Objective Juvenile localized scleroderma (LS) is a chronic inflammatory skin disorder associated with substantial morbidity and disability. Although a wide range of therapeutic strategies has been reported in the literature, a lack of agreement on treatment specifics and accepted methods for clinical assessment has made it difficult to compare approaches and identify optimal therapy. Our objective was to develop standardized treatment plans, clinical assessments, and response criteria for active, moderate to high severity juvenile LS. Methods A core group of pediatric rheumatologists, dermatologists, and a lay advisor was engaged by the Childhood Arthritis and Rheumatology Research Alliance (CARRA) to develop standardized treatment plans and assessment parameters for juvenile LS using consensus methods/nominal group techniques. Recommendations were validated in 2 face‐to‐face conferences with a larger group of practitioners with expertise in juvenile LS and with the full membership of CARRA, which encompasses the majority of pediatric rheumatologists in the US and Canada. Results Consensus was achieved on standardized treatment plans that reflect the prevailing treatment practices of CARRA members. Standardized clinical assessment methods and provisional treatment response criteria were also developed. Greater than 90% of pediatric rheumatologists responding to a survey (66% of CARRA membership) affirmed the final recommendations and agreed to utilize these consensus plans to treat patients with juvenile LS. Conclusion Using consensus methodology, we have developed standardized treatment plans and assessment methods for juvenile LS. The high level of support among pediatric rheumatologists will support future comparative effectiveness studies and enable the development of evidence‐based guidelines for the treatment of juvenile LS.

BACKGROUND Recently, an internal tandem duplication of the FLT3 gene (FLT3/ITD) was found in approximately 20% of adult acute myeloid leukemia (AML) cases and associated with a poor outcome. However, there are few studies on FLT3/ITD in childhood AML, and the clinical significance of FLT3/ITD is thus unclear. METHODS FLT3/ITD was analyzed in 80 children with de novo AML. The genomic DNA polymerase chain reaction (PCR) assay was performed to identify FLT3/ITD. Genescan analysis to determine the allelic distribution was then performed for those PCR products with aberrant bands. Direct sequencing of PCR products was also carried out in each sample with FLT3/ITD. RESULTS The incidence of FLT3/ITD was 11.3% (9 out of 80 patients) in AML, with 25% (3 out of 12 patients) in acute promyelocytic leukemia (APL) and 8.8% (6 out of 68 patients) in non‐M3 AML. The size of duplicated fragments varied from 21 base pairs (bp) to 75 bp, and the mutant to wild type ratio of FLT3 ranged from 0.28 to 16.60 in the nine patients with FLT3/ITD. The incidence of FLT3/ITD in childhood AML in patients > 10 years of age was 24%, compared to 5% of those patients ≤ 10 years of age (P = 0.011). The six non‐M3 AML patients with FLT3/ITD were all older than 10 years of age. In APL, FLT3/ITD was found in 2 of 2 patients with S‐form PML/RARα, compared with 1 in 10 patients with non‐S form PML/RARα(P = 0.045). There were no cytogenetic abnormalities or fusion transcripts derived from common specific translocations found in non‐M3 AML patients with FLT3/ITD. There was no significant difference in treatment outcome between APL patients with FLT3/ITD and those without FLT3/ITD. The authors failed to find a correlation between the treatment outcome and the presence of FLT3/ITD in non‐M3 AML patients. Instead, the authors found that all three patients with a mutant FLT3 to wild type ratio of greater than 2.0 died within eight months after diagnosis; two of them failed to achieve complete remission. CONCLUSIONS The current study shows that the mutant FLT3 to wild type ratio, but not the presence of FLT3/ITD itself, may serve as a potential marker to improve risk‐assessment in childhood AML. Cancer 2002;94:3292–8. © 2002 American Cancer Society. DOI 10.1002/cncr.10598

Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA gene-edited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.

In children with cancer, most invasive fungal infections can be treated successfully. Current antifungal prophylaxis should protect patients from fungal infection.