Treatment of Primary Aggressive Gastrointestinal Lymphomas with Intensive Chemotherapy: A 14-Year Experience

Abstract Background. Aggressive lymphomas accounts for about 80% of primary gastrointestinal non-Hodgkin`s lymphomas (PGIAL). In adults the most common type is diffuse large B-cell lymphoma (DLBCL). Burkitt lymphoma (BL) is rare and mainly affects children. R-CHOP chemotherapy can induce favorable result for localized-stage. But the presence of adverse factors (AF) and advanced stage decrease the efficacy of this therapy: 3-year progression-free survival (PFS) and overall survival (OS) are about 50% and 60% respectively. The optimal treatment strategy for this pts still remains unknown. Aim. Efficacy and safety assessment of the modified chemotherapy protocol NHL-BFM-90 (m NHL-BFM-90 and LB-M-04) in the treatment of the PGIAL with advanced stage and AF. Patients. 74 previously untreated pts with PGIAL underwent mNHL-BFM-90 or LB-M-04 treatment between January 2002 and December 2015; out of them, 45 pts - primary gastric lymphoma (PGL), 29 pts - primary intestinal lymphoma (PIL); median age 39 years (range 14-72); age ≥60 years 10 pts (13,5%); M\F=44\30; stage >I 58 pts (78,3%); B-symptoms 30 pts (40,5%); Bulky disease 28 pts (37,8%). Patients characteristics in groups presented in Table 1. In the PIL group compared with the PGL was predominance of male (M\F=20\9 versus 21\24), stage II-IV (89,6% versus 71%), high level of LDH (72% versus 49%), Bulky disease (55% versus 27%). In pts with high Ki-67 (>40%) FISH test on t(8;14) was performed. Burkitt`s lymphoma diagnosed in 5 pts (11%) with PGL and 9 pts (31%) with PIL. In the PIL group more than half (58,6%) pts received surgical treatment before chemotherapy, and only 2 pts (4,4%) - in the PGL group. Of the 74 pts, 60 (81%) were diagnosed with DLBCL, 14 (19%) - BL. All pts with DLBCL received treatment according to the mNHL-BFM-90 program (2 courses A and 2 courses B) that was modified in the following way: doxorubicin (50mg\m2) was added on the third day of course A. All patients with BL received treatment according to the LB-M-04 program (2 courses A and 2 courses C) that was modified in the following way: doxorubicin (50mg\m2) was added on the third day of course A, methotrexate was administered on the 1st day of course C at a dose 1500mg/m2 for 12 hours. No one received consolidation radiotherapy from both groups. Results. In DLBCL group the overall response rate (ORR) was 95%. Complete remission (CR) was achieved in 38 from 40 pts (95%) in PGL, and 17 from 20 pts (85%) PIL. With a median follow-up of 74 months (range, 1-156) disease-free and overall survival of 60 pts with DLBCL constituted 86.7% and 91,7%, respectively. In BL group all pts achieved CR and alive with no signs of progression with a median follow-up of 110 months (range, 62-154). Hematologic toxicity of grade 3 and 4 was observed in 80% of pts. Severe complications became the reason for subsequent switch to CHOP therapy after 2 courses in 6 pts with PGL DLBCL. There was no treatment-related mortality. Conclusions. The mNHL-BFM-90 and LB-M-04 demonstrated acceptable toxicity and high efficacy in patients with PGIAL. Burkett lymphoma is not rare in adults with PGIAL and detection of t(8;14) can improve treatment outcomes. Table 1 Characteristics of the patients with aggressive primary gastrointestinal non-Hodgkin`s lymphomas. Table 1. Characteristics of the patients with aggressive primary gastrointestinal non-Hodgkin`s lymphomas. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Rituximab - Inmunotherapy Combined with Chemotherapy, CHOP for the Treatment of Patients with Difusse Large B - Cell Lymphoma (DLBCL).

Blood ◽

10.1182/blood.v106.11.4745.4745 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4745-4745

Author(s):

Jorge H. Milone ◽

Fernando Bezares ◽

Maria del Carmen Ardaiz ◽

Dardo Riveros ◽

Luis Palmer ◽

...

Keyword(s):

Overall Survival ◽

High Risk ◽

B Cell Lymphoma ◽

Complete Response ◽

High Risk Group ◽

Hematologic Toxicity ◽

Gastric Bleeding ◽

Bulky Disease ◽

Free Survival

Abstract Several studies (GELA 98.5, MInT) have demonstrated the benefit of combination rituximab (R) with chemotherapy to improve event free and overall survival in patients with DLBCL. We analyzed retrospectively the safety of combination R-CHOP for 6 cycles (rituximab 375 mg/m2 day 1; cyclophosphamide 750 mg/m2 day 1; doxorrubicin 50 mg./m2 day 1; vincristine 1.4 mg/m2 day 1 and prednisone 100 mg/m2 day 1 to 5) the tolerance and adverse effects. We evaluated the response (R), event free survival (EFS) and the overall survival (OS). Between March to December 2004, 28 patients with DLBCL were evaluated, 17 men and 11 women, with a median age 57 years old (range 28 – 84). They were IPI low 21,4 %, low - intermediate 25%, high - intermediate 35,7 % and high risk 17,9 %. Elevated LDH was present en 14 patients, bulky disease > 7 cm in 50% of cases. During the treatment they presented hematologic toxicity grade III 21,4 % and grade IV 25% of cases; 1 patient had anaphilactic reaction; 2 patients pneumonia; 1 patient sepsis; 4 patients neutropenia and fever; and gastric bleeding 1 patient. Response was achieve in 71,4 %: complete response (CR) in 57,1%, parcial (PR) in 14.3 %, and there was no response in 8 patients (28.6%). With follow up of 10 months (range 2 to 18.5) 15 patients were in CR 53,6%, 8 patients died, 7 of then primary no responders. Analyzed by IPI, 60% of CR in intermediate high and high was obtained. The R-CHOP combination is a feasible and safe treatment in our hospitals, and 71,4 % of response was obtained in all patients and 60% of CR in high risk group.

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PET-CT Adapted Therapy After 3 Cycles of ABVD for All Stages of Hodgkin Lymphoma. Interim Analysis in 173 Patients

Blood ◽

10.1182/blood.v116.21.1772.1772 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1772-1772

Author(s):

Santiago Pavlovsky ◽

Astrid Pavlovsky ◽

Isolda Fernandez ◽

Miguel Pavlovsky ◽

Virginia Prates ◽

...

Keyword(s):

Overall Survival ◽

Hodgkin Lymphoma ◽

Progressive Disease ◽

Cell Transplant ◽

Advanced Stage ◽

Event Free Survival ◽

Bulky Disease ◽

Free Survival ◽

Pet Ct

Abstract Abstract 1772 Background: Hodgkin Lymphoma (HL) is the most curable type of Lymphoma with an overall survival at 5 years of 80%. ABVD can be considered as gold standard for first line treatment for all stages of HL. Dividing patients (pts.) in different prognostic groups has aimed to reduce chemo and radio toxicity in those patients with good prognosis. A negative PET-CT, either early during treatment of ABVD or after completion of it, has shown to be a powerful prognostic tool (Hutchings: Blood 2006; Gallamini: Haematologica 2006). Our cooperative group has an experience with 584 patients with HL in early or advanced stage treated with 3 or 6 cycles of ABVD plus involved field radiotherapy with a complete remission (CR) of 91% and an event free survival (EFS) and overall survival (OS) at 60 months of 79% and 95%.(S Pavlovsky, Clin Lymp My & Leuk, 2010). Aims: Test the efficacy of treatment to all stages of HL adjusted to PET-CT results after 3 cycles of ABVD. Evaluate the outcome of pts. who have a negative PET-CT after 3 cycles of ABVD and receive no further treatment. Intensify therapy only in pts. who have persistent hyper metabolic lesions in PET-CT after 3 cycles of ABVD. Method: Since October 2005, 198 newly diagnosed pts. with HL have been included in a prospective multicenter trial. Initially all patients received 3 cycles of ABVD. After the third cycle, pts. were evaluated with a PET-CT. Those pts. who achieved CR with a negative PET-CT, received no further treatment. Those with more than 50% of anatomic reduction of initial masses but persistent hyper metabolic lesions by PET-TC after 3 ABVD were considered in partial remission (PR) and completed 6 cycles of ABVD and radiotherapy (RT) on PET-CT positive areas. Those patients with less than PR after 3 cycles of ABVD received ESHAP and if CR, high doses of chemotherapy and an autologous stem cell transplant (ASCT). All patients were re-evaluated at the end of treatment. The median follow up is of 30 months (3-62). Results: One hundred and seventy three patients completed three cycles of ABVD followed by a PET-CT. The median age at diagnosis was 29 years. One hundred and thirty-six (79%) had localized stage (I-II) at diagnosis and 37 (21%) presented with advanced stage (III-IV). Of 155 pts. 77 (50%) pts had IPS 0–1, 66 (43%) had IPS 2–3 and 12 (8%) had IPS 4–5. Twenty six (17%) pts. had bulky disease at diagnosis. One hundred and thirty-seven (79%) pts. achieved CR with negative PET-CT after 3 cycles of ABVD. Thirty-six (21%) were PET-CT positive, of them 32 pts achieved PR and completed a total of 6 cycles of ABVD plus RT in hyper metabolic lesions. Twenty five achieved CR (72%), 5 persisted with PR and 2 died of progressive disease. Four pts showed progressive disease (PD) after 3 ABVD and received ESHAP and ASCT, 2 achieved and remained in CR, 1 is in PR and 1 died of progressive disease. Of 173 pts who completed treatment with ABVD × 3 cycles, ABVD × 6 cycles plus RT on PET-TC positive areas or ESHAP plus ASCT, 164 pts (95%) achieved CR. Of these 164 pts., 14 pts (8%) relapsed. The EFS and OS at 36 months is 83% and 97% respectively. Patients with early negative PET-TC have an event-free survival of 87% compared to 62% (P=0,001) for pts with early positive PET CT. The OS at 36 months was 100% versus 86% respectively (<0.001). Conclusion: Treating patients with ABVD, evaluating response after 3 cycles with PET-CT, and adapting further therapy, leads to a high rate of CR avoiding more aggressive chemotherapy and radiotherapy. Three courses of ABVD without RT are adequate in patients with early CR defined by negative PET-CT. In early positive PET-CT it is possible to intensify therapy improving the otherwise bad prognosis; more aggressive treatment might also be suitable. These results need to be confirmed by a larger group of patients and a longer follow-up. Disclosures: No relevant conflicts of interest to declare.

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Epidemiologic and Clinical Patterns of Lymphoma in Qatar 2013-2017: A Population-Based Cohort Study

Blood ◽

10.1182/blood-2021-144637 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4584-4584

Author(s):

Ahmed A Adel ◽

Aimilia Exarchakou ◽

Anas Hamad ◽

Ruba Yasin ◽

Hafedh Ghazouani ◽

...

Keyword(s):

Overall Survival ◽

B Cell ◽

Conflicts Of Interest ◽

Disease Free Survival ◽

B Cell Lymphoma ◽

Descriptive Statistics ◽

World Health ◽

Treatment Modalities ◽

Epidemiological Characteristics

Abstract Background: Lymphoma: either most common non-Hodgkin (NHL) or less common Hodgkin (HL), are well-known hematological malignancies. With advancement in treatment modalities, the survival in both lymphomas especially the "poor prognosis" non-Hodgkin lymphoma has evolved in the last decades. Hence, patient's outcome may be diverse and quite complicated; with some need extended time for observation, and others having multiple chemotherapy treatments. In this review, we will focus on the clinic-epidemiological patterns of various malignant lymphoma subtypes in Qatar in recent years (2013-2017) Objective: The primary aim is to investigate and compare the overall survival (OS) for both types of lymphoma; HL and NHL at 1, 3 and 5-years of follow up in adult lymphoma patients in Qatar between January 2013 - December 2017. Other objectives include comparing between the most frequent histological varieties, clinical and epidemiological characteristics of HL and NHL lymphoma in Qatar. The secondary objectives included clinical characteristics, treatments used, treatment response, disease-free survival and overall survival. Methods: A retrospective, descriptive study of consecutive cases was carried out at NCCCR, Qatar between 2013-2017. Inclusion criteria included: ≥ 18 years of age, male or female, any clinical stage at diagnosis, who had received any chemotherapy regimen, with a known outcome. Descriptive statistics was performed for all variables, and survival was assessed using Kaplan-Meier curves. Data was abstracted by Qatar National Cancer Registry and the 2008 World Health Organization (WHO) classification of hematopoietic and lymphoid tumors is used as reference for disease staging and pathological classification. We used STATA version 13.0 (StataCorp., College Station, TX) for exploratory data analysis and descriptive statistics. Results: During the period 2013-2017, 414 men and women were diagnosed with lymphoma in the state of Qatar. The median age at diagnosis being 49 years (interquartile range IQR 36-95 years; p<0.001)) for all lymphoma patients combined. Males were more likely to develop both lymphoma types; HL and NHL than females; accounting for 2/3 of cases in each, yet statistically insignificant (74% and 70%, p=0.45). Based on subtypes, mature B-cell neoplasms (61 cases, 60%) were the most common among 13 identifiable NHL-B subtypes. Majority of HL cases belonged to Lymphocyte rich subtype (54 cases, 49%). With a median follow up of 17.3 months, the 1-year, 3-year and 5-year OS for the entire population of lymphoma patients were 99%, 82% and 64% (Figure 12). When stratified by major subtypes; HL and NHL, some trends became evident at 3-years follow-up (94% versus 82%). The 5-year OS were 67% and 60%, respectively. Throughout the study period, the OS in HL group were higher than NHL (p<0.001), yet median OS was not reached. Conclusions: Diffuse large B-cell lymphoma constitutes the most frequent subtype for all lymphomas in Qatar. Overall, the survival was generally better for HL than NHL 67% and 60% respectively. Survival can be slightly deflated than other countries or regions especially HL, this is in part due to higher immigration rate in the country, so changes in survival over time (especially for longer periods) need to be examined alongside trends in incidence rates to interpret improvement in cancer control policies implemented. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Clinical Outcome of Patients with Follicular Lymphoma and Bulky Disease After Rituximab-CHOP Immunochemotherapy with and without Consolidating Radiotherapy.

Blood ◽

10.1182/blood.v114.22.2722.2722 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2722-2722

Author(s):

Fabienne McClanahan ◽

Thomas Hielscher ◽

Michael Rieger ◽

Manfred Hensel ◽

Kai Neben ◽

...

Keyword(s):

Follicular Lymphoma ◽

Conflicts Of Interest ◽

Survival Rates ◽

B Cell Lymphoma ◽

Bulky Disease ◽

Mediastinal Lymphoma ◽

Significant Difference ◽

Tumour Bulk ◽

New Location

Abstract Abstract 2722 Poster Board II-698 Background: As the clinical management of patients with bulky disease remains challenging, many centres apply involved-field radiotherapy (IF-RT) after completion of immunochemotherapy. This strategy remains controversial. Patients and Methods: To evaluate the benefit of consolidating IF-RT in addition to immunochemotherapy, we retrospectively analyzed relapse patterns and survival of patients presenting with bulky follicular lymphoma (FL). Bulky disease was defined as abdominal/ mediastinal lymphoma mass >7.5 cm and/ or peripheral lymphoma mass >5 cm. All patients were treated within a prospective randomized trial on 126 patients with FL with six cycles of standard CHOP-chemotherapy in combination with 1, 3 or 6 cycles of Rituximab, followed by consolidating IF-RT in patients with bulky disease. 42 eligible patients with bulky disease were identified and form the foundation of this analysis, of which 26 were irradiated and 16 were not, violating the protocol. Results: With the exception of number of affected nodal regions, there was no significant difference between the irradiated and the non-irradiated group with regards to presenting characteristics (p > .05). Among all patients, bulks were located below the diaphragm in 91%. A second tumour bulk was present in 9 patients (22%). Female to male ratio was 1.3:1, and the median age at diagnosis was 54 years (range 23–73). According to FLIPI, 10% were classified as low risk (0–1), 45% as intermediate risk (2), and 45% as high risk (3–5). B symptoms were absent in 69%. Eleven patients (26 %) had received one course of Rituximab, 17 (41%) three courses and 14 (33%) six courses. There was no significant difference between the irradiated and the non-irradiated group with regards to previous exposure to immunochemotherapy (p = .628). After a median follow-up of 60 months, a total of 21 patients (50%) had progressed or relapsed and 9 patients (21%) had died. With the exception of one patient who died from congestive heart failure following chemotherapy-related cardiomyopathy, the main cause of death was disease progression or relapse. Highly malignant transformation into diffuse large B-cell lymphoma was observed in 5 cases. In the irradiated group, relapse occurred in 12 of 26 patients. Half of these relapses were located within the original bulk or within the bulk plus a new location, and 50% at a new location altogether; 42% occurred within the previously irradiated area. In the non-irradiated group, 9 of 16 patients relapsed. The corresponding rates regarding relapse location were 67% for original plus new location and 33% for new location only. There was no statistically significant difference between exposure to radiotherapy after immunochemotherapy and the likelihood of a relapse per se (p = .751) or at a specific location (p = .66). At the last follow-up, 31% of irradiated patients had achieved CR and 23% PR. Among the non-irradiated group, the corresponding rates were 25% and 19%. There was no significant difference in remission rates at any staging examination throughout the clinical trial between the two treatment groups (p > .05). 6-year progression-free- and overall survival rates were 52% and 80% after IF-RT and 48% and 73% without IF-RT (p = 1.00, p = .68 respectively). Conclusion: In this analysis, there was no difference in relapse rate, relapse location, PFS and OS between patients with bulky FL treated with and without consolidating IF-RT. Although patient numbers are limited, this is the first analysis of its kind conducted in the Rituximab era. Disclosures: No relevant conflicts of interest to declare.

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Outcome of BEAM-Autologous and BEAM-Alemtuzumab Allogeneic Transplantation in Relapsed Advanced Stage Follicular Lymphoma

Blood ◽

10.1182/blood.v120.21.2022.2022 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2022-2022

Author(s):

Victor Noriega ◽

Anjum Bashir Khan ◽

Stephen Devereux ◽

Robert E. Marcus ◽

Michelle Kenyon ◽

...

Keyword(s):

Overall Survival ◽

Follicular Lymphoma ◽

Conflicts Of Interest ◽

Chronic Gvhd ◽

Disease Free Survival ◽

Allogeneic Transplantation ◽

High Grade ◽

Advanced Stage

Abstract Abstract 2022 Introduction: Follicular Lymphoma is the most common indolent lymphoma, characterized by an indolent course, multiple recurrence, responses to chemotherapy, risk of transformation into a high grade lymphoma and with a median overall survival of 10–12 years. Transplantation (autologous and allogeneic) has improved the overall outcome of this disease, however a continuous pattern of relapse is observed essentially in the autologous setting. Allogeneic transplant has shown encouraging results in terms of long term overall survival (OS) and disease free survival (DFS), with acceptable transplant related mortality (TRM) and with significantly lower relapse rate. Objective: To analyse retrospectively the outcome of relapsed follicular lymphoma patients who received BCNU (carmustine), cytarabine, etoposide, melphalan-alemtuzumab allogeneic HSCT (BEAM-C allo) or BEAM-autologous HSCT (BEAM-auto). Results: The study includes 74 consecutive patients with relapsed advanced stage follicular lymphoma who received BEAM-C allo (n=38) and BEAM-auto (n=36) between 1992 and 2010. Patients characteristics are summarized in Table 1. Median follow-up of surviving patients was 6.1 years. Patients undergoing allo transplants were younger than those who unbderwent and autologous procedure (50 vs 54 years, p=0.018). 1y and 5y TRM was higher in the allo transplant group (27% and 27% vs 6% and 6%; p=0,011). The Cumulative incidence of relapse (CIR) was lower in the allo at 1, 2 and 5 years (11%, 14% and 18% vs 28%, 49% and 60%, p=0,000). Significant differences were not observed in 1, 2 and 5 years OS between allo and auto transplant groups (74%, 74% and 69% vs 85%, 69% and 51%; p=0,217), but we found a strong trend in DFS difference between both groups at 1, 2 and 5 years (65%, 61% and 58% vs 69%, 43% and 33%; p=0.089) observing a plateau around 60% after 2 years in the allograft group. The rate of graft versus host disease (GvHD) was low with 14% acute GvHD (2.6% grade 3–4 GvHD) and 28% chronic GvHD (10% of extensive chronic GvHD). Analysis of the whole cohort (n=74) showed that patients in CR before transplant (n=28) had better 1, 2 and 5 years DFS following a allotransplant (69%, 69% and 69% vs 79%, 36% and 18%; p=0.012). These differences did not affect the 1, 2 and 5 years OS (76%, 76% and 76% vs 93%, 76% and 56%; p=0,214). TRM for the allo transplant group was 24% and 0% R in the auto (p=0,064) in patients when achieved CR before transplant. There were no difference in OS (p=0,785) and DFS (p=0,954) between allo or auto patients in partial response (PR) before transplant. A subgroup analysis of patients with high grade transformation before transplant did not show any differences in OS (p=0,823) or EFS (p=0,526).between allo and auto groups. Conclusions: Long term follow-up of Follicular Lymphoma patients has shown a continuous pattern of relapse when patients receive an autologous transplant, after 5 years. whereas patients undergoing allo transplant, despite a higher mortality, have a 5 year OS and DFS of 60% with a plateau been achieved in both curves after 2 years suggesting that these patients may be cured. Prospective randomised studies are still required to answer the the role of these two approaches in follicular Lymphoma. Disclosures: No relevant conflicts of interest to declare.

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MYC Translocations Are Associated with Poor Overall Survival in DLBCL Patients in Both the Chemotherapy and Immunochemotherapy Eras.

Blood ◽

10.1182/blood.v114.22.443.443 ◽

2009 ◽

Vol 114 (22) ◽

pp. 443-443

Author(s):

Ahmet Dogan ◽

Matthew J Maurer ◽

William R Macon ◽

David J Inwards ◽

Ivana N Micallef ◽

...

Keyword(s):

Overall Survival ◽

Mayo Clinic ◽

Conflicts Of Interest ◽

B Cell Lymphoma ◽

Tissue Microarrays ◽

Newly Diagnosed ◽

University Of Iowa ◽

Poor Overall Survival ◽

New Treatment

Abstract Abstract 443 Background: MYC translocations have been reported to have inferior outcome in aggressive non-Hodgkin lymphomas. Here we present MYC translocation prevalence and outcome from two cohorts of newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients treated in the chemotherapy (C) and immunochemotherapy (IC) eras. Methods: Tissue microarrays were created from 302 newly diagnosed DLBCL patients evaluated at the Mayo Clinic with availabel paraffin tissue. 233 DLBCL patients first diagnosed from March 1986-July 2001 were retrospectively identified based on a diagnosis of DLBCL and treatment with anthracycline-based chemotherapy. 69 DLBCL patients diagnosed from March 2002-October 2005 and treated with immunochemotherapy were prospectively enrolled in the University of Iowa / Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource. Central pathology review was performed on all samples to confirm the diagnosis of DLBCL. Interphase FISH was performed using a breakapart strategy for MYC and BCL6 gene regions and a dual fusion strategy for t(14;18)(IGH&/BCL2). Results: Chemotherapy (C) era patients were primarily treated with CHOP (88%); immunochemotherapy (IC) era patients were all treated with an R-CHOP based regimen. The median age at diagnosis was 65 years (range, 22-92) for C patients and 65 years (range, 20-82) for IC patients. Median follow-up for C patients was 11.3 years (range, 2.7-21.3) with 145 (62%) deaths; for IC patients, the median follow-up was 5.0 years (range, 2.1-6.4) with 17 deaths (25%). FISH was successful in 195 of 302 patients (65%). MYC translocations were identified in 6 of 141 C patients (4%) and 3 of 54 IC patients (6%). MYC translocations were associated with inferior overall survival in the C patients (p=0.001), the IC patients (p=0.04), and in the combined group (p≤0.001). Median survival of patients with MYC translocations was 19 months and 16 months for C and IC respectively, compared to 112 months (C) and unreached (IC) for DLBCL patients without MYC translocations. 4 of the 9 MYC translocation patients had a double hit (2 with both MYC and BCL2 translocations and 2 with translocations of MYC, BCL2, and BCL6). Associations of MYC and outcome remained significant in all patients after adjusting for treatment and IPI (p<0.05). Conclusions: MYC translocations are present in approximately 5% of DLBCL patients and are associated with poor outcome in patients treated with C or IC. New treatment approaches are needed for DLBCL patients with MYC translocations. Disclosures: No relevant conflicts of interest to declare.

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Concurrent Expression Of MYC/BCL2 Protein In Newly Diagnosed DLBCL Is Not Associated With An Inferior Survival Following EPOCH-R Therapy

Blood ◽

10.1182/blood.v122.21.3029.3029 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3029-3029 ◽

Cited By ~ 7

Author(s):

Kieron Dunleavy ◽

Stefania Pittaluga ◽

Margaret Shovlin ◽

Svetlana Pack ◽

Seth M. Steinberg ◽

...

Keyword(s):

Overall Survival ◽

T Cells ◽

Clinical Outcome ◽

B Cell ◽

Conflicts Of Interest ◽

B Cell Lymphoma ◽

Newly Diagnosed ◽

Cell Of Origin ◽

Bcl2 Protein

Abstract Background While several studies have now demonstrated that patients with MYC-rearranged DLBCL have a worse outcome following treatment with CHOP -with or without rituximab - recent reports suggest that concurrent expression of MYC and BCL2 protein by immunohistochemistry (IHC), independent of a MYC rearrangement, is associated with an inferior clinical outcome following R-CHOP (Johnson et al. JCO 2012 Oct 1; 30 (28): 3452-9). We previously reported that DLBCL patients with a MYC rearrangement have a similar outcome to MYC negative cases (4 year EFS of 83% versus 76% respectively: p=0.46) following dose-adjusted (DA)-EPOCH-R (Dunleavy et al. Ann Oncol 2011 (22) Suppl 4 # 71). Methods To assess the prognostic role of MYC and BCL2 protein expression, we performed immunohistochemistry for MYC and BCL2 in patients with newly diagnosed DLBCL who received DA-EPOCH-R or short-course (SC)-EPOCH-RR (if HIV infected). Primary mediastinal B-cell lymphoma (PMBL) cases were excluded as they have a different biology. Tumors were scored positive for MYC if ≥ 40% of cells stained positive. For BCL2, the staining intensity was compared with that in control T cells present in the tumor samples – tumor cells were considered positive if they stained the same or more intensely than T cells. We used the Hans algorithm, as previously described, to predict cell of origin as germinal center B-cell like (GCB) or non-GCB type and correlated this with outcome. Results Of 66 patients enrolled on study, characteristics were median (range) age: 48 (18-76) years; male sex 47 (71%); IPI score low versus intermediate/high 18 (27%) versus 48 (73%); HIV positive 22 (33%). IHC was positive for MYC in 28/48 (58%) cases and positive for BCL2 in 24/51 (47%). 36/51 (71%) and 15/51 (29%) of cases were of GCB and non-GCB origin respectively. At a median follow-up time of greater than 10 years, progression-free survival (PFS) and overall survival (OS) were 67.5% and 75% for all patients. We compared survival in the 4 groups: MYC+/BCL2+, MYC+/BCL2-, MYC-/BCL2+ and MYC-/BCL2-. PFS and OS were not significantly inferior in any group (global p value=0.5 (PFS) and 0.8 (OS)). Cell of origin did however predict outcome and at 10 years follow-up, PFS was 78% (GCB) versus 43% (non-GCB) (p=0.016) and OS 80% (GCB) versus 65% (non-GCB) (p=0.24). There was a significant association between MYC+/BCL2+ cases and non-GCB subtype (p=0.01) but as 42% were of GCB origin, MYC+/BCL2+ status alone did not predict a poor outcome. Conclusions In DLBCL patients treated with DA-EPOCH-R and SC-EPOCH-RR, concurrent expression of MYC and BCL2 protein did not correspond with a worse clinical outcome. However, cell of origin (GCB versus non-GCB) was predictive of outcome. MYC+/BCL2+ cases segregate with the non-GCB subtype. The overall survival of PMBL cases was 97% at 5 years follow-up. We are currently prospectively studying the DA-EPOCH-R regimen in MYC-rearranged DLBCL in a multicenter study (NCT01092182). Disclosures: No relevant conflicts of interest to declare.

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Fractionated Cyclophosphamide, Vinblastine with Prednisolone and Daily Oral Etoposide Based Treatment of AIDS-Related Plasmablastic Lymphomas (PBL): A Highly Active and Well Tolerated Regimen

Blood ◽

10.1182/blood.v118.21.2690.2690 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2690-2690

Author(s):

Manju Sengar ◽

Tanuja Shet ◽

Reena Nair ◽

Epari Sridhar ◽

Hari Menon ◽

...

Keyword(s):

Overall Survival ◽

Partial Response ◽

Conflicts Of Interest ◽

Significant Proportion ◽

Outpatient Basis ◽

Oral Etoposide ◽

Ki 67 ◽

Bulky Disease ◽

Prognostic Features

Abstract Abstract 2690 Background: Aggressive biology, tumor re-growth on treatment and poor tolerance to chemotherapy, are the factors responsible for dismal outcomes in patients with AIDS- related PBL. Treatment with CHOP, CHOP-like regimens or more intensive protocols (HyperCVAD, CODOX-M/IVAC) has failed to improve median survival beyond 15 months. To overcome the problems of tumor re-growth secondary to cancer cell resistance and treatment related toxicity, we devised a regimen in which drugs with proven anti-lymphoma activity were given in fractionated and continuous manner. Continuous daily dosing of oral etoposide for 2–3 weeks provides an effective concentration of drug for extended time periods. Anthracyclines were omitted to reduce the incidence of myelosuppression and mucositis. This regimen was tested prospectively to assess the efficacy and tolerability Methods: Between August 2007 to February 2011, consecutive patients with untreated AIDS-related PBL and age >18 years were counseled for treatment with the proposed regimen at our center. Diagnosis of PBL required absent or weak expression of CD20, expression of MUM-1 or CD 38 or CD138 to suggest plasma cell differentiation. Paraffin blocks were evaluated for expression of EBER, HHV-8 and Ki-67. All patients who were willing for treatment and follow up and did not have CNS involvement or concurrent infections were enrolled. Anti-retroviral therapy (ART) was started concurrently with chemotherapy if not received before. The 3-weekly regimen included cyclophosphamide 375 mg/m2 and vinblastine 4mg/m2 intravenously on day 1 and 8, oral etoposide 50 mg daily for 2 weeks and prednisolone 40 mg/m2//day for the first week of each cycle. Ten weekly doses of intrathecal methotrexate were given as CNS prophylaxis. Radiation was given to the bulky and extranodal sites. Mid and end of therapy responses were evaluated clinically and radiologically (CT or PET-CT). Results: Eighteen patients (males-11, females-7) with median age of 37.5 years (range, 22–51 years) were treated with the above mentioned regimen. Two-thirds of patients were not on ART at diagnosis. Ten patients had tuberculosis as an AIDS-defining illness. Median CD4 count at diagnosis was 175/μL (range 75–407/μL). Significant proportion of patients had adverse prognostic features like B symptoms (9/18), performance status (ECOG) ≥2 (11/18), stage III/IV disease (14/18), bulky disease (15/18), multiple extranodal sites (6/18), raised serum LDH (9/18). Extranodal disease was seen in 17/18 patients commonest being bone followed by anal canal. All except one patient received treatment with chemotherapy (median cycles-6, range 4–8). This patient did not follow up after the initial staging evaluation. Complete responses were seen in 15/17 patients after chemotherapy and 2 patients had partial response. Sixteen patients received radiation. All patients except one had complete response after RT. Patient who continued to have partial response at the end of radiation progressed after 7 months and died. At median follow up of 19 months (range, 3–48 months) both overall survival and event free survival are 87.7%. Median overall survival has not yet been achieved. Treatment was well tolerated with 6 episode of febrile neutropenia which were managed on outpatient basis. One patient was hospitalized for pneumonitis for 7 days. There were no treatment related deaths. On paraffin blocks expression of EBER was seen in 55%. None of them were positive for HHV-8. Six patients had Ki-67 of >90%. Conclusion: This is the first reported series from a single center which has shown improved response rates and survival for AIDS related PBL with a novel regimen as compared to available data till date. However the study has limitations of small size and short follow up. Disclosures: No relevant conflicts of interest to declare.

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Long-Term Follow-up Analysis of HD2000 Trial Comparing ABVD Versus BEACOPP Versus Copp/EBV/CAD in Patients with Newly Diagnosed Advanced-Stage Hodgkin's Lymphoma: A Study from the Fondazione Italiana Linfomi

Blood ◽

10.1182/blood.v124.21.499.499 ◽

2014 ◽

Vol 124 (21) ◽

pp. 499-499 ◽

Cited By ~ 1

Author(s):

Francesco Merli ◽

Stefano Luminari ◽

Caterina Mammi ◽

Nicola Cascavilla ◽

Alessia Bari ◽

...

Keyword(s):

Overall Survival ◽

Hodgkin’S Lymphoma ◽

Conflicts Of Interest ◽

Previous Analysis ◽

Hodgkin's Lymphoma ◽

Advanced Stage ◽

Term Outcome ◽

Long Term Outcome

Abstract PURPOSE: The HD2000 trial compared doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) versus bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) versus the combination of cyclophosphamide, vincristine, procarbazine, prednisone (COPP) with epidoxorubicin, bleomycin, vinblastine (EBV), lomustine, doxorubicin, and vindesine (CAD) (MOPP/EBV/CAD [CEC]) in 305 eligible patients with advanced-stage Hodgkin's lymphoma (HL). The previous analysis with 41 months median follow-up had indicated that BEACOPP was associated with a significantly improved Progression Free Survival (PFS) compared with ABVD, with a predictable higher acute toxicity. At time of previous analysis none of the study arms resulted in a better Overall Survival (OS). We here report analysis of long-term outcome and toxicity. PATIENTS AND METHODS: Three hundred and five eligible patients with stage IIB, III, or IV were randomly assigned to receive six courses of ABVD (n=103), four escalated plus two standard courses of BEACOPP (n=100), or six courses of CEC (n=102), plus a limited radiation therapy program; radiotherapy was administered in 46, 42, and 42 patients in the three arms, respectively. Study enrolment was completed in June 2007. In January 2014 we updated the study follow-up with the aim of providing data on survival and on late events. RESULTS: At time of current analysis the median follow-up was 119 months (range 1-169) with 92% of patients with a last contact later than January 2012. In the prolonged observation period 23 additional failures (cumulative=82)were recorded, including 17 new relapses/progression (cum=71) and 6 deaths not related to lymphoma progression (cum=11). Additional relapses and progressions were observed in 5, 7 and 5 patients treated with ABVD (cum=31), BEACOPP (cum=17), and CEC (cum=23), respectively. No death unrelatedto lymphoma progression was recorded among patients treated with ABVD, while 8 (+4) and 3 (+2) events were documented among patients treated with BEACOPP or CEC, respectively. The 10-year PFS was 69%, 74% and 74% in the ABVD, BEACOPP and CEC arm, respectively (P=0.639). Using ABVD as reference, Hazard Ratio for PFS for BEACOPP and CEC was 0.73 (CI95% 0.43-1.25) and 0.80 (0.47-1.36); this result was adjusted by IPS. Overall 42 patients died (+19), 13 (+5) in the ABVD arm, 15 (+7) in the BEACOPP arm and 14 (+7) in the CEC arm. The 10-year overall survival rates were 84%, 84% and 86% for ABVD, BEACOPP and CEC, respectively (P =0.883). A total of 11 second malignancies were documented including 2 MDS/AML (1 BEACOPP and 1 CEC), 2 non-Hodgkin’s Lymphoma (1 BEACOPP and 1 CEC), and 7 solid cancers: 2 lung cancer (BEACOPP), 2 bladder cancer (2 CEC), 1 sarcoma (BEACOPP), 1 Kaposi sarcoma (BEACOPP) and 1 thyroid cancer (ABVD). The risk of second malignancy at 10-year was 6.7, 4.4 and 0.9 for BEACOPP, CEC and ABVD, respectively; the difference between BEACOPP and ABVD was statistically significant (P=0.027). CONCLUSION : With the updated follow-up of the HD2000 trial we confirm that patients with advanced HL have similar high chances of survival when treated with ABVD, BEACOPP or CEC. With this long-term analysis we were not able to confirm the previously observed superiority of BEACOPP over ABVD in terms of PFS mainly due to a higher rate of secondary malignancies observed after BEACOPP. Disclosures No relevant conflicts of interest to declare.

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Low-Grade Mucosa-Associated Lymphoid Tissue Lymphoma Involving the Kidney: Report of 3 Cases and Review of the Literature

Archives of Pathology & Laboratory Medicine ◽

10.5858/2006-130-86-lmltli ◽

2006 ◽

Vol 130 (1) ◽

pp. 86-89 ◽

Cited By ~ 4

Author(s):

Libo Qiu ◽

Pamela D. Unger ◽

Robert W. Dillon ◽

James A. Strauchen

Keyword(s):

Lymphoid Tissue ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Lymphoid Cells ◽

Low Grade ◽

The Third ◽

First Case ◽

Abundant Cytoplasm ◽

History Of

Abstract Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue involving the kidney is rare. We report a series of 3 cases. The first case occurred in an 83-year-old woman who presented with back pain. The second case was a 53-year-old man with a history of sarcoidosis who was found, in the course of evaluation of sarcoidosis, to have a right renal mass. The third case occurred in a 72-year-old man who had a history of periorbital mucosa–associated lymphoid tissue lymphoma and had been treated with surgery and radiation 1 year prior to this presentation. Histologically, all 3 patients showed infiltrate of uniform small-to-medium–sized lymphocytes with irregular nuclear contours and abundant cytoplasm resembling centrocytes or monocytoid lymphoid cells. The first patient received chemotherapy without complications. The second patient underwent a partial nephrectomy and was asymptomatic at the subsequent follow-up. The third patient developed a pulmonary embolism following nephrectomy, and further follow-up is not available.

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