Univariable and multivariable analyses of risk factors for all CNS relapse and isolated CNS relapse only
| Risk factor . | All patients . | Landmark . | ||
|---|---|---|---|---|
| Survival time lost (mo) . | P . | Survival time lost (mo) . | P . | |
| All CNS relapses, UVA | ||||
| EOT HD-MTX | 0.52 (−3.04-4.09) | .77 | 0.43 (−3.13-3.99) | .82 |
| Sex | 0.71 (−2.99-4.40) | .71 | 0.14 (−3.58-3.85) | .94 |
| Age (for a 10-y increase) | 1.61 (0.58-2.64) | .002 | 1.64 (0.61-2.66) | .002 |
| Advanced stage | 2.53 (−2.27-7.33) | .30 | 1.22 (−3.66-6.11) | .62 |
| Extranodal sites ≥2 | 4.39 (1.00-7.79) | .011 | 1.99 (−1.48-5.47) | .26 |
| ECOG ≥2 | 0.86 (−2.94-4.67) | .66 | 0.40 (−3.39-4.19) | .84 |
| Renal/adrenal involvement | 7.64 (2.28-13.00) | .005 | 6.06 (0.62-11.51) | .029 |
| Raised LDH | 3.02 (−0.29-6.34) | .074 | 1.63 (−1.67-4.94) | .33 |
| ITs given | 1.10 (−2.48-4.68) | .55 | ||
| HD-MTX doses ≥2 | −2.87 (−8.57-2.84) | .33 | ||
| Cumulative dose >6 g/m2 | −2.19 (−5.47-1.09) | .19 | ||
| All CNS relapses, MVA | ||||
| Age (for a 10-y increase) | 1.60 (0.59-2.61) | .002 | 1.33 (0.39-2.27) | .006 |
| Renal/adrenal involvement | 7.65 (2.31-13.00) | .005 | 5.45 (0.23-10.66) | .041 |
| Isolated CNS relapse, UVA | ||||
| EOT HD-MTX | 0.71 (−2.51-3.94) | .66 | 0.79 (−2.93-4.51) | .68 |
| Sex | 0.46 (−2.89-3.81) | .79 | 0.59 (−3.39-4.56) | .77 |
| Age (for a 10-y increase) | 1.42 (0.51-2.34) | .002 | 1.47 (0.44-2.49) | .005 |
| Advanced stage | 0.24 (−4.48-4.95) | .92 | −0.52 (−5.81-4.77) | .85 |
| Extranodal sites ≥2 | 2.21 (−0.89-5.31) | .16 | 0.82 (−2.79-4.42) | .66 |
| ECOG ≥ 2 | −0.69 (−3.90-2.52) | .67 | −1.63 (−5.11-1.85) | .36 |
| Renal/adrenal involvement | 3.89 (−0.54-8.32) | .086 | 2.29 (2.45-7.03) | .34 |
| Raised LDH | 1.17 (−1.86-4.19) | .45 | 0.03 (−3.27-3.32) | .99 |
| ITs given | 1.21 (−2.59-5.00) | .53 | ||
| HD-MTX doses ≥2 | −2.43 (−7.95-3.10) | .39 | ||
| Cumulative dose >6 g/m2 | −3.59 (−6.84 to −0.35) | .030 | ||
| Isolated CNS relapse, MVA | ||||
| Age (for a 10-y increase) | 1.41 (0.52-2.31) | .002 | 1.47 (−0.44-2.49) | .005 |
| Risk factor . | All patients . | Landmark . | ||
|---|---|---|---|---|
| Survival time lost (mo) . | P . | Survival time lost (mo) . | P . | |
| All CNS relapses, UVA | ||||
| EOT HD-MTX | 0.52 (−3.04-4.09) | .77 | 0.43 (−3.13-3.99) | .82 |
| Sex | 0.71 (−2.99-4.40) | .71 | 0.14 (−3.58-3.85) | .94 |
| Age (for a 10-y increase) | 1.61 (0.58-2.64) | .002 | 1.64 (0.61-2.66) | .002 |
| Advanced stage | 2.53 (−2.27-7.33) | .30 | 1.22 (−3.66-6.11) | .62 |
| Extranodal sites ≥2 | 4.39 (1.00-7.79) | .011 | 1.99 (−1.48-5.47) | .26 |
| ECOG ≥2 | 0.86 (−2.94-4.67) | .66 | 0.40 (−3.39-4.19) | .84 |
| Renal/adrenal involvement | 7.64 (2.28-13.00) | .005 | 6.06 (0.62-11.51) | .029 |
| Raised LDH | 3.02 (−0.29-6.34) | .074 | 1.63 (−1.67-4.94) | .33 |
| ITs given | 1.10 (−2.48-4.68) | .55 | ||
| HD-MTX doses ≥2 | −2.87 (−8.57-2.84) | .33 | ||
| Cumulative dose >6 g/m2 | −2.19 (−5.47-1.09) | .19 | ||
| All CNS relapses, MVA | ||||
| Age (for a 10-y increase) | 1.60 (0.59-2.61) | .002 | 1.33 (0.39-2.27) | .006 |
| Renal/adrenal involvement | 7.65 (2.31-13.00) | .005 | 5.45 (0.23-10.66) | .041 |
| Isolated CNS relapse, UVA | ||||
| EOT HD-MTX | 0.71 (−2.51-3.94) | .66 | 0.79 (−2.93-4.51) | .68 |
| Sex | 0.46 (−2.89-3.81) | .79 | 0.59 (−3.39-4.56) | .77 |
| Age (for a 10-y increase) | 1.42 (0.51-2.34) | .002 | 1.47 (0.44-2.49) | .005 |
| Advanced stage | 0.24 (−4.48-4.95) | .92 | −0.52 (−5.81-4.77) | .85 |
| Extranodal sites ≥2 | 2.21 (−0.89-5.31) | .16 | 0.82 (−2.79-4.42) | .66 |
| ECOG ≥ 2 | −0.69 (−3.90-2.52) | .67 | −1.63 (−5.11-1.85) | .36 |
| Renal/adrenal involvement | 3.89 (−0.54-8.32) | .086 | 2.29 (2.45-7.03) | .34 |
| Raised LDH | 1.17 (−1.86-4.19) | .45 | 0.03 (−3.27-3.32) | .99 |
| ITs given | 1.21 (−2.59-5.00) | .53 | ||
| HD-MTX doses ≥2 | −2.43 (−7.95-3.10) | .39 | ||
| Cumulative dose >6 g/m2 | −3.59 (−6.84 to −0.35) | .030 | ||
| Isolated CNS relapse, MVA | ||||
| Age (for a 10-y increase) | 1.41 (0.52-2.31) | .002 | 1.47 (−0.44-2.49) | .005 |
Survival time is measured up to 10 y; for example, in univariable analysis, a patient given EOT HDMTX has a CNS-relapse-free life expectancy over 10 y that is 0.43 mo shorter than for a patient given i-HD-MTX. The MVA shows variables remaining significant with backward selection (P value for rejection =.05). With a rare event, lifetime lost is not easily clinically interpretable, but at 3 years, this translates to a difference in cumulative incidence of 6.58% for patients with renal and adrenal involvement when compared with those without, and an increase in incidence of 1.12% for each decade of age.
ECOG, Eastern Cooperative Group performance status; EOT, end of treatment; HD-MTX, high-dose methotrexate; IT, intrathecal; LDH, lactate dehydrogenase; MVA, multivariable analysis; UVA, univariable analysis.