Burkitt’s Lymphoma

Burkitt’s Lymphoma Jenny Wilson Dept Radiation Oncology Pretoria Academic Hospital IAEA Paed Oncol Madagascar March 2007 Burkitt’s Lymphoma     Identified Dennis Burkitt 1957 in Uganda Small noncleaved cell lymphoma (WHO) Classic starry sky appearance Doubling time 24 – 48 hrs IAEA Paed Oncol Madagascar March 2007 Endemic Burkitt’s lymphoma induced translocations – immortalisation lymphocytes  Areas of high malarial prevelance  EBV   Increase B cell stimulation Reduce T cell activity  Translocation c-myc on ch8 and one of the immunoglobulin light or heavy chain loci on ch2,14 and 22 IAEA Paed Oncol Madagascar March 2007 Demographics Endemic Burkitt’s Lymphoma million children in endemic belt  1-4 / 10 000 children  >50% childhood Ca in endemic areas  M>F  40-100/ IAEA Paed Oncol Madagascar March 2007 Clinical Presentation Endemic Burkitt’s genome present 96%  Av age 5 - 7  60% facial  Abdo 20-40%  Bone marrow 7-25 %  CNS 20-39 % IAEA Paed Oncol Madagascar March 2007  EBV Sporadic Burkitt’s Lymphoma  Av age 11  90% abdominal involvement  Jaw mass 14%  Bone marrow 21%  CNS – 11% IAEA Paed Oncol Madagascar March 2007 Staging Investigations diagnosis  Bone marrow  CSF cytology  CXR  FBC  Blood chem, renal fxns, LDH  CT scan – local and abdo/pelvis IAEA Paed Oncol Madagascar March 2007  Histological Staging Burkitt’s Murphy /Modified St Jude for childhoodNHL l ll A single tumor ( extranodal) or single anatomic area (nodal) with exclusion mediastinum and abdomen A single tumor ( extranodal) with regional nodal involvement Two or more nodal areas on same side diaphragm Two single (extranodal) tumours with/withoudal regional nodes on same side diaphragm Primary GIT tumor (usually ileocaecal) +/-associated mesenteric nodes only Two single tumors ( extranodal) on opposite sides diaphragm Two or more nodal areas above and below diaphragm Primary intrathoracic tumors Extensive primary intraabdominal disease All paraspinal or epidural tumors regardless of other tumor sites Bone marrow / CNS involvement IAEA Paed Oncol Madagascar March 2007 lll IV Prognostic factors Burkitt’s lymphoma  Extent of disease  CNS involvement  LDH  Age IAEA Paed Oncol Madagascar March 2007 Prognostic factors Burkitt’s lymphoma Survival by marrow involvement M1<5% 5%25% IAEA Paed Oncol Madagascar March 2007 Cairo 2003 Prognostic factors Burkitt’s lymphoma Survival by LDH IAEA Paed Oncol Madagascar March 2007 Cairo 2003 Prognostic factors Burkitt’s lymphoma Survival by CNS inolvement IAEA Paed Oncol Madagascar March 2007 Cairo 2003 Prognostic factors Burkitt’s lymphoma Survival by Age IAEA Paed Oncol Madagascar March 2007 Cairo 2003 Burkitt’s Lymphoma: Initial Cyclo based Chemotherapy  Single agent low dose cyclo : 1965 – Burkitt reported 4/6 pts with facial disease in CR after single dose cyclophos 40mg/m2  Limited disease : 40mg/m2 / 14d • H&N – 66% 5 yr survival • Abdomen – 33% 5yr survival  Extensive disease – no long term survivors  COM +/- P regimens  25% - 35% overall survival in Africa IAEA Paed Oncol Madagascar March 2007 Burkitt’s chemotherapy: trials  Over time the intensity of treatment and the success rate increased  More intense and more contracted treatment with high doses of both methotrexate and Ara-C resulted in better control rates with long term overall CR >80%  High complication rate with need for support   Haematological toxicity Tumor lysis syndrome IAEA Paed Oncol Madagascar March 2007 Tumor Lysis syndrome  This must be expected in all children with a high tumor burden  Hypertension and CCF possible  Direct kidney involvement or ureteric compression in 2030% at Dx  Pre-emptive alkaline diuresis with a uricolytic must be started before onset of chemotherapy  In the setting of TLS gluc/insulin infusions with Ca++ supplementation should be added  Ideally renal functions and electrolytes should be monitored at least daily  In the absence of dialysis lower slower doses of chemotherapy allow therapy. IAEA Paed Oncol Madagascar March 2007 Olowu A.Pediatr Blood Cancer 2006:46:446-453 Burkitt’s chemotherapy – CCG trials 1997 – 1995 407 9ts 551 – “orange regime” vs LMB89 503 D-COMP vs COMP 552 –Hi dose CHOP,AraC,M,E top,6TG 551 – COMP vs 10 drug LSA2L2 IAEA Paed Oncol Madagascar March 2007 Cairo 2003 Burkitt’s Lymphoma : LMB89 SFOP trial  Risk    stratification ( 451 eligible) (52) (386) (123) Grp A complete resection stage l /abdo ll Grp B all the rest Grp C any CNS involvement >25% blasts in bone marrow IAEA Paed Oncol Madagascar March 2007 SFOP trial 579 pts 89-96 IAEA Paed Oncol Madagascar March 2007 LMB89 pt characteristics IAEA Paed Oncol Madagascar March 2007 Patte et al Blood 2001 LMB 89 SFOP trial IAEA Paed Oncol Madagascar March 2007 SFPO trial LMB89 IAEA Paed Oncol Madagascar March 2007 Patte et al Blood 2001 Toxicity MLB89  Treatment  toxicity deaths 7 (1.5%)  Overall     each pt experienced 2.5 RBC transfusion 1.7 platelet transfusion 3 episodes febrile neutropaenia 1 episode G3/4 mucositis IAEA Paed Oncol Madagascar March 2007 OK in Africa ?  Hesseling  set up several trials in Malawi using LMB89 but lower doses chemo Initially removed Adria and reduced other chemo Still had mortality 25%  IAEA Paed Oncol Madagascar March 2007 Hesseling P, Pediatr Blood Cancer 2005;44:245-250 Hesseling second run  Initially d1&8 (lll/lVl) 300mg Cyclo COMP d22+36 1mg Vinc ( 2mg vinc d8 ll/lll 60mg pred 500mg cyclo 2mg vinc 60mg prednisone 2mg methotrexate IAEA Paed Oncol Madagascar March 2007 Hesseling 2nd run deaths shortly after therapy  6 avoidable    14 3 undertreated 3 parental refusal  33% in remission at 12 months IAEA Paed Oncol Madagascar March 2007 Cyclophosphamide as monotherapy 107 pts 15 unconfirmed Dx 92 evaluable Av age 7. 64% H+N 73 traced 40 alive 33 died mean follow up 59.5mo (29 – 104) IAEA Paed Oncol Madagascar March 2007 Kazembe 2003 Burkitts and HIV Survival pre HAART IAEA Paed Oncol Madagascar March 2007 Lim 2005 Burkitts and HIV Survival post HAART Lim 2005 IAEA Paed Oncol Madagascar March 2007 Radiotherapy in Burkitt’s Lymphoma ? palliative  Single fraction 3-8Gy   Essentially Repeat if needed IAEA Paed Oncol Madagascar March 2007 IAEA Paed Oncol Madagascar March 2007