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312 citation(s) found for "Markovic, Svetomir".

Primary Diffuse Large B-Cell Lymphoma of the Colon: Surgery for Local Disease Control Does Not Improve Outcome.
Katipamula, Rajini, Ristow, Kay M., Johnston, Patrick B. , Inwards, David J. , Micallef, Ivana N. , Porrata, Luis F. , White, William L. , Ansell, Stephen M. , Colgan, Joseph P. , Habermann, Thomas M. , Markovic, Svetomir N. , Witzig, Thomas E.

Mayo Clinic

Blood | October 13, 2019 | Volume: 110 | Issue: 11 | Pages: 3444-3444

10.1182/blood.v110.11.3444.3444 Get It

Abstract Purpose: Primary colorectal large B-cell lymphoma is rare and accounts for less than 1% of all malignancies in the colon. Standard treatment for limited stage diffuse large B-cell lymphomas (DLBCL) includes systemic therapy combined with involved field radiation therapy. However, radiation therapy may often not be feasible in patients with primary colon lymphoma. For primary DLBCL of the colon particularly the cecum, surgical resection prior to the administration of systemic chemotherapy has been considered to improve local control. The goal of this study was therefore to determine whether surgical resection improves the outcome of patients with primary DLBCL of the colon. Methods: Clinical information and outcomes on all the patients with primary DLBCL of the colon seen at Mayo Clinic, Rochester, between January 1980 and June 2005 were retrospectively reviewed. Results: There were 28 patients identified with primary colon DLBCL. Pre-existing conditions like colon polyps, Crohn’s disease and diverticulosis were uncommon. The most common presenting symptom was bleeding per rectum seen in 13 patients (46.5%). Other symptoms included abdominal pain, diarrhea and anemia. All patients had early stage disease (stage1–22 patients, stage2–6 patients) at diagnosis. Of the 28 patients, 16 underwent initial surgery followed by chemotherapy, 7 were treated with chemotherapy alone, and 5 patients had inadequate data to determine time to progression or overall survival. Chemotherapy was anthracycline based, with the most common regimen being CHOP (Cyclophosphamide, Doxorubicin, Vincristine, Prednisone). There was no difference in overall survival or time to progression between the 16 patients who received combined modality therapy compared to the 7 patients who received chemotherapy alone. Of the 16 patients who underwent surgical resection followed by chemotherapy, all 5 patients who relapsed, relapsed at other sites in the colon. Conclusion: Surgery as part of combined modality therapy did not appear to improve the outcome of patients with primary DLBCL of the colon. Systemic chemotherapy with an anthracycline-based regimen in combination with rituximab is therefore likely to be sufficient treatment for these patients. Follow-up for these patients should include a colonoscopy to monitor for recurrences at other sites in the colon.
The Prognostic Importance of T and NK-Cells in a Consecutive Series of Newly Diagnosed Patients with Chronic Lymphocytic Leukemia.
Palmer, Shanique R., Hanson, Curtis A. , Porrata, Louis F., LaPlant, Betsy, Geyer, Susan M. , Call, Timothy G. , Bowen, Deborah A., Jelinek, Diane F., Zent, Clive S. , Markovic, Svetomir N. , Kay, Neil E. , Shanafelt, Tait D.

Mayo Clinic

Blood | October 13, 2019 | Volume: 110 | Issue: 11 | Pages: 3080-3080

10.1182/blood.v110.11.3080.3080 Get It

Abstract Background: Patients with CLL have a variable clinical course. Current novel prognostic indicators (ZAP-70, CD38, IgVH gene mutation status, FISH) are able to identify early-stage CLL patients at high risk of rapid disease progression. These prognostic factors focus on characteristics of the malignant B cell clone and are not currently changeable factors. Identification of modifiable characteristics of the host unrelated to the leukemic B-cell but that relate to CLL-specific survival may provide opportunities for therapeutic intervention. Since the immune system is likely to modulate disease progression in CLL patients, we evaluated critical features of that system in relation to the size of the circulating clonal B-cell population in a CLL cohort. Methods: 186 consecutive patients with CLL who were evaluated at Mayo Clinic within 2 months of diagnosis between 2000 and 2002 were identified. The primary end-point of the study was to assess if host immunity affected time to treatment (TTT). Baseline flow cytometry analysis was available for 166 patients (88%) and was used to calculate the absolute number of T-cell and natural kill (NK)-cells present at diagnosis. The size of the T-cell/NK-cell compartment relative to the size of the malignant monoclonal B-cell (MBC) compartment was then evaluated by calculating the NK:MBC ratio and T:MBC ratio. Relationships with other prognostic parameters and with TTT were evaluated. Results: Patients exhibited substantial variation in the absolute number of T-cells and NK cells as well as T:MBC and NK:MBC ratios at the time of diagnosis. Higher T:MBC and NK:MBC ratios were observed among patients with early Rai stage and mutated IgVH genes (all P≤0.0002). As continuous variables, both the T:MBC ratio (p value=0.03) and NK:MBC ratio (p value=0.02) were associated with TTT. Since they correlated with TTT as continuous variables, thresholds to classify MBC, T:MBC ratio, and NK:MBC were identified using the method of Contal and O’Quigly. On multivariate Cox modeling including stage, CD38, absolute MBC count, T:MB ratio, and NK:MB ratio, the independent predictors of TTT were disease stage, T:MB ratio, and NK:MB ratio (Table 1). Conclusion: Measurable characteristics of the host immune system appear to relate to the rate of disease progression in patients with newly diagnosed CLL. These characteristics can be modified and continued evaluation of immunomodulatory drugs, vaccination strategies, and cellular therapies to delay/prevent disease progression are warranted. Additional studies exploring how interactions between the host immune system and the leukemic clone influence clinical outcomes are needed.
A Phase II Trial of the Oral mTOR Inhibitor Everolimus (RAD001) in Relapsed Aggressive Non-Hodgkin Lymphoma (NHL).
Reeder, Craig B. , Gornet, Michel K., Ansell, Stephen M. , Micallef, Ivana N. , Porrata, Luis F. , Johnston, Patrick B. , LaPlant, Betsy, Kabat, Brian, Inwards, David J. , Call, Timothy G. , Markovic, Svetomir, Zeldenrust, Steven R., Habermann, Thomas M. , Maurer, Matthew J. , Colgan, Joseph P. , Markovic, Svetomir N. , Zent, Clive S. , Tun, Han W. , Witzig, Thomas E.

Mayo Clinic

Blood | October 13, 2019 | Volume: 110 | Issue: 11 | Pages: 121-121

10.1182/blood.v110.11.121.121 Get It

Abstract Background: The phosphatidylinositol 3-kinase/mammalian target of rapamycin (mTOR) signal transduction pathway integrates signals from multiple receptor tyrosine kinases to control cell proliferation and survival. Everolimus (RAD001, Novartis Pharmaceuticals) is an oral investigational antineoplastic agent that targets mTOR. Objectives: To learn the anti-tumor activity and toxicity of single-agent RAD001 in pts with relapsed/refractory aggressive NHL. Patients and Methods: Patients were eligible if they had measurable disease, a platelet count >75,000, an absolute neutrophil count >1,000, and a creatinine and bilirubin <2x laboratory upper limit of normal. Patients received RAD001 10 mg PO daily and were evaluated monthly. Dose reductions to 5 mg daily and 5 mg every other day were allowed. Response was assessed after 2 cycles and periodically thereafter. Patients could remain on drug until progression or toxicity. Results: Thirty-seven pts were treated - 20 (54%) with relapsed diffuse large cell (DLC), 14 (38%) with relapsed mantle cell (MCL), 2 high grade, and 1 follicular grade III. The median age was 72 years (range, 45–92). Patients had received a median of 4 prior therapies (range, 1–15). The overall response rate was 32% (12/37; 95% CI:20–49%) with 1 complete response and 11 partial responses. The ORR was 35% (7/20) in the DLC group and 29% (4/14) in the MCL patients. Patients have received a median of 2 cycles (range, 1–16+) of therapy. The median time to progression for all 37 patients is 3.1 months (95%CI; 2.0 – 4.7). The median duration of response for the 12 responders is 5.5 months (95% CI; 2.3 – 9.2) and 5 pts remained progression free at 6 months. Three patients are currently maintaining a response with a median time of 10.5 months (range, 2.9–15.6+months). RAD001 was well tolerated. The incidence of grade 3 anemia, neutropenia, and thrombocytopenia in this heavily pretreated pt population was 11%, 16%, and 30%. Two pts developed grade 4 neutropenia. Grade 2 hypercholesterolemia occurred in 11%; grade 2 hyperglycemia in 16%; grade 3 hyperglycemia in 11% and 1 pt had grade 4 hypertriglyceridemia. Summary: RAD001 has single-agent activity in relapsed aggressive NHL and provides proof-of-concept that targeting the mTOR pathway in NHL is clinically relevant.
Absolute Lymphocyte Count Is Independent of the Anaplastic Lymphoma Kinase and Predicts Survival in Primary Anaplastic Large Cell Lymphoma.
Porrata, Luis F. , Ristow, Kay M., Haberman, Thomas M, Inwards, David J. , Ansell, Stephen M. , Micallef, Ivana N. , Johnston, Patrick B. , White, William L. , Witzig, Thomas E. , Colgan, Joseph P. , Markovic, Svetomir N.

Mayo Clinic

Blood | October 13, 2019 | Volume: 110 | Issue: 11 | Pages: 1335-1335

10.1182/blood.v110.11.1335.1335 Get It

Abstract Peripheral blood absolute lymphocyte count (ALC) at diagnosis is a predictor of survival in B-cell lymphomas. The role of ALC at diagnosis on survival in T-cell lymphoma has not been studied. Thus, we studied the role of ALC at diagnosis on clinical outcome in adult patients with primary anaplastic large cell lymphoma (PALCL) that were diagnosed, treated, and followed at the Mayo Clinic, Rochester. Between 1985 and 2006, 50 patients with PALCL qualified for the study. ALC was identified to be a strong predictor for complete response (CR), area under the curve (AUC = 0.83, p < 0.002). The median follow-up was 31.8 months (range: 1–212.6 months). ALC, as a continuous variable was a predictor for overall survival (OS) (HR = 0.143; 95%CI = 0.042–0.416; p < 0.0001) and progression-free survival (PFS) (HR = 0.150; 95%CI = 0.047–0.415; p < 0.0001) .Superior OS and PFS (Figure 1) were observed with an ALC ≥ 1.0 x 109/L (N = 31) versus an ALC < 1.0 x 109/L (N=19) (median OS: not reached vs 7.5 months, OS rates at 5 years, 81% vs 36%, p < 0.0006, respectively; and median PFS: not reached vs 6.3 months; PFS rates at 5 years, 77% vs 37%, p < 0.0007, respectively). Multivariate analysis demonstrated ALC to be an independent prognostic indicator for OS (HR = 0.196; 95%CI = 0.125–0.693; p < 0.002) and PFS (HR = 0.191; 95%CI = 0.053–0.559; p < 0.0008) when compared to anaplastic lymphoma kinase, international prognostic index, and cutaneous versus systemic presentation. Figure 1 Figure 1.
Peripheral Blood Lymphocyte/Monocyte Ratio At Diagnosis and Survival in Nodular Lymphocyte-Predominant Hodgkin's Lymphoma,
Porrata, Luis F. , Ristow, Kay M., Inwards, David J. , Ansell, Stephen M. , Micallef, Ivana N. , Johnston, Patrick B. , Nowakowski, Grzegorz S. , Thompson, Carrie A. , Colgan, Joseph P. , Habermann, Thomas M. , Witzig, Thomas E. , Markovic, Svetomir N.

Mayo Clinic

Blood | October 13, 2019 | Volume: 118 | Issue: 21 | Pages: 3642-3642

10.1182/blood.v118.21.3642.3642 Get It

Abstract Abstract 3642 Purpose: The reactive pathologic background in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) consists of lymphocytes and histocytes. Lymphopenia is a negative prognostic factor in NLPHL as it is also in Classical Hodgkin Lymphoma (cHL). In cHL, tumor-associated macrophages recruited from circulating monocytes are a negative prognostic factor for survival. Thus, we studied if the peripheral blood absolute lymphocyte count/absolute monocyte count ratio at diagnosis (ALC/AMC-DX), as a surrogate biomarker of the host response against the neoplastic lymphocytic and/or histiocytic (L&H) cells, affects survival in NLPHL. Patients and Methods: We performed a retrospective analysis of the association between ALC/AMC-DX and survival in 103 consecutive NLPHL patients that were followed at Mayo Clinic from 1974 to 2010. Receiver operating characteristic (ROC) and area under the curve (AUC) were used for ALC/AMC-DX cut-off value analysis and proportional-hazards models were used to compare survival based on the ALC/AMC-DX ratio. Results: The cohort included 67 (65%) males and 36 (35%) females. Eighty-three percent of patients presented with stage I/II and 17% with stage III/IV. Sixty-five (63%) patients were treated with radiation alone; 20 (20%) patients with chemotherapy alone; and 18 (17%) patients with chemotherapy and radiation. The median follow-up period was 8.9 years (range: 0.3–31 years). An ALC/AMC-DX ≥ 2.1 was the best cut-off value for survival with an empirical AUC of 0.82 (95% confidence interval [CI], 0.78 to 0.88), a sensitivity of 70% (95% CI, 61% to 76%) and specificity of 84% (95%CI, 59% to 82%). The cut-off value for ALC/AMC-DX ≥ 2.1 was validated by the k-fold cross validation method, showing a cross validation ROC with an AUC of 0.82 (95% CI, 0.72 to 0.93) for an ALC/AMC-DX ≥ 2.1. Using Kaplan-Meier analysis, we studied overall survival (OS), lymphoma-specific survival (LSS), progression-free survival (PFS), and time to progression (TTP) based on ALC/AMC-DX ≥ 2.1. Patients with an ALC/AMC-DX ≥ 2.1 experienced an superior OS, LSS, PFS, and TTP compared with patients with an ALC/AMC-DX < 2.1: [OS: median was 22.1 years vs 6.3 years, 10-years OS rates of 89% (95%CI, 80% to 98%) vs 44% (95%CI, 27% to 65%), p < 0.0001, respectively; LSS: median was not reached vs 7.3 years, 10-years LSS rates of 99% (95%CI, 90% to 100%) vs 45% (95%CI, 29% to 67%), p < 0.0001, respectively; PFS: median was 20.6 years vs 4.6 years, 10-years PFS rates of 84% (95%CI, 80% to 97%) vs 26% (95%CI, 18% to 55%), p < 0.0001, respectively; and TTP: median was not reached vs 5.5 years, 10-years TTP rates of 93% (95%CI, 85% to 99%) vs 29% (95%CI, 19% to 57%), p < 0.0001, respectively]. After adjusting for the International Prognostic Factors and the International Prognostic Score, ALC/AMC-DX remained an independent prognostic factor for OS {hazard ratio (HR), 0.42, 95%CI, 0.23 to 0.64, p< 0.004]; LSS [HR, 0.14; 95%CI, 0.04 to 0.23, p <0.0004]; PFS [HR, 0.14; 95%CI, 0.03 to 0.34, p < 0.001], and TTP [HR, 0.16, 95%CI, 0.04–0.34, p <0.002]. Conclusion: ALC/AMC-DX is an independent prognostic factor for survival and provides a single biomarker to predict clinical outcomes in NLPHL. Disclosures: No relevant conflicts of interest to declare.
Prognostic Factors and Survival of Patients with Primary Mediastinal Large B-Cell Lymphoma.
Nowakowski, Grzegorz S. , Kaur, Prabhjot , Macon, William R. , Ristow, Kay M., Ansell, Stephen M. , Porrata, Luis F. , Micallef, Ivana N. , Johnston, Patrick B. , Inwards, David J. , Habermann, Thomas M. , Witzig, Thomas E. , Markovic, Svetomir N. , Colgan, Joseph P.

Mayo Clinic

Blood | October 12, 2019 | Volume: 106 | Issue: 11 | Pages: 4698-4698

10.1182/blood.v106.11.4698.4698 Get It

Abstract Background: Primary Mediastinal Large B-cell Lymphoma (PMLBCL) is a biologically and pathologically distinct subset of large B-cell lymphoma of thymic origin. The natural history of PMLBCL is not well defined. While earlier reports suggested that PMLBCL is an aggressive disease with a poorer prognosis when compared to other large cell B cell lymphomas, recent studies report more favorable results. Some of the outcome variability reported in previous studies may be related to the inclusion of other pathological lymphoma subtypes involving mediastinum. Thus, we reviewed the pathology and clinical course of patients with PMLBCL seen at our institution. Methods: We reviewed the biopsies on all patients diagnosed with mediastinal B-cell non-Hodgkin lymphoma (NHL) between 10/1983 and 10/2004. The pathological criteria for diagnosis of PMLBCL was a diffuse infiltrate of neoplastic CD20+ large B-cells within the mediastinum that frequently had "clear" cytoplasm and were often associated with fibrosis. We then reviewed the clinical data for patients with a pathological diagnosis of PMLBCL. Results: 121 patients were diagnosed with mediastinal B cell NHL and had tissue available for review. Of these, 88 fulfilled the pathological diagnostic criteria for PMLBCL. The median age at presentation was 37 years (range 18–83). The male to female ratio was 1.06. Age adjusted IPI was: 0, 1, 2, 3 in 18%, 56%, 18% and 8% of the patients respectively. The most commonly used treatments were: CHOP (70%), R-CHOP (22%) and ProMACE-CYTABOM (6%). 62% of the patients received adjuvant radiotherapy. 24% of the patients received high dose chemotherapy with autologous stem cell transplantation (2 patients in first remission). The median follow up was 66 months. The 2 and 5 year survival was 72% and 68% respectively. On univariate analysis, age >60 (p=0.012) and presence of B symptoms (p=0.0094) were associated with an adverse outcome. On multivariate analysis, only the presence of B symptoms (p=0.039) was an independent predictor of shortened overall survival. The 2 year survival of patients with age adjusted IPI of 0–1 or 2–3 was 86% and 68% respectively (p=0.023). Patients treated with adjuvant radiation therapy had a 5 year survival of 74% versus 53% in patients who did not receive adjuvant radiation (p=0.042). However, there was a higher percentage of Ann Arbor stage 3 and 4 disease patients found in the group who did not receive radiotherapy treatment (66% vs 17% respectively). Conclusions: The overall survival rates seen in patients with a confirmed pathological diagnosis of PMLBCL were superior to that reported in earlier studies and similar to that reported with the use of more intensive chemotherapy regimens. While many authors report a high proportion of female patients with PMLBCL, we did not observe any gender differences. While patients receiving adjuvant radiation therapy had a better outcome than those that did not, the retrospective nature of this study and differences in stage distribution preclude conclusions regarding the role of adjuvant radiation therapy. Randomized studies will be necessary to assess the optimal treatment for PMLBCL.
Peripheral Blood Lymphocyte/Monocyte Ratio At Diagnosis Is Independent of the Cell of Origin in Predicting Survival in Diffuse Large B-Cell Lymphoma,
Porrata, Luis F. , Ristow, Kay M., Inwards, David J. , Ansell, Stephen M. , Micallef, Ivana N. , Johnston, Patrick B. , Nowakowski, Grzegorz S. , Thompson, Carrie A. , Colgan, Joseph P. , Habermann, Thomas M. , Witzig, Thomas E. , Markovic, Svetomir N.

Mayo Clinic

Blood | October 12, 2019 | Volume: 118 | Issue: 21 | Pages: 3652-3652

10.1182/blood.v118.21.3652.3652 Get It

Abstract Abstract 3652 Purpose: Gene expression profiling has shown biologically distinct cell of origin categories for diffuse large B-cell lymphoma (DLBCL): germinal center B-cell like (GCB), and activated-B-cell like (ABC). GCB, DLBCL patients experienced better clinical outcomes compared with ABC, DLBCL patients. However, gene microarray technology is not broadly available in a non-research setting. Absolute lymphocyte count (ALC) at diagnosis is a prognostic factor for survival in DLBCL. Recently, gene-expression profiling and immunohistochemistry-based studies in non-Hosgkin's lymphoma demonstrate the important role of monocytes and their progeny, particularly lymphoma-associated macrophages, in promoting lymphomagenesis. thus, we studied if the peripheral blood absolute lymphocyte count/absolute monocyte count at diagnosis (ALC/AMC-DX), as a surrogate biomarker of the host response against the cell of origin in DLBCL, affects survival in DLBCL. Patients and Methods: We perfromed a retrospective analysis of the association between ALC/AMC-DX and survival in 131 consecutive DLBCL patients that were followed at Mayo Clinic from 2004 to 2010, with available tissue immunostaining for CD10, BCL6, MUM 1, and BCL 2 (Hans' algorithm) to identified GCB and ABC DLBCL patients. Receiver operating characteristic (ROC) and area under the curve (AUC) analyses were used for ALC/AMC-DX cut-off value determientaion and proportional-hazards models wee used to compare survival based on the ALC/AMC-DX. Results: The cohort included 91 (70%) GCb DLBCL patients and 40 (30%) ABC, DLBCL patients. All patients were treated with rituximab, cyclosphosphamide, adriamycin, vincristine, and prednisone (R-CHOP-21). The median follow-up period was 2.1 years (range 0.1–6.9 years). An ALC/AMC-DX >= 1.5 was the best cut-off value for survival with an empircal AUC of 0.83 (95% CI, 0.77 to 0.89), a sensitivity of 83% (95% CL, 72% to 92%) and specificity of 79% (95%CI, 72% to 85%). The cut-off value for ALC/AMC-DX >= 1.5 was validated by the k-fold cross validation method, showing a cross validation ROC with an AUC of 0.89 (95%CI, 0.80 to 0.95) for an ALC/AMC-DX >=1.5. Using Kaplan-Meier analysis, the overall survival (OS), defined as the time from diagnosis to last follow-up or death due to any cause; and progression-free survival (PFS), defined as the time from diagnosis to death of any cause, relapse, progression, or last follow-up, based on ALC/AMC-DX >= 1.5 were evaluated. patients with an ALC/AMC-DX >=1.5 experienced a superior OS and PFS compared with patients with an ALC/AMC-DX < 1.5: [OS: median was not reached vs 20.8 months, 5-years OS rates of 83% (95%CI, 70% to 95%) vs 36% (95%CI, 20% to 55%), p < 0.0001, respectively; and PFS: median was not reached vs 10.8 months, 5-years PFS rates of 70% (95%CI, 58% to 88%) vs 28% (95% CI, 17% to 46%), p < 0.0001, respectively]. Multivariate Cox stepwise regression analysis identified cell of origin, International Prognostic Index (IPI) and ALC/AMC-DX as the strongest predictors for OS and PFS, with ALC/AMC-DX out-performing cell of origin and IPI: OS [HR = 0.17, 95%CI, 0.07 to 0.36, p < 0.0001] and PFS [HR=0.21, 955CI, 0.11 to 0.39, p < 0.001]. conclusion: ALC/AMC-DX is independent of the cell of origin to predict survival and provides a single biomarker to predict clinical outcomes in DLBCL. Confirmatory studies are required. Disclosures: No relevant conflicts of interest to declare.
Primary Parotid MALT Lymphoma: Clinical Characteristics and Treatment – a Single Institution Experience
Jones, Jason M. , Ristow, Kay M., Kurtin, Paul J. , Thompson, Carrie A. , Porrata, Luis F. , Martenson, James A., Nowakowski, Grzegorz S. , Habermann, Thomas M. , McPhail, Ellen Darcy , Colgan, Joseph P. , Markovic, Svetomir N. , Witzig, Thomas E.

Mayo Clinic

Blood | October 12, 2019 | Volume: 118 | Issue: 21 | Pages: 1580-1580

10.1182/blood.v118.21.1580.1580 Get It

Abstract Abstract 1580 Background: Extranodal Marginal Zone Lymphomas of Mucosa Associated Lymphoid Tissue (MALT) account for approximately 5% of all non-Hodgkin Lymphoma cases. Specific MALT lymphomas are characterized by distinct clinical features, treatment strategies, and outcome, depending on site of the disease. While previous reports have described clinical course and treatment of gastric and pulmonary MALT lymphomas, a paucity of data exist describing primary parotid MALT lymphoma. This is a single institution experience. Methods: Patients with primary parotid MALT lymphoma were identified from the Mayo Clinic Lymphoma Database since 1986. This database includes all consenting patients with lymphoma seen at Mayo Clinic Rochester. Clinical characteristics, treatment, and outcomes were collected. Pathology was reviewed by a lymphoma pathologist; WHO criteria were used for diagnosis. PFS and OS were assessed using the Kaplan-Meier method and Cox proportional hazard model was used to asses the impact of variables on PFS and OS. Results: Seventy-six consecutive patients with primary parotid MALT lymphoma were evaluated and treated at Mayo Clinic from 1986 to 2010. The median age at diagnosis was 60 years (18–90). 58 (76%) were female. 42 (55.3%) patients had a history of Sjögren's Disease and 51 (67.1%) had a history of autoimmune disorders. 52 (68.4%), 4 (5.3%), and18 (23.7%) had stage I, II, and IV disease, respectively. 2 cases did not have complete staging information. 6 (7.8%) and 2 (2.6 %) had bone marrow and lung involvement, respectively. No patients had GI tract, liver, or CNS involvement. Median estimated OS (overall survival) was 18.3 years and median PFS (progression free survival) was 7.9 years. ALC<0.96 (p=0.0162) were associated with shorter survival. Age, ECOG performance score, stage, LDH, and history of Sjögren's disease were not prognostic for overall survival. The treatment approach and PFS are outlined in the table. For stage I disease, outcomes were excellent with local therapy. The median estimated PFS was 7.9 years with 72% of patients undergoing surgery surviving at 8 years. Patients receiving radiotherapy had an estimated median PFS of 15.7 years and median OS of 18.3 years. In contrast, patients being observed had a median PFS of 5.5 years. The use of systemic therapy with chemotherapy, immunotherapy or in combination was associated with a median PFS of 7.4 years. Summary: Primary parotid MALT lymphoma is strongly associated with Sjögren's disease. This lymphoma is usually limited to the parotid and associated with a favorable prognosis. For limited disease, local treatment with radiation or surgery appears to be an effective treatment options. For extensive disease, both immunotherapy and chemotherapy are efficacious treatments. Further prospective studies and long-term follow up are needed to determine the optimal treatment approaches and efficacy of chemotherapy/immunotherapy regimens. Disclosures: No relevant conflicts of interest to declare.
Elevation of Serum Free Light Chains Are Common In Lymphoma and Associated with Poor Event Free and Overall Survival
Katzmann, Jerry A., Micallef, Ivana N. , Inwards, David J. , Ansell, Stephen M. , Porrata, Luis F. , Johnston, Patrick B. , Nowakowski, Grzegorz S. , Thompson, Carrie A. , Kurtin, Paul J. , Macon, William R. , Maurer, Matthew J. , Cerhan, James R. , Link, Brian K. , Colgan, Joseph P. , Habermann, Thomas M. , Markovic, Svetomir N. , Gupta, Mamta , Syrbu, Sergei , Witzig, Thomas E.

Mayo Clinic

Blood | October 12, 2019 | Volume: 116 | Issue: 21 | Pages: 4136-4136

10.1182/blood.v116.21.4136.4136 Get It

Abstract Abstract 4136 Background: The serum free light chain (FLC) assay quantitates free kappa and free lambda immunoglobulin light chains. This assay has prognostic value in MGUS, multiple myeloma (MM), solitary plasmacytoma, and amyloid light chain (AL) amyloidosis, and has been incorporated in response criteria for both MM and AL amyloidosis. We previously showed elevated FLC was associated with poor outcome in diffuse large B-cell lymphoma (DLBCL) patients from a phase II cooperative group clinical trial (Blood (ASH Annual Meeting Abstracts) 2009 November 20, 2009; 114(22): 136). Here we replicate those findings in a large clinic based epidemiology cohort, as well as examine FLC abnormalities in other lymphoma subtypes. Methods: Newly diagnosed lymphoma patients were prospectively enrolled in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER). Serum FLC was quantitated from enrollment research serum draws within 9 months of diagnosis using the Freelite FLC assay (The Binding Site, Ltd., Birmingham, UK). Elevated FLC was defined as either kappa or lambda above the published reference range. Monoclonal elevated FLC was defined as elevated FLC with an abnormal FLC ratio; polyclonal elevated FLC was defined as elevated FLC with an FLC ratio in the normal reference range. Clinical data was abstracted using a standard protocol for the MER and patients were followed systematically for event-free (progression, retreatment, or death due to any cause) and overall survival (EFS and OS, respectively). Cox proportional hazards models were used to evaluate the unadjusted association between FLC and outcome. Results: 1118 lymphoma patients diagnosed between September 2002 and February 2008 with available serum were assayed. At a medium follow-up of 49 months (range 1–94), 484 patients (43%) had an event and 249 patients died (22%). Elevated FLC was present in 27% of lymphomas, with prevalence ranging from 13% in follicular lymphoma (FL) to 64% for mantle cell lymphoma (MCL) and 77% for lymphoplasmacytic lymphoma. Elevated FLC was present in 27% of DLBCL and associated with poor EFS (monoclonal hazard ratio (HR)=2.56, polyclonal HR=1.99, all p<0.001) and OS (monoclonal HR=3.22, polyclonal HR=2.91, all p<0.0001), replicating our previous findings. Elevated FLC was generally polyclonal (FLC ratio normal) across lymphoma subtypes, though monoclonal elevated FLC (FLC ratio abnormal) was common in MCL and the post-follicular lymphomas. Elevated FLC was associated with inferior EFS in all lymphomas combined (monoclonal HR=1.92, 95% CI:1.44-5.55, polyclonal HR=1.38, 95% CI:1.09-1.74); this association remained consistent in most subtypes (see table). In addition, elevated FLC was associated with poor EFS in MCL (monoclonal) and Hodgkin lymphoma (HL; polyclonal). Elevated FLC was also significantly associated with OS in HL (polyclonal HR=6.24, 95% CI 2.44–15.9), FL (polyclonal HR=5.85, 95% CI 2.62–13.0), post follicular lymphomas (polyclonal HR=4.16, 95% CI 1.17–14.8), as well as for all lymphomas combined (monoclonal HR=2.24, 95% CI 1.52–3.29, polyclonal HR=2.33, 95% CI 1.74–3.11). Conclusions: A significant percentage of lymphoma patients have elevated FLC. Our previous discovery of elevated FLC predicting poor outcome in DLBCL was confirmed in a large, independent dataset. Prevalence and type of elevated FLC (monoclonal vs. polyclonal) varies by lymphoma subtype. Elevated monoclonal and polyclonal FLC is associated with poor outcome broadly in lymphoma, as well as specifically for a number of lymphoma subtypes, supporting FLC as a potentially useful prognostic biomarker in many lymphoma subtypes. Disclosures: No relevant conflicts of interest to declare.
Utility of Stem Cell Collection in Anticipation of Future Need for Autologous Stem Cell Transplant in Follicular Lymphoma Patients
Klebig, Robin, Ansell, Stephen M. , Gastineau, Dennis A. , Johnston, Patrick B. , Micallef, Ivana N. , Nowakowski, Grzegorz S. , Porrata, Luis F. , Ristow, Kay M., Thompson, Carrie A. , Towns, Jessica N, Inwards, David J. , Colgan, Joseph P. , Habermann, Thomas M. , Markovic, Svetomir N. , Witzig, Thomas E.

Mayo Clinic

Blood | October 12, 2019 | Volume: 118 | Issue: 21 | Pages: 1926-1926

10.1182/blood.v118.21.1926.1926 Get It

Abstract Abstract 1926 Background: Follicular lymphoma (FL) is the second most common non Hodgkin lymphoma in the United States, comprising up to 30% of all non Hodgkin lymphomas. Typically an indolent disease, relapses are common. High dose therapy followed by autologous stem cell transplant is an option that has shown to produce prolonged progression-free and relapse-free survival in patients who relapse. Adequate bone marrow reserve for peripheral stem cell mobilization has been shown to be adversely effected by prior regimens such as fludarabine and radioimmunotherapy. Concerns regarding stem cell mobilization at the point of relapse have led some to collect stem cells early in the course of disease to allow for potential subsequent transplant after relapse. Recent advances in stem cell mobilization have resulted in a 3% collection failure rate for lymphoma patients at the point of planned transplant at our institution versus a historical rate of up to 30%. We studied the utilization of stem cells collected for potential future use in FL patients in remission or prior to therapy at the point of relapse or progression in order to determine the utility of this approach. Methods: Record review of patients diagnosed with FL through the Mayo Clinic Tumor Registry and the Mayo Clinic Lymphoma Data Base who had cryopreserved stem cells for potential future transplant at relapse. Cost of stem cell storage at our institution was reviewed as was the subsequent use of the collected cells. Results: 73 patients with FL had stem cells collected and stored. 37 (51%) were collected prior to a double dose yttrium-90 (90Y) ibritumomab tiuxetan trial for relapsed lymphoma as required by the study. The median age at collection of this group was 56 years (range 28–70). Stem cells remain in storage for a median of 44 months (range 8–119). The median cost of cryopreservation and storage is $4,094 based on the median storage time of 44 months (range $3,628 to 5,065) with a collection cost of $3,524.20 and an annual storage fee of $155.39. This does not include the cost of filgrastim for mobilization, nor line placement. At 5 years, 60% of the cells were not utilized, and at 10 years, 56% of the cells were not utilized. 36 (49%) of the total number of patients were not part of the double dose 90Y ibritumomab tiuxetan trial, but were collected in remission for possible future use or in the setting of relapsed, progressed or transformed disease for potential future transplant. Five of these patients required the use of plerixafor for adequate mobilization. The median age at collection of this group was 47 years (range 24–76). Stem cells remain in storage for a median of 39 months (range 2–128). The median cost of cryopreservation and storage is $4,029 based on the median storage time of 39 months (range $3,550 to 5,182) with a collection cost of $3,524.20 and an annual storage fee of $155.39. This does not include the cost of filgrastim or plerixafor for mobilization, nor line placement. At 5 years, 89% of these cells were not used, and at 10 years, 71% of cells were not used. Conclusion: The utilization of stem cells collected early in the course of FL patients is low, with the majority of cells not being utilized at 10 years. Given improved mobilization techniques resulting in 97% efficacy of stem cell collection at relapse, routine collection and storage of stem cells early in the course FL is not recommended. Disclosures: Micallef: Genzyme: Membership on an entity's Board of Directors or advisory committees, Research Funding.