Application of the Central Nervous System International Prognostic Index (CNS-IPI) score in daily practice: a retrospective analysis apart from the clinical trial at two centers in Brazil

Fischer, Thais; Zing, Natalia PC; Fortier, Sergio C.; Schmidt, Jayr; Silveira, Talita B.; Chiattone, Carlos S.

doi:10.1016/j.htct.2023.02.003

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Hematology, Transfusion and Cell Therapy

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Sumário

Original article • Hematol., Transfus. Cell Ther. 46 (2) • 2024 • https://doi.org/10.1016/j.htct.2023.02.003 copy

Application of the Central Nervous System International Prognostic Index (CNS-IPI) score in daily practice: a retrospective analysis apart from the clinical trial at two centers in Brazil

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Introduction:

The diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL) and, despite all the progress in this field, central nervous system infiltration (CNSi) still occurs at an incidence of 2-10%. The objective of the present study was to evaluate the Central Nervous System International Prognostic Index (CNS-IPI) score in daily practice regarding the reproducibility in a heterogeneous cohort apart from a clinical trial.

Methods:

Primary DLBCL patients were eligible for this study, between January 2007 and January 2017. All patients were treated with rituximab-based chemotherapy, mostly R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). The CNSi was diagnosed by liquor (positive cytology and/or immunophenotype), computerized tomography, magnetic resonance image and/or fluorodeoxy-glucose-positron emission tomography, requested only in symptomatic patients when the CNSi was clinically suspected. The CNS-IPI was assessed by graphical comparison and calibration.

Results:

After applying the inclusion/exclusion criteria, 322 patients were available for the analysis. The median follow-up was 60 months and the median age was 58 years. Seven patients experienced CNSi, characterizing an incidence of 2.17% (7/322). Comparing groups of patients with and without CNSi, we observed that the lactate dehydrogenase (LDH), number of extranodal sites, IPI, kidney/adrenal and absence of complete response were statistically different. The CNS-IPI model stratified patients in a three-risk group model as low-, intermediate- and high-risk. In our cohort, using the same stratification, we obtained an equivalent the 2-year rate of CNS relapse of 0.0%, 0.8% and 13.8%, respectively.

Conclusion:

Our study reinforces the reproducibility of the CNS-IPI, specifically apart from clinical trials, and suggests the CNS-IPI score as a tool to guide therapy.

Keywords:
Lymphoma; Non-Hodgkin lymphoma; Central nervous system; Rituximab; Methotrexate; Intrathecal

	Total N (%)	Patients without CNSi N (%)	CNSi N (%)	p-value
	322 (100)	315 (100)	7 (100)
Median follow-up (months)	60 (1-96)
ACCC	171 (53.1)	168 (53.3)	3 (42.9)	0.710
SCMSP	151 (46.9)	147 (46.7)	4 (57.1)
Public system	183 (56.8)	179 (56.8)	4 (57.1)	0.648
Private system	139 (43.2)	136 (43.2)	3 (42.9)
Median age (years)	58 (19-94)	58 (19-94)	65 (42-75)	0.297
Male	154 (47.8)	153 (48.6)	1(14.3)	0.123
Female	168 (52.2)	162 (51.4)	6 (85.7)
Age of diagnosis
<60 years	174 (54.0)	172 (54.6)	2 (28.6)	0.254
≥60 years	148 (46.0)	143 (45.4)	5 (71.4)
High LDH	151 (46.9)	145 (46.0)	6 (85.7)	0.054
ECOG^* * 256 patients. (256 pts)
0-1	221 (68.6)	218 (69.2)	3 (42.9)	0.447
>2	35 (10.9)	34 (10.8)	1 (14.3)
Stage
I-II	152 (47.2)	150 (47.6)	2 (28.6)	0.451
III-IV	165 (51.2)	160 (50.8)	5 (71.4)
NA	5 (1.6)	5 (1.6)
Number of extranodal sites
0–1	274 (85.1)	270 (85.7)	4 (57.1)	0.006
2	31 (9.6)	31 (9.8)	0 (0.0)
3 or more	17 (5.3)	14 (4.4)	3 (42.9)
Bulky mass^* * 256 patients.
Yes	93 (28.9)	89 (28.3)	4 (57.1)	0.110
No	229 (71.1)	226 (71.7)	3 (42.9)
B symptoms	148 (46.0)	143 (45.4)	5 (71.4)	0.257
Positive BM	28 (8.7)	26 (8.3)	2 (28.6)	0.125
Kidney/adrenal	15 (4.7)	13 (4.1)	2 (28.6)	0.037
Lung/pleura	33 (10.2)	33 (10.5)	0 (0.0)	0.466
Peritoneum	5 (1.6)	5 (1.6)	0 (0.0)	0.737
Testis	4 (1.2)	4 (1.3)	0 (0.0)	0.764
Orbit	3 (0.9)	2 (0.6)	1 (14.3)	0.64
IPI
0–1	118 (36.6)	118 (37.5)	0 (0.0)	<0.000
2	74 (23.0)	72 (22.9)	2 (28.6)
3	64 (19.9)	64 (20.3)	0 (0.0)
4–5	30 (9.3)	26 (8.3)	4 (57.1)
NA	36 (11.2)	35 (11.1)	1 (14.3)
CNS-IPI
0–1	117 (36.3)	117 (37.1)	0 (0.0)	0.001
2–3	133 (41.3)	131 (41.6)	2 (28.6)
4–6	36 (11.2)	32 (10.2)	4 (57.1)
NA	36 (11.2)	35 (11.1)	1 (14.3)
Type of CNS prophylaxis
None	258 (80.1)	254 (80.6)	4 (57.1)	<0.000
Intrathecal	52 (16.1)	52 (16.5)	0 (0.0)
MTX-HD	7 (2.2)	5 (1.6)	2 (28.6)
Intrathecal + MTX-HD	5 (1.6)	4 (1.3)	1 (14.3)
Complete response at the end of treatment
Yes	236 (73.3)	236 (74.9)	0 (0.0)	<0.000
No	41 (12.7)	38 (12.1)	3 (42.9)
NA	45 (14.0)	41 (13.0)	4 (57.9)

Patient	Age (years), sex	Ann Harbor stage, B symptoms (A/B); bulky	Extranodal	IPI	CNS- IPI ^A	CNS prophylaxis was indicated (baseline)?	Diseases status	Classification of CNS relapse	Time to relapse CNS (months)	Time to CNS to death or last contact (days)	OS (months)
1	75y, F	IVB	Uterus	NA	NA	No	Relapsed disease	Parenchyma -cerebellum	52	0	52
2	73y, F	IA	No	4	4	No	Primary refractory	Parenchyma + Meninges – Cranial nerves	3	19	4
3	42y, F	IVB; bulky	BM	4	4	No	Primary refractory	Cerebral spinal fluid	8	1	8
4	57y, F	IVB; bulky	Orbit	2	2	QTIT + MTX-HD	Primary refractory	Direct extension – Skull base – meninges	2	27	3
5	65y, M	II; bulky	No	2	2	MTX-HD	Relapsed disease	Parenchyma	15	62	17
6	63y, F	IVB; bulky	Liver, kidney/ adrenal and BM	4	4	No	Primary refractory	Parenchyma	5	8	6
7	65y, F	IVB	Heart, kidney/adrenal	4	4	MTX-HD	Relapsed disease	Parenchyma	6	279	15

CNS prophylaxis	CNS-IPI				Total	p-value
CNS prophylaxis	Low-risk N (%)	Intermediate-risk N (%)	High-risk N (%)	NA	Total	p-value
Yes	24 (20.5)	21 (15.8)	14 (38.9)	5 (13.9)	64 (100)	0.15
No	93 (79.5)	112 (84.2)	22 (61.1)	31 (86.9)	258 (100)

Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH) R. Dr. Diogo de Faria, 775 cj 133, 04037-002, São Paulo / SP - Brasil - São Paulo - SP - Brazil
E-mail: htct@abhh.org.br

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[1] * Corresponding author at: Ac Camargo Cancer Center, Rua Professor Antonio Prudente, 211, Sao Paulo, SP 01509-010, Brazil. E-mail address: thais.fischer@accamargo.org.br (T. Fischer).