The aggressive peripheral T-cell lymphomas make up less than 10% of all lymphomas diagnosed each year in the United States. They provide a wide variety of clinical syndromes, many of which have been well defined only in the past few decades. The results of therapy for patients with aggressive peripheral T-cell lymphomas have been much worse than observed for patients with aggressive B-cell lymphomas. This undoubtedly reflects, at least in part, that only a minority of patients with aggressive peripheral T-cell lymphoma are included in clinical trials. It is not surprising that the most effective therapy for diffuse large B-cell lymphoma—the most common of the aggressive lymphomas—was the most effective treatment in these trials. Since peripheral T-cell lymphomas are clinically and biologically distinct entities, there would have been no reason to expect that the same treatment would work equally for them.
The aggressive peripheral T-cell lymphomas, despite their relative infrequency, include a wide variety of illnesses (Table 1
These tumors can be subdivided into those developing primarily in (1) lymph nodes and (2) extranodal sites. The subtypes of aggressive peripheral T-cell lymphomas will be dealt with in the rest of this paper, and are divided into those of primary nodal and primary extranodal origin.
The ability of pathologists to diagnose aggressive peripheral T-cell lymphoma has been much less reproducible than their ability to diagnose aggressive B-cell lymphomas. For example, expert hematopathologists using modern classification systems are able to diagnose aggressive B-cell lymphomas, with few exceptions, in a highly reproducible manner.2
However, a recent study of the WHO classification system for the aggressive T-cell lymphomas found an approximately 10% lower rate of agreement by expert hematopathologists than was seen for B-cell lymphomas (Table 2
The application of gene expression studies has the potential to improve our ability to diagnose aggressive peripheral T-cell lymphomas. A recent review suggested that gene expression patterns will have an impact on our ability to classify aggressive peripheral T-cell lymphomas and are likely to be particularly important with certain subtypes.4
For example, it appears that angioimmunoblastic T-cell lymphoma, anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma, and adult T-cell leukemia/lymphoma have robust and reproducible molecular signatures.5
In contrast, peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) was molecularly heterogeneous, with some tumors showing the molecular signature of angioimmunoblastic T-cell lymphoma. PRIMARILY NODAL AGGRESSIVE PERIPHERAL T-CELL LYMPHOMAS Peripheral T-Cell Lymphoma Not Otherwise Specified
Patients with PTCL-NOS present at a median age of 60 years with a striking male predominance (Table 3
). About 70% of patients will have widespread disease. The distinction between these patients and those with diffuse large B-cell lymphoma can be made on biopsy only when the tumor cells mark as mature T-cells. Unfortunately, the treatment outcome for patients with PTCL-NOS has been much poorer, with shorter survival and one-third to one-fourth the chance to remain free of disease for 5 years.
We now know that not all tumors with a PTCL-NOS diagnosis are the same. Some of them have gene expression patterns characteristic of angioimmunoblastic T-cell lymphoma.5
There appears to be more than one other subgroup, though these are not yet well defined. It obviously confounds the interpretation of clinical trials and suggests that not all patients will benefit maximally from the same treatment.
The most common treatment for patients with PTCL-NOS has been an anthracycline-containing regimen like cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Because of the poor results seen to date, many physicians offer an autologous transplant in first remission, although it is unclear that this yields a significant advantage. A number of new drugs are being studied in these patients (Table 4
), although none have yet made it into first-line therapy. For patients with aggressive peripheral T-cell lymphomas, we are in desperate need of an improved treatment regimen that could serve as a standard in the same way that CHOP has for patients with diffuse large B-cell lymphoma. For patients who relapse, both autologous and allogeneic hematopoietic stem cell transplantation can be curative.6,7
At least one report suggested that for patients with recurrent disease, allogeneic transplantation is superior.8 Angioimmunoblastic T-Cell Lymphoma
Angioimmunoblastic T-cell lymphoma is the second most common of the aggressive peripheral T-cell lymphomas.3
It occurs more frequently in northern Europe.3
The typical patient with this tumor is aged >60 years, presents with systemic symptoms, and has widespread disease and an elevated level of lactate dehydrogenase. As might be expected, survival has been poor, with a large international review3
showing a 5-year failure-free rate of 18% and a 5-year overall rate of 32%.