<Emphasis Type="Italic">GSTP1</Emphasis> and <Emphasis Type="Italic">MDR1</Emphasis> Genotypes and Central Nervous System Relapse in Childhood Acute Lymphoblastic Leukemia

The probability of event-free survival of childhood acute lymphoblastic leukemia (ALL) approaches 80% or more with the use of modern multiagent chemotherapeutic regimens. One major contribution to this success has been reduction of the rate of central nervous system (CNS) relapses to less than 5%. However, heterogeneity is observed with regard to the incidence of CNS relapse in homogenously treated patient populations. One potential explanation for this heterogeneity is variation in the genetic background of these populations. Glutathione S-transferase P1 and P-glycoprotein are implicated in resistance to a variety of chemotherapeutic agents and have been localized to the blood-brain barrier. In a matched case-control study, we investigated the associations between CNS relapse in childhood ALL and the presence of phenotypically relevant single nucleotide polymorphisms within the GSTP1 (codon 105 and 114) and MDR1 genes (ABCB1; coding for Pgp; exon 26, C3435T). Significant reductions in risk of CNS relapse were observed for patients homozygous for the GSTP1 Val105 allele as well as for patients with the MDR1 3435T/T or C/T genotype. For both genotypes, the effect was restricted to patients at intermediate or high risk of treatment failure. These results suggested a modulating role for host genetic variation in the development of CNS relapse in childhood ALL treated according to Berlin-Frankfurt-Münster protocols.     

Phenotyping of malignant hematopoietic cells

Summary 1255 cases of leukemia-lymphoma were tested between 1972 and 1984 by multiple marker analysis. Routine leukemia phenotyping was performed using standard morphological and cytochemical techniques in combination with clinical and histo-pathological information; the main emphasis was put on immunological surface marker analysis using erythrocyte rosette assays, TdT and a large panel of poly- and monoclonal antibody tests. The 1255 cases were divided into these major types and subtypes: 349 cases of ALL and related immature T- and Burkitt-lymphomas (cALL, pre B-ALL, B-ALL and Burkitt-lymphomas, T-ALL and immature, mostly leukemic T-lymphomas, Null-ALL), 454 cases of mature T- and B-cell malignancies (T-CLL, mycosis fungoides, Sezary-syndrome, T-lymphomas, B-CLL, hairy cell leukemia, multiple myeloma, B-lymphomas), 263 cases of acute myeloid leukemias (AML, AMMoL/AMoL), 182 cases of chronic myeloid leukemias (CML in chronic phase, CMoL, CML in blast crisis), 6 cases of erythroleukemia and 1 case of megakaryoblastic leukemia. A simplified classification scheme which has been used in our laboratories is presented. Phenotyping is of diagnostic, prognostic and therapeutic relevance, most evidently for patients with ALL. Routine leukemia phenotyping should be performed with highly standardized techniques and reagents and by combining information from several fields in the multiple marker analysis. New areas of leukemia research might become very useful for the routine procedure of phenotyping.Abbreviations ALL acute lymphoblastic leukemia - AML acute myeloblastic leukemia - AMMoL acute myelomonoblastic leukemia - AMoL acute monoblastic leukemia - cALL common ALL - CLL chronic lymphocytic leukemia - CML chronic myelocytic leukemia - CML-BC CML in blastic crisis - CMoL chronic monocytic leukemia     

急性髓系白血病Bcl—2基因表达及其临床意义

目的：探讨Ｂｃｌ－２基因在急性髓系白血病（ＡＭＬ）中的作用。方法：应用ＡＰＡＡＰ法检测６７例ＡＭＬ患者骨髓单个核细胞Ｂｃｌ－２基因表达，半固体培养法检测ＣＦＵ－Ｌ形成能力，并观察临床化疗效果．结果：发现ＡＭＬ患者Ｂｃｌ－２基因表达显著高于正常对照组（Ｐ〈０．００１），分化较成熟的Ｍ３型白血病表达率显著低于其它各亚型白血病（Ｐ〈０．０１），Ｂｃｌ－２蛋白表达表达与ＣＦＵ－Ｌ形成无相关性同，与患者外周     

Haploidentical Hematopoietic Stem Cell Transplantation in Leukemia’s: Experience from a Cancer Center in India

There has been a surge in haploidentical hematopoietic stem cell transplantation (HSCT) in India recently. However, there is a paucity of data on haploidentical HSCT from India. The report is an analysis of data of haploidentical HSCT performed at our center. Analysis of patients with acute leukemia or chronic myeloid leukemia who underwent haploidentical HSCT during 2014–2019 was performed. The graft versus host disease (GVHD) prophylaxis was post-transplant Cyclophosphamide with Mycophenolate-mofetil and Cyclosporine. All patients were transfused peripheral blood stem cells from donors. Overall survival (OS) was calculated using the Kaplan–Meier method. Twenty-one patients underwent haploidentical HSCT. Fourteen-patients were males. The median age of patients was 15 years. Fludarabine with total body irradiation was the most common conditioning regimen (n = 15, 71.4%). The median duration for neutrophil and platelet engraftment was 14 days. Cumulative incidence of acute and chronic GVHD was 19%, and 38% respectively. The median follow-up was 26 months and the two-year OS was 38%. Twelve (57%) patients died during the study period, 8 patients (38%) died from transplant-related mortality (TRM), and 4 from disease relapse. Sepsis was the cause of death in six of the eight TRM. Nine out of 21 patients (42.8%) are leukemia-free on follow-up. Haploidentical HSCT is a promising modality of treatment in patients who have no suitable matched donors. Though the TRM remains high, good disease control was achieved in 42.8% of patients. Multi-drug resistant bacterial infection remains a challenge in performing haploidentical HSCT in developing countries.     

急性白血病患者雌激素受体多药耐药相关蛋白的检测及临床意义

目的 :探讨雌激素受体 (ER)、多药耐药相关蛋白 (MRP)表达与临床疗效的关系 ,为耐药白血病寻找新的治疗途径。方法 :采用免疫组化ABC法检测了 37例急性白血病 (AL)复发难治患者骨髓单个核细胞的ER与MRP表达。结果 :①ER阳性组CR率为 91.6 7% (11/ 12 ) ,阴性组为 2 8.0 0 % (7/ 2 5 ) ,ER阳性组CR率显著优于阴性组 (P <0 .0 1)。②MRP阳性组CR率为 2 3.81% (5 / 2 1) ,MRP阴性组为 81.2 5 % (13/ 16 ) ,MRP阳性组CR率明显差于阴性组 (P <0 .0 1)。③ 37例AL患者中 ,8例ER +/MRP -与 17例ER - /MRP +患者其ER与MRP表达的一致性很好 (Kappa系数 =0 .83,P <0 .0 1)。另有ER +/MRP +4例 ,ER - /MRP - 8例 ,其ER与MRP表达缺乏一致性。结论 :ER与MRP表达有一定的一致性 ,且与临床疗效有一定关系 ;ER与MRP检测有助于疗效和预后的判定     

Stimulatory effect on DNA synthesis of thymus and spleen extract from leukemic AKR mice

Summary A 30,000–50,000 molecular weight (MW) extract of thymus and spleen from 11 age groups of untreated AKR mice, 1–210 days old, was tested for in vitro effect on thymide incorporation into normal AKR lymph node cells, normal spleen cells, and leukemic thymocytes. Extracts from mice up to 5 months of age mostly had slightly inhibitory effect but concomitant with emergence of thymus leukemia in the 6-month-old mice, the extract acquired a strongly mitogenic effect on normal lymph node cells. Seven-month-old, non-leukemic animals again yielded extracts with inhibitory effect.Supported by the US Health Education and Welfare grant no. IROI CA 26109-01, Commission of the European Communities contract no. 251-77-1 BIO DK, and The Carlsberg Foundation     

儿童混合表型急性白血病15例临床特征分析北大核心CSCD

目的分析儿童混合表型急性白血病(MPAL)的临床特点、治疗及预后, 为临床优化诊疗方案及提高缓解率提供参考。方法基于2016年世界卫生组织(WHO)的诊断标准, 回顾性分析2012年1月至2020年12月苏州大学附属儿童医院收治的15例MPAL患儿的骨髓细胞形态、免疫分型、细胞遗传学、分子生物学特征以及治疗方案、预后等病例资料。计数数据组间比较采用χ^(2)检验, 符合正态分布的计量资料组间比较采用t检验, 非正态分布的计量资料组间比较采用秩和检验。采用Kaplan-Meier(K-M)法估计生存率, 比较应用Log-rank法。结果苏州大学附属儿童医院8年共收治15例MPAL患儿, 男8例, 女7例, 中位年龄为6.8岁;9例患儿表达B淋系+髓系表型, 5例表达T淋系+髓系表型, 1例表达B淋系+T淋系表型;11例患儿进行了染色体核型检查, 2例为正常核型, 2例为复杂核型, 6例为假二倍体, 1例为亚二倍体;5例患儿检测到融合基因, 其中3例AML-ETO阳性, 1例BCR-ABL阳性, 1例MLL阳性;13例患儿在化疗后完全缓解, 总完全缓解率为86.6%, 2年总生存率为(68.2±13.4)%。15例患儿中14例授受了诱导化疗, 1例因个人原因放弃了治疗。首选急性淋巴细胞白血病(ALL)化疗方案10例, 第1个疗程完全缓解1例, 总完全缓解率10%;首选急性髓系白血病(AML)化疗方案4例, 第1个疗程完全缓解3例, 总完全缓解率75%, 未缓解的1例更换ALL方案后缓解;8例行造血干细胞移植(HSCT)和6例未行HSCT组2年总生存率分别为(70.0±18.2)%、(66.7±19.2)%, 差异无统计学意义(χ^(2)=0.318, P=0.573)。结论儿童MPAL是一种罕见的恶性肿瘤, 以淋系和髓系抗原共表达为主, 单纯化疗或HSCT在短期内均可获得较好的预后, 但长期疗效还有待进一步观察。     

Antibiotic strategy after the empiric phase in patients treated for a hematological malignancy

 Empiric broad-spectrum antibiotic therapy has become a generally accepted strategy in the treatment of febrile neutropenic patients. Particularly in patients with prolonged neutropenia, subsequent adaptation of such a regimen will be the rule rather than exception. Since there are no uniformly accepted guidelines for the modification of antibiotic therapy during the post-empiric phase, we assessed the impact of a set of rules that evolved during the first randomized trials. Evaluation of the clinician's compliance with these rules in 1951 febrile neutropenic episodes was the subject of the present analysis. Treatment was modified in 761 (39%) cases, and these changes were made according to the rules in 76%. For 75% of the alterations in treatment during the evening and night shifts, no reasonable explanation was established, while 93% of the modifications during the normal working hours were made for objective reasons. The empiric regimen was more frequently changed in patients with a clinical focus of infection at the onset of fever than in patients who showed fever as the only symptom of a possible infection. The perceived need for modification amounted to 69% in pulmonary infections, to 51% in skin and soft-tissue infections, to 44% in patients with abdominal complaints, and to 37% in upper respiratory tract infections. Glycopeptides constituted 22% of modifications, particularly in patients with a central venous catheter, and systemically active antifungals were administered in 16% of cases. Especially inexperienced clinicians tend to adjust antibiotic therapy, in spite of the fact that persistence of fever alone seldom reflects inadequate treatment when the clinical condition of the patient is stable or improving. On the other hand, the development of subsequent infectious events emphasizes that a genuine need for modification does frequently exist. Received: 4 December 1995 / Accepted: 7 December 1995     

DAPTO等方案诱导治疗急性双表型白血病11例报告

报告１１例急性双表型白血病的诱导化疗结果。５例ＡＢＬ经ＤＡＰＴＯ方案诱导化疗，４例于２８－５０天内完全缓解，持续ＣＲ时间７－１４月，存活时间８－１８月，１例仍无病生存，其余６例应用ＤＶＰ等方案化疗，ＣＲ２例，持续ＣＲ分别为４和８月，６例患者作１例生存１６月外，余未超过７月。     

明胶酶A在急性白血病细胞中的表达及其临床意义

目的　探讨急性白血病 (AL)细胞中明胶酶A(MMP2 )的表达及其临床意义。方法　应用明胶酶谱法检测了 4 6例初治AL患者MMP2的表达 ,同时应用逆转录 PCR(RT PCR)测定了MMP2活化相关基因基质金属蛋白酶抑制剂 2 (TIMP2 )、基质金属蛋白酶 1(MT1 MMP)的表达 ,并在体外进行了白血病细胞株穿膜试验研究。结果　 4 6例AL患者中 2 4例 (5 2 2 % )MMP2表达阳性 ,MMP2阳性组与阴性组发生髓外浸润的比例分别为 5 0 0 %和 18 2 % (P值均 <0 0 5 ) ;外周血幼稚细胞百分率分别为 (77 2 1± 13 9) %和 (6 2 95± 17 2 ) % (P值均 <0 0 1)。同时 4 6例AL患者中TIMP2、MT1 MMP阳性表达分别为 2 7例 (5 8 7% )、33例 (71 7% )。体外穿膜试验证实了MMP2对白血病细胞侵袭能力的影响。结论　活性MMP2可能参与白血病细胞从骨髓释出并浸润组织的过程