Key Points• Children with AL given haplo-HSCT after ab T-and B-cell depletion are exposed to a low risk of acute and chronic GVHD and NRM.• The leukemia-free, GVHDfree survival of patients given this type of allograft is comparable to that of HLAmatched donor HSCT recipients.Allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA-haploidentical relative (haplo-HSCT) is a suitable option for children with acute leukemia (AL) either relapsed or at high-risk of treatment failure. We developed a novel method of graft manipulation based on negative depletion of ab T and B cells and conducted a prospective trial evaluating the outcome of children with AL transplanted with this approach. Eighty AL children, transplanted between September 2011 and September 2014, were enrolled in the trial. All children were given a fully myeloablative preparative regimen. Anti-T-lymphocyte globulin from day 25 to 23 was used for preventing graft rejection and graft-versus-host disease (GVHD); no patient received any posttransplantation GVHD prophylaxis. Two children experienced primary graft failure. The cumulative incidence of skin-only, grade 1-2 acute GVHD was 30%; no patient developed extensive chronic GVHD. Four patients died, the cumulative incidence of nonrelapse mortality being 5%, whereas 19 relapsed, resulting in a 24% cumulative incidence of relapse. With a median follow-up of 46 months for surviving patients, the 5-year probability of chronic GVHD-free, relapsefree survival (GRFS) is 71%. Total body irradiation-containing preparative regimen was the only variable favorably influencing relapse incidence and GRFS. The outcomes of these 80 patients are comparable to those of 41 and 51 children given transplantation from an HLA-identical sibling or a 10/10 allelic-matched unrelated donor in the same period. These data indicate that haplo-HSCT after ab T-and B-cell depletion represents a competitive alternative for children with AL in need of urgent allograft. This trial was registered at www.clinicaltrials.gov as #NCT01810120. (Blood. 2017;130(5):677-685)
Five anti-tumor necrosis factor (anti-TNF) agents have received regulatory approval for use in rheumatology: adalimumab, golimumab, infliximab, certolizumab, and etanercept. Apart from their well-documented therapeutic value, it is still uncertain to what extent they are associated with an increased risk of infectious adverse events. Areas covered: We conducted a systematic review and meta-analysis of published randomized studies to determine the effect of anti-TNF drugs on the occurrence of infectious adverse events (serious infections; tuberculosis; opportunistic infections; any infection). We searched Medline, Embase, and the Cochrane Library up to May 2014 to identify eligible studies in adult patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis that evaluated anti-TNF drugs compared with placebo or no treatment. Expert opinion: Our study encompassed data from 71 randomized controlled trials involving 22,760 participants (range of follow-up: 1-36 months) and seven open label extension studies with 2,236 participants (range of follow-up: 6-48 months). Quantitative synthesis of the available data found statistically significant increases in the occurrence of any infections (20%), serious infections (40%), and tuberculosis (250%) associated with anti-TNF drug use, while the data for opportunistic infections were scarce. The quality of synthesized evidence was judged as moderate. Further evidence from registries and long-term epidemiological studies are needed to better define the relationship between anti-TNF agents and infection complications.
BACKGROUND:Aggressive fibromatosis (AF) is a rare tumor of intermediate malignancy that has a strong potential for local invasiveness and recurrence. To date, there are no general recommendations for the clinical management of pediatric AF.METHODS:The authors retrospectively analyzed 94 patients aged ≤21 years, including 23 patients who underwent complete surgery (Group I), 42 patients who underwent incomplete surgery with microscopic residual tumor (Group II), and 29 patients who underwent either biopsy or macroscopically incomplete surgery (Group III).RESULTS:The 5‐year event‐free survival (EFS) and overall survival rates were 44% and 99%, respectively. Local recurrences developed in 22% of patients in Group I, in 76% of patients in Group II, and in 76% of patients in Group III. Two of 7 patients with abdominal disease died of tumor progression, whereas none of the patients with extra‐abdominal AF died of their disease. Systemic treatment was given to 15 patients as first‐line treatment and to 34 patients at time the time they developed recurrent disease: The response rate was 47% in the former patients and 50% in the latter patients. Objective responses were observed in 11 of 19 patients who received combined methotrexate plus vinblastine/vinorelbine, in 7 of 15 patients who received alkylating‐agent chemotherapy, and in 4 of 11 patients who received other therapies (tamoxifen, sulindac, interferon alfa).CONCLUSIONS:The current analysis suggested that the clinical course of AF in children may resemble that of AF in adults. Local recurrences did not affect the chance of responding to systemic therapy or the survival rate. The completeness of initial resection was the main factor that influenced EFS, whereas disease control after marginal resection was much the same as that achieved after intralesional surgery/biopsy. Good responses to systemic treatments, and particularly to low‐dose chemotherapy, were observed as reported previously in adults. Cancer 2010. © 2010 American Cancer Society.
Pseudomonas aeruginosa is one leading gram-negative organism associated with nosocomial infections. Bacteremia is life-threatening in the immunocompromised host. Increasing frequency of multi-drug-resistant (MDRPA) strains is concerning. We started a retrospective survey in the pediatric hematology oncology Italian network. Between 2000 and 2008, 127 patients with Pseudomonas aeruginosa bacteremia were reported from 12 centers; 31.4% of isolates were MDRPA. Death within 30 days of a positive blood culture occurred in 19.6% (25/127) of total patients; in patients with MDRPA infection it occurred in 35.8% (14/39). In the multivariate analysis, only MDRPA had significant association with infection-related death. This is the largest series of Pseudomonas aeruginosa bacteremia cases from pediatric hematology oncology centers. Monitoring local bacterial isolates epidemiology is mandatory and will allow empiric antibiotic therapy to be tailored to reduce fatalities.
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