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Background Natural killer/T-cell lymphoma (NKTCL) is an aggressive lymphoma with poor prognosis mainly seen in Asian and South American countries, most patients have nasal involvement. Non-nasal NKTCL have a dismal prognosis. However, data about this very specific population is mostly known in Asians but little known in Latin American (LATAM) population. Our aim is to describe the clinical characteristics and survival of newly diagnosed NKTCL patients in Peru Methods: This is a retrospective study, including all patients with a pathological diagnosis of NKTCL patients >13 years at the Instituto Nacional de Enfermedades Neoplasicas (INEN) and Oncosalud between 2002 and 2019. The estimate of the survival curves was performed by the Kaplan-Meier method, and the difference was computed by the log-rank test. Results: 60 patients were included for the analysis. The median age was 37 years (range 15-83). 62% were male, 51% had B-symptoms, 56% had stage III/IV disease, 54% had elevated serum LDH, 29% had nodal involvement. The most frequent non-nasal sites were oropharynx, soft tissue, cutaneous, gastrointestinal and orbit with 24%, 17%, 12%, 7% and 5%, respectively. 79% patients received systemic chemotherapy, 7% received radiotherapy alone and 14% did not received chemotherapy because poor performance status. Of patients who received chemotherapy only 20% received a L-asparaginase-based chemotherapy. The median follow-up time was 8 months (1-103). The median overall survival (OS) was 14 months (interquartile range [IQR] 4-29), 1y OS was 51% (95% CI 33-67), 3y OS 21% (95% CI 7-40), 5y OS 14% (95% CI 3-34), figure 1. The median overall survival according to LDH level was 10 months regardless of the levels (p=0.84), figure 2. The median OS for female and male were 8 and 10 months, respectively p=0.59) Conclusions: Peruvian patients with non-nasal NKTCL are younger, with presence of B-symptoms, advance stage and elevated LDH levels compared to those reported in nasal NKTCL. The most frequent non nasal NKTCL is located on the oropharynx. OS of non-nasal NKTCL is extremely poor. Elevated LDH and sex are not prognostic factors for OS. A larger cohort and follow-up are needed to evaluate prognostic factors in this population. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma subtype seen in Caucasian countries. Recent data were published on FL from Latin America (LATAM), presenting information of 12 countries. However, this information is widely variable because of the diversity of the Latin population (Caucasian and mestizo individuals). Our aim was to evaluate the clinical features, treatment patterns outcomes of non-Caucasian patients with FL from a single cancer center. Our second aim was to validate FLIPI1, FLIPI2, PRIMA and POD-24 score in our cohort. Methods: This is a retrospective study, including all patients with a pathological diagnosis of FL at the National Institute of Neoplastic Diseases in Lima, Peru from 2010 to 2019. All cases were reviewed by specialized pathologists. Baseline clinical and pathological data were collected. Responses were assessed based on the Lugano criteria. Overall survival (OS) was estimated using the Kaplan-Meier method. Differences were compared with the log-rank test. Results From 2010 to 2019 4480 patients with B-cell lymphoma were diagnosed, 449 patients (10%) had grade 1 to 3A FL, 302 patients had the five variables for FLIPI, 242 for FLIPI2, 257 for the 2 variables for PRIMA prognostic index and 209 received systemic treatment and had enough information to evaluate POD24. The median age for the entire cohort was 59 years old (range 24-92), 49% of patients were ≥60 years, 46% were male, 22% had extranodal involvement, 34% had bulky disease (≥6 cm in diameter), 68% had stage III/IV disease, 32% had hemoglobin 4. Low, intermediate and high FLIPI were seen in 39%, 27% and 34% of patients, respectively. Low, intermediate and high-risk FLIPI2 was seen in 23%, 54% and 23% of patients, respectively. Low, intermediate, and high PRIMA was seen in 53%, 12% and 35%, respectively. 209 patients received systemic treatment, 60% received CHOP ± rituximab (R), 13% CVP ± R, 15% CHOP, 11% CVP. Response data were available in 158 patients with complete response in 35%, partial response in 57% and no response in 8%, for an overall response rate of 92%. 19% of patient had disease progression within 24 months of first treatment initiation (POD24). For the entire cohort, the median follow-up time was 2.6 years (Interquartile range [IQR] 0.08-13.6), the median OS was not reached (IQR 4.2-not reached). 5y was OS 72% (95% CI 65-77). 5y OS for low, intermediate and high FLIPI were 90% (95% CI 81-94.5), 65% (95% CI 47.3-78.2) and 60.1% (95% CI 46.6-72.4), respectively (p Conclusion: FL has a lower incidence in non-Caucasian patients in Peru compared to those reported for Western countries or other LATAM Caucasian population. FL patients showed higher rates of high FLIPI and FLIPI2 than previously reported in the literature. Chemoimmunotherapy is the standard approach to FL patients, which is associated with high rates of overall response, but low rate of complete response. The OS rates are shorter than those reported in the previously LATAM cohort. Our study validates the prognostic value of FLIPI1, FLIPI2, PRIMA and POD24. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Differences in the Distribution of non-Hodgkin Lymphoma in public versus private institution in a Latin American country: A cohort of 5,807 cases. Background: Non-Hodgkin lymphoma (NHL) is the most frequent hematological malignancy. B-cell (BCL) and T-cell (TCL) NHL subtypes differs in high income and low-and middle-income countries. In Peru, the healthcare system (HCS) is divided mainly into public and private institutions. We previously demonstrated that there is a difference in the distribution of NHL between the HCS. We aimed to describe the subtypes of NHL seen according to healthcare facilities in a large cohort. Methods: We reviewed medical records at National Cancer Institute and Oncosalud, both the leading public and private cancer centers in Peru, respectively. All patients diagnosed with NHL from 2010-2019 according to the 2016 WHO classification were included. Baseline characteristics were compared between public and private institutions using Student's t test and Chi-square as appropriate. Results: A total of 5,807 NHL were included from both institutions. The median age was 60 years (range 15-103), 50.6% were male. Most patients NHL cases were encountered at the public institution (92.4%, n = 5,368); 82.9% (n = 4,815) were BCL and 17.1% (n = 992) TCL. Differences of BCL and TCL frequencies were seen among institutions. More BCL cases were seen at the private institution (86.1%, n = 378 versus 82.7%, n = 4,437, respectively) whereas TCL were common in the public institution (17.3%, n = 931 versus 13.9%, n = 61, respectively) (p < 0.065). The most frequent BCL was DLBCL with 68.6% (n = 3045) and 54.2% (n = 205) seen in public and private institutions, respectively (p < 0.001). The second most frequent BCL was follicular lymphoma (FL) with 11.2% (n = 495) and 20.9% (n = 79) seen in the public and private institutions, respectively (p < 0.001). Chronic lymphocytic lymphoma (CLL) and Burkitt lymphoma (BL) were most frequent in private institution (CLL 6.3%, n = 24 vs. 3.5%, n = 154, p = 0.004; BL 3.4%, n = 13 vs. 1.4%, n = 60, p = 0.001). The most frequent TCL was peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) (24.5%, n = 228) for the public institution and mycosis fungoides (MF) (42.6%, n = 26) for the private institution. The second most frequent TCL was natural killer/TCL (NKTCL) (23.5%, n = 219) for the public institution, and PTCL, NOS (21.3%, n = 13) for the private institution. There was significant difference in the number of NKTCL and MF cases seen during the study period among institutions (NKTCL public 23.5%, n = 219 vs. private 4.9%, n = 3, p = 0.001; MF public 9.1%, n = 90 vs. private 42.6%, n = 26, p Conclusions: The distribution of NHL subtypes differs according to the type of healthcare system in Peru. Our large cohort confirms that DLBCL and NKTCL are more frequent in patients treated at the public cancer center than in private center. On the contrary FL, CLL, BL and MF are more frequent in private cancer center. The difference in the distribution of BCL and TCL was not statistically significant. Disclosures No relevant conflicts of interest to declare.

Background: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy with dismal prognosis and associated with clonal T-cell expansion driven by Human T-Lymphotropic Virus 1 (HTLV-1) infection. Comprehensive genomic studies in Japan have identified recurrent alterations affecting TCR-NF-kB signaling (i.e. PRKCB, PLCG1, CARD11, VAV1, and IRF4), T-cell trafficking pathways (i.e. CCR4 and CCR7), and the tumor suppressor genes CDKN2A and TP53. HTLV-1 endemic regions include Africa, the Caribbean, and South America in addition to Japan. Retrospective studies from the Western population have reported distinctive features from the Japanese cohort, e.g. younger age, more common lymphomatous presentation, and worse outcomes. Our group sought to evaluate the unique molecular features of ATLL in a large cohort of patients from the Caribbean and South America. Methods: We performed a multimodal genomic study on specimens from 169 patients encountered in the United States (Miami), Peru, Brazil, France, and Spain. Data types included Oncoscan/Copy Number Variation (CNV) data for 129 patients, RNA-seq data for 97 patients, and whole exome sequencing (WES) data for 125 patients. Patients were ethnically classified based upon single nucleotide polymorphisms, under 3 main groups: African (n=80), native American (n= 32), or South Asian/Islander (n=12). 46 specimens without WES data could not be ethnically classified. Somatic variants were called using Mutect. Putative driver mutations were identified by frequency-based criteria. CNV significance was determined using GISTIC2.0. Data were compared to whole exome and targeted sequencing data published by Kataoka et al. Results: Our cohort replicated trends reported in Japanese datasets but included several distinctive findings. South American and Caribbean patients had fewer mutations in CCR4 and CD58. Three putative tumor suppressors not previously implicated in ATLL were identified based on recurrent damaging mutations. These included ANKRD11 (n=3), DGKZ (n=3), and PTPN6 (n=3). Both ANKRD11 and PTPN6 were only mutated in Afro-Caribbean patients with aggressive (acute and lymphomatous) cases. CNV analysis revealed ANKRD11 deletions in a significant portion of cases (n=16). As previously reported, STAT3 mutations were more common in indolent subtypes. IRF4 mutations (n=14) or amplifications (n=19) were only observed in aggressive ATLL subtypes. L70V was the most common IRF4 variant (n=5). Among Japanese samples, K59R mutations were seen twice as often as L70V mutations. Both K59R and L70V are located within the IRF4 DNA binding domain. In samples from patients with disease relapse (N = 10), IRF4 was the only gene mutated significantly more often (p = 0.03). 3 of 10 patients who were previously treated with interferon (IFN)-based therapy relapsed with new IRF4 mutations (L70V n=2, and K59R n=1), suggesting IRF4 may be associated with IFN resistance. A total of 11 patients in the Western cohort had FOXO3 mutations including R177W (n=7) and D199N (n=3) variants. These only occurred in Afro-Caribbean patients with aggressive subtypes. R177W is located within the FOXO3DNA binding domain, suggesting that dysregulation of its transcriptional targets may contribute to disease. In the Japanese cohort, only one patient had a FOXO3 mutation, (D199N). The majority of primary ATLL samples analyzed by Western Blot showed significantly reduced or no expression of FOXO3, or ANKRD11. Conclusion: The genomic landscape of ATLL encountered in patients from South America and the Caribbean resembles that of ATLL in Japanese patients. However, our study identified novel variants and tumor suppressor genes not previously implicated in ATLL that differ from the Japanese population. Furthermore, we correlate our genomic analysis with clinical findings to implicate ATLL driver genes in IFN resistance and disease prognosis. Functional Studies to determine the prognostic and functional roles of the gene alterations we identified in ATLL are ongoing. Disclosures Gru: StemLine: Honoraria, Research Funding, Speakers Bureau; CRISPT Therapeutics: Research Funding; Innate Pharma: Research Funding.

Introduction Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematological malignancy with multi-organ and frequent skin involvement, and poor clinical outcomes. Based on the limited available data, the estimated incidence is 0.44% of all hematologic malignancies, representing less than 1% of acute leukemias, and 0.7% of cutaneous lymphomas. Due to the rarity of this entity, there have been relatively few studies characterizing the molecular profile of BPDCN. We examined a cohort of 51 patients with BPDCN using OncoScan chromosome microarray, which provides genome-wide copy number abnormality (CNA) analysis. Methods An international cohort of BPDCN cases were collected from centers in Brazil (Laboratorio de Patologia, Botucatu), Swtizerland (University of Zurich), France (Hospital St. Louis, Paris), Peru (Instituto Nacional de Enfermedades Neoplasicas, Lima), Canada (Department of Pathology, University of Montreal), Italy (Derpartment of Pathology, University of Bologna), and US (Department of Pathology - The Ohio State University, Department of Hematopathology - MD Anderson Cancer Center; and Department of Pathology - University of Virginia). A total of 58 tissue blocks from 51 patient samples were retrieved. The diagnosis of BPDCN was done and confirmed by at least three independent hematopathologists or dermatopathologists in accordance with the WHO classification (Lyon 2017). For the purpose of the molecular analysis substratification, cases were classified as 'BPDCN' if they were positive for TCF4, and 'BPDCN-like' if they were negative for TCF4. Immunohistochemistry for CD123, CD4, and CD56 was performed in all cases. Exclusion criteria included expression of MPO, lysozyme, CD3, CD19, CD20, CD22, and/or EBV. DNA was extracted from FFPE samples via standard techniques and processed on OncoScan CNV Plus microarray (ThermoFisher Scientific) according to manufacturer's recommended protocol. Copy number abnormalities and select single nucleotide variants and insertions/deletions (74 mutations in 9 genes) were analyzed on Chromosome Analysis Suite software (ChAS v4.1; ThermoFisher Scientific). Additional analysis was performed using Nexus Copy Number (BioDiscovery, version 10.0). Results To date, we have successfully analyzed 45 cases of BPDCN with Oncoscan, revealing widespread CNA in the vast majority of cases (44/45; 98%). Alterations of chromosome 9 were common in this cohort, particularly CNAs involving CDKN2A/B at 9p21.3. Twenty-five cases (56%) demonstrated CNA including CDKN2A/B, with ten of these cases demonstrating a homozygous loss of CDKN2A/B (22%). Alterations of chromosome 13 were also frequently detected with loss of RB1 (located at 13q14.2) detected in 24 cases (53%). The RUNX1 gene (21q22.12) was a common target of CNAs in this cohort, seen in nine cases (20%). Eight of these cases showed a copy number gain of RUNX1, which is a recurrent finding in a variety of hematological malignancies, particularly myeloid neoplasms. The remaining case with RUNX1 CNA showed a focal, homozygous loss of the gene, demonstrating that dysregulation of RUNX1 through CNA is a common event in BPDCN. We observed frequent deletions of ETV6 (53%), IKZF1 (33%), and TP53(16%) in our cohort. The ARHGAP26 gene (5q31.3), which is associated primarily with juvenile myelomonocytic leukemia, was included in CNA in 13 cases (29%), with both gains and losses observed in this cohort. Oncoscan can detect a limited number of single nucleotide variants in nine genes that are frequently mutated in cancers (BRAF, EGFR, IDH1, IDH2, KRAS, NRAS, PIK3CA, PTEN, and TP53). Mutations were detected in ten cases (22%), with NRAS and TP53 variants detected in three cases each and KRAS and IDH2 variants detected in two cases each. Conclusions Our preliminary data demonstrates complex genomic alterations in BPDCN, with the RB1 locus on chromosome 13, the CDKN2A/B locus on chromosome 9, and the ETV6 locus on chromosome 12 most commonly detected. However, widespread genomic alterations were detected involving a variety of cancer-associated genes further characterizing CNA in BPDCN. Analysis of additional BPDCN cases is progress. Disclosures Khoury: Kiromic: Research Funding; Angle: Research Funding; Stemline Therapeutics: Research Funding. Porcu: Viracta: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Innate Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; Daiichi: Honoraria, Research Funding; Kiowa: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Spectrum: Consultancy; DrenBio: Consultancy. Gru: StemLine: Honoraria, Research Funding, Speakers Bureau; CRISPT Therapeutics: Research Funding; Innate Pharma: Research Funding.

Background Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma subtype, being nodal involvement its main characteristic. However, data about Extranodal (EN) involvement is not reported in Latin American patients. Our aim was to evaluate the clinical features, treatment patterns outcomes of Peruvian patients with ENFL from two cancer centers and validate FLIPI1, FLIPI2, PRIMA and POD-24 prognostic index in our cohort. Methods: This is a retrospective study, including all patients with a pathological diagnosis of FL grade 1 to 3A treated at the National Institute of Neoplastic Diseases and Oncosalud, both in Lima, Peru from 2010 to 2019. All cases were reviewed by specialized pathologists. Baseline clinical and pathological data were collected. Responses were assessed based on the Lugano criteria. Overall survival (OS) was estimated using the Kaplan-Meier method. Differences were compared with the log-rank test. Results A total of 86 patients were evaluated. The median age was 61 years (30-91), 43% were male, 20% had bulky disease (≥6 cm in diameter), 51% had stage III/IV disease, 31% had hemoglobin 4. The most frequent EN sites were gastrointestinal, bone marrow, cutaneous and breast with 22%, 21% and 9%, and 6%% respectively. Low, intermediate and high-risk FLIPI1 was seen in 56%, 23% and 21% of patients, respectively. Low, intermediate and high-risk FLIPI2 was seen in 28%, 58% and 14% of patients, respectively. Low, intermediate, and high PRIMA was seen in 57%, 10% and 33%, respectively. 55 patients (64%) received any treatment, 47% received CHOP ± rituximab (R), 16% CVP ± R, 22% radiotherapy alone, 9% CHOP, 15% other treatments. Response data were available in 44 patients with complete response in 45%, partial response in 43% and no response in 12%, for an overall response rate of 88%. From patients who received CHOP/CVP ± R, 13% patients had disease progression within 24 months of first treatment initiation (POD24). For the entire cohort (N=88) the median follow-up time was 2.1 years (interquartile range [IQR] 0.08-11.3), median overall survival was 8.25 years (IQR 4.4-not reached [NR]). 5y OS was71.7% (95% CI 55.3-82.9), figure 1. For the FLIPI group 5y OS for low, intermediate and high FLIPI were 86.9% (95% CI 64.7-95.6), 60.1% (95% CI 24.4-83.2) and 75.7% (95% CI 30.4-93.7), respectively (p=0.07; Figure 2). For the FLIPI2 group (N=58) 5y OS for low, intermediate and high FLIPI2 were 79.5% (95% CI 39.3-94.5), 77% (95% CI 55.3-89.2) and 86% (95% CI 33.4-97.8), respectively (p=0.86). For the PRIMA group (N=38) 5y OS for low, intermediate and high PRIMA was 86% (95%55.6-96.6), 100% (95% CI 100), and 80% (95% CI 42-95), respectively (p=0.80). Patients who had and did not have POD24 had median OS of NR (IQR 0.6-NR) and NR (IQR 2.69-NR), respectively. 5y OS for patients who had and did not have POD24 was 71.2 % (95% CI 48-85) and 75% (12.7-96), respectively (p Conclusion: Peruvian patients with ENFL showed a higher rate of female patients. Gastrointestinal involvement was the most common primary site. The OS rates is similar to our nodal involvement cohort. Chemoimmunotherapy is the standard approach to FL patients, which is associated with high rates of overall response. In our study FLIPI, FLIPI2, PRIMA and POD24 were not predictors for OS, but larger cohorts and longer follow-up are needed to find more accurate predictors of survival in these patients. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Introduction: T-cell lymphomas are a relatively rare and heterogeneous group of lymphoid neoplasms. Its incidence relies on viral infections incidence as Human T-cell lymphotropic virus type I-II (HTLV-I/II) and Ebstein Bar virus (EBV). Specifically, these viruses have a significantly higher incidence in Latin-American populations. Our objective was to calculate the incidence and survival of T-cell lymphomas in the largest Peruvian population based on a national registry. Methods: We conducted a multicenter, retrospective registry study of non-Hodgkin T cell lymphoma. The data was extracted from Instituto Nacional de Enfermedades Neoplasicas and Oncosalud-AUNA, Lima-Peru, from January 2010 to December 2019, a total of 948 patients who were diagnosed as mature T cell non-Hodgkin lymphoma based on the World Health Organization Classification 2008 were enrolled. T-lymphoblastic lymphoma/leukemia was excluded. Overall survival was calculated based on death dates from the Peruvian national identification registry (RENIEC). Results: The median age was 51 years (range, 1-94), and male and female patients were 512 (54%) and 436 (46%). Among the 948 patients enrolled, Peripheral T-cell lymphoma was the common neoplasm accounting for 23% (n=221), and Extra-Nodal NK T-lymphoma (22%, n=213), Adult T-cell lymphoma (22%, n=205), Anaplasic Large cell lymphoma (14%, n=131), Cutaneous T-cell lymphoma (14%, n=129) (Figure 1a). At the time of diagnosis, extranodal disease was found in 68.6% (650) of patients. By July 2021, only 15.3% of cases were in remission and 37% (350) were alive. Median global overall survival of T-cell lymphomas was 1 year (0.8-1.1), Cutaneous T-cell lymphoma had the highest survival and Adult T-cell lymphoma had the lowest survival (Table 1 and Figure 1b). Conclusion: This initial report shows a relatively high frequency of mature T-cell lymphomas in Latin-America real-world setting, and confirms that T-cell lymphomas patients had a dismal outcome. The clinical outcome for patients with T-cell lymphomas subtypes is poor with standard therapies, and novel agents and new modalities are needed to improve survival. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common variant of non-Hodgkin lymphoma (NHL) accounting for approximately 30% of the NHL cases worldwide. Previous reports have associated certain viral infections with the development of DLBCL such as HIV and EBV, both infections related with an aggressive clinical course and worse outcome. The human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus regarded as the pathogenic agent for adult T-cell lymphoma/leukemia. HTLV-1 is endemic in Japan, the Caribbean basin, South America, and parts of Africa. In Peru, up to 3% of the healthy adult population carries HTLV-1. As data on the impact of HTLV-1 infection in DLBCL outcomes is scarce, we aim to describe the clinical features and outcomes of HTLV-1-positive patients with a pathological diagnosis of DLBCL. Methods: We retrospectively reviewed medical records of patients diagnosed and managed for DLBCL at the National Institute of Neoplastic Diseases in Lima-Peru between 2007 and 2019. Patients were evaluated for HTLV-1 infection at the time of diagnosis. Positive HTLV-1 cases were matched to negative HTLV-1 controls based on age, sex, and cancer staging. Treatment responses were assessed according to the Lugano criteria. Overall survival (OS) and event-free survival (EFS) curves were estimated using the Kaplan-Meier method and compared with the Log-rank test to determine the impact of HTLV-1 infection. Multivariate Cox regression models were reported with adjusted Hazar Ratios (aHR) with a 95% confidence interval (95% CI). Results: A total of 192 patients with DLBCL were identified and had sufficient data for analysis. Seventy (37%) cases were positive for HTLV-1 infection and 122 (63%) were not. Table 1 summarizes the clinical features and outcomes of DLBCL patients according to HTLV-1 status. Overall, the majority of patients were ≥65 years (59%), had ECOG performance status ≤2 (95%) and were stage III-IV (51%) at diagnosis. One third (n=64) of patients had extranodal involvement with 71 affected sites of which bone marrow involvement was frequently found in HTLV-1-negative DLBCL cases (55% vs. 7%, p Conclusion: To the best of our knowledge, this is the largest case series describing the clinical characteristics and outcome of HTLV-1-positive DLBCL patients. A study from Japan on early stage localized (head and neck) B-cell-NHL (n=198, HTLV-1 seropositive n=21 and with DLBCL n=12) treated with radiotherapy and/or multi-agent chemotherapy found poorer prognosis on HTLV-1 carriers compared to non-carriers (5-year OS: HTLV-1-positive n=21, 49% vs. HTLV-1-negative n=177, 78%, p=0.007; Hiroaki et al BJH 2003). In this study, we included DLBCL patients with both early and advanced stage disease along with localized and extranodal involvement. We found that HTLV-1 infection had no significant impact on 5-year OS and EFS rates when using conventional therapy for DLBCL. Moreover, we did not find differences in relapsed and mortality rates. Further investigation is needed to confirm the potential impact of HTLV-1 infection in DLBCL outcome. Disclosures No relevant conflicts of interest to declare.

Background: The human T-cell lymphotropic virus type 1 (HTLV-1) is an oncogenic retrovirus that affects CD4+ T-cell lymphocytes and is the cause for adult T-cell leukemia/lymphoma (ATLL), an aggressive peripheral T-cell neoplasm. Hodgkin-like ATLL subtype is a unique entity usually indistinguishable from Hodgkin lymphoma (HL) in the setting of HTLV-1 infection. HTLV-1 proviral integration and TCR Cb1 gene rearrangement testing are often necessary to differentiate both entities. However, less is known on HTLV-1 carriers diagnosed with HL (HTLV-1+ HL). We aim to compare survival outcomes between HTLV-1+ HL and matched controls treated at the National Cancer Institute in Peru. Methods: We reviewed medical records of patients diagnosed and managed for HL at the National Cancer Institute (Instituto Nacional de Enfermedades Neoplasicas, INEN) in Lima-Peru between 2002 and 2019. All patients should have had serologic evaluation for HTLV-1 infection at the time of diagnosis and should have had no suspicion (or confirmation) of a T-cell neoplasm during pathological examination. To investigate the impact of HTLV-1 infection on survival, we matched HTLV-1+ HL cases to HTLV-1-negative HL patients (controls) based on age, sex, cancer staging, and comorbidities. Treatment responses were assessed according to the Lugano criteria. Survival curves (event-free and overall survival) were estimated using the Kaplan-Meier method and compared with the Log-rank test. Multivariate Cox regression analysis was fitted and reported as Hazard Ratios (HR) with a 95% confidence interval (95% CI). Results: A total of 68 HL patients were identified and had sufficient data for analysis. Twenty cases had HTLV-1+ HL and 48 HTLV-1-negative HL. Table 1 summarizes the clinical features and outcomes of HL patients. In all patients the median age at diagnosis was 55 years with a female/male ratio of 1:1. Histological subtypes of HL were not statistically different among both groups with mixed cellularity as the most common subtype (HTLV-1+ HL 50% vs. HTLV-1-negative HL 38%), followed by nodular sclerosis (HTLV-1+ HL 15% vs. 31%), lymphocyte-rich (HTLV-1+ HL 15% vs. 15%), and nodular lymphocyte-predominant (HTLV-1+ HL 5% vs. 4%). ECOG performance status ≤2, advanced-stage disease (III-IV), presence of B symptoms, and presence of extranodal disease at the time of diagnosis were not different in both groups. Co-infections were presented in 5 (7.4%) HL patients (1 strongyloidiasis and 3 tuberculosis in the HTLV-1+ HL group, and 1 tuberculosis in the HTLV-1 negative HL group). All HTLV-1-negative HL patients were treated with first-line ABVD regimen compared to 18 (90%) HTLV-1+ HL patients; the remaining HTLV-1+ HL patients received involved-field radiation (n=1) and best supportive care (n=1). HTLV-1+ HL patients had inferior response rates (complete and partial response) compared to the matched control group (CR: 60% vs. 71%, and PR: 15% vs. 27%, respectively, p=0.015). At a median follow-up of 5-years, the overall survival was 55% in HTLV-1+ HL versus 67% in the matched control group (aHR: 1.39, 95%CI [0.6-3.4], p=0.47) (Figure 1). In the multivariate analysis, HTLV-1 infection was not a significant prognostic factor for worse event-free or overall survival. Relapsed rates were not different between both groups (HTLV-1+ HL 25% vs. 20.8%), however, more deaths were seen in the HTLV-1+ HL group (60% vs. 35%) but this was not statistically significant. Conclusion: To the best of our knowledge, this is the first case series describing the characteristics and outcome of HTLV-1 carriers diagnosed with HL. We found lower response rates to conventional treatment in HTLV-1+ HL patients compared to HTLV-1 negative individuals. However, long-term outcomes and relapsed rates were not different among groups. Further investigation is needed to confirm the potential impact of HTLV-1 infection in HL outcome. Disclosures No relevant conflicts of interest to declare.

Background:Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and fatal myeloid malignancy characterized by clonal proliferation of immature plasmacytoid dendritic cells. BDCN has been frequently described in men and age above 60 years, and usually involves the skin and bone marrow. Immunophenotyping is based on CD123+, CD4+ and CD56+ expression and is necessary rule out other myeloid malignancies. Objective: We aimed to describe the clinical characteristics and immunophenotype of BPDCN cases diagnosed at two tertiary Peruvian cancer institutions between 2018-2019. Methods: We retrospectively reviewed medical records of patients diagnosed of BPDCN at two tertiary Peruvian cancer centers (Instituto Nacional de Enfermedades Neoplasicas and Oncosalud-AUNA, Lima-Peru) between 2008 and 2019. Clinical characteristics, treatments, outcomes and immunophenotype by pathology or flow cytometry review, were collected. Patients were classified according to their maturation stage using CD34 and CD117 expression into three subgroups: Immature-Intermediate blastic (IIB-BPDCN; partial expression of CD117 and absence or minimal expression of CD34), mature (M-BPDCN; absence of CD34 and CD117) and unknown(U-BPDCN). Overall survival (OS) and event-free survival (EFS) curves were estimated using the Kaplan-Meier method and compared with the Log-rank test to determine the impact of immunophenotype. Results: Thirty-eight cases were included during the study period. The median age at diagnosis was 38 years (7-82), only six (16%) were older than 65 years, and a notorious female predominance (F/M ratio: 1.7:1) was observed. Twenty-four cases had CD34/117 expression available and were classified according to the maturation stage in IIB-BPDCN (13) and M-BPDCN(11), additionally 14 cases had unknown stage (U-BPDCN). Table 1 summarizes clinical characteristics, treatment and outcomes according to their immunophenotype. Bone marrow infiltration was more frequent in immature phenotypes (92% IIB-BPDCN vs 73% M-BPDCN, p=0.001), as well as skin infiltration was more common in mature phenotype (72% vs 31%, p=0.008). CNS infiltration at diagnosis was 15% and 55% in IIB-BPDCN and M-BPDCN, respectively. Sixteen patients received treatment based on ALL-like protocols, 8 AML-like, 5 CHOP-like and 9 patients only palliative care. At 5 years median follow-up, median EFS and OS was 12 and 16 months, respectively. IIB-BPDCN had the lowest survival (4 months EFS and 6 months OS). Conclusions: We describe a Peruvian cohort of BPDCN patients with younger age at diagnosis and female predominance than reported previously by other series, however further studies in Latino population are required to confirm these results. Immature phenotypes based on CD34 and CD117 expression were associated with high rate of bone marrow infiltration and fatal outcomes. New successful target therapies must be warranted for this rare and fatal condition. Disclosures No relevant conflicts of interest to declare.

Background:Plasmablastic lymphoma (PBL) is an aggressive lymphoma associated mainly to HIV infection, although cases in immunocompetent patients are described as well. Objective:To describe the clinicopathologic features and determine the overall survival of lymphoma patients according human immunodeficiency virus (HIV) status in Peruvian patients. Methods:We reviewed the pathology databases of 2 cancer centers and a general hospital from Peru. Forty cases were documented between 2005 and 2020. Categorical variables were compared using Fisher's exact test. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Statistical analysis was based on SPSS Program version 23. All cases were reviewed by two pathologists. Results:32 patients (80%) were HIV-positive. The median age for the whole cohort was 40 years (range, 22-86). The median age for HIV-positive and HIV-negative PBL patients were 37 years (range 22-67 years) and 57 years (range 27-86 years), respectively. The proportion of patients ≥60 years was lower in HIV-positive than in HIV-negative patients (8% and 37%, respectively; p= 0.046). 80% of patients in the whole cohort were female, and 84% and 62% in the HIV-positive and HIV-negative group, respectively. Extra-oral primary sites were the most frequent primary sites in both groups (66% and 88%, respectively). There were no statistically significant differences in Ann Arbor stage, Ki-67 expression, LDH levels, IPI scores, albumin levels, and neutrophil/lymphocyte ratio between HIV-positive and HIV-negative patients. All cases showed large lymphoid cells, of plasmablastic morphology with expression of at least one plasma cell marker (CD138, CD38, MUM1), CD45 positivity, variable expression of EMA, CD79 and CD30 and absence of expression of CD20, CD3, CD68 and LMP1; the proliferative index Ki67 varied between 60 and 90%. A small proportion of patients (18%) did not receive chemotherapy because of poor performance status or a personal decision. DA-EPOCH regimen was used in 52% and 25% of HIV+ and HIV- patients, respectively and CHOP/CHOEP regimen in 48 % and 75%, respectively. The overall response rate was 68% and 57% in HIV+ and HIV- patients with complete response (CR) in 32% and 14%, respectively. In the HIV-positive group, 66% of patients were antiretroviral therapy (ART)-naïve. The median progression-free survival (PFS) was 38 months and 7 months for HIV+ and HIV- patients, and the 1-year PFS was 74% and 0%, respectively. The median overall survival (OS) was 43 months (range 0.2-86.5) in HIV-positive patients and 10 months (range 0.5-19.0 months) in HIV-negative patients and the 1-year OS were 59% y 38%, respectively (p=0.27). Conclusions: PBL is a rare lymphoma, specially, if not related to HIV infection. In this study, 60 years or older was the only variable that showed significant difference. In our cohort, HIV-positive patients had better prognosis than HIV-negative PBL patients. Disclosures No relevant conflicts of interest to declare.

In this issue of Blood , Quintanilla-Martinez and colleagues describe a series of Hydroa vacciniforme–like lymphoma (HVLL) and find that this is an Epstein-Barr virus (EBV)-associated lymphoproliferative disorder with a diverse (αβ-, γδ-, or NK-cell) phenotype and a broad clinical spectrum, in most cases showing a prolonged clinical course, but with a distinct risk for progression to systemic disease. 1

SPIB is an Ets transcription factor that is expressed exclusively in mature B cells, T-cell progenitors, and plasmacytoid dendritic cells. In the present study, we developed a novel mAb against the SPIB protein and characterized its expression in major hematolymphoid neoplasms, including a series of 45 cases of blastic plasmacytoid dendritic cell (BPDC) neoplasms and their potential cutaneous mimics. We found that SPIB is expressed heterogeneously among B- and T-cell lymphoma types. Interestingly, SPIB is expressed in a large proportion of nongerminal center type DLBCLs. In cutaneous neoplasms, SPIB is overexpressed in all BPDC neoplasms, but none of its cutaneous mimics. SPIB remains overexpressed in all cases that lack 1 or 2 of the markers used for BPDC neoplasms (ie, CD4, CD56, TCL1, and CD123). We conclude that SPIB expression can be used as a tool for diagnosing BPDC neoplasms, but it needs to be tested in conjunction with the growing arsenal of markers for human plasmacytoid dendritic cells.

Background: Recent studies have shown that diffuse large B-cell lymphoma (DLBCL) cases with gene expression profiles similar to germinal center (GC) B cells had a much better prognosis than DLBCL cases with gene expression profiles resembling activated B cells. DLBCL can be classified into three immunohistochemical expression patterns: GC B-cell pattern (pattern A) expressing CD10 and/or Bcl-6 but not MUM1; activated GC B-cell pattern (pattern B) expressing at least one of GC B-cell markers and MUM1; and activated non-GC B-cell pattern (pattern C) expressing MUM1 but not GC B-cell markers. Purpose: To determine the frequency of these patterns, the immunohistochemical expression intensity of MUM1, BCL6 and BCL2, as well as International Prognostic Index (IPI) and therapeutical response. Methods: Immunohistochemical analysis on paraffin-embedded tissues was performed using the streptavidin-avidin-biotin method in 62 cases of DLBCL. The intensity of immunohistochemical expression was performed as follows: positive (more than 50% expression), positive/negative (expression 20 to 50%), and negative (less than 20%expression). Results: The average age was 60 years. Females were slightly more frequent than males. 84% cases were primary nodal. According to IPI, 60% of cases were low (L) or intermediate-low (IL) risk, and 40% were intermediate-high (IH) or high risk (H). The corresponding A, B and C patterns, by immunohistochemistry, were 10%, 19% and 65% respectively. The majority of patients were treated with CHOP. Complete response (CR) was achieved in 54%, partial response (PR) in 11%, and no response (NR) in 23%. 9 % were not assessed. 4/6, 8/10, 17/36 of the cases had CR in the patterns A, B, C respectively. 5/6, 8/12, 22/40 of the cases were L-IL in the same patterns, without significant difference between these groups. The immunohistochemical expression intensity for either marker was not statistically significant. Conclusions: The most frecuent pattern was C. The activated patterns were most common. The correlation between different pattern expression, IPI and therapeutical response didn’t show statistical differences, probably due to the small size of the sample.