Prophylactic high-dose methotrexate (HD-MTX) is often used for diffuse large B-cell lymphoma (DLBCL) patients at high risk of central nervous system (CNS) relapse, despite limited evidence demonstrating efficacy or the optimal delivery method. We conducted a retrospective, international analysis of 1,384 patients receiving HD-MTX CNS prophylaxis either intercalated (i-HD-MTX) (n=749) or at the end (n=635) of R-CHOP/R-CHOP-like therapy (EOT). There were 78 CNS relapses (3-year rate 5.7%), with no difference between i-HD-MTX and EOT; 5.7% vs 5.8%, p=0.98, 3-year difference: 0.04% (-2.0% to 3.1%). Conclusions were unchanged on adjusting for baseline prognostic factors or on 6-month landmark analysis (n=1,253). In patients with high CNS international prognostic index (n=600), 3-year CNS relapse rate was 9.1% with no difference between i-HD-MTX and EOT. On multivariable analysis, increasing age and renal/adrenal involvement were the only independent risk factors for CNS relapse. Concurrent intrathecal prophylaxis was not associated with reduction in CNS relapse. R-CHOP delays of ≥7 days were significantly increased with i-HD-MTX versus EOT, with 308/1573 (19.6%) i-HD-MTX treatments resulting in delay to subsequent R-CHOP (median 8 days). Increased risk of delay occurred in older patients when delivery was later than day 10 in the R-CHOP cycle. In summary, we found no evidence that EOT delivery increases CNS relapse risk versus i-HD-MTX. Findings in high-risk subgroups were unchanged. Rates of CNS relapse in this HD-MTX-treated cohort were similar to comparable cohorts receiving infrequent CNS prophylaxis. If HD-MTX is still considered for certain high-risk patients, delivery could be deferred until R-CHOP completion.

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Integrating natural observation, Interviews, and quantitative analysis, Ms study used a recursive research approach to compare the sociolinguistic judgments of four groups: 38 Puerto Ricans who were encultured on the US mainland, 38 return migrants to Puerto Rico, 161 Americans encultured in the Greater New York metropolitan area (Continental Americans), and 86 bilingual Puerto Ricans encultured on the island of Puerto Rico (Island Puerto Ricans). These participants evaluated alternative sociolinguistic strategies to critical incidents presented in English. Four alternative responses to five critical incidents were surveyed (20 responses in all). Discriminant analysis of group judgments on three subscales (evaluation, social cooperation, and dynamism) showed that while the participants had much in common, there were significant differences and surprising similarities on one or more subscales for 17 of the 20 alternate responses to the critical incidents. Bilingual-bicultural experts and group members interpreted the data in open-ended Interviews; analysis of the interview transcripts revealed both subtle and striking differences in the norms and values underlying sociolinguistic behavior in one or another Community. Mainland and migrantPuerto Ricans were surprisingly alike in their judgments, which in the majority of cases were more like those of Island Puerto Ricans than of continental Americans. Nevertheless, differences revealed possibilities for misunderstandings with mainland and migrant Puerto Ricans in their interactions with both continental Americans and island Puerto Ricans. Areas identified with the potential for sociopragmatic failure included obligations to strangers, the categorization of truth and lies, the use of time in caringfor others, approaches to conflict resolution, and balancing social responsibilities.

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