Minimal Disseminated Disease in High-Risk Burkitt's Lymphoma Identifies Patients With Different Prognosis

Abstract Abstract 2944 Poster Board II-920 Introduction: The chromosomal translocation t(8;14)(q24;q32) represents a specific tumor marker in Burkitt's lymphoma (BL). This chromosomal aberration involves the MYC oncogene on chromosome 8 and the immunoglobulin heavy-chain (IgH) locus on chromosome 14. We have previously demonstrated that this genetic abnormality can be used as a marker of Minimal Disseminated Disease (MDD) in BL (Mussolin et al, JCO, 2007). The aim of the study was to assess of the prevalence of MDD in BL at diagnosis in children enrolled in the AIEOP LNH-97 clinical protocol and the evaluation of its impact on prognosis. Patients and Methods: We established a simplified long-distance PCR (LD-PCR) assay which can amplify up to 15-20 Kb DNA sequence making it possible to detect the t(8;14) at the genomic level with the sensitivity of 10-4. The assay was based on 4 separate PCR reactions in which one primer complementary to the first exon of the MYC gene is used with one of four primers for the IgH locus (1 for the JH region and 1 for each of the 3 constant regions). Results: LD-PCR was applied to prospectively study 124 BL biopsies and detected a specific PCR product in 88 of them (71%). Of the 88 positive BL patients we studied both the tumor and the bone marrow (BM) at diagnosis in 76: BM was positive by LD-PCR in 25 patients (33%), whereas only 10 (13%) were positive at the standard morphological and/or immunophenotypical analyses. Most of the MDD positive patients (88%) belonged to the R4 Risk Group according to BFM definition (stage III or stage IV according to St. Jude staging classification and LDH≥1000 U/l). The 3-year progression-free survival (PFS) was 68% (SE 10%) in MDD positive R4 patients compared with 96% (SE 4%) in MDD negative R4 patients (p= 0.02), whereas there was no difference in PFS between children with morphological involvement of BM at diagnosis versus those who had negative BM (PFS=62.5% (SE 17%) vs. PFS= 87% (SE 6%), respectively, p= 0.09). By multivariate analysis (including MDD, gender, LDH, CNS involvement) MDD was predictive of higher risk of failure (Hazard Ratio: 8.4 , p= 0.04). Conclusions: We demonstrated that MDD identifies a poor prognosis subgroup among high risk Burkitt's lymphoma patients. We suggest that a more effective risk-adapted therapy, possibly including anti-CD20 monoclonal antibody, should be considered in these patients. Disclosures: No relevant conflicts of interest to declare.

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Minimal Disseminated Disease in High-Risk Burkitt's Lymphoma Identifies Patients With Different Prognosis

Journal of Clinical Oncology ◽

10.1200/jco.2010.32.8161 ◽

2011 ◽

Vol 29 (13) ◽

pp. 1779-1784 ◽

Cited By ~ 30

Author(s):

Lara Mussolin ◽

Marta Pillon ◽

Emanuele S.G. d'Amore ◽

Valentino Conter ◽

Matilde Piglione ◽

...

Keyword(s):

Bone Marrow ◽

High Risk ◽

Progression Free Survival ◽

Burkitt’S Lymphoma ◽

Burkitt's Lymphoma ◽

Long Distance ◽

Tumor Biopsy ◽

Minimal Disseminated Disease ◽

Anti Cd20 ◽

Disseminated Disease

Purpose To study minimal disseminated disease (MDD) in children with Burkitt's lymphoma (BL) and to determine its impact on prognosis. Patients and Methods We established a simplified long-distance polymerase chain reaction (LD-PCR) assay that can amplify up to 15 to 20 Kb of DNA sequence, making it possible to detect the t(8;14) at the genomic level with sensitivity of 10−4. We prospectively studied diagnostic biopsies and bone marrow aspirates from 134 patients affected by BL. Results A specific LD-PCR product was detected in 96 (72%) of 134 BL biopsies. Among 84 patients with t(8;14) positivity on tumor biopsy and bone marrow (BM), 26 (31%) had LD-PCR–positive BM, and 15 (18%) were positive at standard morphologic analysis. Twenty (85%) of 26 MDD-positive patients belonged to the R4 risk group, according to Berlin-Frankfurt-Munster definition. The 3-year progression-free survival was 68% (SE, 10%) in MDD-positive patients in R4 compared with 93% (SE, 5%) in MDD-negative patients in R4 (P = .03). By multivariate analysis (including MDD, sex, lactate dehydrogenase, CNS involvement), only MDD was predictive of higher risk of failure (hazard ratio, 4.7; P = .04). Conclusion MDD identifies a poor-prognosis subgroup among children with high-risk BL. To improve disease control in these patients, a more effective risk-adapted therapy, possibly including anti-CD20 monoclonal antibody, should be considered.

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Remission of HIV-related naïve and high-risk Burkitt’s lymphoma treated by autologous stem cell transplantation plus cART

Stem Cell Research & Therapy ◽

10.1186/s13287-018-1089-5 ◽

2018 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Haiyan Min ◽

Jianwei Yang ◽

Sanbin Wang ◽

Pengfei Tao ◽

Yuqin Song ◽

...

Keyword(s):

Stem Cell ◽

High Risk ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Burkitt’S Lymphoma ◽

Burkitt's Lymphoma

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Minimal Disseminated Disease in Nonmetastatic Retinoblastoma With High-Risk Pathologic Features and Association With Disease-Free Survival

JAMA Ophthalmology ◽

10.1001/jamaophthalmol.2016.4158 ◽

2016 ◽

Vol 134 (12) ◽

pp. 1374 ◽

Cited By ~ 11

Author(s):

Viviana E. Laurent ◽

Ana Vanesa Torbidoni ◽

Claudia Sampor ◽

Daniela Ottaviani ◽

Valeria Vazquez ◽

...

Keyword(s):

High Risk ◽

Disease Free Survival ◽

Free Survival ◽

Pathologic Features ◽

Minimal Disseminated Disease ◽

Disseminated Disease ◽

Disease Free

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Ofatumumab Can Induce Remission in Refractory Burkitt's Lymphoma – A Case Report

Blood ◽

10.1182/blood.v120.21.4895.4895 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4895-4895

Author(s):

Matjaz Sever ◽

Samo Zver ◽

Barbara Jezersek Novakovic ◽

Joze Pretnar

Keyword(s):

Bone Marrow ◽

Flow Cytometry ◽

Stem Cell ◽

Case Report ◽

High Risk ◽

Pneumocystis Carinii ◽

Burkitt’S Lymphoma ◽

Burkitt's Lymphoma ◽

Cycle Phase ◽

Hodgkin's Lymphomas

Abstract Abstract 4895 Introduction: Burkitt's lymphoma (BL) is a rare condition accounting between 1– 5% of Non Hodgkin's lymphomas. Standard treatment consists of intensive chemotherapy with fractionated alkylating agents and cell cycle phase specific agents that cross the blood brain barrier. Patients who achieve only partial response after front-line treatment or in first relapse can be treated with autologous stem cell transplantation (SCT) or in rare cases with allogeneic SCT. Rituximab added to various chemotherapy regimens can improve the results. Ofatumumab is a new anti-CD20 monoclonal antibody active in refractory or high risk patients with chronic lymphocytic leukemia (CLL). We present a patient with refractory BL after standard chemo/immunotherapy and autologous SCT who achieved remission after ofatumumab treatment. Case report: A 31-year old male patient was diagnosed with Burkitt's lymphoma (stage IIIb) in April 2011. He was put on BMF protocol but progressed after two cycles. Rituximab was added in therapy. After two additional cycles there was no response to treatment. A salvage protocol DA-R-EPOCH was employed and after four cycles patient went into partial remission. Stem cell mobilization was performed with rituximab/cyclophosphamide/filgrastim and plerixafor because of poor initial mobilization result. In September 2011 patient received autologous SCT after BEAM conditioning. Six weeks after the procedure assessment of disease showed presence of 0.14 % BL cells on bone marrow flow cytometry and residual disease in abdomen on PET-CT. The patient started with ofatumumab according to protocol used in CLL and began with local radiotherapy. After seven weeks on ofatumumab bone marrow showed no residual BL on flow cytometry. Due to high risk disease and poor graft function after autologous SCT we decided for additional allogeneic SCT which was performed in January 2012 after myeloablative conditioning with cyclophosphamide and total body irradiation. The donor was a 9/10 HLA match. Post transplant period was complicated with cytomegalovirus reactivation and side effects of cyclosporine. On day +66 the patient presented with Pneumocystis carinii pneumonia that required ventilation support. Bone marrow examination in April 2012 showed no residual BL. After short improvement the patient's condition was complicated with secondary pneumonia, acute respiratory distress syndrome and septic shock. The patient expired on day +94 after allogeneic SCT. Conclusion: Ofatumumab induced remission in a patient with refractory BL after two chemotherapy regimens, rituximab and autologous SCT. The patient went into remission after eleven weeks on ofatumumab CLL protocol and was able to proceed to allogeneic SCT. He remained in remission three months post SCT. The cause of patient's death was infection. Studies would be required to address ofatumumab's role in refractory BL. Disclosures: Off Label Use: Ofatumumab is registered for treatment of CLL.

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