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1 - Serum and tumor cytokines according to MYD88 mutational status 2- Discrepancies in cell of origin distribution between gene expression and immunohistochemistry

Purpose: Mutations in MYD88 are found in different lymphoproliferative disorders associated with particular biologic characteristics and clinical impact. The aim of this study was to analyze the incidence of MYD88 mutations and its clinical impact in diffuse large B-cell lymphoma (DLBCL).Experimental Design: The incidence, clinicobiological features, and outcome of 213 patients (115 M/98 F; median age, 65 years) with DLBCL treated with immunochemotherapy in a single institution according to MYD88 mutational status as assessed by an allele-specific PCR assay were analyzed. The cell of origin (COO) was determined in 129 cases by gene expression.Results: MYD88 mutations were found in 47 cases (22%), including L265P in 39 and S219C and M232F in 4 cases, respectively. Patients with MYD88 L265P were older, presenting frequent extranodal involvement, and mostly corresponded to activated B-cell like (ABC) subtype, whereas no preference in COO was observed in patients with other MYD88 mutations. Five-year overall survival (OS) for MYD88 wild-type, MYD88 L265P, and other variants was 62%, 52%, and 75%, respectively (P = 0.05). International Prognostic Index (IPI) (HR, 2.71; P < 0.001) and MYD88 L265P (HR, 1.786; P = 0.023) were independent variables predicting OS in the multivariate analysis. However, MYD88 L265P lost its independent value when COO was included in the model.Conclusions: Our findings indicate that MYD88 L265P mutations, but no other variants, identify a subgroup of DLBCL mainly of ABC origin, with extranodal involvement and poor outcome. Clin Cancer Res; 22(11); 2755–64. ©2016 AACR.

OBJECTIVES Few data regarding follow-up of patients after COVID-19 discharge are available. We aim to describe the long-term outcomes of survivors of hospitalization for COVID-19 followed up first at an outpatient facility and subsequently by telephone. METHODS Observational prospective study conducted at a tertiary general hospital. Clinical and radiological progression was assessed and data recorded on a standardized reporting form. Patients were divided into three groups according to PaO2/FiO2 at hospitalization: PaO2/FiO2 > 300, PaO2/FiO2 300-200 and PaO2/FiO2 < 200. A logistic multivariate regression model was performed to identify factors associated with persistence of symptoms. RESULTS Facility follow-up: 302 patients were enrolled. Median follow-up was 45 days after discharge; 78% (228/294) of patients had COVID-19-related symptoms (53% asthenia, 56% respiratory symptoms) and 40% (122/302) had residual pulmonary radiographic lesions. PaO2/FiO2 300 was associated with resolution of chest radiographic lesions; OR = 0.56 (0.42 to 0.74), (p, Graphical abstract Image 1

The frequency of aggressive subtypes of B-cell non-Hodgkin lymphoma (B-NHL), such as high-grade B-cell lymphomas (HGBL) with MYC and BCL2 and/or BCL6 rearrangement (HGBL-DH/TH) or Burkitt-like lymphoma (BL) with 11q aberration, is not well known in the HIV setting. We aimed to characterise HIV-associated aggressive B-NHL according to the 2017 WHO criteria, and to identify genotypic and phenotypic features with prognostic impact. Seventy-five HIV-associated aggressive B-NHL were studied by immunohistochemistry (CD10, BCL2, BCL6, MUM1, MYC, and CD30), EBV-encoded RNAs (EBERs), and fluorescence in situ hybridisation (FISH) to evaluate the status of the MYC, BCL2, and BCL6 genes and chromosome 11q. The 2017 WHO classification criteria and the Hans algorithm, for the cell-of-origin classification of diffuse large B-cell lymphomas (DLBCL), were applied. In DLBCL cases, the frequencies of MYC and BCL6 rearrangements (14.9 and 27.7%, respectively) were similar to those described in HIV-negative patients, but BCL2 rearrangements were infrequent (4.3%). MYC expression was identified in 23.4% of DLBCL cases, and coexpression of MYC and BCL2 in 13.0%, which was associated with a worse prognosis. As for BL cases, the expression of MUM1 (30.4%) conferred a worse prognosis. Finally, the prevalence of HGBL-DH/TH and BL-like with 11q aberration are reported in the HIV setting. The phenotypic and genotypic characteristics of HIV-associated aggressive B-NHL are similar to those of the general population, except for the low frequency of BCL2 rearrangements in DLBCL. MYC and BCL2 coexpression in DLBCL, and MUM-1 expression in BL, have a negative prognostic impact on HIV-infected individuals.

Simple Summary T-LGLL and CLPD-NK are two indolent lymphoproliferative syndromes whose main symptoms derive from the cytopenia(s). A proportion of patients harbor STAT3 mutations that appear to play an important role in the pathogenesis of the disease. The aim of our retrospective study was to describe the main clinicobiological characteristics, response to therapy and outcome in a large cohort of T-LGLL and CLPD-NK patients diagnosed at a single institution. The impact of STAT3 mutations on the behaviour of the disease and the survival of these patients compared to the age- and sex-matched general population are also evaluated. For the first time, we show that the survival of patients with these two diseases does not differ from that of a matched general Spanish population, confirming the indolent course of these entities. Abstract T-cell large granular lymphocytic leukemia (T-LGLL) and chronic lymphoproliferative disorder of natural killer (NK) cells are two infrequent diseases characterized by clonal expansions of cytotoxic T lymphocytes and NK cells, respectively. Somatic mutations of STAT3 are involved in the pathogenesis of these entities. We describe the clinicobiological features, mutational status of STAT3/STAT5B, treatment and outcome of 131 patients. Neutropenia was the most frequent finding at diagnosis, followed by anemia. Concurrent hematological disorders were diagnosed in 37% of patients and autoimmune conditions and solid tumors in 17% and 15%, respectively. All patients who needed treatment belonged to the CD8+CD57+ group. Remarkably, patients included in the CD4+ group had a higher association with solid tumors (p = 0.037). STAT3 mutations were found in 17% of patients, mainly Y640F and D661Y mutations. Patients carrying STAT3 mutations more frequently presented with anemia, neutropenia, high LDH, high large granular lymphocyte counts and need for treatment (p = 0.0037). Methotrexate was the most frequently used agent (72% of cases). The overall response rate to all treatments was 50%. The 10-year overall survival of this series was 78%, with no differences according to the mutational status of STAT3. We compared the survival of these patients with the general Spanish population and no differences were found, confirming the indolent nature of these hematological malignancies. Our study further extends findings documented by others on the clinical behavior of the disease and the impact of STAT3, and for the first time analyzes survival compared to a matched general Spanish population.

This study examined the impact of prednisone (PDN) on cytomegalovirus (CMV) infection after allogeneic stem cell transplantation (allo-SCT) according to donor and recipient CMV serostatus. Seventy-five patients underwent allo-SCT from June 2010 to July 2012. The risk of CMV infection according to donor and recipient serostatus was defined as follows: high risk (HR; D-/R+), intermediate risk (IR; D+/R+ and D+/R-), and low risk (D-/R-). Forty-five patients (60%) developed CMV infection, and 46 patients (61%) received steroids (PDN ≥ 1 mg/kg/day) to treat acute graft-versus-host disease. CMV infection was more common in those treated with steroids than in those not treated with steroids (70% versus 44%, respectively, P .05). Overall, 40% of patients had recurrent CMV infection (50% PDN versus 24% no PDN, P .05). Steroids had no impact on the incidence of CMV infection or its recurrence in HR patients; however, steroids did prolong the need for antiviral treatment. The incidence of CMV infection in IR patients was higher in those receiving PDN (80% PDN versus 41% no PDN, P = .01); recurrence rates were also higher (55% PDN versus 18% no PDN, P = .02). We analyzed CMV-specific immune reconstitution in the first 22 patients of the series and observed that patients on steroids had lower levels of CMV-specific lymphocytes TCD8 (P .05 on days +60, +100, and +180) and that CMV-specific immune reconstitution (defined as lymphocytes CD8/IFN ≥ 1 cell/µL) was achieved later (after day +100 post-SCT) in the steroid group.

This study was supported by the Ministerio de Economía y Competitividad, Grant n. SAF2015-67633-R ,and PI16/00420 which are part of Plan Nacional de I+D+I and are co-financed by the European Regional Development Fund (FEDER-“Una manera de hacer Europa”) and the CERCA program from Generalitat Catalunya. European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement n. 306240; Generalitat de Catalunya Suport Grups de Recerca AGAUR 2017-SGR1009, and Departament de Salut (SLT002-16-00350), Instituto de Salud Carlos III (ISCIII) International Cancer Genome Consortium for Chronic Lymphocytic Leukemia (ICGC-CLL Genome Project), and project PM15/00007, which is part of Plan Nacional de I+D+I and are co-financed by FEDER. NG is a recipient of a predoctoral fellowship from Agaur and EC is an Academia Researcher of the "Institució Catalana de Recerca i Estudis Avançats" (ICREA) of the Generalitat de Catalunya., Giménez, N., Martínez-Trillos, A., Montraveta, A., Lopez-Guerra, M., Rosich, L., Nadeu, F., Valero, J.G., Aymerich, M., Magnano, L., Rozman, M., Matutes, E., Delgado, J., Baumann, T., Gine, E., González, M., Alcoceba, M., Terol, M.J., Navarro, B., Colado, E., Payer, A.R., Puente, X.S., López-Otín, C., Lopez-Guillermo, A., Campo, E., Colomer, D., Villamor, N.

Resumen Antecedentes y objetivo Los linfomas con reordenamiento de MYC (MYC-R) diferentes al linfoma de Burkitt (LB) son muy agresivos, con un pronostico desfavorable cuando se tratan con regimenes estandar. El objetivo del estudio fue investigar las caracteristicas y el resultado de una serie de linfomas MYC-R, comparando los resultados del tratamiento de los regimenes basados en R-CHOP y un regimen intensivo especifico para LB (BURKIMAB). Pacientes y metodos Estudio retrospectivo de pacientes diagnosticados de MYC-R. Se evaluaron las translocaciones de MYC, BCL2 y BCL6 mediante hibridacion in situ fluorescente. Se trato a los pacientes, bien con inmunoquimioterapia basada en R-CHOP, bien con el regimen tipo Burkitt, BURKIMAB. Resultados Se estudiaron 34 casos de linfomas MYC-R: 21 tratados con R-CHOP y 13 tratados con BURKIMAB. No se produjeron diferencias en cuanto a tasa de RC; 45% (9/20) para R-CHOP y 42% (5/12) para BURKIMAB (p = 0,99). Aunque la supervivencia global (SG) y la supervivencia libre de progresion (SLP) de los pacientes tratados con BURKIMAB fueron mejores que las de los pacientes tratados con R-CHOP (SG a 3 anos: 46 frente a 24%; SLP a 3 anos: 46 frente a 10%), las diferencias no fueron estadisticamente significativas. Conclusion Los linfomas MYC-R muestran resultados desfavorables, aun cuando se tratan con inmunoquimioterapia intensiva para LB.

Background and objective MYC-rearranged (MYC-R) lymphomas other than Burkitt lymphoma (BL) are very aggressive, with poor prognosis when treated with standard regimens. We aimed to study the characteristics and outcome of a series of MYC-R lymphomas comparing the treatment results between R-CHOP based and a specific intensive regimen for BL (BURKIMAB). Patients and methods Retrospective study of patients diagnosed with MYC-R. Translocations of MYC, BCL2 and BCL6 were evaluated by fluorescent in situ hybridization. Patients were treated with either, R-CHOP based immunochemotherapy or the Burkitt type regimen, BURKIMAB. Results Thirty-four MYC-R lymphoma cases were studied: 21 treated with R-CHOP and 13 treated with BURKIMAB. There were no differences in CR rate; 45% (9/20) for R-CHOP and 42% (5/12) for BURKIMAB (p = 0.99). Although overall survival (OS) and progression free survival (PFS) of BURKIMAB-treated patients were better than those of R-CHOP-treated (3y-OS: 46 vs. 24%; 3y-PFS: 46 vs. 10%), the differences were not statistically significant. Conclusion MYC-R lymphomas show poor outcomes even when treated with intensive immunochemotherapy for BL.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma with heterogeneous outcomes. To improve accuracy of the international prognostic index score, new biological variables are being investigated. The aim of this study was to determine the prognostic significance of serum levels of different cytokines, namely soluble interleukin-2 receptor (sIL2-R), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF). We analyzed 197 de novo DLBCL patients (91 M/106 F; median age 66 years) treated with immunochemotherapy in a single institution. Serum cytokine determination was performed with ELISA, using the upper normal values as cut-offs. sIL-2R, IL-6 and TNF were elevated in 133, 130 and 144 cases, respectively. Elevation of each of these cytokines correlated with worse performance status, presence of B symptoms, advanced stage, elevated LDH and β2-microglobulin (P

Purpose: Mutations in MYD88 are found in different lymphoproliferative disorders associated with particular biologic characteristics and clinical impact. The aim of this study was to analyze the incidence of MYD88 mutations and its clinical impact in diffuse large B-cell lymphoma (DLBCL). Experimental Design: The incidence, clinicobiological features, and outcome of 213 patients (115 M/98 F; median age, 65 years) with DLBCL treated with immunochemotherapy in a single institution according to MYD88 mutational status as assessed by an allele-specific PCR assay were analyzed. The cell of origin (COO) was determined in 129 cases by gene expression. Results: MYD88 mutations were found in 47 cases (22%), including L265P in 39 and S219C and M232F in 4 cases, respectively. Patients with MYD88 L265P were older, presenting frequent extranodal involvement, and mostly corresponded to activated B-cell like (ABC) subtype, whereas no preference in COO was observed in patients with other MYD88 mutations. Five-year overall survival (OS) for MYD88 wild-type, MYD88 L265P, and other variants was 62%, 52%, and 75%, respectively (P = 0.05). International Prognostic Index (IPI) (HR, 2.71; P < 0.001) and MYD88 L265P (HR, 1.786; P = 0.023) were independent variables predicting OS in the multivariate analysis. However, MYD88 L265P lost its independent value when COO was included in the model. Conclusions: Our findings indicate that MYD88 L265P mutations, but no other variants, identify a subgroup of DLBCL mainly of ABC origin, with extranodal involvement and poor outcome. Clin Cancer Res; 22(11); 2755–64. ©2016 AACR.

Bosutinib is a second-generation tyrosine kinase inhibitor (2GTKI) approved at 400 mg once daily (QD) as first-line therapy in patients with chronic myeloid leukemia (CML) patients and at 500 mg QD in patients who are resistant to or intolerant of prior therapy. In clinical practice, bosutinib is often given to patients who have failed imatinib, nilotinib, and dasatinib (i.e., as fourth-line treatment), despite the limited data on its clinical benefit in this setting. We have retrospectively evaluated the results of bosutinib in a series of 62 CML patients who have failed to prior treatment with all three, imatinib, nilotinib, and dasatinib. Median time on TKI treatment before bosutinib start was 105 (9–163) months, and median duration on bosutinib was 9 months (1–30). Overall, probabilities to achieve complete cytogenetic response (CCyR) and major molecular response (MMR) were 25% and 24% respectively. After a median follow-up period of 14 months, the event-free survival and progression-free survival were 68 and 85%, respectively. Sixty-four percent of patients in CCyR at the time of bosutinib start were able to achieve MMR. In contrast, patients without CCyR, probabilities to obtain CCyR and MMR were 25% and 14%. Bosutinib was well tolerated in this heavily pretreated patients’ cohort. Pleural effusions and diarrhea were the most frequent grade II–IV side effects, leading to treatment discontinuation in 16% of patients. Bosutinib is an effective treatment option for patients who have failed previous 2GTKIs due to intolerance. However, efficacy seems to be related to the molecular response that the patient achieved prior to bosutinib.

Background The co-existence at diagnosis of follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) components (FL/DLBCL) has been considered a transformed lymphoma and accordingly treated although clinicobiological information on these patients is scarce. The aim of this study was to analyze the initial features and outcome of FL/DLBCL patients in the rituximab era. Patients and methods All patients consecutively diagnosed at a single institution with FL/DLBCL (n = 40), as well as those with pure FL (n = 328) or de novo DLBCL (n = 510) as controls. Results The proportion of the DLBCL component was highly variable (median 50%). In 29 FL/DLBCL cases analyzed, the cell of origin was GCB in 86%, ABC in 10% and unclassifiable in 4%. NOTCH1-2 was mutated in 10% of these cases. The proportion of DLBCL component did not impact on overall survival (OS). Regarding initial characteristics, patients with FL/DLBCL were closer to FL in terms of primary nodal origin, good performance status and advanced stage, whereas the other features were intermediate between FL and DLBCL. FL/DLBCL patients were treated as DLBCL with no further intensification. Complete response and primary refractory rates were 65% and 20%, respectively, with these figures being similar to DLBCL and worse than FL. Progression-free survival and OS were intermediate between FL and DLBCL (5-year OS: 85%, 73% and 63% for FL, FL/DLBCL and DLBCL, respectively). FL/DLBCL histology did not reach independent prognostic value for OS in the multivariate analyses. Conclusions The outcome of FL/DLBCL patients is not worse than that of de novo DLBCL. These cases should be treated with immunochemotherapy as DLBCL, but intensification with ASCT may not be necessary. The biological insights of FL/DLBCL warrants further genetic and molecular studies.

This study has retrospectively analyzed the efficacy of single-agent prednisone, usually given after failure of other therapies, in 30 patients with myelofibrosis (MF) and severe anemia. Initial dose was 0.5-1 mg/kg daily, with tapering to the minimum effective dose in responders. Twelve patients (40%) achieved anemia response according to the revised International Working Group for Myelofibrosis Research and Treatment criteria, after a median time of 1.1 months on treatment. Median response duration was 12.3 months. Patients with constitutional symptoms or > 2% circulating blasts had a trend for a lower response rate. A platelet increase > 50 × 10(9)/L was observed in three out of 11 patients with baseline counts < 100 × 10(9)/L. Median survival from prednisone start was significantly longer in anemia responders (5.0 years, 95% CI = 3.5-6.5, vs 1.5 years, 95% CI = 0.2-2.8; p = 0.002). Prednisone can improve the anemia and thrombocytopenia in selected MF patients after failure to standard therapies.

The role of bosutinib as rescue treatment of Philadelphia chromosome-positive chronic myeloid leukemia (CML) patients after failing three previous tyrosine kinase inhibitors (TKIs) is currently unknown. We report here the largest series (to our knowledge) of patients treated with bosutinib in fourth-line, after retrospectively reviewing 30 patients in chronic phase, and pretreated with imatinib, nilotinib, and dasatinib. With a median follow up of 11.1 months, the probability to either maintain or improve their CCyR response was 56.6% (17/30) and 11 patients (36.7%) achieved or maintained their baseline MMR. In patients not having baseline CCyR, the probabilities of obtaining CCyR, MMR, and MR4.5 were 13, 11, and 14%, respectively. The probabilities of obtaining MMR and deep molecular response MR4.5 in patients with baseline CCyR were 40.0% (6/15) and 20.0% (3/15). At 20 months, progression-free survival was 73%. Grade 3-4 hematological toxicities were more frequent in resistant than intolerant patients (45.4 vs. 0.0%). Nonhematological toxicities were also more frequent in resistant patients, being diarrhea the most conspicuous one. Bosutinib seems to be an appropriate treatment option for patients resistant or intolerant to three prior TKI's.

B-cell chronic lymphoproliferative disorders (B-CLPD) encompass a group of hematologic tumors that often present with leukemic involvement.1 Their heterogeneity and the lack of relatively specific diagnostic markers for most of these diseases make their diagnosis challenging, especially in cases that only have blood involvement or when histology is not available. With the currently used immunophenotypic and molecular markers, around 10% of B-CLPD cases remain unclassifiable and are categorized as B-CLPD, not otherwise specified (B-CLPD, NOS).

Prospective identification of patients with chronic lymphocytic leukemia (CLL) destined to progress would greatly facilitate their clinical management. Recently, whole-genome DNA methylation analyses identified three clinicobiologic CLL subgroups with an epigenetic signature related to different normal B-cell counterparts. Here, we developed a clinically applicable method to identify these subgroups and to study their clinical relevance. Using a support vector machine approach, we built a prediction model using five epigenetic biomarkers that was able to classify CLL patients accurately into the three subgroups, namely naive B-cell-like, intermediate and memory B-cell-like CLL. DNA methylation was quantified by highly reproducible bisulfite pyrosequencing assays in two independent CLL series. In the initial series (n=211), the three subgroups showed differential levels of IGHV (immunoglobulin heavy-chain locus) mutation (P

Therapeutic options for patients with polycythemia vera (PV) and essential thrombocythemia (ET) resistant or intolerant to hydroxyurea are limited. Busulfan is effective as first-line therapy, but there is scarce information on this drug as second-line treatment. The efficacy of busulfan in patients with advanced PV or ET refractory or intolerant to hydroxyurea was assessed in 36 patients (PV n = 15, ET n = 21) treated for a median of 256 days. Complete hematological response (CHR) was achieved in 83 % of patients, after a median time of 203 days (range 92-313). The probability of sustained CHR at 1 and 2 years was 87 and 62 %, respectively. Time to CHR was shorter in patients treated with ≥14 mg of busulfan per week than with lower doses (141 versus 336 days, p = 0.01). Partial molecular response was achieved in three out of nine (33 %) patients. Busulfan was stopped in 27 patients (75 %) due to CHR achievement in 18 cases (67 %), hematological toxicity in 8 cases (30 %), and disease transformation in 1 case. With a median follow-up of 721 days, six patients have died, with the probability of survival at 2 years being 85 %. The probability of thrombosis at 2 years was 11 %. Transformation into acute leukemia or myelodysplastic syndrome was observed in three cases, all of them in a JAK2V617F-negative clone carrying additional mutations. Busulfan, at a dose of 2 mg/day, is an effective option for elderly patients with PV or ET who fail to hydroxyurea, but a significant rate of transformation was observed.

Mutations in Toll-like receptor (TLR) and myeloid differentiation primary response 88 (MYD88) genes have been found in chronic lymphocytic leukemia (CLL) at low frequency. We analyzed the incidence, clinicobiological characteristics, and outcome of patients with TLR/MYD88 mutations in 587 CLL patients. Twenty-three patients (3.9%) had mutations, 19 in MYD88 (one with concurrent IRAK1 mutation), 2 TLR2 (one with concomitant TLR6 mutation), 1 IRAK1, and 1 TLR5. No mutations were found in IRAK2 and IRAK4. TLR/MYD88-mutated CLL overexpressed genes of the nuclear factor κB pathway. Patients with TLR/MYD88 mutations were significantly younger (83% age ≤50 years) than those with no mutations. TLR/MYD88 mutations were the most frequent in young patients. Patients with mutated TLR/MYD88 CLL had a higher frequency of mutated IGHV and low expression of CD38 and ZAP-70. Overall survival (OS) was better in TLR/MYD88-mutated than unmutated patients in the whole series (10-year OS, 100% vs 62%; P = .002), and in the subset of patients age ≤50 years (100% vs 70%; P = .02). In addition, relative OS of TLR/MYD88-mutated patients was similar to that in the age- and gender-matched population. In summary, TLR/MYD88 mutations identify a population of young CLL patients with favorable outcome.

MYC-rearranged (MYC-R) lymphomas other than Burkitt lymphoma (BL) are very aggressive, with poor prognosis when treated with standard regimens. We aimed to study the characteristics and outcome of a series of MYC-R lymphomas comparing the treatment results between R-CHOP based and a specific intensive regimen for BL (BURKIMAB).Retrospective study of patients diagnosed with MYC-R. Translocations of MYC, BCL2 and BCL6 were evaluated by fluorescent in situ hybridization. Patients were treated with either, R-CHOP based immunochemotherapy or the Burkitt type regimen, BURKIMAB.Thirty-four MYC-R lymphoma cases were studied: 21 treated with R-CHOP and 13 treated with BURKIMAB. There were no differences in CR rate; 45% (9/20) for R-CHOP and 42% (5/12) for BURKIMAB (P=.99). Although overall survival (OS) and progression free survival (PFS) of BURKIMAB-treated patients were better than those of R-CHOP-treated (3y-OS: 46 vs. 24%; 3y-PFS: 46 vs. 10%), the differences were not statistically significant.MYC-R lymphomas show poor outcomes even when treated with intensive immunochemotherapy for BL.

We have analyzed in lymph nodes at diagnosis of 75 patients with follicular lymphoma (FL) the relationship between different T-cell subpopulations, assessed by immunohistochemistry (IHC) and flow cytometry (FC), with the outcome. CD4+ cells were the most abundant T-cells in tumor tissue sections, whilst CD57+ cells were the less frequent. In addition to nonambulatory performance status, advanced stage and FLIPI, low CD4+CD57+/CD4+ ratio (p = .041), and low CD4+/CD8+ ratio (p = .008) predicted poor overall survival (OS). Multivariate analysis showed that CD4+CD57+/CD4+ ratio was the most important variable for OS. In conclusion, T-cell subpopulations, including CD4+CD57+/CD4+ ratio analyzed by FC, could identify FL patients with favorable outcome.