The natural history of neurolymphomatosis

Abstract

Background: Neurolymphomatosis is a lymphoid malignancy of the peripheral nervous system and its natural history is poorly understood.

Methods: We performed PubMed search and extracted clinical data for Kaplan-Meier statistics to determine outcome parameters over time. Kruskal-Wallis test was performed to compare prognostic factors.

Results: Our search identified 559 patients and their median age was 61 years. Median overall survival (OS) was 12.0 (range 10.0-15.0) months. Diffuse large B-cell lymphoma was the most frequent histology, involving the brachial plexus, cranial nerves, and sciatic nerve. None had molecular profiling. There was a progressive lengthening of OS in successive decades, from 0.5 (95% CI 0.0-0.8) to 26.4 (95% CI 18.0-34.8) months between 1951 and 2022 (r² = 0.0528, p < 0.00001). Time from first treatment (treatment 1) to progression increased from 2.0 to 36.0 (95% CI 6.5-50.7) months (r² = 0.0961, p = 0.00236). Time from symptom onset to diagnosis remained unchanged (r² = 0.0000556, p = 0.939). Patients were most frequently treated with methotrexate, rituximab, and/or radiation either alone or in combination. Primary neurolymphomatosis had a better prognosis than secondary neurolymphomatosis. No OS difference was noted between B- and T-cell disease, but low-grade B-cell performed better than Burkitt's lymphoma.

Discussion: Better outcome for patients with neurolymphomatosis is noted over time. But timely diagnosis remains a major problem that needs improvement.

Fig. 1. Consort diagram and outcome parameters.

a Consort diagram for article inclusion and exclusion. b Graphical depiction of outcome parameters: (i) OS (green), (ii) time from treatment 1 to progression (gold), (iii) time from symptom onset to diagnosis (red), and (iv) time from symptom onset to death (blue).

Fig. 2. Survival in the entire NL population and stratified by decade of publication.

a Median OS for the entire NL population was 12.0 (95% CI 10.0–15.0) months. Decade analyses were done from <1990–2022. b Median OS increased from a median of 0 (95% CI 0–1.6) to 26.2 (95% CI 0–189.4) months. c Median time from treatment 1 to progression also increased from 2 to 36.0 (95% CI 6.5–50.7) months. d Median time from symptoms onset to diagnosis stayed flat, 6.0 to 4.0 (95% CI 0–88.0) months. e Median time from symptoms onset to death increased from 0 (95% CI 0–5.3) to 26.2 (95% CI 5.3–188.0) months. See also Supplementary Table 4A–D.

Fig. 3. Kruskal-Wallis analysis of survival according to treatment regimens.

a Analysis of OS showed a chi-squared value of 63.493 with 8 degrees of freedom and p < 0.00001. b Analysis of time from treatment 1 to progression showed a chi-squared value of 26.8 with 7 degrees of freedom and p = 0.00036. c Analysis of time from symptom onset to diagnosis showed a chi-squared value of 3.9978 with 8 degrees of freedom and p = 0.8573. d Analysis of time from symptom onset to death showed a chi-squared value of 69.849 with 8 degrees of freedom and p < 0.00001. See also Supplementary Table 5A–D.

Fig. 4. Survival of NL patients according to prognostic factors.

a OS dichotomized at age 55, with a median OS of 23.0 (95% CI 17.1–N/A) months for patients at age ≤55 years and 10.0 (95% CI 10.0–13.4) months for those at age >55 years (p = 0.01227). b Time from treatment 1 to progression dichotomized at age 45, with a median of 12.0 (95% CI 6.0–22.0) months for patients at age ≤45 years versus 6.4 months (95% CI 6.4–9.4) months for those at age >45 years (p = 0.03707). c Median OS was 15.0 (95% CI 11.0–33.0) months for patients with primary NL and 10.0 (95% CI 10.0–10.0) months for those with secondary NL (p = 0.01715). d No difference in OS between B- and T-cell lymphomas, median OS 13.0 (95% CI 10.0–16.0) compared to 10.0 (95% CI 10.0–19.0) months, respectively (p = 0.16173).

Fig. 5. Kruskal-Wallis analysis of survival according to histological subtypes of B-cell lymphoma.

a Analysis of OS showed a chi-squared value of 36.033 with 14 degrees of freedom and p = 0.01032. b Analysis of time from treatment 1 to progression showed a chi-squared value of 9.9899 with 10 degrees of freedom and p = 0.4414. c Analysis of time from symptom onset to diagnosis showed a chi-squared value of 4.9476 with 7 degrees of freedom and p = 0.6664. d Analysis of time from symptom onset to death showed a chi-squared value of 35.834 with 14 degrees of freedom and p = 0.01105. See also Supplementary Table 6A–D.

Fig. 6. Kruskal-Wallis analysis of survival according to peripheral nerve involvement.

a Analysis of OS showed a chi-squared value of 49.824 with 10 degrees of freedom and p = 0.00602. b Analysis of time from treatment 1 to progression showed a chi-squared value of 21.558 with 10 degrees of freedom and p = 0.01572. c Analysis of time from symptom onset to diagnosis showed a chi-squared value of 2.9153 with 10 degrees of freedom and p = 0.9396. d Analysis of time from symptom onset to death showed a chi-squared value of 33.352 with 10 degrees of freedom and p = 0.1534. See also Supplementary Table 8A–D.