Treatment outcome in T-cell lymphoblastic lymphoma in adults - a population-based study from the Swedish Lymphoma Registry

Background. T-cell lymphoblastic lymphoma (T-LBL) is a rare neoplasm of precursor lymphoblast origin, for which there is no standard treatment for adults. Results of current treatment strategies in selected populations do exist but are largely unreported for unselected series. Here, we aimed to investigate treatment outcome in a population-based cohort. Material and methods. Patients were identified through the Swedish Lymphoma Registry and data was retrospectively collected for all adult (>= 18 years) Swedish T-LBL patients diagnosed during 2000-2009. Results. A total of 39 patients with median age 40 years (range 18-78) were identified with females being significantly older than males (median age 66 vs. 37, p = 0.027). The five-year overall survival for all patients was 42%. Female gender was associated with shorter survival also when adjusted for treatment strategy and age [hazard ratio (HR) 4.29; p = 0.002]. Thirty patients received intensive chemotherapy, otherwise used for treatment of acute lymphoblastic leukemia (ALL), which resulted in an overall response rate of 97% and a five-year progression-free survival (PFS) of 49%. In this group only CNS involvement at diagnosis predicted shorter PFS (HR 13.3; p = 0.03). Among patients treated with hyper-CVAD the addition of mediastinal irradiation resulted in prolonged time to progression compared to patients receiving only chemotherapy (p = 0.047). The major reason for treatment failure was relapse and in this series 18-fluoro-deoxyglucose positron emission tomography (PET) did not predict this risk. Conclusion. This population-based study indicates that all fit T-LBL patients should be considered for intensive treatment. Our results also suggest a beneficial effect of mediastinal irradiation in combination with hyper-CVAD treatment. Relapsing patients have a dismal outcome irrespective of salvage treatment

Clinical factors and outcome in T-cell lymphoma: a population-based perspective

The heterogeneous group of T-cell lymphomas consist mostly of aggressive diseasess, with generally unfavourable outcome compared to aggressive B-cell lymphomas following similar therapy. This thesis focus on outcome and risk factors for inferior survival, in an unselected population-based cohort of T-cell lymphoma patients. In the first study, outcome of the precursor malignancy T-cell Lymphoblastic Lymphoma was investigated. This lymphoma has many similarities to T-cell Acute Lymphoblastic Leukemia, and intensive chemotherpay developed for leukemia is known to result in better outcome, than standard lymphoma therapies. The study confirms the superior survival after intensive therapy also in a population-based setting. Intensive as opposed to non-intensive treatment was the main prognostic factor for survival, while age was not associated with an inferior outcome among intensively treated patients. The other three studies focus on outcome in peripheral T-cell lymphomas (PTCL). The second study investigates outcome according to treatment and standard clinical factors at diagnosis. Male gender was found to be associated with inferior survival. Intensification of first-line treatment with up-front autologous stem cell transplantation (auto SCT) consolidation was found to be associated with a favourable outcome in patients younger than 70 years. Relapsing patients had a dismal outcome, with a median post relapse survival of 6 months. Study number three focused on the occurance of central nervous system (CNS) relapse in PTCL. In all, 28 patients (4.5%) experienced CNS relapse, most commonly with leptomeningeal involvement. Extensive extranodal involvement, skin or gastrointestinal involvement was associated with a higher risk for secondary CNS spread. At relapse patients had a very poor survival, irrespective of CNS involvement or not, with no survival difference between the groups. The last study investigates the impact of comorbidity in PTCL. Using the Charlson Comorbidity Index (CCI), presence of concomittant disease was found to be independently associated with inferior survival. CCI was the only factor at diagnosis that showed an association with survival after first-line auto SCT. The association with favourable outcome in patients treated with auto SCT found in the second study, was still significant when adjusting for CCI. In patients ≥75 years, a similar survival in patients treated with curative and low-intensity chemotherapy was found. This was not changed when adjusting for the CCI. In summary, the studies included in this thesis provides information on risk factors and population-based outcomes in T-cell lymphomas. Associations between treatment intensification and better outcome suggests a beneficial effect of these strategies in younger patients. The thesis also provides information on previously poorly documented disease, and patient-related, factors in PTCL, and will possibly serve as comparative data for future population-based studies

Real world data on prognostic factors and treatment in peripheral T-cell lymphomas: a study from the Swedish Lymphoma Registry.

Peripheral T-cell Lymphomas (PTCLs) are rare lymphomas with mostly poor outcome with current treatment. Addition of etoposide to CHOP and up-front consolidation with autologous stem cell transplantation (autoSCT) have shown promising results, but have never been tested in randomized trials. As a complement to retrospective analyses of clinical trials, we aimed at analyzing prognostic factors and outcome in an unselected, population-based cohort. Through the Swedish Lymphoma Registry we identified 755 PTCL patients diagnosed during a 10-year period. In addition to International Prognostic Index (IPI) factors, male gender was associated with an adverse overall survival (OS) (HR 1.28, p=0.011) and progression-free survival (PFS) (HR 1.26, p=0.014). In an intention-to-treat analysis in 252 nodal PTCL and EATL patients (excluding ALK-positive ALCL), up-front autoSCT was associated with a superior OS (HR 0.58, p=0.004) and PFS (HR 0.56, p=0.002) compared to patients treated without autoSCT. Addition of etoposide to CHOP resulted in superior PFS in patients up to 60 years (HR 0.49, p=0.008). This study is the largest population-based PTCL cohort reported so far and provides important information on outcome in PTCL outside the setting of clinical trials

Central nervous system relapse in peripheral T-cell lymphomas: A Swedish lymphoma registry study.

Central Nervous System (CNS) relapse in non-Hodgkin lymphomas (NHL) carries a very poor prognosis. Risk factors and outcome have been studied in aggressive B-cell lymphomas but very little is known about the risk in peripheral T-cell lymphoma (PTCL). We aimed at analyzing risk factors for CNS involvement at first relapse or progression, and the outcome of these patients, in a large population-based cohort of PTCL patients. Twenty-eight out of 625 patients (4.5%) developed CNS disease over time. In multivariable analysis disease characteristics at diagnosis independently associated with an increased risk of later CNS involvement were involvement of >1 extranodal site (Hazard Ratio [HR] 2.60, 95% Confidence Interval [95% CI] 1.07-6.29, p=0.035), skin (HR 3.51, 95% CI 1.26-9.74, p=0.016) and gastrointestinal involvement (HR 3.06, 95% CI 1.30-7.18, p=0.010). The outcome of relapsed/refractory patients was very poor and CNS involvement was not associated with a significantly worse outcome compared to relapsed/refractory patients without CNS involvement in multivariable analysis (HR 1.6, 95% CI 0.96-2.6, p=0.074). The results from the present study indicate that CNS relapse in PTCL occurs at a frequency similar to what is seen in aggressive B-cell lymphomas, but the poor outcomes in relapse are largely driven by systemic rather than CNS disease

Impact of comorbidity on survival in peripheral T-cell lymphomas : A Swedish Lymphoma Registry study

Comorbidity impacts survival in B-cell lymphoma patients, but the influence in peripheral T-cell lymphomas (PTCLs) has been little studied. To investigate the impact of comorbidity on outcome in PTCL, we identified adult patients with newly diagnosed PTCL from 2000 to 2009 in the Swedish Lymphoma Registry. Data on comorbidity at diagnosis were retrospectively collected according to the Charlson Comorbidity Index (CCI). Comorbid conditions were present in 263 out of 694 (38%) patients. A CCI score of ≥2 was associated with inferior overall survival (OS) (hazard ratio [HR] 1.63, P 0 was associated with inferior OS (HR 2.40, P = .013). Chemotherapy regimens were classified as curative or low-intensity treatments. Among patients aged ≥75 years (n = 214), low-intensity and curative treatment groups had similar OS (HR 0.8, P = .6), also when adjusted for CCI. In summary, our results demonstrate CCI to be independently associated with survival in PTCLs. Even limited comorbidity impacted survival after front-line auto SCT, which needs to be considered in treatment decisions. Intensive anthracycline-based chemotherapy in elderly PTCL patients might be of limited benefit

Impact of comorbidity in older patients with peripheral T-cell lymphoma : an international retrospective analysis of 891 patients

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive neoplasms with poor outcomes, commonly affecting older patients with comorbidities. This study aims to describe outcomes of older patients with PTCL in a large international cohort. Patients aged $70 years with PTCL diagnosed from 1 January 2010 to 31 December 2015 in the Swedish Lymphoma Registry (SLR) and California Cancer Registry (CCR) were identified. Data on comorbidity were retrospectively collected according to the Charlson Comorbidity Index (CCI), and clinical outcomes were extracted. A total of 891 patients were included (SLR, n 5 173; CCR, n 5 718). Median age was 77 (SLR) and 78 (CCR) years. Included subtypes were as follows: angioimmunoblastic T-cell lymphoma, n 5 226; anaplastic large-cell lymphoma, n 5 122; enteropathy-associated T-cell lymphoma (EATL), n 5 31; hepatosplenic TCL, n 5 7; natural killer–/T-cell lymphoma, n 5 62; PTCL not otherwise specified, n 5 443. CCI data were available in 775 patients (87%), and CCI scores were divided into the groups CCI 5 0 (39%), CCI 5 1 (22%), and CCI . 1 (39%). Median age did not differ among the CCI groups (P 5 .72). Patients with a CCI . 1 had a worse median overall survival (4.4 months) compared with patients with CCI 5 0 (11.9 months) and CCI 5 1 (8.4 months; P, .001). Comorbidity and advancing age in as little as 5-year increments are important adverse factors in this group. Most patients died of lymphoma within a year from diagnosis, underscoring the importance of developing new treatments

Nationwide Assessment of Patient Trajectories in Mantle Cell Lymphoma: The Swedish MCLcomplete Project

Mantle cell lymphoma (MCL) is a B-cell malignancy currently considered incurable. Although some patients obtain prolonged remission after first-line chemoimmunotherapy, many will need several treatment lines. Here, we present a nationwide assessment of treatment strategies, time to progression and survival in MCL. All patients diagnosed with MCL 2006–2018 were identified in the Swedish Lymphoma Register. Information on all lines of therapy was extracted from the medical records. Overall and progression-free survival (OS and PFS) were assessed through August 2021. In total, 1367 patients were included (median age, 71 years) and median follow-up was 6.8 years. Two hundred and one (15%) were managed initially with watch-and-wait, but 1235 (90%) eventually received treatment. The most frequently used first-line regimens were rituximab-bendamustine (BR) (n = 368; 30%) and Nordic MCL2 (n = 342; 28%). During follow-up, 630 patients (46%) experienced relapse/progression and 546 (40%) received second-line treatment. The most frequently used second-line regimen was BR (n = 185; 34%) but otherwise a wide variety of second-line treatments were used. Further, 382 and 228 patients experienced a second or third relapse/progression, respectively. Median PFS after first (PFS-1), second (PFS-2), third (PFS-3), and fourth (PFS-4) treatment lines was 29.4, 8.9, 4.3, and 2.7 months. Patients with early progression, defined as a PFS-1 <24 months, had an inferior median OS of 13 versus 37 months in patients with later relapse. For patients treated with frontline BR, however, time to relapse had no impact on later outcome. By use of nationwide population-based data, we provide important benchmarks for future studies of all treatment lines in MCL