A Proposal for a Novel Approach to Fitness in the Elderly Patients: The "NO-Chain" Algorithm
Authors: Riva Marta , Molteni Alfredo , Cairoli Roberto 
Published: November 2019

Abstract
A proper assessment of elderly patients is a relevant clinical problem in the onco-hematological setting. In this context, age and extra-hematological morbidity are of primary importance, but performance status and overall functionality related to geriatric age, as physical abilities, cognitive aspects and ability to self-management are not negligible. Thus, a defined multi-dimensional assessment is needed to differentiate between fit, unfit and frail older adults (Klepin ASH Education Program 2014).
We propose a tool to evaluate the tolerance to more or less intensive treatments in over 60 years aged patients, and to estimate the impact on the outcome. Our algorithm is based on 4 main variables universally recognized: age, performance status, comorbidities and geriatric aspects (functional, physical and cognitive).
1- As regards age, two cut-off values were considered: 70-years limit because it represents the threshold below which the allogeneic bone marrow transplantation may still run; and the 85-year limit because it denotes the edge beyond which chemotherapy (also non-intensive) should not be administered.
2- About performance status, it was chosen the ECOG (Eastern Cooperative Oncology Group) scale more or equal to 3 as the limit beyond which chemotherapy should be avoided.
3- Considering co-morbidities, the SIE, SIES GITMO group consensus-based definition of inability to intensive and non-intensive chemotherapy in acute myeloid leukemia (Ferrara et al. Leukemia 2013) was chosen to identify both patients candidate to intensive or candidate to only non-intensive chemotherapy.
4- Approaching the geriatric assessment, two levels of impairment were considered: the most important level of seriousness occurs when the Activities of Daily Living (ADL) functional scale is not overtaken; the lowest level of seriousness is verified if at least one among the functional Instrumental Activities of Daily Living (IADL) scale or the physical Short Physical Performace Battery (SPPB) scale or the cognitive Mini Mental State Examination (MMSE) scale are not overcome.
The stratification of patients works with some steps that must be excluded in order to get over the various levels of fitness (Figure 1).
We call this approach the NO-chain algorithm. It foresees that:
- Patient with at least one of the following features are considered frail: 85 or more years of age; at least 3 of ECOG; assessed functional impairment with the ADL scale <3; presence of major comorbidities including at least one of the six criteria, according to the SIE, SIES GITMO consensus-based definition of inability to non-intensive chemotherapy in acute myeloid leukemia.
- Not-frail patient with at least one of the following features are considered unfit: age over 70 years; at least one of criteria, according to the SIE, SIES GITMO consensus-based definition of inability to intensive chemotherapy in acute myeloid leukemia; at least one among functional impairment assessed by IADL scale <4 or reduced physical performance by SPPB scale <9 or intellectual deficit by the MMSE scale <24.
- All patients who get through all these steps are considered fit and potentially eligible for allogeneic stem cell transplantation.
Although the used cut-off levels might need amelioration in the practice, the basic principle of this algorithm is the definition of fitness actually correlated to the patient's condition in itself, regardless of the hematological disease. The algorithm was originally developed for elderly patients with acute myeloid leukemia (AML), but subsequently applied to patients with myelodysplastic syndrome (MDS) and to the other hematological malignancies. The application is undoubtedly different, depending on the disease the patient is affected by and its classification. For instance: an AML frail patients, regardless of biological risk, can be candidate only to supportive care; a low-risk MDS frail patients may still be candidate to pharmacological therapy as erythropoiesis stimulating agents or iron chelation therapy. The validation of this algorithm has to be carried out within each hematologic malignancy and must take into account the specific application.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.