Bcl-2与乳腺癌耐药蛋白基因在老年急性髓系白血病中表达的意义

目的 探讨Bcl-2和乳腺癌耐药蛋白(BCRP)基因在老年急性髓系白血病(AML)中的表达及其相关性.方法 RT-PCR法检测20例老年AML患者及20例老年非恶性血液病对照组的骨髓白细胞BCRP mRNA,同时流式细胞仪(FCM)检测其骨髓单个核细胞(BMMNC) Bcl-2蛋白表达.结果 AML组Bcl-2总阳性率较对照组显著增高,其中初治组阳性率与对照组无显著差异,而难治与复发组阳性率明显高于初治组和对照组(P＜0.05);BCRP总阳性率明显高于对照组,其中初治组和难治与复发组阳性率均较对照组明显增高(P＜0.05),而初治组和难治与复发组间无显著差异(P＞0.05).Bcl-2+组和BCRP+组完全缓解(CR)率明显低于Bcl-2-组和BCRP-组,早期复发率明显高于Bcl-2-组和BCRP-组(均P＜0.05).Bcl-2和BCRP基因在初治组和难治/复发组表达不相关(P＞0.05).结论 Bcl-2和BCRP基因均与临床耐药密切相关,二者高表达均提示预后不良,但二者无相关性,联合检测Bcl-2和BCRP基因对评价AML预后有较大意义.     

去甲氧柔红霉素联合治疗老年性急性非淋巴细胞白血病初治患者的远期疗效

目的:评价去甲氧柔红霉素(IDA)在老年性急性非淋巴细胞白血病初治患者治疗中的远期疗效。方法:应用IDA加阿糖胞苷(Arac)治疗老年急性非淋巴细胞白血病初治患者27例(治疗组),并与柔红霉素加Arac治疗方案(对照组)对比分析。结果:治疗组与对照组完全缓解(CR)率分别为66.7%和52.1%,部分缓解(PR)率分别为14.8%和16.7%,差异无统计学意义(P>0.05);但治疗组获得CR后维持CR时间为(46.44±31.54)个月,较对照组(22.40±14.95)个月明显延长(P<0.01),所有CR患者中治疗组与对照组3年无病存活率分别为61.1%和20%,差异有统计学意义(P<0.05),5年无病存活率分别为33.3%和8%,差异无统计学意义(P>0.05)。结论:IDA加Arac作为老年性急性非淋巴细胞白血病初治患者的诱导缓解方案能明显延长患者的CR期,有较好的远期疗效。     

急性淋巴细胞白血病Ki-67抗原和Bcl-2的表达及临床意义

目的：通过增殖相关抗原Ki-67和抗凋亡蛋白Bcl-2的检测，观察其在急性淋巴细胞白血病（ALL）和慢性淋巴细胞白血病（CLL）中的表达，探讨其与ALL免疫学分型，临床疗效和预后的关系。方法：采用链霉菌抗生物素蛋白-碱性磷酸酶（SAP）免疫组织化学染色的方法，对120例白血病患者的骨髓或外周血进行Ki-67抗原和Bcl-2蛋白的检测。结果：（1）Ki-67抗原在成人ALL中的表达高于其在急性非淋巴细胞白血病（ANLL），CLL中的表达，Bcl-2蛋白在成人ALL中的表达明显低于ANLL，CLL中的表达。（2）在成人ALL各免疫表型中，T细胞，伴有髓系抗原标记的急性淋巴细胞白血病（My^ ALL)的Ki-67和Bcl-2阳性表达率较高。（3）完全缓解（CR）率在Ki-67和Bcl-2两项同时低表达组中最高，在仅一项低表达组中次之，在两项均高表达组中最低。（4）Ki-67高表达组的生存期比低表达组短，且差异有显著性意义。而Bcl-2的表达在两组之间无差异。结论：对成人ALL患者进行增殖相关抗原Ki-67和抗凋亡蛋白Bcl-2的检测，能反映患者肿瘤细胞的增殖活性和凋亡抑制情况，与白血病的类型，临床疗效和预后密切相关。     

急性白血病bcl-2、bax测定的临床意义

目的探讨急性白血病(AL)患者bcl-2、bax的表达与临床治疗及预后的关系。方法采用S-P免疫组化法检测AL患者骨髓单个核细胞(BMMNC)上bcl-2及bax的表达水平,行AL疗效分析。结果急性髓细胞白血病(AML)和急性淋巴细胞白血病(ALL)患者bcl-2表达分别为(46.12±27.29)%和(57.94±32.19)%,均明显高于正常对照组(15.4±5.64)%(P<0.01),AML与ALL间bcl-2表达差异无统计学意义(P>0.05);49例AL临床治疗有效组bcl-2表达为(36.81±30.35)%,无效组为(56.36±26.78)%,无效组高于有效组(P<0.05)。各组间bax差异均无统计学意义(P>0.05)。结论bcl-2水平对判断AL疗效和预后有重要价值。     

碱性成纤维细胞生长因子在急性白血病中的表达

目的探讨碱性成纤维细胞生长因子(bFGF)在急性白血病(AL)中的表达及其临床意义。方法应用酶联免疫法(ELISA)检测AL初治及复发患者化疗前后血清bFGF的水平,并与正常对照组比较。结果47例AL初治患者血清bFGF水平为(60.57±25.62)pg/L,8例复发患者为(72.26±21.44)pg/L,均明显高于正常人对照组的(24.06±5.97)pg/L,差异有统计学意义(P<0.01);11例完全缓解(CR)患者血清bFGF水平(27.33±9.04)pg/L,较CR前明显下降(P<0.01),接近于正常人对照组的水平(P>0.05);急性淋巴细胞白血病(ALL)难治组血清bFGF的水平为(85.20±31.45)pg/L,明显高于非难治组的(60.03±22.97)pg/L,两者差异有统计学意义(P<0.05);但急性髓细胞白血病(AML)难治组血清bFGF水平(63.36±16.62)pg/L与非难治组的(55.02±22.84)pg/L差异无统计学意义(P>0.05)。结论血清bFGF的检测对了解AL的发生、发展及疗效观察和预后判断有一定临床价值。     

急性淋巴细胞白血病免疫分型的特点及其临床意义

目的:为了探讨急性淋巴细胞白血病(ALL)各亚型免疫分型的特点及其临床意义。方法:采用CD45/SSC双参数散点图设门,应用三色流式细胞术,对81 例ALL的初诊患者骨髓标本进行免疫分型,并对其中45例进行核型分析。结果:①B细胞系列的ALL(B ALL)中CD19表达最常见(阳性率为100%),而T细胞系列的ALL(T ALL)中CD5和CD7表达阳性率最高,均为90%;B -ALL和T- ALL都存在抗原交叉表达的现象;两组患者的完全缓解(CR)率差异无统计学意义(P>0.05);②伴髓系抗原表达的急性淋巴细胞白血病(My+ALL)比较常见,本组达到39.5%,常累及B淋巴系统(占My+ ALL的84.4%);各髓系抗原中以CD13 表达阳性率最高;此类患者的CR率较高,儿童CR率为72.2%,成人为78.6%;③急性杂合性白血病(HAL)的发病率为19.8%,以髓系、B系共同表达者居多;并且CD34表达阳性率较高(81.3%),该类患者CR率较低(儿童和成人分别为50%和40%);④CD34在B ALL,My+ALL和HAL中表达阳性率较高,而T ALL中少见(P<0.05)。结论:免疫分型在诊断特殊类型的ALL(如HAL,My+ALL)中具有显著优势;CD19和CD5诊断B- ALL和T- ALL的灵敏度较好,但特异性不高,存在抗原交叉表达;CD34和髓系抗原的表达与CR率无相关性,但在HAL,CD34的表达与CR率成负相关。     

61例成人急性非淋巴细胞白血病诱导化疗—HA和DA方案的比较

本文报告HA和DA方案治疗急性非淋巴细胞白血病(ANLL)61例,其中33例用HA方案,CR18例(54.3%);28例用DA方案,CR16例(57.1%),两种方案CR率相似(P>0.05)。HA和DA方案治疗的MBDI分别为39.0%、44.8%(P>0.5);病人的中位缓解时间为10月和10.5月;2年持续CR率为48%和43%,HA方案的心脏毒性较DA的小,HA方案对白血病细胞的杀伤及效果表明,它完全可以取代DA方案,具有实用价值。     

老年急性白血病Survivin、Cox-2蛋白的表达

目的 探讨老年急性白血病(AL)骨髓细胞中Survivin、Cox-2蛋白的表达及其相关性.方法 采用免疫组化S-P法检测35例老年AL患者治疗前后骨髓细胞中Survivin、Cox-2蛋白的表达情况.结果 病例组、急性非淋巴细胞白血病(ANLL)组、急性淋巴细胞白血病(ALL)组Survivin、Cox-2蛋白阳性表达率均明显高于对照组,差异有显著性(均P＜0.01);完全缓解(CR)者Survivin、Cox-2蛋白阳性表达率低于部分缓解(PR)、未缓解(NR)者,差异有显著性(P＜0.01);Spearman秩和相关分析显示Survivin、Cox-2蛋白表达呈显著正相关(rs=0.495,P＜0.01).结论 Survivin、Cox-2均与老年AL的发生、发展、疗效及预后密切相关,且两者有一定的协同作用.     

运动预适应对急性心肌缺血大鼠心肌细胞凋亡及凋亡蛋白表达的影响

目的探讨运动预适应(EP)对非动脉硬化大鼠及动脉硬化大鼠急性心肌缺血心肌细胞B细胞淋巴瘤(Bcl)-2、Bcl-2相关X蛋白(Bax)蛋白表达及半胱氨酸蛋白酶(Caspase)-3蛋白的影响。方法选取7周龄SD大鼠90只,随机分为5组:对照组(A组)、急性心肌缺血组(B组)、动脉硬化+急性心肌缺血组(C组)、EP+急性心肌缺血组(D组)、动脉硬化+EP+急性心肌缺血组(E组),其中A组10只,其余各组20只。C、E组予维生素D3连续灌胃4 d,喂高脂饲料(猪油、胆固醇、胆酸、丙基硫氧嘧啶)6 w制备动脉硬化模型。B、C、D、E组腹腔注射3 mg/kg异丙肾上腺素(ISO),复制大鼠急性心肌缺血损伤模型。D、E组建立EP大鼠模型进行间歇性游泳运动,以尾部负重体重的3%重物。建模后24 h内采用脊髓脱臼法处死大鼠,取左心室心肌组织,采用免疫组化检测Bcl-2及Bax蛋白的表达,Western印迹检测Caspase-3蛋白。结果与A组比较,B、C、D、E组心肌细胞Bcl-2的表达均显著降低(P<0.05),而Bax表达均显著升高(P<0.05);B组与C组心肌细胞Bcl-2的表达差异无统计学意义(P>0.05),但C组Bax的表达显著升高(P<0.05);D组、E组心肌细胞Bcl-2的表达较B组、C组显著升高(P<0.05),而Bax的表达显著降低(P<0.05);与D组比较,E组Bcl-2的表达显著降低,而Bax的表达显著升高(P<0.05)。与A组相比,B、C、D、E组心脏Caspase-3蛋白表达水平显著升高(P<0.01);与B组、C组相比,D组、E组心脏Caspase-3蛋白表达水平显著降低(P<0.01)。与D组比较,E组心脏Caspase-3蛋白表达水平无明显差异(P>0.05);与A组比较,B、C、D、E组细胞凋亡指数(AI)显著增高(P<0.05),其中C组AI最高;与B组、C组比较,D组、E组AI显著降低(P<0.05),而D组比E组AI稍低(P<0.05)。结论EP可能改善急性心肌缺血或是在合并动脉硬化基础上急性心肌缺血大鼠的心肌细胞凋亡,可能基于凋亡相关基因Bcl-2表达升高、Bax表达降低调控及下调Caspase-3蛋白所致。     

急性白血病患者血管内皮生长因子及其受体表达的动态观察

目的探讨急性白血病(AL)患者治疗前后骨髓中血管内皮生长因子(VEGF)及其受体的表达差异以及这种表达与血管生成的相关性.方法应用EnVision免疫组织化学二步法,检测122例次成人AL患者骨髓中造血细胞VEGF及其两种特异性受体fms-样酪氨酸激酶受体(Flt-1)、激酶插入嵌合受体(KDR)蛋白的表达情况.结果化疗后获得完全缓解(CR)的患者,其VEGF、KDR蛋白的表达在治疗前为6.0(3.3～12.0)和5.3(3.3～8.0),获CR后为5.3(3.3～9.0)和2.0(1.0～4.0)差异有显著性(P<0.05;P<0.01),而在化疗后未获得CR患者中的表达差异无显著性.在缓解后复发患者中的表达又升高到初发时的水平.各组初发患者Flt-1的表达水平与对照组之间差异无显著性,但CR期Flt-1的表达水平在CR组为3.3(1.7～5.3),复发组为3.3(2.0～5.3)与初发及对照组差异有显著性(P<0.01).微血管数处于高水平组的VEGF及KDR表达显著高于微血管处于低水平组者(P<0.01).骨髓原始细胞与急性髓系白血病(AML)初发患者VEGF和KDR的表达之间成正相关(r=0.429,0.359;P=0.005,0.02);与急性淋巴细胞白血病(ALL)初发患者VEGF的表达之间成正相关(r=0.522,P=0.03).结论 VEGF及其两种特异性细胞受体Flt-1, KDR在造血细胞及血管内皮细胞中表达.提示VEGF可能是白血病细胞的一种自分泌因子,同时作为一种旁分泌因子调控患者骨髓中的血管新生反应.VEGF及其细胞受体KDR可能构成抗血管新生和抗白血病治疗的新靶点.     

Predictive value for treatment outcome in acute myeloid leukemia of cellular daunorubicin accumulation and P-glycoprotein expression simultaneously determined by flow cytometry

To evaluate the clinical relevance of multidrug resistance (MDR) phenotype, the intracellular daunorubicin accumulation (IDA) and P- glycoprotein (P-gp) expression were investigated in 87 adult patients with acute leukemia: 69 patients with de novo acute myeloid leukemia (AML), 10 with AML at relapse, and eight with secondary leukemia to myelodysplastic syndromes (MDS-AML). IDA and P-gp expression were determined by double-labeling flow cytometry analysis. Of 87 patients, 36 expressed P-gp (41%). P-gp expression was more frequently observed in AML at relapse and MDS-AML as compared with de novo AML (P = .0001). P-gp expression was significantly associated with CD34 expression (P = .0003) and chromosome 7 abnormalities (P = .027). A significantly reduced IDA was observed in P-gp+ as compared with P-gp- patients (P = .0007). Of the 87 patients, 51 achieved complete remission (CR). A reduced IDA was observed in patients in failure as compared with patients in CR (22% +/- 17% v 42% +/- 21%; P = 10(-4). Twelve of 36 P- gp+ patients as compared with 40 of 51 P-gp- patients achieved CR (33% v 78%; P = 10(-4). The prognostic value of IDA and P-gp expression was confirmed in multivariate analysis. These data suggest that the determination of IDA and P-gp expression may be useful in designing therapy for patients with AML.     

Predictable prognostic factor of CD56 expression in patients with acute myeloid leukemia with t(8:21) after high dose cytarabine or allogeneic hematopoietic stem cell transplantation

CD56 expression in acute myeloid leukemia (AML) has been associated with extramedullary leukemia and multidrug resistance, but its clinical and prognostic significance has not been clearly identified. This study examined CD56 expression in 37 adult de novo AML patients with t(8:21). CD56 was expressed in 25 cases (67.6%). Complete remission (CR) rates were similar in both groups (91.7% vs. 88.7%; P = 0.73), but the relapse rates differed considerably (60% vs. 25%; P = 0.02). The median duration of disease-free survival (DFS) was significantly shorter in the CD56+ (median, 12.2 +/- 6.4 months) than in the CD56- group (median, not reached) (P = 0.02). In addition, the median duration of survival differed significantly in the CD56+ group (median, 14.9 +/- 4.4 months) compared with the CD56- group (median, not reached) (P = 0.01). Of the fifteen transplanted patients who achieved CR, allogeneic HST was performed from their siblings. The median duration of DFS in the CD56+ patients was significantly shorter than the CD56- patients (median, 24.4 +/- 4.5 months vs. median, not reached; P = 0.02). We concluded that CD56 expression correlates to a reduced DFS and survival for AML patients with t(8:21), including those patients who underwent transplantation.     

Postremission therapy in older patients with de novo acute myeloid leukemia: a randomized trial comparing mitoxantrone and intermediate-dose cytarabine with standard-dose cytarabine

The treatment of older patients with acute myeloid leukemia (AML) remains unsatisfactory, with complete remission (CR) achieved in only approximately 50% and long-term disease-free survival in 10% to 20%. Three hundred eighty-eight patients (60 years of age and older) with newly diagnosed de novo AML were randomly assigned to receive placebo (P) or granulocyte-macrophage colony-stimulating factor (GM-CSF) or GM in a double-blind manner, beginning 1 day after the completion of 3 days of daunorubicin and 7 days of cytarabine therapy. No differences were found in the rates of leukemic regrowth, CR, or infectious complications in either arm. Of 205 patients who achieved CR, 169 were medically well and were randomized to receive cytarabine alone or a combination of cytarabine and mitoxantrone. With a median follow-up of 7.7 years, the median disease-free survival times were 11 months and 10 months for those randomized to cytarabine or cytarabine/mitoxantrone, respectively. Rates of relapse, excluding deaths in CR, were 77% for cytarabine and 82% for cytarabine/mitoxantrone. Induction randomization had no effect on leukemic relapse rate or remission duration in either postremission arm. Because cytarabine/mitoxantrone was more toxic and no more effective than cytarabine, it was concluded that this higher-dose therapy had no benefit in the postremission management of older patients with de novo AML. These results suggest the need to develop novel therapeutic strategies for these patients. (Blood. 2001;98:548-553)     

c-IAP1与Smac基因在白血病中的表达及临床意义

目的:探讨c-IAP1及其拮抗素Smac基因在白血病中的表达及对成人急性白血病(AL)患者预后的意义。方法:应用半定量逆转录-聚合酶链反应检测103例AL患者c-IAP1、Smac的mRNA表达水平,20例健康人为正常对照,K562、Kg-1α细胞株为阳性对照。结果:初治AL患者中c-IAP1、Smac的表达较正常对照者明显升高,2者的表达为高度正相关,治疗缓解后c-IAP1、Smac的表达明显下降,复发后c-IAP1、Smac:基因的表达又复升高。c-IAP1 mRNA和Smac mRNA在慢性粒细胞性白血病慢性期组的表达率和表达水平均高于正常对照组,但差异无统计学意义。初治AL患者中,c-IAP1、Smac表达阳性的患者缓解率均低于表达阴性的患者。结论:AL的发病可能与c-IAP1和Smac的高表达有关,而且是AL复发的高危因素;c-IAP1和Smac高表达的患者完全缓解率低,预后不良。     

Myeloid antigen expression provides favorable outcome in patients with adult acute lymphoblastic leukemia: a single-center study

Between July 1992 and July 2001, 81 patients with de novo adult acute lymphoblastic leukemia (ALL) treated according to the German Multicenter Study Group for Adult ALL (GMALL) 01/81 protocol were evaluated in order to analyze the effect of aberrant myeloid antigen expression on prognosis. We observed myeloid antigen aberrant expression in 21 of the adult ALL cases. We did not observe any effect of aberrant myeloid antigen expression on the time to achieve remission, relapse rate, and death rate. After 5 years of follow-up, cumulative disease-free survival of myeloid antigen (My) (+) and My (-) adult ALL patients was 67% and 43%, respectively. These data were not found to be statistically significant (P=0.29), but we did find a statistically significant difference in overall survivals between these two groups (85% vs 50%) (P=0.05). Twenty-nine patients died and the remaining 52 patients were followed for a median of 31 months. We could not find any special effect of the known prognostic factors on prediction of relapse in multivariate analysis. However, myeloid antigen expression was the most significant factor, which affected long-term survival in our patients (P=0.01). These data indicate that myeloid antigen expression is useful for predicting a favorable outcome of adult patients with ALL.     

WT1基因及CD34在急性白血病中的表达及意义

目的研究WT1基因与CD34在急性白血病（AL）中表达的相关性及其临床意义。方法采用实时定量RT-PCR方法检测92例初治AL患者骨髓细胞WT1基因的表达,同时应用流式细胞仪测定骨髓细胞CD34的表达。结果初治AL患者WT1基因、CD34表达的阳性率分别为67．4％（62／92）、44．6％（41／92）,WT1基因、CD34阳性表达者的缓解率显著低于阴性表达者（P〈0．01）;WT1基因与CD34表达呈正相关（rn=0．5304,χ^z=25．88,P〈0．05）;WT1^＋CD34^＋、WT1^＋CD34、WT1-CD34^-AL患者第一次缓解率比较有统计学差异（P〈0．01）。结论WT1基因、CD34在AL患者骨髓细胞中的表达呈正相关,且阳性表达者的缓解率低、疗效差、预后不良。     

Significance of trilineage myelodysplasia in de novo acute myeloid leukaemia during remission rather than at diagnosis

Patients with trilineage myelodysplasia (TMDS) in de novo acute myeloid leukaemia (AML) at diagnosis and remission were clinically evaluated between 1983 and 1996. AML with TMDS (AML/TMDS) was observed in 20 (12%) of 162 patients with de novo AML at diagnosis. Complete remission (CR) was achieved with combination chemotherapy in 12 (67%) of 18 AML/TMDS cases. This CR rate was relatively worse than the rate of 78% (106/136 cases) of AML without TMDS, but this difference was not significant. Disease-free survival curves also showed no difference between AML/TMDS and AML without TMDS. During remission, eight (67%) of 12 AML/TMDS cases had myelodysplastic remission marrow (AML/MRM). AML/MRM was also seen in seven (7%) of 106 AML cases without TMDS. The actuarial disease-free survival was significantly lower in AML/MRM than in AML without MRM ( P  = 0.0003). All of the AML/MRM cases exhibited early leukaemic relapse; median remission duration was only 9 months. Clonal changes occurred in two cases of AML/TMDS and five cases of AML/MRM at the time of relapse. These findings suggest that TMDS during remission predicts a poorer prognosis and early leukaemic relapse when compared with the absence of TMDS.     

Outcome of biphenotypic acute leukemia.

BACKGROUND AND OBJECTIVE: Although biphenotypic leukemia is now a defined entity, outcome of this rare form of acute leukemia has not been well documented. We present the first comprehensive study analyzing induction and consolidation therapy of biphenotypic leukemia and correlate outcome to prognostic factors. DESIGN AND METHODS: In this retrospective study, the incidence of biphenotypic leukemia was found to be 3.6% from 693 adult and pediatric acute leukemias referred to our center for treatment over the last 8 years. Of these, 15 were B-lymphoid/myeloid, 8 were T-lymphoid/myeloid, one was T/B lymphoid and one had trilineage differentiation. RESULTS: Induction of remission in de novo cases was achieved in 70% of patients and relapse of disease occurred in 15%. The use of combined lymphoid and myeloid drugs for induction resulted in a high incidence of early deaths (25%). The overall probability of survival at 2 years was 39.4%. Patients with secondary disease had a uniformly poor outcome with low remission rates and high relapse rates. INTERPRETATION AND CONCLUSIONS: Prognosis was most strongly related to the presence of the Philadelphia chromosome (p=0.03) and age under 15 years (p=0.01). We conclude that patients with biphenotypic leukemia should have risk stratification with treatment tailored to their prognostic factors.     

急性白血病患者细胞周期蛋白E及依赖激酶抑制剂表达的意义

目的：探讨细胞周期蛋白E（cyclin E)、细胞周期蛋白依赖激酶抑制剂（p27KIP1)对成人初治急性白血病（AL）发展及预后的作用。方法：用流式细胞术检测60例AL及17例对照cyclin E、p27 KIP1、多药耐药基因蛋白p170表达及细胞周期分布;逆转录－聚合酶链反应检测46例成人AL患者及17例对照的骨髓cyclin E、p27KIP1、多药耐药蛋白的mRNA水平。结果：60例AL患者全周期及G2／M期cyclinE表达均高于对照组（＜0．01或0．05）;p27KIP1全周期表达亦均高于对照组,但G2／M期差异无显著性（P＞0．05）;cyclinE与p27KIP1的表达呈正相关;AL患者cyclin E高表达组缓解率（44．8％）低于正常表达组（77．4％）（P＜0．01）;复发率（92．3％）高于正常表达组（41．7％）（P＝0．003;p27KIP1表达对AL缓解率、复发率的影响无统计学意义（P＞0．05,P＝0．89）。结论：cyclinE在成人AL有异常高表达,并可能促使AL的发展,是AL缓解率、复发率的重要危险因素。     

Clinicobiological features and outcome of acute promyelocytic leukemia occurring as a second tumor: the GIMEMA experience

We analyzed the clinicobiological features and treatment outcome of a series of acute promyelocytic leukemias (APLs) occurring as a second tumor (APL-st's, n = 51) and compared these with a large group of de novo APL cases (n = 641), both observed by the Italian cooperative group GIMEMA. In the APL-st group, 37 patients had received radiotherapy and/or chemotherapy for their primary malignancy (PM), while 14 had been treated by surgery alone. Compared with de novo APL patients, APL-st patients were characterized by a predominance of females (P <.003), higher median age (P <.05), and worse performance status (P <.005). The median time elapsed between PM and APL-st was 36 months, with a longer latency for patients treated with surgery alone. No significant differences were found with regard to karyotypic lesions or type of promyelocytic leukemia/retinoic acid receptor alpha (PML/RARalpha) fusion in the 2 cohorts. A high prevalence of PMs of the reproductive system was observed among the female APL-st population (24 [71%] of 34 patients in this group had suffered from breast, uterine, or ovarian cancer). Thirty-one APL-st and 641 de novo APL patients received homogeneous APL therapy according to the all-trans retinoic acid (ATRA) and idarubicin regimen (the AIDA regimen). The complete remission (CR), 4-year event-free survival (EFS), and 4-year overall survival (OS) rates were 97% and 93%, 65% and 68%, and 85% and 78% in the APL-st and de novo APL groups, respectively. In spite of important clinical differences (older age and poorer performance status), the APL-st group responded as well as the de novo APL group to upfront ATRA plus chemotherapy, probably reflecting genetic similarity.