Abstract
The WHO (World Health) Organization Classification recognizes two distinct subtypes of anaplastic large cell lymphoma: Primary systemic and Primary cutaneous types, which have differences in immunophenotype, genetics, and clinical behavior. It is now known that approximately 60% of systemic ALCLs express the anaplastic lymphoma kinase (ALK) protein (ALK-pos) and have a significantly superior survival to ALK-neg cases. Since ALK-neg ALCL appear to have a prognosis similar to peripheral T-cell lymphoma unspecified (PTCL-U), it has been suggested that they should be classified as PTCL-U. Herein, we report the clinical features of newly diagnosed systemic and cutaneous ALCL from the International T-cell Lymphoma Study Group.
Materials and Methods: 186 cases of ALCL were identified by the WHO disease definitions: systemic ALCL 163 (88%) (ALK-pos 91 (56%), 72(44%) ALK-neg), and 23 (17%) cutaneous ALCL (cut ALCL). The median age of ALK-pos, ALK-neg and cut ALCL was 32, 57.5 and 54, respectively. There was a male predominance for all subtypes. Most cases of systemic ALCL presented with stage III or IV disease (64% ALK-pos, 58% ALK-neg) and in contrast, 87% of cut ALCL had localized disease. The majority of patients with systemic ALCL were treated with CHOP-type chemotherapy. Most patients with cut ALCL (91%) received additional therapy: 13 (62%) CHOP-type chemotherapy, 11(52%) chemoradiation, 4 (19%) radiation alone.
Results: The 5y failure free survival (FFS) and overall survival (OS) was superior for ALK-pos ALCL (70.5% and 58%) compared to ALK-neg ALCL (49% and 36%) (p=.022 and p=.014 for FFS and OS, respectively). Comparison of ALK-pos (n=16) and ALK-neg ALCL (n=23) patients with limited stage disease (defined as stage I or II, no B symptoms and non-bulky) failed to demonstrate a significant difference in FFS (p=.54) or OS (p=.21). Both ALK-pos and ALK-neg ALCL had a superior FFS (ALK-pos p< .001; ALK-neg p=.012) and OS (ALK-pos p<.001; ALK-neg p=.032) than PTCL-U. In contrast to PTCL-U, an apparent plateau was observed on the FFS curve for ALK-neg ALCL. For cut ALCL, the 5y FFS and OS was 90% and 57%, superior to systemic ALCL. The administration of chemotherapy did not appear to impact outcome in patients with cut ALCL (p=.64). Among the prognostic factors analyzed, the international prognostic index (IPI) was the most effective for defining risk categories in ALK-neg ALCL. For ALK-pos ALCL both the IPI and anemia (Hb < 11.0 g/L) were effective in risk-group stratification in multivariate analysis.
Conclusions: Similar to prior reports, ALK-pos ALCL has a superior outcome to ALK-neg ALCL. For limited stage patients, this survival difference is not apparent, suggesting that a small subgroup of patients with ALK-neg ALCL may have a more favorable prognosis, similar to ALK-pos ALCL. The IPI is effective in both ALK-neg and ALK-pos ALCL at risk stratification. Finally, contrary to prior reports, ALK-neg ALCL patients appear to have a superior outcome to PTCL-U and an apparent plateau in the FFS curve. These results suggest that ALK-neg ALCL should still be distinguished from both ALK-pos ALCL and PTCL-U.
Anaplastic Large Cell Lymphoma ALK-Negative: About a Rare Pediatric Case Report
