Post Graduate Institute of Medical Education and Research

Minimal/measurable residual disease (MRD) is a key prognostic factor in B-lymphoblastic leukemia/lymphoma (B-ALL/LBL), commonly assessed via multiparametric flow cytometry (MFC). This study evaluated 12 leukemia-associated immunophenotype (LAIP) markers-CD81, CD86, CD123, CD58, CD9, CD73, CD13/CD33, CD44, CD97, CD66c, CD49f, and CD304-to determine their suitability for MRD detection. Marker expression was analyzed in 103 B-ALL cases at diagnosis, and 54 post-therapy follow-up samples, including 16 MRD-positive cases. Additionally, 25 non-B-ALL bone marrow samples were examined for marker expression in hematogones. Clinical and genetic correlation was also performed. Median age of patients was 9 years (range: 0.3-89), with male: female ratio of 1:1. We found that CD97, CD73, CD86, and CD58 are excellent markers for MRD analysis in B-ALL, as they are expressed in more than 85% of cases at baseline, and their expression is preserved in more than 75% of cases post-therapy. Two other extremely promising markers are CD81 and CD49f, both of which are expressed as LAIP in more than 50% of B-ALL cases, with retention of expression in more than 85% of cases post-therapy, and importantly, expression as LAIP in some post-therapy samples despite their absence at baseline. Hyperdiploidy was significantly associated with expression of CD86, CD97, CD123, CD66c, and CD9; BCR::ABL1 fusion was associated with CD49f, CD81, and CD66c. CD97, CD73, CD86, and CD58 are the best amongst newer markers in B-ALL MRD assessment. Our findings support integrating these into MRD panels to enhance post-therapy MRD detection, thus improving prognostication and guiding treatment decisions.

Cerebral infarction is a frequent and serious complication of tuberculous meningitis (TBM), contributing substantially to morbidity and mortality. Moreover, studies on infarct patterns and associated factors/predictors remain limited in TBM. ACT-TBM trial (Aspirin or Clopidogrel Therapy in the Treatment of Tuberculous Meningitis) evaluated the efficacy and safety of adjunctive antiplatelet therapy (aspirin or clopidogrel) to standard antitubercular therapy in TBM for the occurrence of stroke or cerebral infarction. Here, we conducted a secondary analysis of the ACT-TBM trial to characterize the patterns, associated factors, and predictors of cerebral infarction in TBM. We utilized data of 237 patients from the ACT-TBM randomized controlled trial conducted at 2 tertiary centers in India (2019-2023). Serial magnetic resonance imaging and magnetic resonance angiography were performed at baseline, 1 month, and 3 months in the primary trial. Cerebral infarctions were categorized by size, vascular territory, and number. Multivariable logistic regression models were performed using variables with P<0.1 on univariable analysis and clinical relevance. Model estimates are reported as adjusted odds ratios (aORs) with 95% CIs. Of the 237 patients enrolled, 226 were included after excluding 11 with missing imaging or incomplete follow-up data. Among these, 84 (37%) had cerebral infarction. Median age of the entire cohort was 26 years (interquartile range, 20-36), and 134 (59.29%) were females. Multiple infarcts were observed in 66 (78.6%) patients. Most frequent location of infarction was in the basal ganglia (n=61, 72.6%), subcortical white matter (n=44, 52.4%), and cortex (n=32, 38.1%). Arterial occlusion occurred in 49 (61.25%) patients with cerebral infarction versus 35 (25.55%) without (P<0.001). In multivariable adjusted models, Grade 3 TBM (aOR, 3.94 [95% CI, 1.19-13.08]; P=0.025), and arterial occlusion (aOR, 4.43 [95% CI, 2.19-8.96]; P<0.001) were associated with infarction. Among those with infarction, 27 (32.14%) patients (13.17% of the available cohort) developed new infarctions on follow-up. Modified antitubercular therapy (antitubercular therapy; aOR, 3.10 [95% CI, 1.18-8.09]; P=0.021) and arterial occlusion (aOR, 4.23 [95% CI, 1.40-12.75]; P=0.01) significantly predicted new infarctions. Presence of exudates was associated with arterial occlusion (aOR, 2.86 [95% CI, 1.08-7.56]; P=0.034). Cerebral infarction is common in TBM and associated with disease severity and arterial occlusion. Modified antitubercular therapy predicted new infarcts, while basal exudates were associated with vascular occlusion, highlighting the need for vigilant monitoring and optimized therapeutic strategies.