Prognostic Impact of Muscle Quantity and Quality and Fat Distribution in Diffuse Large B-Cell Lymphoma Patients

Baseline CT scans of 116 patients (48% female, median 64 years) with diffuse large B-cell lymphoma (DLBCL) were retrospectively reviewed to investigate the prognostic role of sarcopenia and fat compartment distributions on overall survival (OS), progression-free survival (PFS), and early therapy termination. Skeletal muscle index (SMI), skeletal muscle density (SMD), and intermuscular adipose tissue (IMAT) were quantified at the level of the third lumbar vertebra (L3) and proximal thigh (PT). Low L3-SMD, but not low L3-SMI, was associated with early therapy termination (p = 0.028), shorter OS (HR = 6.29; 95% CI = 2.17–18.26; p < 0.001), and shorter PFS (HR = 2.42; 95% CI = 1.26–4.65; p = 0.008). After correction for sex, International Prognostic Index (IPI), BMI, and R-CHOP therapy (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), low L3-SMD remained associated with poor OS (HR = 3.54; 95% CI = 1.10–11.40; p = 0.034) but not with PFS. Increased PT-IMAT was prognostic for poor OS and PFS after correction for sex, IPI, BMI, and R-CHOP therapy (HR = 1.35; CI = 1.03–1.7; p = 0.03, and HR = 1.30; CI = 1.04–1.64; p = 0.024, respectively). Reduced muscle quality (SMD) and increased intermuscular fat (IMAT), rather than low muscle quantity (SMI), are associated with poor prognosis in DLBCL, when measured at the L3 level, and particularly at the level of the proximal thigh. The proximal thigh represents a novel radiological landmark to study body composition.

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CD5 expression is potentially predictive of poor outcome among biomarkers in patients with diffuse large B-cell lymphoma receiving rituximab plus CHOP therapy

Annals of Oncology ◽

10.1093/annonc/mdn392 ◽

2008 ◽

Vol 19 (11) ◽

pp. 1921-1926 ◽

Cited By ~ 51

Author(s):

D. Ennishi ◽

K. Takeuchi ◽

M. Yokoyama ◽

H. Asai ◽

Y. Mishima ◽

...

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Poor Outcome ◽

Large B Cell Lymphoma ◽

Large B Cell ◽

Chop Therapy

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Tumor necrosis could reflect advanced disease status in patients with diffuse large B cell lymphoma treated with R-CHOP therapy

Annals of Hematology ◽

10.1007/s00277-016-2822-8 ◽

2016 ◽

Vol 96 (1) ◽

pp. 17-23 ◽

Cited By ~ 8

Author(s):

Moo-Kon Song ◽

Joo-Seop Chung ◽

Dong-Yeop Shin ◽

Sung-Nam Lim ◽

Gyeong-won Lee ◽

...

Keyword(s):

B Cell ◽

Tumor Necrosis ◽

Advanced Disease ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Disease Status ◽

Large B Cell Lymphoma ◽

Large B Cell ◽

Chop Therapy

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Diffuse large B-cell lymphoma in Southeast Asian cohort: expression patterns of B-cell receptor (BCR) repertoire and its linkage with molecular subtypes and response to R-CHOP therapy

Journal of Clinical Pathology ◽

10.1136/jclinpath-2019-205837 ◽

2019 ◽

Vol 72 (9) ◽

pp. 630-635 ◽

Cited By ~ 2

Author(s):

Noraidah Masir ◽

Ariz Akhter ◽

Tariq M Roshan ◽

Chandramaya Sabrina Florence ◽

Faridah Abdul-Rahman ◽

...

Keyword(s):

Southeast Asia ◽

B Cell ◽

Targeted Therapies ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Cell Receptor ◽

B Cell Receptor ◽

Large B Cell Lymphoma ◽

Large B Cell ◽

Chop Therapy

AimsHeightened B-cell receptor (BCR) activity in diffuse large B-cell lymphoma (DLBCL) is well established, and a subset of patients with relapsed DLBCL can benefit from BCR-targeted therapies. Universal outreach of such emerging therapies mandates forming a global landscape of BCR molecular signalling in DLBCL, including Southeast Asia.Methods79 patients with DLBCL (nodal, 59% and extranodal, 41%) treated with rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) therapy were selected. Expression levels of BCR and linked signalling pathway molecules were inter-related with Lymph2Cx-based cell of origin (COO) types and overall survival (OS).ResultsActivated B-cell (ABC) type DLBCL constituted 49% (39/79) compared with germinal centre B-cell (GCB) type DLBCL (29/79; 37%) and revealed poor prognosis (p=0.013). In ABC-DLBCL, high BTK expression exerted poor response to R-CHOP, while OS in ABC-DLBCL with low BTK expression was similar to GCB-DLBCL subtype (p=0.004). High LYN expression coupled with a poor OS for ABC-DLBCL as well as GCB-DLBCL subtypes (p=0.001). Furthermore, high coexpression of BTK/LYN (BTKhigh/LYNhigh) showed poor OS (p=0.019), which linked with upregulation of several genes associated with BCR repertoire and nuclear factor-kappa B pathway (p<0.01). In multivariate analysis, high BTK and LYN expression retained prognostic significance against established clinical predictive factors such as age, International Prognostic Index and COO (p<0.05).ConclusionsOur data provide a clear association between high BCR activity in DLBCL and response to therapy in a distinct population. Molecular data provided here will pave the pathway for the provision of promising novel-targeted therapies to patients with DLBCL in Southeast Asia.

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Primary skeletal muscle diffuse large B-cell lymphoma in the gluteal region

Journal of the American Academy of Dermatology ◽

10.1016/j.jaad.2018.05.916 ◽

2018 ◽

Vol 79 (3) ◽

pp. AB229

Keyword(s):

Skeletal Muscle ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Gluteal Region ◽

Large B Cell Lymphoma ◽

Large B Cell

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Diffuse Large B-cell Lymphoma Involving the Skeletal Muscle

Internal Medicine ◽

10.2169/internalmedicine.56.7953 ◽

2017 ◽

Vol 56 (10) ◽

pp. 1269-1270

Author(s):

Ko Harada ◽

Kosuke Kimura ◽

Masaya Iwamuro ◽

Fumio Otsuka

Keyword(s):

Skeletal Muscle ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

Large B Cell

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Statin-independent prognosis of patients with diffuse large B-cell lymphoma receiving rituximab plus CHOP therapy

Annals of Oncology ◽

10.1093/annonc/mdp490 ◽

2010 ◽

Vol 21 (6) ◽

pp. 1217-1221 ◽

Cited By ~ 13

Author(s):

D. Ennishi ◽

H. Asai ◽

Y. Maeda ◽

K. Shinagawa ◽

K. Ikeda ◽

...

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

Large B Cell ◽

Chop Therapy

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FcγRIIIa Gene Polymorphisms May Correlate with Response to Frontline R-CHOP Therapy for Diffuse Large B-Cell Lymphoma.

Blood ◽

10.1182/blood.v108.11.2457.2457 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2457-2457

Author(s):

Dong Hwan Kim ◽

Hee Du Jung ◽

Sang Kyun Sohn ◽

Je-Jung Lee ◽

Deok-Hwan Yang ◽

...

Keyword(s):

B Cell ◽

Gene Polymorphisms ◽

Response Rate ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Effector Cells ◽

Large B Cell Lymphoma ◽

The Impact ◽

Large B Cell ◽

Chop Therapy

Abstract Background: The precise mechanism of rituximab (R) plus CHOP (R-CHOP) therapy in diffuse large B-cell lymphoma (DLBCL) is not fully elucidated. Besides overcoming bcl-2 mediated chemoresistance, antibody-dependent cellular cytotoxicity (ADCC), which is activated by effector cells via IgG fragment C receptors (FcR), was also proposed as a mechanism of Rituximab. The current study evaluated the impact of FcR polymorphism on the response to R-CHOP therapy for DLBCL with the basis that FcR polymorphism can affect R’s affinity for ADCC effector cells. Patients and Methods: The FcγRIIIa and FcγRIIa gene polymorphisms were determined in DLBCL patients receiving R-CHOP (n=113) comparing to CHOP therapy (n=85). Results: The FcγRIIIa valine (V) allele was significantly correlated with higher complete response rate to R-CHOP compared to phenylalalnine (F) allele (88% in V/V versus 79% in V/F versus 50% in F/F, p=0.002), while no difference was found between FcγRIIa polymorphism. In addition, V/V allele was associated with faster achievement of response than other alleles. The impact of FcγRIIIa gene polymorphism on response rate was not noted in CHOP group. In terms of overall or event-free survival, no difference was found according to FcγRIIIa or FcγRIIa alleles. Conclusion: The FcγRIIIa SNP is predictive of response to R-CHOP, but does not correlate with survival in DLBCL patients.

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Clinical Relevance Of Cachexia Assessed By An Anthropometric Tool In Elderly Patients With Diffuse Large B-Cell Lymphoma Treated By Immunochemotherapy

Blood ◽

10.1182/blood.v122.21.2926.2926 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2926-2926

Author(s):

Helene Lanic ◽

Jerome Kraut ◽

Romain Modzelewski ◽

Florian Clatot ◽

Jean-Michel Picquenot ◽

...

Keyword(s):

Skeletal Muscle ◽

Weight Loss ◽

Elderly Patients ◽

Ct Scan ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract Background Cancer Cachexia is a metabolic syndrome that can be present even in absence of weight loss and associated with significantly impaired survival. Muscle wasting represents a key-symptom of this syndrome and we recently demonstrated the strong prognosis impact of sarcopenia assessed by computed tomography (CT)-scan in diffuse large B-cell lymphoma (DLBCL) (Lanic et al. Leukemia & Lymphoma 2013). Conversely, the clinical relevance of loss of fat mass (adipopenia) remains unclear. The aim of this study was (i) to investigate the prognostic impact of a multidimensional tool combining a nutritional parameter (albuminemia) and body composition measurements (skeletal muscle and body fat composition) in elderly patients with DLBCL treated by chemotherapy and rituximab (R) (ii) to document the evolution of sarcopenia after immunochemotherapy. Methods This retrospective analysis included 80 DLBCL patients older than 70 years (y) and treated by R-CHOP or R-miniCHOP. Skeletal muscle (SM), visceral (V) and subcutaneal (S) adipose (A) tissues were measured by analysis of stored CT images at the Lumbar vertebrae 3 (L3) level. The surface of the muscular and adipose tissues was selected according to CT Hounsfield unit. Values were normalized for stature to calculate the L3 SM index (LSMI, in cm2/m2), the LVAI and the LSAI and used to define sarcopenia and visceral/subcutaneal adipopenia. Results The characteristics of the patients were as follows: median age = 78 y [70-95]; 36 males; IPI 0-2 = 22, 3-5 = 58; treatment by R-CHOP (n = 45) or R-miniCHOP (n = 35); median body mass index (BMI; in kg/m2) = 23.9. According to the sex-specific defined cut-offs for LSMI (< 55.8 cm²/m² for men and 38.9 cm²/m² for women), 44 DLBCL patients (55 %, 23 males) were considered as sarcopenic. With a median follow-up of 39 months, the 2y overall survival (OS) in the sarcopenic population was 46% as compared to 84% in the non-sarcopenic group (HR = 3.12; CI95%, 1.66-5.88; p=0.0004). The median LSAI was 76.3 cm2/m2 [10-167] in females and 47.4 cm2/m2[22-100] in males. The median LVSAI was 43.5 cm2/m2[3-141] in females and 50.4 cm2/m2[14-159] in males. Adipopenia, defined by a low LVAI and/or a low LSAI was also highly predictive of the outcome. The 2y OS of the low LVAI population was 48% as compared to 82% for the non-adipopenic group (HR = 2.20; CI95%, 1.19-4.05; p=0.01). The 2y OS in the low LSAI population was 48% as compared to 80% in the non-adipopenic group (HR = 2.28; CI95%, 1.23-4.21; p=0.008). A Three-point cachexia score (CS) including adipopenia, sarcopenia and hypo-albuminemia (defined by an albuminemia < 35 g/L) was build and delineates three distinct risk-groups (Figure 1). More importantly the CS remains predictive of the prognosis in a multivariate analysis including BMI (< or >= 25 kg/m2), age (< or >= 80y), IPI and gender (HR=2.5; CI95%= 1.14-5.39; p =0.02). LMSI was subsequently reassessed in thirty seven patients during the routine CT scan follow-up [mean = 10 months after pre-treatment CT scan (range 2.8-19.2)]. 15 (40%) patients displayed a 5% decrease of their LSMI, whereas 13 (35%) and 9 (25%) displayed no significant change or increase (>5%) of the LMSI respectively. Conclusion Our study demonstrates that sarcopenia and adipopenia estimated by CT-scan define cachexia more accurately than BMI or weight loss in elderly DLBCL patients. These factors can be integrated in a cachexia scoring tool which predicts the outcome independently of the BMI and of the IPI. CT scan follow-up indicates that cachexia is a reversible process that should be integrated as part of the therapeutic target in combination with lymphoma treatment. A prospective multicentric trial (registered as NCT01715961/Clinical.gov) is ongoing to validate these anthropometric and nutritional parameters and compare to geriatric assessment scales. Disclosures: No relevant conflicts of interest to declare.

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