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Patients with Philadelphia chromosomepositive acute lymphoblastic leukemia (Ph ؉ ALL) have poor prognosis despite intensive therapeutic intervention. Recently, imatinib, a BCR-ABL tyrosine kinase inhibitor, has been proven to be an effective treatment for Ph ؉ ALL, but nearly all patients rapidly acquire resistance. High-dose imatinib administration might overcome this resistance; however, systemic toxicities would likely limit this approach. Therefore, a new delivery system allowing for the specific targeting of imatinib is urgently needed. Because almost all Ph ؉ ALL cells express CD19 on their surface, we have developed an immunoliposome carrying anti-CD19 antibody (CD19-liposomes). The internalization efficiency of the CD19-liposomes approached 100% in all Ph ؉ ALL cells but was very low in CD19 ؊ cells. The cytocidal effect of imatinib-encapsulated CD19-liposomes (imatinib-CD19-liposomes) on Ph ؉ ALL cell lines and primary leukemia cells from patients with Ph ؉ ALL was much greater than that of imatinib with or without control liposomes. Importantly, the imatinib-CD19-liposomes did not affect the colony formation of CD34 ؉ hematopoietic cells, even at inhibitory concentration of free imatinib. Taken together, these data clearly demonstrate that the imatinib-CD19-liposomes induced specific and efficient death of Ph ؉ ALL cells. This new therapeutic approach might be a useful treatment for Ph ؉ ALL with fewer side effects than free imatinib. IntroductionDespite the successes of high-dose chemotherapy followed by hematopoietic stem cell transplantation for the treatment of leukemia, Philadelphia chromosome-positive (Ph ϩ ) acute lymphoblastic leukemia (ALL) remains refractory to most therapeutic modalities currently available. The Philadelphia chromosome includes one of several forms of fusion genes between bcr and c-abl, and these fusions play a substantial role in the pathogenesis of chronic myelogenous leukemia (CML) and ALL. 1 The p190 bcr-abl fusion gene is detected in 20% to 35% of patients with ALL, and the prognosis of these patients is particularly poor. [2][3][4] Allogenic stem cell transplantation is the only curative therapeutic option today. Long-term survival rates are between 35% and 65% in cases of first complete remissions, but survival rates quickly decline in cases of second and third remissions. [4][5][6][7][8][9] Additionally, the relapse rate for Ph ϩ ALL remains quite high even with transplantation. [4][5][6][7][8][9] Recently, targeted molecular therapy has been introduced to treat such refractory cases, and a BCR-ABL tyrosine kinase inhibitor, imatinib (Glivec, STI571), proved to be a useful agent for Ph ϩ ALL as well as CML. 10 However, in contrast to patients with CML, most of the patients with Ph ϩ ALL quickly become resistant to imatinib. 10,11 In a phase 2 clinical trial examining cases of relapsed or refractory Ph ϩ ALL, only 6% of patients maintained a complete response for more than 4 weeks, in contrast to an overall response rate of 29%. 12 Moreover, the median estimated time...

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Rosai-Dorfman disease (RDD) is a rare histiocytosis typically with bilateral painless cervical lymphadenopathy. Laboratory data are nonspecific, and the presence of emperipolesis in large foamy S-100⁺ CD1a^- histiocytes is the prominent histologic feature. The pathogenesis of RDD still remains elusive. According to published studies, we propose that RDD cells might represent intermediate recruiting monocytes with differentiation blockade. Both disturbance of homoeostasis and inherent genomic alterations could contribute to initiation of the disorder through signal transduction. Several inflammatory molecules such as macrophage colony-stimulating factor, IL-1β, IL-6, and tumor necrosis factor-α also play a pivotal role in the development of this rare entity. Additional studies are needed to further elucidate the essence of the disease.

Introduction: The prognostic significance of the systemic immune-inflammation index (SII) in breast cancer is unknown. Here, we aimed to explore the connection between pretreatment SII and the survival of patients with triple-negative breast cancer (TNBC). Methods: We enrolled 160 TNBC patients treated in our hospital between May 2000 and June 2012. We employed the Kaplan-Meier curve and log-rank test to assess overall survival (OS), disease-free survival (DFS), and distant metastasis-free survival (DMFS). We identified the prognostic significance of SII using the Cox regression model. Results: The Kaplan-Meier curve revealed the median OS as 44.2 and 82.4 months in high and low SII TNBC patients, respectively ( P <0.001). According to univariate and multivariate analyses, increased SII correlated with poor OS (HR =2.91, 95% CI: 2.00–4.23, P <0.001; HR =2.60, 95% CI: 1.74–3.88, P <0.001). The DFS and DMFS of patients with high SII were 18.8 and 23.8 months, respectively, while those of patients with low SII were 29 and 45.2 months, respectively, ( P <0.001). Further univariate analyses showed a significant correlation between SII and DFS and DMFS ( P <0.01), while results from multivariate analyses suggested that SII is an independent prognostic factor for DFS ( P =0.045), but not for DMFS ( P =0.078). The area under the receiver operating characteristics curves for SII to differentiate between long and short OS, DFS, and DMFS were 0.69, 0.60, and 0.64, respectively. Conclusion: Our findings may point to SII having an independent prognostic significance in TNBC patients. Prospective in-depth studies, using a larger sample size, are required to further investigate the precise role of SII in TNBC before clinical use.

ImportanceProgrammed cell death ligand 1 inhibitors combined with chemotherapy has changed the approach to first-line treatment in patients with extensive-stage small cell lung cancer (SCLC). It remained unknown whether adding a programmed cell death 1 (PD-1) inhibitor to chemotherapy provided similar or better benefits in patients with extensive-stage SCLC, which would add evidence on the efficacy of checkpoint inhibitors in the treatment of extensive-stage SCLC.ObjectiveTo evaluate the efficacy and adverse event profile of the PD-1 inhibitor serplulimab plus chemotherapy compared with placebo plus chemotherapy as first-line treatment in patients with extensive-stage SCLC.Design, Setting, and ParticipantsThis international, double-blind, phase 3 randomized clinical trial (ASTRUM-005) enrolled patients at 114 hospital sites in 6 countries between September 12, 2019, and April 27, 2021. Of 894 patients who were screened, 585 with extensive-stage SCLC who had not previously received systemic therapy were randomized. Patients were followed up through October 22, 2021.InterventionsPatients were randomized 2:1 to receive either 4.5 mg/kg of serplulimab (n = 389) or placebo (n = 196) intravenously every 3 weeks. All patients received intravenous carboplatin and etoposide every 3 weeks for up to 12 weeks.Main Outcomes and MeasuresThe primary outcome was overall survival (prespecified significance threshold at the interim analysis, 2-sided P &amp;lt; .012). There were 13 secondary outcomes, including progression-free survival and adverse events.ResultsAmong the 585 patients who were randomized (mean age, 61.1 [SD, 8.67] years; 104 [17.8%] women), 246 (42.1%) completed the trial and 465 (79.5%) discontinued study treatment. All patients received study treatment and were included in the primary analyses. As of the data cutoff (October 22, 2021) for this interim analysis, the median duration of follow-up was 12.3 months (range, 0.2-24.8 months). The median overall survival was significantly longer in the serplulimab group (15.4 months [95% CI, 13.3 months-not evaluable]) than in the placebo group (10.9 months [95% CI, 10.0-14.3 months]) (hazard ratio, 0.63 [95% CI, 0.49-0.82]; P &amp;lt; .001). The median progression-free survival (assessed by an independent radiology review committee) also was longer in the serplulimab group (5.7 months [95% CI, 5.5-6.9 months]) than in the placebo group (4.3 months [95% CI, 4.2-4.5 months]) (hazard ratio, 0.48 [95% CI, 0.38-0.59]). Treatment-related adverse events that were grade 3 or higher occurred in 129 patients (33.2%) in the serplulimab group and in 54 patients (27.6%) in the placebo group.Conclusions and RelevanceAmong patients with previously untreated extensive-stage SCLC, serplulimab plus chemotherapy significantly improved overall survival compared with chemotherapy alone, supporting the use of serplulimab plus chemotherapy as the first-line treatment for this patient population.Trial RegistrationClinicalTrials.gov Identifier: NCT04063163