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Welcome to Dr. Hamid Sanatinia's Virtual Headquarters
Lymphoma, CNS

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MSK REGIMEN:
Pre-RT chemotherapy:
MTX 3.5 g/m2 infused over 2 hours Q other wk X 5.
Intra-Ommaya MTX (12 mg) given weekly on alternate weeks after administration of systemic MTX.
LEUCOVORIN rescue 24 hours after each dose of systemic (10 mg every 6 hours, for at least 12 doses) & intra-Ommaya (10 mg every 12 hours for eight doses) MTX.
VINCRISTINE 1.4 mg/m2 (maximum dose, 2.8 mg) given concomitantly with each cycle of systemic MTX.
PROCARBAZINE 100 mg/m2/d for 7 days was given with the first, third, and fifth cycle of MTX.

Chemotherapy followed by 45 Gy of whole-brain RT.

All patients with evidence of ocular lymphoma received 30 to 40 Gy of ocular RT.

Three weeks after the completion of RT, patients received two courses of high-dose cytarabine; each course consisted of two doses of 3 g/m2 infused over 3 hours separated by 24 hours.

REF:JCO 18, Issue 17 (September), 2000: 3144-3150: Objective response rate to the induction chemotherapy regimen was 90%; overall median survival is 60 months

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METHOTREXATE PRIOR TO XRT
A brief course of IV methotrexate before cranial irradiation is associated with 2-year & median survival rates superior to those reported for XRT alone & similar to more intensive combined-modality regimens. Neurotoxicity remains an important competing risk for these patients.
JCO 18: 519, 2000

METHOTREXATE 1 g/m2 IV during a 6-hour period on days 1 and 8.
LEUCOVORIN 15 mg PO Q6hrs X 72 hours, start 24 hrs after the MTX infusion.
RADIOTHERAPY start on day 15. A whole-brain dose of 45 Gy followed by a boost of 5.4 Gy.
IT chemotherapy to be given only to patients whose cytologic CSF studies are positive. 60 mg of Ara-C given twice weekly for 3 weeks starting on day 1 or as soon as possible after diagnosis of CSF involvement. Weekly Ara-C continued for three doses after clearance of the CSF.

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CHOD/BVAM + XRT

CYCLOPHOSPHAMIDE, DOXORUBICIN, VINCRISTINE, & DEXAMETHASONE (CHOD) X 1 cycle
CARMUSTINE (BCNU), VINCRISTINE, ARA-C, & methotrexate (BVAM) X 2 cycles,
followed by cranial XRT (45 Gy whole brain + a 10-Gy boost for single lesions).

REF=Int J Radiat Oncol Biol Phys 50(2):457,2001
N=31; median age = 59 years (21-70); 39% = poor performance status; 21 patients had no PCNSL at the end of treatment. The 5-year actuarial probability of survival = 31% (95% CI: 11%-57%); median survival = 38 months. Patients < 60 years had a survival significantly longer than those > or = 60 years (4-year survival: 58% (95% CI: 34-82%) vs. 29% (95% CI: 5-53%), respectively; p = 0.04).

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VINCRISTINE 1.4 mg/m2 day 1,
MTX 3 g/m2 days 3 & 10,
procarbazine 100 mg/m2 days 1-14
Q 4 weeks X 2 courses.
Patients who achieved CR referred to XRT,
Those with progressive disease were excluded from further study;
All the remaining patients received a 3rd course of CHT followed by RT.

REF=Oncology 2001;60(2):134-140
N=13; 12 responded to CHT (ORR = 92%, CR = 77%): 9 underwent consolidation RT, 3 did not. 2 patients experienced severe acute toxicity; lethal pulmonary thromboembolism & transient renal failure. 5 patients relapsed: 2 after CHT & 3 after RT. Relapse was local in all cases, with a case of concomitant hepatic involvement. In contrast to high-dose cytarabine-containing CHT, salvage therapy with temozolomide produced good results. 2 patients died of treatment-related neurotoxicity. 6 patients are alive with a median f/u of 17 months, & 2-year OS=61%. The median survival of the 9 patients who completed the planned treatment is 25+ months with 2-year OS=80%.

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Both historical data & a prospective study completed by RTOG show that cranial irradiation alone achieves a median survival of only 12-18 months with a 5 year survival of 3-4% in patients with primary CNS lymphoma.The addition of high-dose methotrexate based chemotherapy has increased median survival to about 40 months with a 22% 5 year survival rate. No other single chemotherapeutic agent has proved more effective in the treatment of this disease than methotrexate.


PCNSL NOTES
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Systemic staging for CNS lymphoma:
Very low likelihood of disease elsewhere. Recommend a good physical exam, blood work including LFTs, & CXR. If negative, no further tests necessary.
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EBV nuclear antigen & genome have been found in a high percentage of immunocompromised PCNSL. EBV is not found in immunocompetent patients.
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The histology of PCNSL is always diffuse type. Follicular lymphoma is never found in PCNSL.
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In most cases, the cells are of B-cell origin.
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Patients at high risk to develop PCNSL:
1. HIV/AIDS
2. Renal/cardiac transplant patients
3. Wiskott-Aldricj Syndrome
4. Combined immunodeficiency syndrome
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