From the Guidelines
No, peripheral T-cell lymphoma (PTCL) does not typically progress to ALK-positive anaplastic large cell lymphoma (ALCL). These are distinct subtypes of T-cell lymphomas with different genetic profiles and clinical behaviors. ALK-positive ALCL is characterized by a specific genetic abnormality - the translocation of the ALK gene (anaplastic lymphoma kinase) with other genes, most commonly NPM1, resulting in the expression of ALK protein. This is a defining feature of ALK-positive ALCL from its onset, not something that develops through progression from other lymphoma types.
Key Considerations
- The NCCN guidelines version 2.2022 1 provide a framework for understanding the different subtypes of T-cell lymphomas and their management, but do not suggest a progression from PTCL to ALK-positive ALCL.
- Studies have shown that brentuximab vedotin in combination with CHP is superior to CHOP for the treatment of patients with previously untreated CD30-positive PTCL, including ALK-positive ALCL 1, but this does not imply a transformation from one to the other.
- The genetic and molecular characteristics of ALK-positive ALCL are distinct from those of other PTCL subtypes, suggesting that these are separate entities rather than a progression from one to another.
Clinical Implications
- If a patient initially diagnosed with PTCL appears to develop ALK-positive features, this would more likely represent a misdiagnosis or the presence of two separate lymphomas rather than a transformation of one type into another.
- Treatment approaches for ALK-positive ALCL and other PTCL subtypes can differ significantly, with ALK-positive ALCL generally having a more favorable prognosis and better response to certain therapies, such as brentuximab vedotin in combination with CHP 1.
- Accurate diagnosis and subclassification of T-cell lymphomas are critical for optimal management and prognosis.
From the Research
Progression of Peripheral T-Cell Lymphoma
- Peripheral T-cell lymphoma (PTCL) is a rare subtype of non-Hodgkin lymphoma with heterogeneous biology and generally aggressive features 2.
- The prognosis of PTCL is generally poor, with the exception of anaplastic large cell lymphoma (ALCL) that is anaplastic lymphoma kinase (ALK)-positive 3.
Relationship Between PTCL and ALK-Positive Anaplastic Lymphoma
- ALK-positive ALCL is an aggressive CD30-positive T-cell lymphoma with a chromosomal translocation involving the ALK gene and the expression of ALK protein 4.
- The prognosis of ALK-positive ALCL is remarkably better than other T-cell lymphomas, with an overall response rate of ~90%, a 5-year relapse-free survival of ~60%, and a 5-year overall survival of 70% 4.
- There is no direct evidence to suggest that PTCL can progress to ALK-positive anaplastic lymphoma, but ALK-negative ALCL has a superior outcome compared to PTCL, not otherwise specified (PTCL-NOS) 5.
Treatment and Outcomes
- Standard first-line treatment for ALK-positive ALCL consists of doxorubicin-containing polychemotherapy, which is associated with excellent results 4.
- The development of novel therapies targeting CD30 and ALK appears promising for the treatment of ALK-positive ALCL 4.
- For patients with PTCL, outcomes using frontline treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapy are typically poor, but the addition of brentuximab vedotin has shown statistically superior progression-free survival and overall survival 6.