INTRODUCTION — The peripheral T cell lymphomas (PTCL) are a heterogeneous group of generally aggressive neoplasms that constitute less than 15 percent of all non-Hodgkin lymphomas (NHLs) in adults. Among these, in decreasing frequency of occurrence, are:
●Peripheral T cell lymphoma, not otherwise specified (PTCL, NOS)
●Anaplastic large cell lymphoma, primary systemic type (ALCL)
●Angioimmunoblastic T cell lymphoma (AITL)
●Extranodal NK/T cell lymphoma, nasal type
●Adult T cell leukemia/lymphoma
●Enteropathy associated T cell lymphoma
●Hepatosplenic T cell lymphoma
●Mycosis fungoides/Sézary syndrome
●Subcutaneous panniculitis-like T cell lymphoma
Treatment of most subtypes of noncutaneous PTCL will be reviewed here.
Discussed separately are:
●Treatment of anaplastic large cell lymphoma (see "Treatment of systemic anaplastic large cell lymphoma")
●Treatment of adult T cell leukemia/lymphoma (see "Treatment and prognosis of adult T cell leukemia-lymphoma")
●Treatment of mycosis fungoides/Sézary syndrome (see "Treatment of advanced stage (IIB to IV) mycosis fungoides" and "Treatment of early stage (IA to IIA) mycosis fungoides")
●Treatment of extranodal NK/T cell lymphoma, nasal type (see "Treatment of extranodal NK/T cell lymphoma, nasal type")
●Treatment of relapsed or refractory PTCL (see "Treatment of relapsed or refractory peripheral T cell lymphoma")
●Clinical presentation, pathologic features, diagnosis, and prognosis of PTCLs (see "Clinical manifestations, pathologic features, and diagnosis of peripheral T cell lymphoma, not otherwise specified")
SPECIAL CONSIDERATIONS DURING THE COVID-19 PANDEMIC — The coronavirus disease 2019 (COVID-19) pandemic has increased the complexity of cancer care. Important issues include balancing the risk from treatment delay versus harm from COVID-19, ways to minimize negative impacts of social distancing during care delivery, and appropriately and fairly allocating limited health care resources. These issues and recommendations for cancer care during the COVID-19 pandemic are discussed separately.
●(See "COVID-19: Considerations in patients with cancer".)
PRETREATMENT EVALUATION — The initial evaluation of patients with NHL must establish the precise histologic subtype, the extent and sites of disease (table 1), and the performance status (table 2A-B) of the patient. General approaches to the diagnostic work-up and staging of NHL are presented separately. (See "Clinical presentation and initial evaluation of non-Hodgkin lymphoma" and "Pretreatment evaluation and staging of non-Hodgkin lymphomas".)
Once the diagnosis has been definitively established, the pretreatment evaluation determines both the bulk of disease and the individual's comorbidities that are likely to have an impact on treatment options. In addition to a history and physical examination, it is our practice to perform the following pretreatment studies in patients with PTCL:
●Laboratory studies include a complete blood count with differential, chemistries with liver and renal function and electrolytes, lactate dehydrogenase (LDH), hepatitis B, HIV, and uric acid. (See "Hepatitis B virus reactivation associated with immunosuppressive therapy".)
●Unilateral bone marrow aspiration and biopsy.
●A contrast-enhanced computed tomography (CT) scan of the chest, abdomen, and pelvis. This study provides critical information on the measurement of disease prior to treatment and aids in staging [1]. Most cases of PTCL are FDG-avid. When available, we obtain a combined positron emission tomography (PET)/CT scan at diagnosis to serve as a baseline for comparison after therapy. (See "Pretreatment evaluation and staging of non-Hodgkin lymphomas", section on 'Imaging'.)
●A study of cardiac ejection fraction (eg, echocardiogram or MUGA) should be performed if anthracyclines are used. (See "Clinical manifestations, diagnosis, and treatment of anthracycline-induced cardiotoxicity" and "Risk and prevention of anthracycline cardiotoxicity".)
●Men and women of childbearing potential should receive counseling about the potential effect of treatment on their fertility and options for fertility-preserving measures. (See "Fertility and reproductive hormone preservation: Overview of care prior to gonadotoxic therapy or surgery".)
OVERVIEW OF TREATMENT — PTCL is a heterogeneous group of T cell lymphomas and survival depends, at least partially, on the subtype identified. In general, without treatment the survival of patients with PTCL is measured in months. With combination chemotherapy, five-year overall survival rates may be as high as 74 and 49 percent among patients with a low (ie, zero to 1) or low-intermediate (ie, 2) score on the International Prognostic Index (IPI), respectively (table 3) [2]. However, such low-risk patients are uncommon and the five-year survival rates after combination chemotherapy are 21 and 6 percent for the more common patient with high-intermediate (ie, 3) or high (ie, 4 to 5) IPI scores, respectively.
Historically, patients with PTCL have been included in trials of chemotherapy regimens for patients with aggressive NHL. However, the rarity and heterogeneity of patients with PTCL have limited the ability to make conclusions regarding treatment based on subset analyses of these trials. It is clear that patients with T cell NHL have inferior rates of response to chemotherapy, progression-free survival (PFS), and overall survival than patients with B cell NHL:
●Overall response rates with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy for T cell NHL range from 50 to 70 percent [3]. In comparison, response rates with CHOP or CHOP plus rituximab in B cell NHL are generally 80 to 90 percent [4].
●The median PFS in PTCL following CHOP chemotherapy is 12 to 14 months with approximately 30 percent of patients being alive and free of disease five years after treatment [5]. By way of comparison, the PFS at five years in diffuse large B cell lymphoma is 54 percent with approximately 60 percent of patients being long-term disease-free survivors [4].
The poor outcomes with conventional chemotherapy have generated interest in more aggressive strategies such as the use of autologous hematopoietic cell transplantation or radiation therapy as consolidation. The role of consolidation therapy in PTCL is controversial and its use varies depending on the lymphoma subtype and the patient's IPI score. (See 'Consolidation therapy' below.)
Our approach is generally consistent with that proposed by consensus guidelines from the National Comprehensive Cancer Network (NCCN), the European Society for Medical Oncology, the British Committee for Standards in Haematology, and the Italian Society of Hematology [6-9].
Management of anaplastic large cell lymphoma, adult T cell leukemia/lymphoma, mycosis fungoides/Sézary syndrome, and extranodal NK/T cell lymphoma, nasal type are discussed separately. (See "Treatment of systemic anaplastic large cell lymphoma" and "Treatment of advanced stage (IIB to IV) mycosis fungoides" and "Treatment of early stage (IA to IIA) mycosis fungoides" and "Treatment of extranodal NK/T cell lymphoma, nasal type".)
INDUCTION THERAPY — Our approach to induction therapy of PTCL is stratified based on tumor expression of CD30, which can be targeted by brentuximab vedotin (BV; CD30-directed antibody linked to the antitubulin agent monomethyl auristatin E).
CD30-positive PTCL — For PTCL in which ≥10 percent of cells express CD30 by immunohistochemistry, we suggest initial treatment with BV+CHP (BV plus cyclophosphamide, doxorubicin, prednisone) rather than alternative chemotherapy regimens. This suggestion is based on superior response rates without added toxicity when BV+CHP was compared with CHOP (CHP+vincristine) for treatment of PTCL.
We generally treat with BV+CHP every three weeks for six cycles; BV+CHP is similar to CHOP (table 4), but vincristine is excluded and, instead, BV 1.8 mg/kg is given intravenously on day 1 of each cycle. BV is approved by the US Food and Drug Administration (FDA) for treatment of CD30-positive PTCL [10]. The dose of BV should be adjusted for mild hepatic impairment, and prescribing information carries a warning about the rare occurrence of progressive multifocal leukoencephalopathy. (See "Progressive multifocal leukoencephalopathy (PML): Epidemiology, clinical manifestations, and diagnosis".)
Our preference for BV+CHP is based on superior survival without added toxicity among 452 patients who were randomly assigned to BV+CHP versus CHOP in the multicenter, double-blind, ECHELON-2 trial [11]. Eligible patients had CD30-positive PTCL (≥10 percent per immunohistochemistry), of whom 70 percent had systemic anaplastic large cell lymphoma (ALCL). After median follow-up of >3 years, BV+CHP was associated with superior rates of complete remission (CR; 68 versus 56 percent, respectively) and objective response (83 versus 72 percent); subgroup analysis demonstrated superior survival in patients with ALCL, but the numbers of patients with other PTCL histologies were small and may have precluded the identification of an overall survival (OS) advantage with BV+CHP for these patients. Treatment-related toxicity was similar between the two groups, except for more grade ≥3 diarrhea (6 versus 1 percent) with BV+CHP; other grade ≥3 toxicity associated with BV+CHP included neutropenia (35 percent), peripheral sensory neuropathy (4 percent), and nausea (2 percent). Adverse events leading to death occurred in 3 and 4 percent of patients treated with BV+CHP and CHOP, respectively.
The role of imaging to evaluate response to therapy is discussed below. (See 'Response assessment' below.)
Induction therapy for CD30-positive ALCL is discussed separately. (See "Treatment of systemic anaplastic large cell lymphoma", section on 'CD30-positive ALCL'.)
CD30 negative — For PTCL in which CD30 is expressed by <10 percent of tumor cells, we suggest treatment that is informed by age, medical fitness, and clinician/patient preference:
●For patients ≤60 years of age, we suggest treatment with CHOEP (CHOP plus etoposide) rather than CHOP (table 4) or more intensive regimens. This preference places greater value on modest improvements in clinical outcome than on increased toxicity with CHOEP, when compared to CHOP. Compared with CHOEP, more intensive induction regimens (eg, infusional EPOCH, HyperCVAD) provide comparable clinical outcomes but greater toxicity.
●For patients >60 years old or for less medically fit individuals of any age, we favor CHOP to avoid the increased toxicity with other regimens.
CHOP is generally administered every three weeks (table 4); we suggest not adding rituximab to the CHOP regimen in this setting [12]. For CHOEP, intravenous etoposide (100 mg/m2) is administered on days 1 through 3 of each 21-day cycle in addition to standard CHOP. Alternatively, standard CHOP may be administered with intravenous etoposide (100 mg/m2) on day 1 followed by oral etoposide (200 mg/m2) on days 2 and 3 of each 21-day cycle. The higher oral dose of etoposide is necessary due to poor bioavailability with oral administration. If infusional EPOCH is selected, it should be administered without rituximab (table 5).
No prospective studies in CD30-negative PTCL have directly compared the regimens described above. Depending on the histology and patient population studied, overall response rates with CHOP are between 50 and 70 percent [3]. The most common severe (grade 3/4) side effect is granulocytopenia (approximately 60 percent). Other common side effects are generally mild to moderate alopecia, nausea, vomiting, and infusion-related reactions. There is approximately 1 percent treatment-related mortality with CHOP.
CHOEP results in superior outcomes when compared with CHOP in patients ≤60 years old, based on retrospective studies. As examples:
●A post-hoc analysis evaluated outcomes from 320 patients with a variety of PTCL histologies who were treated on prospective trials with six to eight cycles of CHOP or CHOEP and followed for a median of 44 months [3]. There was no difference in three-year OS. However, in patients ≤60 years old who had a normal LDH (lactate dehydrogenase) at diagnosis, CHOEP was associated with a trend toward superior three-year event-free survival (EFS) when compared with CHOP (61 percent [95% CI 49-73 percent] versus 48 percent [95% CI 30-66 percent]), when patients with ALK-positive ALCL were excluded from the analysis. This benefit was not seen in patients >60 years old.
●In an analysis of the Swedish Lymphoma Registry, for patients ≤60 years old, compared with CHOP, treatment with CHOEP was associated with superior PFS (HR 0.49; 95% CI 0.29-0.83) but no difference in OS, in 252 patients with PTCL (excluding ALK-positive ALCL) [13].
Compared with CHOP, other intensive regimens are associated with increased toxicity but not with improved outcomes. As an example, a phase III trial that compared CHOP with a more intensive regimen (etoposide, ifosfamide, cisplatin alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine) in 88 patients with newly diagnosed PTCL reported no difference in two-year EFS, but greater toxicity with the more intensive regimen [14]. A single institution retrospective analysis of 135 patients with PTCL reported no improvement in three-year OS, but more early treatment-related early deaths with more intensive regimens such as HyperCVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone) compared with CHOP [15]. In trials of aggressive non-Hodgkin lymphoma that included PTCL (typically a minority of the participants), compared with CHOP, more aggressive regimens offered no improvement in clinical outcomes and were associated with increased toxicity. These studies are discussed in more detail separately. (See "Initial treatment of advanced stage diffuse large B cell lymphoma", section on 'Choice of regimen'.)
CONSOLIDATION THERAPY — The poor outcomes in certain subgroups of patients with PTCL after conventional chemotherapy alone have generated interest in the use of hematopoietic cell transplantation (HCT) or radiation therapy (RT) as consolidation therapy. The role of consolidation therapy in PTCL is controversial. However, there is a general consensus that HCT is not indicated after the attainment of a first complete remission (CR) in the following two subgroups:
●Most patients with ALK-positive anaplastic large cell lymphoma (ALCL). Such patients have five-year overall survival (OS) rates ranging from 70 to 93 percent after anthracycline-based chemotherapy. (See "Treatment of systemic anaplastic large cell lymphoma", section on 'Autologous HCT in first remission'.)
●Patients with localized PTCL, not otherwise specified (PTCL, NOS) and a low or low-intermediate International Prognostic Index (IPI) score (table 3). Five-year OS rates are 74 and 49 percent among patients with a low (ie, zero to 1) or low-intermediate (ie, 2) IPI score, respectively [2].
PTCL patients who do not fit into these two categories have five-year OS rates of 20 percent or less after combination chemotherapy alone [2]. Such patients should be considered for consolidation therapy. The choice among autologous HCT, RT, or a combination of the two depends on the patient's candidacy for HCT and the extent of initial disease. Consolidation RT is largely reserved for use in patients with localized (stage I or II) PTCL. Autologous HCT, preferably given in the context of a clinical trial, is generally offered in addition to radiation for patients initially presenting with localized disease and an intermediate or high IPI score. Autologous HCT, administered without RT, is offered to those who had extensive disease at the time of diagnosis.
Autologous transplantation — Autologous HCT has been evaluated for the treatment of PTCL in retrospective analyses, database studies, and small prospective trials enrolling a very select group of patients with good performance status. Overall, autologous HCT appears to be most beneficial for patients in first CR relative to second or subsequent CR or partial remission (PR) [13,16-19]. With autologous HCT in first CR, OS rates may be as high as 85 percent at three years and 30 percent at five years post-autologous HCT, but vary depending on the lymphoma subtype and IPI score (table 3). There is no proven role for consolidation with allogeneic HCT for PTCL in first remission [20].
As mentioned above, our general approach to the use of autologous HCT for consolidation after CR is as follows:
●We do not routinely perform autologous HCT for patients with PTCL, NOS in first CR who have localized disease and a low or low-intermediate IPI score (table 3). This is principally because such patients demonstrate five-year OS rates ranging from 50 to 75 percent after chemotherapy plus consolidation RT.
●For patients who are candidates for autologous HCT with PTCL, NOS and a high-intermediate or high IPI score, we generally offer consolidation with autologous HCT in first CR since such patients demonstrate five-year OS rates of 20 percent or less after combination chemotherapy alone.
Treatment-related morbidity and mortality with autologous HCT are relatively low (≤3 percent); however, patients who undergo autologous HCT are at risk for bacterial, viral, and fungal infections, the time course of which varies in the post-transplant period, according to the degree of immune deficiency and cytopenia induced by the transplantation procedure. (See "Overview of infections following hematopoietic cell transplantation".)
The following are summaries of the largest studies investigating autologous HCT in PTCL:
●In a phase II trial, 160 patients with previously untreated PTCL (not ALK-positive ALCL) were treated with six cycles of biweekly CHOEP [21]. Etoposide was omitted in patients >60 years of age. In total, 115 (72 percent) attained a CR or PR and proceeded with high dose chemotherapy and autologous HCT. Treatment-related mortality was 4 percent. At a median follow-up of 60.5 months, estimated OS rates and progression-free survival (PFS) at five years were 51 percent (95% CI 43-59 percent) and 44 percent (95% CI 36-52 percent), respectively. On subset analysis, patients with ALK-negative ALCL had significantly better outcomes when compared with the other histologic subtypes. Differences in outcomes among the other histologic subtypes did not attain statistical significance. Estimated rates of OS and PFS at five years according to histologic subtype were as follows:
•ALK-negative ALCL (31 patients) – Five-year OS 70 percent, five-year PFS 61 percent
•Angioimmunoblastic T cell lymphoma (AITL, 30 patients) – Five-year OS 52 percent, five-year PFS 49 percent
•Enteropathy associated T cell lymphoma (EATL, 21 patients) – Five-year OS 48 percent, five-year PFS 38 percent
•PTCL, NOS (62 patients) – Five-year OS 47 percent, five-year PFS 38 percent
●An analysis of the CIBMTR database identified 40 patients with PTCL (including ALCL) undergoing autologous HCT in first CR [19]. The estimated rates of PFS and OS at one year were 75 and 80 percent, respectively. Corresponding rates at three years were 58 and 70 percent. Non-relapse mortality at one and three years was 4 and 6 percent.
●A retrospective analysis of 115 patients with PTCL who underwent high dose therapy and autologous HCT between January 1990 and December 1999 included 37 patients in first CR, 28 in second or subsequent CR, 44 in partial remission (PR), and 6 with refractory disease [16]. An estimated 56 percent of patients were alive at five years. Among those with a CR, the estimated disease-free survival at five years was 60 percent. Patients transplanted in first CR had a significantly higher rate of five-year OS when compared with patients transplanted in second or subsequent CR or PR (80 versus 50 percent, respectively). No patient with refractory disease was a long-term disease-free survivor.
●Another retrospective analysis evaluated 83 patients with PTCL treated between 2000 and 2006 (32 patients with PTCL, NOS and 27 with AITL) [22]. The treatment plan consisted of four to six cycles of CHOP followed by stem cell mobilization with dexamethasone, carmustine, melphalan, etoposide, and cytarabine or etoposide, methylprednisolone, cytarabine, and cisplatin. Patients then underwent cyclophosphamide/total body irradiation conditioning followed by autologous HCT. The following outcomes were noted:
•On intent-to-treat analysis, 55 of the 83 patients completed chemotherapy and underwent autologous HCT. The most common reason for not undergoing autologous HCT was progressive disease, which occurred in 24 patients.
•The three-year OS rate was 48 percent and varied with the PTCL prognostic index score.
A number of smaller prospective trials have evaluated the role of autologous HCT as part of the initial treatment of PTCL [23-29]. In general, these trials included heterogeneous patient populations and utilized a variety of induction and conditioning regimens. Several included patients with ALK-positive ALCL, a group now known to have a superior prognosis even with treatment strategies that do not incorporate HCT. In these studies, OS rates ranged from 86 percent at three years to approximately 30 percent at 5 to 12 years post-autologous HCT. Universally, these trials have tended to include a select group of younger patients. This fact, combined with the heterogeneous nature of the treatments and non-randomized design of the trials, makes it impossible to render a definitive assessment of the utility of autologous HCT in first CR for PTCL. A large, international randomized trial is desperately needed to answer this important question.
Radiation — With the exception of extranodal NK/T cell lymphoma, the role of RT in managing PTCL remains undefined. In general, we offer RT in the following situations:
●Patients with localized (stage I or II) disease who achieve a CR with chemotherapy.
●Some patients with localized disease who achieve a PR with chemotherapy. RT is generally offered to such patients who are not HCT candidates. However, if a patient is a candidate for HCT, the choice to use RT in this setting is complicated by the degree of response to chemotherapy. As an example, a patient with measurable residual disease (MRD; also referred to as minimal residual disease) may benefit from going straight to HCT. In comparison, a patient with more substantial residual disease may be offered a second-line chemotherapy regimen prior to HCT or may be offered RT administered before or after HCT.
●Control of symptoms from localized disease in the palliative setting.
Data on the use of consolidation radiation therapy in this setting are limited to retrospective analyses and clinical experience [30-33]. Such analyses have noted a high rate of local relapse (30 to 40 percent at five years) with chemotherapy administered alone or with standard radiation doses used for B cell lymphomas. There has been a suggestion that higher radiation doses (eg, ≥40 Gy) may provide better local control for patients with PTCL after CR is obtained with chemotherapy.
Our practice is consistent with the National Comprehensive Cancer Network (NCCN) guidelines, which recommend consolidative RT in all PTCL patients with stage I or II disease who achieve remission after standard anthracycline-based chemotherapy. Unlike in diffuse large B cell lymphoma where chemotherapy is abbreviated if RT is used for consolidation, patients with limited stage PTCL are treated with a full course of six to eight cycles of CHOP prior to the incorporation of radiation. This is principally because it is not known if the addition of RT allows for the truncation of CHOP chemotherapy with similar long-term outcomes.
PTCL SUBTYPES — Although the most common PTCL histology is PTCL, not otherwise specified (PTCL, NOS), there are several subtypes of PTCL with unique features that require treatment modifications. These are discussed in the following sections.
Anaplastic large cell lymphoma — Anaplastic large cell lymphoma, T/null cell type (ALCL) has a more favorable outcome than other subtypes of PTCL. Management of ALCL is discussed separately. (See "Treatment of systemic anaplastic large cell lymphoma".)
Angioimmunoblastic T cell lymphoma — Small, uncontrolled prospective studies and retrospective analyses of angioimmunoblastic T cell lymphoma (AITL) include:
●A prospective, uncontrolled trial of 39 patients with AITL investigated a staged treatment approach in which patients were initially treated with prednisone [34]. Those who did not attain a complete remission (CR) with prednisone or those with life-threatening disease at the time of diagnosis were treated with an anthracycline-based combination chemotherapy regimen. When compared with those who received prednisone therapy, patients treated with combination chemotherapy had superior CR rates (64 versus 29 percent, respectively) and a longer median survival (19 versus 11 months, respectively).
●An analysis of 28 patients with AITL enrolled on prospective trials of CHOP or CHOP-like chemotherapy reported three-year event-free survival (EFS) and overall survival (OS) rates of 50 and 68 percent, respectively [3].
●Retrospective studies have reported high survival rates with autologous HCT, especially for patients in first CR at the time of HCT. As an example, a retrospective trial of autologous HCT in 146 patients with AITL yielded two- and four-year OS rates of 67 and 59 percent, respectively [35]. When compared with those who had chemotherapy-sensitive disease without a CR, patients who had achieved a CR prior to autologous HCT had superior rates of progression-free survival (PFS) at two years (70 versus 42 percent) and four years (56 versus 30 percent). Patients who had refractory disease at the time of autologous HCT had the worst outcome with a PFS of 23 percent at 24 and 48 months.
●A retrospective analysis of 45 patients with AITL who underwent myeloablative (25 patients) or reduced intensity allogeneic HCT reported one- and three-year OS rates of 66 and 64 percent, respectively, with 53 percent of patients being alive without disease progression at three years [36]. OS and PFS were significantly better for those patients with chemotherapy-sensitive disease at the time of HCT.
Hepatosplenic T cell lymphoma — There are limited data on the treatment of hepatosplenic T cell lymphoma. While up to half of patients may achieve a CR with chemotherapy, remissions are typically short lived with a median OS of approximately one year [37]. No standard therapy exists, though autologous or even allogeneic transplantation should be considered in patients who achieve a CR. Although the data to support these aggressive strategies are limited, the outcome with chemotherapy alone is poor. Patients with severe thrombocytopenia may benefit from splenectomy prior to the initiation of chemotherapy [38].
Subcutaneous panniculitis-like T cell lymphoma — Subcutaneous panniculitis-like T cell lymphoma is a very rare entity often presenting with an associated hemophagocytic syndrome (HPS). While previous classification systems included a gamma-delta variant, the current World Health Organization classification system only recognizes those cases with a mature alpha-beta T cell phenotype.
●Alpha beta – Patients with the alpha/beta variant have more indolent disease confined to the subcutis, are less likely to have HPS, and have a favorable prognosis with a five-year OS rate of 82 percent (91 percent in the absence of HPS) [39]. Some of these patients can be managed like the more indolent cutaneous T cell lymphomas. (See "Treatment of early stage (IA to IIA) mycosis fungoides".)
●Gamma delta – This entity has been renamed cutaneous gamma/delta T cell lymphoma in the 2008 World Health Organization classification. These patients are more likely to have HPS. The five-year OS rate is 11 percent [40]. These patients should be treated with aggressive, anthracycline-based chemotherapy with consideration of autologous or allogeneic HCT if remission is achieved. (See 'Induction therapy' above.)
Extranodal NK/T cell lymphoma, nasal type — The treatment of patients with extranodal NK/T cell lymphoma, nasal type is discussed in more detail separately. (See "Treatment of extranodal NK/T cell lymphoma, nasal type".)
Enteropathy-associated T cell intestinal lymphoma — Enteropathy-associated T cell intestinal lymphoma (EATL) is a rare condition that occurs most commonly in patients with gluten-sensitive enteropathy (ie, celiac disease). (See "Clinical manifestations, pathologic features, and diagnosis of enteropathy-associated T cell lymphoma".)
Patients who achieve remission and are candidates for autologous HCT may benefit from HCT in first remission. The five-year OS rate with anthracycline-based chemotherapy alone is approximately 10 to 20 percent [41-43]. With HCT, case reports have suggested that some patients may achieve longer survival rates.
Data regarding the use of autologous HCT for EATL mostly come from case reports and case series [44-49]. As examples:
●A retrospective study of 26 patients with EATL treated with an intensive chemotherapy regimen (ifosfamide, etoposide, epirubicin, and methotrexate) followed by autologous HCT reported rates of PFS and OS at five years of 52 and 60 percent, respectively [47].
●Another retrospective study of 44 patients with EATL treated with induction chemotherapy followed by autologous HCT reported rates of relapse, PFS, and OS of 39, 54, and 59 percent at four years, respectively [50]. When compared with those with more advanced disease, patients in first CR or partial remission (PR) at the time of HCT had a trend towards improved survival at four years (66 versus 36 percent).
Patients with EATL are usually malnourished at the time of diagnosis. In addition, intra-abdominal perforation, fistula formation, and infection frequently complicate management, especially in those who required surgical resection. Nutritional supplementation and vigorous control of infection are integral to any treatment program [51,52]. Given its association with celiac disease, patients should be maintained on a gluten-free diet. (See "Management of celiac disease in adults".)
Adult T cell leukemia-lymphoma — Adult T cell leukemia-lymphoma (ATL) is a peripheral T cell neoplasm associated with infection by the human T-lymphotropic virus, type I. Although it is considered one of the highly aggressive T cell non-Hodgkin lymphoma variants, the disease course is variable and sometimes quite indolent. Treatment of ATL is discussed separately. (See "Treatment and prognosis of adult T cell leukemia-lymphoma".)
PATIENT FOLLOW-UP
Response assessment — The prognostic utility of mid-treatment (after three cycles) positron emission tomography (PET) in T cell lymphoma is controversial. Our practice is to obtain a mid-treatment PET, but based on the available data, computed tomography (CT) is also reasonable. One month following the completion of planned therapy (or sooner if the outcome is unfavorable), the response to treatment should be documented by history, physical examination, and laboratory studies (complete blood count, lactate dehydrogenase [LDH], and biochemical profile). The post-treatment imaging study of choice is the PET/CT scan, which provides information on the size and activity of residual masses and allows for the distinction between active disease and fibrosis. PET/CT should be obtained six to eight weeks after completion of chemotherapy and 12 weeks after the completion of radiation therapy [53].
Disease response is determined using information gathered from the history, physical, and PET/CT scan (table 6).
A discussion of the accuracy of PET/CT in the follow-up of patients with lymphoma is presented separately. (See "Pretreatment evaluation and staging of non-Hodgkin lymphomas".)
If a partial remission (PR) is obtained, consolidation radiation therapy may be considered for patients with localized disease who are not candidates for transplantation. Otherwise, patients with a PR are frequently considered for second-line chemotherapy agents and/or transplantation. (See 'Consolidation therapy' above and "Treatment of relapsed or refractory peripheral T cell lymphoma".)
Surveillance for relapse — Following the completion of therapy, restaging, and documentation of complete remission (CR), patients are seen at periodic intervals to monitor for treatment complications and assess for possible relapse. The frequency and extent of these visits depends on the comfort of both the patient and physician. There have been no prospective, randomized trials comparing various schedules of follow-up. When planning the post-treatment surveillance strategy, care should be taken to limit the number of CT scans, particularly in younger individuals, given concerns about radiation exposure and the risk for second malignancies. (See "Radiation-related risks of imaging".)
Our approach to patient surveillance is to schedule patient visits every three months during the first two years, then every six months starting two years after CR. Starting at year 5, patients are seen once per year. At these visits we perform a history and physical examination, complete blood count, chemistries, and LDH. We obtain a CT scan of the chest, abdomen, and pelvis every six months for the first 18 months after documentation of an initial CR. We only obtain additional PET/CT scans to further evaluate any concerning findings noted on CT scans. We do not obtain routine CT scans after 18 months unless there are signs, symptoms, or exam findings to suggest relapse.
Relapsed disease can be suggested by changes on imaging studies but can only be confirmed by biopsy. As such, a biopsy should always be obtained to document relapsed disease before proceeding to salvage therapy. (See "Treatment of relapsed or refractory peripheral T cell lymphoma".)
CLINICAL TRIALS — Often there is no better therapy to offer a patient than enrollment onto a well-designed, scientifically valid, peer-reviewed clinical trial. Additional information and instructions for referring a patient to an appropriate research center can be obtained from the United States National Institutes of Health (www.clinicaltrials.gov). (See "Treatment of relapsed or refractory peripheral T cell lymphoma", section on 'Clinical trials'.)
SUMMARY AND RECOMMENDATIONS
●The peripheral T cell lymphomas (PTCL) are a heterogeneous group of generally aggressive neoplasms that constitute less than 15 percent of all non-Hodgkin lymphomas (NHLs) in adults. There is no general consensus regarding the optimal treatment regimen for these patients and all patients should be encouraged to participate in clinical trials. We offer the following suggestions for patients who are not candidates for or choose not to participate in clinical trials.
●Our choice of induction therapy for PTCL is stratified based on tumor expression of CD30, which is targeted by the CD30-directed antibody-drug conjugate brentuximab vedotin (BV):
•For PTCL in which ≥10 percent of cells express CD30 by immunohistochemistry, we suggest treatment with BV+CHP (BV plus cyclophosphamide, doxorubicin, prednisone) rather than CHOP (CHP+vincristine), based on superior response rates without added toxicity (Grade 2C). (See 'CD30-positive PTCL' above.)
•For PTCL in which CD30 is expressed by <10 percent of tumor cells, we suggest treatment with a combination chemotherapy regimen that is informed by age, medical fitness, and clinician/patient preference (see 'CD30 negative' above):
-For patients ≤60 years old, we suggest treatment with CHOEP (CHOP plus etoposide) rather than CHOP (table 4) or more intensive regimens (Grade 2C). This preference places greater value on modest improvements in clinical outcome than on increased toxicity with CHOEP, when compared to CHOP.
-For patients >60 years old or for less medically fit individuals of any age, we favor CHOP to avoid the increased toxicity with other regimens.
●After the completion of induction chemotherapy, patients should be evaluated for the use of consolidation therapy with radiation therapy and/or autologous hematopoietic cell transplantation (HCT). Those with limited stage disease who achieve a partial response may attain a complete remission (CR) if consolidation radiation is administered. The use of autologous HCT in first CR is principally based on the PTCL subtype and the International Prognostic Index (IPI) score (table 3):
•For patients with PTCL, not otherwise specified (PTCL, NOS) in first CR and a low or low-intermediate IPI score, we suggest observation rather than autologous HCT (Grade 2C). (See 'Consolidation therapy' above.)
•For patients with PTCL, NOS and a high-intermediate or high IPI score, we suggest the use of autologous HCT in first CR rather than observation or allogeneic HCT (Grade 2C). (See 'Consolidation therapy' above.)
•For patients with angioimmunoblastic T cell lymphoma (AITL), we suggest autologous HCT in first CR rather than observation (Grade 2C). Those who can tolerate chemotherapy but are not candidates for autologous HCT can be treated with chemotherapy followed by observation. Patients who have comorbidities that prevent the use of combination chemotherapy may be considered for initial treatment with steroids (eg, prednisone). (See 'Angioimmunoblastic T cell lymphoma' above.)
•For patients with enteropathy-associated T cell intestinal lymphoma (EATL) who have a good performance status and chemotherapy-sensitive disease, we suggest treatment with intensive chemotherapy followed by autologous HCT rather than chemotherapy alone (Grade 2C). (See 'Enteropathy-associated T cell intestinal lymphoma' above.)
