ALBERT

Description: Background: MYC protein is expressed in 30-50% of diffuse large B cell lymphoma (DLBCL) and is associated with concomitant expression of BCL2 in 20% to 35% of cases. DLBCLs with co-expression of MYC and BCL2 are called double-expressor lymphomas (DELs); whereas double-hit lymphomas (DHLs) have MYC and BCL2 or BCL6 rearrangement as detected by fluorescence in situ hybridization (FISH) or standard cytogenetics and are currently classified by the World Health Organization as high grade B cell lymphoma (HGBL). MYC/BCL2 double expression is an independent risk factor of DLBCL relapse or progression. In several studies, DELs were shown to have worse outcomes than other DLBCLs, but not as much aggressiveness as the DHLs (HGBL). Poor response to standard chemotherapy CHOP or R-CHOP is seen with DHLs and DELs with a median overall survival of

Description: Background: Novel molecular and immunophenotypic markers in Diffuse Large B-Cell Lymphoma (DLBCL) are of interest for potential therapeutic guidance in addition to prognostication. The cell-surface marker CD30 is expressed by several types of non-Hodgkin lymphomas, including DLBCL. A piqued interest to explore the prevalence of this marker in different DLBCLs is driven by the availability of an FDA-approved anti-CD30 monoclonal antibody; brentuximab. We identified the prevalence of CD30 in de novo and relapsed DLBCL in a single medical center and investigated its relation with the clinical and biochemical characteristics of our patients as well as their survival data. Methods: This is an IRB-approved retrospective cohort study of consecutive patients diagnosed with de novo DLBCL at the Washington, DC Veterans Affairs Medical Center between 1995 and 2014. Patients with other lymphoma types or unavailable archived pathology specimens for testing were excluded. Additional pathology review of all specimens diagnosed as DLBCL was undertaken by our pathologist and questionable cases were excluded. Clinical and laboratory data including age, rituximab use, chemotherapy regimen, hepatitis C (HCV) and Human Immunodeficiency Virus (HIV) infection, organ involvement, stage, and prognostic scores were collected both at diagnosis as well as at relapse. Immunohistochemistry (IHC) was performed on formalin-fixed, paraffin-embedded tissue sections from all patients to examine the following expressions: CD3, CD5, CD10, CD20, CD30, bcl-2, bcl-6, MUM-1, and MYC. CD30 expression was assessed; absence of tumor cell staining interpreted as 0% expression, and the percentage of positive tumor cells reported. CD30-positive and CD30-negative clinical and pathologic variables and overall survival (OS) were analyzed. Distributions were estimated using Kaplan-Meier analysis, and log-rank test was used to assess the survival differences. Statistical analysis was performed using SPSS software version 20.0. Results: A total of 69 subjects with DLBCL were identified and 42 met the inclusion criteria with available archived pathology blocks for review and testing. Median age at diagnosis was 66 years. Only one female was in the study. Nodal and extranodal disease was 29.2% and 70.8%, respectively at diagnosis while only 2.4% of patients had only nodal disease at relapse. Localized (I&II) and advanced (III &IV) disease stages were noted in 34.3% and 65.7%, respectively and only 6.8% of patients had localized disease at relapse. Viral serology revealed HIV in 7.1% and HCV in 9%. LDH at diagnosis was on average 386.7 ± 270.9 IU/L. Chemotherapy regimens used included CHOP±R, EPOCH±R, ProMACE CytaBOM, and rituximab/gemcitabine/oxaliplatin/dexamethasone with the majority receiving R-EPOCH as first line chemotherapy (33.3%). Prevalence of positive IHC markers were as follows; CD3 (2.4 %), CD5 (7.2%), CD10 (28.6%), CD20 (100%), CD30 (7.1%), bcl-2 (71.4%), bcl-6 (71.4%), MUM-1(15%), c-MYC (38.1%) and P53 (16.5%). None of the CD30-positive patients had c-MYC rearrangement. Median overall survival (OS) was 23.3 months for the whole cohort. It was noted to be higher in the CD30-positive group compared to the CD30-negative group (28.7 and 34 months, respectively). The difference in OS was not statistically significant, however. CD30 status and stage at presentation was not analyzed given the low prevalence of CD30 in our cohort. Conclusions: In conclusion, our study identified 7.1% CD30-positive patients with de novo or relapsed DLBCL, all of which had greater than 50% CD30 expression. While rate of expression does not correlate with response to brentuximab, 7.1% in our cohort could potentially benefit from brentuximab. Our cohort had a low prevalence of CD30 expression. However, higher OS for the CD30 positive cohort was noted, despite not being significant. The low prevalence of CD30 expression in our cohort maybe explained by the fact that they had a higher prevalence of MYC expression suggesting a possible mutually exclusive relationship. A larger cohort is necessary to assess if this relationship is reproducible and statistically significant. Possible implications of such a mutually exclusive relationship includes the option to omit FISH for MYC rearrangement testing in cases with high CD30 expression. Figure Kaplan-Meier curve for the overall survival stratified according to CD30 status (p=0.389). Figure. Kaplan-Meier curve for the overall survival stratified according to CD30 status (p=0.389). Disclosures No relevant conflicts of interest to declare.

Description: Abstract 4869 The information regarding monoclonal gammopathy of unknown significance (MGUS) derives mainly from studies of Caucasian individuals. In contrast, this study describes the characteristics of 492 African American (AA) male patients identified with MGUS from the electronic database at the Washington VAMC. Review of their individual electronic records showed that none of the patients initially had evidence of myeloma or other symptomatic plasma cell or lymphoproliferative disorder. The median age at diagnosis of MGUS was 68 years old (range 28.5 to 95.6 years). The distribution of monoclonal immunoglobulin (M Ig) subtypes were IgG 78.1%, IgA 14.8%, IgM 6.9%; light chain only in the urine 2.9% or in the serum 1.0%, The light chain distribution of the M Igs was 60% kappa, 40% lambda. Fifty-nine patients (12%) had diclonal and 4 (0.8%) had triclonal M Igs. The median amount of M Ig was 0.26 g/dL; 47.8% were too small to quantitate. Ninety-four (25.5%) of 368 tested had Bence-Jones proteinuria, with a similar kappa:lambda distribution and 4 patients showed both light chains. Clinical characteristics were as follows: hepatitis C 15.5%, HIV 5.1%, other significant infections 26.8%, and chronic autoimmune or inflammatory disorders 10.3%. The patients were followed clinically for a median of 4.1 years (range 0.35 to 21.02 years), and the median interval between the first and last electrophoresis was 1.41 years (range 0 to 19.97 years). During this period 21 patients (4.3%) progressed to a malignant plasma cell disorder (myeloma 20, solitary plasmacytoma 1). 133 patients (27.0%) died of other causes, and in 26 (5.3%) the M protein had resolved. The actuarial risk determined by a Kaplan Meier plot of progression to a symptomatic plasma cell disorder was 13.5 % at 11 years. The initial M Ig in the patients who progressed was IgG in 15, IgA in 4, and isolated BJ proteinuria in 2. The only recognized predicting characteristic for progression was the detection of Bence-Jones proteinuria at diagnosis of MGUS: Thirteen of 20 (65%) progressing patients tested were positive as compared to 81 of 348 (23.0%) of the non-progressors (p = .0003) A number of features distinguish this AA MGUS cohort from previous series of Caucasian patients. MGUS was detected at an earlier age: 8.9% (5.2% excluding HCV and HIV patients) were under the age of 50. The percentage of AA patients with very low level M proteins was more than threefold that previously reported. The percentage of patients with IgM M Ig was less than one-half noted in previous studies. The actuarial risk of progression to a symptomatic plasma cell disorder as calculated from a Kaplan Meier plot appears to be comparable to previous reports in predominantly Caucasian series. Dr. Desai worked on this project following completion of her internal medicine residency. She is now a Hematology Oncology fellow at Montefiore Medical Center, New York NY. Disclosures No relevant conflicts of interest to declare.

Description: Chronic neutrophilic leukemia (CNL) is a well-recognized, extremely rare myeloproliferative neoplasm (MPN) with only ~200 reported cases until 2017. The current WHO diagnostic criteria include leukocytosis of ≥ 25 x 109/L with ≥ 80% neutrophils/bands, 〈 10% circulating neutrophil precursors and