Advanced Stage Burkitt Lymphoma Research Articles

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.

Advanced Burkitt Lymphoma in Sub-Saharan Africa Pediatric Units: Results of the Third Prospective Multicenter Study of the Groupe Franco-Africain d'Oncologie Pédiatrique.

PURPOSETo evaluate the results of an intensive polychemotherapy regimen for Burkitt lymphoma (BL) in sub-Saharan African pediatric centers.PATIENTS AND METHODSChildren with advanced-stage BL (stages II bulky, III, and IV) treated with the GFAOP–Lymphomes Malins B (GFALMB) 2009 protocol in 7 centers between April 2009 and September 2015 were prospectively registered. Treatment regimen contained a prephase with cyclophosphamide followed by 2 induction courses (cyclophosphamide, vincristine, prednisone, high-dose methotrexate [HDMTX]), 2 consolidation courses (cytarabine, HDMTX), and a maintenance phase only for stage IV. HDMTX was given at the dose of 3 g/m2.RESULTSFour hundred patients were analyzed: 7% had stage II bulky, 76% stage III, and 17% stage IV disease. Median age was 7.3 years, and sex ratio was 1.9:1 (male:female). A total of 221 patients received the whole protocol treatment and 195 achieved complete remission (CR), 11 of them after a second-line treatment. Treatment abandonment rate was 22%. One hundred twenty-five patients died, of whom 49 deaths were related to treatment toxicity. A total of 275 patients are alive, including 25 despite treatment abandonment, but only 110 are known to be in CR with a follow-up > 1 year, indicating a high rate of loss to follow-up. Twelve-month overall survival (OS) was 60% (95% CI, 54% to 66%) and 63%, 60%, and 31%, respectively, for stage II bulky, III, and IV. Patients with stage III disease who started second induction course within 34 days had OS of 76%, versus 57% (P = .0062) beyond 34 days.CONCLUSIONThe GFA-LMB2009 protocol improved patients’ survival. Early dose intensity of treatment is a strong prognostic factor. Improving supportive care and decreasing loss to follow-up are crucial.

HIV-Associated Burkitt Lymphoma: Case Report and Literature Review

IntroductionHIV associated Burkitt lymphoma (BL) is a highly aggressive lymphoma. Compared to other AIDS related non-Hodgkin lymphoma's its clinical presentation is less predictable and characterized by rapid clinical changes. The paradigm shift to treat HIV associated disease with highly effective intensive chemotherapy regimens while managing immunosuppression has made it possible to achieve remission and long-term survival. Southern Louisiana has one the of the highest incidence rates of HIV and cancers in the US. The authors present a challenging case of a 33-year old HIV+ male from southern Louisiana with advanced stage BL. The patient presented with advanced disease and a poor performance status. His initial providers recommended palliation only and significant education was needed to allow aggressive treatment. The patient tolerated induction chemotherapy and remains in remission. This is a case based review of local and nationwide epidemiology and the trial data supporting different treatment options for HIV associated Burkitt lymphoma. CaseOur patient is a 33 year-old male who presented with severe cachexia, poor performance status and clinical symptomatic cord compression. He was diagnosed with advanced stage Burkitt lymphoma including bone marrow involvement. His CD4 count was 277 with an HIV viral load of 571,000 copies/mL. Although he had a poor performance status and his primary team favored palliation only he underwent induction chemotherapy with 4 cycles of infusional dose adjusted R-EPOCH with IT CNS chemoprophylaxis. HAART therapy with efavirenz/emtricitabine/tenofovir was started during his initial admission. He tolerated this regimen well, clinically dramatically improved being independent in his ADL/IADLs, and remains in remission. DiscussionThe pathogenesis of HIV-associated Burkitt lymphoma is linked to oncogenic virus co-infection (40% EBV association) and chronic HIV antigen stimulation that provoke expansion of polyclonal B-cells. This leads to oncogenic chromosomal translocations - most notably t(8;14) causing constitutive expression of oncogene c-Myc. HIV patients have a 60 to 200-fold increased incidence of NHL. Relative risk for BL in HIV patients is 261-fold higher compared to the general population. Unlike the nationwide reported 19 per 100,000 person-years, data from a large HIV clinic in southern Louisiana continues to show an incidence rate of 23 per 100,000 person-years. Louisiana continues to have comparatively high incidence rates in HIV (4th in US) and cancer (11th in US) with the highest rates in southern Louisiana parishes. It is important for community physicians, especially in these areas, to feel more confident when treating these HIV associated malignancies.Historically highly immunosuppressive chemotherapy has been avoided in HIV patients with lymphoma as studies in the 1990's showed increased toxicity. The addition of the monoclonal C20 antibody rituximabin the treatment of AIDS associated NHLs was also controversial, as trial results showed increase infectious death rates. However, these clinical trials confirmed similar death rates from infections in individuals with a CD4 count >50. In addition concomitant use of HAART with chemotherapy has improved overall survival. Although the more dose intense Burkitt regimens have not been studied extensively in HIV-associated BL, CODOX-M/IVAC and DA-EPOCH +/- Rituximab (depending on CD4 count) have shown good efficacy and tolerance and are treatment regimens of choice this disease. A recent trial with 14 patients with HIV associated BL receiving RD-CODOXM/IVAC had 86% progression free survival rate at 1 year; patients receiving concomitant HAART had 100% PFS rate at 1 year. In another trial, 10 HIV associated BL patients receiving DA-EPOCH-R showed a 100% overall survival rate at 57 months. ConclusionHIV associated Burkitt lymphoma should be treated with HAART and high dose chemotherapy. Long-term remission has been shown with regimens including CODOX-M/IVAC and DA-EPOCH +/-Rituximab (R use discouraged in low CD4 counts). This case based report outlines the relatively high prevalence of disease in Southern Louisiana and emphasizes that remission is possible in patients with poor performance status and advanced disease. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Clinical characteristics, treatment and outcome of childhood Burkitt's lymphoma at the Uganda Cancer Institute

Burkitt's lymphoma (BL) is a major cause of death among Ugandan children. We studied clinical characteristics and outcomes of childhood BL over time at the Uganda Cancer Institute (UCI). A total of 1217 children (766 boys, 451 girls, mean age 6.69 years) diagnosed with BL between 1985 and 2005 were included. There were no significant changes in the proportion of boys and girls diagnosed, or in mean age at diagnosis. Facial tumor (n=945, 77.65%) and abdominal disease (n=842, 69.19%) were the most common presentations. The proportion of children presenting with hepatic mass, malignant pleocytosis, and advanced-stage (stage C and D) BL increased during the study period (P<0.01). A total of 1085 children out of 1206 (89.97%) received at least one cycle of chemotherapy, and 832 of 1099 (75.71%) demonstrated objective response (i.e. complete or partial remission). The most common symptoms at BL diagnosis were fever (n=621, 51.03%), anemia (n=593, 48.73%), and weight loss (n=588, 48.32%). Significant increases in the proportion of children with fever, and significant changes in the proportion of children with anemia, night sweats and severe infection were observed. HIV positivity was 3.87%, but no substantial differences in the proportion of HIV-positive children were observed. Mortality was not significantly different over time: it was similar in boys and girls, higher in older children (compared with younger ones), in those with advanced-stage BL, and HIV-positive children, but lower in children with facial tumors compared with other tumor presentations, and among those who received chemotherapy.

Abstract B93: Clinical characteristics, treatment, and outcome of childhood Burkitt's lymphoma in the Uganda Cancer Institute

Abstract Introduction: Burkitt's lymphoma (BL), the most common type of childhood cancer in Africa, is a major cause of cancer death among Ugandan children. We conducted a study about trends in the clinical characteristics and outcome of childhood BL over time in the Uganda Cancer Institute (UCI). Subjects and methods: Medical records of individuals with BL aged less than 18 years admitted to the UCI between 1985 and 2005 were reviewed. The study period was divided into the following periods of diagnosis: 1985–1990, 1991–1995, 1996–2000, and 2001–2005. Results: Of the 1,237 medical records of children with BL obtained from UCI patient registers, 1,217 had sufficient recorded information and could be included in our study: 766 (62.94%) boys and 451 (37.60%) girls; the mean age at diagnosis was 6.69 years. There were no significant changes in the proportion of boys and girls diagnosed, nor in the mean age at diagnosis throughout the study period. The most common tumor presentations were facial tumor (77.65%), abdominal disease (69.19%), systemic presentation with generalized lymphadenopathy (42.07%), and hepatic mass (37.80%). Presentation with hepatic mass (p=0.001) and malignant pleocytosis (p&amp;lt;0.001) increased during the study period, whereas other tumor presentations remained similar. Most children presented with stage C (32.12%) or D (26.67%) BL, and there was an increase in the proportion of children presenting with advanced-stage BL during the study period (p=0.005). Overall 89.97% of children in the present study received at least one cycle of chemotherapy, and overall remission was observed in 75.71% of them. The most common symptoms at BL diagnosis were fever (51.03%), anemia (48.73%), and weight loss (48.32%). Significant increases in the proportion of children presenting with fever were observed during the study period (p=0.007), as well as significant changes in the proportion of children presenting with anemia, night sweats (p&amp;lt;0.001 each) and severe infection (p=0.002) between periods of diagnosis. HIV positivity was 3.87%, and no substantial differences in the proportion of children who where HIV positive were revealed in different periods of diagnosis (p=0.205). Five-year mortality was not significantly different during the study period. Conclusions: Mortality was similar in boys and girls, but higher in older children with BL compared to younger ones. Mortality was lower in children who presented with facial tumors compared to other tumor presentations, and higher in those presenting with advanced-stage BL and HIV-positive children. Mortality was substantially lower among those who received chemotherapy. Citation Information: Cancer Prev Res 2011;4(10 Suppl):B93.

Treatment of a CNS relapse while on therapy for Burkitt lymphoma

The treatment of Burkitt lymphoma (BL) has come a long way in regards to survival, with the majority of even the advanced stage patients being cured. The prognosis for relapsed BL remains dismal, despite attempts to further intensify therapy. We report on a patient with advanced stage BL who relapsed in the CNS while on therapy. The patient was successfully treated with an intensified regimen based on a concentration times time (C x T) CNS-directed model. Our experience shows both the feasibility and efficacy of such an approach in a patient with an otherwise very poor prognosis.

Abdominal compartment syndrome in a newly diagnosed patient with Burkitt lymphoma

We present the radiological and clinical aspects of a patient with advanced-stage Burkitt lymphoma who presented with an acute abdomen complicated by abdominal compartment syndrome.

Burkitt lymphoma in adults: a prospective study of 72 patients treated with an adapted pediatric LMB protocol

Background: We conducted a phase II study to evaluate in 72 adult patients the efficacy of the intensive LMB chemotherapy regimen, previously reported by the Société Française d'Oncologie Pédiatrique for children with Burkitt lymphoma and L3 acute lymphoblastic leukemia.Patients and methods: Treatment began with a prephase (low-dose steroids, vincristine and cyclophosphamide), except in patients with low tumor burden. Group A (resected stage I and abdominal stage II disease) received three courses of vincristine, cyclophosphamide, doxorubicin and prednisone. Group B (not eligible for groups A or C) received five courses of chemotherapy comprising high-dose methotrexate, infusional cytarabine and intrathecal (IT) methotrexate. Group C (patients with central nervous system and/or bone marrow involvement with <30% of blast cells) received eight courses containing intensified high-dose methotrexate, high-dose cytarabine, etoposide and triple IT injections.Results: The 2 year event-free survival and overall survival rates for the 72 patients were 65% and 70%, respectively. Age ≥33 years and high lactate dehydrogenase value were associated with a shorter survival. No response to COP was also associated with a poor outcome in group B.Conclusion: Patients with advanced-stage Burkitt lymphoma, including those with bone marrow and/or central nervous system involvement, can be cured with a short-term intensive chemotherapy regime tailored to the tumor burden.

HiC-COM: a 2-month intensive chemotherapy regimen for children with stage III and IV Burkitt's lymphoma and B-cell acute lymphoblastic leukemia.

We designed a protocol that included 2 months of intensive Cytoxan (cyclophosphamide; Bristol-Myers Co, Evansville, IN), high-dose methotrexate (MTX), high-dose cytarabine (ara-C), and vincristine (HiC-COM) to improve event-free survival (EFS) for patients with advanced-stage Burkitt's lymphoma and B-cell acute lymphoblastic leukemia (ALL). We also wished to test the feasibility of rapidly cycling Cytoxan and high-dose ara-C based on signs of early marrow recovery. Twenty patients including 12 with stage III Burkitt's lymphoma and eight with stage IV Burkitt's lymphoma or B-cell ALL were entered onto this pilot study. The rate of complete remission was 95%. Four patients have relapsed. The 2-year actuarial EFS was 75% (median follow-up, 37 months). Two of the initial five patients developed transverse myelitis, which we believe may have been secondary to the concomitant administration of intrathecal (IT) and high-dose systemic ara-C. We conclude that this short but intensive regimen is highly effective for patients with advanced Burkitt's lymphoma and B-cell ALL. EFS has improved over previous less intensive regimens, and is comparable to regimens of longer duration.

Bacterial contamination rate of urine collected in a urine bag from healthy non-toilet-trained male infants

6. Gill PS, Levine AM, Krailo M, et al. AIDS-related lymphomas: results of prospective trials. J Clin Oncol 1987;5:1322-8. 7. Classification system for human immunodeficiencyvirus (HIV) infection in children under 13 years of age. MMWR 1987; 36:225-30,35. 8. Patte C, Philip T, Rodary C, et al. Improved survival rate in children with stage III and IV B ceil non-Hodgkin's lymphoma and ieukemin ~:~ing multi agent che~notbera~7: results of a study of 114 children from the French Pediatric Oncology So, ciety. J Clin Oncol 1986;4:1219-26. 9. Murphy SB, Bowman WP, Abromowitch M, et al. Results of treatment of advanced-stage Burkitt's lymphoma and B-cell (SIg+) acute lymphoblastic leukemia with high-dose fraction. ated cyclophosphamide and coordinated high-dose metholrcx. ate and cytaraN~e..! Cli~ On'co! 1,986:4:!732 9.

Results of treatment of advanced-stage Burkitt's lymphoma and B cell (SIg+) acute lymphoblastic leukemia with high-dose fractionated cyclophosphamide and coordinated high-dose methotrexate and cytarabine.

To address the problem of historically poor results in the treatment of children with advanced-stage Burkitt's lymphoma and B cell (SIg+) acute lymphoblastic leukemia (ALL), an intensive chemotherapy regimen was devised using the most effective single agents in high-dose short courses. Treatment commenced with a fractionated schedule of intravenous (IV) cyclophosphamide (300 mg/m2 every 12 hours for six doses) followed immediately by Adriamycin (50 mg/m2) and vincristine (1.5 mg/m2) with combined intrathecal (IT) methotrexate and cytarabine. Predictably, this treatment produced virtually complete disappearance of all tumor and profound myelosuppression. Immediately on hematologic recovery, IV high-dose methotrexate (1,000 mg/m2 over 24 hours) followed by IV cytarabine (400 mg/m2 over the next 48 hours) was administered with leucovorin rescue and repeated IT treatments. The treatment sequence described above is repeated four times, with the dose of cytarabine doubled in succeeding courses, up to 3,200 mg/m2. The entire planned therapy required approximately 24 weeks. Since 1981, we treated a total of 29 children with this approach, 19 of whom had massive unresectable intraabdominal tumor. According to initial extent of disease, 17 were classified as stage III, four as stage IV non-Hodgkin's lymphoma (NHL), and eight as B cell ALL. Eight of the 12 patients with stage IV NHL or B cell ALL had initial involvement of the CNS. Twenty-seven of 29 patients (93%) attained a complete remission. Fourteen of 17 stage III NHL patients remain disease free, for periods ranging from 3+ months to 4 1/2+ years. The actuarial estimate of the proportion of stage III patients remaining disease free at 2 years is 81%. Results in patients with initial involvement of the CNS and/or marrow are much less favorable, with only two of ten patients who attained remission apparently being cured. In addition to stage, the initial serum lactic dehydrogenase (LDH) level emerged as a prognostic indicator, higher levels (over 1,000 IU/L) being associated with the worst prognosis (P less than .05). Major toxicity consisted of severe hematopoietic suppression and febrile episodes associated with neutropenia. We conclude that this treatment is highly effective for advanced-stage Burkitt's tumors in children free of initial CNS involvement.