Version May 2024
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 in adults.
This topic discusses management of the following subtypes of PTCL:
●Peripheral T cell lymphoma, not otherwise specified (PTCL, NOS)
●Angioimmunoblastic T cell lymphoma (AITL)
●Enteropathy-associated T cell lymphoma (EATL)
Classification of lymphomas and clinical presentation and diagnosis of these PTCL subtypes are discussed separately:
●(See "Classification of hematopoietic neoplasms", section on 'Lymphoid neoplasms'.)
●(See "Clinical manifestations, pathologic features, and diagnosis of angioimmunoblastic T cell lymphoma".)
Management of PTCL, NOS; AITL; and EATL is divided into induction chemotherapy and post-induction management. Because these diseases are less responsive to chemotherapy than many other types of lymphoma, induction therapy is often guided by interim response assessment. After completion of induction therapy, post-induction management is guided by disease stage, prognosis, and medical fitness.
Management of relapsed and refractory PTCL is discussed separately. (See "Treatment of relapsed or refractory peripheral T cell lymphoma".)
This topic does not discuss management of the following categories of T cell lymphomas, which are discussed separately:
●(See "Initial treatment of systemic anaplastic large cell lymphoma (sALCL)".)
●(See "Treatment and prognosis of adult T cell leukemia-lymphoma".)
●(See "Treatment of Sézary syndrome".)
●(See "Treatment of extranodal NK/T cell lymphoma, nasal type".)
PRETREATMENT EVALUATION — The initial evaluation of patients with non-Hodgkin lymphoma (NHL) must establish the histologic subtype, disease stage (table 1), and the patient’s suitability for intensive treatments, including hematopoietic cell transplantation (HCT).
General approaches to the diagnostic work-up and staging of NHLs are presented separately. (See "Clinical presentation and initial evaluation of non-Hodgkin lymphoma" and "Pretreatment evaluation and staging of non-Hodgkin lymphomas".)
Diagnosis and classification of T cell NHLs are discussed separately. (See "Classification of hematopoietic neoplasms", section on 'Mature T cell or NK cell lineage'.)
Clinical and laboratory assessment — Pretreatment evaluation determines the disease stage and identifies comorbidities that may influence treatment choices. PTCL most often involves nodal sites, but many patients present with extranodal involvement, such as liver, bone marrow, gastrointestinal (GI) tract, and skin.
●Clinical – History should include the presence of constitutional symptoms (unexplained fevers, sweats, weight loss).
Physical examination must evaluate node-bearing areas and the size of the liver and spleen.
●Laboratory – Studies include:
•Hematology – Complete blood count with differential count.
•Serum chemistries – Basic metabolic panel, including electrolytes; liver function tests, including lactate dehydrogenase (LDH); and renal function tests, including uric acid.
•Infectious – Hepatitis B and human immunodeficiency virus (HIV) testing. (See "Hepatitis B virus reactivation associated with immunosuppressive therapy".)
●Bone marrow examination – Unilateral bone marrow aspiration and biopsy.
●Imaging – Positron emission tomography (PET)/computed tomography (CT) is performed prior to treatment; it is performed again after three cycles of treatment (PET3) and following completion of initial therapy (end-of-induction PET). Most cases of PTCL are fluorodeoxyglucose (FDG)-avid.
Contrast-enhanced CT of the chest, abdomen, and pelvis is helpful for staging and initial measurement of disease.
●Heart – Echocardiogram or radionucleotide ventriculogram to estimate cardiac ejection fraction if an anthracycline may be used.
●Fertility – People of childbearing potential should receive counseling about potential effects of treatment on fertility and options for fertility-preserving measures. (See "Fertility and reproductive hormone preservation: Overview of care prior to gonadotoxic therapy or surgery".)
Pathology — Pathology findings are important for classifying PTCL subtypes and they affect treatment choices and prognosis.
PTCL should be diagnosed and classified according to either the International Consensus Classification [1] or the World Health Organization 5th edition [2], as discussed separately. (See "Classification of hematopoietic neoplasms", section on 'Mature T cell or NK cell lineage'.)
An excisional or incisional biopsy specimen is preferred, but core needle biopsies may be acceptable in some circumstances. A fine needle aspirate is not adequate for initial diagnosis and classification. The biopsy specimen should be reviewed by a hematopathologist with expertise in PTCL.
Evaluation of the biopsy specimen should confirm the T cell immunophenotype by immunohistochemistry and/or flow cytometry, while molecular studies can analyze T cell receptor (TCR) rearrangement and other features. Pathologic evaluation should include:
●CD30 expression – For the purpose of selecting front-line therapy, we consider CD30 expression by ≥1 percent of tumor cells to define a CD30-positive PTCL. (See 'Overview of management' below.)
Immunohistochemical detection of CD30 expression is not standardized. It is important to ensure that CD30 expression is assessed for tumor cells and not inflammatory cells, such as immunoblasts that can also express CD30.
●Molecular analysis – Molecular findings are associated with prognosis, but they do not guide current management.
As an example, most patients with PTCL, not otherwise specified (NOS) can be grouped according to either GATA3 overexpression (one-third of patients) or TBX21 overexpression (one-half of cases) [3,4]. PTCL, NOS with GATA3 overexpression is associated with a very poor prognosis [3,5,6]. PTCL, NOS with TBX21 overexpression is generally associated with a better prognosis, although a subset of TBX21-high tumors with a cytotoxic gene expression profile and/or DNMT3A mutations have very poor prognosis [3,7].
Fitness/transplant eligibility — Medical fitness influences management choices for PTCL.
Performance status should be assessed (table 2).
We assess comorbid conditions (eg, heart, lung, kidney, liver disease) that might affect treatment, including eligibility for autologous HCT. Many institutions limit autologous HCT to patients ≤65 to 70 years without major medical comorbidities, but practices vary. Eligibility criteria for autologous HCT are discussed separately. (See "Determining eligibility for autologous hematopoietic cell transplantation".)
Prognosis — Application of a prognostic scoring system is important for post-induction management decisions. (See 'Postinduction management' below.)
The International Prognosis Index (IPI) (table 3) [8] or the Prognostic Index for PTCL (PIT) [9] can be used to estimate prognosis in patients with PTCL. Disease-specific prognostic indices, including one specific to angioimmunoblastic T cell lymphoma (AITL), have been developed, but the IPI and PIT are acceptable for routine clinical use [10].
The IPI was originally developed for aggressive B cell lymphomas [8], but it is widely used for T cell lymphomas. PIT was specifically developed for patients with PTCL [9]. Both IPI and PIT have prognostic value in PTCL and were associated with outcomes of patients with PTCL in multiple studies [9,11-17]. (See "Clinical manifestations, pathologic features, and diagnosis of peripheral T cell lymphoma, not otherwise specified", section on 'International Prognostic Index (IPI)'.)
Inferior survival has been associated with male sex, age ≥60 years, stage III/IV, performance status ≥2, bulky tumor (ie, ≥10 cm), and elevated serum LDH [18].
OVERVIEW OF MANAGEMENT — PTCL comprises a heterogeneous group of T cell lymphomas. This topic discusses management of the following subtypes:
●Peripheral T cell lymphoma, not otherwise specified (PTCL, NOS)
●Angioimmunoblastic T cell lymphoma (AITL)
●Enteropathy-associated T cell lymphoma (EATL)
We strongly encourage participation in a clinical trial, when available.
Management of PTCL involves:
●Selection of an induction regimen – Induction therapy is stratified according to CD30 expression by the tumor cells (algorithm 1):
•CD30 positive – We consider cases of PTCL in which CD30 is expressed by ≥1 percent of tumor cells to be CD30 positive. Front-line therapy of CD30-positive PTCL generally includes brentuximab vedotin (BV), a CD30-directed antibody-drug conjugate. (See 'CD30 positive' below.)
CD30 expression is highly variable, and it is uncertain if response to BV is directly related to the percentage of tumor cells that express CD30. The package insert for BV does not specify a threshold for CD30 expression for use with chemotherapy in the front-line setting.
•CD30 negative – For cases with little or no CD30 expression, standard induction therapy generally uses anthracycline-based chemotherapy and is guided by age and medical fitness:
-Medically fit, younger patients – More intensive chemotherapy regimens are generally limited to patients ≤60 or 65 years without major comorbidities. (See 'Fit, younger patients' below.)
-Older or less-fit patients – For older patients or those with significant comorbid illnesses, lower intensity therapy is generally used to avoid excess toxicity. (See 'Older or less-fit patients' below.)
●Response-guided therapy – Because the response to induction therapy is often incomplete or transient, many experts use response-guided treatment, in which positron emission tomography (PET) is repeated after three cycles of induction chemotherapy (PET3) (algorithm 1). This approach enables quicker recognition of refractory disease and earlier implementation of care for refractory disease. (See 'PET3 response' below.)
●End-of-induction PET – After completing induction therapy, end-of-induction PET guides further management. (See 'End-of-induction PET' below.)
●Post-induction management – Post-induction management is stratified according to disease stage, prognostic score, and fitness (algorithm 2), as discussed below. (See 'Postinduction management' below.)
●Monitoring – After completing therapy, patients are monitored for relapse and treatment-related adverse effects, as discussed below. (See 'Monitoring' below.)
Our approach to management of PTCL is consistent with guidelines from the United States National Comprehensive Cancer Network (NCCN), the European Society for Medical Oncology, the British Committee for Standards in Haematology, and the Italian Society of Hematology [19-22].
INDUCTION THERAPY — The choice of induction regimen for PTCL is stratified according to tumor expression of CD30 (algorithm 1), which can be targeted by brentuximab vedotin (BV), a CD30-directed monoclonal antibody linked to monomethyl auristatin E. We consider cases in which immunohistochemistry (IHC) demonstrates CD30 expression by ≥1 percent of tumor cells to be CD30 positive, but CD30 expression is not standardized and some patients with lower levels of CD30 expression respond to BV. Although the most definitive trial (ECHELON-2, described below) required CD30 expression by ≥10 percent of tumor cells for enrollment, there is no consensus threshold, the package insert does not specify a minimum level of expression, and there is no clear correlation between level of expression and response [23,24].
We use response-guided therapy, in which positron emission tomography (PET) is repeated after the first three cycles of induction therapy (PET3) (algorithm 1), because a significant proportion of patients do not respond robustly, or they relapse early during treatment. Response-guided therapy enables early recognition of refractory disease and avoids excessive toxicity from ineffective systemic therapy. Results from PET3 inform the decision whether to complete induction therapy with three additional chemotherapy cycles or proceed to management for refractory disease. (See 'PET3 response' below.)
CD30 positive — For patients with CD30-positive PTCL, we suggest BV+CHP (brentuximab vedotin, cyclophosphamide, doxorubicin, prednisone) (algorithm 1), rather than other chemotherapy regimens, based on acceptable toxicity and a trend toward superior outcomes for patients with CD30-positive PTCL [23,25].
●BV+CHP administration – BV+CHP is similar to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) (table 4), but vincristine is replaced by BV 1.8 mg/kg intravenously on day 1 of each cycle. The dose of BV should be adjusted for mild hepatic impairment.
Three initial cycles of BV+CHP are followed by interim restaging with PET3. (See 'PET3 response' below.)
Further management is guided by the PET3 response (algorithm 1) (see 'PET3 response' below):
•Complete response (CR) or partial response (PR) - For patients with complete response (CR) or partial response (PR) on PET3, we complete induction therapy by treating with three additional cycles of BV+CHP (six cycles total).
•Refractory disease (ie, less than PR) - Patients with a PET3 response less than PR are managed for refractory disease. (See "Treatment of relapsed or refractory peripheral T cell lymphoma".)
The US Food and Drug Administration (FDA) approved BV in combination with CHP for initial treatment of adults with CD30-expressing PTCL, including angioimmunoblastic T cell lymphoma (AITL) and PTCL, not otherwise specified (NOS). The European Medicines Agency approved BV+CHP only for adult patients with previously untreated systemic anaplastic large cell lymphoma (sALCL). Prescribing information for BV carries a warning about the rare occurrence of progressive multifocal leukoencephalopathy. (See "Progressive multifocal leukoencephalopathy (PML): Epidemiology, clinical manifestations, and diagnosis".)
●Outcomes – The preference for BV+CHP as initial therapy for CD30-positive PTCL is based on results from the ECHELON-2 trial that randomly assigned patients with CD30-positive T cell lymphomas to BV+CHP versus CHOP [23,25].
ECHELON-2 reported superior outcomes with BV+CHP, but the benefits were not statistically significant for histologies other than sALCL; importantly, the trial was not powered to determine efficacy according to non-sALCL subtypes. Among 452 enrolled patients, only one-third had non-sALCL subtypes: PTCL, NOS (13 percent); AITL (13 percent); and enteropathy-associated T cell lymphoma (EATL; 1 percent). For the entire trial population, BV+CHP achieved superior overall survival (OS) and progression-free survival (PFS), but with median follow-up of four years, there was no significant difference in OS or PFS for the 72 patients who had non-sALCL subtypes [23]. For patients with AITL, estimated five-year OS was 68 versus 63 percent with CHOP, while for PTCL, NOS, five-year OS was 46 versus 36 percent. There was no apparent correlation between the level of CD30 expression and the likelihood of response among patients with non-sALCL histologies.
Treatment-related toxicity was similar in both trial arms of ECHELON-2. There was more grade ≥3 diarrhea (6 versus 1 percent) with BV+CHP; other grade ≥3 adverse events included neutropenia (35 percent), peripheral sensory neuropathy (4 percent), and nausea (2 percent) [25]. Adverse events leading to death occurred in 3 and 4 percent of patients treated with BV+CHP and CHOP, respectively. With longer follow-up, peripheral neuropathy resolved in three-quarters of affected patients in both trial arms [23].
Outcomes for patients with anaplastic large cell lymphoma (ALCL) in ECHELON-2 are presented separately. (See "Initial treatment of systemic anaplastic large cell lymphoma (sALCL)", section on 'Induction therapy'.)
An ongoing phase 2 study (NCT03113500) is evaluating the safety and efficacy of adding BV to CHOEP-based chemotherapy (BV plus cyclophosphamide, doxorubicin, vincristine, etoposide, prednisone), followed by BV consolidation in patients with newly diagnosed CD30-positive PTCL.
CD30 negative — For CD30-negative PTCL, we stratify treatment according to age and medical fitness (algorithm 1). Many experts consider an age threshold for more aggressive treatments to be 60 or 65 years, but we favor functional assessment of fitness, rather than a strict age limit. (See 'Fitness/transplant eligibility' above.)
The mainstay of induction therapy for CD30-negative PTCL is anthracycline-based chemotherapy. Compared with non-anthracycline-containing regimens, anthracycline-based therapy was associated with a trend toward superior survival (hazard ratio [HR] 0.71 [95% CI 0.48-1.05]) in a study of 499 patients with PTCL [26].
Fit, younger patients — For medically fit, younger patients with CD30-negative PTCL, we suggest CHOEP rather than CHOP (table 4) or more intensive regimens. Compared with CHOP, CHOEP is associated with better clinical outcomes and moderately increased toxicity; other intensive regimens are associated with similar outcomes but substantially greater toxicity.
●CHOEP administration – Many experts limit use of CHOEP to medically fit patients ≤60 or 65 years because of toxicity.
In CHOEP, intravenous etoposide 100 mg/m2 on days 1 through 3 of each 21-day cycle is added to the CHOP regimen (table 4). An alternate version of CHOEP administers intravenous etoposide 100 mg/m2 on day 1 of CHOP, 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.
PET3 is performed after the first three cycles of CHOEP (algorithm 1) in order to decide whether to give three additional cycles of induction or treat for refractory PTCL (as described above for BV+CHP). (See 'PET3 response' below.)
●Outcomes – No randomized trials have directly compared CHOEP with CHOP, but most studies indicate that CHOEP is associated with better outcomes in patients ≤65 years. Further treatment intensification of CHOEP or addition of agents to a CHOP backbone were not associated with improved outcomes for patients with PTCL, but many caused greater toxicity [27].
Studies that compared CHOEP and CHOP follow; outcomes with other regimens are presented below. (See 'Other induction regimens' below.)
•Swedish lymphoma registry – Outcomes were more favorable with CHOEP than with CHOP in this registry study of 755 patients, which included 256 patients with PTCL, NOS; 104 with AITL; and 68 with EATL [28]. For patients ≤60 years, CHOEP was associated with superior PFS (HR 0.49 [95% CI 0.29-0.83]) and trends toward better OS (HR 0.58 [95% CI 0.33-1.01]) and higher overall response rate (ORR; 81 versus 70 percent).
•Dutch registry – This national registry, which included 1427 patients (AITL 21 percent; PTCL, NOS 44 percent; ALCL 35 percent), reported that CHOEP was associated with superior survival [29]. Five-year OS was superior for patients treated with CHOEP compared with CHOP (64 versus 44 percent, respectively), and there was a trend toward higher CR rate (60 versus 49 percent). ORR was 44 percent for patients with AITL and 32 percent for PTCL, NOS. The risk of mortality was similar with both regimens when adjusted for age, PTCL subtype, prognostic score, and subsequent transplantation (except for patients with anaplastic lymphoma kinase [ALK]-positive ALCL, who had superior survival with CHOEP).
•German studies – CHOEP was associated with superior, three-year event-free survival (EFS) in patients ≤60 years (61 versus 48 percent), but there was no difference in OS among 320 patients with PTCL (including 70 with PTCL, NOS and 28 with AITL) in a series of prospective studies by the German High-Risk Lymphoma Study Group [30]. No benefit for CHOEP was seen in patients >60 years, due to additional toxicity and treatment delays.
•Czech registry – Among patients in the Czech lymphoma registry, CHOEP was associated with superior, five-year OS (66 versus 48 percent) and better, five-year PFS (59 versus 33 percent) compared with CHOP, on an intention-to-treat basis [18]. However, it is uncertain if long-term outcomes were related to the induction regimen alone, as more patients who received CHOEP were planned for autologous hematopoietic cell transplantation (HCT; 57 versus 41 percent of patients).
•Korean registry – A retrospective review of 748 patients who received anthracycline-based therapy reported that addition of etoposide to CHOP-like therapy did not improve outcomes, but it was associated with longer hospitalizations and more transfusions [31].
Ongoing studies include a phase 3 trial of CHOP versus CHOP plus azacitidine plus chidamide (NCT05075460) and a study of CHOP plus lenalidomide (NCT04423926).
Older or less-fit patients — For older or less medically fit individuals of any age with CD30-negative PTCL, we favor CHOP induction therapy (table 4) to avoid the increased toxicity associated with CHOEP.
●CHOP administration – CHOP (table 4) is given every three weeks for three cycles, followed by PET3 (algorithm 1) to guide completion of six total cycles of CHOP (for patients with CR or PR) versus management for refractory disease (as discussed above).
●Outcomes – Outcomes with CHOP in the ECHELON-2 trial are presented above. (See 'Fit, younger patients' above.)
Outcomes are generally inferior for older patients with PTCL. As an example, among 320 patients with PTCL in a series of prospective German studies, patients ≤60 years had more favorable OS (HR 1.7 [95% CI 1.2-2.5]) and EFS (HR 1.5 [95% CI 1.1-2.2]) compared with older patients [30]. The most common grade ≥3 adverse event associated with CHOP is neutropenia (approximately 60 percent), while other adverse events include mild to moderate alopecia, nausea, vomiting, and infusion-related reactions; treatment-related mortality with CHOP is approximately 1 percent.
Interim restaging — We assess response to induction therapy by PET after three cycles of induction therapy (PET3 response). PET is again performed after completing six cycles of treatment (end-of-induction PET response).
Response criteria — Response to therapy is judged using the five-point PET scale (Deauville score) (table 5), according to Lugano criteria [32]:
●CR – PET score 0 to 3 (with or without a residual mass) and no evidence of bone marrow involvement.
●PR – PET score 4 or 5 with reduced uptake compared with baseline, no new progressive lesions, and bone marrow activity less than baseline.
●Stable disease – PET score 4 or 5 (unchanged from baseline), no new lesions, and bone marrow activity unchanged from baseline.
●Progressive disease – PET score 4 or 5 (increased compared with baseline), new sites of disease, and new or recurrent bone marrow activity.
PET3 response — PET3 response guides further management (algorithm 1):
●CR or PR – Complete the planned course of induction chemotherapy (usually six cycles total). (See 'Induction therapy' above.)
●Stable or progressive disease – Proceed to treatment for relapsed/refractory (r/r) PTCL, as described separately. (See "Treatment of relapsed or refractory peripheral T cell lymphoma".)
END-OF-INDUCTION PET — Positron emission tomography (PET) is repeated within six to eight weeks of completing chemotherapy [33], with response judged as described above. (See 'Response criteria' above.)
Post-induction management is guided by stage and prognostic score, along with the findings from the end-of-induction PET, as described below (algorithm 2). (See 'Postinduction management' below.)
POSTINDUCTION MANAGEMENT — We consider the following features in selecting postinduction management for patients with PTCL (algorithm 2):
●Prognostic score – Either the International Prognosis Index (IPI) (table 3) [8] or the Prognostic Index for PTCL (PIT) [9] can be used to estimate prognosis in patients with PTCL. (See 'Prognosis' above.)
We consider adverse prognosis for PTCL to be either:
•IPI score ≥2
•PIT score ≥1
There are no consensus criteria for an adverse clinical prognostic score in PTCL. The association of outcomes with prognostic scores for PTCL is discussed separately. (See "Clinical manifestations, pathologic features, and diagnosis of peripheral T cell lymphoma, not otherwise specified", section on 'International Prognostic Index (IPI)'.)
●Stage – Stage at diagnosis (table 1), together with the prognostic score (described above), are used to stratify post-induction management:
•Stage I and favorable prognosis (See 'Stage I with favorable prognostic score' below.)
•Stages II-IV or adverse prognostic score (See 'Advanced stage or adverse prognosis' below.)
●Age and fitness for transplantation – Management of patients with advanced stage PTCL or an adverse prognostic score, is informed by eligibility for hematopoietic cell transplantation (HCT). Many institutions limit HCT to patients ≤65 years who have no major medical comorbidities. Details of eligibility for autologous HCT are discussed separately. (See "Determining eligibility for autologous hematopoietic cell transplantation".)
Stage I with favorable prognostic score — Management is guided by results from the end-of-induction PET (algorithm 2).
●Complete response (CR) or partial response (PR) - For CR or PR in patients with stage I PTCL and a favorable prognostic score, we suggest radiation therapy (RT), based on good outcomes and modest toxicity. Management should be individualized; some patients choose observation to avoid the inconvenience and possible adverse effects (AEs) of RT. AEs associated with HCT are not warranted, considering the favorable prognosis in this setting.
●Stable disease or progressive disease - Patients with stable or progressive disease on end-of-induction positron emission tomography (PET) are treated for refractory PTCL, as discussed separately. (See "Treatment of relapsed or refractory peripheral T cell lymphoma".)
Outcomes in this setting are generally favorable. As an example, one study reported 50 to 75 percent five-year OS [11]. Small retrospective studies of adjuvant RT for early-stage PTCL have reported mixed results:
●There was a trend toward superior outcomes when RT was used as consolidation therapy among 118 patients with stage I to II PTCL in data from the Swedish lymphoma registry [28]. Compared with patients who received chemotherapy only, for the 32 patients who received RT after chemotherapy, there was a trend toward improved five-year OS (73 versus 53 percent, respectively; HR 0.58 [95% CI 0.32-1.05]) and improved five-year PFS (60 versus 45 percent, respectively; HR 0.57 [95% CI 0.32-1.03]). However, when compensating for other risk factors, there was no risk reduction associated with RT.
●In a multicenter study of 75 patients with stage I to II PTCL, there was no difference in outcomes among the 15 patients treated with combined modality therapy compared with 38 who received chemotherapy alone [34]. Median OS was 6.5 years and median event-free survival (EFS) was 2.1 years. When analyzing only the 40 patients who responded to induction chemotherapy, there was still no difference in OS or EFS between treatment modalities.
●For patients with stage I PTCL, NOS, the rates of OS and failure-free survival (FFS) were superior for 25 patients who received initial RT followed by chemotherapy, compared with 16 who received chemotherapy only in a retrospective study from the International Peripheral T-Cell Lymphoma (IPTCL) Project [35].
●Addition of RT to chemotherapy was associated with improved OS and PFS in 35 patients with stage I to II PTCL, NOS in a single-institution study [36]. For patients treated with RT after chemotherapy, three-year OS and PFS rates were 50 and 33 percent, respectively, compared with 23 and 15 percent, respectively, for chemotherapy alone.
●Compared with chemotherapy alone, there was no difference in OS, PFS, or local control in patients who received RT after chemotherapy in a single-institution study of 39 patients with stage I to II PTCL [37].
Monitoring for relapse after completion of therapy is described below. (See 'Monitoring' below.)
Advanced stage or adverse prognosis — Postinduction management of patients with advanced-stage PTCL or an adverse prognostic score is guided by the end-of-induction response and eligibility for autologous HCT. (See 'End-of-induction PET' above.)
Transplant-eligible patients — Eligibility criteria for autologous HCT vary, but many institutions limit autologous HCT to patients ≤65 years or ≤70 years without major medical comorbidities. (See 'Fitness/transplant eligibility' above.)
CR on end-of-induction PET — For patients with CR on the end-of-induction PET, we suggest either observation or autologous HCT, rather than allogeneic HCT (algorithm 2). Autologous HCT is associated with acceptable toxicity, and there is limited evidence of more favorable outcomes compared with observation alone; by contrast, allogeneic HCT is associated with substantial toxicity that outweighs its potential benefits in this setting.
Selection of postinduction management should be individualized, using shared decision-making that weighs the risks and benefits of transplantation. This conversation should include recognition that autologous HCT may cause toxicity without providing a clear benefit for the individual patient, that it is not always possible to obtain a CR after relapse, and that relapsed PTCL has a dismal prognosis.
Our approach is consistent with that of transplantation experts from the American Society of Blood and Marrow Transplantation [38], the United States National Comprehensive Cancer Network (NCCN) [39], and the European Society for Blood and Marrow Transplantation [40].
●Autologous HCT versus observation – No randomized trials have directly compared autologous HCT with observation in this setting, and results from prospective and retrospective studies are mixed. Although there are trends toward more favorable outcomes with transplantation in patients with CR, these findings are subject to biases associated with nonrandomized studies of transplantation. As examples, transplant-eligible patients are usually fitter or younger compared with others, while transplantation is more frequently offered to those with more aggressive disease. In general, one-quarter to one-half of patients in prospective studies who planned to undergo autologous HCT did not do so, usually because of early disease progression or relapse.
•Meta-analyses – Comparison of autologous HCT versus observation yielded mixed results in meta-analyses:
-A meta-analysis from 2014 reported a trend toward superior survival for patients who underwent autologous HCT in first complete response (CR1) for T cell lymphomas [41]. The study analyzed 1021 patients from 21 prospective studies, but most studies included patients who were transplanted in settings other than CR1 (eg, less than CR after induction, transplantation after relapse) or with other types of T cell lymphomas. Four of the studies compared outcomes after autologous HCT for PTCL in CR1 (128 patients) versus observation alone (468 patients); in these studies, there was no significant difference in survival with autologous HCT in CR1 (hazard ratio [HR] 0.81 [95% CI 0.31-2.13]).
-Another meta-analysis reported widely divergent outcomes when comparing prospective studies versus retrospective studies of autologous HCT in CR1 [42]. Compared with 599 patients in 16 retrospective studies, 179 patients in 3 prospective studies had inferior outcomes with transplantation (overall survival [OS] 54 versus 68 percent; progression-free survival [PFS] 33 versus 55 percent), whereas transplantation-related mortality was 2 percent in prospective studies versus 6 percent in retrospective studies. The difference in outcomes may be due to better control of confounding factors in prospective studies.
•Other studies - Results were also mixed from retrospective studies:
-Swedish registry – Autologous HCT in CR1 was associated with superior outcomes in 128 patients with PTCL and enteropathy-associated T cell lymphoma (EATL) [28]. According to intention-to-treat analysis, and with median follow-up >8 years, patients ≤70 years who underwent autologous HCT had superior OS (48 versus 26 percent; HR 0.58 [95% CI 0.40-0.84]) and PFS (41 versus 20 percent; HR 0.56 [95% CI 0.39-0.81]) compared with no transplantation. However, when analyzing only patients who were transplanted after achieving CR, there was no survival advantage for transplantation, according to univariate and multivariate analysis [43].
-COMPLETE – The Comprehensive Oncology Measures for Peripheral T-cell Lymphoma Treatment (COMPLETE) registry reported that compared with 83 patients who were not transplanted, 36 patients who underwent autologous transplantation in CR1 had superior OS (HR 0.37 [95% CI 0.15-0.89]) [44]. There were too few patients of any histologic subtype (35 patients had angioimmunoblastic T cell lymphoma [AITL]; 55 had PTCL, not otherwise specified [NOS]; 30 had anaplastic lymphoma kinase [ALK]-negative ALCL) to achieve statistical significance; however, for patients with AITL, two-year OS was 93 percent with autologous HCT versus 53 percent without transplantation, and the corresponding two-year PFS rates were 69 versus 41 percent, respectively.
-LYSA – This retrospective Lymphoma Study Association (LYSA) study reported no survival advantage with autologous HCT [45]. Among 269 patients (≤65 years) with PTCL (including 68 with ALK-positive ALCL) who achieved CR or PR after induction therapy, there was no difference in five-year OS for the 134 patients who were assigned to autologous HCT compared with 135 not assigned to transplantation; however, 16 percent of patients never proceeded to HCT, generally due to refractory disease.
-Dutch registry – This study reported superior outcomes with autologous HCT compared with observation, but more than one-third of patients had ALCL [29]. Among those transplanted in CR1, survival was superior with autologous HCT (84 percent five-year OS versus 47 percent).
-Czech registry – This study reported no survival benefit for consolidation with autologous HCT [18]. Compared with no transplantation, five-year OS with autologous HCT did not differ significantly (49 percent with autologous HCT versus 60 percent without transplantation). However, among 79 patients selected for transplantation, three-quarters of patients never received the planned autologous HCT.
-United States multicenter study – A retrospective multicenter study reported improved survival for patients who underwent autologous HCT in CR1, but in multivariable analysis, this advantage was not seen when adjusted for initial treatment response [46]. More than one-half of patients had ALCL. Among 26 transplanted patients, three-year OS and PFS were 74 and 58 percent, respectively, compared with 53 and 30 percent among 211 patients who were observed without transplantation.
An ongoing phase 3 trial by the LYSA group (TRANSCRIPT; NCT05444712) will randomly assign 204 patients with PTCL (excluding ALK-positive ALCL) to autologous HCT versus no consolidation therapy.
●Autologous HCT versus allogeneic HCT - Allogeneic HCT can provide long-term disease control for patients with PTCL, but it is associated with greater toxicity and transplantation-related mortality than autologous HCT. Comparisons of transplantation techniques are confounded by the recognition that allogeneic HCT is usually performed in patients who did not reach CR, whereas autologous HCT is more commonly offered to patients who achieved CR [47,48].
Studies that compared transplantation techniques for patients in CR1 include:
•A phase 3 clinical trial that was designed to compare autologous HCT versus allogeneic HCT in CR1 was closed prematurely in the face of high rates of transplant-related mortality with allogeneic HCT and interim analysis that indicated a significant survival difference was unlikely [49]. Three-year OS was similar between transplantation techniques (70 percent with autologous HCT versus 57 percent with allogeneic HCT), as were PFS and EFS. The causes of death differed between transplantation techniques; progressive disease accounted for most deaths in the autologous HCT group, whereas allogeneic HCT was associated with 31 percent nonrelapse mortality. There were no relapses among the patients who underwent allogeneic HCT, but 8 of 26 patients died of transplant-related toxicity. By comparison, for patients who underwent autologous HCT, there was no transplant-related mortality, but there were 13 relapses among 36 patients (36 percent). Approximately one-third of patients in both arms did not proceed to transplantation due to lack of response.
•The phase 2 FIL study reported outcomes after autologous or allogeneic HCT in CR1 for patients with PTCL, but it was not powered to evaluate the differences between the two transplantation techniques [50]. Patients ≤60 years received allogeneic HCT or autologous HCT according to donor availability; 23 received allogeneic HCT, and 14 underwent autologous HCT. With median follow-up of 40 months, four-year OS, PFS, and disease-free survival rates were 49, 44, and 65 percent, respectively.
Other studies using autologous HCT or allogeneic HCT in CR1 for patients with PTCL are presented below. (See 'Transplantation' below.)
Less than CR — For patients with less than CR on end-of-induction PET, management is guided by the nature of the residual disease (algorithm 2).
●Partial response (PR) with limited residual disease – For patients with limited residual disease (eg, a single residual site of PET activity) after induction therapy, we treat with radiation therapy (RT) plus autologous HCT.
We consider that the risk of relapse in this setting outweighs the AEs of autologous HCT. While we favor RT attempt to convert the PR to a CR before proceeding to autologous HCT, it is acceptable to proceed directly to autologous HCT and administer RT later.
Comparisons of autologous HCT with observation or allogeneic HCT in patients with CR after induction therapy for PTCL are presented above. (See 'CR on end-of-induction PET' above.)
Additional studies of autologous HCT and allogeneic HCT for PTCL are discussed below. (See 'Transplantation' below.)
●PR with more extensive residual disease, stable disease, or progressive disease – We treat patients with a PR that is not amenable to RT, stable disease, or progressive disease as relapsed/refractory (r/r) PTCL. (See "Treatment of relapsed or refractory peripheral T cell lymphoma".)
Not transplant eligible — Postinduction management of patients who are not eligible for transplantation due to age (eg, >65 years) or comorbid medical conditions is guided by the response to induction therapy and the location of disease:
●CR or PR – For patients with CR or PR after induction chemotherapy, we offer RT to consolidate the response and then monitor the patients for disease relapse. (See 'Monitoring' below.)
●Less than CR/PR – For patients with a response that is less than CR or PR, we offer RT to symptomatic sites of disease or manage as r/r PTCL. (See "Treatment of relapsed or refractory peripheral T cell lymphoma".)
MONITORING — After completing therapy, patients are seen at periodic intervals to monitor for treatment complications and assess for possible relapse. The frequency and nature of follow-up visits depend on the comfort of both the patient and clinician.
Our approach to patient surveillance is to schedule patient visits every three to six months during the first two years, every six months in years 3 to 5, and then annually or as clinically indicated.
Monitoring includes:
●Clinical – History and physical examination, complete blood count, chemistries, and lactate dehydrogenase (LDH).
●Imaging – Surveillance positron emission tomography (PET) or CT no more than every six months for the first two years, then annually as clinically indicated.
Care should be taken to limit PET and/or CT, particularly in younger individuals, given concerns about radiation exposure and the risk for second malignancies. (See "Radiation-related risks of imaging".)
Relapse can be suggested by changes on imaging studies but must be confirmed by biopsy. (See "Treatment of relapsed or refractory peripheral T cell lymphoma".)
TREATMENT MODALITIES
Chemotherapy
Standard induction regimens — Selection of induction therapy for PTCL is described above. (See 'Overview of management' above.)
Standard induction regimens include:
●BV+CHP (brentuximab vedotin, cyclophosphamide, doxorubicin, prednisone). (See 'CD30 positive' above.)
●CHOEP (cyclophosphamide, doxorubicin, vincristine, prednisone, plus etoposide). (See 'Fit, younger patients' above.)
●CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) (table 4). (See 'Older or less-fit patients' above.)
Other induction regimens — Addition of agents to a CHOP backbone, intensification of therapy, and alternative agents have not been associated with superior outcomes for patients with PTCL and are generally more toxic than CHOP or CHOEP [27]. Most studies of these regimens included small numbers of patients. Only VIP-reinforced-ABVD (etoposide, ifosfamide, cisplatin alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine) or addition of alemtuzumab or romidepsin to CHOP (described below) have been directly compared with CHOEP or CHOP in randomized trials.
●VIP-reinforced-ABVD – A randomized trial of 88 evaluable patients with PTCL (including 10 with anaplastic lymphoma kinase [ALK]-positive anaplastic large cell lymphoma [ALCL]) reported that VIP-reinforced-ABVD was more toxic than CHOP but did not achieve superior outcomes [51]. VIP-reinforced-ABVD achieved 45 percent two-year event-free survival (EFS) compared with 41 percent two-year EFS with CHOP after median follow-up of nine years.
●Alemtuzumab plus CHOP – The phase 3 ACT-2 trial, which randomly assigned 116 patients with PTCL (excluding ALK-positive ALCL) to alemtuzumab plus CHOP (A-CHOP) versus CHOP, reported no differences in overall survival (OS), progression-free survival (PFS), or EFS, but response rates were higher with A-CHOP (60 percent complete response [CR] versus 43 percent) [52]. Compared with CHOP, A-CHOP caused more cytopenias, grade ≥3 infections (40 versus 21 percent), and deaths due to infections (four versus one).
●Romidepsin plus CHOP – The phase 3 romidepsin plus CHOP (Ro-CHOP) trial randomly assigned 421 patients (18 to 80 years) with PTCL (excluding ALK-positive ALCL) to Ro-CHOP versus CHOP [53]. There was no difference in two-year OS (64 versus 63 percent, respectively) or two-year PFS (43 versus 36 percent) for the entire population and no significant differences based on prespecified subgroup analysis. A retrospective subgroup analysis reported that for angioimmunoblastic T cell lymphoma (AITL) and other T follicular helper (TFH) cell PTCL, Ro-CHOP was associated with more prolonged PFS (median PFS 20 versus 11 months; hazard ratio [HR] 0.69 [95% CI 0.48-1.00]). Grade ≥3 thrombocytopenia (50 versus 10 percent), neutropenia (49 versus 33 percent), and anemia (47 versus 17 percent) were more common with Ro-CHOP.
●Lenalidomide plus CHOP – Treatment of 71 patients with AITL reported 42 percent two-year PFS and 41 percent CR with lenalidomide plus CHOP; this was not appreciably better than treatment with CHOP in other studies [54].
●Dose-adjusted (DA)-EPOCH – Treatment with DA-EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) reported 73 percent two-year OS and 53 percent two-year PFS in 41 patients (median age 64 years [range 32 to 79 years]; 17 patients had AITL and 21 had PTCL, not otherwise specified [NOS]) [55]. For the entire population, overall response rate (ORR) was 78 percent (including 61 percent CR), while for patients ≤60 years, ORR was 94 percent (including 71 percent CR). The most common grade ≥3 adverse events were neutropenia (75 percent), anemia (41 percent), thrombocytopenia (22 percent), and febrile neutropenia (9 percent).
●MegaCHOEP – The German High-Grade Non-Hodgkin Lymphoma Study Group reported 45 percent three-year OS and 26 percent three-year EFS with MegaCHOEP in 33 patients with PTCL (including 13 with ALK-negative ALCL) [56]. ORR was 56 percent (including 49 percent CR). Only two-thirds of patients received all planned therapy because of excessive toxicity in six patients, including two treatment-related deaths, and progressive or stable disease in four patients.
●HyperCVAD – A retrospective single-institution study reported that, compared with CHOP, there was no improvement in three-year OS but more early treatment-related deaths with HyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone) [57]. The Australasian Leukaemia and Lymphoma Group reported that outcomes with modified HyperCVAD in 26 patients with PTCL were similar to outcomes with CHOP-like chemotherapy but were associated with significant toxicity [58].
●GEM-P – The randomized, phase 2 CHEMO-T study compared GEM-P (gemcitabine, cisplatin, methylprednisolone) with CHOP in patients with PTCL (≥18 years; patients with ALK-positive ALCL were excluded) [59]. The trial was closed by the data monitoring board after enrollment of 87 patients, when the 46 percent CR rate with GEM-P appeared unlikely to be superior to CHOP (62 percent).
●Azacitidine plus romidepsin – Treatment with azacitidine plus romidepsin in 10 treatment-naïve patients with PTCL was associated with 70 percent ORR (including 50 percent CR) in a multicenter phase 2 study [60].
Radiation therapy — The role of radiation therapy (RT) in managing PTCL is not well-defined, but we generally offer RT in the following situations:
●Transplant-eligible patients – Use of RT varies according to response, stage, and prognostic score:
•Advanced-stage or adverse prognostic score – We offer RT in association with autologous transplantation to patients with PR after induction therapy, as discussed above. (See 'Less than CR' above.)
•Stage I with favorable prognostic score – We offer adjuvant RT to consolidate a CR or PR. (See 'Stage I with favorable prognostic score' above.)
●Not transplant eligible – We offer adjuvant RT to consolidate a CR or PR in patients with stage I PTCL who are not eligible for transplantation due to age or fitness. (See 'Not transplant eligible' above.)
●Symptom relief – RT can provide symptom relief as a component of management for relapsed or refractory PTCL or for palliation. (See "Treatment of relapsed or refractory peripheral T cell lymphoma".)
For patients who receive adjuvant RT, positron emission tomography (PET) is generally performed within 12 weeks after completing treatment [33].
Transplantation — The role of hematopoietic cell transplantation (HCT) as consolidation therapy in first complete response (CR1) is discussed above. (See 'Transplant-eligible patients' above.)
Autologous HCT — Autologous hematopoietic cell transplantation (HCT) uses myeloablative conditioning therapy, followed by infusion of an autologous graft.
Comparisons of autologous HCT with observation or allogeneic HCT are presented above. (See 'Transplant-eligible patients' above.)
Other informative studies of autologous HCT for PTCL include:
●NLG-T-01 – This prospective study by the Nordic Lymphoma Group (NLG) reported outcomes for 115 patients who underwent autologous HCT among 166 enrolled patients; 18 percent of patients had ALK-negative systemic anaplastic large cell lymphoma (sALCL) [61]. Five-year OS was 51 percent, five-year PFS was 44 percent, treatment-related mortality was 4 percent, and progression or relapse within two years occurred in 18 percent. Five-year outcomes according to disease subtype included AITL (52 percent OS, 49 percent PFS); PTCL, NOS (47 percent OS, 38 percent PFS); and enteropathy-associated T cell lymphoma (EATL; 48 percent OS, 38 percent PFS), but differences among subtypes were not statistically significant. A subsequent publication that added 28 new patients reported 44 percent five-year OS and 39 percent five-year PFS [62].
●German study – In a prospective study of 83 patients (including 32 with PTCL, NOS; 27 with AITL, 13 with ALK-negative sALCL), three-year OS and PFS were 48 and 36 percent, respectively [63]. Two-thirds of enrolled patients were able to proceed to autologous HCT.
●GEL-TAMO – This Spanish Grupo Español de Linfomas y Trasplantes de Médula Ósear (GEL-TAMO) reported that for 37 patients with PTCL (excluding ALK-positive ALCL), transplantation in CR1 was associated with 63 percent five-year PFS [64].
●CIBMTR – Analysis of 39 patients with PTCL undergoing autologous HCT in CR1 in the Center for International Bone Marrow Transplant Registry (CIBMTR) database reported that the one-year OS and one-year PFS were 80 and 75 percent, respectively, while the three-year OS and PFS were 70 and 58 percent, respectively [47]. One-year and three-year nonrelapse mortality were 4 and 6 percent, respectively.
●Others – Other studies that also reported outcomes with autologous HCT for PTCL included transplantation in settings other than CR1 or various T cell lymphomas [16,17,65-75].
Allogeneic HCT — There is no demonstrated role for allogeneic hematopoietic cell transplantation (HCT) in CR1 for patients with PTCL. Comparisons of allogeneic HCT with autologous HCT for PTCL are presented above. (See 'CR on end-of-induction PET' above.)
Other informative studies of allogeneic HCT in PTCL include:
●A registry study of 1942 patients who underwent allogeneic HCT for PTCL reported that rates of OS, PFS, relapse/progression, and nonrelapse mortality rate were similar for 237 patients who received haploidentical grafts with posttransplant cyclophosphamide immunosuppression, compared with 1705 patients who received matched related or matched unrelated grafts [76]. Three-year OS and three-year PFS were approximately 60 and 50 percent, respectively.
●The Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) registry reported that four-year OS was 63 percent, two-year relapse rate was 19 percent, and four-year transplant-related mortality was 24 percent for 138 patients who underwent allogeneic HCT in CR1 or first partial response [77].
●A single-center study reported outcomes for 29 patients with PTCL who proceeded to allogeneic HCT in CR1 (among 49 enrolled patients) [78]. For allogeneic HCT in CR1, one-year OS was 76 percent and two-year OS was 73 percent, compared with rates of 59 and 55 percent for the entire study population (including those who were transplanted). One-year toxicity-related mortality after allogeneic HCT was 8 percent.
●In a single-institution retrospective study, 44 patients who underwent allogeneic HCT in CR1 had 54 percent five-year OS and 54 percent five-year PFS; 24 received reduced-intensity conditioning, and 20 received myeloablative conditioning [79].
OUTCOMES BY PTCL SUBTYPE — Because of their rarity, most studies of outcomes for patients with PTCL have included a variety of subtypes; only a few studies have focused on a specific subtype.
●PTCL, not otherwise specified (NOS) – Management of PTCL, NOS is described above. (See 'Induction therapy' above.)
PTCL, NOS has a dismal prognosis with low sensitivity to anthracycline-based chemotherapy [80]. The following studies reported outcomes for patients with PTCL, NOS who were mainly treated with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone):
•A retrospective study of PTCL, NOS by the IIL (Intergruppo Italiano Linfomi) registry reported that treatment with CHOP-like therapy was associated with 43 percent five-year overall survival (OS) and 53 percent complete response (CR) [9].
•A retrospective study by the IPTCL (International Peripheral T-Cell Lymphoma Project) reported 32 percent five-year OS and 43 percent progression-free survival (PFS) for 340 patients with PTCL, NOS [35]. In this report, there was no difference in survival for patients treated with anthracycline-based combination chemotherapy compared with those receiving combination chemotherapy without an anthracycline.
•A prospective observational study by ITCP (International T-cell Project) reported 32 percent five-year OS and 23 percent five-year PFS [81].
•Among 70 patients with PTCL, NOS in a series of prospective German studies, three-year OS was 54 percent, and three-year event-free survival (EFS) was 41 percent [30].
•Treatment of 64 patients with PTCL, NOS in a Korean study reported that after median follow-up of 30 months, three-year OS and PFS were 53 and 44 percent, respectively [17].
●Angioimmunoblastic T cell lymphoma (AITL) – AITL is the second most common subtype of PTCL.
Analysis of several studies did not find a significant difference between CHOP and more intensive treatments, such as ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone) [54]. Other studies of AITL include:
•Induction regimens
-A retrospective study of 157 patients by Lymphoma Study Association (LYSA) in which patients received mainly CHOP and ACVBP reported 51 percent two-year OS, 38 percent two-year EFS, and 46 percent CR [82]. There was no difference in outcomes between CHOP and ACVBP.
-A retrospective Japanese study of 207 patients, treated mainly with CHOP or THP-COP (pirarubicin, cyclophosphamide, vincristine, prednisolone), reported 54 percent three-year OS, 38 percent three-year PFS, and 66 percent CR [83].
-A phase 2 study by LYSA of 25 patients treated with rituximab (R)-CHOP reported 62 percent two-year OS, 42 percent two-year PFS, and 44 percent CR [84].
-A retrospective study of 78 patients treated with lenalidomide-CHOP reported 59 percent two-year OS, 42 percent two-year PFS, and 41 percent CR [54].
-A prospective, uncontrolled trial of 39 patients with AITL investigated a staged treatment approach in which patients were initially treated with prednisone [85]. Those who did not attain a CR with prednisone or who had life-threatening disease at diagnosis were treated with an anthracycline-based combination chemotherapy regimen. 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).
-Analysis of 28 patients with AITL enrolled in prospective trials of CHOP or CHOP-like chemotherapy reported that the three-year OS and EFS were 68 and 50 percent, respectively [30].
•Autologous HCT – Retrospective studies have reported high rates of survival with autologous hematopoietic cell transplantation (HCT), especially for transplantation in first complete response (CR1) [75].
-A retrospective study of autologous HCT in 146 patients with AITL yielded 67 percent two-year OS and 59 percent four-year OS [75]. Compared with those who did not achieve CR, patients who had achieved a CR prior to autologous HCT had superior two-year PFS (70 versus 42 percent) and four-year PFS (56 versus 30 percent). Patients with refractory disease at the time of autologous HCT had the worst outcome (23 percent two-year PFS).
-An observational study by ITCP of 282 patients (treated mainly with CHOP) reported 50 percent three-year OS, 38 percent three-year PFS, and 51 percent CR [10]. Patients who underwent autologous transplantation in CR1 had better outcomes (five-year OS 89 percent and 79 percent five-year PFS) compared with transplant-eligible patients ≤65 years who did not undergo transplantation (52 percent five-year OS and 31 percent five-year PFS). The study also reported no significant difference in five-year OS for patients receiving chemotherapy regimens with etoposide versus no etoposide (50 versus 43 percent, respectively).
•Allogeneic HCT – A retrospective analysis of 45 patients with AITL who underwent myeloablative (25 patients) or reduced intensity conditioning allogeneic hematopoietic cell transplantation (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 [86]. OS and PFS were significantly better for those patients with chemotherapy-sensitive disease at the time of HCT.
●Enteropathy-associated T cell intestinal lymphoma (EATL) – This rare condition occurs most commonly in patients with gluten-sensitive enteropathy (ie, celiac disease).
EATL is closely, but not exclusively, associated with celiac disease [87]. Many patients are malnourished at diagnosis, and they should be maintained on a gluten-free diet. Nutritional supplementation and vigorous control of infection are important because patients may experience intra-abdominal perforation, fistula formation, and infections (especially in those who required surgical resection) [88,89]. (See "Clinical manifestations, pathologic features, and diagnosis of enteropathy-associated T cell lymphoma".)
Informative studies include:
•Induction therapy – Five-year OS with anthracycline-based chemotherapy alone is approximately 10 to 20 percent [90-92]. With HCT, case reports have suggested that some patients may achieve longer survival rates.
•Autologous HCT – Patients who achieve CR may benefit from autologous hematopoietic cell transplantation (HCT).
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 60 percent five-year OS and 52 percent five-year PFS [93].
-Another retrospective study of 44 patients with EATL treated with induction chemotherapy followed by autologous HCT reported four-year OS (59 percent), PFS (54 percent), and relapse rate (39 percent) at four years, respectively [94]. When compared with those with more advanced disease, patients in first CR or partial remission at the time of HCT had a trend towards improved survival at four years (66 versus 36 percent).
-Other studies have also reported outcomes of autologous HCT for EATL [95-99].
SUMMARY AND RECOMMENDATIONS
●Description – Peripheral T cell lymphomas (PTCL) are uncommon, heterogeneous, and generally aggressive. This topic discusses management of:
•PTCL, not otherwise specified (NOS)
•Angioimmunoblastic T cell lymphoma (AITL)
•Enteropathy-associated T cell lymphoma (EATL)
●Pretreatment evaluation – Includes classification of PTCL subtype, fitness, and prognosis. (See 'Pretreatment evaluation' above.)
●Overview – Management is guided by tumor expression of CD30, fitness, and age. We use response-guided therapy for early recognition of inadequate responses and to enable prompt implementation of care for primary refractory disease. (See 'Overview of management' above.)
●Induction therapy – Stratified by tumor expression of CD30 (algorithm 1) (see 'Induction therapy' above):
•CD30 positive – For PTCL in which ≥1 percent of tumor cells express CD30, we suggest BV+CHP (brentuximab vedotin plus cyclophosphamide, doxorubicin, prednisone), rather than other regimens (Grade 2C). (See 'CD30 positive' above.)
•CD30 negative – Treatment of CD30-negative PTCL is guided by age and fitness:
-Fit, younger patients – For fit, younger patients (eg, ≤65 years), we suggest CHOEP (cyclophosphamide, doxorubicin, vincristine, prednisone plus etoposide) rather than CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) (table 4) or more intensive regimens (Grade 2C). (See 'Fit, younger patients' above.)
-Older or less fit – For older or less-fit patients, we suggest CHOP, in order to avoid the increased toxicity with other regimens (Grade 2C). (See 'Older or less-fit patients' above.)
●Interim restaging - Restage with positron emission tomography (PET) after three initial induction cycles (PET3) (algorithm 1). (See 'PET3 response' above.)
•Complete response (CR) or partial response (PR) – Finish original induction therapy (usually six cycles total). (See 'Induction therapy' above.)
•Stable or progressive disease – Manage for relapsed/refractory (r/r) PTCL. (See "Treatment of relapsed or refractory peripheral T cell lymphoma".)
●End-of-induction response – Repeat PET after completing induction therapy (see 'End-of-induction PET' above):
●Postinduction management – Stratified by stage, prognosis, and fitness (algorithm 2). (See 'Postinduction management' above.)
●Stage I with favorable prognosis (See 'Stage I with favorable prognostic score' above.)
•CR or PR - We suggest adjuvant radiation therapy (RT) (Grade 2C).
•Progressive disease - Treat for r/r PTCL (See "Treatment of relapsed or refractory peripheral T cell lymphoma".)
●Advanced disease (stage II-IV or adverse prognosis) – Post-induction management is stratified as follows:
•Transplant eligible – For fit, younger patients (eg, ≤65 years) with stage II to IV disease or adverse prognosis, management is guided by end-of-induction PET (algorithm 2) (see 'Transplant-eligible patients' above):
-CR – We suggest either observation or autologous hematopoietic cell transplantation (HCT), rather than allogeneic HCT (Grade 2C).
-Limited residual disease – For limited residual disease (eg, a single persistent site), we suggest RT, followed by autologous HCT, rather than either intervention alone (Grade 2C).
-Extensive residual disease or progressive disease – Treat for r/r PTCL. (See "Treatment of relapsed or refractory peripheral T cell lymphoma".)
•Not transplant eligible (See 'Not transplant eligible' above.)
-CR or limited residual disease - We suggest adjuvant RT (Grade 2C).
-More extensive residual disease - Treat for r/r PTCL (See "Treatment of relapsed or refractory peripheral T cell lymphoma".)
●Treatment modalities – Regimens and outcomes are discussed above. (See 'Treatment modalities' above.)
●PTCL subtypes – Outcomes for specific PTCL subtypes are presented. (See 'Outcomes by PTCL subtype' above.)
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