Burkitt lymphoma

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20 regimens on this page 27 variants on this page

Note 1: Regimens specifically intended for HIV-related Burkitt lymphoma can be found on the HIV-associated lymphoma page.

Note 2: "Burkitt-like lymphoma" is not considered an entity by the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue 2008 criteria. The correct terminology is "B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma." However, Burkitt-like lymphoma is still used in common parlance and the term is retained here; treatment is usually similar to treatment for Burkitt lymphoma but regimens evaluated on Diffuse large B-cell lymphoma are also sometimes used.

Untreated, pre-phase

COP

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COP: Cyclophosphamide, Oncovin (Vincristine), Prednisone

Regimen

Study	Evidence
Diviné et al. 2005 (LMB95)	Phase II
Ribrag et al. 2016 (LMBA-02)	Non-randomized

This regimen is for group B (unresected stage I, non-abdominal stage II and any stage III or IV disease without CNS or bone marrow involvement) or group C (CNS and/or bone marrow involvement).

Chemotherapy

• Cyclophosphamide (Cytoxan) 300 mg/m²/day IV once on day 1
• Vincristine (Oncovin) 1 mg/m² (max dose of 2 mg) IV once on day 1
• Prednisone (Sterapred) 60 mg/m²/day PO/IV on days 1 to 7

CNS prophylaxis (group B)

• Methotrexate (MTX) 15 mg IT once on day 1
• Hydrocortisone (Cortef) (dose not specified) IT once on day 1 (admixed with MTX)

CNS treatment (group C)

• Methotrexate (MTX) 15 mg IT once per day on days 1, 3, 5
• Cytarabine (Cytosar) 40 mg IT once per day on dyas 1, 3, 5
• Hydrocortisone (Cortef) (dose not specified) IT once per day on days 1, 3, 5 (admixed with MTX & Ara-C)

One cycle

Patients in LMB95 proceeded one week later to COPADM. Patients in LMBA-02 were randomized to COPADM versus R-COPADM.

References

1. Diviné M, Casassus P, Koscielny S, Bosq J, Sebban C, Le Maignan C, Stamattoulas A, Dupriez B, Raphaël M, Pico JL, Ribrag V; GELA; GOELAMS. Burkitt lymphoma in adults: a prospective study of 72 patients treated with an adapted pediatric LMB protocol. Ann Oncol. 2005 Dec;16(12):1928-35. Epub 2005 Nov 10. link to original article contains verified protocol PubMed
2. Ribrag V, Koscielny S, Bosq J, Leguay T, Casasnovas O, Fornecker LM, Recher C, Ghesquieres H, Morschhauser F, Girault S, Gouill SL, Ojeda-Uribe M, Mariette C, Cornillon J, Cartron G, Verge V, Chassagne-Clément C, Dombret H, Coiffier B, Lamy T, Tilly H, Salles G. Rituximab and dose-dense chemotherapy for adults with Burkitt's lymphoma: a randomised, controlled, open-label, phase 3 trial. Lancet. 2016 Apr 11. [Epub ahead of print] link to original article PubMed

Cyclophosphamide & Prednisone

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Regimen

Study	Evidence
Oriol et al. 2008 (PETHEMA)	Non-randomized

Chemotherapy

• Cyclophosphamide (Cytoxan) 200 mg/m²/day IV over 1 hour once per day on days 1 to 5
• Prednisone (Sterapred) 60 mg/m²/day IV bolus once per day on days 1 to 5

CNS prophylaxis

• Cytarabine (Cytosar) 40 mg IT once on day 1, admixed with methotrexate and dexamethasone
• Methotrexate (MTX) 15 mg IT once on day 1, admixed with cytarabine and dexamethasone
• Dexamethasone (Decadron) 20 mg IT once on day 1, admixed with cytarabine and methotrexate

One cycle

Patients proceeded one week later to PETHEMA induction.

References

1. Oriol A, Ribera JM, Bergua J, Giménez Mesa E, Grande C, Esteve J, Brunet S, Moreno MJ, Escoda L, Hernandez-Rivas JM, Hoelzer D. High-dose chemotherapy and immunotherapy in adult Burkitt lymphoma: comparison of results in human immunodeficiency virus-infected and noninfected patients. Cancer. 2008 Jul 1;113(1):117-25. link to original article contains verified protocol PubMed

Untreated

BASIC

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BASIC: Brief, Anthracycline-Sparing, Intensive Cyclophosphamide

Regimen

Study	Evidence
Kasamon et al. 2012	Non-randomized

Chemotherapy

• Cyclophosphamide (Cytoxan) 1500 mg/m² IV over 1 hour once on day 1
• Vincristine (Oncovin) 1.4 mg/m² (max dose of 2 mg) IV once on day 1
• Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
• Rituximab (Rituxan) 375 mg/m² IV once per day on days 1 & 8
• Methotrexate (MTX) 3000 mg/m² IV over 2 hours once on day 8

Supportive medications

• Mesna (Mesnex) 900 mg/m² IV "in divided doses" on day 1
• Folinic acid (Leucovorin) 25 mg/m² IV Q6H, starting 24 hours after start of IV Methotrexate (MTX), until clearance
• Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 3 and continuing until post-nadir ANC >500/uL

CNS prophylaxis

• Cytarabine (Cytosar) 100 mg IT once per day on days 1, 4, 11 (also day 8 if no IV MTX given)
• Hydrocortisone (Cortef) 50 mg IT is optional (no parameters given)

14-day cycle for 2 cycles

Treatment followed immediately by BASIC intensification.

References

1. Kasamon YL, Brodsky RA, Borowitz MJ, Ambinder RF, Crilley PA, Cho SY, Tsai HL, Smith BD, Gladstone DE, Carraway HE, Huff CA, Matsui WH, Bolaños-Meade J, Jones RJ, Swinnen LJ. Brief intensive therapy for older adults with newly diagnosed Burkitt or atypical Burkitt lymphoma/leukemia. Leuk Lymphoma. 2013 Mar;54(3):483-90. Epub 2012 Aug 17. link to original article link to PMC article contains verified protocol PubMed

CALGB 9251

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Regimen

Study	Evidence
Rizzieri et al. 2004 (CALGB 9251)	Phase II

This is an earlier version of CALGB 10-002 that demonstrates that cranial radiation can be omitted in the treatment of Burkitt lymphoma. The regimen omits rituximab. We are unlikely to add this regimen to the site at this time, here for reference only.

References

1. Rizzieri DA, Johnson JL, Niedzwiecki D, Lee EJ, Vardiman JW, Powell BL, Barcos M, Bloomfield CD, Schiffer CA, Peterson BA, Canellos GP, Larson RA. Intensive chemotherapy with and without cranial radiation for Burkitt leukemia and lymphoma: final results of Cancer and Leukemia Group B Study 9251. Cancer. 2004 Apr 1;100(7):1438-48. link to original article PubMed

CALGB 10-002

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Regimen

Study	Evidence
Rizzieri et al. 2014 (CALGB 10-002)	Phase II

Cycle 1

• Cyclophosphamide (Cytoxan) 200 mg/m² IV once per day on days 1 to 5
• Prednisone (Sterapred) 60 mg/m² PO once per day on days 1 to 7

Supportive medications

• Allopurinol (Zyloprim) 300 mg PO once per day on days 1 to 14 (includes first week of cycle 2)

One-week cycle, followed by alternation of the following:

Cycles 2, 4, 6

• Ifosfamide (Ifex) 800 mg/m² IV over 1 hour once per day on days 1 to 5
• Dexamethasone (Decadron) 10 mg/m² (route not specified) once per day on days 1 to 5
• Methotrexate (MTX) 150 mg/m² IV load, followed by 1.35 g/m² over 23.5 hours on day 1
• Vincristine (Oncovin) 2 mg IV push once on day 1
• Cytarabine (Cytosar) 1000 mg/m² IV over 2 hours once per day on days 4 & 5
• Etoposide (Vepesid) 80 mg/m² IV over 1 hour once per day on days 4 & 5
• Rituximab (Rituxan) as follows:
  • Cycle 2: 50 mg/m² IV once on day 8, then 375 mg/m² IV once per day on days 10 & 12
  • Cycles 4 & 6: 375 mg/m² IV once on day 8

CNS prophylaxis

• Cytarabine (Cytosar) 40 mg intrathecal on day 1
• Methotrexate (MTX) 15 mg intrathecal on day 1
• Hydrocortisone (Cortef) 50 mg intrathecal on day 1

Supportive medications

• Mesna (Mesnex) (dose not specified but presumably equal to ifosfamide dose) mixed with Ifosfamide (Ifex)
• Folinic acid (Leucovorin) 25 mg/m² IV or PO once 36 hours after start of IV Methotrexate (MTX), then 10 mg/m² Q6H until methotrexate level < 0.05
• Filgrastim (Neupogen) 5 mcg/kg SQ once per day, starting on day 7 and continuing until ANC > 500/uL

21-day cycles

Cycles 3, 5, 7

• Cyclophosphamide (Cytoxan) 200 mg/m² IV once per day on days 1 to 5
• Dexamethasone (Decadron) 10 mg/m² PO or IV once per day on days 1 to 5
• Methotrexate (MTX) 150 mg/m² IV load, followed by 1.35 g/m² over 23.5 hours on day 1
• Vincristine (Oncovin) 2 mg IV push once on day 1
• Doxorubicin (Adriamycin) 25 mg/m² IV once per day on days 4 & 5
• Rituximab (Rituxan) 375 mg/m² IV once on day 8 of cycles 3, 5, 7

CNS prophylaxis

• Cytarabine (Cytosar) 40 mg intrathecal on day 1
• Methotrexate (MTX) 15 mg intrathecal on day 1
• Hydrocortisone (Cortef) 50 mg intrathecal on day 1

Supportive medications

• Folinic acid (Leucovorin) 50 mg/m² IV or PO once 36 hours after start of IV Methotrexate (MTX), then 10 mg/m² Q6H until methotrexate level < 0.05
• Filgrastim (Neupogen) 5 mcg/kg SQ once per day, starting on day 7 and continuing until ANC > 500/uL

21-day cycles

References

1. Rizzieri DA, Johnson JL, Byrd JC, Lozanski G, Blum KA, Powell BL, Shea TC, Nattam S, Hoke E, Cheson BD, Larson RA; Alliance for Clinical Trials In Oncology (ACTION). 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. 2014 Apr;165(1):102-11. Epub 2014 Jan 15. link to original article contains verified protocol PubMed

CODOX-M/IVAC

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CODOX-M: Cyclophosphamide, Oncovin (Vincristine), DOXorubicin, Methotrexate
IVAC: Ifosfamide, Vepesid (Etoposide), Ara-C (Cytarabine)

Regimen #1, "Original Magrath"

Study	Evidence
Magrath et al. 1996	Phase II

Part 1: CODOX-M

• Cyclophosphamide (Cytoxan) 800 mg/m² IV once on day 1, then 200 mg/m² IV once per day on days 2 to 5
• Vincristine (Oncovin) 1.5 mg/m² IV once per day on days 1 & 8
• Doxorubicin (Adriamycin) 40 mg/m² IV once on day 1
• Methotrexate (MTX) as follows:
  • Age 65 years or younger: 300 mg/m² IV over 1 hour, then 2700 mg/m² IV over the next 23 hours on day 10 (total dose: 3000 mg/m²)
  • Age >65 years: 100 mg/m² IV over 1 hour, then 900 mg/m² IV over the next 23 hours on day 10 (total dose: 1000 mg/m²)

Supportive medications

• Folinic acid (Leucovorin) 15 mg/m² IV Q3H, starting 36 hours after start of IV Methotrexate (MTX) until 48 hours, then Q6H until methotrexate level undetectable
• Folinic acid (Leucovorin) 15 mg PO once 24 hours after intrathecal Methotrexate (MTX)
• Filgrastim (Neupogen) 5 mcg/kg SQ once per day, starting on day 13 and continuing until ANC >1,000/uL

CNS prophylaxis

• Cytarabine (Cytosar) 70 mg IT once per day on days 1 & 3
• Methotrexate (MTX) 12 mg IT once on day 15

Part 2: IVAC

• Ifosfamide (Ifex) as follows:
  • Age 65 years or younger: 1500 mg/m² IV over 1 hour once per day on days 1 to 5
  • Age >65 years: 1000 mg/m² IV over 1 hour once per day on days 1 to 5
• Etoposide (Vepesid) 60 mg/m² IV over 1 hour once per day on days 1 to 5
• Cytarabine (Cytosar) as follows:
  • Age 65 years or younger: 2000 mg/m² IV over 3 hours Q12H on days 1,2 (4 doses)
  • Age >65 years: 1000 mg/m² IV over 3 hours Q12H on days 1,2 (4 doses)

Supportive medications

• Mesna (Mesnex) as follows:
  • Age 65 years or younger: 300 mg/m² (mixed with Ifosfamide (Ifex)) over 1 hour, then 300mg/m² IV every four hours x 2, on days 1 to 5
  • Age >65 years: 200 mg/m² (mixed with Ifosfamide (Ifex)) over 1 hour, then 200mg/m² IV every four hours x 2, on days 1 to 5
• Folinic acid (Leucovorin) 15 mg PO once 24 hours after intrathecal methotrexate
• Filgrastim (Neupogen) 5 mcg/kg SQ once per day, starting on day 7 and continuing until ANC >1,000/uL

CNS prophylaxis

• Methotrexate (MTX) 12 mg IT once on day 5

Regimen #2, "Modified Magrath"

Study	Evidence
LaCasce et al. 2004	Phase II, <20 pts

All modifications are in Part 1: CODOX-M. Also note that dose reductions for age > 65 years were not described in this publication.

Part 1: CODOX-M

• Cyclophosphamide (Cytoxan) 800 mg/m² IV once per day on days 1 & 2
• Vincristine (Oncovin) 1.4 mg/m² (max dose of 2 mg) IV once per day on days 1 & 10
• Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
• Methotrexate (MTX) 3000 mg/m² IV once on day 10

CNS prophylaxis

• Cytarabine (Cytosar) 50 mg intrathecal on day 1 (all patients), day 3 (high-risk only)
• Methotrexate (MTX) 12 mg intrathecal on day 1
• Hydrocortisone (Cortef) 50 mg intrathecal admixed with all chemotherapy

Supportive medications

• Folinic acid (Leucovorin) 200 mg/m² IV once 24 hours after start of IV Methotrexate (MTX), then 15 mg/m² Q6H until methotrexate level undetectable
• Filgrastim (Neupogen) 5 mcg/kg SQ once per day on days 3 to 8, held for MTX, and restarted after clearance continuing until ANC >1,000/uL

Part 2: IVAC

• Ifosfamide (Ifex) 1500 mg/m² IV over 1 hour once per day on days 1 to 5
• Etoposide (Vepesid) 60 mg/m² IV over 1 hour once per day on days 1 to 5
• Cytarabine (Cytosar) 2 g/m² IV over 3 hours Q12H on days 1,2 (4 doses)

CNS prophylaxis

• Methotrexate (MTX) 12 mg intrathecal on day 5, admixed with Hydrocortisone (Cortef)
• Hydrocortisone (Cortef) 50 mg intrathecal on day 5, admixed with Methotrexate (MTX)

Supportive medications

• Mesna (Mesnex) 300 mg/m² (mixed with Ifosfamide (Ifex)) over 1 hour, then 300mg/m² IV every four hours x 2, on days 1 to 5
• Filgrastim (Neupogen) 5 mcg/kg SQ once per day, starting on day 6 and continuing until ANC >1,000/uL

High-risk patients receive 2 cycles each of R-CODOX-M and R-IVAC (alternating). Low-risk patients (i.e. single site of disease <10cm with normal LDH) receive 3 cycles of R-CODOX-M.

References

1. Magrath I, Adde M, Shad A, Venzon D, Seibel N, Gootenberg J, Neely J, Arndt C, Nieder M, Jaffe E, Wittes RA, Horak ID. Adults and children with small non-cleaved-cell lymphoma have a similar excellent outcome when treated with the same chemotherapy regimen. J Clin Oncol. 1996 Mar;14(3):925-34. link to original article contains verified protocol PubMed
2. Mead GM, Sydes MR, Walewski J, Grigg A, Hatton CS, Pescosta N, Guarnaccia C, Lewis MS, McKendrick J, Stenning SP, Wright D; UKLG LY06 collaborators. 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. 2002 Aug;13(8):1264-74. Erratum in: Ann Oncol. 2002 Dec;13(12):1961. Norbert, P [corrected to Pescosta, N]. link to original article contains verified protocol PubMed
3. Lacasce A, Howard O, Lib S, Fisher D, Weng A, Neuberg D, Shipp M. Modified magrath regimens for adults with Burkitt and Burkitt-like lymphomas: preserved efficacy with decreased toxicity. Leuk Lymphoma. 2004 Apr;45(4):761-7. link to original article contains verified protocol PubMed
4. Mead GM, Barrans SL, Qian W, Walewski J, Radford JA, Wolf M, Clawson SM, Stenning SP, Yule CL, Jack AS; UK National Cancer Research Institute Lymphoma Clinical Studies Group; Australasian Leukaemia and Lymphoma Group. A prospective clinicopathologic study of dose-modified CODOX-M/IVAC in patients with sporadic Burkitt lymphoma defined using cytogenetic and immunophenotypic criteria (MRC/NCRI LY10 trial). Blood. 2008 Sep 15;112(6):2248-60. Epub 2008 Jul 8. link to original article contains verified protocol PubMed
5. Maruyama D, Watanabe T, Maeshima AM, Nomoto J, Taniguchi H, Azuma T, Mori M, Munakata W, Kim SW, Kobayashi Y, Matsuno Y, Tobinai K. Modified cyclophosphamide, vincristine, doxorubicin, and methotrexate (CODOX-M)/ifosfamide, etoposide, and cytarabine (IVAC) therapy with or without rituximab in Japanese adult patients with Burkitt lymphoma (BL) and B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma and BL. Int J Hematol. 2010 Dec;92(5):732-43. Epub 2010 Dec 1. link to original article contains verified protocol PubMed

COPAD

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COPAD: Cyclophosphamide, Oncovin (Vincristine), Prednisone, ADriamycin (Doxorubicin)

Regimen

Study	Evidence
Diviné et al. 2005 (LMB95)	Phase II, <20 pts in this subgroup

This regimen is for group A (completely resected stage I or abdominal stage II disease).

Chemotherapy

• Cyclophosphamide (Cytoxan) 500 mg/m²/day IV (in 2 fractions) on days 2 to 4
• Vincristine (Oncovin) 1.4 mg/m² (max dose of 2 mg) IV once per day on days 1 & 6
• Prednisone (Sterapred) 60 mg/m²/day PO/IV on days 1 to 6
• Doxorubicin (Adriamycin) 60 mg/m² IV once on day 2

3 cycles; intervals were as short as possible, as soon as the ANC was >1.5 × 10⁹/L and platelet count was >100 × 10⁹/L

References

1. Diviné M, Casassus P, Koscielny S, Bosq J, Sebban C, Le Maignan C, Stamattoulas A, Dupriez B, Raphaël M, Pico JL, Ribrag V; GELA; GOELAMS. Burkitt lymphoma in adults: a prospective study of 72 patients treated with an adapted pediatric LMB protocol. Ann Oncol. 2005 Dec;16(12):1928-35. Epub 2005 Nov 10. link to original article contains verified protocol PubMed

COPADM

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COPADM: Cyclophosphamide, Oncovin (Vincristine), Prednisone, ADriamycin (Doxorubicin), Methotrexate

Regimen

Study	Evidence	Comparator	Efficacy
Diviné et al. 2005 (LMB95)	Phase II
Ribrag et al. 2016 (LMBA-02)	Phase III	R-COPADM	Seems to have inferior EFS

This regimen is for group B (unresected stage I, non-abdominal stage II and any stage III or IV disease without CNS or bone marrow involvement) or group C (CNS and/or bone marrow involvement). Diviné et al. 2005 list the dose of HD-MTX as 3 mg/m² but this is presumed to be a typo. Treatment is preceded by pre-phase COP.

COPADM #1

• Cyclophosphamide (Cytoxan) 500 mg/m²/day IV (in 2 fractions) on days 2 to 4
• Vincristine (Oncovin) 1.4 mg/m² (max dose of 2 mg) IV once on day 1
• Prednisone (Sterapred) 60 mg/m²/day PO/IV on days 1 to 6
• Doxorubicin (Adriamycin) 60 mg/m² IV once on day 2
• Methotrexate (MTX) 3000 mg/m² IV over 3 hours once on day 1

Supportive medications

• Folinic acid (Leucovorin) 15 mg/m² (route not specified) q6h on days 2 to 4

CNS prophylaxis (group B)

• Methotrexate (MTX) 15 mg IT once per day on days 2 & 6
• Hydrocortisone (Cortef) (dose not specified) IT once per day on days 2 & 6 (admixed with MTX)

CNS treatment (group C)

• Methotrexate (MTX) 15 mg IT once per day on days 2, 4, 6
• Cytarabine (Cytosar) 40 mg IT once per day on dyas 2, 4, 6
• Hydrocortisone (Cortef) (dose not specified) IT once per day on days 2, 4, 6 (admixed with MTX & Ara-C)

One cycle

As soon as the ANC was >1.5 × 10⁹/L and platelet count was >100 × 10⁹/L, patients proceeded to:

COPADM #2

• Cyclophosphamide (Cytoxan) 1000 mg/m²/day IV (in 2 fractions) on days 2 to 4
• Vincristine (Oncovin) 1.4 mg/m² (max dose of 2 mg) IV once per day on days 1 & 6
• Prednisone (Sterapred) 60 mg/m²/day PO/IV on days 1 to 6
• Doxorubicin (Adriamycin) 60 mg/m² IV once on day 2
• Methotrexate (MTX) 3000 mg/m² IV over 3 hours once on day 1

Supportive medications

• Folinic acid (Leucovorin) 15 mg/m² (route not specified) q6h on days 2 to 4

CNS prophylaxis (group B)

• Methotrexate (MTX) 15 mg IT once per day on days 2 & 6
• Hydrocortisone (Cortef) (dose not specified) IT once per day on days 2 & 6 (admixed with MTX)

CNS treatment (group C)

• Methotrexate (MTX) 15 mg IT once per day on days 2, 4, 6
• Cytarabine (Cytosar) 40 mg IT once per day on dyas 2, 4, 6
• Hydrocortisone (Cortef) (dose not specified) IT once per day on days 2, 4, 6 (admixed with MTX & Ara-C)

One cycle

As soon as the ANC was >1.5 × 10⁹/L and platelet count was >100 × 10⁹/L, patients in group B proceeded to CYM consolidation, and patients in group C proceeded to CYVE consolidation.

References

1. LMB 81: Patte C, Philip T, Rodary C, Bernard A, Zucker JM, Bernard JL, Robert A, Rialland X, Benz-Lemoine E, Demeocq F, et al. Improved survival rate in children with stage III and IV B cell non-Hodgkin's lymphoma and leukemia using multi-agent chemotherapy: results of a study of 114 children from the French Pediatric Oncology Society. J Clin Oncol. 1986 Aug;4(8):1219-26. link to original article PubMed
2. LMB 84: Patte C, Philip T, Rodary C, Zucker JM, Behrendt H, Gentet JC, Lamagnère JP, Otten J, Dufillot D, Pein F, et al. High survival rate in advanced-stage B-cell lymphomas and leukemias without CNS involvement with a short intensive polychemotherapy: results from the French Pediatric Oncology Society of a randomized trial of 216 children. J Clin Oncol. 1991 Jan;9(1):123-32. link to original article PubMed
3. Diviné M, Casassus P, Koscielny S, Bosq J, Sebban C, Le Maignan C, Stamattoulas A, Dupriez B, Raphaël M, Pico JL, Ribrag V; GELA; GOELAMS. Burkitt lymphoma in adults: a prospective study of 72 patients treated with an adapted pediatric LMB protocol. Ann Oncol. 2005 Dec;16(12):1928-35. Epub 2005 Nov 10. link to original article contains verified protocol PubMed
4. Ribrag V, Koscielny S, Bosq J, Leguay T, Casasnovas O, Fornecker LM, Recher C, Ghesquieres H, Morschhauser F, Girault S, Gouill SL, Ojeda-Uribe M, Mariette C, Cornillon J, Cartron G, Verge V, Chassagne-Clément C, Dombret H, Coiffier B, Lamy T, Tilly H, Salles G. Rituximab and dose-dense chemotherapy for adults with Burkitt's lymphoma: a randomised, controlled, open-label, phase 3 trial. Lancet. 2016 Apr 11. [Epub ahead of print] link to original article PubMed

DA-R-EPOCH

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DA-R-EPOCH: Dose Adjusted Rituximab, Etoposide, Prednisone, Oncovin (Vincristine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin)

Synonyms: DA-EPOCH-R, EPOCH-R, REPOCH

Structured Concept: C63461 (NCI-T), C1882521 (NCI-MT/UMLS)

Regimen

Study	Evidence
Dunleavy et al. 2013	Phase II, <20 pts in this subgroup

Chemotherapy

• Rituximab (Rituxan) 375 mg/m² IV over 3 hours once on day 1
• Etoposide (Vepesid) 50 mg/m²/day IV continuous infusion on days 1 to 4 (total dose per cycle: 200 mg/m²)
• Prednisone (Sterapred) 60 mg/m² PO BID on days 1 to 5
• Vincristine (Oncovin) 0.4 mg/m²/day IV continuous infusion on days 1 to 4 (total dose per cycle: 1.6 mg/m²)
• Cyclophosphamide (Cytoxan) 750 mg/m² IV over 2 hours once on day 5
• Doxorubicin (Adriamycin) 10 mg/m²/day IV continuous infusion on days 1 to 4 (total dose per cycle: 40 mg/m²)

Supportive medications

• Filgrastim (Neupogen) 300 mcg SC once per day, starting on day 6 and continuing until ANC greater than 5×10⁹/L above the nadir level
• Trimethoprim/Sulfamethoxazole (Bactrim DS) one tablet PO TIW
• Omeprazole (Prilosec) 20 mg PO once per day or equivalent
• Docusate (Colace), Sennosides (Senna), and Lactulose as needed for constipation

21-day cycle for 6 cycles if ANC >1,000 and platelets >100

If counts are below those levels, check daily CBC and continue growth factor support until counts are adequate and next cycle can start.

Dose-adjustments for EPOCH protocol (note this is different than some other DA-EPOCH regimens):

• Start cycle 1 as described above.
• Obtain CBCs twice per week for nadir measurements.
• If nadir ANC ≥500, increase etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
• If nadir ANC <500, use same doses as last cycle.
• If nadir platelet count <25, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
  • Decreases below the cycle 1 starting dose only apply to cyclophosphamide, i.e., the lowest etoposide and doxorubicin would be dosed is at the original cycle 1 dose.

CNS prophylaxis

• Methotrexate (MTX) as follows:
  • Cycles 3 to 6: 12 mg IT once per day on days 1 & 5

References

1. Dunleavy K, Pittaluga S, Shovlin M, Steinberg SM, Cole D, Grant C, Widemann B, Staudt LM, Jaffe ES, Little RF, Wilson WH. Low-intensity therapy in adults with Burkitt's lymphoma. N Engl J Med. 2013 Nov 14;369(20):1915-25. link to original article link to supplement contains verified protocol in supplement PubMed

GMALL-B-ALL/NHL 2002

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GMALL: German Multicenter Study Group for the Treatment of Adult Acute Lymphoblastic Leukemia

Regimen

Study	Evidence
Hoelzer et al. 2014 (GMALL-B-ALL/NHL 2002)	Non-randomized

This regimen is fairly similar to the GMALL-R regimen, with some minor differences. See text for details.

References

1. Hoelzer D, Walewski J, Döhner H, Viardot A, Hiddemann W, Spiekermann K, Serve H, Dührsen U, Hüttmann A, Thiel E, Dengler J, Kneba M, Schaich M, Schmidt-Wolf IG, Beck J, Hertenstein B, Reichle A, Domanska-Czyz K, Fietkau R, Horst HA, Rieder H, Schwartz S, Burmeister T, Gökbuget N; German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia. Improved outcome of adult Burkitt lymphoma/leukemia with rituximab and chemotherapy: report of a large prospective multicenter trial. Blood. 2014 Dec 18;124(26):3870-9. Epub 2014 Oct 30. link to original article contains verified protocol PubMed

GMALL-R

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GMALL-R: German Multicenter Study Group for the Treatment of Adult Acute Lymphoblastic Leukemia, Rituximab

Regimen

Study	Evidence
Ribera et al. 2013 (Burkimab)	Phase II

Numbering of days is based on prephase->A->B->C; however, certain patient populations received different ordering of regimen, see below.

Prephase

• Cyclophosphamide (Cytoxan) 200 mg/m² IV over 1 hour once per day on days 1 to 5
• Prednisone (Sterapred) 60 mg/m² IV bolus once per day on days 1 to 5

Cycle A

• Rituximab (Rituxan) 375 mg/m² IV over 4 hours once on day 7
• Vincristine (Oncovin) 2 mg IV bolus once on day 8
• Methotrexate (MTX) 1500 mg/m² IV over 24 hours once on day 8
  • Older than 55 years: reduce Methotrexate (MTX) dose by 50%
• Ifosfamide (Ifex) 800 mg/m² IV over 1 hour once per day on days 8 to 12
• Dexamethasone (Decadron) 10 mg/m² IV bolus once per day on days 8 to 12
• Teniposide (Vumon) 100 mg/m² IV over 1 hour once per day on days 11 & 12
• Cytarabine (Cytosar) 150 mg/m² IV over 1 hour BID on days 11 & 12
  • Older than 55 years: reduce Cytarabine (Cytosar) dose by 50%

Supportive medications

• Folinic acid (Leucovorin) (dose/route/schedule not specified), starting 12 hours after Methotrexate (MTX) infusion

Cycle B

• Rituximab (Rituxan) 375 mg/m² IV over 4 hours once on day 28
• Vincristine (Oncovin) 2 mg IV bolus once on day 29
• Methotrexate (MTX) 1500 mg/m² IV over 24 hours once on day 29
  • Older than 55 years: reduce Methotrexate (MTX) dose by 50%
• Cyclophosphamide (Cytoxan) 200 mg/m² IV over 1 hour once per day on days 29 to 33
• Dexamethasone (Decadron) 10 mg/m² IV bolus once per day on days 29 to 33
• Doxorubicin (Adriamycin) 25 mg/m² IV over 15 minutes once per day on days 32 & 33

Supportive medications

• Folinic acid (Leucovorin) (dose/route/schedule not specified), starting 12 hours after Methotrexate (MTX) infusion

Cycle C

• Rituximab (Rituxan) 375 mg/m² IV over 4 hours once on day 49
• Vindesine (Eldisine) 3 mg/m² (maximum dose 5 mg) IV bolus once on day 50
• Methotrexate (MTX) 1500 mg/m² IV over 24 hours once on day 50
  • Older than 55 years: reduce Methotrexate (MTX) dose by 50%
• Dexamethasone (Decadron) 10 mg/m² IV bolus once per day on days 50 to 54
• Etoposide (Vepesid) 250 mg/m² IV over 1 hour once per day on days 53 & 54
• Cytarabine (Cytosar) 2000 mg/m² IV over 3 hours BID on day 54
  • Older than 55 years: reduce Cytarabine (Cytosar) dose by 50%

Supportive medications

• Folinic acid (Leucovorin) (dose/route/schedule not specified), starting 12 hours after Methotrexate (MTX) infusion

Give regimen as follows:

• Advanced stage and younger than 55 years: A->B->C for 2 courses (6 total cycles)
• Older than 55 years: Alternate A & B for 3 courses (6 total cycles)
• Localized stage: 4 total cycles (unclear from protocol if this means A alternating with B or A->B->C->A)

CNS Prophylaxis

• Methotrexate (MTX) 15 mg intrathecal once on days 1, 8, 12, 29, 33
• Cytarabine (Cytosar) 40 mg intrathecal once on days 1, 8, 12, 29, 33
• Dexamethasone (Decadron) 20 mg intrathecal once on days 1, 8, 12, 29, 33

8 doses total

References

1. Ribera JM, García O, Grande C, Esteve J, Oriol A, Bergua J, González-Campos J, Vall-Llovera F, Tormo M, Hernández-Rivas JM, García D, Brunet S, Alonso N, Barba P, Miralles P, Llorente A, Montesinos P, Moreno MJ, Hernández-Rivas JÁ, Bernal T. Dose-intensive chemotherapy including rituximab in Burkitt's leukemia or lymphoma regardless of human immunodeficiency virus infection status: final results of a phase 2 study (Burkimab). Cancer. 2013 May 1;119(9):1660-8. Epub 2013 Jan 29. link to original article contains verified protocol PubMed

R-CODOX-M/R-IVAC

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R-CODOX-M: Rituximab, Cyclophosphamide, Oncovin (Vincristine), DOXorubicin, Methotrexate

R-IVAC: Rituximab, Ifosfamide, Vepesid (etoposide), Ara-C (Cytarabine)

Regimen

Study	Evidence
Jacobson et al. 2014	Expert Recommendation

In the Jacobson et al. 2014 review, the authors describe a "Modified Magrath regimen of R-CODOX/R-IVAC" based on the timing and dosage of LaCasce et al. 2004. However, LaCasce et al. 2004 did not include rituximab in the schema. Others have published retrospective series of this regimen; doses here are based on the review article.

Part 1: R-CODOX-M

• Rituximab (Rituxan) as follows:
  • Cycle 1: 375 mg/m² IV once no earlier than day 3
  • Cycle 2 onwards: 375 mg/m² IV once on day 1
• Cyclophosphamide (Cytoxan) 800 mg/m² IV once per day on days 1 & 2
• Vincristine (Oncovin) 1.4 mg/m² (max dose of 2 mg) IV once per day on days 1 & 15
• Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
• Methotrexate (MTX) 3000 mg/m² IV over 2 to 4 hours once on day 15

CNS prophylaxis

• Cytarabine (Cytosar) 50 mg intrathecal once on day 1 (admixed with MTX) and again on day 3 in high-risk patients
• Methotrexate (MTX) 12 mg intrathecal once on day 1

CNS Treatment (for CSF positive)

• Treatment as per CNS prophylaxis PLUS:
• Cytarabine (Cytosar) 50 mg intrathecal once on day 5 of cycle 1 only
• Methotrexate (MTX) 12 mg intrathecal once on day 15 of cycle 1 only

Supportive medications

• Folinic acid (Leucovorin) 200 mg/m² IV once 24 hours after start of IV Methotrexate (MTX), then 15 mg/m² Q6H until methotrexate level undetectable
• Pegfilgrastim (Neulasta) 6 mg SC once on day 3

Part 2: R-IVAC

• Rituximab (Rituxan) 375 mg/m² IV once on day 1
• Ifosfamide (Ifex) 1500 mg/m² IV over 2 hours once per day on days 1 to 5
• Etoposide (Vepesid) 60 mg/m² IV over 1 hour once per day on days 1 to 5
• Cytarabine (Cytosar) 2 g/m² IV over 3 hours Q12H on days 1 & 2 (4 doses total)

CNS prophylaxis

• Methotrexate (MTX) 12 mg intrathecal once on day 5

CNS Treatment (for CSF positive)

• Treatment as per CNS prophylaxis PLUS:
• Cytarabine (Cytosar) 50 mg intrathecal once on day 3 of cycle 1 only

Supportive medications

• Mesna (Mesnex) 300 mg/m² (mixed with Ifosfamide (Ifex)) over 1 hour, then 300mg/m² IV every four hours x 2, on days 1 to 5
• Pegfilgrastim (Neulasta) 6 mg SC once on day 6

Patients with "extensive disease and elevated LDH" receive 2 cycles each of R-CODOX-M and R-IVAC (alternating). Patients with low-risk disease (i.e. single site of disease <10cm with normal LDH) receive 3 cycles of R-CODOX-M.

References

1. Maruyama D, Watanabe T, Maeshima AM, Nomoto J, Taniguchi H, Azuma T, Mori M, Munakata W, Kim SW, Kobayashi Y, Matsuno Y, Tobinai K. Modified cyclophosphamide, vincristine, doxorubicin, and methotrexate (CODOX-M)/ifosfamide, etoposide, and cytarabine (IVAC) therapy with or without rituximab in Japanese adult patients with Burkitt lymphoma (BL) and B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma and BL. Int J Hematol. 2010 Dec;92(5):732-43. Epub 2010 Dec 1. link to original article contains verified protocol PubMed
2. Barnes JA, Lacasce AS, Feng Y, Toomey CE, Neuberg D, Michaelson JS, Hochberg EP, Abramson JS. Evaluation of the addition of rituximab to CODOX-M/IVAC for Burkitt's lymphoma: a retrospective analysis. Ann Oncol. 2011 Aug;22(8):1859-64. Epub 2011 Feb 21. link to original article PubMed
3. Jacobson C, LaCasce A. How I treat Burkitt lymphoma in adults. Blood. 2014 Nov 6;124(19):2913-20. Epub 2014 Sep 25. link to original article contains verified protocol PubMed

R-CODOX-M/R-IVAC (Doxil substituted)

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R-CODOX-M: Rituximab, Cyclophosphamide, Oncovin, DOXil, M ethotrexate

R-IVAC: Rituximab, Ifosfamide, Vepesid (etoposide), AC Ara-C (cytarabine)

Regimen

Study	Evidence
Evens et al. 2013	Phase II

Low risk patients (R-CODOX-M alone)

• Rituximab (Rituxan) 500 mg/m² IV once on days 0 & 8
• Cyclophosphamide (Cytoxan) 800 mg/m² IV over 1 hour once on day 1; 200 mg/m² IV over 1 hour once per day on days 2 to 5
• Vincristine (Oncovin) 1.5 mg/m² (max dose of 2 mg) IV push once on days 1 & 8
• Doxorubicin liposomal (Doxil) 40 mg/m² IV once "per protocol" on day 1
• Methotrexate (MTX) 300 mg/m² IV over 1 hour, followed by 2700 mg/m² IV over next 23 hours on day 10

CNS prophylaxis

• Cytarabine (Cytosar) 70 mg intrathecal once on day 1
• Methotrexate (MTX) 12 mg intrathecal (or 6 mg into Ommaya) once on day 3

Supportive medications

• Folinic acid (Leucovorin) 200 mg/m² IV once 36 hours after start of IV Methotrexate (MTX), then 15 mg/m² IV Q6H until methotrexate level is <5e10^-8
• Filgrastim (Neupogen) 5 mcg/kg SQ once per day on days 6 & 7, then on day 14 onwards until ANC >1,500/uL

3 consecutive cycles

Part 1: R-CODOX-M

• Rituximab (Rituxan) 500 mg/m² IV once on days 0 & 8
• Cyclophosphamide (Cytoxan) 800 mg/m² IV over 1 hour once on day 1; 200 mg/m² IV over 1 hour once per day on days 2 to 5
• Vincristine (Oncovin) 1.5 mg/m² (max dose of 2 mg) IV push once on days 1 & 8
• Doxorubicin liposomal (Doxil) 40 mg/m² IV once "per protocol" on day 1
• Methotrexate (MTX) 300 mg/m² IV over 1 hour, followed by 2700 mg/m² IV over next 23 hours on day 10

CNS prophylaxis

• Cytarabine (Cytosar) 70 mg intrathecal once on days 1 & 3
• Methotrexate (MTX) 12 mg intrathecal (or 6 mg into Ommaya) once on day 15

Supportive medications

• Folinic acid (Leucovorin) 200 mg/m² IV once 36 hours after start of IV Methotrexate (MTX), then 15 mg/m² IV Q6H until methotrexate level is <5e10^-8
• Filgrastim (Neupogen) 5 mcg/kg SQ once per day on days 6 & 7, then on day 14 onwards until ANC >1,500/uL

Part 2: R-IVAC

• Rituximab (Rituxan) 375 mg/m² IV on days 0 & 6 or 7 (2 doses per cycle)
• Ifosfamide (Ifex) 1500 mg/m² IV over 3 hours once per day on days 1 to 5
• Etoposide (Vepesid) 60 mg/m² IV over 1 hour once per day on days 1 to 5
• Cytarabine (Cytosar) 2 g/m² IV over 3 hours Q12H on days 1,2 (4 doses per cycle)

CNS prophylaxis

• Methotrexate (MTX) 15 mg intrathecal once on day 5

Supportive medications

• Mesna (Mesnex) 500 mg/m² mixed with first Ifosfamide (Ifex), then 1000 mg/m²/day IV continuous infusion on days 1 to 5
• Folinic acid (Leucovorin) 15 mg PO q6h x 4 doses, starting 24 hours after intrathecal Methotrexate (MTX)
• Filgrastim (Neupogen) 5 mcg/kg SQ once per day, starting on day 6 or 7 and continuing until ANC >1,500/uL

Four alternating cycles of R-CODOX-M & R-IVAC

References

1. Evens AM, Carson KR, Kolesar J, Nabhan C, Helenowski I, Islam N, Jovanovic B, Barr PM, Caimi PF, Gregory SA, Gordon LI. A multicenter phase II study incorporating high-dose rituximab and liposomal doxorubicin into the CODOX-M/IVAC regimen for untreated Burkitt's lymphoma. Ann Oncol. 2013 Dec;24(12):3076-81. Epub 2013 Oct 20. link to original article contains verified protocol PubMed

R-COPADM

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R-COPADM: Rituximab, Cyclophosphamide, Oncovin (Vincristine), Prednisone, ADriamycin (Doxorubicin), Methotrexate

Regimen

Study	Evidence	Comparator	Efficacy
Ribrag et al. 2016 (LMBA-02)	Phase III	COPADM	Seems to have superior EFS

This regimen is for group B (unresected stage I, non-abdominal stage II and any stage III or IV disease without CNS or bone marrow involvement) or group C (CNS and/or bone marrow involvement). Diviné et al. 2005 list the dose of HD-MTX as 3 mg/m² but this is presumed to be a typo. Treatment is preceded by pre-phase COP.

COPADM #1

• Rituximab (Rituxan) 375 mg/m² IV once per day on days 1 & 6
• Cyclophosphamide (Cytoxan) 500 mg/m²/day IV (in 2 fractions) on days 2 to 4
• Vincristine (Oncovin) 1.4 mg/m² (max dose of 2 mg) IV once on day 1
• Prednisone (Sterapred) 60 mg/m²/day PO/IV on days 1 to 6
• Doxorubicin (Adriamycin) 60 mg/m² IV once on day 2
• Methotrexate (MTX) 3000 mg/m² IV over 3 hours once on day 1

Supportive medications

• Folinic acid (Leucovorin) 15 mg/m² (route not specified) q6h on days 2 to 4

CNS prophylaxis (group B)

• Methotrexate (MTX) 15 mg IT once per day on days 2 & 6
• Hydrocortisone (Cortef) (dose not specified) IT once per day on days 2 & 6 (admixed with MTX)

CNS treatment (group C)

• Methotrexate (MTX) 15 mg IT once per day on days 2, 4, 6
• Cytarabine (Cytosar) 40 mg IT once per day on dyas 2, 4, 6
• Hydrocortisone (Cortef) (dose not specified) IT once per day on days 2, 4, 6 (admixed with MTX & Ara-C)

One cycle

As soon as the ANC was >1.5 × 10⁹/L and platelet count was >100 × 10⁹/L, patients proceeded to:

COPADM #2

• Rituximab (Rituxan) 375 mg/m² IV once per day on days 1 & 6
• Cyclophosphamide (Cytoxan) 1000 mg/m²/day IV (in 2 fractions) on days 2 to 4
• Vincristine (Oncovin) 1.4 mg/m² (max dose of 2 mg) IV once per day on days 1 & 6
• Prednisone (Sterapred) 60 mg/m²/day PO/IV on days 1 to 6
• Doxorubicin (Adriamycin) 60 mg/m² IV once on day 2
• Methotrexate (MTX) 3000 mg/m² IV over 3 hours once on day 1

Supportive medications

• Folinic acid (Leucovorin) 15 mg/m² (route not specified) q6h on days 2 to 4

CNS prophylaxis (group B)

• Methotrexate (MTX) 15 mg IT once per day on days 2 & 6
• Hydrocortisone (Cortef) (dose not specified) IT once per day on days 2 & 6 (admixed with MTX)

CNS treatment (group C)

• Methotrexate (MTX) 15 mg IT once per day on days 2, 4, 6
• Cytarabine (Cytosar) 40 mg IT once per day on dyas 2, 4, 6
• Hydrocortisone (Cortef) (dose not specified) IT once per day on days 2, 4, 6 (admixed with MTX & Ara-C)

One cycle

As soon as the ANC was >1.5 × 10⁹/L and platelet count was >100 × 10⁹/L, patients in group B proceeded to CYM consolidation, and patients in group C proceeded to CYVE consolidation.

References

1. Ribrag V, Koscielny S, Bosq J, Leguay T, Casasnovas O, Fornecker LM, Recher C, Ghesquieres H, Morschhauser F, Girault S, Gouill SL, Ojeda-Uribe M, Mariette C, Cornillon J, Cartron G, Verge V, Chassagne-Clément C, Dombret H, Coiffier B, Lamy T, Tilly H, Salles G. Rituximab and dose-dense chemotherapy for adults with Burkitt's lymphoma: a randomised, controlled, open-label, phase 3 trial. Lancet. 2016 Apr 11. [Epub ahead of print] link to original article PubMed

R-HyperCVAD/R-MA

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R-HyperCVAD: Rituximab, Hyperfractionated Cyclophosphamide, Vincristine, Adriamycin (Doxorubicin), Dexamethasone
R-MA: Rituximab, Methotrexate, Ara-C (Cytarabine)

Regimen

Study	Evidence
Thomas et al. 2006	Pilot, <20 pts

Part A (cycles 1, 3, 5, 7)

• Rituximab (Rituxan) as follows:
  • Cycles 1 & 3: 375 mg/m² IV over 2 to 6 hours once per day on days 1 & 11
• Cyclophosphamide (Cytoxan) 300 mg/m² IV over 2 hours Q12H on days 1 to 3 (6 total doses)
• Vincristine (Oncovin) 2 mg IV once per day on days 4 & 11
• Doxorubicin (Adriamycin) 50 mg/m²/day IV continuous infusion on day 4 (total dose per cycle: 50 mg/m²)
• Dexamethasone (Decadron) 40 mg PO/IV once per day on days 1 to 4, 11 to 14

CNS prophylaxis

• Methotrexate (MTX) 12 mg (6 mg if given via Ommaya reservoir) IT once on day 2
• Cytarabine (Cytosar) 100 mg IT once on day 7

Given each cycle for a total of 16 intrathecal treatments. If CNS disease present, therapy augmented to twice-weekly alternating (MTX, ara-C) treatments until CSF cell count normalizes and cytology is negative, then continues for 4 more alternating weekly treatments; prophylaxis course then resumes.

Supportive care:

• Mesna (Mesnex) 600 mg/m²/day IV continuous infusion on days 1 to 3, starting 1 hour before Cyclophosphamide (Cytoxan) and completed 12 hours after the last dose of Cyclophosphamide (Cytoxan)
• Filgrastim (Neupogen) 10 mcg/kg SC once per day starting 24 hours after completion of chemotherapy, given until WBC >3 x 10⁹/L or bone pain present
• ONE of the following antibiotics:
  • Quinolone
  • Trimethoprim/Sulfamethoxazole (Bactrim DS) (160/800 mg) dose/route not specified
• Fluconazole (Diflucan) dose/route not specified
• ONE of the following antivirals:
  • Acyclovir (Zovirax) dose/route not specified
  • Valacyclovir (Valtrex) dose/route not specified

Dose modifications

• Vincristine (Oncovin) reduced to 1 mg for bilirubin > 2 mg/dL or NCI common toxicity criteria Grade 2+ peripheral neuropathy, omitted for bilirubin > 3 mg/dL or for ileus
• Doxorubicin (Adriamycin) reduced by 50% for bilirubin 2 to 3 mg/dL, by 75% for bilirubin 3 to 5 mg/dL (eliminated for bilirubin > 5 mg/dL or for gastric/small-bowel involvement with Course 1 to reduce duration of myelosuppression given risk of perforation)

Next cycle to start no sooner than 14 days or as soon as "unmaintained" WBC count is > 3 x 10⁹/L and platelet count > 50 x 10⁹/L

Part B (cycles 2, 4, 6, 8)

• Rituximab (Rituxan) as follows:
  • Cycles 2 & 4: 375 mg/m² IV over 2 to 6 hours once per day on days 2 & 8
• Methotrexate (MTX) 1000 mg/m²/day IV continuous infusion on day 1 (total dose per cycle: 1000 mg/m²)
• Cytarabine (Cytosar) 3000 mg/m² IV over 2 hours Q12H on days 2 & 3 (4 total doses)

CNS prophylaxis

• Methotrexate (MTX) 12 mg (6 mg if given via Ommaya reservoir) IT once on day 2
• Cytarabine (Cytosar) 100 mg IT once on day 7

Given each cycle for a total of 16 intrathecal treatments. If CNS disease present, therapy augmented to twice-weekly alternating (MTX, ara-C) treatments until CSF cell count normalizes and cytology is negative, then continues for 4 more alternating weekly treatments; prophylaxis course then resumes.

Supportive care:

• Folinic acid (Leucovorin) 50 mg IV x1 12 hours after Methotrexate (MTX) is complete, then 15 mg IV Q6H x 8 doses until serum methotrexate level <0.1 µM
• Filgrastim (Neupogen) 10 mcg/kg SC once per day starting 24 hours after completion of chemotherapy, given until WBC >3 x 10⁹/L or bone pain present
• ONE of the following antibiotics:
  • Quinolone
  • Trimethoprim/Sulfamethoxazole (Bactrim DS) (160/800 mg) dose/route not specified
• Fluconazole (Diflucan) dose/route not specified
• ONE of the following antivirals:
  • Acyclovir (Zovirax) dose/route not specified
  • Valacyclovir (Valtrex) dose/route not specified

Dose modifications

• Cytarabine (Cytosar) reduced to 1000 mg/m² for patients >=60 years old, creatinine >=1.5 mg/dL or 0 hour MTX level >= 20 µmol/L
• Methotrexate (MTX) reduced by 50% for creatinine clearance 10 to 50 mL/min (eliminated for < 10 mL/min), by 25% to 75% for delayed excretion and/or nephrotoxicity with prior course (dependent on severity) or by 50% for pleural effusions/ascites with drainage of fluid as feasible.

Next cycle to start no sooner than 14 days or as soon as "unmaintained" WBC count is > 3 x 10⁹/L and platelet count > 50 x 10⁹/L

References

1. Thomas DA, Faderl S, O'Brien S, Bueso-Ramos C, Cortes J, Garcia-Manero G, Giles FJ, Verstovsek S, Wierda WG, Pierce SA, Shan J, Brandt M, Hagemeister FB, Keating MJ, Cabanillas F, Kantarjian H. Chemoimmunotherapy with hyper-CVAD plus rituximab for the treatment of adult Burkitt and Burkitt-type lymphoma or acute lymphoblastic leukemia. Cancer. 2006 Apr 1;106(7):1569-80. link to original article contains verified protocol PubMed

Consolidation/Intensification therapy

BASIC

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BASIC: Brief, Anthracycline-Sparing, Intensive Cyclophosphamide

Regimen

Study	Evidence
Kasamon et al. 2012	Non-randomized

Treatment preceded by BASIC induction.

Chemotherapy, part 1

• Rituximab (Rituxan) 375 mg/m² IV once on day 1
• Cyclophosphamide (Cytoxan) 50 mg/kg IV over 1 to 2 hours once per day on days 2 to 5

Supportive medications

• Mesna (Mesnex) 40 mg/kg/day IV "in divided doses" on days 2 to 5
• Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 11 and continuing until post-nadir ANC >1000/uL

One course, followed once post-nadir ANC > 1000/uL by:

Chemotherapy, part 2

• Rituximab (Rituxan) 375 mg/m² IV once per week for 4 doses

CNS treatment

• (only given if there was prior CNS involvement):
• Cytarabine (Cytosar) 100 mg IT once per week for 4 doses, then once every other week for 4 doses
• Hydrocortisone (Cortef) 50 mg IT is optional (no parameters given)

References

1. Kasamon YL, Brodsky RA, Borowitz MJ, Ambinder RF, Crilley PA, Cho SY, Tsai HL, Smith BD, Gladstone DE, Carraway HE, Huff CA, Matsui WH, Bolaños-Meade J, Jones RJ, Swinnen LJ. Brief intensive therapy for older adults with newly diagnosed Burkitt or atypical Burkitt lymphoma/leukemia. Leuk Lymphoma. 2013 Mar;54(3):483-90. Epub 2012 Aug 17. link to original article link to PMC article contains verified protocol PubMed

CYM

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CYM: CYtarabine, Methotrexate

Regimen

Study	Evidence
Diviné et al. 2005 (LMB95)	Phase II

This regimen is for group B (unresected stage I, non-abdominal stage II and any stage III or IV disease without CNS or bone marrow involvement). Treatment preceded by COPADM.

Chemotherapy

• Cytarabine (Cytosar) 100 mg/m²/day IV continuous infusion on days 2 to 6 (total dose per cycle: 500 mg/m²)
• Methotrexate (MTX) 3000 mg/m² IV over 3 hours once on day 1

Supportive medications

• Folinic acid (Leucovorin) 15 mg/m² (route not specified) q6h on days 2 to 4

CNS prophylaxis

• Methotrexate (MTX) 15 mg IT once on day 2
• Cytarabine (Cytosar) 30 mg IT once on day 6
• Hydrocortisone (Cortef) 15 mg IT once per day on days 2 & 6 (admixed with chemo)

2 cycles; intervals were as short as possible, as soon as the ANC was >1.5 × 10⁹/L and platelet count was >100 × 10⁹/L

Treatment followed by COPADM maintenance.

References

1. Diviné M, Casassus P, Koscielny S, Bosq J, Sebban C, Le Maignan C, Stamattoulas A, Dupriez B, Raphaël M, Pico JL, Ribrag V; GELA; GOELAMS. Burkitt lymphoma in adults: a prospective study of 72 patients treated with an adapted pediatric LMB protocol. Ann Oncol. 2005 Dec;16(12):1928-35. Epub 2005 Nov 10. link to original article contains verified protocol PubMed

CYVE

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CYVE: CYtarabine, VEpesid (Etoposide)

Regimen

Study	Evidence
Diviné et al. 2005 (LMB95)	Phase II, <20 pts in this subgroup

This regimen is for group C (CNS and/or bone marrow involvement). Note the unusual schedule of cytarabine; presumably the low-dose and high-dose portions are given at separate times in the 24 hour period but this detail is not further specified in the manuscript. Treatment preceded by COPADM.

Chemotherapy

• Cytarabine (Cytosar) as follows:
  • 50 mg/m² IV over 12 hours once per day on days 1 to 5
  • 3000 mg/m² IV over 3 hours once per day on days 2 to 5
• Etoposide (Vepesid) 200 mg/m² IV once per day on days 2 to 5

2 cycles; intervals were as short as possible, as soon as the ANC was >1.5 × 10⁹/L and platelet count was >100 × 10⁹/L

Treatment followed by COPAD alternating with CYVE maintenance.

References

1. Diviné M, Casassus P, Koscielny S, Bosq J, Sebban C, Le Maignan C, Stamattoulas A, Dupriez B, Raphaël M, Pico JL, Ribrag V; GELA; GOELAMS. Burkitt lymphoma in adults: a prospective study of 72 patients treated with an adapted pediatric LMB protocol. Ann Oncol. 2005 Dec;16(12):1928-35. Epub 2005 Nov 10. link to original article contains verified protocol PubMed

Maintenance therapy

COPAD/CYVE

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COPAD: Cyclophosphamide, Oncovin (Vincristine), Prednisone, ADriamycin (Doxorubicin)
CYVE: CYtarabine, VEpesid (Etoposide)

Regimen

Study	Evidence
Diviné et al. 2005 (LMB95)	Phase II, <20 pts in this subgroup

This regimen is for group C (CNS and/or bone marrow involvement). Treatment preceded by CYVE consolidation. Note that the days of administration for the CYVE cycles are counted from the start of the respective COPAD cycles.

COPAD

• Cyclophosphamide (Cytoxan) 500 mg/m² IV once per day on days 1 & 2
• Vincristine (Oncovin) 1.4 mg/m² (max dose of 2 mg) IV once on day 1
• Prednisone (Sterapred) 60 mg/m²/day PO on days 1 to 5
• Doxorubicin (Adriamycin) 60 mg/m² IV once on day 2

CNS treatment

Note: this is only given with the first cycle of maintenance; patients with positive CNS at diagnosis were to also undergo 24 Gy of cranial irradiation.

• Methotrexate (MTX) 15 mg IT once on day 2
• Cytarabine (Cytosar) 40 mg IT once on day 2
• Hydrocortisone (Cortef) 15 mg IT once on day 2 (admixed with MTX & Ara-C)

CYVE

• Cytarabine (Cytosar) 50 mg/m² SC BID on days 28 to 32
• Etoposide (Vepesid) 150 mg/m² IV once per day on days 28 to 30

4 alternating cycles (COPAD -> CYVE -> COPAD -> CYVE)

References

1. Diviné M, Casassus P, Koscielny S, Bosq J, Sebban C, Le Maignan C, Stamattoulas A, Dupriez B, Raphaël M, Pico JL, Ribrag V; GELA; GOELAMS. Burkitt lymphoma in adults: a prospective study of 72 patients treated with an adapted pediatric LMB protocol. Ann Oncol. 2005 Dec;16(12):1928-35. Epub 2005 Nov 10. link to original article contains verified protocol PubMed

COPADM

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COPADM: Cyclophosphamide, Oncovin (Vincristine), Prednisone, ADriamycin (Doxorubicin), Methotrexate

Regimen

Study	Evidence
Diviné et al. 2005 (LMB95)	Phase II

This regimen is for group B (unresected stage I, non-abdominal stage II and any stage III or IV disease without CNS or bone marrow involvement). Treatment is preceded by CYM consolidation.

Chemotherapy

• Cyclophosphamide (Cytoxan) 500 mg/m² IV once per day on days 1 & 2
• Vincristine (Oncovin) 1.4 mg/m² (max dose of 2 mg) IV once on day 1
• Prednisone (Sterapred) 60 mg/m²/day PO on days 1 to 5
• Doxorubicin (Adriamycin) 60 mg/m² IV once on day 2
• Methotrexate (MTX) 3000 mg/m² IV over 3 hours once on day 1

Supportive medications

• Folinic acid (Leucovorin) 15 mg/m² (route not specified) q6h on days 2 to 4

CNS prophylaxis

• Methotrexate (MTX) 15 mg IT once on day 2
• Hydrocortisone (Cortef) 15 mg IT once on day 2 (admixed with MTX)

One cycle

References

1. Diviné M, Casassus P, Koscielny S, Bosq J, Sebban C, Le Maignan C, Stamattoulas A, Dupriez B, Raphaël M, Pico JL, Ribrag V; GELA; GOELAMS. Burkitt lymphoma in adults: a prospective study of 72 patients treated with an adapted pediatric LMB protocol. Ann Oncol. 2005 Dec;16(12):1928-35. Epub 2005 Nov 10. link to original article contains verified protocol PubMed