Interplay of leucocyte-platelet complexes and clinical response to eltrombopag in immune thrombocytopenia patients.

Eltrombopag (ELT) is a thrombopoietin-receptor agonist that stimulates platelet (PLT) production in patients with primary immune thrombocytopenia (ITP). One potential mechanism of ELT is modulating the inflammatory response by increasing PLTs binding to leucocytes. This study examined the effect of ELT on leucocyte-PLTs complexes in 38 ITP patients. Patients, predominantly females with a mean age of 59 years, underwent treatments like corticosteroids, intravenous immunoglobulin and splenectomy. Compared to healthy donors, ITP patients exhibited lower percentages of lymphocyte with bound PLTs, but similar monocyte- or neutrophil with bound PLTs. ELT treatment increased PLTs counts and all types of leucocyte with bound PLTs. Network analysis showed dynamic changes in leucocyte with bound PLTs relationships due to ELT. Machine learning indicated that higher percentages of monocytes with bound PLTs were linked to a better clinical response to ELT. A possible mechanism was an increased IL-10 production in monocytes with bound PLTs from responder patients. This study provides insights into the immunological changes in ITP patients undergoing ELT and suggests potential predictive biomarkers for treatment response and disease monitoring.

Avatrombopag in immune thrombocytopenia: A real-world study of the Spanish ITP Group (GEPTI).

Avatrombopag is the newest thrombopoietin receptor agonist (TPO-RA) approved to treat immune thrombocytopenia (ITP). Real-world evidence regarding effectiveness/safety is limited. The Spanish ITP Group (GEPTI) performed a retrospective study with patients starting avatrombopag for the first time. A total of 268 ITP patients were recruited. The median (interquartile range [IQR]) follow-up time was 47.5 (30.4-58.9) weeks. Among the 193 patients with baseline platelet counts <50 × 109/L, 174 (90.1%) of them achieved response (PC ≥50 × 109/L), and 113 (87.6%) of the 129 who persisted on avatrombopag at last visit had platelet levels above such threshold. Results were similar when only those patients switching to avatrombopag due to previous treatment failure were considered (n = 104). Patients reached response in 13 (7-21) days. Among patients with baseline levels ≥50 × 109/L, 73/75 (97.3%) reported response, which was maintained by 53 (94.6%) of the 56 who continued on avatrombopag at the end of the study. Loss-of-response was always <10%. ITP duration did not influence response. Approximately 79% (34/43) of heavily pretreated (≥4 lines) patients with baseline platelet counts <50 × 109/L switching after previous failure achieved PC ≥50 × 109/L. Previous use of eltrombopag and/or romiplostim did not influence response, regardless of whether previous TPO-RA(s) succeeded or failed. Avatrombopag allowed dose-reduction/suspension of corticosteroids in 40/50 (80.0%) patients with baseline platelet counts <50 × 109/L. Overall, 40/268 (14.9%) thrombocytosis and 12/268 (4.5%) thromboembolic events were reported. Our real-world cohort supports the use of avatrombopag to manage ITP, regardless of disease severity and treatment history.

Brentuximab vedotin in the treatment of cutaneous T-cell lymphomas: Data from the Spanish Primary Cutaneous Lymphoma Registry.

BACKGROUND: Brentuximab vedotin (BV) has been approved for CD30-expressing cutaneous T-cell lymphoma (CTCL) after at least one previous systemic treatment. However, real clinical practice is still limited. OBJECTIVES: To evaluate the response and tolerance of BV in a cohort of patients with CTCL. METHODS: We analysed CTCL patients treated with BV from the Spanish Primary Cutaneous Lymphoma Registry (RELCP). RESULTS: Sixty-seven patients were included. There were 26 females and the mean age at diagnosis was 59 years. Forty-eight were mycosis fungoides (MF), 7 Sézary syndrome (SS) and 12 CD30+ lymphoproliferative disorders (CD30 LPD). Mean follow-up was 18 months. Thirty patients (45%) showed at least 10% of CD30+ cells among the total lymphocytic infiltrate. The median number of BV infusions received was 7. The overall response rate (ORR) was 67% (63% in MF, 71% in SS and 84% in CD30 LPD). Ten of 14 patients with folliculotropic MF (FMF) achieved complete or partial response (ORR 71%). The median time to response was 2.8 months. During follow-up, 36 cases (54%) experienced cutaneous relapse or progression. The median progression free survival (PFS) was 10.3 months. The most frequent adverse event was peripheral neuropathy (PN) (57%), in most patients (85%), grades 1 or 2. CONCLUSIONS: These results confirm the efficacy and safety of BV in patients with advanced-stage MF, and CD30 LPD. In addition, patients with FMF and SS also showed a favourable response. Our data suggest that BV retreatment is effective in a proportion of cases.

Cutaneous Involvement of Angioimmunoblastic T-Cell Lymphoma Masquerading as B-Cell Reactive Lymphoid Hyperplasia.

ABSTRACT: A 59-year-old woman presented with a persistent eruption manifested as multiple agminated miliary facial papules. Histopathological examination showed prominent nodular dermal lymphoid infiltrates with hyperplastic follicles that were initially interpreted as B-cell reactive lymphoid hyperplasia. Several years later, an additional biopsy showed a dense perifollicular infiltrate with reactive primary and secondary follicles. Accompanying T cells corresponded to CD3/CD4/PD1/CXCL13-positive cells and scattered Epstein-Barr virus-positive B cells were identified by in situ hybridization. A monoclonal T-cell population was demonstrated by TCRγ and TCRß Polymerase Chain Reaction amplification, as well as a minor abnormal circulating T-cell population by flow cytometry (0.62% of the white blood cells, CD4+CD3s-CD7-). A biopsy specimen from an enlarged right supraclavicular lymph node disclosed nodal involvement by angioimmunoblastic T-cell lymphoma. The observation of B-cell dermal nodular infiltrates with well-demarcated lymphoid aggregates forming primary lymphoid follicles may lead to overlook the T-cell component in some cases of angioimmunoblastic T-cell lymphoma. In such cases, a careful assessment of the apparently minor T-cell component is important to establish a correct diagnosis.

Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma With Secondary Cutaneous Involvement: A Diagnostic Challenge.

ABSTRACT: A 45-year-old woman presented with a solitary breast nodule that histologically corresponded to a dense dermal/subcutaneous infiltration of atypical cytotoxic T-lymphocytes (CD3+, CD8+, CD56+, TIA-1+, CD5-, CD4-, CD30-, EBV-), resembling subcutaneous panniculitic T-cell lymphoma. The presence of TCRδ gene rearrangement and the absence of ßF1 expression let to suspect the diagnosis of primary cutaneous γδT-cell lymphoma. As a consequence of jejunum perforation following chemotherapy treatment, a mucosal atypical lymphoid infiltration with marked epitheliotropism was observed in the resected intestinal sample, and the diagnosis of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) was finally established. Disease progression appeared with multiple erythematous plaques showing a dense lichenoid atypical cytotoxic T-cell infiltrate with intense epidermotropism, mimicking primary cutaneous epidermotropic aggressive CD8+ T-cell lymphoma. MEITL is an uncommon and aggressive peripheral T-cell lymphoma that often presents in adults with gastrointestinal symptoms. Secondary cutaneous involvement is a rare phenomenon that may show clinicopathologic and immunohistochemical features that overlap with different subtypes of primary cutaneous cytotoxic T-cell lymphomas. In the absence of gastrointestinal symptoms, the diagnosis may be challenging, and only the evidence of underlying MEITL may allow to establish the definite diagnosis.

Use of eltrombopag for patients 65 years old or older with immune thrombocytopenia.

BACKGROUND: Eltrombopag is useful for immune thrombocytopenia (ITP). However, results of clinical trials may not accurately mirror clinical practice reality. Here we evaluated eltrombopag for primary and secondary ITP in our ≥65-year-old population. METHODS: A total of 106 primary ITP patients (16 with newly diagnosed ITP, 16 with persistent ITP, and 74 with chronic ITP) and 39 secondary ITP patients (20 with ITP secondary to immune disorders, 7 with ITP secondary to infectious diseases, and 12 with ITP secondary to lymphoproliferative disorders [LPD]) were retrospectively evaluated. RESULTS: Median age of our cohort was 76 (interquartile range, IQR, 70-81) years. 75.9% of patients yielded a platelet response including 66.2% complete responders. Median time to platelet response was 14 (IQR, 8-21) days. Median time on response was 320 (IQR, 147-526) days. Sixty-three adverse events (AEs), mainly grade 1-2, occurred. The most common were hepatobiliary laboratory abnormalities (HBLAs) and headaches. One transient ischemic attack in a newly diagnosed ITP and two self-limited pulmonary embolisms in secondary ITP were the only thrombotic events observed. CONCLUSION: Eltrombopag showed efficacy and safety in ITP patients aged ≥65 years with primary and secondary ITP. However, efficacy results in LPD-ITP were poor. A relatively high number of deaths were observed.

Phase 2 study of efgartigimod, a novel FcRn antagonist, in adult patients with primary immune thrombocytopenia.

Primary immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder, characterized by a low platelet count (<100 × 109 /L) in the absence of other causes associated with thrombocytopenia. In most patients, IgG autoantibodies directed against platelet receptors can be detected. They accelerate platelet clearance and destruction, inhibit platelet production, and impair platelet function, resulting in increased risk of bleeding and impaired quality of life. Efgartigimod is a human IgG1 antibody Fc-fragment, a natural ligand of the neonatal Fc receptor (FcRn), engineered for increased affinity to FcRn, while preserving its characteristic pH-dependent binding. Efgartigimod blocks FcRn, preventing IgG recycling, and causing targeted IgG degradation. In this Phase 2 study, 38 patients were randomized 1:1:1 to receive four weekly intravenous infusions of either placebo (N = 12) or efgartigimod at a dose of 5 mg/kg (N = 13) or 10 mg/kg (N = 13). This short treatment cycle of efgartigimod in patients with ITP, predominantly refractory to previous lines of therapy, was shown to be well tolerated, and demonstrated a favorable safety profile consistent with Phase 1 data. Efgartigimod induced a rapid reduction of total IgG levels (up to 63.7% mean change from baseline), which was associated with clinically relevant increases in platelet counts (46% patients on efgartigimod vs 25% on placebo achieved a platelet count of ≥50 × 109 /L on at least two occasions, and 38% vs 0% achieved ≥50 × 109 /L for at least 10 cumulative days), and a reduced proportion of patients with bleeding. Taken together, these data warrant further evaluation of FcRn antagonism as a novel therapeutic approach in ITP.

Anthracycline-induced cardiotoxicity in diffuse large B-cell lymphoma: NT-proBNP and cardiovascular score for risk stratification.

OBJECTIVE: To evaluate the role of N-terminal pro-brain-type natriuretic peptide (NT-proBNP) and a cardiovascular (CV) risk score named FRESCO for predicting anthracycline-induced cardiotoxicity (AIC) in diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 130 consecutive DLBCL patients treated in first-line with anthracycline-containing immunochemotherapy. Competitive risk between NT-proBNP, FRESCO, and time to AIC was considered. RESULTS: Cumulative incidence of AIC was 12.2% and 17.5% at 1 and 5 years, respectively. Median time to development cardiotoxicity was 6.4 months, with half of the cases showing heart failure and the other half silent AIC. Both NT-proBNP levels and FRESCO score were independently associated with higher risk of AIC (P = 0.001 and P = 0.03, respectively). Patients with NT-proBNP ≥600 pg/mL or those with FRESCO ≥4.5% had 3.97 or 2.54 times higher risk of AIC than those with lower values (P = 0.001 and P = 0.048, respectively). According to the previous cutoffs, three groups of patients with a significantly different risk of AIC could be identified (P < 0.0001). CONCLUSIONS: Doxorubicin-containing chemotherapy is associated with increased risk of silent and overt AIC. Baseline NT-proBNP levels and FRESCO CV risk score are accurate predictors of AIC and can identify groups of patients at different risk, in which personalized cardiologic evaluation should be offered.

Do Patients and Physicians Agree When They Assess Quality of Life?

Patient and physician agreement on the most significant symptoms is associated with treatment outcomes and satisfaction with care. Thus, we sought to assess patient and physician agreement on patient-reported quality of life (QoL), and whether patient-related variables predict disagreement. In this cross-sectional, multisite study, patients and physicians completed the FACT-BMT at day 90. Agreement was analyzed with the intraclass coefficient correlation (ICC). Rates of underestimation and overestimation were calculated. Logistic regression models identified predictors of disagreement. We analyzed 96 pairs of questionnaires completed by 96 patients and 11 physicians. The patients' median age was 54 years, 52% were men, and 52% had undergone allogeneic hematopoietic cell transplantation (HCT). The physicians' median age was 42, 64% were men, and they had worked in the HCT field for an average of 12 years. Agreement on QoL was moderate (ICC = .436). Exploratory analyses revealed poor agreement for emotional (ICC = .092) and social (ICC = .270) well-being and moderate agreement for physical (ICC = .457), functional (ICC = .451), and BMT concerns (ICC = .445). Patients' well-being was underestimated by physicians in 41% to 59% of the categories of well-being parameters, and overestimated in 10% to 24%. Patient's anxiety predicted less disagreement in all scales except in social well-being, for which nonsignificant associations were observed. Patient-related variables explained 12% to 19% of the variance in disagreement across well-being scales. Patient and physician agreement on QoL was suboptimal, particularly in emotional and social well-being. The implementation of patient-reported outcomes in the daily care of HCT recipients may contribute to improving patient-centered care.

Use of eltrombopag for secondary immune thrombocytopenia in clinical practice.

Eltrombopag is a second-line treatment in primary immune thrombocytopenia (ITP). However, its role in secondary ITP is unknown. We evaluated the efficacy and safety of eltrombopag in secondary ITP in daily clinical practice. Eighty-seven secondary ITP patients (46 with ITP secondary to autoimmune syndromes, 23 with ITP secondary to a neoplastic disease subtype: lymphoproliferative disorders [LPDs] and 18 with ITP secondary to viral infections) who had been treated with eltrombopag were retrospectively evaluated. Forty-four patients (38%) had a platelet response, including 40 (35%) with complete responses. Median time to platelet response was 15 days (95% confidence interval, 7-28 days), and was longer in the LPD-ITP group. Platelet response rate was significantly lower in the LPD-ITP than in other groups. However, having achieved response, there were no significant differences between the durable response of the groups. Forty-three patients (49·4%) experienced adverse events (mainly grade 1-2), the commonest being hepatobiliary laboratory abnormalities. There were 10 deaths in this case series, all of which were related to pre-existing medical conditions. In routine clinical practice, eltrombopag is effective and well-tolerated in unselected patients with ITP secondary to both immune and infectious disorders. However, the response rate in LPD-ITP is low.

Contribution of cerebrospinal fluid sCD19 levels to the detection of CNS lymphoma and its impact on disease outcome.

Flow cytometry (FCM) is more sensitive than conventional cytology for detection of occult leptomeningeal lymphoma; however, some FCM-negative patients show central nervous system (CNS) recurrence. Here, we evaluated the cerebrospinal fluid (CSF) levels of 13 B-cell-associated markers and their contribution to the diagnosis of CNS lymphoma in 91 diffuse large B-cell lymphomas (DLBCL) and 22 Burkitt lymphomas (BLs). From all markers tested, CD19 was the most informative. Thus, higher soluble CD19 (sCD19) levels were associated with a greater frequency of neurological symptoms in DLBCL and BL and with parenchymal CNS lymphoma in DLBCL; sCD19 emerged as a powerful predictor of event-free and overall survival in DLBCL and BL, particularly when combined with FCM detection of CNS disease. These results support the utility of combined FCM detection of lymphoma cells and assessment of sCD19 levels in CSF, for more accurate identification of CNS disease in DLBCL and BL patients.

Eltrombopag safety and efficacy for primary chronic immune thrombocytopenia in clinical practice.

BACKGROUND: Eltrombopag is effective and safe in chronic immune thrombocytopenia (ITP). However, clinical trials may not accurately reflect what happens in clinical practice. We evaluated the efficacy and safety of eltrombopag in primary chronic ITP in a real-world setting. METHODS: A total of 164 primary patients with chronic ITP from 40 Spanish centers, who had been treated with eltrombopag, were retrospectively evaluated. RESULTS: The median age of our cohort (72% women) was 63 yr (interquartile range, IQR, 45-75 yr). The median time with ITP diagnosis was 81 months (IQR, 30-192 months). The median number of therapies prior to eltrombopag was 3 (IQR, 2-4). At the time of eltrombopag start, 45 patients (30%) were receiving concomitant treatment for ITP. Forty-six patients (30%) had bleeding signs/symptoms the month before the treatment started. The median platelet count at eltrombopag initiation was 22 × 10(9) /L (IQR, 8-39 × 10(9) /L). A total of 135 patients (88.8%) achieved a platelet response. The median time to platelet response was 12 d (95% CI, 9-13 d). Maintained platelet response rate during the 15-month period under examination was 75.2%. Twenty-eight patients (18.4%) experienced adverse events, mainly grades 1-2. CONCLUSION: Eltrombopag is highly effective and well tolerated in unselected patients with primary chronic ITP.

Use of eltrombopag after romiplostim in primary immune thrombocytopenia.

The thrombopoietin receptor agonists (THPO-RAs), romiplostim and eltrombopag, are effective and safe in immune thrombocytopenia (ITP). However, the value of their sequential use when no response is achieved or when adverse events occur with one THPO-RA has not been clearly established. Here we retrospectively evaluated 51 primary ITP adult patients treated with romiplostim followed by eltrombopag. The median age of our cohort was 49 (range, 18-83) years. There were 32 women and 19 men. The median duration of romiplostim use before switching to eltrombopag was 12 (interquartile range 5-21) months. The reasons for switching were: lack of efficacy (n = 25), patient preference (n = 16), platelet-count fluctuation (n = 6) and side-effects (n = 4). The response rate to eltrombopag was 80% (41/51), including 67% (n = 35) complete responses. After a median follow-up of 14 months, 31 patients maintained their response. Efficacy was maintained after switching in all patients in the patient preference, platelet-count fluctuation and side-effect groups. 33% of patients experienced one or more adverse events during treatment with eltrombopag. We consider the use of eltrombopag after romiplostim for treating ITP to be effective and safe. Response to eltrombopag was related to the cause of romiplostim discontinuation.

Successful discontinuation of eltrombopag after complete remission in patients with primary immune thrombocytopenia.

Eltrombopag is effective and safe in immune thrombocytopenia (ITP). Some patients may sustain their platelet response when treatment is withdrawn but the frequency of this phenomenon is unknown. We retrospectively evaluated 260 adult primary ITP patients (165 women and 95 men; median age, 62 years) treated with eltrombopag after a median time from diagnosis of 24 months. Among the 201 patients who achieved a complete remission (platelet count >100 × 10(9) /l), eltrombopag was discontinued in 80 patients. Reasons for eltrombopag discontinuation were: persistent response despite a reduction in dose over time (n = 33), platelet count >400 × 10(9) /l (n = 29), patient's request (n = 5), elevated aspartate aminotransferase (n = 3), diarrhea (n = 3), thrombosis (n = 3), and other reasons (n = 4). Of the 49 evaluable patients, 26 patients showed sustained response after discontinuing eltrombopag without additional ITP therapy, with a median follow-up of 9 (range, 6-25) months. These patients were characterized by a median time since ITP diagnosis of 46.5 months, with 4/26 having ITP < 1 year. Eleven patients were male and their median age was 59 years. They received a median of 4 previous treatment lines and 42% were splenectomized. No predictive factors of sustained response after eltrombopag withdrawal were identified. Platelet response following eltrombopag cessation may be sustained in an important percentage of adult primary ITP patients who achieved CR with eltrombopag. However, reliable markers for predicting which patients will have this response are needed.

Sustained response after discontinuation of short-and medium-term treatment with eltrombopag in patients with immune thrombocytopenia.

Eltrombopag is effective and safe in chronic immune thrombocytopenia (ITP) patients not responding to previous therapy. However, when eltrombopag is discontinued, platelet counts usually return to baseline within 2 weeks. Here, we describe the clinical characteristics of the, to the best of our knowledge, largest case series of patients with ITP, who presented sustained responses after discontinuing eltrombopag (n = 12). The median time from diagnosis to eltrombopag initiation was 24 months (range, 1-480). The median number of prior therapies was 5 (range, 1-7), and the median duration of eltrombopag treatment was 5 months (range, 1-13). Three patients received eltrombopag for only 1 month. The treatment was well-tolerated. The median (range) follow-up of this case series was of 7 months (6-20), during which all patients maintained a safe platelet count without the need for anti-ITP treatment. The communication of such cases may support the conduction of new studies to investigate which predictive factors could identify ITP patients with sustained responses after discontinuing eltrombopag without additional therapy. The need of long-term use of eltrombopag should be re-examined.

Detection and outcome of occult leptomeningeal disease in diffuse large B-cell lymphoma and Burkitt lymphoma.

The benefit of intrathecal therapy and systemic rituximab on the outcome of diffuse large B-cell lymphoma at risk of central nervous system disease is controversial. Furthermore, the effect of intrathecal treatment and rituximab in diffuse large B-cell and Burkitt lymphoma with occult leptomeningeal disease detected by flow cytometry at diagnosis is unknown. Untreated diffuse large B-cell (n=246) and Burkitt (n=80) lymphoma at clinical risk of central nervous system disease and having had pre-treatment cerebrospinal fluid were analyzed by flow cytometry and cytology. Spinal fluid involvement was detected by flow cytometry alone (occult) in 33 (13%) diffuse large B-cell and 9 (11%) Burkitt lymphoma patients, and detected by cytology in 11 (4.5%) and 5 (6%) patients, respectively. Diffuse large B-cell lymphoma with occult spinal fluid involvement had poorer survival (P=0.0001) and freedom from central nervous system relapse (P<0.0001) compared to negative cases. Burkitt lymphoma with occult spinal fluid involvement had an inferior freedom from central nervous system relapse (P=0.026) but not survival. The amount of intrathecal chemotherapy was quantitatively associated with survival in diffuse large B-cell lymphoma with (P=0.02) and without (P=0.001) occult spinal fluid involvement. However, progression of systemic disease and not control of central nervous system disease was the principal cause of treatment failure. In diffuse large B-cell lymphoma, systemic rituximab was associated with improved freedom from central nervous system relapse (P=0.003) but not with survival. Our results suggest that patients at risk of central nervous system disease should be evaluated by flow cytometry and that intrathecal prophylaxis/therapy is beneficial.

Immune thrombocytopenia in systemic lupus erythematosus: Prevalence, risk factors, and a novel predictive model for risk assessment.

INTRODUCTION: Immune thrombocytopenia (ITP) is a potentially severe manifestation of systemic lupus erythematosus (SLE) reported in 7-40% of SLE patients. ITP has been associated with a higher risk of organ damage and mortality. OBJECTIVES: To describe which factors are associated with the presence of ITP in SLE patients. METHODS: Retrospective case-control study. Cases were defined as SLE patients who had ever developed ITP and were sex- and age-matched with two controls. A predictive model was constructed to identify SLE patients who were at risk of developing ITP. RESULTS: ITP prevalence in our SLE cohort was 8.35%. Cases had a higher frequency of hemolytic anemia, while controls had a higher prevalence of arthritis at SLE diagnosis. During SLE progression, cases tested positive for anticardiolipin, anti-ß2-glycoprotein 1, and lupus anticoagulant antibodies more frequently. Cases received mycophenolic acid and azathioprine more often than controls and had a higher SLICC/ACR score. The model demonstrated a sensitivity of 87.53%, a positive predictive value of 81.92%, a specificity of 80.50%, area under the curve of 83.92%, a F1 of 83% and an overall accuracy of 83.68%. The variables that best explain the model were hemolytic anemia, arthritis, oral ulcers, Raynaud's phenomenon, low C4, low CH50, anticardiolipin and anti-ß2GP1 antibodies. CONCLUSION: SLE patients who develop ITP have a distinct phenotype characterized by more hemolytic anemia and less arthritis at SLE onset, and higher prevalence of antiphospholipid syndrome antibodies during SLE progression. This phenotype is associated with heightened organ damage and the need for more intensive therapies and stricter follow-up. Our predictive model has demonstrated an impressive ability to identify SLE patients at risk of developing ITP.

Chromogenic LMO2 mRNA ISH Expression Correlates with LMO2 Protein and Gene Expression and Captures Their Survival Impact in Diffuse Large B-Cell Lymphoma, NOS.

BACKGROUND: LMO2 is a relevant gene involved in B-cell ontogeny and a survival predictor of aggressive large B-cell lymphomas (aLBCL). Most studies assessing LMO2 mRNA expression have relied on microarray platforms or qRT-PCR methods, overlooking tissue morphology. In this study, we evaluate LMO2 RNA expression by chromogenic in situ hybridization (CISH) in normal tissue and in a series of 82 aLBCL. METHODS: LMO2 CISH was performed in formalin-fixed paraffin-embedded tissues, scored by three different methods, and correlated with a transcriptome panel. RESULTS: We obtained statistically significant results correlating the methods of evaluation with LMO2 protein expression and gene expression results. Normal tonsil tissue showed high levels of LMO2, particularly within the light zone of the germinal center. Conversely, in aLBCL, a notable reduction in LMO2 expression was noted, remarkably in cases carrying MYC rearrangements. Furthermore, significant results were obtained through overall survival and Cox regression survival analysis, incorporating International Prognostic Index data alongside LMO2 expression levels. CONCLUSIONS: We show a reliable method to identify LMO2 mRNA expression by CISH, effectively capturing many of the reported biologic features of LMO2.