Diagnosis and management of primary intraocular lymphoma: an update

Figures & data

Table 1 Response criteria for PIOL as published by the IPCG (adapted from Abrey et al 2005)

Response	Corticosteroid dose	Ocular examination
Complete remission	None	Normal
Unconfirmed complete remission	Any	Minor retinal pigment epithelium abnormality
Partial remission	Irrelevant	Decrease in retinal infiltrate or vitreous cells
Progressive disease	Irrelevant	Recurrent or new ocular disease

Table 2 Summary of clinical studies over the past 20 years (in chronological order) using chemotherapy or immunotherapy alone as treatment for PIOL

Author(s) and year of publication	Treatment modalitya	Chemotherapeutic agentsa	No. of PIOL patients	Ocular response	Ocular relapses	Survival
Strauchen 1989	High-dose IV chemo	Cytarabine	6	5/6 (1 CR, 4 PR)	1/5	Not reported on an individual basis
Soussain 1996	High-dose IV chemo + autologous bone marrow transplantation	Thiotepa, busulfan, cyclophosphamide	5	5/5 (5 CR)	2/5	3 alive in CR at 26+ months, 2 alive after ocular relapse at 27+, 16+ months
Fishburne 1997	High-dose IA chemo + BBBD, IO chemo	MTX (as IO treatment)	4	4/4 (4 CR)	0/4	Not reported on an individual basis
Sandor 1998	High-dose IV chemo, IT chemo	Thiotepa, vincristine, MTX, dexamethasone, cytarabine	5	5/5 (3 CR, 2 PR)	0/5	3 alive in CR, 2 died of cerebral or spinal disease
De Smet 1999	IO chemo	MTX, thiotepa	1	1/1 (1 CR)	0/1	1 alive in CR at 30+ months
Soussain 2001	High-dose IV chemo + hematopoietic stem cell rescue	Thiotepa, busulfan, cyclophosphamide	11	10/11 (9 CR, 1 PR)	2/10	7 alive in CR, 1 alive with ocular PD, 2 died due to tumor progression, 1 died due to unknown causes; median follow-up 41 months for all study patients
Smith 2002	High-dose IV/IA chemo ± BBBD, IT chemo, PO chemo, IO chemo	MTX (as IO treatment)	16	16/16 (16 CR)	3/16	6 deaths, all due to intracranial progression
Abrey 2003	High-dose IV chemo + hematopoietic stem cell rescue	MTX, cytarabine, carmustine, etoposide, melphalan	2	2/2	1/2	1 in CR at 36.8+ months, 1 alive with intracranial disease at 37.4+ months
Batchelor, Kolak 2003	High-dose IV chemo	MTX	9	7/9 (6 CR, 1 PR)	3/7	4 alive in CR at 8+, 15+, 20+, 36+ months; 2 died of intracranial disease
Batchelor, Carson 2003	High-dose IV chemo	MTX	5	4/5 (4 CR)	Not reported on an individual basis	Not reported on an individual basis
Mason 2003	IT chemo	MTX, cytarabine	2	2/2	0/2	2 alive in CR at 5+ years
Jahnke 2004	PO chemo	Trofosfamide	2	2/2 (2 CR)	1/2	1 alive in CR at 8+ months, 1 alive with ocular relapse at 18+ months
Rubenstein 2004	IT immunotherapy	Rituximab	1	1/1	Not reported on an individual basis	Not reported on an individual basis
Jahnke 2005	High-dose IV chemo, PO chemo	Ifosfamide, trofosfamide	8	8/8 (6 CR, 2 PR)	2/8	5 alive in CR, 2 alive in PR, 1 died due to suspected intracranial progression; overall survival 6+ to 35+ months

^a Patients may or may not have received all listed modalities and agents; see referenced articles for details.

Abbreviations: PIOL, primary intraocular lymphoma; IV, intravenous; CR, complete remission; PR, partial remission; IA, intraarterial; BBBD, blood-brain barrier disruption; IO, intraocular; MTX, methotrexate; IT, intrathecal; PO, oral.

Table 3 Summary of clinical studies over the past 20 years (in chronological order) using chemotherapy/immunotherapy and radio-therapy as treatment for PIOL

Author(s) and year of publication	Treatment modalitya	Chemotherapeutic agentsa	No. of PIOL patients	Ocular response	Ocular relapses	Survival
Valluri 1995	High-dose IV chemo, IT chemo, WBRT, ORT	MTX, cytarabine	3	3/3 (3 CR)	0/3	3 alive in CR 31+, 30+, 30+ months after completion of therapy
Cassoux 2000	Retrospective series with various modalities	Retrospective series with various regimens	44	Not reported on an individual basis	Not reported on an individual basis	12 alive in CR and 14 have died after an average follow-up of 33.1 months
Ferreri 2001	High-dose IV chemo, PO chemo, WBRT	Vincristine, MTX, procarbazine	2	2/2 (2 CR)	1/2	1 alive in CR at 44+ months; 1 died due to neurotoxicity after 24 months
Ferreri 2002	High-dose IV chemo, IT chemo, WBRT, ORT	MTX, cytarabine, CHOP	22	15/22 (13 CR, 2 PR)	9/15	2-year failure-free survival 34%, 2-year overall survival 39%
Hoffman 2003	Retrospective series with various modalities	Retrospective series with various regimens	10	Not reported on an individual basis	2	1 alive in CR at 103+ months, 1 alive with disease at 24+ months, 8 have died; median overall survival 16 monthsb
Hormigo 2004	(High-dose) IV chemo, IT chemo, PO chemo, WBRT, ORT	MTX, cytarabine, vincristine, procarbazine, thiotepa, CHOP, rituximab	31	29/31 (24 CR, 5 PR)	8/29	Median survival 60 months for isolated PIOL vs 35 months for PIOL + intracranial disease (p < 0.05)
Berenbom 2006	(High-dose) IV chemo, PO chemo, WBRT, ORT	MTX, vincristine, rituximab, procarbazine, cytarabine, carboplatin, dexamethasone	12	Not reported on an individual basis	2/12	1 alive in CR, 4 alive with cerebral disease, 7 died of cerebral disease
Grimm, Pulido, Omuru 2006	Retrospective series with various modalities	Retrospective series with various regimens	225	Not reported on an individual basis	Not reported on an individual basis	Median progression-free survival 18.7 months, median overall survival 33.1 months
Grimm, Pulido, Janke 2006	Retrospective series with various modalities	Retrospective series with various regimens	81	Not reported on an individual basis	47 total relapses: 30% ocular, 15% ocular + cerebral	Median progression-free survival 29.6 months, median overall survival 57 months
Isobe 2006	Chemo, WBRT, ORT	Retrospective series with various regimens	15	13/15 CR or CRu	1/13	Median overall survival 41 months, 2-year overall survival 74%
Jahnke, Korfel 2006	Retrospective series with various modalities	Retrospective series with various regimens	19	17/19 (13 CR, 4 PR)	6/17	Median progression-free survival 10 months, median overall survival 22.5 monthsb

^a Patients may or may not have received all listed modalities and agents; see referenced articles for details.

^b Survival data also includes patients with secondary intraocular lymphoma.

Abbreviations: PIOL, primary intraocular lymphoma; IV, intravenous; IT, intrathecal; WBRT, whole-brain irradiation; ORT, ocular radiation therapy; MTX, methotrexate; CR, complete remission; PO, oral; PR, partial remission; CHOP, cyclophosphamide/doxorubicin/vincristine/prednisone; CRu, unconfirmed complete remission.

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