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Lymphoma, Aggressive

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MDR

CHOP
COP
CVP
CVPP
ESHAP
MINE
MIN-ESHAP (MDAAC REGIMEN)
m-BACOD
Rituxamab
ProMace-CytaBom
CHOP + RITUXIMAB
HyperCVAD

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CHOP

Cyclophosphamide 750 mg/m2 IVB day 1
Doxorubicin 50 mg/m2 IV day 1
Vincristine 1.4 mg/m2 IVB (max 2 mg) day 1
Prednisone 100 mg PO days 1 - 5

Repeat cycle every 21 to 28 days for a minimum of 6 cycles or until 2 cycles after disapperance of the disease.

Reference: Armitage JO, et al: Cancer 50:1695 (1982)


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COP

CYCLOPHOSPHAMIDE 800-1000 mg/m2 IV DAY 1
VINCRISTINE 2 mg IV DAY 1
PREDNISONE 60 mg/m2/day or 100 mg/day PO DAYS 1-5 then taper off over next 3 days

REPAT Q 14-28 days

REF:
Cancer 28:306, 1971
Blood 49:325, 1977

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CVP
CYCLOPHOSPHAMIDE 300-400 mg/m2/day PO DAYs 1-5
VINCRISTINE 1.4 mgm2 (2 mg max) IV DAY 1
PREDNISONE 100 mg/day PO DAYS 1-5 then taper off over next 3 days

REPAT Q21 days

REF:
Ann Intern Med 76:227, 1972
JCO 9:770, 1991

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CVPP
LOMUSTINE 75 mg/m2/day PO DAY 1
VINBLASTINE 4 mg/m2 IV DAYs 1 & 8
PROCARBAZINE 100 mg/m2/day PO DAYs 1-14
PREDNISONE 40 mg/m2/day PO DAYS 1-14 then taper off over next 3 days (cycles 1 & 4)


REPEAT Q28 days

REF:
Cancer 46:654, 1980

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ESHAP

Etoposide 40 mg/m2 IV days 1-4
Methylprednisolone 500 mg IV days 1-4
Cytarabine 2000 mg/m2 IV day 5
Cisplatin 25 mg/m2 CIV days 1-4


Ref: Velasquez W, et al: Proc ASCO 8:256 (abstract) (1986).
Cabanillas F: Ann Oncol 2 (suppl 1):31-32, 1991.
Cabanillas F, Rodiquez A, Swan F, et al: Proc Am Soc Clin Oncol 10:273, 1991.
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MINE (MDACC PROTOCOL; OUTPATIENT REGIMEN)

Effective for patients ineligible for transplantation who have experienced a CR lasting more than 1 year & those older than 60, even if they have maintained a CR for <1 year. Please note that an investigational agent is always preferred over MINE.

Premedication:
ondasentron 8 mg/d IVPB, d 1-3 (total 24 mg)
Chemotherapy:
MESNA 1.5 g/m2/d IVPB with IFOSFAMIDE over 1 hour, DAYS 1-3 (total 4.5 g/m2)
IFOSFAMIDE 1.5 g.m2/d IVPB over 1 hour, DAYS 1-3 (total 4.5 g/m2)
MITOXANTRONE 10 mg/m2 IVPB, DAY 1
ETOPOSIDE 80 mg/m2/d IVPB over 1 hour, DAYS 1-3 (total 240 mg/m2)
PRN ANTIEMETIC:
ABH CAPSULES (LORAZEPAM 0.5 mg/haloperidol 0.5 mg/diphenhydramine 12.5 mg) 1 PO Q6 hours prn

MONITORING:
1. Weigh patient QD. Notify MD if weight increased by >1kg
2. Urinanalysis, DAY 3. Do not wait for report to give drug. Notify MD if RBC>50/hpf

Note: MINE should not be given to patients who fail ESHAP. Instead these patients should be given high dose or investigational agents. MINE cannot be used to rescue patients who have relpased after receiving a platinum-based regimen.
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MIN-ESHAP (MDAAC REGIMEN)

MINE ---outpatient
ESHAP---inpatient for pts older than 60

MINE Q 3 wks X 6 or less cycles until CR follwoed by ESHAP for 3 cycles or less. ESHAP was given to for 6 or less cycles in patients who still had measurable disease after MINE.


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m-BACOD

Methotrexate 200 mg/m2 IV/4h days 8 & 15
Bleomycin 4 U/m2 IVB day 1
Doxorubicin 45 mg/m2 IVB day 1
Cyclophosphamide 600 mg/m2 IVB day 1
Vincristine 1 mg/m2 IVB* day 1
Dexamethasone 6 mg/m2 PO days 1-5
Leucovorin 10 mg/m2 PO q6hX6 start 24
hours after MTX

repeat cycle every 21 days.

*Maximum dose of vincristine is 2 mg.

Ref: Skarin AT, et al: Proc ASCO 2:220 (abstract) 1983).
Shipp MA, et al: Ann Int Med 140:757 (1986).
Canellos GP, et al: Semin Hematol 24:2 (Suppl 1)(1987).

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Rituxamab 375 mg/m2 q week x 4 doses.

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ProMace-CytaBom

PREDNISONE 60 mg/m2 po days 1-14
DOXORUBICIN 25 mg/m2 IV day 1
CYCLOPHOSPHAMIDE 650 mg/m2 IV day 1
ETOPOSIDE 120 mg/m2 IV day 1
CYTARABINE 300 mg/m2 IV day 8
BLEOMYCIN 5 units IV day 8
VINCRISTINE 1.4 mg/m2 IV day 8
METHOTREXATE 120 mg/m2 IV day 8
LEUCOVORIN 25 mg/m2 IV 24 hours after MTC then Q6h for 5 doses

REPEAT Q28 days


REF: JCO 9:25, 1991
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CHOP + RITUXIMAB

Cyclophosphamide 750 mg/m2 day 1;
Vincristine Doxorubicin 50 mg/m2 day 1;
1.4 mg/m2 (up to a maximal dose of 2 mg) on day 1;
Prednisone 40 mg/m2 per day X five days.
Rituximab 375 mg/m2 day 1 of each of the eight cycles of CHOP.
The rituximab infusion was interrupted in the event of fever, chills, edema, congestion of the head and neck mucosa, hypotension, or any other serious adverse event and was resumed when such an event was no longer occurring. No radiation therapy was scheduled or recommended at the end of treatment.

Patients who had grade 4 (severe) neutropenia or febrile neutropenia after any cycle of chemotherapy were given granulocyte colony-stimulating factor. If grade 4 neutropenia persisted during the next cycle, the doses of cyclophosphamide and doxorubicin were decreased by 50 percent. For patients with grade 3 (moderate) or 4 thrombocytopenia, the doses of cyclophosphamide and doxorubicin were decreased by 50 percent. If the neutrophil count was lower than 1500 per cubic millimeter or the platelet count was lower than 100,000 per cubic millimeter before a scheduled cycle, the cycle was delayed for up to two weeks, and then treatment was stopped. The doses of rituximab were not modified, but rituximab was discontinued when CHOP was stopped. Treatment was stopped if lymphoma progressed or the patient declined to continue or at the discretion of the investigator in cases of intercurrent illness or adverse events.

REF: NEJM 346:235, 2002

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Hyper-CVA/MTX-Ara-C

Cyclophosphamide 300 mg/m2 IV over 3 hours x 6 doses (Days 1-3)

Doxorubicin 25 mg/m2/day C.I. over 24 hours X 2 days to begin 12 hours after last cyclophosphamide (days 4 & 5)

Vincristine 1.4 mg/m2 (max 2 mg) IV days 4 & 11

Decadron 40 mg/d days 1-4 & 11-14

ALTERNATE Q 21 DAYS

Methotrexate 1 grams/m2 C.I. over 24 hours on DAY 1

Ara-C 3 grams (1 grams if older than 55)/m2 over 2 hours Q 12 hours X 4 doses (days 2 & 3)

Leucovorin Rescue 50 mg PO at end of MTX infusion & then 25 mg PO Q 6 hours X 48 hours

Neupogen to be used
Acyclovir, bactrim & diflucan strongly recommended.

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ANAPLASTIC large cell lymphoma (ALCL)

also called Ki-1 lymphoma, is a morphologically & immunologically distinct subset of NHL originally described by Stein et al,1 that accounts for 2-8% of all lymphomas. This disease is characterized by the proliferation of pleomorphic large neoplastic lymphoid cells, which strongly express the CD30 antigen (Ki-1 antigen), usually growing in a cohesive pattern & preferentially spreading in the lymph node sinuses. The REAL classification included the B-cell type of ALCL among the morphologic variants of diffuse large B-cell lymphoma, limiting the term of anaplastic large cell lymphoma to T- & null-cell types. Two distinct clinical forms of primary ALCL are now recognized: limited to the SKIN & SYSTEMIC.
The purely cutaneous ALCL may be indistinguishable from lymphomatoid papulomatosis & regressing atypical histiocytosis &, like these two entities, may undergo spontaneous regression.
Systemic ALCL has an aggressive clinical course & patients frequently present with systemic symptoms, advanced-stage disease, and extranodal localizations. Response to treatment & overall survival of systemic ALCL in children is good. In adults, however, whether or not prognosis of ALCL is different from other diffuse large cell lymphomas is still controversial.


INTERNATIONAL PROGNOSTIC INDEX (IPI)
REF: NEJM 329:987-994, 1993

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