DIAGNOSIS INITIAL EVALUATION ESSENTIAL: Hematopathology review of all slides with at least one paraffin block representative of the tumor. Rebiopsy if consult material is nondiagnostic. FNA s are generally inadequate. Recommend core or excisional biopsy. Adequate immunophenotyping to establish diagnosis - Paraffin Panel: - CD3, CD10, CD20, CD45 (LCA), Ki-67, BCL2, BCL6, and TdT - Flow cytometry immunophenotyping (optional if paraffin IHC has been performed): kappa/lambda light chains, IgM, CD3, CD5, CD10, CD19, CD20, CD45, and TdT Molecular genetic analysis - For Burkitt lymphoma: FISH to detect MYC gene rearrangements - For Double-hit lymphoma: FISH to detect the BCL2 and BCL6 gene rearrangements OF USE IN CERTAIN CIRCUMSTANCES: FISH for BCL2 and BCL6 rearrangements In situ hybridization: EBER STRONGLY RECOMMENDED: FNA or core biopsy for tissue banking by protocol Perform gene mutation panel if available Physical exam: Performance status (ECOG) B symptoms (fever, sweats, weight loss) CBC with differential, albumin, AST, ALT, total bilirubin, alkaline phosphorus, serum calcium, uric acid, phosphate, magnesium, BUN, creatinine, LDH Screening for HIV1and 2, hepatitis B and C (HBcAb, HBaAg, HCVAb) Chest X-ray, PA and Lateral CT with contrast of neck, chest, abdomen and pelvis Echo or MUGA Lumbar Puncture with cytology evaluation Bilateral bone marrow biopsy with aspirate PET/CT Scan Useful in selected cases: UGI/barium enema/endoscopy MRI of brain with gadolinium or CT of brain Pregnancy test in women of childbearing potential Discussion of fertility issues and sperm banking See Page 2 for Clinical Presentations and Primary Treatment
INDUCTION THERAPY Burkitt Lymphoma 1 Dose adjusted Rituximab and EPOCH (Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin) with intrathecal chemotherapy and GCSF 2 Rituxmab and HCVAD (Cyclophosphamide, Vincristine, Doxorubicin, Dexamethasone) alternately with Rituximab and Methotrexate and Cytarabine with intrathecal chemotherapy and GCSF Rituximab and CODOX-M/ Rituximab and IVAC (Cyclophosphamide, Vincristine, Doxorubicin, high-dose Methotrexate alternately with Ifosphamide, Etoposide, high-dose Cytarabine) with intrathecal chemotherapy and GCSF 2 Double- Hit or Triple- Hit Lymphoma 1 Regimens as above for Burkitt Lymphoma Consideration of consolidation in 1 st complete remission with high dose chemotherapy and Autologous Stem Cell Transplantation (ASCT) in selected patients continued on the next page 1 R-CHOP: Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone is not adequate adequate therapy 2 GCSF: Granulocyte Colony-Stimulating Factor (Filgrastin or Pegfilgrastim) 5
RESPONSE EVALUATION 1 FOLLOW-UP Complete Response (CR) Recommend to continue: Routine follow-up and management with infectious disease specialists Routine cancer screening tests with primary cancer physician Year -2: Every 3-4 months Repeat CT s with contrast Years 3-5: Every 6 months Repeat CT s with contrast Year 5 and beyond Partial response (PR), Stable Disease, Progressive Disease and recurrence Consider non-overlapping chemotherapy option per DLBCL guidelines Consider high dose chemotherapy plus ASCT for patients who enter into second remission with good performance status and well controlled concomitant medical issues 1 By Revised Response Criteria for Malignant Lymphoma( see suggested readings)
SUGGESTED READINGS Aukema, SM et al. (2011). Double-hit B-cell lymphomas. Blood 117(8):2319-2331. Barnes JA, LaCasce AS, Feng Y, et al. (2011). Evaluation of the addition of rituximab to CODOX-M/IVAC for Burkitt s lymphoma: a retrospective analysis. Ann Oncol 22:1859-1864. Blum KA, Lozanski G, Byrd JC, et al. (2004). Adult Burkitt leukemia and lymphoma. Blood 104:3009-3020. Cheson, BD, Pfistner, B, Juweid, ME, et al. (2007). Revised Response Criteria for malignant Lymphoma. J Clin Oncol 25; 5: 579-586. Dunleavy K, Little RF, Pittaluga S, et al. (2008). A prospective study of dose-adjusted (DA) EPOCH with rituximab in adult with newly diagnosed Burkitt lymphoma: A regimen with high efficacy and low toxicity. Annals of Oncology 19 (suppl_4):iv83-84. Dunleavy K, Pittaluga S, Shovlin M, et al. (2013). Low-intensity therapy in adults with Burkitt s lymphoma. N Engl J Med 369(20):1915-25. doi: 10.1056/NEJMoa1308392. Griffin TC, Weitzman S, Weinstein H, et al. A study of rituximab and ifosfamide, carboplatin, and etoposide chemotherapy in children with recurrent/refractory B-cell (CD10+) non-hodgkin lymphoma and mature B-cell acute lymphoblastic leukemia: a report from the Children s Oncology Group. Pediatr Blood Cancer, 52:177-171. Magrath I, Adde M, Shad A. et al. (1996). Adults and children with small non-cleaved-cell lymphoma have a similar excellent outcome when treated with the same chemotherapy regimen. J Clin Oncol 14:925-934. Mead GM, Sydes MR, Walewski J, et al. (2002). An international evaluation of CODOX-M and CODOX-M alternating with IVAC in adult Burkitt s lymphoma: results of United Kingdom Lymphoma Group LY06 study. Ann Oncol 13:1264-1274. LaCasce A, Howard O, Lib S, et al. (2004). Modified magrath regimens for adults with Burkitt and Burkitt-like lymphoma: preserved efficacy with decreased toxicity. Leuk Lymphoma, 45:761-767. Oki Y, Noorani M, Davis RE, et al. (2013). Double hit lymphoma; MD Anderson Experience. ASH 55 th Annual Meeting and Exposition. Abstract #1776 Rizzieri DA, Johnson JL, Byrd JC, et al. (2014). Improved efficacy using rituximab and brief duration, high intensity chemotherapy with filgrastim support for Burkitt or aggressive lymphomas: cancer and Leukemia Group B study 10 002. Br J Haematol, 165:102-111. Thomas DA, Faderl S, O Brien S, et al. (2006). Chemoimmunotherapy with hyper-cvad plus rituximab for the treatment of adult Burkitt and Burkitt type lymphoma or acute lymphoblastic leukemia. Cancer 106:1569-1580. Thomas DA, Kantarjian HM, Cortes J, et al. (2008). Long-term outcome after hyper-cvad and rituximab chemoimmunotherapy for Burkitt (BL) or Burkitt-like (BLL) leukemia/lymphoma and mature B-cell acute lymphocyte leukemia (ALL) [abstract]. Blood 112:Abstract 1929.
DEVELOPMENT CREDITS This practice guideline is based on majority expert opinion of the Lymphoma Center Faculty at the University of Texas MD Anderson Cancer Center. It was developed using a multidisciplinary approach that included input from the following medical oncologists, radiation oncologists, surgical oncologists, and interventional radiologists: Michelle Fanale, MD Ŧ L. Jeffrey Medeiros, MD Yasuhiro Oki, MD Chelsea Pinnix, MD Jason Westin, MD Ŧ Core Development Team Lead