中国南方汉族急性淋巴细胞白血病患者572例的HLA基因和单倍型分析

 目的　研究HLA-A、B、DRB1基因和单倍型与中国南方汉族急性淋巴细胞白血病（ALL）的疾病相关性。方法　应用最大似然性方法分别计算南方汉族ALL患者组572例和5645名南方汉族健康供者HLA-A、B、DRB1基因和单倍型频率,采用χ2检验方法比较其分布差异。结果　ALL组HLA-A33、B58和DRB1*17基因频率均低于对照组[HLA-A33（7.15 %比9.3 %,OR＝0.73,P＜0.05）、B58（5.93 %比8.75 %,OR＝0.64,P＜0.05）和DRB1*17（5.15%比6.30 %,OR＝0.82,P＜0.05）];A3、B51和DRB*12基因频率均高于对照组[A3（2.1 %比1.26 %,OR＝1.7,P＜0.05）,B51（7. 25 %比5.78 %,OR＝1.3,P＜0.05）和DRB*12（16.13 %比12.99 %,OR＝1.35,P＜0.05）];HLA-A33-B58-DRB1*17单倍型频率低于对照组（2.46 %比4.14 %,OR＝0.35,P＜0.05）,A2-B51- DRB1*12单倍型频率高于对照组（1.24 %比0.89 %,OR＝1.66,P＜0.05）。结论　携带有A33-B58-DRB1*17单倍型个体可能与降低ALL的发病风险有相关性,A3基因和A2-B51- DRB1*12可能与增加ALL发病风险有弱相关性。     

雌激素受体基因ESR1多态性与乳腺癌易感性的关系

目的：研究雌激素受体α（ESR1）基因单核苷酸多态性（SNPs）与乳腺癌易感性的关系。方法：运用聚合酶链反应（PCR）和限制性片段长度多态性（RFLP）分析的方法检测193例中国汉族女性乳腺癌患者和71名正常女性对照者ESR1基因上rs11155816位点的基因型,以SPSS 11.0软件卡方检验处理数据。结果：rs11155816位点等位基因频率符合Hardy-Weinberg遗传平衡定律。rs11155816位点的等位基因及基因型与患者肿瘤位置及是否存在远处转移相关,差异有显著性（P〈0.05）;与年龄、大小、组织学类型、受体表达无关。rs11155816位点等位基因及基因型频率在乳腺癌人群与正常对照者间分布差异有显著性,乳腺癌人群中等位基因A频率高于正常人群（23.8%比15.5%,P〈0.05）。结论：rs11155816位点基因的多态性与乳腺癌患者的肿瘤位置和远处转移相关,等位基因A携带者乳腺癌发病风险较高。     

硒蛋白S基因G-105A、G-254A位点多态性与湖南汉族人群胃癌遗传易感性的相关研究

目的 探讨湖南汉族人群硒蛋白S(SelS)基因G-105A、G-254A位点多态性与胃癌遗传易感性的相关研究.方法 采用聚合酶链反应—限制性片断长度多态性(PCR-RFLP)方法,检测113例湖南汉族胃癌患者及111例健康对照者基因型和等位基因频率,分析胃癌患者与健康对照者G-105A、G-254A位点等位基因频率及基因型频率的差异.结果 G-105A位点GG、GA和AA基因型在胃癌组和健康对照组间分别为100.0％、0.0％、0.0％和100.0％、0.0％、0.0％;G、A等位基因频率在胃癌组和健康对照组分别为100.0％、0.0％和100.0％、0.0％,胃癌组和健康对照组基因型和等位基因频率分布无差异.G-254A位点CC、CT和TT基因型在胃癌和健康对照组间分别为50.0％、37.2％、12.8％和65.8％、28.8％、5.4％;C、T等位基因频率在胃癌组和健康对照组分别为69.0％、31.0％和80.2％、19.8％.胃癌组和健康对照组基因型和等位基因频率分布差异有统计学意义(P＜0.05).湖南汉族人群中携带T等位基因的个体患胃癌的风险是CC基因型个体的1.89倍(OR=1.89,95％CI:1.10～ 3.23).结论 SelSG-254A位点多态性与胃癌的发病具有相关性,T等位基因可能是湖南汉族人群胃癌发病的危险因素之一;湖南汉族人群可能无G-105A这一位点的多态性分布.     

蛋白磷酸酶2A-Aα亚基基因5＇侧翼区多态性在广东汉族人群中的分布

目的：探讨蛋白磷酸酶2A-Aα亚基基因PPP2RIA启动子区的遗传多态性在中国南方汉族人群中的分布特征。方法：随机选取部分广东汉族人群,获取全血基因组DNA。PCR扩增获得PPP2RIA基因5′-侧翼区的目的片段产物直接再测序,筛查并确证潜在的基因多态性位点,采用HaploView软件进行该人群多态性等位基因分布频率的分析、并与HapMap结果进行分布特征比较。结果：PCR扩增和成功测序63例健康人（126条染色体）PPP2RIA基因-1 844～＋201nt的目的片段,序列比对发现该人群中6个已知多态性位点及其人群最小等位基因频率分别为-1 039 G〉T（＋Ins）（rs10414793,但其中T等位基因型含有29个碱基片段的插入）（8.73%）、-568 G〉A（rs1864007）（25.40%）、-241 -/G（rsl 1453459）（26.90%）、＋87 T〉C（rs13344984）（7.94%）、＋107 -/C（rs3833207）（30.16%）和＋108 A〉G（rs1 7554825）（7.94%）;且其中2个位点在该人群中的分布与HapMap公布的国外人群数据存在不同（P〈0.05）;同时,该人群中还发现-512 G〉A（2.38%）的潜在新多态性位点。结论：筛查PPP2RIA基因5′-侧翼区在中国广东汉族人群中多态性位点的等位基因分布,为进一步开展多态性功能性分析提供基础。     

TSP1基因G1678A和A2210G基因多态性与贲门腺癌发病风险的关联

目的探讨凝血酶敏感蛋白-1(TSP1)基因第10外显子G1678A和第13外显子A2210G单核苷酸多态性（SNP）与中国北方人群贲门腺癌（GCA）遗传易感性的关系。方法采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析方法检测145名GCA患者和198名健康对照的TSP1 G1678A和A2210G多态性分布情况。结果TSP1 G1678A多态性位点的基因型及等位基因型频率在贲门腺癌患者组和对照组之间,其总体分布差异均无统计学意义（P>0.05）。根据吸烟状况和上消化道肿瘤家族史分层分析发现,与GG和GA基因型相比,携带AA基因型可能增加非吸烟个体贲门腺癌的发病风险（经性别、年龄和上消化道肿瘤家族史校正后的OR为1.79, 95%CI为1.46~2.11）。TSP1 A2210G位点G等位基因频率在对照组人群中<1%,它可能不是我国北方人群中的常见多态。结论TSP1基因第10外显子AA基因型可能是影响我国北方人群中非吸烟个体贲门腺癌发病风险的因素之一。     

HLA-B等位基因与新疆地区鼻咽癌相关性及其临床意义

目的 探讨HLA-B等位基因多态性与新疆地区鼻咽癌的关系及其临床意义。方法 纳入226例患者作为鼻咽癌组,207例健康志愿者作为健康对照组。采用PCR-SSP法对HLA-B等位基因进行检测。采用χ²检验两组之间、汉族和维吾尔族之间、鼻咽癌不同临床特征之间HLA-B等位基因频率差异。Kaplan-Meier法计算生存率并Logrank单因素分析与HLA-B等位基因频率关系。结果 鼻咽癌组HLA-B*46等位基因频率高于健康对照组(P=0.000),且HLA-B*46等位基因频率在汉族存在差异性(P=0.000),而维吾尔族未发现差异性(P>0.05)。<30岁组HLA-B*44等位基因频率高于≥30岁组(P=0.029);分化型非角化性癌和T₁+T₂期HLA-B*48等位基因频率分别高于未分化型非角化性癌和T₃+T₄期(P=0.029)。鼻咽癌5年OS、DFS、DMFS、LRFS率与HLA-B*46(P=0.118~0.502)、HLA-B*44(P=0.761~0.804)及HLA-B*48(P=0.308~0.727)表达状态无关。结论 HLA-B*46等位基因可能为新疆地区汉族鼻咽癌的易感基因,而HLA-B*44可能与较早发病年龄有关,HLA-B*48可能与病理类型及T分期有关。故HLA-B等位基因可能与鼻咽癌发生、发展有关。     

转化生长因子βⅠ型受体多态性与食管鳞状细胞癌发病风险的关联

目的：探讨转化生长因子βI型受体（transforming growth factor-beta receptor type 1 gene,TGFBR1）＊6A和Int7G24A多态性与中国北方人群食管鳞状细胞癌（esophageal squamous cell carcinoma,ESCC）遗传易感性的关系。方法：选择482名食管鳞癌患者和584名正常健康体检者作对照,分别采用PCR和聚合酶链反应-限制性片段长度多态性（PCR-RFLP）的方法,检测两组受试者外周血单个核细胞染色体DNA中,TGFBR1第1外显子＊6A和第7内含子Int7G24A的多态性分布情况。同时对ESCC患者术后的切除肿瘤组织采用免疫组织化学方法检测TGFBR1的蛋白表达情况,并与其基因型进行相关分析。结果：TGFBR1基因＊6A多态性位点的基因型及等位基因型频率,在ESCC患者组和对照组之间,其分布差异均无统计学意义（P〉0.05）。TGFBR1基因Int7G24A多态性位点的基因型和等位基因型频率,在ESCC组和对照组间分布的差异均具有统计学意义（P〈0.05）,A等位基因携带者患ESCC的风险是G等位基因的1.38倍（经性别、年龄和上消化道肿瘤家族史校正后的OR=1.38,95%CI=1.04～1.75）,与GG基因型相比,携带AA基因型可显著增加ESCC的发病风险（校正后的OR=2.23,95%CI=1.19～3.81）。当按肿瘤分期进行分层分析时发现,与GG基因型相比,Ⅲ期和Ⅳ期ESCC患者中携带GA和AA基因型可显著增加发病风险（校正后的OR=1.61,95%CI=1.10～2.21）。ESCC组织中TGFBR1的蛋白阳性表达率（32.1%）显著低于癌旁正常组织（97.7%）（P〈0.01）,TGFBR1在ESCC中的蛋白表达与＊6A和Int7G24A位点的基因型之间无明显相关性（P〉0.05）。结论：转化生长因子βI型受体Int7G24A位点A等位基因可能是我国北方人群食管癌的遗传易感基因,携带A等位基因的个体可增加食管鳞癌的发病风险。     

CYP1A1*2A基因多态性与宁夏汉族乳腺癌遗传易感性研究

[目的]分析宁夏汉族CYP1A1＊2A基因多态性与乳腺癌遗传易感性的关系。[方法]应用聚合酶链反应—限制性片段长度多态性（PCR-RFLP）技术分别对144例乳腺癌患者和154例对照的CYP1A1＊2A基因多态性进行测定,分析两组基因型及等位基因频率的分布特点。[结果]CYP1A1＊2A等位基因T、C在乳腺癌组和对照组分布的差异无显著性（P〉0.05）,其中等位基因C的乳腺癌发病风险比值比（OR）为1.34（95%CI：0.97～1.86）。CYP1A1＊2A各基因型分布两组间差异也无显著性（P〉0.05）,杂合子突变TC、纯合子突变CC分别与野生型TT相比,乳腺癌发病风险OR分别为1.32（95%CI：0.80～2.18）和1.86（95%CI：0.92～3.78）。[结论]CYP1A1＊2A基因多态性其突变纯合子和杂合子有增加乳腺癌风险的趋势,但未达到显著水平。CYP1A1＊2A基因多态性可能与宁夏汉族人群乳腺癌的发病有关系。     

新疆维吾尔族霍奇金淋巴瘤HLA—A高分辨基因多态性分析

目的：研究人类白细胞抗原（humanleukocyteantigen,HLA—A）高分辨等位基因型与新疆地区维吾尔族霍奇金淋巴瘤（hodgkin’Slymphoma,HL）易感性的关系,以揭示遗传因素在HL发病中的作用。方法：采用病例一对照的研究设计和DNA测序分型（SBT）法,对45例维吾尔族HL患者和110名健康者进行HLA—A基因座位的精确分型,计算HLA_A基因座位等位基因的相对频率（RF）及基因频率（AF）。结果：1）病例组共检出33个高分辨等位基因型,对照组中共检出44个高分辨等位基因型,HLA-A基因座位上等位基因频率分布均满足Hardy-Weninberg遗传平衡检验,P=0．61。2）与新疆地区维吾尔族人群比较,维吾尔族HL患者中等位基因HLA-A＊01：01：01：01（45．48％＂US16．04％）、A＊03：01（39．68％VS18．35％）、A＊01：01（33．91％vs18．35％）、A＊02：07（28．18％VS13．73％）高分辨等位基因分布频率较高,差异有统计学意义,P〈0．01。HLA—A＊02：01（69．05％vs85．47％）和A＊1l：01（16．81％VS32．34％）则相对较低,差异有统计意义,P〈0．01。3）新疆地区维吾尔族HL患者与维吾尔族健康人抗原型均以A2最为多见,各型在病例组与对照组之间分布差异无统计学意义,P〉0．05。结论：HLA-A＊01：01：01：01、A＊03：01、A＊01：01和A＊02：07基因型与维吾尔族HL存在阳性关联,可能为维吾尔族HL发病的易感基因,而HLA-A＊02：01、A＊ll：01可能为维吾尔族HL发病的拮抗基因。     

亚甲基四氢叶酸还原酶基因单核苷酸多态性与儿童急性淋巴细胞白血病的相关性

 【摘要】　目的　探讨亚甲基四氢叶酸还原酶基因（MTHFR）单核甘酸多态性与儿童急性淋巴细胞白血病（ALL）发病风险的关系。方法　分别收集45例ALL患儿（ALL组）及45名健康儿童（对照组）外周血各2 ml,提取基因组DNA,应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）法,检测MTHFR C677T和A1298C基因型,比较不同基因型对儿童ALL发病风险的影响。采用Logistic回归模型计算比值比（OR）和95 %可信区间（95 % CI）。结果　对照组MTHFR 677CC、CT和TT基因型基因分布频率分别为31.1 %（14／45）、51.1 %（23／45）和17.7 %（8／45）,ALL组3种基因型分布频率分别为51.1 %（23／45）、40.0 %（18／45）和8.9 %（4／45）,两者比较差异有统计学意义（χ2＝7.48,P＝0.04）;MTHFR 677 T等位基因在ALL组中的检出率为48.8 %（22／45）,在对照组中的检出率为69.9 %（31／45）;T等位基因携带者发生ALL的风险是CC基因型的0.4倍（95 % CI 0.21～0.83）。对照组MTHFR 1298AA、AC和CC基因型基因分布频率分别为57.8 %、40.0 %和2.2 %,ALL组中3种基因型分布频率分别为18.8 %、44.4 %和6.8 %,两者比较差异无统计学意义（χ2＝11.23,P＝0.23）;MTHFR 1298 C等位基因ALL组中的检出率为42.2 %（19／45）,对照组中的检出率为51.1 %（23／45）;C等位基因的存在并不会提高儿童ALL发生的风险（OR＝1.3,95 % CI 0.21～0.83）。结论　MTHFR 677 T等位基因的存在会显著降低儿童发生ALL的风险,而MTHFR 1298各基因型与儿童ALL的发生均无明显相关性。     

Immunophenotypic and HLA studies in childhood acute lymphoblastic leukemia in Trinidad, West Indies

Between October 1983 and May 1986, 17 cases of childhood acute lymphoblastic leukemia (ALL) were admitted to the General Hospital, Port of Spain, Trinidad. Fifteen of those cases were under 10 years of age, seven of whom presented with joint or bone pains. Boys outnumbered girls by almost 5:1 and the ethnic distribution showed a preponderance of patients of East Indian origin. At last follow-up (May 1989), the survival rate of the 15 under-10-year-old patients was 71%. Immunophenotype studies on nine of the 17 patients revealed six carrying T cell markers and three carrying markers suggestive of a pre-B phenotype. HLA tissue typing on 10 patients showed an enhanced frequency of the HLA-B40 antigen when compared with controls (p less than 0.05). This antigen was present in six of the patients typed and four carried the HLA-A2 and B40 antigens together, two of whom also carried the CW3 antigen and the other two carried untypable C antigens. Three of the four carrying HLA-A2 and B40 have died. Two of the three pre-B cases also carried the HLA-A2 and B40 antigens. HLA studies on three of the four families showed that HLA-A2 and B40 were on the same chromosome, i.e., a haplotype inherited from the mother in each case. None of the cases carried the HLA-B5 antigen although this antigen had a frequency of 37.8% in the control group (p less than 0.05). None of the controls with the HLA-B40 antigen carried the CW3 antigen. Further evidence of a disease association must await typing of the D locus antigens but current evidence would suggest an association between HLA-B40 and childhood ALL in Trinidad.     

The increase of MICA gene A9 allele associated with gastric cancer and less schirrous change

Since surgical resection is the principal treatment of gastric cancer, early detection is the only effective strategy against this disease at present. Recently, a new polymorphic gene family, the major histocompatibility complex class I chain-related (MIC) genes located about 40 kb centromeric to HLA-B gene has been proposed. This family consists of five genes (A, B, C, D and E). Among them, MICA has five various alleles (A4, A5, A5.1, A6 and A9), which can be used as a polymorphic marker for genetic mapping and for disease susceptibility. The MICA polymorphism was studied in our gastric cancer patients to see if there is any possible correlation with genetic predisposition and clinicopathological factors. Genomic DNA was extracted from fresh or frozen peripheral blood leukocytes in 107 patients with gastric adenocarcinoma who underwent gastrectomy in our hospital and 351 noncancer controls. MICA polymorphism was analysed by using PCR-based technique. The results showed both phenotypic and allele frequencies of allele A9 in patients with gastric cancer were significantly higher than controls (33 vs 17.6%, P=0.005; 17 vs 9.9%, P=0.02). Gastric adenocarcinoma with allele A9 was associated with less schirrous change than those without (P=0.014). MICA gene A9 allele might confer the risk of gastric cancer and associate with less schirrous change. The mechanisms among them deserve further investigation.     

Genetic predisposition to acute lymphocytic leukemia in American blacks. A Pediatric Oncology Group study

Recent reports have shown an association between genes lying within the major histocompatibility complex (MHC), particularly HLA and factor B (Bf), and acute lymphocytic leukemia (ALL) in white children. The frequencies of Bf and complement component C4 phenotypes in 90 black American children with ALL were examined to determine if a genetic association existed. The Bf and C4 results for the black children with ALL were compared with frequencies in healthy black Americans from the same geographic region. The BfF allele was carried by 95.6% of the black ALL patients compared with 86.1% of the controls (P = 0.017; relative risk = 3.5). In contrast, only 2.2% of the patients with ALL were homozygous for BfS compared with 9.8% of the controls (P = 0.043; relative risk = 0.2). These findings are similar to those observed in white American children. The C4A6 phenotype was found in 11.9% of the black children with ALL compared with 0.6% of the controls (P = 0.0026; relative risk = 22.7). These findings represent the first reported association of a particular allele whose gene lies within the MHC with ALL in black American children. The results suggest that the occurrence of ALL in black American children may be partially due to a genetic influence.     

Susceptible and Protective Associations of HLA Alleles and Haplotypes with Cervical Cancer in South India

Background: Human leukocyte antigen (HLA) genes have been implicated in cervical cancer in several populations. Objectives: To study the predispositions of HLA alleles/haplotypes with cervical cancer. Materials and Methods: Clinically diagnosed and PAP smear confirmed cervical cancer patients (n 48) and age matched controls (n 47) were genotyped for HLA-A,-B,-DRB1* and DQB1* alleles by PCR-SSP methods. Results: The frequencies of alleles DRB1*04 (OR=2.57), DRB1*15 (OR=2.04), DQB1*0301 (OR=4.91), DQB1*0601 (OR=2.21), B*15 (OR=13.03) and B*07 (OR=6.23) were higher in cervical cancer patients than in the controls. The frequencies of alleles DRB1*10 (OR=0.22) and B*35 (OR=0.19) were decreased. Strong disease associations were observed for haplotypes DRB1*15-DQB1*0601 (OR=6.56; < 3.5.10-4), DRB1*14-DQB1*0501 (OR=6.51; <0.039) and A*11-B*07 (OR=3.95; <0.005). The reduced frequencies of haplotypes DRB1*10-DQB1*0501 (OR=0.45), A*03-B*35 (OR=0.25) and A*11-B*35 (OR= 0.06) among patients suggested a protective association. HLA-C* typing of 8 patients who possessed a unique three locus haplotype 'A*11-B*07-DRB1*04' (8/48; 16.66%; OR=6.51; <0.039) revealed the presence of a four locus haplotype 'A*11-B*07-C*01-DRB1*04' in patients (4/8; 50%). Amino acid variation analysis of susceptible allele DQB1*0601 suggested 'tyrosine' at positions 9 and 37 and tyrosine-non-tyrosine genotype combination increased the risk of cervical cancer. Conclusions: Strong susceptible associations were documented for HLA alleles B*15, B*07, DRB1*04, DRB1*15, DQB1*0301, DQB1*0601 and haplotypes DRB1*15-DQB1*0601 and DRB1*14-DQB1*0501. Further, protective associations were evidenced for alleles B*35 and DRB1*10 and haplotypes A*11-B*35 and DRB1*10-DQB1*0501 with cervical cancer in South India.     

HLA-A,HLA-B,HLA-DRB1 Polymorphisms and Risk of Cervical Squamous Epithelial Cell Carcinoma: A Population Study in China

Cervical cancer is the second most common cancer in women. HLA class I and II alleles polymorphismshave been shown to be associated with cervical cancer risk, but results have varied among different populations.In this study, the HLA-A, -B, and –DRB1 alleles among 100 southern Chinese women with cervical squamouscell carcinoma (SCC) were compared to 254 controls. Our results showed that B*51:01:02 allele frequencywas significantly higher in patients with SCC than in healthy controls (P = 3.17x 10-5, Pc = 0.005, OR = 26.7).Statistical analysis also revealed a significantly decreased frequency of B*51:01:01 (P = 7.01x 10-4, Pc = 0.03, OR= 0.12) in patients with SCC when compared with healthy controls. These results indicate that HLA-B*51:01:02may confer susceptibility to SCC and HLA-B*51:01:01 may contribute to resistance to the development of SCCin Chinese women. None of the HLA-A-B or HLA-A-B-DRB1 haplotypes were significantly different in casesand controls after multiple testing corrections, indicating the individual allele associations to be independent ofthe identified haplotypes. These results support the hypothesis that some HLA-B alleles could be involved withsusceptibility for developing SCC.     

Meta-analysis of human leukocyte antigen genetic polymorphisms and susceptibility to chronic myelogenous leukemia in Chinese population

Human leukocyte antigen (HLA) genetic polymorphisms are assumed to be correlated to the risk of chronic myelogenous leukemia (CML) in various ethnicities. Up to now, no clear consensus has been reached. Our goal is to address this issue in Chinese population. By searching the data in PubMed, Embase and four Chinese databases (prior to July 2010), the association of HLA genetic polymorphisms with CML has been fixed as the research objective. We studied a totality of 12 studies, comprising 2281 CML cases and 41000 health controls. The data demonstrated that HLA-A*11, A*74, HLA-B*40, B*47, B*55 and B*81 alleles were correlated with the increasing risk of CML. Nevertheless, HLA-DRB1*13 allele seemed to contribute to the genetic protection to CML. Conclusively we suggested that certain HLA alleles might be in association with the pathogenesis of CML in Chinese population. Due to little statistical scale, larger studies and particularly in a mono-people background, our hypothesis need to be further investigated in the future.     

HLA class I in acute promyelocytic leukemia (APL): possible correlation with clinical outcome.

The majority of patients with acute promyelocytic leukemia (APL) possess either a bcr1 or a bcr3 type fusion between PML and RARalpha genes. The junction sequences may possibly be a target for immune response and influence susceptibility to the disease. In this case, HLA class I allele frequencies would be different between bcr1 and bcr3 patients. To test this hypothesis, we typed 102 APL patients for HLA-A, -B and -Cw alleles. The A*1, A*30, B*51, B*41, Cw*0602, and Cw*1701 alleles showed a different distribution between bcr1 and bcr3 patients, but in no case was this statistically significant after correction for the number of comparisons or was confirmed in an independent panel. Moreover, no difference was detected between bcr1 and bcr3 when HLA alleles were grouped according to their peptide binding specificities. Comparing HLA frequencies, clinical features at diagnosis and clinical outcome of the 64 patients homogeneously treated with all-trans retinoic acid and idarubicin (AIDA protocol) we observed a statistically significant association between HLA-B*13 and risk of relapse by univariate and multivariate regression analysis. Should this finding be confirmed in larger future studies, this observation would be of outmost importance in identifying patients at high risk of relapse in which more aggressive consolidation therapies should be used.