Primary and secondary CNS-Lymphoma Prof. Nossrat Firusian, Recklinghausen, Germany.
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Transcript of Primary and secondary CNS-Lymphoma Prof. Nossrat Firusian, Recklinghausen, Germany.
Primary and secondary
CNS-Lymphoma
Prof. Nossrat Firusian,
Recklinghausen, Germany
Primary CNS-Lymphoma:
Non Hodgkin-Lymphoma arising in and confined to CNS.
a) Microglioma
b) Reticulum Cell Sarcoma
c) Perivascular Lymphoma
Lymphocytic origin established
How a Lymphoma develops within the CNS,
which lacks Lymph Nodes and Lymphatics.
However Lymphocytes do traffic in and out of
CNS normaly ans these Lymphocytes are
probably the source of PCNSL.
Hypothetical scheme of lymphocyte differentiation
Extranodal Lymphomas
1. Mucosa associated Lymphoma(MALT)
2. Cutaneous LymphomaT-Cell-Lymphoma (CD 30 + or -)
3. Intravascular large B-Cell-Lymphoma
4. Orbital Lymphoma
5. Primary Effusion Lymphoma
CNS-Lymphoma6. a) Brain b) Meningeal c) Ocular d) Spinal
7. Burkitt‘s Lymphoma
Primary CNS-Lymphoma:
Brain-Manifestation
Ocular-Lymphoma
Leptomeningeal-Lymphoma
Spinal-Cord-Lymphoma
Secondary CNS-Lymphoma:
Metastatic involvement of
Brain
Subarachnoidal Cavity
Ocular Compartments
Entities associated with CNS-Lymphoma as secondary manifestation
Centroblastic Lymphoma Immunoblastic Lymphoma
Main entities associated with CNS-Lymphoma as secondary manifestation Lymphoblastic Leukemia
Type I - L1
Type II – L2
Type III – L3
Entities associated with CNS-Lymphomaas secondary manifestation
Burkitt-Lymphoma
Entities associated with CNS-Lymphoma as
secondary manifestation
Diffuse Large B Cell Lymphoma
Different Locations of CNS-Lymphoma
1. Brain-Lymphoma
2. Ocular-Lymphoma
3. Leptomeningeal-Lymphoma
4. Spinal-Cord-Lymphoma
Diagnostic Procedures in PCNS-Lymphoma
1. Clinical-neurological Investigation
2. MRT of Brain without and with Gadolinium
3. Cerebrospinal Fluid examination associated with Cytophotometric
4. Ophthalmologic Investigation, Slit-Lamp
5. Systemic staging• CT, Thorax + Abdomen• Bone marrow• Testicle• HIV-virology
6. Histologic Confirmation
MRT-Investigation in Primary CNS-Lymphoma
T1-without ContrastSingle occipital lesion with
hyperintensity right
T2 FLAIR
Transversal and sagittal-Investigation after Gadolinium.Gadolinium revealing remarkable enhancing.
Primary Brain-Lymphoma
Sagittal MRTT Contrast
Transversal+ Contrast
Sagittal+ Contrast
MRT in Primary CNS-Lymphoma
a – c: T2-MRT-Investigation revealing multiple lesions within both hemisphere
e: FLAIR-Sequence revealing
remarkable enhancementf – g: Remarkable decreased enhancement after Administration of Gadolinium
MRT-Investigation of Primary CNS-Lymphoma in Patients with AIDS
T1-MRT after Administration of
Gadolinium
T2-MRT after Gadolinium
CNS-Lymphoma
a) Brain-Lymphomab) Leptomeningeal-Lymphoma
a) b)
Leptomenigeal-Lymphoma
Cytology of CSF in Patient with Leptomeningeal Lymphoma as secondary Involvement in Connection with ALL
Principles of Management
Surgery: Avoid Corticosteroids before diagnostic Biopsy for diagnosis
Chemotherapy: Should be considered at diagnosis for every Patient.
Must penetrate the blood-brain barrier.
High-dose MTX (1,5 - 8 g/m²) with excellent penetration of CNS.
Lipophilic (Procarbazine)
Must have anti-lymphoma activity should be given before Radiotherapy
Radiotherapy:Must be whole brain 3600 – 4500 cGy Avoid boost
3600 cGy Ocular-Lymphoma
May be deferred in Patients age 60 years or older, who have a complete response to Chemotherapy
Chronology of different therapeutic modalities
Corticosteroid ‹ 12 months but initially excellent Effect
Cranial Radiotherapy 12 – 18 months
WBRT + CorticosteroidsOcular
Neuraxis
(5-year survival 3-4%)
SurgeryResection 3 – 5 months
Chemotherapyas Preradiation Modality:
Assessment of response in intact Blood-Brain barrier before RT reduce
late neurologic toxicity
Chemotherapy of CNS-Lymphoma
Systemic Non-Hodgkin-Lymphoma
Regimens CHOP
Short-lasting remission‹ 12 months quickly development of leptomennigeal or multifocal brain recurrence
RTOG-StudyCHOP + WBRT
Median Survival12,8 months
High-dose Methotrexate with potential to penetrate BBB and known Activity against Lymphoma
1g/m² - 8 g/m²actual 3 g/m²
Median Survival (Mo)40 – 60
MTX, WBRT + HDACRadiation-Dosis 30.000 Gy
Median Survival 5 Y. survival 50%
MTX, WBRT + HDACPatient ‹ 60 Y.
Median Survival (Mo) › 70 3 Y. survival 92% vs 60%
MTX, Procarbazine, VCR, HDAC + WBRT Median Survival 60 months
Unable to penetrate an intakt Blood-Brain-Barrier
Follow Up under Therapy with remarkable improvement under comb. CT
Gadolinium enhanced magnetic resonance imaging scans demonstrating a complete response of primary central nervous system lymphoma to high-dose methotrexate, procarbazine and vincristine. Note the prominent and diffuse enhancment pattern and periventricular location so characteristic of primary central nervous system lymphoma.
Intensification of Chemotherapy
Sloan-Kettering Cancer Center
Methotrexate Week 1 35
Vincristine Week 1 35
Procarbazine Week 15
WBR Week …..11
High-Dose Cytarabine
Week …..16, 20
Median Survival 40 Months
Chemotherapy for BBB-Disruption
McAllister
Cyclophosphamide1, 2
Intraarterial Methotrexate 1, 2
Leucovorin 2
Procarbazine3 – 7
Duxamethason 3 - 7
WBR
Median Survival 40,7 Months
No difference in Comparison toHD – MTX
HD – Cytarabine
New Developments in Therapy of CNS-Lymphoma
1. High-dose MTX
2. High-dose ARAC + Thiotepa
3. HCT (Thiotepe + BCNU)4. Autolog. Bone-marrow
Transplantation
30 Pat.
Complete Therapy 21 / 30
CR 21 / 30
Kaplan-Meier curve
A Kaplan-Meier curve demonstrating overall (•) and disease-free (hatch marks) survival 52 patients treated with methotrexate, procarbazine, vincristine, cranial irradiation and high-dose cytarabine. Median survival is 60 months.
Recurrent Disease of PCNS
• No established second line Therapy
• WBRT If Patients did not receive as part of initial Therapy
• Ocular Radiotherapy in Patient with ocular Relapse (Bilateral)
• HD MTX In Patient with long disease-free interval
HD Cytarabine Tenrozolomide High-dose with Thiotepa, Busulfan and Cyclophosphamide followed by autologous Stem-Cell-Rescue - 3 year Survival
• Leptomeningeal Relapse: Intrathecal or intraventricular MTX + Radiotherapy
Therapy of PCNSL in Immunocompromised Patients
1. Systemic Therapy more toxic in immunodeficient Patients
2. EBV-DNA-Identification in CSF by PCR
3. AIDS-related PCNSL occurs in Patients with CD4 25 x 106 cell/L
4. Most important Component of PCNSL-Therapy in immunodeficient Patient: Reduction of Immunosupressiva, HAART
5. HAART + Ganciclovir
6. HAART + Corticosteroid + cranial Radiotherapy
7. HD MTX 3 g/m²
8. Monitoring of CSF-EBV-Level
Case-ReportQuestion for Auditorium
Case-ReportMRT-Transversal
Case-Report
Plan-Radiologyafter
combined-modality-Treatment
Case-ReportClinic: Severe Headace, Fever, vomitus and opistotonus
CSF-Cytology
CSF-Report
Magnification
CSF-Cytology
Case-Report MRT-Investigation of Neurocranium
Case-Report MRT-Investigation
Conclusion
1) Precise histologic or cytologic Investigations are essential for Treatment of CNS-Lymphoma
2) HD-MTX is for time being unique therapeutic options for Patients with PCNS-Lymphoma
3) Additional Components (ARA-C, Procarbazine) important for younger Patients
4) WBR should be considered in Connection with recurrent disease
5) In Patients with immunodeficiency induced by Post-Transplantation immunosuppressive or AIDS: Tapering of immunosuppressive Medication, HAART and EBV-Monitoring