The prognostic significance of minimal residual disease in adult Egyptian patients with precursor acute lymphoblastic leukemia

BackgroundMinimal residual disease (MRD) studies in adult acute lymphoblastic leukemia (ALL) give highly significant prognostic information superior to other standard criteria as age, gender and total leucocytic count (TLC) in distinguishing patients at high and low risk of relapse.ObjectivesWe aimed to determine the value of MRD monitoring by flowcytometry (FCM) in predicting outcome in adult Precursor ALL patients.Patients and methodsBone marrow (BM) samples were analyzed by 4-color FCM collected at diagnosis and after induction therapy (MRD1) to correlate MRD positivity with disease free survival (DFS) and overall survival (OS).ResultsStudy included 57 adult ALL patients (44 males and 13 females) with a median age of 22 years (18–49). DFS showed no significant difference with age, gender and initial TLC (p = 0.838, 0.888 and 0.743, respectively). Cumulative DFS at 2 years was 34% for B-lineage ALL (n: 35) and 57% for T-lineage ALL (n: 18) (p = 0.057). Cumulative DFS at 2 years was 7% for MRD1 positive (high risk, HR) versus 57% for MRD1 negative patients (Low risk, LR) (p < 0.001). Cumulative DFS at 2 years was 29% for HR patients (n: 26) versus 55% for LR (n: 27) according to GMALL classification (p = 0.064). Cumulative OS did not differ according to age, gender and TLC (p = 0.526, 0.594 and 0.513, respectively). Cumulative OS at 2 years was 36% for B ALL (n: 39) versus 77% for TALL (n: 18) (p = 0.016) and was 49% for Philadelphia chromosome (Ph) negative patients versus 0% for Ph-positive patients (p < 0.001). Regarding MRD1, OS at 2 years was 18% for MRD1 HR (n: 17) versus 65% for MRD1 LR (n: 38) (p < 0.001). OS was 35% for high-risk patients (n: 30) and 62% for low-risk patients (n: 27) classified according to GMALL risk stratification (p = 0.017).ConclusionMRD by FCM is a strong independent predictor of outcome in terms of DFS and OS and is a powerful informative parameter in guiding individual treatment in ALL patients.     

儿童急性淋巴细胞白血病并发急性胰腺炎的临床特点分析

目的:分析儿童急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)并发急性胰腺炎(acute pancreatitis,AP)患儿的临床特点。方法:收集2013年2月至2020年2月天津市儿童医院收治的ALL并发AP患儿11例,均采用中国儿童白血病协作组-急性淋巴细胞白血病-2008(CCLG-ALL 2008)方案联合化疗,总结患儿的危险度分层、主要临床表现、发生胰腺炎的所处治疗阶段、发病原因、培门冬酶(polyethylene glycol conjugated asparaginase,PEG-ASP)的累积用量,整理患儿的胰酶指标、影像学检查、血常规、肝肾功能、血脂血糖、凝血功能等化验结果,对比患儿治疗效果及转归,分析其临床特点。结果:全组11例患儿中,男性7例,女性4例,年龄范围1～14岁,中位年龄6岁;急性B淋巴细胞白血病(type B acute lymphoblastic leukemia,B-ALL)10例,急性T细胞型淋巴母细胞白血病(type T acute lymphoblastic leukemia,T-ALL)1例;初始联合...     

Glucocorticoid receptor in childhood acute lymphoblastic leukemia

Glucocorticoid(GC)hasbeenusedinthetreatmentofchildhoodacutelymphoblasticleukenda(ALL)formanyyears.IthasprovedthattheeffectofGCismediatedthroughaglucocortic0idreceptor(GCR)ofthetargetcell.[1]Therefore,manyexpertshaveconcentratdtheirattentiononGCR,butthereisnoreportonthestudyofGCRinchildho0dALLinChina.InununologicalclassificationofALLmaydifferentiatethecelloriginandclustersofdifferentiation(CD)inleukendacell.Itisoneoftheimportantindicatorstoguidecombinationchemotherapyandt0makeapr0gnos…     

儿童与成人急性B淋巴细胞白血病免疫表型的差异分析

目的:对儿童和成人急性B淋巴细胞白血病(B-ALL)免疫表型存在的差异进行分析,探讨不同年龄段B-ALL分型特征和临床意义。方法:以260例儿童和127例成人B-ALL患者为研究对象,使用流式细胞术对患者初发时骨髓标本进行免疫表型检测,分析抗原表达情况。结果:在全部B-ALL患者中B系抗原阳性率高的抗原有CD19,CD22,CD79a,分别达到了100%,99.73%,99.19%;而成熟B系抗原CD20和cIgM阳性率为31.27%和21.29%,阳性率较低。 CD10的阳性率为94.88%,在成人组和儿童组中存在明显差异,儿童组明显高于成人组(P＜0.05)。造血干/祖细胞抗原CD34、HLA-DR、CD38、cTdT阳性率分别为76.82％、98.38％、98.92％和92.72%,其中儿童患者CD34明显低于成人患者(P＜0.05)。髓系相关抗原CD33、CD13和CD15的表达最常见,分别达20.49％、20.49％、7.01％,其中CD33和CD15在儿童组中阳性率明显低于成人组(P＜0.05)。结论:免疫分型对儿童与成人B-ALL的诊断和微小残留病检测方案选择具有重要意义。     

成人急性淋巴细胞白血病治疗进展

【指示性摘要】尽管应用各种不同的诱导缓解方案,80％-95％的成人急性淋巴细胞白血病（ALL）可获得形态学上的完全缓解,但大部分病人很快复发。能否获得免疫学或分子水平的微小残留病（MRD）状态及达到MRD的速度极为重要。缓解后治疗是病人长期生存的关键。接受异基因移植的病人复发率明显降低。但在年龄35—40岁以上的移植患者中,较高的移植相关死亡率抵消了异基因移植的生存优势。相配无关供体移植的应用日益广泛,可用于所有高危病人。降低强度的移植可能增加老年患者的生存率。伊马替尼甲磺酸的应用彻底改变了ph阳性ALL的治疗方法,特别是该型老年患者。诊断时有CNS累及的患者,只要给予及时治疗,对预后无明显不利影响。     

成人急性淋巴细胞白血病治疗进展

尽管应用各种不同的诱导缓解方案,80%-95%的成人急性淋巴细胞白血病(ALL)可获得形态学上的完全缓解,但大部分病人很快复发.能否获得免疫学或分子水平的微小残留病(MRD)状态及达到MRD的速度极为重要.缓解后治疗是病人长期生存的关键.接受异基因移植的病人复发率明显降低.但在年龄35-40岁以上的移植患者中,较高的移植相关死亡率抵消了异基因移植的生存优势.相配无关供体移植的应用日益广泛,可用于所有高危病人.降低强度的移植可能增加老年患者的生存率.伊马替尼甲磺酸的应用彻底改变了ph阳性ALL的治疗方法,特别是该型老年患者.诊断时有CNS累及的患者,只要给予及时治疗,对预后无明显不利影响.     

Cranial irradiation in children with lymphoblastic acute leukemia: results and damages.

From 1973 to 1976, 81 children with lymphoblastic acute leukemia were treated with cranial prophylactic irradiation at the Istituto di Radioterapia “L. Galvani” dell'Universitá di Bologna. We divided the patients into 6 groups according to different characteristics. At the beginning of 1978 the survival rate was 82%; 60 patients (74%) were in complete continuous remission. We studied the encephalic post irradiation syndrome that is present in children over 2 years of age only when doses are higher than 2500 rad and in children under 2 years of age when doses exceed 2000 rad. This complication occurs frequently in the experience of other authors; however, it is absent under certain doses with which it is possible to obtain the same good results.We feel that among the different techniques and methods, the best radiological treatment is daily bilateral cranial irradiation for patients early in remission; we recommend doses of 2400 rad for children above 2 years of age and 1950 rad for those under 2 years.     

A report about treatment refusal and abandonment in children with acute lymphoblastic leukemia in China, 1997-2007

Background

To analyze the causes and consequence of treatment refusal and abandonment in childhood acute lymphoblastic leukemia (ALL) treated in Wuhan Union Hospital of China.

Methods

We collected recorded data and interviewed families of the children with ALL diagnosed between January 1997 and August 2007, who refused or abandoned treatment.

Results

323 patients were diagnosed with ALL. 173 patients (173/323, 53.6%) refused therapy and 35 (35/323, 10.8%) cases abandoned treatment. 191 (191/208, 91.8%) of these children were telephone/mail-visited. Different people had different reasons for refusal or abandonment. Financial difficulty and belief of ALL incurability were the main reasons for abandonment. Transportation difficulties and fear of severe side effects were also important reasons. Of the 173 patients who refused treatment, 13 patients lost follow-up. 160 parents were interviewed and 1 (6.3%) child was still alive at the date of last follow-up. Of the 35 patients who abandoned treatment, 4 patients lost follow-up. 31 parents were interviewed and 2 (6.5%) children were still alive at the date of last follow-up.

Conclusion

Medical insurance and a systemic health education are extremely required for childhood ALL in low middle income countries.     

CDKN2A deletions in acute lymphoblastic leukemia of adolescents and young adults: an array CGH study

Deletion in chromosome 9p involving the CDKN2A locus (9p21.3) is known in many malignancies. To detect this deletion in adolescent ALL patients we used oligo array CGH and studied 54 patients aged 10–25 years. Deletion rate was 25/54 (46%), of these 19/25 (76%) were homozygous. Small deletions (<200 kb) were found in 8/25 (32%) and the smallest deletion was <30 kb. The only gene affected in all deletions was CDKN2A. We were unable to demonstrate prognostic value of the deletion, however patients with deletion belonged more often (P = 0.06) to unfavorable biological category. Our results indicate that CDKN2A deletions <200 kb may not be detected by conventional methods.     

Salvage therapy with mitoxantrone,etoposide and cytarabine in relapsed or refractory acute lymphoblastic leukemia

The survival of patients with relapsed or refractory acute lymphoblastic leukemia (ALL) is poor. We performed a retrospective analysis of 40 patients treated with five days of mitoxantrone 8 mg/m²/day, etoposide 100 mg/m²/day, and cytarabine 1000 mg/m²/day (MEC). The complete remission rate was 30% and median remission duration was 11.2 months. Median overall survival was 6.5 months. In univariate analysis, patients in first relapse had improved overall survival compared to ≥second relapse (p = 0.02). Thirty-day mortality rate was 7.5%. In relapsed or refractory ALL, MEC demonstrated moderate activity, but did not improve survival compared to published salvage chemotherapy regimens.     

Clinical significance of aberrant DNA methylation in childhood acute lymphoblastic leukemia

Methylation profile was analyzed in ninety-five patients with childhood acute lymphoblastic leukemia (ALL). Methylation of both MGMT and p16 genes were associated with higher age (p = 0.01 and p = 0.03, respectively). Methylation of both p15 and SHP1 genes occurred more frequently in T-ALL than in precursor B-ALL (p = 0.02 and p = 0.01, respectively). In contrast, methylation of the DAPK gene was more frequent in precursor B-ALL (p = 0.01). Patients with methylation of multiple genes more likely had T cell phenotype, and are classified as medium/high risk (p = 0.004 and p = 0.03, respectively). These results suggest that methylation status is associated with clinicopathological features in childhood ALL.     

儿童急性淋巴细胞白血病完全缓解后骨髓幼稚淋巴细胞比例升高分析

目的 探讨儿童急性淋巴细胞白血病（ALL）完全缓解（CR）后骨髓幼稚淋巴细胞比例升高（5％～15％）的临床意义及对预后的影响.方法 回顾性分析ALL CR后幼稚淋巴细胞增多患儿的临床资料,按骨髓幼稚淋巴细胞比例分为≤5％组（阴性对照组）,＞5％且≤10％组,＞10％且≤15％组,分析各组ALL复发情况.结果 ALL患儿CR后治疗期间出现骨髓幼稚淋巴细胞比例增高占40.54％（30/74）,其中骨髓幼稚淋巴细胞比例＞5％且≤10％时复发率为21.05 ％（4/19）,与阴性对照组的复发率15.91％（7／44）比较差异无统计学意义（P=0.895）;骨髓幼稚淋巴细胞比例＞10％且≤15％时复发率为54.54 ％（6／11）,与阴性对照组比较差异有统计学意义（P=0.014）.儿童T-ALL与B-ALL出现骨髓幼稚淋巴细胞比例升高所占比例差异无统计学意义（P=0.078）.结论 儿童ALL CR后治疗阶段骨髓幼稚淋巴细胞轻度（＞5％且≤10％）升高可能是骨髓正常的B系淋巴细胞反应性增生的结果,预后相对良好;而骨髓幼稚淋巴细胞比例＞10％且≤15％时,这些幼稚细胞极可能是白血病细胞,提示预后不良.     

Induction therapy for adults with acute lymphoblastic leukemia

Conclusions The authors believe this therapy is comparable with or better than that used in other studies for adult leukemia, with a higher CR rate and excellent survival. They continue to enroll patients in anticipation of answering questions regarding the relative efficacy of allogeneic and autologous transplant and intensive consolidation maintenance.     

Immunologic monitoring in adults with acute lymphoblastic leukemia

Investigation of minimal residual disease (MRD) by immunophenotyping and molecular techniques has proven to be a powerful approach for disease monitoring in patients with acute leukemia. Multiparameter flow cytometry, through the use of triple or quadruple marker combinations, identifies aberrant or uncommon phenotypic profiles in more than 90% of adult patients with acute lymphoblastic leukemia (ALL) at diagnosis. These profiles allow identification of residual leukemic cells in bone marrow or peripheral blood once morphologic complete remission is achieved. Until now, most immunophenotypic MRD studies in ALL have focused on children. In contrast, information on the value of MRD in adults with ALL is scanty and usually restricted to polymerase chain reaction studies. In this review, we focus on technical aspects of MRD detection by flow cytometry and on the clinical data concerning the value of immunologic MRD studies as a tool for relapse prediction in adult ALL. Although prospective studies are needed, we assert that immunophenotypic MRD studies are clinically useful. Such studies should be incorporated into the routine management of adult ALL patients for identification of those at high risk of relapse, who could benefit from new alternative therapeutic approaches, and to distinguish these patients from others who could be cured with more conventional approaches.     

High CXCR4 and low VLA-4 expression predicts poor survival in adults with acute lymphoblastic leukemia

Data regarding the prognostic significance of CXCR4 and VLA-4 in ALL are limited. Especially, VLA-4 has not been evaluated at the time of diagnosis in both adult and childhood ALL patients. We prospectively analyzed the expression of VLA-4 and CXCR4 in 54 patients (VLA-4 in 29 adults and 25 children and CXCR4 in 22 adults and 24 children) newly diagnosed with ALL by flow cytometry. Expression levels of VLA-4 and CXCR4 were not different between adults and children with ALL. High CXCR4 and low VLA-4 expression each correlated with worse prognosis in adults; patients with high CXCR4 expression had shorter disease-free survival (p = 0.01) and overall survival (p = 0.04) and patients with low VLA-4 expression had shorter disease-free survival (p = 0.02). Expression levels of CXCR4 and VLA-4 did not predict patient prognosis in children. Analysis of CXCR4 and VLA-4 expression at diagnosis in adults with ALL can provide useful information on patient prognosis.