**1. Introduction**

Mantle Cell Lymphoma (MCL) is a non-Hodgkin's lymphoma (NHL), with aggressive behavior and poor prognosis representing less than 10% of all NHLs [1,2]. MCL is an NHL frequent in advanced age; the median age at diagnosis ranges from 60 to 70 [3]. The prognosis of elderly lymphoma patients is, of course, worse than that of younger patients; this is probably due to the presence of age-related conditions and comorbidities that could increase the risk of side effects after treatments and worsen the prognosis. Sometimes, the chemotherapy regimen needs to be changed during the course of therapy, with a deescalation of doses or a reduction in the cycles [4]. The risk of relapse or progression is very high and, nowadays, no clear and shared prognostic factors are available. Furthermore, the MCL International Prognostic Index (MIPI), proposed as the prognostic index, found controversial evidence in the literature [5,6]. The potential prognostic role of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (2-[18F]- FDG PET/CT) and its features is yet an open question [7]. Several recent papers [8–10]

**Citation:** Albano, D.; Pasinetti, N.; Dondi, F.; Giubbini, R.; Tucci, A.; Bertagna, F. Prognostic Role of Pre-Treatment Metabolic Parameters and Sarcopenia Derived by 2-[18F]-FDG PET/CT in Elderly Mantle Cell Lymphoma. *J. Clin. Med.* **2022**, *11*, 1210. https://doi.org/ 10.3390/jcm11051210

Academic Editors: Arnoldo Piccardo and Christos Sachpekidis

Received: 27 December 2021 Accepted: 22 February 2022 Published: 23 February 2022

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demonstrated that metabolic response after first-line therapy, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were significantly related with progression free survival (PFS), not with overall survival (OS). A detection of shared prognostic criteria could be fundamental with the aim to stratify patients and personalize the patient management and treatment. In this scenario, the potential prognostic role of sarcopenia and its indexes are not evaluated. Sarcopenia can be considered a multi-factorial syndrome, defined by a progressive and generalized loss of strength and skeletal muscle mass, which may increase the risk of adverse events (until death) and reduce the quality of life [11]. In HL and diffuse large B cell lymphoma (DLBCL), the sarcopenia estimated by CT (low-dose CT of PET or high-dose CT) has been shown to be an independent prognostic factor [12,13], while in MCL, these analyses are anecdotal with low numbers [14,15] of patients included and mixed with other lymphoma histotypes [16,17].

For these reasons, the aim of this retrospective study was to analyze and compare the prognostic value of PET/CT features and sarcopenia, estimated by CT of PET in elderly MCL.

#### **2. Materials and Methods**

#### *2.1. Patients*

We have retrospectively screened about 42.011 2-[18F]-FDG PET/CT scans performed in our Nuclear Medicine Department from January 2010 until December 2020 for any reason. Among them, 140 had a histological diagnosis of MCL. The other patients had different oncological or not oncological diseases. These patients were further selected according to some inclusion criteria: (1) patients who performed a baseline PET/CT scan and an end-of-treatment (eot) PET/CT after first line chemotherapy; (2) patients without a previous history of other malignancies; (3) patients with an age at the time of MCL diagnosis ≥65 years; (4) patients with at least 12 months of follow-up from the baseline 2-[18F]-FDG PET/CT. Finally, 53 patients were recruited (Figure 1). The medical records of these patients were analyzed with attention to the main epidemiological (gender, age at diagnosis, BMI), clinical (B symptoms, MIPI score, β2-microglobulin level and lactate-dehydrogenase (LDH) level), histopathological (blastoid variant), size (bulky disease, splenomegaly), PET/CT semiquantitative data and sarcopenia features. MIPI score, β2-microglobulin and LDH values were dichotomized using a cutoff value of 2, 2.8 mg/L and 245 U/L respectively.

**Figure 1.** Flowchart of patients included.

All patients were treated according to the institution's standard protocol with chemotherapy regimen. In 22 cases R-BAC (Rituximab, Bendamustine and Cytarabine) regimen was performed up to six cycles of immuno-chemotherapy and in three cases, up to four cycles; in ten cases R-CHOP (Rituximab, Cyclophosphamide, Hydroxydoxorubicine, Oncovin and Prednisone) regimen was done up to six cycles and in five, up to three cycles; in three cases R-hyper-CVAD (rituximab, hyper-fractionated cyclophosphamide, vincristine, adriamycin, and dexamethasone alternating with rituximab, high-dose methotrexate, and high-dose cytarabine) regimen was chosen and in the remaining ten patients MCL 0208 trial which consisted of high-dose chemotherapy plus Rituximab, followed by Lenalidomide and autologous stem cell transplantation as maintenance therapy was used.

There was a minimal overlap (n 11 patients) with a previous paper already published [9].
