A high survival rate, 75.6% at 5 years, was achieved for childhood with de novo AML in the AML99 trial. The treatment strategy was well tolerated with only 1.7% induction death rate and 3.5% remission death rate. Low-risk children were successfully treated with chemotherapy alone.

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Purpose: The biological effect of interleukin-6 (IL-6) signaling in oral squamous cell carcinoma (OSCC) and whether IL-6 receptor (IL-6R)-mediated signaling can be a therapeutic target for OSCC are unclear. The aim of this study was to investigate the effects of inhibition of IL-6R-mediated signaling on OSCC progression and to evaluate the availability of tocilizumab, a humanized antihuman IL-6R antibody, as a therapeutic agent for OSCC. Experimental Design: We evaluated expression levels of IL-6 and IL-6R in 58 OSCC tissues and 4 OSCC cell lines by real-time quantitative reverse transcription-PCR and/ or immunohistochemstry. We investigated the effects of tocilizumab on OSCC growth in vitro and in xenografts. Xenografts were analyzed by immunohistochemistry for phosphorylated signal transducer and activator of transcription 3 (pSTAT3), Ki-67, and CD31, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay was done. Results: Expression levels of IL-6 at both mRNA and protein levels in OSCC tissues were significantly higher than those in normal mucosal tissues. In addition, OSCC cell lines expressed higher levels of both IL-6 and IL-6R mRNA than did HaCaT keratinocytes. Tocilizumab significantly reduced in vivo growth of SAS cells with a drastic reduction of STAT3 phosphorylation in tumor cells in mice. Inhibition of IL-6 signaling significantly decreased vascular endothelial growth factor mRNA expression in SAS, and microvessel density and vessel diameter in SAS tumors in tocilizumab-treated mice. Conclusions: Therapeutic approaches targeting IL-6R by tocilizumab may be effective for OSCC treatment by at least inhibiting angiogenesis. (Clin Cancer Res 2009;15(17):5426-34)

Purpose: The peptides derived from ideal cancer-testis antigens, including LY6K, CDCA1, and IMP3 (identified using genome-wide cDNA microarray analyses), were used in immunotherapy for head and neck squamous cell cancer (HNSCC). In this trial, we analyzed the immune response to and safety and efficacy of vaccine therapy.Experimental Design: A total of 37 patients with advanced HNSCC were enrolled in this trial of peptide vaccine therapy, and the OS, PFS, and immunologic response were evaluated using enzyme-linked ImmunoSpot (ELISPOT) and pentamer assays. The peptides were subcutaneously administered weekly with IFA. The primary endpoints were evaluated on the basis of differences between HLA-A Ã 2402-positive [A24(þ)] patients treated with peptide vaccine therapy and -negative [A24(À)] patients treated without peptide vaccine therapy among those with advanced HNSCC.Results: Our cancer vaccine therapy was well tolerated. The OS of the A24(þ) vaccinated group (n ¼ 37) was statistically significantly longer than that of the A24(À) group (n ¼ 18) and median survival time (MST) was 4.9 versus 3.5 months, respectively; P < 0.05. One of the patients exhibited a complete response. In the A24(þ) vaccinated group, the ELISPOT assay identified LY6K-, CDCA1-, and IMP3-specific CTL responses in 85.7%, 64.3%, and 42.9% of the patients, respectively. The patients showing LY6K-and CDCA1-specific CTL responses demonstrated a longer OS than those without CTL induction. Moreover, the patients exhibiting CTL induction for multiple peptides demonstrated better clinical responses.Conclusions: The immune response induced by this vaccine may improve the prognosis of patients with advanced HNSCC.

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A B S T R A C T PurposeTo evaluate a less intensive chemotherapeutic regimen specifically designed for patients with Down syndrome (DS) and acute myeloid leukemia (AML), and to determine the prognostic factors for event-free survival. Patients and MethodsSeventy-two patients with AML-DS were treated with remission induction chemotherapy consisting of pirarubicin (25 mg/m 2 /d for 2 days), cytarabine (100 mg/m 2 /d for 7 days), and etoposide (150 mg/m 2 /d for 3 days). Patients received four courses of intensification therapy of the same regimen. Prophylaxis for CNS leukemia was not included. ResultsAll but two patients were younger than 4 years, and 67 of the 72 patients (93%) were diagnosed as acute megakaryoblastic leukemia (AMKL). Seventy of the 72 patients (97.2%) achieved a complete remission (CR), and the estimated 4-year event-free survival (EFS) rate was 83% Ϯ 9%. Nine patients relapsed, and one died as a result of pneumonia during CR. Multivariate analysis revealed that the presence of monosomy 7 was a greater risk factor of adverse outcome (odds ratio ϭ 5.67; P ϭ .027). ConclusionA less intensive chemotherapeutic regimen produces excellent outcomes in standard-risk AML-DS patient. Risk-oriented therapy should be considered for future trials in AML-DS.We would like to emphasize that the TRM in the current study was only 1.4% (one of 72 patients) which is much lower than those of previous reports. 7-9,16 On the other hand, relapse and induction failure were found in 11 of 72 patients (14%), which is more frequent than in other reports with intensive regimens. 6,8,13 On the basis of the results of the present study, we have designed a risk-oriented therapy protocol for our next trial with AML-DS. The patients with M1 marrow after induction therapy should be classified into a standard-risk group and receive the same dose of pirarubicin and cytarabine regimen. In POG 8498, daunorubicin was used only in induction, with a total dose of 135 mg/m 2 , and high-dose cytarabine in consolidation. Although this study included only small cohort of 14 DS patients, all were alive as last updated in 2005. 31 We will include high-dose cytarabine for patients with M2 or M3 marrow after induction therapy, classified into a high-risk group, who might have adverse prognostic factors such as age older than 3 and the presence of monosomy 7. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTThe author(s) indicated no potential conflicts of interest.

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