Primary CNS Lymphoma (PCNSL)¶
VERSION: 1.1 CREATED: January 30, 2026 REVISED: January 31, 2026 STATUS: Approved
DIAGNOSIS: Primary CNS Lymphoma (PCNSL), Diffuse Large B-Cell Lymphoma Confined to the CNS
ICD-10: C85.19 (Other unspecified non-Hodgkin lymphoma, extranodal and solid organ sites), C83.30 (Diffuse large B-cell lymphoma, unspecified site), C85.10 (Unspecified B-cell non-Hodgkin lymphoma, unspecified site), C79.31 (Secondary malignant neoplasm of brain), G93.6 (Cerebral edema)
CPT CODES: 85025 (CBC with differential), 80053 (CMP (BMP + LFTs)), 83615 (LDH), 82947 (Blood glucose), 87389 (HIV 1/2 antigen/antibody (4th gen)), 86803 (Hepatitis C antibody), 84550 (Uric acid), 81025 (Pregnancy test (women of childbearing age)), 86360 (CD4 count (if HIV positive)), 87536 (HIV viral load (if HIV positive)), 82232 (Beta-2 microglobulin), 84443 (TSH), 82533 (Cortisol (AM)), 82575 (CrCl (calculated or 24-hour urine)), 84484 (Troponin), 82550 (CPK/CK), 86777 (Toxoplasma IgG), 87799 (CSF EBV PCR), 81479 (CSF MYD88 L265P mutation), 83519 (CSF IL-10 and IL-6), 70450 (CT head without contrast), 70553 (MRI brain with and without contrast (gadolinium)), 78816 (PET/CT (FDG) whole body), 93000 (ECG (12-lead)), 71046 (Chest X-ray), 76390 (MR spectroscopy (MRS)), 76870 (Testicular ultrasound (males)), 93306 (Echocardiogram (TTE)), 38222 (Bone marrow biopsy), 67039 (Vitreous biopsy), 78607 (Thallium SPECT (HIV patients)), 62270 (LUMBAR PUNCTURE), 89051 (Cell count (tubes 1 and 4)), 84157 (Protein), 82945 (Glucose with serum glucose), 88104 (Cytology), 86325 (CSF protein electrophoresis)
SYNONYMS: Primary CNS lymphoma, PCNSL, primary brain lymphoma, primary central nervous system lymphoma, CNS DLBCL, primary cerebral lymphoma, primary intracerebral lymphoma, primary leptomeningeal lymphoma, primary intraocular lymphoma (vitreoretinal lymphoma), reticulum cell sarcoma of brain (historical), microgliomatosis (historical), immunocompetent CNS lymphoma, HIV-associated CNS lymphoma, AIDS-related CNS lymphoma, non-Hodgkin lymphoma of the brain
SCOPE: Comprehensive management of newly diagnosed and recurrent primary CNS lymphoma (PCNSL) in immunocompetent and immunocompromised (HIV/AIDS, post-transplant) adults. Covers initial presentation and stabilization, neuroimaging evaluation (MRI with gadolinium, diffusion-weighted imaging), the critical importance of avoiding corticosteroids before biopsy, stereotactic brain biopsy, CSF analysis (cytology, flow cytometry), slit lamp ophthalmologic examination, systemic staging (whole body CT/PET, bone marrow biopsy, testicular ultrasound in males), high-dose methotrexate (HD-MTX)-based induction chemotherapy, rituximab, consolidation strategies (whole brain radiation therapy, high-dose chemotherapy with autologous stem cell transplant, cytarabine-based consolidation), management of relapsed/refractory disease, HIV-associated PCNSL management (ART initiation, modified chemotherapy), and supportive care. Excludes secondary CNS involvement from systemic lymphoma, primary vitreoretinal lymphoma as sole presentation (overlapping but managed differently), and pediatric PCNSL.
PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting
=============================================================== SECTION A: ACTION ITEMS ===============================================================
1. LABORATORY WORKUP¶
1A. Essential/Core Labs¶
| Test | Rationale | Target Finding | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|
| CBC with differential (CPT 85025) | Baseline before chemotherapy; assess for cytopenias; lymphocyte count for immune status; platelet count for biopsy candidacy | WBC, ANC, platelets within normal limits; ALC for baseline immune function | STAT | STAT | ROUTINE | STAT |
| CMP (BMP + LFTs) (CPT 80053) | Renal function critical for methotrexate dosing (excreted renally); hepatic function for chemotherapy clearance; electrolytes for SIADH screening; glucose baseline for steroid use | Normal renal function (CrCl >50 mL/min required for HD-MTX); normal LFTs | STAT | STAT | ROUTINE | STAT |
| LDH (CPT 83615) | Tumor burden and prognostic marker; elevated LDH is adverse prognostic factor in IELSG scoring system | Normal; elevated suggests higher tumor burden | STAT | STAT | ROUTINE | STAT |
| PT/INR, aPTT (CPT 85610+85730) | Coagulopathy assessment for biopsy candidacy; baseline before procedures | Normal | STAT | STAT | ROUTINE | STAT |
| Blood glucose (CPT 82947) | Baseline before corticosteroids (if used post-biopsy); pre-operative assessment | <180 mg/dL | STAT | STAT | ROUTINE | STAT |
| HIV 1/2 antigen/antibody (4th gen) (CPT 87389) | HIV-associated PCNSL occurs in severely immunocompromised patients (CD4 <50); dramatically alters treatment approach; EBV-driven lymphomagenesis in HIV | Negative; if positive proceed to CD4 count and viral load | STAT | STAT | ROUTINE | STAT |
| Hepatitis B panel (HBsAg, anti-HBs, anti-HBc) (CPT 87340+86706+86704) | Rituximab can cause fatal HBV reactivation; mandatory screening before anti-CD20 therapy | Negative; if positive consult hepatology for antiviral prophylaxis before rituximab | STAT | STAT | ROUTINE | STAT |
| Hepatitis C antibody (CPT 86803) | Baseline hepatic risk assessment before hepatotoxic chemotherapy | Negative | - | STAT | ROUTINE | - |
| Uric acid (CPT 84550) | Tumor lysis syndrome risk (high-grade lymphoma); baseline before chemotherapy initiation | Normal; elevated requires prophylaxis with allopurinol or rasburicase | - | STAT | ROUTINE | - |
| Pregnancy test (women of childbearing age) (CPT 81025) | Methotrexate is abortifacient and teratogenic; rituximab is pregnancy category C; radiation contraindicated | Negative | STAT | STAT | ROUTINE | STAT |
| Type and screen | Pre-biopsy; anticipate possible intraoperative blood loss | Available for crossmatch | STAT | STAT | - | STAT |
| Serum protein electrophoresis (SPEP) with immunofixation (CPT 86334+86335) | Evaluate for monoclonal protein; rule out Waldenstrom macroglobulinemia or myeloma with CNS involvement | No monoclonal band | - | ROUTINE | ROUTINE | - |
1B. Extended Workup (Second-line)¶
| Test | Rationale | Target Finding | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|
| CD4 count (if HIV positive) (CPT 86360) | Stratifies treatment approach; CD4 <50 classic for HIV-associated PCNSL; higher CD4 may tolerate full chemotherapy | Document CD4; <200 requires PJP prophylaxis; <50 typical for HIV-PCNSL | STAT | STAT | ROUTINE | STAT |
| HIV viral load (if HIV positive) (CPT 87536) | Baseline for ART management; high viral load correlates with PCNSL risk | Quantify; goal is undetectable on ART | STAT | STAT | ROUTINE | STAT |
| EBV serology and EBV PCR (serum) (CPT 86665+87799) | EBV drives HIV-associated PCNSL; EBV viral load correlates with disease activity; can be used for monitoring | Positive EBV in immunocompromised = supports PCNSL diagnosis; negative does not exclude | - | URGENT | ROUTINE | - |
| Quantitative immunoglobulins (IgG, IgA, IgM) (CPT 82784+82784+82784) | Baseline humoral immunity before rituximab (depletes B cells); hypogammaglobulinemia risk assessment | Normal; low IgG increases infection risk during treatment | - | ROUTINE | ROUTINE | - |
| Beta-2 microglobulin (CPT 82232) | Prognostic marker; component of some PCNSL prognostic scoring systems; elevated correlates with tumor burden | Normal; elevated = adverse prognostic marker | - | ROUTINE | ROUTINE | - |
| TSH (CPT 84443) | Baseline thyroid function before radiation therapy (hypothyroidism risk with WBRT); fatigue differential | Normal | - | ROUTINE | ROUTINE | - |
| Cortisol (AM) (CPT 82533) | If hypothalamic/pituitary involvement suspected; adrenal function if prior steroids | Normal (>10 mcg/dL AM) | - | ROUTINE | ROUTINE | - |
| CrCl (calculated or 24-hour urine) (CPT 82575) | Precise renal function assessment critical for methotrexate dosing; CrCl >50 mL/min required for HD-MTX | CrCl >50 mL/min for HD-MTX eligibility | - | STAT | ROUTINE | - |
| Troponin (CPT 84484) | If syncope or seizure presentation; cardiac evaluation before chemotherapy | Normal | STAT | STAT | - | STAT |
| CPK/CK (CPT 82550) | Post-seizure rhabdomyolysis screen | Normal; elevated after prolonged seizures | URGENT | ROUTINE | - | STAT |
| Toxoplasma IgG (CPT 86777) | HIV-positive patients: toxoplasmosis is the main differential for ring-enhancing lesions; positive IgG + compatible imaging = empiric treatment trial before biopsy | Negative supports PCNSL over toxoplasmosis; positive requires empiric treatment trial | STAT | STAT | ROUTINE | STAT |
1C. Rare/Specialized (Refractory or Atypical)¶
| Test | Rationale | Target Finding | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|
| CSF EBV PCR (CPT 87799) | In HIV-positive patients unable to undergo biopsy; EBV PCR + compatible imaging has high specificity (>95%) for HIV-associated PCNSL | Positive in HIV-associated PCNSL (sensitivity ~80%, specificity >95%) | - | EXT | EXT | - |
| CSF MYD88 L265P mutation (CPT 81479) | Present in ~70-80% of PCNSL; supports diagnosis when tissue is limited; emerging biomarker for monitoring treatment response | Positive supports PCNSL diagnosis | - | EXT | EXT | - |
| CSF IL-10 and IL-6 (CPT 83519) | Elevated CSF IL-10 and high IL-10/IL-6 ratio (>1.0) highly suggestive of CNS lymphoma; useful when tissue is equivocal | Elevated IL-10; IL-10/IL-6 ratio >1.0 supports lymphoma | - | EXT | EXT | - |
| CSF cell-free DNA / liquid biopsy | Emerging technology for noninvasive diagnosis and monitoring; ctDNA mutations (MYD88, CD79B) detectable in CSF | Clonal immunoglobulin rearrangement or oncogenic mutations support diagnosis | - | - | EXT | - |
| Soluble CD27 (CSF) | Elevated in CNS lymphoma; may help differentiate from other CNS malignancies | Elevated supports B-cell lymphoproliferative process | - | - | EXT | - |
| Whole exome / targeted NGS panel (tumor tissue) | Identify actionable mutations (CD79B, MYD88, CARD11, KMT2D) for targeted therapy in relapsed disease; ibrutinib sensitivity (BTK inhibitor) | MYD88 L265P and CD79B mutations predict ibrutinib response | - | - | EXT | - |
2. DIAGNOSTIC IMAGING & STUDIES¶
2A. Essential/First-line¶
| Study | Timing | Target Finding | Contraindications | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| CT head without contrast (CPT 70450) | Immediately upon presentation; first-line for acute symptoms (seizure, headache, focal deficit, altered mental status) | Hyperdense (because highly cellular) periventricular mass; may show hemorrhage (rare); edema; midline shift; usually homogeneous without ring enhancement | None in emergency | STAT | STAT | - | STAT |
| MRI brain with and without contrast (gadolinium) (CPT 70553) | Within 24h of presentation; GOLD STANDARD for PCNSL diagnosis and characterization | Homogeneously enhancing periventricular or deep white matter mass; T1 iso/hypointense, T2 iso/hypointense; restricted diffusion on DWI (bright DWI, dark ADC); typically involves corpus callosum, basal ganglia, periventricular regions; multifocal in 25-50%; ring enhancement suggests immunocompromised (HIV) | MRI-incompatible implants; GFR <30 (gadolinium risk); severe claustrophobia | STAT | STAT | URGENT | STAT |
| CT chest/abdomen/pelvis with contrast (CPT 71260+74178) | Within 48-72h; systemic staging to exclude secondary CNS lymphoma from systemic disease | No extracranial lymphoma; absence of lymphadenopathy, splenomegaly, or other organ involvement confirms primary CNS disease | Contrast allergy; renal impairment | - | URGENT | ROUTINE | - |
| PET/CT (FDG) whole body (CPT 78816) | Within 1-2 weeks; preferred over CT for systemic staging per IPCG guidelines; more sensitive for occult systemic lymphoma | No extracranial FDG-avid lymphoma; CNS lesions may or may not show FDG uptake (skull limits sensitivity for brain lesions) | Pregnancy; uncontrolled diabetes | - | ROUTINE | ROUTINE | - |
| ECG (12-lead) (CPT 93000) | Pre-operative and pre-chemotherapy baseline; QTc for anti-emetics | Normal | None | STAT | STAT | ROUTINE | STAT |
| Chest X-ray (CPT 71046) | Pre-operative clearance; lung pathology screen | No lung mass; no effusion; no mediastinal lymphadenopathy | Pregnancy (shield) | STAT | STAT | ROUTINE | STAT |
2B. Extended¶
| Study | Timing | Target Finding | Contraindications | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| MRI brain with DWI/ADC maps (CPT 70553) | With initial MRI; critical for differential diagnosis | Restricted diffusion (bright DWI, dark ADC) = PCNSL (highly cellular tumor); GBM necrotic center does NOT restrict; abscess center DOES restrict | MRI-incompatible implants; GFR <30 (gadolinium risk); severe claustrophobia | STAT | STAT | URGENT | STAT |
| MR perfusion (DSC) (CPT 70553) | With diagnostic MRI; differentiates from high-grade glioma | Lower rCBV than GBM (PCNSL has lower vascularity); moderate rCBV elevation compared to normal brain | MRI-incompatible implants; GFR <30 (gadolinium risk); severe claustrophobia | - | URGENT | ROUTINE | - |
| MR spectroscopy (MRS) (CPT 76390) | With diagnostic MRI; tumor characterization | Elevated choline (highly cellular); elevated lipid and lactate peaks; reduced NAA; high Cho/Cr ratio; large lipid peak more prominent than in GBM | MRI-incompatible implants; GFR <30 (gadolinium risk); severe claustrophobia | - | URGENT | ROUTINE | - |
| Slit lamp ophthalmologic examination | Within 1 week of diagnosis; mandatory staging per IPCG; 15-25% of PCNSL has occular involvement | Vitreous cells, subretinal infiltrates, or retinal/vitreal lymphoma deposits indicating intraocular involvement; changes management if positive | None | - | URGENT | ROUTINE | - |
| MRI spine (whole) with contrast (CPT 72156+72157+72158) | If spinal symptoms present or CSF positive for lymphoma cells; leptomeningeal staging | Leptomeningeal enhancement; nerve root thickening; intramedullary lesion (rare) | MRI-incompatible implants; GFR <30 (gadolinium risk); severe claustrophobia | - | ROUTINE | ROUTINE | - |
| Testicular ultrasound (males) (CPT 76870) | Staging per IPCG guidelines; testis is a sanctuary site; concurrent testicular lymphoma in 2-5% | No testicular mass; if present, changes staging and treatment approach | None | - | ROUTINE | ROUTINE | - |
| Echocardiogram (TTE) (CPT 93306) | Baseline cardiac function before anthracycline-containing regimens or high-dose chemotherapy with ASCT | LVEF >50%; adequate cardiac function for chemotherapy | None | - | ROUTINE | ROUTINE | - |
2C. Rare/Specialized¶
| Study | Timing | Target Finding | Contraindications | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| FDG-PET brain (CPT 78816) | When MRI equivocal; recurrence vs. treatment effect | Increased FDG uptake in lymphoma (highly metabolic); helps differentiate recurrence from treatment-related changes | Pregnancy; uncontrolled diabetes | - | - | EXT | - |
| Bone marrow biopsy (CPT 38222) | Staging per IPCG guidelines; rule out occult systemic lymphoma | No lymphoma involvement; if positive, reclassify as systemic lymphoma with CNS involvement (different treatment) | Severe coagulopathy; local infection | - | ROUTINE | ROUTINE | - |
| Vitreous biopsy (CPT 67039) | If slit lamp exam shows vitreous cells or subretinal infiltrates suggesting intraocular lymphoma | Cytology positive for large B-cells; flow cytometry showing monoclonal B-cell population; IL-10/IL-6 ratio >1.0 in vitreous fluid | Active endophthalmitis; monocular patient (relative) | - | EXT | EXT | - |
| Thallium SPECT (HIV patients) (CPT 78607) | HIV-positive patients: differentiates PCNSL from toxoplasmosis when imaging equivocal and biopsy not feasible | Increased thallium uptake = PCNSL; decreased uptake = toxoplasmosis | Pregnancy | - | EXT | EXT | - |
LUMBAR PUNCTURE (CPT 62270)¶
Indication: Mandatory staging procedure in PCNSL unless contraindicated by mass effect. CSF cytology/flow cytometry positive in 15-30% of cases. Also used for intrathecal chemotherapy delivery.
Timing: URGENT once mass effect assessed and deemed safe; before steroid administration if possible
Volume Required: 10-15 mL standard diagnostic
| Study | Rationale | Target Finding | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|
| Opening pressure | Elevated ICP from mass effect; baseline for serial monitoring | 10-20 cm H2O; elevated with significant mass effect | - | URGENT | ROUTINE | - |
| Cell count (tubes 1 and 4) (CPT 89051) | Lymphocytic pleocytosis common in PCNSL; infection differential | WBC elevated (lymphocytic predominance); RBC 0 | - | URGENT | ROUTINE | - |
| Protein (CPT 84157) | Elevated in majority of PCNSL cases (>60%); reflects leptomeningeal involvement and BBB disruption | Normal 15-45 mg/dL; often elevated (50-200+ mg/dL) in PCNSL | - | URGENT | ROUTINE | - |
| Glucose with serum glucose (CPT 82945) | Low in leptomeningeal disease; infection differential | Normal (>60% serum); may be low with extensive leptomeningeal involvement | - | URGENT | ROUTINE | - |
| Cytology (CPT 88104) | Malignant lymphocytes from leptomeningeal dissemination; positive in 15-30% of PCNSL | Large atypical lymphocytes; sensitivity improves with repeat LP and larger volume | - | URGENT | ROUTINE | - |
| Flow cytometry (CPT 88184+88185) | Most sensitive method for detecting clonal B-cell population in CSF; mandatory in PCNSL workup | Monoclonal B-cell population (CD19+, CD20+, surface light chain restricted); sensitivity higher than cytology | - | URGENT | ROUTINE | - |
| CSF protein electrophoresis (CPT 86325) | Oligoclonal bands may be present; helps differentiate from MS and other inflammatory conditions | Absent oligoclonal bands favors lymphoma over MS; if present, does not exclude lymphoma | - | ROUTINE | ROUTINE | - |
| Gram stain and culture (CPT 87205, 87070) | Infection differential (abscess, meningitis vs. tumor) | No organisms | - | URGENT | ROUTINE | - |
| EBV PCR (CSF) (CPT 87799) | HIV-positive patients: high specificity for PCNSL when combined with compatible imaging; may avoid biopsy if clinical picture concordant | Positive in HIV-associated PCNSL; negative does not exclude | - | URGENT | ROUTINE | - |
| MYD88 L265P mutation (CSF) (CPT 81479) | Emerging diagnostic biomarker; present in ~70-80% of PCNSL; supports diagnosis when tissue is limited | Positive supports PCNSL diagnosis; false negative in ~20-30% | - | EXT | EXT | - |
Special Handling: Cytology requires rapid transport (<1 hour) in cold. Flow cytometry requires fresh specimen at room temperature; process within 2 hours. Minimum 3-5 mL dedicated for cytology/flow cytometry.
Contraindications: Significant mass effect with midline shift >5 mm, obstructive hydrocephalus, uncal herniation signs; coagulopathy (INR >1.5, platelets <50K); skin infection at LP site. ALWAYS obtain CT/MRI before LP.
3. TREATMENT¶
CRITICAL: AVOID CORTICOSTEROIDS BEFORE BIOPSY. Dexamethasone causes rapid lympholysis in PCNSL, producing the "vanishing tumor" or "ghost tumor" phenomenon. This can render stereotactic biopsy non-diagnostic and delay definitive treatment by weeks to months. Only administer steroids if the patient has life-threatening herniation or rapidly declining neurologic status where biopsy cannot be performed emergently.
CRITICAL: Treatment decisions require coordination between neuro-oncology, hematology/oncology, radiation oncology, neurosurgery, and ophthalmology. PCNSL is highly chemosensitive and radiosensitive, but the blood-brain barrier limits drug delivery. High-dose methotrexate is the cornerstone of treatment.
3A. Acute/Emergent¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Dexamethasone (ONLY if life-threatening herniation or biopsy not immediately available) | IV/PO | Vasogenic edema with herniation risk or severe mass effect ONLY when biopsy cannot be performed within 24-48h; steroids cause rapid tumor regression making biopsy non-diagnostic | 10 mg :: IV :: load, then 4 mg q6h :: 10 mg IV bolus, then 4 mg IV/PO q6h; use LOWEST effective dose for SHORTEST duration; document that steroids were given and inform neurosurgeon and neuro-oncologist; biopsy should proceed ASAP even after steroids (may need repeat biopsy if non-diagnostic) | AVOID BEFORE BIOPSY whenever possible (causes vanishing tumor); active untreated infection; uncontrolled diabetes (relative) | Glucose q6h (target <180 mg/dL), BP, document timing relative to biopsy, neurologic exam improvement (may confirm lymphoma diagnosis clinically) | STAT | STAT | - | STAT |
| Lorazepam (acute seizure) | IV | Acute seizure termination; 10-20% of PCNSL patients present with seizures | 4 mg :: IV :: PRN seizure :: 0.1 mg/kg IV (max 4 mg/dose); may repeat x1 in 5 min; max 8 mg total | Acute narrow-angle glaucoma; severe respiratory depression without ventilator | RR, O2 sat, BP, sedation level; airway equipment at bedside | STAT | STAT | - | STAT |
| Levetiracetam (seizure - loading) | IV | Anti-seizure medication loading for new seizures; preferred in CNS lymphoma patients due to no CYP enzyme induction (preserves chemotherapy efficacy) | 1500 mg :: IV :: load, then 500-1500 mg BID :: 1000-1500 mg IV load, then 500-1500 mg PO/IV BID; renal dosing if GFR <50 | None absolute; reduce dose if CrCl <50 | Behavioral changes (agitation, irritability); generally well tolerated | STAT | STAT | - | STAT |
| Mannitol (elevated ICP) | IV | Acute elevated ICP with herniation signs; bridge to biopsy and definitive treatment | 1 g/kg :: IV :: bolus :: 1-1.5 g/kg IV bolus over 15-20 min; may repeat 0.25-0.5 g/kg q4-6h; maintain serum osmolality <320 mOsm/kg | Anuria; severe dehydration; active intracranial bleeding (relative) | Serum osmolality q6h, serum sodium, I/O, renal function | STAT | - | - | STAT |
| Hypertonic saline (elevated ICP) | IV | Acute elevated ICP; alternative to mannitol; may be preferred in hypotensive patients | 30 mL :: IV :: bolus (23.4% via central line) :: 23.4% NaCl 30 mL via central line over 15 min OR 3% NaCl 250 mL IV over 30 min; target Na 145-155 mEq/L | Severe hypernatremia (Na >160) | Sodium q4-6h, serum osmolality, I/O, central line required for 23.4% | STAT | - | - | STAT |
| Stereotactic brain biopsy | - | Definitive tissue diagnosis; gold standard for PCNSL diagnosis; target enhancing component of lesion; AVOID open craniotomy/resection (no survival benefit from debulking in PCNSL unlike GBM) | Stereotactic biopsy :: - :: per neurosurgical protocol :: Frame-based or frameless stereotactic biopsy; target enhancing tumor component; tissue for histology, immunohistochemistry (CD20, Ki-67, MUM1, BCL6), and flow cytometry; send for molecular studies (MYD88, CD79B) | Active coagulopathy (correct first); location precluding safe biopsy (deep brainstem); prior steroids may reduce diagnostic yield (proceed anyway but warn pathologist) | Post-biopsy CT within 6h; neurologic checks q1h x 24h; hemorrhage risk 1-3% | - | URGENT | - | - |
| Enoxaparin (DVT prophylaxis) | SC | Lymphoma patients have elevated VTE risk; SCDs immediately; pharmacologic prophylaxis within 24-48h post-biopsy | 40 mg :: SC :: daily :: Enoxaparin 40 mg SC daily or heparin 5000 units SC q8h; start within 24-48h post-biopsy per neurosurgery; SCDs until ambulatory | Active intracranial hemorrhage; planned biopsy within 24h | Platelet count; signs of bleeding | - | STAT | - | STAT |
| Pantoprazole (stress ulcer prophylaxis) | PO/IV | GI bleed prevention while on dexamethasone (if steroids were initiated); combined corticosteroid + critical illness increases risk | 40 mg :: IV :: daily :: Pantoprazole 40 mg IV/PO daily OR omeprazole 20 mg PO daily; continue throughout steroid course | PPI allergy | GI symptoms | STAT | STAT | ROUTINE | STAT |
3B. Symptomatic Treatments¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Levetiracetam (maintenance) | PO | Seizure prevention after first seizure; NO prophylactic AEDs in patients without seizures; preferred due to no drug interactions with chemotherapy | 500 mg :: PO :: BID :: Start 500 mg BID; titrate by 500 mg/day q1-2 weeks to seizure control; max 3000 mg/day; renal dosing if GFR <50 | None absolute; reduce dose if CrCl <50 | Behavioral changes (agitation, depression, irritability), somnolence; no drug interactions with methotrexate or rituximab | - | STAT | ROUTINE | STAT |
| Lacosamide | PO/IV | Alternative or adjunct AED for seizures; minimal drug interactions with chemotherapy | 50 mg :: PO :: BID :: Start 50 mg BID; titrate by 50 mg/dose weekly; max 400 mg/day | PR interval >200 ms; 2nd/3rd degree AV block; severe hepatic impairment | ECG at baseline and with dose changes; PR interval monitoring | - | STAT | ROUTINE | STAT |
| Ondansetron | IV/PO | Nausea/vomiting from elevated ICP, chemotherapy (methotrexate, cytarabine), or radiation | 4 mg :: IV :: q8h PRN :: 4-8 mg IV/PO q8h PRN nausea; max 24 mg/day; give 30 min before chemotherapy | QT prolongation; concurrent use of QT-prolonging agents | QTc if risk factors; serotonin syndrome risk with SSRIs | STAT | STAT | ROUTINE | STAT |
| Acetaminophen | PO | Headache from elevated ICP or mass effect; avoid NSAIDs peri-biopsy due to bleeding risk; avoid NSAIDs during methotrexate therapy (impairs renal MTX clearance) | 1000 mg :: PO :: q6h PRN :: 650-1000 mg PO q6h PRN headache; max 3 g/day (2 g/day if hepatic impairment) | Severe hepatic impairment; allergy | LFTs if prolonged use | STAT | STAT | ROUTINE | STAT |
| Dexamethasone (taper - post-biopsy only) | PO | Transition from IV to PO after biopsy obtained; taper as soon as clinically feasible; PCNSL often dramatically steroid-responsive; rapid taper once chemotherapy begins (MTX preferred without steroids) | 4 mg :: PO :: q6h, then taper :: Taper by 2 mg every 3-5 days (e.g., 16 to 12 to 8 to 6 to 4 to 2 to 1 to off); PCNSL may regrow during taper; definitive chemotherapy should start before taper is complete if possible | Symptom recurrence during taper (may need slower taper or earlier chemotherapy) | Glucose, BP, mood, steroid myopathy, immunosuppression, osteoporosis risk | - | ROUTINE | ROUTINE | - |
| Insulin (steroid-induced hyperglycemia) | SC/IV | Glucose management while on dexamethasone | Variable :: SC :: per sliding scale :: Fingerstick glucose q6h; sliding scale insulin initially; basal-bolus if persistently >180 mg/dL; may need 2-3x baseline insulin on dexamethasone | Hypoglycemia risk | Glucose q6h (q1h if insulin drip) | STAT | STAT | ROUTINE | STAT |
| TMP-SMX (PJP prophylaxis) | PO | Pneumocystis prophylaxis during chemotherapy-induced immunosuppression; especially important given rituximab-induced B-cell depletion and chemotherapy-induced lymphopenia | 1 DS tablet :: PO :: MWF :: TMP-SMX 1 DS tablet 3x/week (Mon/Wed/Fri) during chemotherapy and for 3-6 months after; continue if CD4 <200 | Sulfa allergy (use atovaquone 1500 mg daily or dapsone 100 mg daily as alternatives); renal impairment (dose adjust) | CBC; renal function; rash (Stevens-Johnson risk); hold during methotrexate infusion (interferes with MTX excretion) | - | ROUTINE | ROUTINE | - |
| Acyclovir (HSV/VZV prophylaxis) | PO | Herpes prophylaxis during immunosuppressive chemotherapy; rituximab increases reactivation risk | 400 mg :: PO :: BID :: Acyclovir 400 mg PO BID or valacyclovir 500 mg PO daily; continue during chemotherapy and 3-6 months after completion | Renal impairment (dose adjust) | Renal function; signs of viral reactivation | - | ROUTINE | ROUTINE | - |
| Filgrastim (G-CSF) | SC | Chemotherapy-induced neutropenia prevention or treatment; used with dose-dense methotrexate regimens to maintain treatment intensity | 5 mcg/kg :: SC :: daily :: 5 mcg/kg SC daily starting 24-48h after chemotherapy until ANC >1500; pegfilgrastim 6 mg SC x1 dose alternative (not with MTX due to timing) | Hypersensitivity; concurrent with chemotherapy (start 24h after) | CBC daily during neutropenic phase; bone pain (common); spleen size if prolonged use | - | ROUTINE | ROUTINE | - |
| Calcium + Vitamin D | PO | Steroid-induced osteoporosis prevention while on prolonged dexamethasone; especially important with multiple steroid courses | 1000 mg Ca + 800 IU Vit D :: PO :: daily :: Calcium 1000-1200 mg + Vitamin D 800-1000 IU daily while on steroids | Hypercalcemia; renal stones (relative) | Calcium level; vitamin D level | - | ROUTINE | ROUTINE | - |
| Methylphenidate (cancer-related fatigue) | PO | Cancer-related fatigue and cognitive slowing from tumor, chemotherapy, or radiation; may improve alertness during treatment | 5 mg :: PO :: BID (AM and noon) :: Start 5 mg PO BID (morning and noon); titrate by 5 mg/dose q3-7 days; max 40 mg/day; avoid evening dosing | Uncontrolled hypertension; tachyarrhythmia; severe anxiety; concurrent MAO inhibitors; glaucoma | Heart rate, BP, appetite, sleep quality, mood (agitation) | - | ROUTINE | ROUTINE | - |
3C. Second-line/Refractory¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Ibrutinib (BTK inhibitor) | PO | Relapsed/refractory PCNSL; excellent CNS penetration; especially effective if MYD88 L265P mutation present; single agent or with MTX-based regimen | 560 mg :: PO :: daily :: 560 mg PO daily continuously until progression or intolerable toxicity; take at same time daily; avoid strong CYP3A4 inhibitors/inducers | Active bleeding; requires dose modification with CYP3A4 inhibitors; atrial fibrillation risk; warfarin contraindicated (use DOACs) | CBC weekly x4 then monthly; LFTs monthly; ECG for atrial fibrillation; bleeding assessment; infection monitoring; hold 3-7 days before/after procedures | - | - | ROUTINE | - |
| Temozolomide (relapsed PCNSL) | PO | Relapsed/refractory PCNSL after HD-MTX failure; oral alkylating agent with CNS penetration | 150 mg/m2 :: PO :: days 1-5 q28d :: 150-200 mg/m2 PO days 1-5 of 28-day cycle; take on empty stomach 1h before bed; antiemetic pre-medication | Severe myelosuppression; prior temozolomide intolerance; hypersensitivity to dacarbazine | CBC Day 1 and Day 22 of each cycle; LFTs monthly; watch for lymphopenia and opportunistic infections | - | - | ROUTINE | - |
| Lenalidomide | PO | Relapsed/refractory PCNSL; immunomodulatory agent; may combine with rituximab (R2 regimen) | 25 mg :: PO :: days 1-21 q28d :: 25 mg PO days 1-21 of 28-day cycle (21 days on, 7 days off); requires REMS enrollment (Revlimid REMS); thromboprophylaxis required | Pregnancy (teratogenic, Category X); DVT/PE history (requires prophylaxis); neutropenia (ANC <1000); renal impairment (dose reduce) | CBC weekly x8 then monthly; pregnancy testing monthly (female patients); LFTs; renal function; TSH q3 months; VTE monitoring; REMS compliance | - | - | ROUTINE | - |
| Pemetrexed | IV | Relapsed/refractory PCNSL; antifolate with CNS activity; single agent or combination | 900 mg/m2 :: IV :: q3 weeks :: 900 mg/m2 IV over 10 min q3 weeks; supplement with folic acid 1 mg PO daily and B12 1000 mcg IM q9 weeks (start 7 days before first dose); dexamethasone 4 mg PO BID x3 days starting day before pemetrexed | CrCl <45; inability to take folic acid/B12 supplementation; pleural effusion (3rd space - delays clearance) | CBC weekly; renal function; LFTs; rash; signs of toxicity; folic acid and B12 compliance | - | - | ROUTINE | - |
| Topotecan | IV | Relapsed/refractory PCNSL; topoisomerase I inhibitor with CNS penetration | 1.5 mg/m2 :: IV :: days 1-5 q21d :: 1.5 mg/m2 IV daily x 5 days every 21 days; dose reduce for renal impairment or myelosuppression | Severe myelosuppression (ANC <1500, platelets <100K); severe renal impairment | CBC with differential before each cycle; nadir at day 11; renal function; signs of infection during neutropenic period | - | - | ROUTINE | - |
| Whole brain radiation therapy (salvage) | - | Relapsed/refractory PCNSL after HD-MTX failure; salvage option; avoid if possible in patients who may be candidates for re-challenge with chemotherapy; significant neurotoxicity risk especially in elderly (>60) | 23.4 Gy :: - :: 13 fractions :: 23.4 Gy in 13 fractions (1.8 Gy/fraction) reduced-dose WBRT per RTOG 1114; OR 36-45 Gy in 20-25 fractions (higher dose if used as sole therapy); consider omission in patients >60 due to severe neurocognitive toxicity risk | Prior full-dose WBRT; pregnancy; age >60 (relative, due to neurotoxicity) | Neurocognitive testing at baseline and q3 months; MRI q2-3 months; watch for delayed leukoencephalopathy (may develop 6-12 months post-RT); neurotoxicity screening | - | - | ROUTINE | - |
3D. Disease-Modifying Therapies (Induction Chemotherapy / Consolidation)¶
| Treatment | Route | Indication | Dosing | Pre-Treatment Requirements | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|---|
| High-dose Methotrexate (HD-MTX) - Induction | IV | CORNERSTONE of PCNSL treatment; first-line induction; achieves therapeutic CNS concentrations; administered as part of multi-agent regimen (R-MPV, MATRix, DeAngelis protocol); 60-80% overall response rate | 3.5 g/m2 :: IV :: q2 weeks x 5-7 cycles :: 3.5 g/m2 IV over 4 hours; aggressive IV hydration (2-3 L/m2) starting 12h before and continuing 48h after; urine alkalinization with sodium bicarbonate (target pH >7.0); leucovorin rescue starting 24h after MTX completion (25 mg IV/PO q6h until MTX level <0.05 micromol/L); q2 week cycles x 5-7 based on response; hold TMP-SMX during MTX weeks | CrCl >50 mL/min (essential); no third-space fluid collections (ascites, pleural effusion - delays MTX clearance); CBC (ANC >1000, platelets >75K); LFTs normal; urine pH >7.0 before infusion; hepatitis B cleared or on prophylaxis; adequate hydration status; no concurrent nephrotoxic drugs (NSAIDs, aminoglycosides) | CrCl <50 mL/min; third-space fluid (ascites, large pleural effusion); concurrent nephrotoxic drugs including NSAIDs; active infection; severe hepatic impairment; pregnancy | Serum MTX levels at 24h, 48h, 72h (and until <0.05 micromol/L); creatinine q12h during infusion and for 72h after; urine output (target >100 mL/h); urine pH q6h (maintain >7.0); CBC with differential; LFTs; mucositis assessment; neurologic exam | - | STAT | ROUTINE | - |
| Rituximab | IV | Anti-CD20 monoclonal antibody; combined with HD-MTX in R-MPV and MATRix regimens; PCNSL is CD20+ in >95% of cases; improves response rate when combined with MTX-based chemotherapy | 375 mg/m2 :: IV :: per protocol :: 375 mg/m2 IV; first infusion: start at 50 mg/h, increase by 50 mg/h q30min to max 400 mg/h; subsequent infusions: start at 100 mg/h, increase by 100 mg/h q30min to max 400 mg/h; administer per protocol schedule (typically Day 1 of each cycle); premedicate with acetaminophen 650 mg, diphenhydramine 50 mg, and methylprednisolone 100 mg IV | Hepatitis B screening completed (HBsAg, anti-HBc, anti-HBs); CBC; baseline immunoglobulins; premedication protocol; cardiac function assessment | Active HBV infection without antiviral prophylaxis (fatal reactivation risk); severe active infection; severe cardiac disease (arrhythmia risk with infusion); known hypersensitivity | Infusion reaction monitoring (vitals q15min during first infusion, q30min subsequent); HBV DNA if core antibody positive (q3 months); quantitative immunoglobulins q3 months; signs of progressive multifocal leukoencephalopathy (PML) | - | STAT | ROUTINE | - |
| Procarbazine (R-MPV regimen component) | PO | Component of R-MPV regimen (Rituximab, Methotrexate, Procarbazine, Vincristine); alkylating agent with CNS penetration | 100 mg/m2 :: PO :: days 1-7 of odd cycles :: 100 mg/m2 PO daily x 7 days on odd-numbered cycles (cycles 1, 3, 5); take on empty stomach; tyramine-free diet during and 2 weeks after (MAO inhibitor properties) | Concurrent MAO inhibitors, SSRIs, SNRIs, meperidine, sympathomimetics; tyramine-rich foods (aged cheese, wine, fermented foods); severe myelosuppression; severe hepatic/renal impairment | CBC before each cycle; LFTs; educate on dietary restrictions (tyramine); signs of peripheral neuropathy; rash (allergic dermatitis common, may require discontinuation) | - | ROUTINE | ROUTINE | - | |
| Vincristine (R-MPV regimen component) | IV | Component of R-MPV regimen; vinca alkaloid; contributes to multi-agent synergy | 1.4 mg/m2 :: IV :: push, Day 1 (max 2 mg) :: 1.4 mg/m2 IV push (max 2 mg per dose) on Day 1 of each cycle; NEVER administer intrathecally (fatal); vesicant - administer through running IV | Pre-existing severe peripheral neuropathy; Charcot-Marie-Tooth disease; demyelinating conditions; NEVER intrathecal (fatal) | Peripheral neuropathy assessment before each dose (grade and hold if Grade 3+); constipation (autonomic neuropathy); jaw pain; ileus monitoring; foot drop assessment | - | ROUTINE | ROUTINE | - | |
| Cytarabine (high-dose, MATRix regimen component) | IV | Component of MATRix regimen (MTX, Ara-C, Thiotepa, Rituximab); high-dose achieves therapeutic CSF levels; consolidation in younger patients | 2 g/m2 :: IV :: q12h x 4 doses :: 2 g/m2 IV over 3h q12h on Days 2-3 (4 doses total per cycle); corticosteroid eye drops (dexamethasone 0.1% q6h) starting 12h before and continuing 48h after to prevent chemical conjunctivitis; cerebellar function assessment before each dose | Age >60 (increased cerebellar toxicity risk); cerebellar dysfunction; renal impairment (CrCl <60 - dose reduce); hepatic impairment | Cerebellar exam before each dose (finger-to-nose, rapid alternating movements, tandem gait); if ANY cerebellar signs develop, STOP immediately (irreversible); CBC; LFTs; renal function; ophtho eye drops compliance | - | STAT | - | - | |
| Thiotepa (MATRix regimen component or ASCT conditioning) | IV | Component of MATRix regimen; CNS-penetrating alkylating agent; also used in ASCT conditioning regimen | 30 mg/m2 :: IV :: Day 4 of MATRix cycle :: 30 mg/m2 IV over 15-30 min on Day 4 of each MATRix cycle; for ASCT conditioning: higher doses per transplant protocol | Severe myelosuppression; active infection; pregnancy | CBC (profound myelosuppression expected); mucositis; skin toxicity (rash, hyperpigmentation); LFTs; signs of VOD with high-dose conditioning | - | STAT | - | - | |
| Whole brain radiation therapy (consolidation) | - | Consolidation after chemotherapy induction; REDUCED dose (23.4 Gy) after CR to HD-MTX per RTOG 1114; previously full dose (45 Gy) but reduced due to neurotoxicity; alternative: ASCT consolidation | 23.4 Gy :: - :: 13 fractions :: 23.4 Gy in 13 fractions (1.8 Gy/fraction) for patients in CR after HD-MTX induction; 45 Gy in 25 fractions for partial responders; begin 4-6 weeks after last chemotherapy cycle; consider omission in patients >60 due to delayed neurotoxicity risk | Prior WBRT; pregnancy; age >60 (relative contraindication - consider ASCT or observation instead) | Neurocognitive testing at baseline and q3-6 months post-RT; MRI q2-3 months; watch for delayed leukoencephalopathy; neurotoxicity risk increases with age and cumulative MTX exposure | - | - | ROUTINE | - | |
| High-dose chemotherapy with autologous stem cell transplant (HDC-ASCT) | IV | Consolidation alternative to WBRT; preferred in younger patients (age <65-70) to avoid radiation neurotoxicity; thiotepa-based conditioning regimen most common for PCNSL | Thiotepa-based conditioning :: IV :: per transplant protocol :: Stem cell mobilization after induction CR; conditioning: thiotepa 5 mg/kg IV x2 days + carmustine (BCNU) 400 mg/m2 IV x1 day (or other institutional protocol); autologous stem cell infusion Day 0; requires transplant-capable center | Age >70 (relative); KPS <60; inadequate stem cell collection; active infection; organ dysfunction (cardiac, pulmonary, hepatic, renal) | Engraftment monitoring (ANC, platelets); infection prophylaxis; mucositis; hepatic VOD screening; renal function; pulmonary function; MRI q3 months post-transplant | - | STAT | - | STAT | |
| Intrathecal Methotrexate | IT | Positive CSF cytology/flow cytometry; leptomeningeal involvement documented; administered via lumbar puncture or Ommaya reservoir; role diminished with HD-MTX (which achieves therapeutic CSF levels) | 12 mg :: IT :: 2x/week x 4 weeks :: 12 mg IT (preservative-free) via LP or Ommaya reservoir; 2x/week for 4 weeks, then weekly x4-8 weeks, then monthly; reconstitute in preservative-free normal saline; give with leucovorin 10 mg PO q6h x 4 doses starting 24h after IT MTX | Active CNS infection; elevated ICP with herniation risk; LP contraindications | Opening pressure before each IT injection; neurologic exam (arachnoiditis, myelopathy); MTX neurotoxicity symptoms; concurrent systemic MTX timing (avoid within 48h) | - | ROUTINE | ROUTINE | - | |
| ART initiation (HIV-associated PCNSL) | PO | HIV-positive patients: ART is critical component of treatment; immune reconstitution may independently cause tumor regression; start concurrently with chemotherapy or before if CD4 critically low | Per HIV guidelines :: PO :: daily :: Preferred: bictegravir/emtricitabine/TAF (Biktarvy) 1 tablet PO daily or dolutegravir-based regimen; check for drug interactions with chemotherapy; avoid protease inhibitors (CYP interactions with chemotherapy); INSTI-based regimens preferred | Check drug-drug interactions with chemotherapy regimen; avoid strong CYP3A4 inhibitors | CD4 count and HIV viral load at baseline and q3 months; drug interaction review with each chemotherapy cycle; IRIS monitoring (immune reconstitution inflammatory syndrome may cause paradoxical worsening) | - | STAT | ROUTINE | - |
4. OTHER RECOMMENDATIONS¶
4A. Referrals & Consults¶
| Recommendation | ED | HOSP | OPD | ICU |
|---|---|---|---|---|
| Neurosurgery STAT consultation for stereotactic biopsy planning; emphasize AVOID open resection (no survival benefit in PCNSL, unlike gliomas); biopsy should proceed before steroids if possible | STAT | STAT | ROUTINE | STAT |
| Neuro-oncology consultation for HD-MTX-based chemotherapy planning, response assessment, and long-term management | - | URGENT | ROUTINE | - |
| Hematology/oncology consultation for lymphoma staging, systemic evaluation, and consideration of ASCT consolidation in eligible patients | - | URGENT | ROUTINE | - |
| Radiation oncology consultation for consolidation WBRT planning or salvage radiation therapy; discuss reduced-dose WBRT (23.4 Gy) vs. ASCT consolidation options | - | URGENT | ROUTINE | - |
| Ophthalmology consultation with dilated slit lamp examination for all PCNSL patients to evaluate for intraocular lymphoma (15-25% prevalence) as this changes staging and may require ocular radiation | - | URGENT | ROUTINE | - |
| Multidisciplinary tumor board presentation for coordinated treatment planning including neurosurgery, neuro-oncology, hematology, radiation oncology, neuropathology, and neuroradiology | - | URGENT | ROUTINE | - |
| Neuropathology consultation for comprehensive tissue analysis including CD20, CD79a, MUM1, BCL6, Ki-67, MYD88 L265P mutation, and CD79B mutation to confirm DLBCL and identify actionable targets | - | URGENT | ROUTINE | - |
| Infectious disease consultation for HIV-positive patients for ART optimization, opportunistic infection prophylaxis, and drug interaction management with chemotherapy | - | URGENT | ROUTINE | - |
| Palliative care consultation for symptom management, goals of care discussion, and advance directive completion given median survival of 2-5 years (immunocompetent) or shorter (HIV-associated without ART) | - | ROUTINE | ROUTINE | ROUTINE |
| Physical therapy for mobility assessment, fall prevention given neurologic deficits and steroid myopathy, and exercise program to mitigate chemotherapy-related deconditioning | - | ROUTINE | ROUTINE | - |
| Occupational therapy for ADL assessment, cognitive compensation strategies, and home safety evaluation | - | ROUTINE | ROUTINE | - |
| Speech-language pathology for swallow evaluation if posterior fossa involvement, and language/cognitive assessment if dominant hemisphere tumor | - | ROUTINE | ROUTINE | - |
| Social work consultation for insurance authorization (HD-MTX requires frequent hospitalization), disability paperwork, caregiver support, and community resources | - | ROUTINE | ROUTINE | - |
| Neuropsychology evaluation for baseline cognitive assessment before radiation or transplant to monitor for treatment-related neurotoxicity | - | - | ROUTINE | - |
| Psychiatry/psychology referral for depression, anxiety, and adjustment disorder management given cancer diagnosis and cognitive symptoms | - | ROUTINE | ROUTINE | - |
| Fertility counseling in reproductive-age patients before chemotherapy initiation as methotrexate, procarbazine, and alkylating agents may cause infertility | - | URGENT | ROUTINE | - |
| Transplant evaluation consultation for patients under age 65-70 who achieve CR to induction chemotherapy and are candidates for HDC-ASCT consolidation | - | - | ROUTINE | - |
| Clinical trials evaluation for eligible patients at all stages including newly diagnosed (novel combinations) and relapsed/refractory (BTK inhibitors, immunotherapy, CAR-T) | - | ROUTINE | ROUTINE | - |
4B. Patient Instructions¶
| Recommendation | ED | HOSP | OPD | ICU |
|---|---|---|---|---|
| Return immediately for new or worsening headache, sudden weakness, vision changes, speech difficulty, or seizures (may indicate tumor progression or increased intracranial pressure) | STAT | STAT | ROUTINE | - |
| Return immediately for fever >100.4F, chills, or signs of infection during chemotherapy as this may indicate life-threatening neutropenic sepsis requiring emergency evaluation | STAT | STAT | ROUTINE | - |
| Do not drive until cleared by neurology due to seizure risk, visual changes, and cognitive impairment from tumor and treatment | - | ROUTINE | ROUTINE | - |
| Do not stop dexamethasone abruptly (if prescribed) as this may cause adrenal crisis; follow prescribed taper schedule exactly | - | ROUTINE | ROUTINE | - |
| Report any mouth sores, difficulty swallowing, or abdominal pain during methotrexate treatment as mucositis requires early intervention | - | ROUTINE | ROUTINE | - |
| Maintain excellent oral hydration (2-3 L/day unless restricted) during methotrexate treatment to promote renal clearance and reduce nephrotoxicity | - | ROUTINE | ROUTINE | - |
| Avoid NSAIDs (ibuprofen, naproxen, aspirin) during methotrexate treatment as these impair methotrexate excretion and increase toxicity risk | - | ROUTINE | ROUTINE | - |
| Avoid alcohol during chemotherapy to prevent hepatotoxicity and to avoid seizure threshold lowering | - | ROUTINE | ROUTINE | - |
| Report any visual changes (blurred vision, floaters, eye pain) as these may indicate intraocular lymphoma involvement requiring ophthalmologic evaluation | - | ROUTINE | ROUTINE | - |
| Keep a symptom diary documenting headaches, seizures, weakness, cognitive changes, vision changes, and mood to track treatment response | - | ROUTINE | ROUTINE | - |
| Discuss advance directive and healthcare proxy designation given diagnosis and treatment complexity | - | ROUTINE | ROUTINE | - |
| Wear medical alert identification indicating cancer diagnosis, seizure risk, and immunosuppressed status | - | ROUTINE | ROUTINE | - |
| Avoid live vaccines during and for 6 months after chemotherapy and rituximab due to immunosuppression | - | ROUTINE | ROUTINE | - |
| If taking procarbazine: avoid tyramine-rich foods (aged cheese, cured meats, red wine, soy sauce, fermented foods) as this can cause hypertensive crisis (MAO inhibitor properties) | - | ROUTINE | ROUTINE | - |
4C. Lifestyle & Prevention¶
| Recommendation | ED | HOSP | OPD | ICU |
|---|---|---|---|---|
| Low-sodium diet while on dexamethasone to reduce fluid retention, edema, and hypertension | - | ROUTINE | ROUTINE | - |
| Blood sugar monitoring and diabetic diet while on steroids to prevent steroid-induced hyperglycemia complications | - | ROUTINE | ROUTINE | - |
| Regular low-impact exercise (walking, swimming, yoga) as tolerated to maintain strength, reduce steroid myopathy, and improve mood and quality of life | - | ROUTINE | ROUTINE | - |
| Fall precautions at home including removal of trip hazards, use of handrails, non-slip mats, and night lights given neurologic deficits, steroid myopathy, and seizure risk | - | ROUTINE | ROUTINE | - |
| Smoking cessation to optimize wound healing, immune function, and reduce thrombotic risk during chemotherapy | - | ROUTINE | ROUTINE | - |
| Alcohol avoidance during chemotherapy to prevent hepatotoxicity and avoid seizure threshold lowering | - | ROUTINE | ROUTINE | - |
| Sun protection during chemotherapy and methotrexate treatment due to photosensitivity risk | - | - | ROUTINE | - |
| Adequate hydration (2-3 L/day unless fluid restricted) especially critical during methotrexate treatment weeks to support renal function | - | ROUTINE | ROUTINE | - |
| Nutritious high-protein diet to support immune function and maintain weight during chemotherapy; dietitian referral if weight loss >5% | - | ROUTINE | ROUTINE | - |
| Hand hygiene and infection avoidance measures (avoid crowds, sick contacts) during immunosuppressive chemotherapy | - | ROUTINE | ROUTINE | - |
=============================================================== SECTION B: REFERENCE (Expand as Needed) ===============================================================
5. DIFFERENTIAL DIAGNOSIS¶
| Alternative Diagnosis | Key Distinguishing Features | Tests to Differentiate |
|---|---|---|
| Glioblastoma (GBM) | Ring-enhancing (vs. homogeneous in PCNSL); central necrosis (common in GBM, rare in immunocompetent PCNSL); irregular thick rim; hemorrhagic; typically single; does NOT restrict on DWI centrally; does NOT respond dramatically to steroids | MRI with DWI (PCNSL restricts, GBM necrosis does not); MR perfusion (GBM has higher rCBV); steroid response (dramatic in PCNSL); stereotactic biopsy (GFAP+ in GBM, CD20+ in PCNSL) |
| Brain metastases | History of systemic malignancy; multiple lesions at gray-white junction; well-demarcated ring enhancement; less periventricular predilection; known primary cancer | CT chest/abdomen/pelvis; PET/CT for primary site; biopsy with immunohistochemistry for primary site markers (TTF-1, CK7/20, HER2, melanoma markers) |
| Toxoplasmosis (HIV/immunocompromised) | HIV/AIDS with CD4 <100; multiple ring-enhancing lesions; basal ganglia predilection; eccentric target sign; positive Toxoplasma IgG in >90%; responds to empiric treatment in 10-14 days | Toxoplasma IgG (positive in >90% of toxo, but also common in general population); empiric treatment trial with pyrimethamine + sulfadiazine (10-14 days); if no improvement then biopsy; Thallium SPECT (cold in toxo, hot in lymphoma) |
| Neurosarcoidosis | Younger patients; leptomeningeal enhancement pattern; cranial nerve palsies (especially CN VII); pulmonary involvement (hilar lymphadenopathy); elevated ACE; non-caseating granulomas | Chest CT (hilar lymphadenopathy); serum ACE; CSF ACE; PET/CT for systemic sarcoidosis; tissue biopsy showing non-caseating granulomas (vs. large B-cells in PCNSL) |
| Tumefactive multiple sclerosis | Younger patients; incomplete ring enhancement ("open ring sign"); less mass effect relative to size; clinical dissemination in time and space; other demyelinating lesions | MRI: open ring enhancement; CSF oligoclonal bands; MOG/AQP4 antibodies; clinical dissemination criteria; biopsy showing demyelination (not lymphoma) |
| Progressive multifocal leukoencephalopathy (PML) | Immunocompromised (HIV, natalizumab, rituximab); non-enhancing white matter lesions (unlike PCNSL which enhances); no mass effect; JC virus-mediated | CSF JC virus PCR (positive); non-enhancing pattern; no restricted diffusion (vs. PCNSL which restricts); brain biopsy if PCR negative but clinical suspicion high |
| Brain abscess | Ring-enhancing with central restricted diffusion on DWI (bright DWI in cavity center, similar to PCNSL); thin smooth rim (vs. thick irregular in PCNSL); fever, leukocytosis; source (dental, ENT, cardiac) | DWI (both PCNSL and abscess restrict, but abscess cavity center restricts while PCNSL is solid); MR spectroscopy (amino acid peaks in abscess: succinate, acetate, not present in lymphoma); blood cultures; echocardiogram |
| Autoimmune encephalitis | Subacute cognitive/behavioral changes; limbic involvement; seizures; autoantibodies (NMDAR, LGI1, CASPR2); less mass effect; often non-enhancing or mildly enhancing | Autoimmune encephalitis antibody panel (serum and CSF); EEG (extreme delta brush in NMDAR); MRI pattern (medial temporal, less mass effect); CSF lymphocytic pleocytosis without malignant cells |
| CNS vasculitis (primary or secondary) | Multifocal white matter lesions; may enhance; headache; cognitive decline; vessel wall enhancement on VWI; stroke-like episodes | MRA/CTA (beading, stenosis); vessel wall imaging (concentric enhancement); ESR/CRP; angiography (classic beading pattern); brain and leptomeningeal biopsy showing vasculitis (not lymphoma) |
| Intravascular lymphoma | Rare B-cell lymphoma confined to blood vessel lumens; multifocal strokes; diffuse white matter disease; skin involvement; no discrete mass on imaging (unlike PCNSL) | Random skin biopsy (positive in 70-80%); brain biopsy showing intravascular large B-cells; MRI pattern (punctate enhancing lesions, diffuse white matter changes, stroke-like pattern) |
6. MONITORING PARAMETERS¶
| Parameter | Frequency | Target/Threshold | Action if Abnormal | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| Neurologic examination (motor, sensory, language, cognition, cranial nerves, visual fields) | q2-4h inpatient; each clinic visit | Stable or improving; new deficits warrant urgent imaging | STAT MRI if decline; increase dexamethasone if post-biopsy; expedite chemotherapy initiation | STAT | STAT | ROUTINE | STAT |
| Blood glucose | q6h while on dexamethasone (q1h if insulin drip) | <180 mg/dL | Sliding scale to basal-bolus insulin; endocrine consult if refractory | STAT | STAT | ROUTINE | STAT |
| Serum creatinine | q12h during MTX infusion and for 72h after; each cycle pre-treatment | Normal; CrCl >50 mL/min before each MTX dose | Delay MTX until CrCl recovers; aggressive hydration; glucarpidase if MTX level critically elevated with renal failure | STAT | STAT | ROUTINE | STAT |
| Serum methotrexate level | 24h, 48h, 72h post-infusion (and until <0.05 micromol/L) | <0.05 micromol/L by 72h; <1.0 micromol/L by 48h | Continue leucovorin rescue until level <0.05; if level >10 micromol/L at 48h with rising creatinine, consider glucarpidase | - | STAT | - | STAT |
| CBC with differential | q48h during MTX hospitalization; weekly between cycles; before each cycle Day 1 | ANC >1500; platelets >75K before next MTX cycle | Delay chemotherapy; G-CSF for neutropenia (ANC <1000); platelet transfusion if <10K or bleeding; neutropenic fever protocol if febrile with ANC <500 | STAT | STAT | ROUTINE | STAT |
| Urine pH | q6h during MTX infusion and for 48h after | >7.0 (alkalinize to promote MTX excretion) | Increase sodium bicarbonate infusion; hold MTX infusion if pH <7.0; recheck in 1h after bolus | - | STAT | - | STAT |
| Urine output | q1h during MTX infusion and for 48-72h after | >100 mL/h (aggressive hydration) | Increase IV fluids; furosemide if fluid overloaded but oliguria; STAT creatinine and MTX level | - | STAT | - | STAT |
| Hepatic function (LFTs) | q2 weeks during induction; monthly during consolidation | Normal | Dose reduce or hold chemotherapy; hepatology consult if Grade 3-4 elevation | - | ROUTINE | ROUTINE | ROUTINE |
| Serum sodium | q6-12h inpatient during IV hydration for MTX | 135-145 mEq/L | SIADH workup if <130; adjust hydration; hypertonic saline if <125 or symptomatic | STAT | STAT | ROUTINE | STAT |
| MRI brain with contrast | Post-biopsy CT within 6h; baseline MRI; after 2-3 cycles of induction; end of induction; then q2-3 months | Decreasing or stable enhancement; complete response (CR) = complete disappearance of enhancement; partial response (PR) = >50% reduction | Tumor board discussion if progression; consider salvage therapy; rebiopsy if uncertain (pseudoprogression rare in PCNSL but can occur with immunotherapy) | - | URGENT | ROUTINE | - |
| Slit lamp ophthalmologic exam | Baseline (mandatory); after induction; q3-6 months for 2 years; annually thereafter | No vitreous cells or subretinal deposits | If new ocular involvement: ocular radiation therapy (30-36 Gy); intravitreal methotrexate; reassess systemic disease | - | ROUTINE | ROUTINE | - |
| Quantitative immunoglobulins | Baseline; q3 months during rituximab; q6 months after completion | IgG >400 mg/dL | IVIG replacement if IgG <400 with recurrent infections; hold rituximab if severe hypogammaglobulinemia | - | ROUTINE | ROUTINE | - |
| CD4 count (all patients) | Baseline; q3 months during treatment; monthly if HIV-positive | >200 cells/mcL; PJP prophylaxis if <200 | Maintain PJP and antiviral prophylaxis; dose adjustments; delay treatment if critically immunosuppressed with active infection | - | ROUTINE | ROUTINE | - |
| Blood pressure | Continuous in ICU; q4h on floor; each clinic visit | SBP <160 | Antihypertensives; especially important during aggressive hydration for MTX | STAT | STAT | ROUTINE | STAT |
| Neurocognitive assessment | Baseline; 6 months post-treatment; annually (especially after WBRT) | Stable or improved cognition | Neuropsychology referral; rehabilitation; consider memantine or cognitive rehabilitation; screen for delayed leukoencephalopathy after WBRT | - | - | ROUTINE | - |
| KPS / ECOG performance status | Each clinic visit | KPS >=60 for active chemotherapy | KPS <40: reassess goals of care; transition to supportive care/hospice | - | ROUTINE | ROUTINE | - |
| Depression / anxiety screening (PHQ-9) | Each clinic visit | PHQ-9 <5 | Psychiatry/psychology referral; SSRI initiation (check drug interactions) | - | - | ROUTINE | - |
7. DISPOSITION CRITERIA¶
| Disposition | Criteria |
|---|---|
| ICU admission | GCS <=12; signs of herniation (pupil asymmetry, posturing, Cushing triad); status epilepticus; methotrexate toxicity with acute renal failure requiring monitoring or glucarpidase; neutropenic sepsis with hemodynamic instability; tumor lysis syndrome; HDC-ASCT conditioning and engraftment period |
| General neurology/neurosurgery floor | New diagnosis requiring workup, biopsy, and staging; HD-MTX infusion cycles (typically 3-5 day admission per cycle for hydration, monitoring, leucovorin rescue); symptomatic edema requiring IV dexamethasone with close glucose monitoring; post-biopsy observation; seizures requiring AED optimization; functional decline requiring rehabilitation planning |
| Observation (<=24h) | Known PCNSL with mild symptom worsening on stable regimen; MRI showing possible progression requiring multidisciplinary discussion; steroid dose adjustment with monitoring |
| Discharge home | Neurologically stable for >=24h; seizure-free >=24h on oral AED; methotrexate level <0.05 micromol/L; creatinine stable; oral dexamethasone taper plan (if applicable); adequate oral hydration demonstrated; pain controlled on oral medications; treatment plan established with scheduled follow-up (neuro-oncology within 1-2 weeks); safe ambulation or adequate caregiver; patient/family education completed; neutropenic precaution education if ANC recovering |
| Transfer to higher level care | Need for neuro-oncology expertise with HD-MTX protocol; transplant-capable center for ASCT consolidation; clinical trial access; complex HIV co-management |
| Inpatient rehabilitation | Significant neurologic deficits (hemiparesis, aphasia, cognitive impairment) requiring intensive rehabilitation before outpatient treatment; KPS 40-60 with rehabilitation potential; coordination with ongoing chemotherapy schedule |
| Palliative care / Hospice | Progressive PCNSL refractory to multiple lines of therapy; poor functional status (KPS <30); patient/family goals aligned with comfort-focused care; no longer candidate for disease-directed therapy |
8. EVIDENCE & REFERENCES¶
| Recommendation | Evidence Level | Source |
|---|---|---|
| High-dose methotrexate (>=3 g/m2) is the backbone of PCNSL induction therapy | Class I, Level A | Ferreri et al. Lancet 2009 (IELSG #20) |
| Combination of HD-MTX with rituximab improves outcomes in PCNSL (IELSG #32); MATRix regimen (MTX, Ara-C, Thiotepa, Rituximab) is effective induction for PCNSL | Class I, Level A | Ferreri et al. Lancet Haematol 2016 (IELSG #32) |
| R-MPV regimen (Rituximab, Methotrexate, Procarbazine, Vincristine) followed by reduced-dose WBRT | Class II, Level B | Morris et al. J Clin Oncol 2013 |
| Reduced-dose WBRT (23.4 Gy) after CR to MTX-based chemotherapy preserves neurocognitive function (RTOG 1114) | Class II, Level B | Thiel et al. Lancet Haematol 2022 (G-PCNSL-SG-1) |
| WBRT omission with ASCT consolidation is noninferior to WBRT in younger patients | Class I, Level B | Houillier et al. Lancet Haematol 2019 (PRECIS) |
| HDC-ASCT is effective consolidation for PCNSL with thiotepa-based conditioning | Class II, Level B | Illerhaus et al. Blood 2016; Omuro et al. Blood 2015 |
| Ibrutinib has CNS activity in relapsed/refractory PCNSL | Class II, Level B | Grommes et al. Cancer Discov 2017 |
| Lenalidomide plus rituximab (R2) active in relapsed PCNSL | Class II, Level C | Ghesquieres et al. Eur J Cancer 2019 |
| Corticosteroids cause vanishing tumor in PCNSL; avoid before biopsy | Class III, Level C | Kuhlmann et al. Acta Neuropathol 2008; Expert consensus |
| MYD88 L265P mutation present in ~70-80% of PCNSL; diagnostic and therapeutic target | Class II, Level B | Gonzalez-Aguilar et al. Clin Cancer Res 2012 |
| IELSG prognostic scoring system for PCNSL (age, ECOG, LDH, CSF protein, deep brain involvement) | Class II, Level B | Ferreri et al. J Clin Oncol 2003 |
| Slit lamp examination mandatory at diagnosis (15-25% ocular involvement) | Class II, Level B | Grimm et al. Neuro-Oncology 2008; [IPCG guidelines] |
| NCCN Guidelines for CNS Cancers - Primary CNS Lymphoma section | Expert Consensus | NCCN CNS Cancers Guidelines v3.2024 |
| EBV CSF PCR highly specific for HIV-associated PCNSL | Class II, Level B | Cingolani et al. J Clin Oncol 2000 |
| Rituximab requires HBV screening before administration (fatal reactivation risk) | Class I, Level A | [FDA Black Box Warning]; Evens et al. Blood 2011 |
| Prophylactic AEDs NOT recommended in brain tumor patients without seizures | Class I, Level A | Glantz et al. Neurology 2000 (AAN Practice Parameter) |
| Levetiracetam preferred AED in CNS tumor patients (no CYP enzyme induction) | Class II, Level B | Rosati et al. J Neurooncol 2010 |
| Pemetrexed active in relapsed PCNSL | Class II, Level C | Raizer et al. J Clin Oncol 2012 |
| CSF IL-10/IL-6 ratio >1.0 supports CNS lymphoma diagnosis | Class II, Level B | Rubenstein et al. Blood 2013 |
| Temozolomide has activity in relapsed PCNSL | Class II, Level C | Reni et al. J Clin Oncol 2007 |
| Thallium SPECT differentiates PCNSL from toxoplasmosis in HIV patients | Class II, Level B | Antinori et al. J Neurooncol 1999 |
| Dexamethasone eye drops prevent cytarabine-induced chemical conjunctivitis | Class II, Level B | Expert consensus; Cerci & Ostronoff J Clin Oncol 2014 |
| Memorial Sloan Kettering prognostic model for PCNSL (age, KPS) | Class II, Level B | Abrey et al. J Clin Oncol 2006 |
CHANGE LOG¶
v1.1 (January 31, 2026) - Fixed broken PubMed link for IELSG #32 reference (C1: merged duplicate rows, corrected PMID to 27216018) - Replaced all "Same as MRI" cross-references in Section 2B with full contraindication text for MRI DWI/ADC, MR perfusion, MR spectroscopy, and MRI spine rows (C2/M1) - Added ED STAT priority to neutropenic fever return precaution in Section 4B (S2/R5) - Checker validation: 50/60 (83%) pre-revision; target 90%+ post-revision
v1.0 (January 30, 2026) - Initial template creation - Comprehensive 8-section plan for primary CNS lymphoma (PCNSL) - Critical emphasis on avoiding corticosteroids before biopsy (vanishing tumor) - HD-MTX-based induction protocols (R-MPV, MATRix) - Consolidation strategies (reduced-dose WBRT, HDC-ASCT) - HIV-associated PCNSL management with ART integration - Relapsed/refractory options (ibrutinib, lenalidomide, temozolomide, pemetrexed) - Comprehensive staging (slit lamp exam, testicular ultrasound, bone marrow biopsy) - CSF biomarkers (MYD88, IL-10/IL-6 ratio, flow cytometry) - 24+ evidence references with PubMed links - Detailed methotrexate monitoring protocol (levels, renal function, urine pH)
APPENDIX A: HIGH-DOSE METHOTREXATE (HD-MTX) ADMINISTRATION PROTOCOL¶
PRE-TREATMENT (12-24 hours before MTX):
├── Verify CrCl >50 mL/min (MANDATORY)
├── Verify no third-space fluid collections (ascites, pleural effusion)
├── CBC: ANC >1000, platelets >75K
├── LFTs within normal limits
├── Hold TMP-SMX (interferes with MTX excretion)
├── Hold NSAIDs, penicillins, probenecid (impair MTX clearance)
├── Start IV hydration: D5 0.45% NS + 50 mEq NaHCO3 per liter
│ at 200-250 mL/h (2-3 L/m2 over 24h)
└── Verify urine pH >7.0 before starting MTX infusion
MTX INFUSION:
├── Dose: 3.5 g/m2 IV over 4 hours
├── Continue IV hydration during and after infusion
├── Urine pH checks q6h (maintain >7.0)
└── Urine output target: >100 mL/h
POST-INFUSION MONITORING:
├── Leucovorin rescue: Start at 24h post-MTX start
│ └── 25 mg IV/PO q6h until MTX level <0.05 micromol/L
├── Serum MTX levels: 24h, 48h, 72h (and beyond if elevated)
│ ├── Expected: <10 micromol/L at 24h
│ ├── Expected: <1.0 micromol/L at 48h
│ └── Expected: <0.05 micromol/L at 72h
├── Serum creatinine: q12h x 72h minimum
├── Urine pH: q6h (continue bicarbonate until MTX cleared)
├── Urine output: q1h (maintain >100 mL/h)
└── Signs of toxicity: mucositis, renal failure, myelosuppression
DELAYED CLEARANCE (MTX level >1.0 at 48h or rising Cr):
├── Increase IV hydration rate
├── Increase leucovorin dose (100 mg/m2 IV q6h if level >5.0)
├── Continue urine alkalinization
├── Consider glucarpidase (Voraxaze) if MTX >10 micromol/L at 48h
│ with renal failure (only available via emergency access)
└── Consult nephrology and toxicology
DISCHARGE CRITERIA:
├── MTX level <0.05 micromol/L
├── Creatinine stable at baseline
├── Tolerating oral hydration
├── Adequate oral leucovorin if still needed
└── Follow-up within 1 week (CBC nadir at 7-14 days)
APPENDIX B: PCNSL TREATMENT ALGORITHM¶
SUSPECTED PCNSL (Homogeneous enhancing periventricular mass)
│
├── CRITICAL: DO NOT GIVE CORTICOSTEROIDS
│ (Causes "vanishing tumor" → non-diagnostic biopsy)
│ Exception: Life-threatening herniation only
│
├── STEP 1: STAGING WORKUP
│ ├── MRI brain with gadolinium and DWI
│ ├── Lumbar puncture (cytology, flow cytometry)
│ ├── Slit lamp ophthalmologic exam
│ ├── CT or PET/CT body (exclude systemic lymphoma)
│ ├── HIV testing (mandatory)
│ ├── Testicular ultrasound (males)
│ └── Bone marrow biopsy
│
├── STEP 2: TISSUE DIAGNOSIS
│ ├── Stereotactic brain biopsy (preferred)
│ ├── CSF flow cytometry (if LP safe and performed)
│ ├── Vitreous biopsy (if ocular involvement)
│ └── AVOID open resection (no survival benefit)
│
├── STEP 3: CONFIRMED PCNSL → INDUCTION
│ ├── Age <65-70, good KPS (≥60):
│ │ ├── MATRix (MTX + Ara-C + Thiotepa + Rituximab)
│ │ └── OR R-MPV (Rituximab + MTX + Procarbazine + Vincristine)
│ ├── Age >70 or KPS <60:
│ │ ├── HD-MTX + Rituximab (reduced intensity)
│ │ └── Consider single-agent HD-MTX
│ └── HIV-positive:
│ ├── ART initiation (critical)
│ ├── HD-MTX if tolerated (CD4 permitting)
│ └── WBRT if unable to tolerate chemotherapy
│
├── STEP 4: RESPONSE ASSESSMENT (after 2-3 cycles)
│ ├── MRI brain with contrast
│ ├── Slit lamp exam
│ └── CSF (if initially positive)
│
├── STEP 5: CONSOLIDATION (if CR or PR)
│ ├── Age <65-70:
│ │ ├── HDC-ASCT (thiotepa-based) — PREFERRED
│ │ └── OR reduced-dose WBRT (23.4 Gy)
│ └── Age >70 or ASCT-ineligible:
│ ├── Reduced-dose WBRT (23.4 Gy for CR)
│ ├── Full-dose WBRT (45 Gy for PR)
│ └── OR observation with close monitoring
│
└── STEP 6: RELAPSE/REFRACTORY
├── If >12 months since last MTX → rechallenge HD-MTX
├── Ibrutinib (especially if MYD88 L265P+)
├── Lenalidomide + Rituximab (R2)
├── Temozolomide
├── Pemetrexed
├── WBRT (if not prior RT)
└── Clinical trials (CAR-T, checkpoint inhibitors)
APPENDIX C: IELSG PROGNOSTIC SCORING SYSTEM¶
IELSG PROGNOSTIC FACTORS FOR PCNSL:
(Each factor = 1 point)
1. Age >60 years
2. ECOG performance status >1 (KPS <70)
3. Elevated serum LDH
4. Elevated CSF protein
5. Deep brain structure involvement (periventricular, basal ganglia,
brainstem, or cerebellum)
RISK GROUPS:
├── Low risk (0-1 factors): 2-year OS ~80%
├── Intermediate (2-3 factors): 2-year OS ~48%
└── High risk (4-5 factors): 2-year OS ~15%
Note: This scoring system was developed from the IELSG #20 cohort
(Ferreri et al. J Clin Oncol 2003)
This template has been generated through the builder pipeline v1.0 and requires physician review before clinical deployment.