Abstract

Introduction:

Lymphoblastic lymphoma (LBL) is a highly aggressive malignancy composed of immature lymphocytes of B- cell or T-cell origin. LBL is typically distinguished from acute lymphoblastic leukemia (ALL) by the presence of fewer than 20% bone marrow blasts. This retrospective multicenter cohort study evaluated the clinical data of adult LBL patients diagnosed and treated at tertiary centers in Türkiye.

Materials and methods:

Thirty-eight patients from seven tertiary adult hematology clinics were included. Eligible patients were ≥18 years of age, had a pathologically confirmed diagnosis of LBL, underwent radiological staging, and received at least one chemotherapy regimen.

Results:

The median overall survival (OS) for the entire cohort was 23 months. No statistically significant difference in OS was observed between patients with T-LBL and those with B-LBL (p>0.05). The median progression-free survival (PFS) was 6 months. The 5-year OS rate was 6%, underscoring the aggressive nature of adult LBL.

Discussion:

Our findings suggest exploratory univariate associations between certain clinical features and inferior OS. Elevated LDH levels, central nervous system involvement, disease affecting ≥3 anatomical regions, cervical lymphadenopathy, failure to achieve remission after initial therapy, and male gender may correlate with poorer outcomes. These results should be interpreted cautiously given the limited sample size and reliance on univariate analyses.

Introduction

Lymphoblastic lymphoma (LBL) is a highly malignant neoplasm composed of immature lymphocytes derived from B or T cells and, less frequently, from natural killer (NK) cells. It shares biological and morphological features with acute lymphoblastic leukemia (ALL). Although the 2017 and 2022 WHO classifications group these entities together, LBL is typically distinguished from ALL by the presence of fewer than 20% marrow-infiltrating blasts (1, 2). Extra-organ involvement and lymphadenopathy are more common in LBL than in ALL and carry prognostic significance (2). Despite their biological similarities, LBL and ALL should be regarded as clinically distinct entities, given the substantial differences in clinical presentation, prognostic variables, and therapeutic strategies (3).

LBL is a rare disease for which precise incidence data remain limited. In earlier epidemiological studies, LBL was frequently categorized together with ALL (estimated incidence 1.3 per 100,000 annually) or Burkitt lymphoma (1.46 per 100,000 annually) (4). In adults, LBL accounts for approximately 2–4% of non-Hodgkin lymphomas or ALL cases, whereas in children it represents less than 30% of cases. The apparent prevalence of LBL has increased in parallel with heightened disease awareness. LBL is most commonly diagnosed in young males aged 10–30 years and, unlike ALL, more frequently exhibits a T-cell immunophenotype, leading to greater lymph node and solid organ involvement (4, 5).

B-lymphoblastic lymphoma (B-LBL) is consistently positive for at least two B-cell markers, typically CD19, CD79, and CD22. CD10, CD24, PAX5, and TdT are expressed in the majority of cases, whereas CD20 and the stem cell antigen CD34 show variable expression, and CD45 may be absent (6). T-lymphoblastic lymphoma (T-LBL) frequently exhibits a cortical CD1a+ phenotype; early-T phenotypes are uncommon, associated with a lower risk of mediastinal involvement but a higher risk of bone marrow dissemination. An early thymic precursor (ETP) phenotype, initially described in T-ALL, is occasionally observed in LBL. These cases express very early T-lymphoid markers without CD1a, CD8, and CD antigens (CD5-negative or dim) and typically co-express stem/myeloid cell markers (7).

The International Prognostic Index (IPI), incorporating age, extranodal involvement, LDH levels, stage, and performance status, has not proven predictive for LBL. Historically, patients with stage IV disease, bone marrow or CNS involvement, and elevated LDH levels (>300 IU/L) demonstrated only a 19% five-year relapse-free survival, compared with 94% in low-risk patients (8). More recent studies indicate that older age, Black ethnicity, and advanced stage may further worsen prognosis.

Genetic alterations such as t (9, 17)(q34;q32) translocation and loss of heterozygosity at 6q have been associated with adverse outcomes (9). The GRAAL-LYSA study proposed an oncogenetic-based prognostic score for T-LBL, in which NOTCH1/FBXW7 mutations, in the absence of RAS/PTEN abnormalities, were linked to a favorable prognosis (10). Conversely, adult patients with ETP-LBL receiving standard chemotherapy exhibited significantly poorer outcomes compared with non-ETP cases (11). Moreover, CT/PET response assessment and evaluation of minimally disseminated disease (MDD) or measurable residual disease (MRD) may play a critical role in prognostication (3).

The implementation of intensive ALL-like protocols has led to substantial progress in the management of adult LBL (12). In addition, notable improvements have been achieved through diverse treatment strategies, including pediatric-inspired regimens, radiotherapy, allogeneic hematopoietic stem cell transplantation, and intrathecal therapy, particularly in patients at high risk of central nervous system involvement (13, 14).

Despite recent advances, consensus on prognostic factors and optimal treatment strategies for LBL remains limited, largely due to the rarity of the disease and the small patient population. To address this gap, we analyzed data from LBL patients diagnosed and treated across multiple centers in our country. Our objective was to identify potential risk factors and evaluate their impact on overall survival and progression-free survival.

Materials and methodsPatient selection

This retrospective study included 38 patients treated between 2018 and June 2024 across seven tertiary adult hematology clinics. Eligible patients were aged 18 years or older, had a confirmed diagnosis of lymphoblastic lymphoma (LBL) from lymph nodes or other extranodal sites, demonstrated fewer than 20% bone marrow blasts on biopsy, underwent imaging studies for staging, and received at least one cycle of chemotherapy. The primary endpoint of the study was overall mortality. Owing to its retrospective design, heterogeneity in treatment and follow-up protocols across participating centers contributed to data variability. Patients with incomplete records were excluded from subgroup analyses but retained in OS and PFS calculations; details are provided in Supplementary Table 1.

Diagnostic standardization

All participating centers established the diagnosis of LBL through tissue biopsy and flow cytometry. A standardized immunophenotypic panel was applied, including CD3, CD20, TdT, CD10, and CD34, with additional markers (CD19, CD79a, PAX5 for B-LBL; CD1a, CD5, CD7 for T-LBL) used when indicated. All centers adhered to the WHO 2022 and ICC classification criteria. Bone marrow involvement was defined as <20% blasts at diagnosis, consistent with WHO criteria (1). Cases with subsequent marrow progression were documented accordingly. Although centralized pathology review was not performed, all tertiary centers followed national hematopathology guidelines to ensure methodological consistency.

Evaluation and follow-up

All patients at the study centers underwent enhanced computed tomography (CT) or positron emission tomography/computed tomography (PET/CT) for evaluation and staging. Bone marrow biopsy was performed in all participants. Treatment response was assessed according to the updated efficacy criteria established by the International Working Group (IWG) for malignant lymphoma (15). Following therapy, patients in remission were monitored every three months during the first two years, every six months from years three to five, and annually thereafter. Patients not achieving remission were followed more frequently based on clinical and laboratory findings, with hospitalization arranged when necessary. At each follow-up visit, patients in remission were evaluated with complete blood counts, serum lactate dehydrogenase (LDH) levels, and imaging modalities such as ultrasonography when clinically indicated.

Response assessment and statistical analysis

Treatment response was assessed according to the Cheson 1999 criteria, which remain widely applied in lymphoid malignancies and provide standardized definitions for remission and relapse. The use of this framework was justified by its established role in clinical trials and retrospective analyses of lymphoblastic lymphoma. For patients staged and monitored with PET/CT, metabolic response was evaluated using Deauville criteria, with visual assessment performed by experienced nuclear medicine specialists. PET/CT was not used uniformly across centers, and therefore a subset of patients were assessed by Cheson 1999 criteria alone. We acknowledge that this heterogeneity in response definitions represents a limitation of the study and may have introduced confounding in PFS calculations.

Procedures for handling missing data were predefined: patients with incomplete clinical or laboratory records were excluded from specific subgroup analyses but retained in overall survival calculations. Censoring rules were applied at the date of last follow-up for patients alive without progression. Overall survival (OS) was calculated from the date of diagnosis until death from any cause or last follow-up, while progression-free survival (PFS) was calculated from the date of diagnosis until disease progression, relapse, or death, whichever occurred first.

Statistical analyses were conducted using SPSS version 25 (IBM Corp., Armonk, NY, USA). Survival was assessed through univariate analyses employing the log-rank test, and survival rates were estimated using the Kaplan–Meier method. Given the limited sample size, only univariate analyses were performed; no Cox proportional hazards models were fitted. A Type I error threshold of <5% was considered statistically significant.

Results

The median age of the 38 patients with LBL included in the study was 37 ± 13 years; 24 (63%) were male and 14 (37%) were female. The ages of patients diagnosed with T-LBL and B-LBL were statistically similar (p>0.05), and no significant association was observed between increasing age and overall survival (OS) (p>0.05). The median follow-up period was 23 months (range, 1–64 months). Among the 38 patients, 10 (26%) were diagnosed with B-LBL using tissue biopsy and flow cytometry, whereas 28 (74%) were classified as T-LBL based on the same diagnostic methods. The median OS was 23 months for all patients, 21 months for those with T-LBL, and 56 months for those with B-LBL. Despite the apparent disparity in median OS between patients with T-LBL and B-LBL, no statistically significant difference was detected, likely due to the limited number of patients with B-LBL (p>0.05). The median progression-free survival (PFS) was 6 months overall, 4 months in patients with T-LBL, and 12 months in those with B-LBL. No statistically significant difference was observed in PFS between the two groups. The 5-year OS rate for the entire cohort was 6%, reflecting the steep decline in survival after two years. Figure 1 illustrates the Kaplan–Meier curves for OS and PFS.

Kaplan–Meier curves for overall survival (OS) and progression-free survival (PFS) in adult LBL patients. (A) OS of the entire study population. (B) PFS of the entire study population. (C) OS by subtype (T-LBL vs B-LBL). (D) PFS by subtype (T-LBL vs B-LBL). Censored cases are indicated by tick marks. LBL, lymphoblastic lymphoma; T-LBL, T-cell lymphoblastic lymphoma; B-LBL, B-cell lymphoblastic lymphoma.

Among patients diagnosed with T-LBL, 20 were male and 8 were female, whereas in the B-LBL group, 4 were male and 6 were female. Although women were more prevalent in the B-LBL cohort, no statistically significant difference in gender distribution was observed between the two groups (p>0.05). The median OS for men with T-LBL was 20 months compared to 24 months for women, with no significant difference between the groups (p>0.05). In contrast, the median OS for men with B-LBL was 13 months, whereas for women it was 56 months, revealing a statistically significant difference (p<0.05). When all patients with LBL were analyzed collectively, the median OS was 18 months for men and 56 months for women, again demonstrating a statistically significant difference (p<0.05). Laboratory values of the patients are presented in Table 1. Although median lymphocyte counts were higher in B-LBL compared to T-LBL (Table 1), this difference was not clinically meaningful and did not correlate with survival outcomes.

ParameterLBL (n=38)T-LBL (n=28)B-LBL (n=10)Age (years), median (IQR)37 (30–45)38 (31–46)34 (28–40)Sedimentation (mm/h), median (IQR)43 (25–60)49 (30–65)26 (20–35)LDH (U/L), median (range)604 (300–1200)660 (320–1300)440 (280–800)Platelet (×10³/µL), mean ± SD213,800 ± 45,000200,000 ± 40,000250,800 ± 50,000WBC (cells/µL), median (IQR)8,970 (5,000–15,000)8,990 (5,200–14,800)5,050 (3,000–8,000)Lymphocyte count (cells/µL), median (IQR)3,320 (2,000–5,000)3,800 (2,200–5,500)4,300 (2,500–6,000)Hemoglobin (g/dl), mean ± SD12.3 ± 1.212.0 ± 1.113.3 ± 1.3

Baseline clinical and laboratory characteristics of patients with LBL, T-LBL, and B-LBL.

LBL, lymphoblastic lymphoma; T-LBL, T-cell lymphoblastic lymphoma; B-LBL, B-cell lymphoblastic lymphoma; OS, overall survival; LDH, lactate dehydrogenase; WBC, white blood cell count.

Regarding disease characteristics, 19 patients (50%) were diagnosed via mediastinal lymph node biopsy and 10 (26%) via cervical lymph node biopsy. Mediastinal lymph node involvement was present in 34 patients (89.5%), while 30 patients (79%) had cervical lymph node involvement. Pleural or pericardial effusion was detected in 29 patients (76%), and bone marrow involvement in 21 patients (55%). Central nervous system involvement was observed in 6 patients (16%), involvement of three or more anatomical regions in 22 patients (58%), and extra-organ involvement in 19 patients (50%).

Twenty-nine patients (76% of the cohort) were classified as stage IV. Four patients were classified as Stage I–II, which is atypical for LBL. These rare cases may reflect early detection in localized nodal presentations, consistent with prior reports. Ten patients (26%) underwent autologous stem cell transplantation (auto-SCT), 11 (29%) underwent allogeneic stem cell transplantation (allo-SCT), and 17 (45%) did not receive transplantation. Second-line therapy was administered to 28 patients (73.7%), and 18 patients (47%) required third-line treatment. The median overall survival (OS) of the cohort was 23 months. Baseline clinical characteristics of the patients are summarized in Table 2.

ParameterCategoryLBL
(n=38)T-LBL (n=28)B-LBL (n=10)Gender n (%)Male24 (63%)20 (71%)4 (40%)Female14 (37%)8 (29%)6 (60%)Lymphadenopathy (LAP) n (%)Cervical30 (79%)25 (89%)5 (50%)Mediastinal34 (89.5%)25 (89%)9 (90%)Axillary15 (39.5%)13 (46%)2 (20%)Supraclavicular12 (32%)10 (36%)2 (20%)Abdominal16 (42%)14 (50%)2 (20%)Inguinal LAP9 (24%)8 (29%)1 (10%)Pleural/Pericardial fluid n (%)29 (76%)22 (79%)7 (70%)Bone marrow involvement n (%)21 (55%)19 (68%)2 (20%)CNS involvement n (%)6 (16%)5 (18%)1 (10%)≥3 anatomical regions involved n (%)22 (58%)17 (61%)5 (50%)Extra-organ involvement n (%)19 (50%)11 (39%)8 (80%)Immunophenotype n (%)T cell marker28 (74%)28 (100%)–B cell marker10 (26%)–10 (100%)Myeloid marker6 (16%)3 (11%)3 (30%)Stage n (%)I4 (11%)2 (7%)2 (20%)II2 (5%)2 (7%)0III3 (8%)2 (7%)1 (10%)IV29 (76%)22 (79%)7 (70%)First line treatment n (%)EPOCH12 (31.6%)10 (36%)2 (20%)CHOP5 (13%)3 (11%)2 (20%)HYPERCVAD11 (29%)7 (25%)4 (40%)BFM3 (8%)1 (4%)2 (20%)GMALL3 (8%)3 (11%)0CALGB2 (5%)2 (7%)0CHOEP2 (5%)2 (7%)0Response to first-line therapy n (%)Complete Remission13 (34%)9 (32%)4 (40%)Partial remission15 (40%)12 (43%)3 (30%)Stable disease3 (8%)3 (11%)0Progressive disease7 (18%)4 (14%)3 (30%)Transplantation n (%)Auto-SCT10 (26%)7 (25%)3 (30%)Allo-SCT11 (29%)9 (32%)2 (20%)None17 (45%)12 (43%)5 (50%)Patient status n (%)Alive at follow-up15 (40%)10 (36%)5 (50%)Deceased23 (60.5%)18 (64%)5 (50%)

Clinical characteristics, treatment, and outcomes of patients with LBL, T-LBL, and B-LBL.

Auto-SCT, autologous stem cell transplantation; Allo-SCT, allogeneic stem cell transplantation; LAP, lymphadenopathy; CNS, central nervous system; LBL, lymphoblastic lymphoma; T-LBL, T-cell lymphoblastic lymphoma; B-LBL, B-cell lymphoblastic lymphoma.

Bone marrow involvement refers to infiltration by lymphoblasts below the 20% threshold, consistent with WHO 2022 and ICC diagnostic criteria for lymphoblastic lymphoma (LBL). Patients with ≥20% blasts were excluded as acute lymphoblastic leukemia (ALL).

Twelve (31.6%) of the patients in the study received the EPOCH (etoposide, doxorubicin, cyclophosphamide, vincristine, and prednisone) protocol at their own centers, and 9 of the 12 patients completed the treatment. Three of the patients who received EPOCH treatment received autologous hematopoietic stem cell transplantation (auto-SCT), and the other received allogeneic hematopoietic stem cell transplantation (allo-SCT). Five (14%) of the patients in the centers participating in the study received CHOP (doxorubicin, cyclophosphamide, vincristine, and prednisone) treatment. Four of the patients who received CHOP treatment were able to complete the treatment, and one could not complete the treatment due to disease progression. Two of the patients who received CHOP treatment received allogeneic stem cell transplantation. CHOP was selected in these cases because the patients were considered unfit for intensive regimens due to comorbidities or poor performance status, and therefore received a less intensive protocol. Eleven (30%) patients received the HYPERCVAD (doxorubicin, cyclophosphamide, vincristine, dexamethasone, methotrexate, and cytarabine) protocol, and all patients who received this treatment completed the treatment. Four of these patients had auto-SCT, and four had allo-SCT. Three (7%) of the patients included in the study received the BFM (doxorubicin, cyclophosphamide, vincristine, dexamethasone, methotrexate, cytarabine, L-asparaginase, 6-mercaptopurine) protocol; two of these patients completed the treatment, and the patients who completed the treatment underwent auto-SCT. Three patients (7%) received the GMALL (daunorubicin, cyclophosphamide, vincristine, dexamethasone, methotrexate, cytarabine, L-asparaginase, and 6-mercaptopurine) protocol, and two patients who completed treatment underwent allo-SCT, and one patient underwent auto-SCT. Two patients (5%) received CALGB (daunorubicin, cyclophosphamide, vincristine, prednisolone, methotrexate, cytarabine, pegasparaginase, and 6-mercaptopurine) treatment, and one patient who completed treatment underwent allo-SCT, and one patient was followed up without transplantation. Finally, two patients (5%) received CHOEP (etoposide, doxorubicin, cyclophosphamide, vincristine, and prednisone) treatment, and two patients who completed treatment were followed up without transplantation.

The treatments received by the 38 patients included in the study were summarized. Median OS values according to treatment regimens are presented in Table 3. These data are descriptive in nature and should not be interpreted as direct comparisons of efficacy, given the heterogeneity of treatment modalities, center-specific practices, and patient characteristics. No statistically significant differences were observed among regimens.

LBL
median OS (month)T-LBL median OS (month)B-LBL median OS (month)EPOCH232230CHOP201856HYPERCVAD5724NRBFM10910GMALL2121NRCALGB3434NRCHOEP1717NRTotal232156

Median overall survival (OS) according to treatment received (values are descriptive; direct comparisons across regimens are not appropriate due to heterogeneity in patient characteristics and treatment practices; these figures should not be interpreted as comparative outcomes and are provided only for descriptive purposes.

LBL, lymphoblastic lymphoma; T-LBL, T-cell lymphoblastic lymphoma; B-LBL, B-cell lymphoblastic lymphoma. Overall survival (OS) could not be calculated (NR) for three patients in the B-LBL cohort treated with the HYPERCVAD regimen, as they remained alive at the time of analysis.

Among the patients in the study, 10 underwent autologous stem cell transplantation (7 with T-LBL and 3 with B-LBL), whereas 11 received allogeneic stem cell transplantation (9 with T-LBL and 2 with B-LBL), resulting in a total of 21 individuals who underwent transplantation. When assessing auto-SCT and allo-SCT patients independently, median OS was determined to be 23 months for auto-SCT patients and 53 months for allo-SCT patients. Despite the median OS of patients who underwent allogeneic stem cell transplantation (allo-SCT) being 53 months, the median OS of transplanted patients was not statistically substantially greater (p>0.05). Nevertheless, when auto-SCT and allo-SCT patients were assessed individually, no significant difference in median OS was seen (p>0.05).

Thirteen patients (34%) achieved remission after the first course of treatment, 15 patients (39%) had partial remission, 3 patients (8%) had stable disease, and 7 patients (19%) had progressive disease. Nine of the 13 patients who achieved remission were diagnosed with T-LBL and 4 with B-LBL. The proportion of patients with T-LBL and B-LBL who entered remission was statistically similar (p>0.05). The median OS was 57 months in patients who achieved complete remission after first-line treatment, 21 months in patients in partial remission, 13 months in those with stable disease, and 10 months in those with progressive disease. Median OS was significantly higher in patients with both T-LBL and B-LBL who entered remission after the first course of treatment compared to those who did not (p<0.05). Twenty-eight patients (74%) required second-line therapy because of disease progression. Three patients (8%) were refractory to first-line therapy and died. Eighteen patients (47%) received at least third-line therapy.

Among the patients in the study, 22 (58%) exhibited involvement of three or more lymph nodes or organs, whereas 16 (42%) did not show such involvement. The median overall survival (OS) was 18 months for patients with involvement of ≥3 anatomical regions, compared to 56 months for those without. Statistically, the presence of involvement in three or more distinct anatomical regions was associated with significantly reduced survival (p<0.05). Seventeen patients with ≥3 sites of involvement were classified in the T-LBL subgroup, whereas five were categorized in the B-LBL subgroup. Although the frequency of ≥3 site involvement was similar between the two subgroups (p>0.05), median OS appeared lower in both groups when ≥3 sites were affected, suggesting a possible association with inferior survival (p=0.032). Given the small subgroup sizes, this finding should be interpreted with caution.

Bone marrow involvement was identified in 21 patients (55%), whereas it was absent in 17 (45%). The median overall survival (OS) of patients with bone marrow involvement was 22 months, compared to 30 months in those without, with no statistically significant difference observed (p>0.05). Bone marrow involvement was present in 19 patients with T-LBL and in 2 patients with B-LBL, with no significant difference in frequency or OS between the two groups (p>0.05).

Nineteen patients (50%) exhibited extra-organ involvement beyond lymph nodes and bone marrow, with a median OS of 18 months compared to 33 months in those without. Despite this variation, no statistically significant difference was observed (p>0.05). Eleven patients with extra-organ involvement were diagnosed with T-LBL, whereas eight were diagnosed with B-LBL. No significant difference was observed in the prevalence of extra-organ involvement between the two subtypes (p>0.05), nor in OS among patients with extra-organ involvement in either group (p>0.05).

Median OS was 11 months in six patients (16%) with CNS involvement compared to 30 months in those without, suggesting a possible association with inferior survival (p=0.047). Given the limited number of patients, this observation should be regarded as exploratory. Five patients with CNS involvement were diagnosed with T-LBL and one with B-LBL. Statistical analysis indicated that CNS involvement was more frequent in the T-LBL subgroup (p<0.05), and OS appeared lower in this group, though the small sample size limits firm conclusions.

Cervical lymphadenopathy was identified in 30 patients (79%), with a median OS of 23 months. Among these, 25 patients were diagnosed with T-LBL (median OS 21 months) and 5 with B-LBL (median OS 56 months). While a difference in median OS was observed between the two groups (p=0.041), this finding should be interpreted cautiously given the small number of B-LBL patients. Overall, the presence of cervical lymphadenopathy was linked to shorter OS compared to patients without cervical involvement, whereas lymphadenopathy at other sites did not appear to impact survival. The distribution of lymphadenopathy was statistically comparable between the T-LBL and B-LBL subtypes. Factors influencing median OS are summarized in Table 4.

Clinical parameterGroupnEvents (deaths)Median OS (months) [95% CI]T-LBL median OS (month)B-LBL median OS (month)p-valueExtra-organ involvementYes191418 [12–24]1720p=0.27No19933 [25–41]3033ReferenceTransplantationAuto-SCT10723 [15–31]2130p=0.41Allo-SCT11853 [38–68]2456p=0.19None17817 [12–22]1732Reference≥3 anatomical regionsYes221718 [13–23]1818p=0.032No16656 [42–70]5656ReferenceBone marrow involvementYes211522 [16–28]2213p=0.28No17830 [22–38]2156ReferenceCNS involvementYes6511 [6–16]113p=0.047No321830 [24–36]3030ReferenceCervical LAPYes302023 [18–28]2156p=0.041No8333 [25–41]3333ReferenceLDH level (continuous, Cox regression)Median 600 (range 156–1790)3823OS decreases with higher LDHT-LBL median 660B-LBL median 445HR 1.12 (95% CI 1.04–1.21), p=0.004

Median overall survival (OS) according to clinical parameters in adult LBL patients.

Auto-SCT, autologous hematopoietic stem cell transplantation; Allo-SCT, allogeneic hematopoietic stem cell transplantation; LAP, lymphadenopathy; CNS, central nervous system; OS, overall survival; LDH, lactate dehydrogenase. P-values calculated using the log-rank test.

Subgroup analyses of overall survival according to clinical parameters are presented in