High-risk Burkitt Lymphoma Research Articles

R-CODOX-M/R-IVAC versus DA-EPOCH-R in patients with newly diagnosed Burkitt lymphoma (HOVON/SAKK): final results of a multicentre, phase 3, open-label, randomised trial

Patients with newly diagnosed high-risk Burkitt lymphoma are treated with high-intensity immune-chemotherapy regimens such as R-CODOX-M/R-IVAC or with lower-intensity regimens such as DA-EPOCH-R. The aim of this study was to make a formal comparison between these regimens. This multicentre, phase 3, open-label, randomised study was done in 26 clinical centres in the Netherlands, Belgium, and Switzerland. Eligible patients were aged 18-75 years with newly diagnosed high-risk Burkitt lymphoma without CNS involvement. Patients were randomly assigned to two cycles of R-CODOX-M/R-IVAC (R-CODOX-M: rituximab 375 mg/m2 on day 1 and 9, cyclophosphamide 800 mg/m2 on day 1, cyclophosphamide 200 mg/m2 on days 2-5, vincristine 1·5 mg/m2 on days 1 and 8, doxorubicin 40 mg/m2 on day 1, and methotrexate 3000 mg/m2 on day 10; R-IVAC: rituximab 375 mg/m2 on days 3 and 7, iphosphamide 1500 mg/m2 on days 1-5, etoposide 60 mg/m2 on days 1-5, and cytarabin 2000 mg/m2 on day 1 and 2) or six cycles of DA-EPOCH-R (dose-adjusted etoposide 50-124 mg/m2 on days 1-4, prednisolone 120 mg/m2 on days 1-5, vincristine 0·4 mg/m2 on days 1-4, dose-adjusted cyclophosphamide 480-1866 mg/m2 on day 5, dose-adjusted doxorubicin 10-24·8 mg/m2 on days 1-4, rituximab 375 mg/m2 on days 1 and 5). Patients older than 65 years received a dose modified R-CODOX-M/R-IVAC. All drugs were intravenous except for prednisolone, which was oral. Patients also received four intrathecal CNS administrations with cytarabin (70 mg) and four with methotrexate (15 mg). Patients were stratified by centre, leukemic disease, and HIV-positivity. The primary endpoint was progression-fee survival. All analyses were done by modified intention-to-treat, excluding randomly assigned patients who were subsequently found to have CNS involvement or diagnosis other than Burkitt lymphoma at study entry. This study is registered with the European Clinical Trial Register, EudraCT2013-004394-27. Due to a slow accrual, the study was closed prematurely on Nov 15, 2021. Between Aug 4, 2014, and Sept 17, 2021, 89 patients were enrolled and randomly assigned to receive R-CODOX-M/R-IVAC (n=46) or DA-EPOCH-R (n=43). Five patients were excluded after random assignment (three in the R-CODOX-M/R-IVAC group [one diagnosis other than Burkitt lymphoma at study entry according to local pathology and two CNS involvement] and two in the DA-EPOCH-R group [one diagnosis other than Burkitt lymphoma at study entry according to local pathology and one CNS involvement]. 84 remaining patients were included in the modified intention-to-treat analysis. 73 (87%) of 84 patients were male, 76 (90%) presented with stage III or IV disease, and nine (11%) had HIV-positive Burkitt lymphoma. Median patient age was 52 years (IQR 37-64). With a median follow-up of 28·5 months (IQR 13·2-43·7), 2-year progression-free survival was 76% (95% CI 60-86%) in the R-CODOX-M/R-IVAC group and 70% (54-82%) in the DA-EPOCH-R group (hazard ratio 1·42, 95% CI 0·63-3·18; p=0·40). There were two deaths in the R-CODOX-M/R-IVAC group (one infection [treatment related] and one due to disease progression [not treatment related]) and one death in the DA-EPOCH-R group (COVID-19 infection [treatment related]). In the R-CODOX-M/R-IVAC group, four patients went off-protocol because of toxic effects, versus none in the DA-EPOCH-R group. Patients treated with R-CODOX-M/R-IVAC had more infectious adverse events (24 [56%] of 43 patients had at least one grade 3-5 infection vs 14 [34%] of 41 patients in the DA-EPOCH-R group). The trial stopped early, but the available data suggest that while DA-EPOCH-R did not result in superior progression-free survival compared with R-CODOX-M/R-IVAC, it was associated with fewer toxic effects and need for supportive care. DA-EPOCH-R appears to be an additional valid therapeutic option for patients with high-risk Burkitt lymphoma without CNS involvement. The Dutch Cancer Society and the Schumacher-Kramer Foundation.

SAFETY AND EFFICACY OF THE “CARMEN” REGIMEN, A NEW DOSE‐DENSE SHORT‐TERM THERAPY IN PATIENTS WITH AGGRESSIVE B‐CELL LYMPHOMA AND MYC REARRANGEMENT

Introduction: Patients (pts) with aggressive B-cell lymphoma and MYC rearrangement exhibits poor outcome after R-CHOP treatment. In the last decade, these pts were treated with a new dose-dense, short-term therapy termed “CARMEN”, at several Italian Centers. Excellent efficacy and safety profile have been reported in HIV/AIDS pts with high-risk Burkitt lymphoma (BL) [Ferreri et al. BJH 2021], but its efficacy in pts with high-grade B-cell lymphoma with MYC rearrangement (HGBCL) remains to be defined. Herein, we report a retrospective series of consecutive pts with BL or HGBCL treated with CARMEN regimen. Methods: Either HIV-negative and HIV-positive pts aged 18-80 years with BL or HGBCL and MYC rearrangement positive by FISH were treated with CARMEN regimen, which includes a single 36-day induction course of sequential doses of cyclophosphamide, vincristine, rituximab, methotrexate, VP16, and doxorubicin plus intrathecal chemotherapy, followed by consolidation with HD-cytarabine ± cisplatin. Pts who did not achieve complete remission (CR) after induction received BEAM/ASCT after consolidation. Results: 63 pts (22 HGBCL;41 BL) received the CARMEN regimen (Table). Treatment was well tolerated: 56 (89%) pts completed the induction, and 55 (87%) completed the consolidation. G4 hematological toxicity during induction was neutropenia in 48 (76%) pts, thrombocytopenia in 24 (38%) and anemia in 7 (11%), which were recorded after consolidation in 34 (62%), 38 (69%) and 1 (2%) pt, respectively. G4 non hematological toxicity was uncommon: mucositis in 4 (6%) pts and tumor lysis syndrome in 1 (2%) during induction, and heart failure and bleeding in 1 (2%) pt each after consolidation. G4 infections were recorded in 4 (6%) pts during induction and in 2 (3%) after consolidation. Induction and consolidation doses were reduced in 6 (9%) and 4 (7%) pts, respectively. Seven HGBCL and 9 BL pts received ASCT, with expected tolerability. 4 HGBCL and 2 BL pts died of toxicity (sepsis in 4;respiratory failure;COVID-19), with a TRM of 9%. After induction, 18 (82%) HGBCL and 37 (90%) BL pts achieved a response, which was CR in 10 (45%) and 26 (63%) pts, respectively. After the whole treatment, 15 (68%) HGBCL pts and 32 (78%) BL pts achieved a CR, and, at a median follow-up of 54 (2-131) months, 15 (100%) HGBCL and 29 (91%) BL pts remain relapse-free, with a 5-yr PFS of 67% and 70%, respectively. 15 HGBCL and 32 BL pts are alive, with a 5-yr OS of 66% and 77%, respectively. HIV seropositivity did not modify outcome. Age and LDH level were independently associated with OS. Conclusions: With the limitations of a retrospective series, this study shows that CARMEN is a safe and active treatment both in HIVnegative and-positive pts with HGBCL and MYC rearrangement and BL. Survival figures in HGBCL pts compare favorably with results reported with R-CHOP or analogous, and are similar to those achieved in BL pts.

Treatment results of modified BFM protocol in pediatric high-risk Burkitt lymphoma.

Chemotherapy with high dose methotrexate is the mainstay of treatment for Burkitt lymphoma (BL), especially to manage central nervous system (CNS) disease. However, methotrexate administration requires close drug level monitoring for appropriate folinic acid rescue, which might not be readily available in all centers. In this study, we assessed the long-term treatment outcomes of a modified Non-Hodgkin lymphoma (NHL)-Berlin-Frankfurt-Munster (BFM) 90 regimen in pediatric high-risk BL without CNS involvement. Between 1999 and 2011, 42 patients (median age: 7 years) with advanced-stage BL were treated with modified NHL-BFM 90 regimen (methotrexate at a dose of 1 g/m2). Demographic data, stage, lactate dehydrogenase (LDH) and treatment results were retrospectively evaluated. The patients were assessed for toxicity, survival and CNS recurrence. Thirty-six patients had Stage III and six had Stage IV disease, respectively. The median LDH level was 1,432 IU/L. Four patients died of infectious and metabolic complications. One patient had local recurrence at the 48 < sup > th < /sup > month of the follow-up and he is in the second remission for 72 months. In Kaplan-Meier analysis, the overall survival and event-free survival rates at 10 years were found as 90 % and 88 %, respectively. None of our patients died of treatment failure. The administration of the reduced dose of methotrexate seems to not compromise treatment success nor increase the risk of CNS recurrence in high-risk BL without CNS involvement. The limitation of the study is that it is not randomized. Our treatment scheme might be considered for centers without methotrexate measurement facility.

Favourable outcomes for high-risk Burkitt lymphoma patients (IPI 3-5) treated with rituximab plus CODOX-M/IVAC: Results of a phase 2 UK NCRI trial.

IntroductionOutcomes after frontline treatment of Burkitt lymphoma (BL) have improved with the introduction of dose‐intense chemotherapy regimens, such as CODOX‐M/IVAC. While rituximab has increased survival rates for most forms of high‐grade B‐cell lymphoma, there has previously been hesitancy about incorporating it into BL treatment, partly due to concerns about increased toxicity. Prospective data using the standard dose CODOX‐M/IVAC regimen in combination with rituximab are lacking. We conducted a single‐arm phase 2 trial to assess the efficacy and toxicity of R‐CODOX‐M/R‐IVAC.MethodsEligible patients were aged 18–65 years, with newly diagnosed BL with MYC rearrangement as the sole cytogenetic abnormality, and high‐risk disease, defined by an International Prognostic Index (IPI) score of 3‐5. Patients received two cycles of R‐CODOX‐M chemotherapy alternating with two cycles of R‐IVAC, followed by two further cycles of rituximab alone. The primary endpoint was 2‐year progression‐free survival.ResultsThirty‐eight patients were registered but after central pathology review, 27 patients had confirmed BL and commenced study treatment. Median age was 35 years, 14.8% patients had central nervous system involvement and 18.5% were HIV positive. Twenty‐two (81.4%) patients completed four cycles of chemotherapy. There were two treatment‐related deaths (7.4%). Two‐year progression‐free and overall survival rates were 77.2% (90% confidence interval [CI]: 56.0‐89.0) and 80.7% (90% CI: 59.6‐91.5), respectively.ConclusionsThis prospective trial demonstrates excellent survival rates with R‐CODOX‐M/R‐IVAC in a high‐risk BL cohort. It provides reassuring evidence regarding the feasibility of this regimen and also provides a benchmark for future studies.

Clinical analysis of a modified LMB89 Group C regimen in the treatment of pediatric high-risk Burkitt lymphoma

目的分析改良LMB 89 C组方案治疗高危儿童伯基特淋巴瘤的疗效。方法对2007年1月至2017年4月接受改良LMB 89 C组方案治疗的172例初治高危伯基特淋巴瘤患儿进行回顾性分析。结果全部172例患儿中位发病年龄6（1~14）岁，男144例（83.7%），女28例（16.3%），St.Jude分期Ⅱ、Ⅲ、Ⅳ期分别为2例（1.2%）、54例（31.4%）、116例（67.4%），46例（26.7%）为白血病期，52例（30.2%）存在中枢神经系统（CNS）侵犯。危险度分组：C1组（CNS1，无睾丸/卵巢侵犯）65例，C2组[CNS2和（或）睾丸/卵巢侵犯]55例，C3组（CNS3）52例。145例联合应用利妥昔单抗。10例未缓解并进展至死亡，5例复发，治疗相关死亡率为2.9%。中位随访时间36.0（0.5~119.0）个月，全组3年总生存（OS）率为（88.9±2.4）%、3年无事件生存（EFS）率为（87.9±2.6）%。C1、C2、C3组3年EFS率分别为（96.9±2.1）%、（90.9±3.9）%、（73.4±6.5）%，C3组低于C1组（χ2=12.939，P=0.001）和C2组（χ2=6.302，P=0.036）。C3组中利妥昔单抗联合化疗、单纯化疗患儿的3年EFS率分别为（79.3±6.8）%、（44.4±16.6）%（χ2=5.972，P=0.015）。多因素分析结果显示，临床分期Ⅳ期（包括白血病期）、中期评估有瘤灶为预后不良的危险因素[HR=4.241（95%CI 1.163~27.332），P=0.026；HR=32.184（95%CI 11.441~99.996），P<0.001]。结论改良LMB 89 C组方案对于高危儿童伯基特淋巴瘤具有较理想的疗效。

Comparative Study of Obinutuzumab (GA101) Vs. Rituximab Against CD20+ rituximab-Sensitive and -Resistant Burkitt (BL) and Acute Lymphoblastic Leukemia (B-ALL): Potential Targeted Therapy in Patients with High Risk BL and Pre-B-ALL

Background: Aggressive non-Hodgkin lymphoma (NHL) represents >90% of all NHL that occur in children and adolescents. Among all NHLs, Burkitt Lymphoma (BL) is the most common NHL in children and adolescents and has an excellent prognosis (≥80% 5 yrs, EFS) following short but intense multi-agent chemotherapy (Cairo et al. Blood, 2007). Patients who relapse with CD20+ B-NHL and B cell Acute lymphoblastic leukemia (B-ALL) have a dismal prognosis, often associated with chemotherapy resistance and may require alternative therapeutic strategies (Cairo et al. JCO, 2012, Barth/Cairo et al. BJH, 2013). Rituximab (RTX) in combination with FAB 96 chemotherapy is a safe and well-tolerated and is associated with >90% EFS in children with newly diagnosed and advanced mature B-Cell NHL (Goldman/Cairo et al. Leukemia, 2013). Resistance to RTX, however, may predispose patients with CD20+ B-NHL/ALL to an increase risk of relapse and/or disease progression (Barth/Cairo et al. BJH, 2012; Tsai et al. Cl. Can. Res, 2012,). Obinutuzumab, a novel glycoengineered type II CD20 antibody, has been shown to enhance cell death and ADCC vs. RTX (Herter et al, Clinc Canc Res, 2013), and was recently approved by FDA and EMA for first line treatment of CLL in combination with chlorambucil.Objective: To evaluate anti-tumor activity of obinutuzumab vs RTX against RTX resistant and sensitive BL and pre-B-ALL tumor targets in-vitro and in-vivo in xenografted NSG mice.Methods: Raji (CD20+) and Loucy (T-ALL, CD20-), (ATCC, Manhass, VA), U698-M (CD20+, DSMZ, Germany) and Raji-4RH (provided by M. Barth, Roswell Park Cancer Institute) were cultured in RPMI with 10% FBS. For in-vitro studies, tumor cells were incubated with 100 µg/ml obinutuzumab (supplied by Christian Klein, PhD, Roche Research & Early Development, Zurich), and/or RTX for 24 hrs. Cell death was evaluated by staining with AnnexinV/7AAD and analysis by flow-cytometry. Loucy cells (CD20-) were used as the negative control. ADCC were performed with K562-IL-15-41BBL expanded NK cells (Ayello/Cairo et al. ASH, 2010) at 20:1 effector: target ratio (E: T, n=3) using an europium release assay (Perkin-Elmer).The lentiviral construct, pSico PolII-eGFP-Luc2, was transfected into Raji, Raji 4RH (RTX resistant), U698M and Loucy for in vivo evaluation by BLI. Six to 8 week old female NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ), mice, bred in-house under pathogen free conditions, were divided into 5 groups: PBS only (control), isotype control (IgG), obinutuzumab 10 mg/kg, obinutuzumab (30 mg/kg), and RTX (30 mg/kg).Mice were xenografted with intravenous injections of Luc+ Raji, Raji4RH, U698M and Loucy cells at 5x106 tumor cells/mouse. 6-8 days after tumor cell injection, mice were then injected every 7 days with the respective therapy for 8 weeks. Mice were monitored for tumor burden and survival for up to 12 weeks ( approx. 80 days) via bioluminescent imaging (BLI) using the IVIS Spectrum system.Results: Obinutuzumab compared to RTX (100 mg/ml, 24hrs), significantly enhanced cell death in Raji 45.1±3.3% vs 32.7±6.8%, (p=0.005), Raji4RH 15.8±2.2% vs 2.1±1.5% (p=0.001) and U698-M 40.5±2.9 % vs 26.36±2.6% (p=0.001) n=6. Obinutuzumab vs RTX also elicited a significant increase ADCC with K562-IL15-41BBL expanded NK cells, in Raji 73.8±8.1% vs 56.81±4.6% (p=0.001), Raji-4RH 40.0±1.6% vs 0.5±1.1%, (p=0.001), and U-698-M 70.0±6 % vs. 45.56± 0.1% (p=0.001) n=3.Further, we found that, in vivo, obinutuzumab was significantly more effective than RTX when administered at the same doses in BL (RTX resistant/sensitive) and pre-B-ALL xenografts. Overall survival in mice receiving 30 mg/kg of obinutuzumab was significantly increased when compared to mice receiving 30 mg/kg of RTX in BL; Raji (p=0.05), Raji4RH (p=0.024) and U698-M (p=0.03) (Figure1: A, B and C).Conclusion: Obinutuzumab significantly enhances cell death and NK mediates ADCC in sensitive and RTX resistant CD20+ B-NHL and B-ALL compared to RTX. These preliminary studies also demonstrate that RTX sensitive/resistant BL and pre-B-ALL xenografted mice display significantly increased survival when given 30 mg/kg of obinutuzumab and decreased tumor burden in BL and Pre-B-ALL xenografts compared to an equal dose of RTX. Obinutuzumab may be a novel agent to investigate as adjuvant therapy in patients with relapsed refractory CD20+ B-NHL and/or B-ALL. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A multicenter phase II study incorporating high-dose rituximab and liposomal doxorubicin into the CODOX-M/IVAC regimen for untreated Burkitt's lymphoma

BackgroundDespite improvement with intensive multi-agent chemotherapy, 2-year progression-free survival (PFS) rates for adults with high-risk Burkitt's lymphoma (BL) remains <55%. Patients and methodsWe conducted a phase II trial for newly diagnosed classic BL utilizing liposomal doxorubicin (Adriamycin) in lieu of doxorubicin and incorporating intravenous rituximab (at 500 mg/m2 twice/cycle) into the CODOX-M/IVAC regimen. Correlative analyses included paired serum and cerebrospinal fluid (CSF) rituximab levels and close examination of cardiac function. ResultsAmong 25 BL patients, the median age was 44 years (23–70) and 4 patients were HIV positive. There were 20 high-risk and 5 low-risk patients. At baseline, 40% of high-risk patients had bone marrow involvement, 35% had bulky disease and 15% had central nervous system involvement. The overall response rate was 100% (complete remission 92%). At 34-month median follow-up, the 2-year PFS and overall survival (OS) rates for all patients were 80% and 84%, respectively (low-risk: both 100%; high-risk: 76% and 81%, respectively). Furthermore, the 2-year PFS, OS, and disease-specific survival (DSS) rates for high-risk, HIV-negative patients were 84%, 89% and 100%, respectively. Adverse events (AEs) appeared to be consistent with prior CODOX-M/IVAC data, although there were several grade 3 cardiac events noted (all declined ejection fraction without clinical symptoms). The mean serum rituximab levels at 24 h after cycles 1 and 3 for patients without relapse were 258 and 306 μg/ml, respectively, versus 131 and 193 μg/ml, respectively, for patients with early progression (P = 0.002 and 0.002, respectively). The mean CSF rituximab levels for all patients were 0.11 and 0.24 μg/ml, respectively, at cycle 1 (24/72 h), which equated to serum:CSF ratios of 0.05% and 0.20%, respectively. ConclusionsThe integration of rituximab into CODOX-M/IVAC for adult BL was feasible and tolerable, while changes in cardiac function warrant continued examination. This regimen was associated with excellent survival rates for HIV-negative BL. Further investigation of the predictive value of serum rituximab is needed. Clinicaltrials.gov NCT00392990.

Corrections to "A multicenter phase II study incorporating high-dose rituximab and liposomal doxorubicin into the CODOX-M/IVAC regimen for untreated Burkitt's lymphoma".

Background Despite improvement with intensive multi-agent chemotherapy, 2-year progression-free survival (PFS) rates for adults with high-risk Burkitt's lymphoma (BL) remains <55%.

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

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

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

To study minimal disseminated disease (MDD) in children with Burkitt's lymphoma (BL) and to determine its impact on prognosis. 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. 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). 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.

Minimal Disseminated Disease Is An Independent Poor Prognosis Marker Among High Risk Burkitt's Lymphoma Patients .

Abstract 2944Poster 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.

An increased frequency of 13q deletions detected by fluorescencein situhybridization and its impact on survival in children and adolescents with Burkitt lymphoma: results from the Children’s Oncology Group study CCG-5961

Burkitt lymphoma (BL), an aggressive B-cell malignancy, is often curable with short intensive treatment regiments. Nearly all BLs contain rearrangements of the MYC/8q24 region; however, recent cytogenetic studies suggest that certain secondary chromosomal aberrations in BL correlate with an adverse prognosis. In this multi-centre study, the frequency and impact on clinical outcome of del(13q) and +7 in addition to MYC rearrangements as detected by fluorescence in situ hybridization (FISH) in children and adolescents with intermediate and high-risk BL registered on Children's Cancer Group study CCG-5961 were investigated. Analysis with 13q14.3 and 13q34 loci specific probes demonstrated deletions of 13q in 38/90 (42%) cases. The loss of either 13q14.3 or 13q34 alone occurred in 14% and 8% respectively, while 20% exhibited loss of both regions. Gain of chromosome 7 was observed in 7/68 (10%) cases and MYC rearrangements were detected in 84/90 (93%). Prognostic analysis controlling for known risk factors demonstrated that patients exhibiting loss of 13q, particularly 13q14.3, had a significant decrease in 5-year overall survival (77% vs. 95%, P = 0.012). These observations indicate that del(13q) occurs in childhood BL at frequencies higher than previously detected by classical cytogenetics and underscores the importance of molecular cytogenetics in risk stratification.

HYPERKALÆMIA, A SEQUEL TO CHEMOTHERAPY OF BURKITT'S LYMPHOMA

Hyperkalæmia developing within 48 hours of chemotherapy was found in retrospective analysis in five of twenty-two evaluable cases of Burkitt's lymphoma in patients treated in the U.S.A. This syndrome was fatal in two of these five patients, and was the suspected cause of sudden post-chemotherapeutic death in two further cases in which serum-potassium levels were not recorded. Clinical and animal studies suggest that hyperkalæmia is related to sudden lysis of large volumes of tumour. Patients at serious risk were found to be those with large tumour masses and/or impairment of renal function. Close observation, parenteral hydration, and diuretic therapy, control of hyperuricæmia, reduction of the initial dose of chemotherapy, and, if necessary, dialysis are suggested during the initial therapy of these high risk Burkitt lymphoma patients.