Successful application of PD-1 knockdown CLL-1 CAR-T therapy in two AML patients with post-transplant relapse and failure of anti-CD38 CAR-T cell treatment.

Patients with relapsed/refractory acute myeloid leukemia (R/R AML) often show resistance to chemotherapy and have dismal outcomes. Therefore, it is urgent to develop new treatment strategies to address this problem. With tremendous achievement of chimeric antigen receptor T cells (CAR-T) therapy against B-cell malignancies, many efforts have been devoted to developing CAR-T therapy for R/R AML but with limited success, in part owing to a lack of specific targets. C-type lectin-like molecule-1 (CLL-1) is highly expressed on AML blasts with no expression on normal hematopoietic stem cells, which makes it an ideal target of immunotherapy for AML. Here, we report 2 R/R AML patients who relapsed after allogeneic stem cell transplantation and failed multiline salvage therapies including anti-CD38 CAR-T therapy, but were successfully treated with PD-1 silenced anti-CLL-1 CAR-T therapy. Both patients achieved molecular complete remission with incomplete hematologic recovery at 28 days of evaluation after CLL-1 CAR-T cell infusion. Cytokine release syndrome in cases 1 and 2 were grade 1 and 2, respectively. At the last follow-up, cases 1 and 2 had maintained continuous remission for 8 and 3 months, respectively. Our results demonstrated that CLL-1 CAR-T cells might be an effective and safe salvage therapy for AML patients with posttransplant relapse.

Bloodstream infections in pediatric patients with acute leukemia: Emphasis on gram-negative bacteria infections.

BACKGROUND/PURPOSE: Acute leukemia is the most common pediatric hematological malignancy. Bloodstream infections (BSIs) are severe complications in these patients during chemotherapy. This study aims to explore clinical features, laboratory, and microbiological characteristics of BSIs in acute leukemic children. METHODS: Patients aged < 18 years, diagnosed with acute myeloid leukemia or acute lymphocytic leukemia with BSIs from January 2004 to December 2013 were enrolled. BSIs was defined as positive isolate(s) of blood culture and associated with clinical findings. Clinical presentations, demographic features, and microbiological findings were retrospectively reviewed. RESULTS: In total, 126 isolates of 115 episodes of BSIs were identified from 69 patients (acute lymphocytic leukemia 56; acute myeloid leukemia 13). Gram-negative bacteria (GNB), gram-positive cocci, and fungi constituted 56.3%, 42.3%, and 2.4% of the pathogens, respectively. Eighty-three and a half percent of BSIs occurred along with neutropenia, and 73% had severe neutropenia. GNB was the leading pathogen of BSIs. The major GNBs were Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa. White blood cell counts, absolute neutrophil counts, and platelet counts were significantly lower in patients of BSIs caused by GNB than gram-positive cocci. Plasma level of C-reactive protein was significant high in patients of GNB BSIs (179.8 mg/L vs. 127.2 mg/L; p = 0.005). Eighty-two percent of patients of E. coli, K. pneumonia, and P. aeruginosa BSIs had sepsis related organ failure or organ dysfunction. P. aeruginosa BSIs had the highest case-mortality (40%). CONCLUSION: Neutropenia was the major risk factor of BSIs in pediatric leukemic patients. BSIs of GNB were associated with severe neutropenia, systemic inflammatory responses, and high mortality.

Clinical and epidemiological characteristics in children with community-acquired mycoplasma pneumonia in Taiwan: A nationwide surveillance.

BACKGROUND: Community-acquired pneumonia (CAP) is the leading cause of hospitalization of children. Mycoplasma pneumoniae is one of the most common pathogens. The disease severity is diverse, and the diagnosis remains a challenge to clinical pediatricians. The aims of this study are to provide a nationwide surveillance of the epidemiology and clinical manifestations of community-acquired mycoplasma pneumonia (CAMP) in children in Taiwan. METHODS: The medical records of children enrolled by the Taiwan Pediatric Infectious Disease Alliance (TPIDA) project during 2010-2011 were reviewed. Hospitalized children with segmental or lobar pneumonia were included. The demographic, clinical, laboratory and radiographic data were analyzed. Nasopharyngeal swabs, pleural effusion, and serum were collected for multiplex viral and bacterial polymerase chain reaction (PCR), mycoplasma immunoglobulin M (IgM), or paired immunoglobulin G (IgG) titer. RESULTS: There were overall 127 children with CAMP. Among them, 16 (12.6%) children had PCR and IgM positivity, 74 (58.3%) children had a positive serologic study, 34 (27.8%) children had positive PCR detection, and three (2.4%) children had paired IgG above a four-fold increase. Enrolled patients were divided into two groups before and after the age of 5 years. Children younger than 5 years or younger had a significantly longer hospitalization, higher intensive care unit (ICU) admission rates, and more complications. They were more frequent to receive oxygen supplementation and even surgical intervention. The white blood cell counts and C-reactive protein levels were higher in children 5 years old or younger. CONCLUSION: Mycoplasma pneumoniae is an important etiology of CAP in children 5 years or younger. They had a longer length of hospitalization, higher inflammatory responses, and more complications, compared to children older than 5 years.

The trend of macrolide resistance and emm types of group A streptococci from children at a medical center in southern Taiwan.

BACKGROUND: Group A streptococcus (GAS) is a common pathogen in children. Macrolide resistance in GAS has been described worldwide. The aims of this study are to analyze macrolide resistance of GAS isolates in southern Taiwan and to clarify the relationship of emm typing and macrolide resistance in the past decade. METHODS: All GAS isolated from patients younger than 18 years at a single tertiary center in southern Taiwan were collected from 2000 to 2012. Antibiotics susceptibility to erythromycin, azithromycin, and clindamycin were determined by agar dilution method, and were interpreted by Clinical and Laboratory Standards Institute (CLSI) standards. emm typing was performed by polymerase chain reaction (PCR). RESULTS: A total of 301 isolates were collected during the period of 13 years. Scarlet fever (38.5%) and acute pharyngitis (32.2%) were the most common diagnosis. Decreased resistance rate of erythromycin from 53.1% in 2000 to 0% in 2010 was found, but it increased rapidly to 65% in 2011. The resistance rate of azithromycin was the lowest (4.2%) in 2005, but was higher than 15% after 2006. The involvement of the erythromycin resistance genes were mefA (53.1%), ermB (35.9%), and ermTR (10.9%). The resistance of clindamycin also increased since 2011. emm12 was the most common serotype and accounted for 44.9% of all isolates. Compared with the non-emm12 group, resistance to erythromycin, azithromycin, and clindamycin were more frequently detected in the emm12 group. CONCLUSION: Increased resistance of GAS to macrolide and clindamycin was found in recent years. emm12 was the main serotype for macrolide resistance.