Transformation Scoring System (TSS): A new assessment index for clinical transformation of follicular lymphoma

Abstract

Although histologic analysis is the gold standard for diagnosing follicular lymphoma (FL) transformation, many patients are diagnosed with transformation by clinical factors as biopsy specimens often cannot be obtained. Despite the frequency of clinical diagnosis, no clinical assessment tool has yet been established for FL transformation in the rituximab era. We derived and validated a transformation scoring system (TSS) based on retrospective analyses of 126 patients with biopsy‐proven FL and histologic transformation (HT) at two hospitals of the National Cancer Center of Japan. In the derivation set (76 patients), the detailed analyses of the clinical characteristics at disease progression showed that lactate dehydrogenase (LDH) elevation, focal lymph nodal (LN) enlargement, hemoglobin <12 g/dl, and poor performance status (PS) (2‐4) were associated with HT. The weights of these variables were decided based on the regression coefficients. Next, we constructed a TSS encompassing the above four factors: LDH, (> upper limit of normal [ULN], ≤ULN ×2) (1 point), (≥ULN ×2) (2 points); focal LN enlargement, (≥3 cm, <7 cm) (1 point), (≥7 cm) (2 points); hemoglobin <12 g/dl (1 point); poor PS (2 points). We identified a high positive predictive value (PPV) (96.4%) and negative predictive value (NPV) (85.4%) for diagnosing HT when a cutoff score of 2 was selected for our TSS. In an external validation set (50 patients), the probability of HT was high with scores ≥2 (PPV, 93.3%; NPV, 82.9%). We developed a TSS that offers a simple, yet, valuable tool, for diagnosing HT, especially in patients who cannot undergo biopsy.

Utility of FDG-PET in predicting the histology of relapsed or refractory lymphoma

“…In iNHL, we also assessed baseline clinicopathological risk factors associated with aggressive transformation, such as Ann-Arbor stage III to IV, elevated LDH and nodal sites >4. 11 , 13 , 14 , 15 , 16 , 17 For patients with grade 1 to 3A FL, Follicular Lymphoma International Prognostic Index (FLIPI) score was also calculated.…”

The outcome of watchful waiting in patients with previously treated follicular lymphoma

“…However, some patients become resistant to subsequent chemotherapy, and progression‐free survival (PFS) and OS tend to shorten with the repeated disease relapse 4 . Presently, lymphoma itself is still the most frequent cause of death, especially for patients who experience transformation into aggressive lymphomas 5,6 . Also, the increase of adverse events due to repeated chemotherapy, including infection or the second primary malignancy, is concerning 5,7 …”

“…4 Presently, lymphoma itself is still the most frequent cause of death, especially for patients who experience transformation into aggressive lymphomas. 5,6 Also, the increase of adverse events due to repeated chemotherapy, including infection or the second primary malignancy, is concerning. 5,7 Watchful waiting (WW) has been traditionally conducted for asymptomatic FL patients 8,9,10,11,12 and is now widely accepted as a standard approach for newly diagnosed FL patients with low-tumor burden.…”

Diagnostic utility and prognostic significance of the Ki‐67 labeling index in diffuse large B‐cell lymphoma transformed from follicular lymphoma: a study of 76 patients

“…A definition for the clinical transformation of FL has been proposed. 4,9 An increase in the maximum standardized uptake value (SUV max ) on positron emission tomography (PET) indicates HT. 9,10 Many histopathological and genetic factors have been found to be correlated with HT: FL grade, tumor microenvironment, mutations, insertions/deletions, copy-number variations, and structural rearrangements.…”