HIV-associated lymphoma
Section editor | |
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Tarsheen Sethi, MD, MSCI Yale University New Haven, CT tarsheen2 |
19 regimens on this page
25 variants on this page
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The most common HIV-associated lymphomas are of DLBCL or Burkitt lymphoma histology; plasmablastic lymphoma and primary effusion lymphomas are also frequently seen in advanced-stage HIV/AIDS. In patients with a normal CD4+ T-cell count and well-controlled HIV, the lymphoma is typically treated as per the histologic subtype. For others, regimens specific to HIV-associated lymphoma have been developed and are included here.
Untreated, pre-phase
CVP
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CVP: Cyclophosphamide, Vincristine, Prednisone
COP: Cyclophosphamide, Oncovin (Vincristine), Prednisone
Regimen
Study | Evidence |
---|---|
Galicier et al. 2007 (LMB86) | Phase II |
Chemotherapy
- Cyclophosphamide (Cytoxan) 300 mg/m2/day IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
- Prednisone (Sterapred) 60 mg/m2/day IV or PO on days 1 to 7
Subsequent treatment
References
- LMB86: Galicier L, Fieschi C, Borie R, Meignin V, Daniel MT, Gérard L, Oksenhendler E. Intensive chemotherapy regimen (LMB86) for St Jude stage IV AIDS-related Burkitt lymphoma/leukemia: a prospective study. Blood. 2007 Oct 15;110(8):2846-54. Epub 2007 Jul 3. link to original article contains verified protocol PubMed
Upfront therapy
CHOP
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CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
CHOP-21: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone every 21 days
ACOP
CAVP
COPA
VACP
VCAP
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kaplan et al. 2005 (AMC010) | 1998-2002 | Phase III (C) | R-CHOP | Did not meet primary endpoint of CR rate |
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive medications
- Combination antiretrovirals were required
- G-CSF (type not specified) 5 mcg/kg SC once per day from days 4 to 13 or until ANC greater than 10k/uL.
- PCP prophylaxis with ONE of the following:
- Cotrimoxazole (dose/route/schedule not specified)
- Dapsone (Aczone) (dose/route/schedule not specified)
- Pentamidine (Nebupent) (dose/schedule not specified)
21-day cycle for 3 cycles for early disease, or minimum of 6 cycles or 2 past CR for advanced disease
Subsequent treatment
- Patients with stage I, IE, or nonbulky stage II disease: IFRT, beginning 3 weeks after the third cycle of chemotherapy
References
- AMC010: Kaplan LD, Lee JY, Ambinder RF, Sparano JA, Cesarman E, Chadburn A, Levine AM, Scadden DT. Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood. 2005 Sep 1;106(5):1538-43. Epub 2005 May 24. link to original article contains verified protocol link to PMC article PubMed
CODOX-M
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CODOX-M: Cyclophosphamide, Oncovin, DOXorubicin, Methotrexate
Regimen
Study | Evidence |
---|---|
Wang et al. 2003 | Retrospective |
Note: Wang et al. 2003 retrospectively identified 8 HIV+ Burkitt lymphoma patients who had undergone treatment with CODOX-M/IVAC per the NCI 77-04 protocol.
- Patients are stratified into high and low risk:
- Low risk patients must fulfill all of the following criteria:
- Serum LDH within the institution's normal range (for the NCI, this was less than 350 IU/L)
- Single extraabdominal mass or completely resected abdominal disease
- Any patients which do not meet low risk criteria are classified as high risk
- Low risk patients must fulfill all of the following criteria:
This regimen is for low risk patients.
Chemotherapy
- 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) 1200 mg/m2 IV over 60 minutes once on day 10, then 240 mg/m2/hour IV continuous infusion over 23 hours (total dose per cycle: 6720 mg/m2)
CNS prophylaxis
- Cytarabine (Ara-C) 70 mg IT once on day 1
- Patients younger than 3 years old received "appropriately reduced doses"
- Methotrexate (MTX) 12 mg IT once on day 3
- Patients younger than 3 years old received "appropriately reduced doses"
Supportive medications
- Folinic acid (Leucovorin) 192 mg/m2 IV once on day 11, starting 36 hours after the start of the day 10 methotrexate, then 12 mg/m2 IV every 6 hours thereafter until serum methotrexate level is less than 50 nmol/L
3 cycles; each cycle starts on the same day that the patient's ANC is greater than 1000/uL
References
- Retrospective: Wang ES, Straus DJ, Teruya-Feldstein J, Qin J, Portlock C, Moskowitz C, Goy A, Hedrick E, Zelenetz AD, Noy A. Intensive chemotherapy with cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) for human immunodeficiency virus-associated Burkitt lymphoma. Cancer. 2003 Sep 15;98(6):1196-205. link to original article contains verified protocol PubMed
CODOX-M/IVAC
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CODOX-M/IVAC: Cyclophosphamide, Oncovin, DOXorubicin, Methotrexate alternating with Ifosfamide, Vepesid (etoposide), Ara-C (cytarabine)
Protocol
Study | Evidence |
---|---|
Magrath et al. 1996 (77-04) | Phase II |
Wang et al. 2003 | Retrospective |
Note: the original protocol of Magrath et al. 1996 did not comment on HIV status. Wang et al. 2003 retrospectively identified 8 HIV+ Burkitt lymphoma patients who had undergone treatment with CODOX-M/IVAC.
- Patients are stratified into high and low risk:
- Low risk patients must fulfill all of the following criteria:
- Serum LDH within the institution's normal range (for the NCI, this was less than 350 IU/L)
- Single extraabdominal mass or completely resected abdominal disease
- Any patients which do not meet low risk criteria are classified as high risk
- Low risk patients must fulfill all of the following criteria:
This regimen is for high-risk patients.
Chemotherapy, Part A: 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) as follows:
- Cycle 1: 1.5 mg/m2 IV once per day on days 1 & 8
- Cycle 3: 1.5 mg/m2 IV once per day on days 1, 8, 15
- Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
- Methotrexate (MTX) 1200 mg/m2 IV over 60 minutes once on day 10, then 240 mg/m2/hour IV continuous infusion over 23 hours (total dose per cycle: 6720 mg/m2)
CNS prophylaxis
- Cytarabine (Ara-C) 70 mg IT once per day on days 1 & 3
- Patients younger than 3 years old received "appropriately reduced doses"
- Methotrexate (MTX) 12 mg IT once on day 15
- Patients younger than 3 years old received "appropriately reduced doses"
Patients with CNS disease at presentation received the following extra doses of intrathecal chemotherapy during cycle 1:
- Cytarabine (Ara-C) 70 mg IT once on day 5 (in addition to doses above)
- Methotrexate (MTX) 12 mg IT once on day 17 (in addition to dose above)
Supportive medications
- Folinic acid (Leucovorin) 192 mg/m2 IV once on day 11, starting 36 hours after the start of the day 10 methotrexate, then 12 mg/m2 IV every 6 hours thereafter until serum methotrexate level is less than 50 nmol/L
- GM-CSF 7.5 mcg/kg SC once per day, starting on day 13 and continuing until ANC greater than 1000/uL
Chemotherapy, Part B: IVAC
- Ifosfamide (Ifex) 1500 mg/m2 IV once per day on days 1 to 5
- Etoposide (Vepesid) 60 mg/m2 IV once per day on days 1 to 5
- Cytarabine (Ara-C) 2000 mg/m2 IV every 12 hours on days 1 & 2 (total dose per cycle: 8000 mg/m2)
CNS prophylaxis
- Methotrexate (MTX) 12 mg IT once on day 5
Patients with CNS disease at presentation received the following extra doses of intrathecal chemotherapy during cycle 2:
- Cytarabine (Ara-C) 70 mg IT once per day on days 7 & 9
- Methotrexate (MTX) 12 mg IT once on day 17 (in addition to dose above)
Supportive medications
- Mesna (Mesnex) 360 mg/m2 IV every 3 hours on days 1 to 5, given at same time as Ifosfamide (Ifex)
- GM-CSF 7.5 mcg/kg SC once per day, starting on day 7 and continuing until ANC greater than 1000/uL
4 cycles (see note)
Note: CODOX-M and IVAC are given in an alternating fashion for a total of 4 cycles (A, B, A, B). Each cycle starts on the same day that the patient's ANC is greater than 1000/uL.
References
- 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
- Retrospective: Wang ES, Straus DJ, Teruya-Feldstein J, Qin J, Portlock C, Moskowitz C, Goy A, Hedrick E, Zelenetz AD, Noy A. Intensive chemotherapy with cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) for human immunodeficiency virus-associated Burkitt lymphoma. Cancer. 2003 Sep 15;98(6):1196-205. link to original article contains verified protocol PubMed
dmCODOX-M - Modified Magrath
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dmCODOX-M: dose-modified Cyclophosphamide, Oncovin, DOXorubicin, Methotrexate
Regimen
Study | Evidence |
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Mead et al. 2008 (MRC/NCRI LY10) | Non-randomized |
- Patients are stratified into high and low risk:
- Low risk patients must fulfill at least 3 of the following criteria:
- Normal LDH
- WHO performance status of 0 or 1
- Ann Arbor stage I or II
- 0 or 1 extranodal sites of disease
- Any patients which do not meet low risk criteria are classified as high risk
- Low risk patients must fulfill at least 3 of the following criteria:
This regimen is for low risk patients.
Chemotherapy
- 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 (maximum dose of 2 mg) IV once per day on days 1 & 8
- Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
- Methotrexate (MTX) as follows:
- Patients 65 years old or younger: 300 mg/m2 IV over 60 minutes once on day 10, then 2700 mg/m2 IV continuous infusion over 23 hours (total dose per cycle: 3000 mg/m2)
- Patients older than 65 years old: 100 mg/m2 IV over 60 minutes once on day 10, then 900 mg/m2 IV continuous infusion over 23 hours (total dose per cycle: 1000 mg/m2)
CNS prophylaxis
- Cytarabine (Ara-C) 70 mg IT once per day on days 1 & 3
- Methotrexate (MTX) 12 mg IT once on day 15
Patients with CNS disease at presentation received the following extra doses of intrathecal chemotherapy:
- Cytarabine (Ara-C) 70 mg IT once on day 5 (in addition to doses above)
- Methotrexate (MTX) 12 mg IT once on day 17 (in addition to dose above)
- Folinic acid (Leucovorin) 15 mg PO once on day 18, 24 hours after intrathecal Methotrexate (MTX)
Supportive medications
- Folinic acid (Leucovorin) 15 mg/m2 IV every 3 hours for 5 doses on day 11, starting 36 hours after start of the day 10 methotrexate, then 15 mg/m2 IV every 6 hours until methotrexate level is less than 50 nmol/L
- Folinic acid (Leucovorin) 15 mg PO once on day 16, 24 hours after intrathecal Methotrexate (MTX)
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 13 and continuing until ANC greater than 1000/uL
- Allopurinol (Zyloprim) PO and/or Rasburicase (Elitek) prior to starting chemotherapy
3 cycles (see note)
Note: Each cycle starts on the same day that the patient's ANC is greater than 1000/uL and unsupported (that is, without transfusion) platelet count greater than 75 x 109/L.
References
- 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 link to PMC article PubMed
dmCODOX-M/IVAC - Modified Magrath
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dmCODOX-M/IVAC: dose-modified Cyclophosphamide, Oncovin, DOXorubicin, Methotrexate alternating with Ifosfamide, Vepesid (etoposide), Ara-C (cytarabine)
Protocol
Study | Evidence |
---|---|
Mead et al. 2008 (MRC/NCRI LY10) | Non-randomized |
- Patients are stratified into high and low risk:
- Low risk patients must fulfill at least 3 of the following criteria:
- Normal LDH
- WHO performance status of 0 or 1
- Ann Arbor stage I or II
- 0 or 1 extranodal sites of disease
- Any patients which do not meet low risk criteria are classified as high risk
- Low risk patients must fulfill at least 3 of the following criteria:
This regimen is for high-risk patients.
Chemotherapy, Part A: dmCODOX-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 (maximum dose of 2 mg) IV once per day on days 1 & 8
- Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
- Methotrexate (MTX) as follows:
- Patients 65 years old or younger: 300 mg/m2 IV over 60 minutes once on day 10, then 2700 mg/m2 IV continuous infusion over 23 hours (total dose per cycle: 3000 mg/m2)
- Patients older than 65 years old: 100 mg/m2 IV over 60 minutes once on day 10, then 900 mg/m2 IV continuous infusion over 23 hours (total dose per cycle: 1000 mg/m2)
CNS prophylaxis
- Cytarabine (Ara-C) 70 mg IT once per day on days 1 & 3
- Methotrexate (MTX) 12 mg IT once on day 15
Patients with CNS disease at presentation received the following extra doses of intrathecal chemotherapy:
- Cytarabine (Ara-C) 70 mg IT once on day 5 (in addition to doses above)
- Methotrexate (MTX) 12 mg IT once on day 17 (in addition to dose above)
- Folinic acid (Leucovorin) 15 mg PO once on day 18, 24 hours after intrathecal Methotrexate (MTX)
Supportive medications
- Folinic acid (Leucovorin) 15 mg/m2 IV every 3 hours for 5 doses on day 11, starting 36 hours after start of the day 10 methotrexate, then 15 mg/m2 IV every 6 hours until methotrexate level is less than 50 nmol/L
- Folinic acid (Leucovorin) 15 mg PO once on day 16, 24 hours after intrathecal Methotrexate (MTX)
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 13 and continuing until ANC greater than 1000/uL
- Allopurinol (Zyloprim) PO and/or Rasburicase (Elitek) prior to starting chemotherapy
Chemotherapy, Part B: IVAC
- Ifosfamide (Ifex) as follows:
- Patients 65 years old or younger: 1500 mg/m2 IV over 60 minutes once per day on days 1 to 5
- Patients older than 65 years old: 1000 mg/m2 IV over 60 minutes once per day on days 1 to 5
- Etoposide (Vepesid) 60 mg/m2 IV over 60 minutes once per day on days 1 to 5
- Cytarabine (Ara-C) as follows:
- Patients 65 years old or younger: 2000 mg/m2 IV over 3 hours every 12 hours on days 1 & 2 (total dose per cycle: 8000 mg/m2)
- Patients older than 65 years old: 1000 mg/m2 IV over 3 hours every 12 hours on days 1 & 2 (total dose per cycle: 4000 mg/m2)
CNS prophylaxis
- Methotrexate (MTX) 12 mg IT once on day 5
Supportive medications
- Mesna (Mesnex) as follows:
- Patients 65 years old or younger: 300 mg/m2 (mixed with Ifosfamide (Ifex)) IV over 60 minutes once per day on days 1 to 5, then 300 mg/m2 IV every four hours for 2 doses on days 1 to 5
- Patients older than 65 years old: 200 mg/m2 (mixed with Ifosfamide (Ifex)) IV over 60 minutes once per day on days 1 to 5, then 200 mg/m2 IV every four hours for 2 doses on days 1 to 5
- Folinic acid (Leucovorin) 15 mg PO once on day 6, 24 hours after intrathecal Methotrexate (MTX)
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 7 and continuing until ANC greater than 1000/uL
4 cycles (see note)
Note: dmCODOX-M and IVAC are given in an alternating fashion for a total of 4 cycles (A, B, A, B). Each cycle starts on the same day that the patient's ANC is greater than 1000/uL and unsupported (that is, without transfusion) platelet count greater than 75 x 109/L.
References
- 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 link to PMC article PubMed
EPOCH, dose-escalated
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EPOCH: Etoposide, Prednisone, Oncovin (Vincristine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin)
Regimen
Study | Evidence |
---|---|
Little et al. 2003 | Non-randomized |
Note: the paper refers to this regimen as dose-adjusted EPOCH but to avoid confusion with the other version of dose-adjusted EPOCH, we refer to it as dose-escalated EPOCH, here.
Chemotherapy
- Etoposide (Vepesid) 50 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 200 mg/m2)
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 5
- Vincristine (Oncovin) 0.4 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg/m2)
- Cyclophosphamide (Cytoxan) as follows:
- CD4+ count less than 100/uL: 187 mg/m2 IV over 15 minutes once on day 5
- CD4+ count greater than 100/uL: 375 mg/m2 IV over 15 minutes once on day 5
- In each subsequent cycle, increase dose by 187 mg/m2 if the neutrophil nadir is greater than 500/uL and platelet nadir is greater than 25 x 109/L. Decrease dose by 187 mg/m2 if the neutrophil nadir is less than 500/uL or platelet nadir is less than 25 x 109/L.
- Doxorubicin (Adriamycin) 10 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m2)
Supportive medications
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 6 and continuing until ANC greater than 5000/uL past nadir
21-day cycle for 6 cycles
References
- Little RF, Pittaluga S, Grant N, Steinberg SM, Kavlick MF, Mitsuya H, Franchini G, Gutierrez M, Raffeld M, Jaffe ES, Shearer G, Yarchoan R, Wilson WH. Highly effective treatment of acquired immunodeficiency syndrome-related lymphoma with dose-adjusted EPOCH: impact of antiretroviral therapy suspension and tumor biology. Blood. 2003 Jun 15;101(12):4653-9. Epub 2003 Feb 27. 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
Protocol
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.
Chemotherapy, prephase
- Cyclophosphamide (Cytoxan) 200 mg/m2 IV over 60 minutes 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
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV over 4 hours once on day 7
Chemotherapy
- Vincristine (Oncovin) 2 mg IV bolus once on day 8
- Methotrexate (MTX) 1500 mg/m2 IV continuous infusion over 24 hours, started on day 8
- Older than 55 years: reduce dose by 50%
- Ifosfamide (Ifex) 800 mg/m2 IV over 60 minutes 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 60 minutes once per day on days 11 & 12
- Cytarabine (Ara-C) 150 mg/m2 IV over 60 minutes twice per day on days 11 & 12
- Older than 55 years: reduce dose by 50%
Supportive medications
- Folinic acid (Leucovorin) (dose/route/schedule not specified), starting 12 hours after Methotrexate (MTX) infusion
Cycle B
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV over 4 hours once on day 28
Chemotherapy
- Vincristine (Oncovin) 2 mg IV bolus once on day 29
- Methotrexate (MTX) 1500 mg/m2 IV continuous infusion over 24 hours, started on day 29
- Older than 55 years: reduce dose by 50%
- Cyclophosphamide (Cytoxan) 200 mg/m2 IV over 60 minutes 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
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV over 4 hours once on day 49
Chemotherapy
- Vindesine (Eldisine) 3 mg/m2 (maximum dose of 5 mg) IV bolus once on day 50
- Methotrexate (MTX) 1500 mg/m2 IV continuous infusion over 24 hours, started on day 50
- Older than 55 years: reduce 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 60 minutes once per day on days 53 & 54
- Cytarabine (Ara-C) 2000 mg/m2 IV over 3 hours twice per day on day 54
- Older than 55 years: reduce 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 x 2 courses (6 total cycles)
- Older than 55 years: Alternate A & B x 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 IT once per day on days 1, 8, 12, 29, 33
- Cytarabine (Ara-C) 40 mg IT once per day on days 1, 8, 12, 29, 33
- Dexamethasone (Decadron) 20 mg IT once per day on days 1, 8, 12, 29, 33
8 doses total
References
- Burkimab: 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 NCT00388193
m-BACOD
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m-BACOD: methotrexate (moderate dose), Bleomycin, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Dexamethasone
Regimen variant #1, "low-dose" #1
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kaplan et al. 1997 (ACTG 142) | 1991-1994 | Phase III (E-de-esc) | m-BACOD; standard-dose | Did not meet primary endpoint of OS |
Note: this is of historical interest, only.
Chemotherapy
- Methotrexate (MTX) 200 mg/m2 IV once on day 15
- Bleomycin (Blenoxane) 4 units/m2 IV once on day 1
- Doxorubicin (Adriamycin) 25 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 300 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
- Dexamethasone (Decadron) 3 mg/m2 PO once per day on days 1 to 5
Supportive medications
- Sargramostim (Leukine) 5 mcg/kg SC once per day on days 4 to 13 (as needed)
CNS prophylaxis
- Cytarabine (Ara-C) as follows:
- Cycle 1: 50 mg IT once per day on days 1, 8, 15, 22
21-day cycle for 2 cycles past complete remission (minimum of 4 cycles)
Regimen variant #2, "low-dose" #2
Study | Evidence |
---|---|
Levine et al. 1991 | Non-randomized |
Note: this is of historical interest, only; the MTX dose is slightly higher than above.
Chemotherapy
- Methotrexate (MTX) 500 mg/m2 IV once on day 15
- Bleomycin (Blenoxane) 4 units/m2 IV once on day 1
- Doxorubicin (Adriamycin) 25 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 300 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
- Dexamethasone (Decadron) 3 mg/m2 PO once per day on days 1 to 5
Supportive medications
CNS prophylaxis
- Cytarabine (Ara-C) 50 mg IT once per day on days 1, 8, 21, 28
4 to 6 cycles
Regimen variant #3, "standard-dose"
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kaplan et al. 1997 (ACTG 142) | 1991-1994 | Phase III (C) | m-BACOD; low-dose | Did not meet primary endpoint of OS |
Note: this is of historical interest, only.
Chemotherapy
- Methotrexate (MTX) 200 mg/m2 IV once on day 15
- Bleomycin (Blenoxane) 4 units/m2 IV once on day 1
- Doxorubicin (Adriamycin) 45 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
- Dexamethasone (Decadron) 6 mg/m2 PO once per day on days 1 to 5
Supportive medications
- Sargramostim (Leukine) 5 mcg/kg SC once per day on days 4 to 13
CNS prophylaxis
- Cytarabine (Ara-C) as follows:
- Cycle 1: 50 mg IT once per day on days 1, 8, 15, 22
21-day cycle for 2 cycles past complete remission (minimum of 4 cycles)
References
- Levine AM, Wernz JC, Kaplan L, Rodman N, Cohen P, Metroka C, Bennett JM, Rarick MU, Walsh C, Kahn J, Miles S, Ehmann WC, Feinberg J, Nathwani B, Gill PS, Mitsuyasu R. Low-dose chemotherapy with central nervous system prophylaxis and zidovudine maintenance in AIDS-related lymphoma: a prospective multi-institutional trial. JAMA. 1991 Jul 3;266(1):84-8. link to original article contains protocol PubMed
- ACTG 142: Kaplan LD, Straus DJ, Testa MA, Von Roenn J, Dezube BJ, Cooley TP, Herndier B, Northfelt DW, Huang J, Tulpule A, Levine AM; National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. Low-dose compared with standard-dose m-BACOD chemotherapy for non-Hodgkin's lymphoma associated with human immunodeficiency virus infection. N Engl J Med. 1997 Jun 5;336(23):1641-8. link to original article contains verified protocol PubMed
R-CDOP
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R-CDOP: Rituximab, Cyclophosphamide, Doxil (Pegylated liposomal doxorubicin), Oncovin (Vincristine), Prednisone
DR-COP: Doxil (pegylated liposomal doxorubicin), Rituximab, Cyclophosphamide, Oncovin, Prednisone
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Levine et al. 2012 (AMC047) | 2007-NR | Phase II |
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Pegylated liposomal doxorubicin (Doxil) 40 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
- "CNS prophylaxis was mandated in patients with involvement of bone marrow, testis, sinuses, or epidural regions and with stage IV and/or at least two extranodal sites, with specific regimen left to physician discretion."
- Highly Active Antiretroviral Therapy (HAART) required; specific regimen left to physician discretion. Use of zidovudine was not allowed.
Supportive medications
- G-CSF prophylaxis, starting on day 3 and continuing until beyond nadir of blood counts, with one of the following:
- Erythropoietin (e.g. Epoetin alfa (Procrit) or Darbepoetin alfa (Aranesp)) at physician discretion
- PCP prophylaxis required
- Oral fluoroquinolone if CD4 cell count less than or equal to 100 and ANC less than 500/uL at entry or during treatment
21- to 28-day cycle for up to 6 cycles
References
- AMC047: Levine AM, Noy A, Lee JY, Tam W, Ramos JC, Henry DH, Parekh S, Reid EG, Mitsuyasu R, Cooley T, Dezube BJ, Ratner L, Cesarman E, Tulpule A. Pegylated liposomal doxorubicin, rituximab, cyclophosphamide, vincristine, and prednisone in AIDS-related lymphoma: AIDS Malignancy Consortium study 047. J Clin Oncol. 2013 Jan 1;31(1):58-64. Epub 2012 Nov 19. link to original article contains verified protocol link to PMC article PubMed NCT00389818
R-CHOP
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R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone
Regimen variant #1, 3 cycles
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kaplan et al. 2005 (AMC010) | 1998-2002 | Phase III (E-esc) | CHOP | Did not meet primary endpoint of CR rate |
Intended for patients with stage I, IE, or nonbulky stage II disease.
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day -2
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive medications
- Combination antiretrovirals were required
- G-CSF (type not specified) 5 mcg/kg SC once per day from days 4 to 13 or until ANC greater than 10k/uL.
- PCP prophylaxis with ONE of the following:
- Cotrimoxazole (dose/schedule not specified)
- Dapsone (Aczone) (dose/schedule not specified)
- Pentamidine (Nebupent) (dose/schedule not specified)
21-day cycle for 3 cycles for early disease, or minimum of 6 cycles or 2 past CR for advanced disease
Subsequent treatment
- IFRT x 40 Gy
Regimen variant #2, prednisone 40 mg/m2
Study | Evidence |
---|---|
Boué et al. 2006 | Phase II |
Ribera et al. 2007x | Phase II |
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- In Boué et al. 2006, first dose was given on day -1
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 5
CNS prophylaxis
- Rivera et al. 2007x: To be given with each cycle; day of administration not reported.
- Methotrexate (MTX) 12 mg IT
- Cytarabine (Ara-C) 40 mg IT
- Hydrocortisone (Cortef) 20 mg IT
Supportive medications
- Combination antiretrovirals were required: one or two protease inhibitors and two nucleoside reverse transcriptase inhibitors
- PCP prophylaxis with ONE of the following:
- Cotrimoxazole 160/800 mg PO TIW
- Pentamidine (Nebupent) 300 mg inhaled (schedule not specified)
21-day cycle for 6 cycles
Subsequent treatment
- Rivera et al. 2007x, patients with bulky disease or a residual mass: IFRT (details not provided)
Regimen variant #3, prednisone 100 mg
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kaplan et al. 2005 (AMC010) | 1998-2002 | Phase III (E-esc) | CHOP | Did not meet primary endpoint of CR rate |
Intended for patients with advanced disease.
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day -2
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive medications
- Combination antiretrovirals were required
- G-CSF (type not specified) 5 mcg/kg SC once per day from days 4 to 13 or until ANC greater than 10k/uL.
- PCP prophylaxis with ONE of the following:
- Cotrimoxazole (dose/schedule not specified)
- Dapsone (Aczone) (dose/schedule not specified)
- Pentamidine (Nebupent) (dose/schedule not specified)
21-day cycle for a minimum of 6 cycles or 2 past CR
Subsequent treatment
- Partial or complete responders: Rituximab maintenance
References
- AMC010: Kaplan LD, Lee JY, Ambinder RF, Sparano JA, Cesarman E, Chadburn A, Levine AM, Scadden DT. Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood. 2005 Sep 1;106(5):1538-43. Epub 2005 May 24. link to original article contains verified protocol link to PMC article PubMed
- Boué F, Gabarre J, Gisselbrecht C, Reynes J, Cheret A, Bonnet F, Billaud E, Raphael M, Lancar R, Costagliola D. Phase II trial of CHOP plus rituximab in patients with HIV-associated non-Hodgkin's lymphoma. J Clin Oncol. 2006 Sep 1;24(25):4123-8. Epub 2006 Aug 8. link to original article contains verified protocol PubMed
- Ribera JM, Oriol A, Morgades M, González-Barca E, Miralles P, López-Guillermo A, Gardella S, López A, Abella E, García M; PETHEMA; GELTAMO; GELCAB; GESIDA. Safety and efficacy of cyclophosphamide, adriamycin, vincristine, prednisone and rituximab in patients with human immunodeficiency virus-associated diffuse large B-cell lymphoma: results of a phase II trial. Br J Haematol. 2008 Feb;140(4):411-9. Epub 2007 Dec 19. link to original article contains verified protocol PubMed
R-CODOX-M
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R-CODOX-M: Rituximab, Cyclophosphamide, Oncovin (Vincristine), DOXorubicin, Methotrexate
Regimen
Study | Evidence |
---|---|
Noy et al. 2015 (AMC 048) | Phase II |
Intended for low-risk HIV-associated Burkitt lymphoma, and the first published prospective regimen to explicitly use rituximab. This is sometimes called modified Magrath but is in fact a second modification to the modified Magrath described by LaCasce et al. 2004.
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
Chemotherapy
- Cyclophosphamide (Cytoxan) 800 mg/m2 IV once per day on days 1 & 2
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once per day on days 1 & 8
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Methotrexate (MTX) 3000 mg/m2 IV once on day 15
CNS prophylaxis
- Cytarabine (Ara-C) 50 mg IT once on day 1
- Methotrexate (MTX) 12 mg IT once on day 1
- Hydrocortisone (Cortef) 50 mg IT once on day 1
Supportive medications
- Folinic acid (Leucovorin) as follows:
- 200 mg/m2 IV once 24 hours after methotrexate, then
- 25 mg/m2 IV every 6 hours until methotrexate level is less than 50 nmol/L
- Pegfilgrastim (Neulasta) 6 mg SC once on day 3
- Filgrastim (Neupogen) (dose not specified) SC once per day, starting once methotrexate level is less than 50 nmol/L (approximately day 18) and continuing until ANC greater than 1000/uL
21- to 28-day cycle for 3 cycles
References
- 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
- Retrospective: 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 contains partial protocol PubMed content property of HemOnc.org
- Retrospective: Kassam S, Bower M, Lee SM, de Vos J, Fields P, Gandhi S, Nelson M, Montoto S, Tenant-Flowers M, Burns F, Marcus R, Edwards SG, Cwynarski K. A retrospective, multi-center analysis of treatment intensification for HIV-positive patients with high-risk diffuse large B-cell lymphoma. Leuk Lymphoma. 2013 Sep;54(9):1921-7. Epub 2013 Jan 4. link to original article PubMed
- AMC 048: Noy A, Lee JY, Cesarman E, Ambinder R, Baiocchi R, Reid E, Ratner L, Wagner-Johnston N, Kaplan L. AMC 048: modified CODOX-M/IVAC-rituximab is safe and effective for HIV-associated Burkitt lymphoma. Blood. 2015 Jul 9;126(2):160-6. Epub 2015 May 8. link to original article contains verified protocol link to PMC article PubMed NCT00392834
R-CODOX-M/R-IVAC
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R-CODOX-M/R-IVAC: Rituximab, Cyclophosphamide, Oncovin (Vincristine), DOXorubicin, Methotrexate alternating with Rituximab, Ifosfamide, Vepesid (Etoposide), Ara-C (Cytarabine)
Protocol
Study | Evidence |
---|---|
LaCasce et al. 2004 | Phase II, <20 pts |
Noy et al. 2015 (AMC 048) | Phase II |
Intended for high-risk HIV-associated Burkitt lymphoma, and the first published prospective regimen to explicitly use rituximab. This is sometimes called modified Magrath but is in fact a second modification to the modified Magrath described in LaCasce et al. 2004. Note that the preferred sequence is A, B, A, B but the authors note that for patients with anasarca or other concerns for retaining MTX, the sequence can be B, A, B, A. Also note that the paper does not specify whether hydrocortisone is used with the day 3 IT chemo; the authors have clarified (December 31, 2017) that this is left to institutional policy.
Part A: R-CODOX-M
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
Chemotherapy
- Cyclophosphamide (Cytoxan) 800 mg/m2 IV once per day on days 1 & 2
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once per day on days 1 & 8
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Methotrexate (MTX) 3000 mg/m2 IV once on day 15
CNS prophylaxis
- Cytarabine (Ara-C) 50 mg IT once per day on days 1 & 3
- Methotrexate (MTX) 12 mg IT once on day 1
- Hydrocortisone (Cortef) 50 mg IT once on day 1
Supportive medications
- Folinic acid (Leucovorin) as follows:
- 200 mg/m2 IV once 24 hours after methotrexate, then
- 25 mg/m2 IV every 6 hours until methotrexate level is less than 50 nmol/L
- Pegfilgrastim (Neulasta) 6 mg SC once on day 3
- Filgrastim (Neupogen) (dose not specified) SC once per day, starting once methotrexate level is less than 50 nmol/L (approximately day 18) and continuing until ANC greater than 1000/uL
Part B: R-IVAC
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
Chemotherapy
- Ifosfamide (Ifex) 1500 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 7500 mg/m2)
- Etoposide (Vepesid) 60 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 300 mg/m2)
- Cytarabine (Ara-C) 2000 mg/m2 IV every 12 hours on days 1 & 2 (total dose per cycle: 8000 mg/m2)
CNS prophylaxis
- Methotrexate (MTX) 12 mg IT once on day 5
Supportive medications
- Mesna (Mesnex) 1500 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 7500 mg/m2)
- Pegfilgrastim (Neulasta) 6 mg SC once on day 6
4 alternating cycles
References
- 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
- Retrospective: 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 contains partial protocol PubMed content property of HemOnc.org
- Retrospective: Kassam S, Bower M, Lee SM, de Vos J, Fields P, Gandhi S, Nelson M, Montoto S, Tenant-Flowers M, Burns F, Marcus R, Edwards SG, Cwynarski K. A retrospective, multi-center analysis of treatment intensification for HIV-positive patients with high-risk diffuse large B-cell lymphoma. Leuk Lymphoma. 2013 Sep;54(9):1921-7. Epub 2013 Jan 4. link to original article PubMed
- AMC 048: Noy A, Lee JY, Cesarman E, Ambinder R, Baiocchi R, Reid E, Ratner L, Wagner-Johnston N, Kaplan L. AMC 048: modified CODOX-M/IVAC-rituximab is safe and effective for HIV-associated Burkitt lymphoma. Blood. 2015 Jul 9;126(2):160-6. Epub 2015 May 8. link to original article contains verified protocol link to PMC article PubMed NCT00392834
R-EPOCH, dose-escalated
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R-EPOCH: Rituximab, Etoposide, Prednisone, Oncovin (Vincristine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin)
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sparano et al. 2010 (AMC034) | 2002-2006 | Randomized Phase II (E-switch-ic) | EPOCH, then R | Not reported1 |
1While this was a randomized trial, the primary efficacy endpoint was a historical control; see article for details.
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once (day not specified), given first
Chemotherapy
- Etoposide (Vepesid) 50 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 200 mg/m2)
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 5
- Vincristine (Oncovin) 0.4 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg/m2)
- Cyclophosphamide (Cytoxan) as follows:
- CD4+ count less than 100/uL: 187 mg/m2 IV over 15 minutes once on day 5
- CD4+ count greater than 100/uL: 375 mg/m2 IV over 15 minutes once on day 5
- In each subsequent cycle, increase dose by 187 mg/m2 if the neutrophil nadir is greater than 500/uL and platelet nadir is greater than 25 x 109/L. Decrease dose by 187 mg/m2 if the neutrophil nadir is less than 500/uL or platelet nadir is less than 25 x 109/L.
- Doxorubicin (Adriamycin) 10 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m2)
Supportive medications
- EITHER Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting 24 hours after EPOCH is completed and continuing until "neutrophil recovery"—no absolute count specified
- OR Pegfilgrastim (Neulasta) 6 mg SC once 24 hours after EPOCH is completed
- Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg PO TIW (e.g. Monday, Wednesday, Friday)
- Fluconazole (Diflucan) 100 mg PO once per day
- Ciprofloxacin (Cipro) 500 mg PO twice per day, starting on day 8 and to continue to at least day 15 or postnadir ANC of at least 1000
- Other fluoroquinolone can be used at discretion of physician
21-day cycle for 6 to 8 cycles
References
- AMC034: Sparano JA, Lee JY, Kaplan LD, Levine AM, Ramos JC, Ambinder RF, Wachsman W, Aboulafia D, Noy A, Henry DH, Von Roenn J, Dezube BJ, Remick SC, Shah MH, Leichman L, Ratner L, Cesarman E, Chadburn A, Mitsuyasu R; AIDS Malignancy Consortium. Rituximab plus concurrent infusional EPOCH chemotherapy is highly effective in HIV-associated B-cell non-Hodgkin lymphoma. Blood. 2010 Apr 15;115(15):3008-16. Epub 2009 Dec 18. link to original article contains verified protocol link to PMC article PubMed NCT00049036
SC-EPOCH-RR
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SC-EPOCH-RR: Short Course Rituximab, Etoposide, Prednisone, Oncovin, Cyclophosphamide, Hydroxydaunorubicin, with dose-dense Rituximab
Regimen
Study | Evidence |
---|---|
Dunleavy et al. 2010 (NCI 97-C-0040) | Phase II |
Dunleavy et al. 2013 (NCI 93-C-0133) | Phase II, <20 pts in this arm |
NCI 97-C-0040 reports on HIV+ DLBCL patients, whereas NCI 93-C-0133 reports on HIV+ Burkitt lymphoma patients. The regimen is the same.
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV over 3 hours once per day on days 1 & 5
Chemotherapy
- Etoposide (Vepesid) 50 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 200 mg/m2)
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 5
- Vincristine (Oncovin) 0.4 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (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 over 96 hours, started on day 1 (total dose per cycle: 40 mg/m2)
CNS prophylaxis
- Methotrexate (MTX) as follows:
- Cycles 3 to 5: 12 mg IT once per day on days 1 & 5
Supportive medications
- Filgrastim (Neupogen) 300 mcg SC once per day, starting on day 6, continue until ANC greater than 5k/uL above nadir
- Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg PO TIW (e.g. Monday, Wednesday, Friday)
- Omeprazole (Prilosec) 20 mg PO once per day (or equivalent)
- Docusate (Colace) and Sennosides (Senna) 2 tablets PO twice per day as necessary for constipation
- Lactulose 20 gms PO every 6 hours as necessary for constipation.
21-day cycle for 3 to 6 cycles, one cycle beyond CR
Dose modifications
- Cyclophosphamide (Cytoxan):
- In the subsequent cycle, decrease dose by 187 mg/m2 if ANC was less than 500/uL for 2 to 4 days or platelets were less than 25 x 109/L for 2 to 4 days.
- In the subsequent cycle, decrease dose by 375 mg/m2 if ANC was less than 500/uL for 5 or more days or platelets were less than 25 x 109/L for 5 or more days.
- If dose-reduced in prior cycle, increase dose by 187 mg/m2, up to maximum of 750 mg/m2, if ANC was greater than 500/uL and platelets were greater than 25 x 109/L for the entire cycle.
References
- NCI 97-C-0040: Dunleavy K, Little RF, Pittaluga S, Grant N, Wayne AS, Carrasquillo JA, Steinberg SM, Yarchoan R, Jaffe ES, Wilson WH. The role of tumor histogenesis, FDG-PET, and short-course EPOCH with dose-dense rituximab (SC-EPOCH-RR) in HIV-associated diffuse large B-cell lymphoma. Blood. 2010 Apr 15;115(15):3017-24. Epub 2010 Feb 3. link to original article contains verified protocol link to PMC article PubMed NCT000019253
- NCI 93-C-0133: 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 contains verified protocol link to PMC article PubMed NCT00001337
Stanford V
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Regimen
Study | Evidence |
---|---|
Spina et al. 2002 | Phase II |
Note: this regimen was for HIV-associated Hodgkin lymphoma, unfavorable stage I or advanced stage.
Chemotherapy
- Doxorubicin (Adriamycin) 25 mg/m2 IV once per week on weeks 1, 3, 5, 7, 9, 11
- Vinblastine (Velban) 6 mg/m2 IV once per week on weeks 1, 3, 5, 7, 9, 11
- Mechlorethamine (Mustargen) 6 mg/m2 IV once per week on weeks 1, 5, 9
- Etoposide (Vepesid) 60 mg/m2 IV once per day for two successive days on weeks 3, 7, 11
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once per week on weeks 2, 4, 6, 8, 10, 12
- Bleomycin (Blenoxane) 5 units/m2 IV once per week on weeks 2, 4, 6, 8, 10, 12
- Prednisone (Sterapred) as follows:
- Weeks 1 to 10: 40 mg/m2 PO every other day
- Weeks 11 & 12: taper by 10 mg/m2 every other day until off
Supportive medications
- Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 3 to 7, 9 to 13, 17 to 21, 23 to 26
- Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg PO once per day throughout the course of treatment
- Fluconazole (Diflucan) 100 mg PO once per day throughout the course of treatment
12-week course
Subsequent treatment
References
- Spina M, Gabarre J, Rossi G, Fasan M, Schiantarelli C, Nigra E, Mena M, Antinori A, Ammassari A, Talamini R, Vaccher E, di Gennaro G, Tirelli U. Stanford V regimen and concomitant HAART in 59 patients with Hodgkin disease and HIV infection. Blood. 2002 Sep 15;100(6):1984-8. link to original article contains verified protocol PubMed
Consolidation and/or maintenance after upfront therapy
Radiation therapy
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IFRT: Involved Field Radiation Therapy
Regimen variant #1, 36 Gy of IFRT
Study | Evidence |
---|---|
Spina et al. 2002 | Phase II |
Preceding treatment
- Stanford V x 12 wk
Radiotherapy
- External beam radiotherapy 36 Gy in 2 Gy fractions, 5 days per week
4-week course
Regimen variant #2, 40 Gy of IFRT
Study | Evidence |
---|---|
Kaplan et al. 2005 (AMC010) | Non-randomized portion of RCT |
Intended for patients with stage I, IE, or nonbulky stage II disease.
Preceding treatment
- R-CHOP x 3
Radiotherapy
- External beam radiotherapy to a total dose of at least 40 Gy
One course
Subsequent treatment
- PR/CR: Rituximab maintenance
References
- Spina M, Gabarre J, Rossi G, Fasan M, Schiantarelli C, Nigra E, Mena M, Antinori A, Ammassari A, Talamini R, Vaccher E, di Gennaro G, Tirelli U. Stanford V regimen and concomitant HAART in 59 patients with Hodgkin disease and HIV infection. Blood. 2002 Sep 15;100(6):1984-8. link to original article contains verified protocol PubMed
- AMC010: Kaplan LD, Lee JY, Ambinder RF, Sparano JA, Cesarman E, Chadburn A, Levine AM, Scadden DT. Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood. 2005 Sep 1;106(5):1538-43. Epub 2005 May 24. link to original article contains verified protocol link to PMC article PubMed
Rituximab monotherapy
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Regimen
Study | Evidence |
---|---|
Kaplan et al. 2005 (AMC010) | Non-randomized portion of RCT |
Preceding treatment
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
1-month cycle for 3 cycles
References
- Kaplan LD, Lee JY, Ambinder RF, Sparano JA, Cesarman E, Chadburn A, Levine AM, Scadden DT. Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood. 2005 Sep 1;106(5):1538-43. Epub 2005 May 24. link to original article contains verified protocol link to PMC article PubMed
Consolidation after salvage therapy
BEAM, then auto HSCT
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BEAM: BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Melphalan
Regimen
Study | Evidence | Efficacy |
---|---|---|
Re et al. 2003 | Phase II | |
Alvarnas et al. 2016 (BMT CTN 0803/AMC 071) | Phase II | 1-year OS: 87% (95% CI, 72-94.5) |
Note: days of chemotherapy are slightly different in Re et al. 2003; see paper for details.
Chemotherapy
- Carmustine (BCNU) 300 mg/m2 IV once on day -6
- Etoposide (Vepesid) 100 mg/m2 IV every 12 hours on days -5 to -2 (total dose: 800 mg/m2)
- Cytarabine (Ara-C) 100 mg/m2 IV every 12 hours on days -5 to -2 (total dose: 800 mg/m2)
- Melphalan (Alkeran) 140 mg/m2 IV once on day -1
Hematopoietic stem cells are reinfused on day 0
References
- Re A, Cattaneo C, Michieli M, Casari S, Spina M, Rupolo M, Allione B, Nosari A, Schiantarelli C, Vigano M, Izzi I, Ferremi P, Lanfranchi A, Mazzuccato M, Carosi G, Tirelli U, Rossi G. High-dose therapy and autologous peripheral-blood stem-cell transplantation as salvage treatment for HIV-associated lymphoma in patients receiving highly active antiretroviral therapy. J Clin Oncol. 2003 Dec 1;21(23):4423-7. Epub 2003 Oct 27. link to original article PubMed
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