No abstract

The result of cytogenetics is one of the most important prognostic factors on the prognosis of AML. HDAC, auto PBPCT and allogeneic BMT after 1 or 2 times of post remission therapy based on 4 prognostic groups(APL: Acute promyelocytic leukemia, GPG: Good prognosis group, IPG: Intermediate prognosis group, PPG: Poor prognosis group by MRC definition) were underwent based on cytogenetics data. We studied CR, relapse, toxic death, DFS and OS. Inclusion criteria were age<65, PS<3 with reasonable organ functions in de novo AML, secondary AML and RAEB-T. The aims of this prospective intention to treat analysis was to compare the CR, recovery kinetics, DFS and OS by giving different therapies of intensity in the different prognostic groups based on cytogentics data. Three plus seven(Idarubicin 12mg/m2(D1–D3), Ara-C 100mg/m2(D1–D7)) were given to de novo AML, secondary AML and RAEB-T. Intermediate dose(8gm/m2) of Ara-C was given followed by HDAC or auto PBPCT to the patients with GPG(t(8:21) & inv(16)). Three times of post remission therapy including HDAC, or auto PBPCT were given to the patients with IPG or PPG(−5, −7, del 5q, complex). If HLA-identical sibling was available, then allo BMT was underwent after 1st post-remission therapy. In cases of APL, three times of post-remission therapy with idarubicin alone were given. ATRA was given to APL group during remission induction therapy and after post-remission maintenance period for 2 years. Up to Mar., 2005, 422 patients(18 centers) were enrolled. Median follow-up was 48months. Among them, 92.3% was de novo AML, and APL, GPG, IPG and PPG were 10.0%, 21.6%, 51.4%, and 14.7% respectively. Overall CR after 1st induction(3+7) were 69.9%(APL: 87.2%, GPG: 84.7%, IPG: 63.8%, PPG: 55.66%, P<0.01). Relapse rate was 12.8%(APL), 40.5%(GPG), 40.5%(IPG) and 45.6%(PPG) respectively(P<0.01). Toxicities profiles including mucositis, hepatic, cardiac and bleeding episodes were similar on 3 different therapy modalities(HDAC, auto PBPCT and allo BMT). In conclusions, this trial seems to be tolerable in terms of toxicities after induction and during post remission therapies. Among GPG, there were no significant statistical differences on OS and LFS in all the therapy modalities(ie, HDAC, Auto, Allo). In IPG, auto arm had a tendency of superior OS and LFS comparing to HDA & allo arm. In PPG, there was significant surperior LFS in allo arm. There were no statistical differences on OS in all the therapy modalities in PPG. This intention to treattrial, which had started in Jan, 2000, has been going on until now. Through this risk based trial using cytogenetics, we might be able to find optimal post-remission therapies for different risk groups with less toxicities.

Background Polar microalgae contain unique compounds that enable them to adapt to extreme environments. As the skin barrier is our first line of defense against external threats, polar microalgae extracts may possess restorative properties for damaged skin, but the potential of microalgae extracts as skin protective agents remains unknown. Purpose This study aimed to analyze compound profiles from polar microalgae extracts, evaluate their potential as skin epithelial protective agents, and examine the underlying mechanisms. Methods Six different polar microalgae, Micractinium sp. (KSF0015 and KSF0041), Chlamydomonas sp. (KNM0029C, KSF0037, and KSF0134), and Chlorococcum sp. (KSF0003), were collected from the Antarctic or Arctic regions. Compound profiles of polar and non-polar microalgae extracts were analyzed using gas chromatography-mass spectrometry (GC-MS). The protective activities of polar microalgae extracts on human keratinocyte cell lines against oxidative stress, radiation, and psoriatic cytokine exposure were assessed. The potential anti-inflammatory mechanisms mediated by KSF0041, a polar microalga with protective properties against oxidative stress, ultraviolet (UV) B, and an inflammatory cytokine cocktail, were investigated using RNA-sequencing analysis. To evaluate the therapeutic activity of KSF0041, an imiquimod-induced murine model of psoriatic dermatitis was used. Results Polar microalgae contain components comparable to those of their non-polar counterparts, but also showed distinct differences, particularly in fatty acid composition. Polar microalgae extracts had a greater ability to scavenge free radicals than did non-polar microalgae and enhanced the viability of HaCaT cells, a human keratinocyte cell line, following exposure to UVB radiation or psoriatic cytokines. These extracts also reduced barrier integrity damage and decreased mRNA levels of inflammatory cytokines in psoriatic HaCaT cells. Treatment with KSF0041 extract altered the transcriptome of psoriatic HaCaT cells toward a more normal state. Furthermore, KSF0041 extract had a therapeutic effect in a mouse model of psoriasis. Conclusions Bioactive compounds from polar microalgae extracts could provide novel therapeutics for damaged and/or inflamed skin.

The results of cytogenetics are one of the most important prognostic factors in the prognosis of AML. Three different post remission therapies were given with the IPG based on the MRC definitions using the cytogenetics results. The inclusion criteria included age&lt;65, PS&lt;3 with reasonable organ functions, cardiac ejection fraction&gt;50%, bilirubin&lt;2.0mg/dl, creatinine&lt;2mg/dl in de novo AML and secondary AML. The aims of this prospective intention to treat analysis were to compare the CR, recovery kinetics, DFS and OS in IPG based on cytogenetics with 3 different consolidation treatment modalities described as follows. Three plus seven(Idarubicin 12mg/m2, D1-D3; Ara-C 100mg/m2, D1–D7) were given to de novo AML and secondary AML. HDAC followed by three times of post remission therapy or auto PBPCT followed by two times of post remission therapy was given to IPG. If an HLA-identical sibling were available, then allo BMT was tried after 1st post-remission therapy. The median age of the cohort(Total 194) is 42.5(±17.6) (HDAC(n:89) : 47.6, auto PBPCT(n:51) : 46.6, and allo BMT(n:54) : 30.5). The median days for ANC &gt;500/μl and platelet&gt;20k/μl during induction were 22 days and 21 days respectively. Grade 3~4 toxicities were found in 34.1%, 27.7% and 47.2% during HDAC, auto PBPCT and allo BMT, respetively(p&lt;0.05). The relapse rate and the toxic death rate were 25.8%, 27.5% and 29.6%(p=0.24) and 9.1%, 5.5% and 16.6%(p&lt;0.05) in HDAC, auto PBPCT and allo BMT, respectively. So far, this trial seems to be tolerable in terms of toxicities, during induction and post remission therapies. Among IPG, the auto PBPCT arm had a tendency of superior median survival over the HDAC or allo BMT in terms of OS and LFS without statistical differences(HDAC:17m and 8m, auto-PBPCT:18m and 12m, allograft:15m and 8m). This intention to treat trial, which started in Jan, 2000, has proceeded until now in order to have better statistical power for the subset analysis.