment options. Comorbidity and geriatric assessment have been extensively studied, but most studies and reviews have focused either exclusively on solid tumors, or on a general sample with a minority of hematologic malignancies. Yet hematologic malignancies have some unique features: e.g. frequent bone marrow involvement; rapid response to chemotherapy, which might lead to dramatic functional improvement; and even in advanced stages, treatments offering good chances of cure or long-term remissions. The purpose of this review is to assess what is known about the impact of these comorbid conditions and what tools might be used to guide therapeutic decisions.

Section snippets

Comprehensive Geriatric Assessment (CGA)

Accurate and consistent assessment of patient fitness is of paramount importance for administering effective and safe treatment to elderly cancer patients. Evidence demonstrates that chronological age alone is not a good predictor of life expectancy, functional reserve, or likelihood of treatment-related complications, and therefore guidelines such as those of the National Comprehensive Cancer Network (NCCN) or the International Society of Geriatric Oncology (SIOG) recommend a CGA of older

Comorbidity

Comorbidity has long been studied for its association with outcomes in several malignancies. The most frequently used instruments are the Charlson comorbidity index (hereafter “Charlson”) and the Cumulative Illness Rating Scale for Geriatrics (CIRS-G).[13], [14] The properties of those instruments, as well as their advantages over ad hoc lists of diseases, have been discussed elsewhere.15 Most of the studies included either all types of cancers confounded or solid tumors only. Some studies,

Functional Status

ECOG performance status is a strong predictor of outcome in older AML patients. A recent study from the Swedish Acute Leukemia Registry demonstrated several aspects of that relationship.39 Older patients with a low PS score had more early deaths than those with good PS, no matter what their age. However, within each age and PS category, the patients who did receive intensive treatment had lower early death rates than the others (Table 2). Although they may represent selection bias, these

Frailty Definitions in Hematologic Clinical Trials

Several lymphoma/leukemia studies have used empirical definitions of frailty to design adapted regimens:

The EORTC 20992 study defined a frail patient as one aged 70 years or older and having either severe comorbidities (by CIRS-G), WHO performance status of 3 or 4, cardiac contraindication to anthracyclines, creatinine clearance < 50 mL/min, baseline neutropenia, or thrombopenia.46 These criteria were chosen as predictors of inability to receive CHOP for large cell lymphoma, and the patients were

Tools Focusing on The Risk of Toxicity From Chemotherapy

Until recently, there were no tools available that could reliably evaluate the individual risk of severe toxicity from different chemotherapy regimens across a range of tumor types. Two new assessment methods that specifically look at the older patient's ability to tolerate chemotherapy were presented at the American Society of Clinical Oncology (ASCO) 2010 Annual Meeting and are in the process of further evaluation: The Chemotherapy Risk Assessment Scale for High-age patients (CRASH) and the

Conclusions and Perspective

Comorbidity does impact the prognosis of older patients with hematologic malignancies. The other parameters of the geriatric assessment have so far received less attention. The end point that has received the most attention is tolerance to treatment, especially neutropenia and febrile neutropenia. This is most likely because of the availability of a prophylactic intervention with growth factors. However, nonhematologic toxicities as a whole are as frequent and are in need of predictive

Disclosures

The authors have no conflict of interest to disclose.

Author Contributions

Concept and design: ME.

Data collection: ME, UW.

Analysis and interpretation of data: ME, UW.

Manuscript writing and approval: ME, UW.

Acknowledgements

John Carron, from Health Interactions, Manchester, UK, contributed to the literature review and the writing of the manuscript. Support for third-party writing assistance for this manuscript was provided by F. Hoffmann-La Roche Ltd. Roche had no input in the scientific content of the article.

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