A multicentre retrospective comparison of central nervous system prophylaxis strategies among patients with high-risk diffuse large B-cell lymphoma

Abstract

Background:Central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) is a devastating complication; the optimal prophylactic strategy remains unclear.Methods:We performed a multicentre, retrospective analysis of patients with DLBCL with high risk for CNS relapse as defined by two or more of: multiple extranodal sites, elevated serum LDH and B symptoms or involvement of specific high-risk anatomical sites. We compared three different strategies of CNS-directed therapy: intrathecal (IT) methotrexate (MTX) with (R)-CHOP ‘group 1' R-CHOP with IT MTX and two cycles of high-dose intravenous (IV) MTX ‘group 2' dose-intensive systemic antimetabolite-containing chemotherapy (Hyper-CVAD or CODOXM/IVAC) with IT/IV MTX ‘group 3'.Results:Overall, 217 patients were identified (49, 125 and 43 in groups 1–3, respectively). With median follow-up of 3.4 (range 0.2–18.6) years, 23 CNS relapses occurred (12, 10 and 1 in groups 1–3 respectively). The 3-year actuarial rates (95% CI) of CNS relapse were 18.4% (9.5–33.1%), 6.9% (3.5–13.4%) and 2.3% (0.4–15.4%) in groups 1–3, respectively (P=0.009).Conclusions:The addition of high-dose IV MTX and/or cytarabine was associated with lower incidence of CNS relapse compared with IT chemotherapy alone. However, these data are limited by their retrospective nature and warrant confirmation in prospective randomised studies.

Absolute peripheral monocyte count at diagnosis predicts central nervous system relapse in diffuse large B-cell lymphoma

“…21 In fact, in the current study, intrathecal prophylaxis was added to patients at high-risk of CNS relapse, but these patients still had a higher incidence of CNS relapse. 22 Therefore, high-dose intravenous methotrexate and/or cytarabine chemotherapy as dose-intensive systemic antimetabolitecontaining chemotherapy may be required in high-risk patients. 22 In conclusion, our findings suggest that the AMC at diagnosis has an independent impact on CNS relapse in patients with DLBCL.…”

“…22 Therefore, high-dose intravenous methotrexate and/or cytarabine chemotherapy as dose-intensive systemic antimetabolitecontaining chemotherapy may be required in high-risk patients. 22 In conclusion, our findings suggest that the AMC at diagnosis has an independent impact on CNS relapse in patients with DLBCL. Novel strategies to prevent CNS relapse should be explored for patients with high AMC.…”

How I treat patients with aggressive lymphoma at high risk of CNS relapse

“…75 The CNS relapse rate was lower in the arm treated with IT and IV MTX (2.7% vs 8%; P 5 .02), acknowledging that other CNS-penetrating agents were used in the MTX arm. Several subsequent retrospective 68,76,77 and 2 prospective studies also support a potential benefit for high-dose systemic MTX in this setting. 78,79 However, these studies are limited by small numbers and nonrandomized and retrospective study designs, with the prospective studies using other CNS-penetrating agents in combination with MTX.…”

“…The regimen we have outlined is adapted from an approach developed at the Peter MacCallum Cancer Centre, Melbourne, Australia. 68 IT MTX is administered once per chemoimmunotherapy cycle (total of 6). Three to 4 weeks after the completion of chemoimmunotherapy, 2 cycles of systemic MTX are administered, 2 to 3 weeks apart.…”

“…Several subsequent retrospective 68,76,77 and 2 prospective studies also support a potential benefit for high-dose systemic MTX in this setting. 78,79 However, these studies are limited by small numbers and nonrandomized and retrospective study designs, with the prospective studies using other CNS-penetrating agents in combination with MTX.…”