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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 1384 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 = .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 = 1253). In patients with a high CNS international prognostic index (n = 600), the 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 a reduction in CNS relapse. R-CHOP delays of ≥7 days were significantly increased with i-HD-MTX vs EOT, with 308 of 1573 (19.6%) i-HD-MTX treatments resulting in a 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 vs 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., (© 2022 by The American Society of Hematology.)

Autoimmune cytopenias (AICs) affect 5% to 9% of patients with chronic lymphocytic leukemia (CLL). Targeted drugs-ibrutinib, idelalisib, and venetoclax-have a prominent role in the treatment of CLL, but their impact on CLL-associated AICs is largely unknown. In this study, we evaluated the characteristics and outcome of preexisting AICs and described the incidence, quality, and management of treatment-emergent AICs during therapy with targeted drugs in patients with CLL. We collected data from 572 patients treated with ibrutinib (9% in combination with an anti-CD20 monoclonal antibody), 143 treated with idelalisib-rituximab, and 100 treated with venetoclax (12% in combination with an anti-CD20 monoclonal antibody). A history of preexisting AICs was reported in 104 (13%) of 815 patients. Interestingly, 80% of patients whose AICs had not resolved when treatment with a targeted drug was started experienced an improvement or a resolution during therapy. Treatment-emergent AICs occurred in 1% of patients during ibrutinib therapy, in 0.9% during idelalisib therapy, and in 7% during venetoclax therapy, with an estimated incidence rate of 5, 6, and 69 episodes per 1000 patients per year of exposure in the 3 treatment groups, respectively. The vast majority of patients who developed treatment-emergent AICs had unfavorable biological features such as an unmutated IGHV and a del(17p) and/or TP53 mutation. Notably, despite AICs, 83% of patients were able to continue the targeted drug, in some cases in combination with additional immunosuppressive agents. Overall, treatment with ibrutinib, idelalisib, or venetoclax seems to have a beneficial impact on CLL-associated AICs, inducing an improvement or even a resolution of preexisting AICs in most cases and eliciting treatment-emergent AICs in a negligible portion of patients., (© 2021 by The American Society of Hematology.)

Background: The effectiveness of medical therapy in paediatric acute severe colitis is scarcely described. We aimed to assess the efficacy of infliximab in children prospectively enrolled at Sapienza University of Rome between May 2010 and 2012., Methods: Clinical assessment and laboratory data were recorded at admission and at day 3 and 5. All patients received corticosteroids; infliximab was administered in refractory patients. Colectomy rate was assessed at 2-year follow-up., Results: Thirty-one patients (mean age 10.6±4.9 years, 52% females) were included: 21 responded to corticosteroids (68%), 10 were refractory and received infliximab (32%). Among the latter, 2 required urgent colectomy (20%); 80% responded, however 50% of these required elective colectomy during follow-up. Patients refractory to corticosteroids showed a significantly shorter interval from ulcerative colitis diagnosis to acute severe colitis compared to responders (7.4±9.6 vs. 23.1±21.6 months, respectively; p=0.01), and a higher rate of colectomy at follow-up (50% vs. 14%, respectively; p=0.007). More than 2 courses of corticosteroids before acute severe colitis were predictive of surgical need (OR 4.4)., Conclusion: Despite its short-term efficacy, infliximab did not modify the long-term surgical rate of paediatric acute severe colitis in our cohort. Children with an early severe colitis commonly need a second-line therapy, whilst frequent courses of corticosteroids are predictive of a poor outcome., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Polychlorinated biphenyls (PCBs) have been hypothesized to increase the risk of non-Hodgkin lymphoma (NHL), although conclusive evidence is still lacking. High levels of PCBs were found in soil in some areas close to a PCB-producing factory in Brescia, North Italy. We conducted a population-based case-control study among residents of the town to investigate the possible association between PCB pollution and NHL in this area., Methods: We included both incident and deceased NHL cases, and a random sample of the town residents as controls, frequency matched to cases as regards age and gender. Exposure to PCBs was estimated on the basis of the lifetime residential history of cases and controls in four different areas of the town-A, B and C (polluted areas) and D (control area)., Results: A total of 495 cases (287 incident cases) and 1467 controls were enrolled. Positive associations were found between NHL and having resided for at least 10 years in the area A, the most polluted area (odds ratio, OR=1.8; p=0.02) and for having resided in any of the polluted areas considered together (A+B+C) (OR=1.4; p=0.08). However, no associations were evident for having resided 20 years or longer in the polluted areas or when analyzing the association with each subject's main residence in his/her lifetime., Conclusion: This study provides some evidence for an association between PCB exposure and NHL, though results should be considered with caution in the absence of individual biological measures of exposure., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: Little information is available on the effect of a follow-up strategy in celiac disease patients during gluten-free diet., Aims: To assess 5 year time course of t-transglutaminase antibodies (t-TG) in celiac disease patients enrolled in a community based follow-up program., Methods: Annual t-TG testing and periodical clinic visit in 2245 patients., Results: Proportion of patients with negative t-TG progressively increased from 83% to 93% during the 5-year follow-up: poor adherence to gluten-free diet (HR 4.764), long duration of gluten-free diet (HR 0.929) and female gender (HR 1.472) were independently associated with serological outcome. In individual patients, 69% tested t-TG "persistently negative", 1% "persistently positive" and 30% "intermittently negative or positive". By applying mathematical modelling to t-TG conversion rates observed in this latter group at beginning and end of the follow-up program, the predicted proportion of t-TG negative population increased from 90% to 95% over 5 years., Conclusions: Time-course of t-TG serology in the community fluctuates in 1/3 of celiac disease patients suggesting inconstant adherence to gluten-free diet and need of follow-up strategy. Periodical serological and clinical follow-up is a viable and efficacious strategy to promote adherence to gluten-free diet as inferred from time-course of t-TG serology., (Copyright © 2010. Published by Elsevier Ltd.)

Intensive chemotherapy given in early chronic phase of chronic myelogenous leukemia (CML) has resulted in high numbers of circulating Philadelphia (Ph) chromosome-negative hematopoietic progenitor cells (HPC). We have autografted 30 consecutive patients with CML in chronic phase with HPC collected in this way to facilitate restoration of Ph-negative hematopoiesis in bone marrow after high-dose therapy. Hematopoietic recovery to greater than 0.5 x10(9)/L neutrophils and to greater than 25 x 10(9)/L platelets occurred in all patients, a median of 13 (range, 9 to 32) days and 16 (range, 6 to 106) days postautograft, respectively. Regenerating marrow cells were Ph-negative in 16 (53%) patients and greater than 66% Ph-negative in 10 (33%) patients. Twenty-eight patients are alive 6 to 76 months (median, 24 months) after autografting. Three patients have developed blast crisis from which 2 have died. Eight patients are in complete cytogenetic remission at a median of 20 (range, 6 to 44) months with a median ratio BCR-ABL/ABL of 0.002 (range, <0.001 to 0.01). Eight patients are in major cytogenetic remission at a median of 22 (range, 6 to 48) months. No patient died as a consequence of the treatment. All patients had some degree of stomatitis that was severe in 15 (50%) patients. Gastrointestinal and hepatic toxicities were observed in about one fourth of patients. Thus, autografting with Ph-negative mobilized HPC can result in prolonged restoration of Ph-negative hematopoiesis for some patients with CML; moreover, most autograft recipients report normal or near normal activity levels, suggesting that this procedure need not to be associated either with prolonged convalescence or with chronic debility.