肿瘤

05 1 8 48　 HD-A+VM2 6+rh G-CSF动员白血病患儿外周血造血干细胞的初步研究 /竺晓凡…∥中国小儿血液 .-2 0 0 4,9(3 ) .-1 2 5～ 1 2 75例高危急性白血病患儿 ,其中急性淋巴细胞白血病(AL L) 4例 ,急性杂合细胞 (AHL) 1例。年龄 9～ 1 3岁。 5例均采用 HD-A+VM2 6+rh G-CSF方案进行动员。4例采集 1次 ,1例采集 2次。全部患儿均能耐受该动员方案治疗。 MNC值为 5 .965 (5 .0 2× 1 0 8～ 7.2× 1 0 8/ Kg)。 CD3 4 +细胞量为 4.3 72 (3 .95× 1 0 6～ 5 .62× 1 0 6/ Kg)。此结果提示 ,G-GSF联合大剂量 Ara-C和 VM2 6的化…     

儿童自体外周血干细胞动员和采集的临床研究

目的　评价环磷酰胺、长春新碱、依托泊苷、泼尼松 (COEP) /吡柔比星、长春新碱、依托泊苷、泼尼松(DOEP)动员方案对儿童急性淋巴细胞白血病和淋巴瘤自体外周血造血干细胞移植动员采集的临床效果。方法　以COEP方案和DOEP方案为动员化疗方案 ,观察采集干细胞效果。结果　 13例 (6例非霍奇金淋巴瘤和 7例急性淋巴细胞白血病 )儿童采用COEP/DOEP方案动员 (8例用COEP方案 ,5例用DOEP方案 ) ,化疗后第 4～10d(平均 6d)白细胞数 <2× 10 9/L ,用粒细胞集落刺激因子后第 4～ 19d(平均 8d)开始采集外周血造血干细胞 ,采集单个核细胞数 (4 19～ 9 96 )× 10 8/kg(平均 6 78× 10 8/kg) ,CD34+细胞数 (2 90～ 12 78)× 10 6/kg(平均 8 90× 10 6/kg) ,粒单造血祖细胞数 (3 4 9～ 4 1 72 )× 10 4/kg(平均 15 5 7× 10 4/kg)。动员的并发症较轻 ,患儿均能耐受。自体外周血干细胞移植后均获快速造血功能重建 ,白细胞开始回升 (中性粒细胞绝对值 >0 5× 10 9/L)的时间为移植后 10～ 2 2d(平均 14d) ,血红蛋白恢复 (>80 g/L)的时间为移植后 10～ 2 8d(平均 17d) ,血小板恢复 (>2 0× 10 9/L)的时间为移植后 10～ 2 0d(平均 19d)。结论　COEP/DOEP方案可以安全高效地完成儿童白血病和淋巴瘤自体外周血干细胞的动     

自身造血干细胞移植治疗儿童晚期神经母细胞瘤临床报道

目的 　神经母细胞瘤是儿童常见的恶性肿瘤 ,即使通过化疗、放疗及手术等综合治疗 ,晚期患儿仍生存率极低。为提高治愈率 ,本中心对 1 1例晚期患儿进行了自身造血干细胞移植术。方法 　本组平均年龄 3 8岁 ( 2～ 6岁 ) ,平均体重 1 5 3kg( 1 1 6kg～ 2 0kg)。 2例为原发于胸腔的Ⅲ期患者 ,9例均为原发于腹腔伴有广泛骨髓转移的IV期患儿。虽然大剂量化疗及积极的手术治疗 ,4例患儿移植时原发肿瘤仍未完全清除 ,属带瘤移植。因对其中 2例未缓解患儿进行了两次移植 ,1 1例患儿共进行了 1 3例次移植。 3例次直接采集骨髓 ,另 1 0例次采用外周血造干细胞进行移植。为减少移植后复发 ,4例患儿采集物经CliniMACS进行了CD+3 4细胞分选的净化处理。所有患儿均采用VP1 6 +卡铂 +马法兰的预处理方案。结果　采集骨髓及外周血得到的单个核细胞分别为 ( 5 7± 0 9)× 1 0 8/kg和 ( 5 7± 1 0 )× 1 0 8/kg ,两者之间无显著性差异 (P >0 0 5) ,所有患儿移植后都获造血重建 ,中性粒细胞恢复至 0 5× 1 0 9/L的平均时间为 1 0 5± 5 7天 ,非输血依赖的血小板大于 2 0× 1 0 9/L的时间为 1 6 8±9 4天 ,血小板大于 50× 1 0 9/L的时间为 33 1± 2 0 1天 ,移植过程中平均输注红细胞2 2± 2 0单位 ( 0～ 8单位 )?     

CD34+CXCR4+与非亲缘脐血移植后粒细胞和血小板重建关系的研究

目的　研究回输CD34+CXCR4 +的输入量在非亲缘脐血移植治疗儿童急性白血病中对中性粒细胞(ANC)和血小板 (BPC)恢复时间的影响。方法　用流式细胞术分析回输CD34+CXCR4 +细胞数 ,并对 2 3例儿童急性白血病在非亲缘脐血移植后的ANC和BPC恢复时间等临床资料进行测定。结果　 2 3例患儿中 ,CD34+CXCR4 +输入量为 (2 1～ 198 6 )× 10 4/kg(中位数 19 9× 10 4/kg)。在 2 1例植入成功患儿中 ,ANC >0 5× 10 9/L的时间为 11～ 4 1d(中位数 2 0d) ;而在 2 0例获得统计资料的患儿中 ,BPC >2 0× 10 9/L的时间为 12～ 12 0d(中位数4 4 5d)。CD34+细胞输入量与ANC、BPC恢复时间的r值分别为 - 0 35 4 (P =0 116 )、- 0 4 30 (P =0 0 5 8) ,CD34+CXCR4 +细胞输入量与ANC、BPC恢复时间的r值分别为 - 0 5 2 7(P =0 0 17)、- 0 6 2 9(P =0 0 0 4 )。结论　CD34+CXCR4 +输入量与非亲缘脐血移植后的造血重建有关。     

急性白血病并发真菌败血症9例

急性白血病 (ＡＬ)患儿化疗后常易出现出血 ,细菌感染等并发症 ,并发真菌败血症较少见 ,我院自 1 984年以来诊治 9例 ,报导如下 :临床资料1 一般资料　 9例中男 6例 ,女 3例。急性淋巴细胞白血病 6例 (Ｌ13例 ,Ｌ2 2例 ,Ｌ31例 ) ,急性非淋巴细胞白血病 3例 (Ｍ32例 ,Ｍ5 1例 )。均发生于化疗巩固期。2 临床表现　发热 9例 ,7例为高热头痛 6例 ,4例为阵发性剧痛 ,腹泻例。呼吸急促 8例 ,咳嗽 7例 ,吐白色粘痰或黄痰 5例 ,胸痛 2例。口腔粘膜有白膜 5例 ,皮肤紫瘢 7例。3 实验室检查　外周血白细胞计数 <1 0× 1 0 9/Ｌ 7例 ,<4 0× 1 0 …     

CD34+细胞自身移植治疗儿童难治性系统性红斑狼疮

目的　探讨CD34+ 细胞分选的自身干细胞移植在儿童难治性系统性红斑狼疮 (SLE)中的治疗效果。方法　 2例病程分别为 5年和 7年、狼疮肾 III级和IV级、主要表现为持续性血小板减少、蛋白尿和胸腔积液的患儿 ,首先经重组人粒细胞集落刺激因子动员、CS 30 0 0血细胞分离机采集外周血 ,获取单个核细胞 ,通过CliniMACSCD34+ 细胞分选仪分别得到了 1 7× 1 0 6 /kg及 1 0× 1 0 6 /kgCD34+ 细胞 ,采集物中分别尚存 2× 1 0 5/kg及 1× 1 0 4 /kg的CD3+ 细胞。然后给予患儿环磷酰胺[50mg/ (kg·d)× 4d]和抗胸腺细胞球蛋白 [5mg/ (kg·d)× 3d]预处理 ,48h后回输冻存的CD34+ 细胞。结果　两患儿分别于移植后 9和 7天即获粒细胞重建 ,自 1 5天起血小板一直维持在正常水平。因停用皮质激素 ,移植 3个月后患儿库欣征完全消退 ,1例患儿还获得了自患病 7年来的首次身高增长 (半年内身高增长了 5cm)。现已分别随访 1 3个月和 6个月 ,原发病症状完全消失、自身免疫相关抗体全部转阴 ,但细胞免疫功能仍未恢复 ,CD4仍处于低水平。结论　CD34+ 细胞自身干细胞移植治疗儿童难治性系统性红斑狼疮近期疗效满意     

自体外周血造血干细胞移植在小儿恶性晚期实体肿瘤的临床应用(英文)

目的　小儿晚期实体肿瘤对常规化疗效果欠佳 ,该文探讨大剂量化疗并自体外周血干细胞移植(APBSCT)治疗小儿高危晚期实体瘤的可行性及疗效。方法　 1 3例恶性实体肿瘤患儿 (恶性淋巴瘤 7例、神经母细胞瘤 6例 ) ,在其完全缓解 (1 2例 ) ,部分缓解 (1例 )后进行了APBSCT治疗。移植时病程中位时间 1 0月。 1 1例用化疗加重组人粒 单细胞集落刺激因子 (rhGM CSF)或重组人粒细胞集落刺激因子 (rhG CSF)动员 ,2例采用常规化疗方案作为动员剂。所采集单个核细胞 (MNC)为 (6 .85± 2 .6 5 )× 1 0 8/kg。CD34+ 细胞为 (1 5 .82± 1 2 .93)×1 0 6/kg。CFU GM集落为 (1 7.87± 1 7.94 )个 / 1 0 4细胞。预处理方案中 6例基本方案为全身放疗加环磷酰胺。 7例未用TBI ,仅以马法兰为主做为预处理方案 (马法兰 +卡铂 +足叶乙甙 5例 ,白消胺 +马法兰 2例 )。结果　移植后白细胞 >0 .5× 1 0 9/L、>1 .0× 1 0 9/L、血小板 >2 0× 1 0 9/L的中位时间分别为 1 2天、1 5天、1 9天。中位随访时间4 8月 (1月～ 1 4 4月 )。至今总生存率 77% (1 0 / 1 3) ,死亡率 2 3% (3/ 1 3) ,无移植相关死亡。结论　APBSCT是治疗小儿晚期实体肿瘤 ,明显改善其预后的重要治疗方法。     

儿童急性白血病长期存活相关因素研究

目的　分析儿童急性白血病长期存活的有关因素。方法　对 43例长期存活 5年以上急性白血病患儿的临床资料进行回顾分析。结果　自改进化疗方案后有 43例存活 5～ 2 3年以上 ,中位存活期 13 5年。37例急性淋巴细胞白血病 (ALL)中有 32例 (86 5 % )强烈化疗≤ 4周完全缓解 (CR) ,至今仍长期存活 ;>4周达CR 5例 (13 5 % )中 2例存活 5年后复发死亡。若起病时白细胞数虽高 ,如能在 2～ 4周获CR后坚持规范治疗 ,仍可改善预后。 37例ALL中 18例应用大剂量甲氨蝶呤 (HD MTX)后无一例发生髓外白血病。 43例中有 9例行干细胞移植治疗。结论　小儿ALL多药联合诱导若 2～ 4周内获CR有益于预后。积极稳妥开展HD MTX有益于髓外白血病防治。对化疗难以根治的白血病患儿可选用干细胞移植     

CD11b对儿童急性白血病脐血移植粒细胞和血小板恢复时间的影响

为了研究CD34+ CD1 1b+ 细胞输入量在脐血移植中对中性粒细胞和血小板恢复时间的影响 ,观察并分析 1 7例儿童急性白血病患者进行无关脐血移植的临床数据。结果显示 ,移植后 1 7例患者中性粒细胞≥ 0 5× 1 0 9 L的时间为 1 1～ 32天 (中位数为 1 7天 ) ;血小板≥ 2 0× 1 0 9 L的时间为 1 2～ 1 1 8天 (中位数为 4 0天 )。CD34+CD1 1b+ 细胞输入量为 1 0 7～ 79 0 0× 1 0 4 Kg(中位数为 9 1 8× 1 0 4 Kg)。CD34+CD1 1b+ 细胞输入量与中性粒细胞恢复时间呈反比 (γ =- 0 4 89,P <0 0 5) ;CD34+CD1 1b+ 细胞输入量与血小板恢复时间无关 (r =- 0 2 38,P >0 0 5)。CD34+ CD1 1b+细胞输入量与造血干细胞移植时的造血重建有关。     

rhG-CSF治疗白血病及肿瘤化疗后白细胞减少的疗效观察

20例小儿白血病、肿瘤患儿在强烈化疗后致粒细胞减少时应用基因重组人粒细胞集落刺激因子（rhG－CSF），当其化疗后外周血白细胞计数低于2．0×109／L或中性粒细胞低于0．5×109／L时予皮下注射rhG－CSF2－5μg／kg·日，5－10天，并与12例同期住院病情、病种相似、年龄相当的化疗后白细胞减少患儿不予rhG－CSF仅给抗感染、输血等对症支持治疗进行比较。结果显示：rhG－CSF组白细胞恢复时间明显短于对照组（P＜0．01），用药组感染发生率为30％，低于对照组67％（P＜0．05）。     

Feasibility of peripheral blood stem cell (PBSC) and peripheral blood mononuclear cell (PBMNC) separation in children with a body weight below 20 KG

Nine children from 10 to 76 months (median 28.0), weighing 8.5 to 19.7 kg (median 13.0 kg) underwent peripheral blood stem cell separation (PBSCS) or peripheral blood mononuclear cell separation (PBMNCS), after insertion of a double-lumen central venous catheter (8–10 French). Separations were performed with a continuous flow blood separator (Fenwall CS 3000 plus), running a specially adopted separation-program. In 7 children (5 with neuroblastoma IV, 1 with multifocal Ewing's sarcoma, and 1 with rhabdomyosarcoma IV), stem cells were mobilized by application of G-CSF at a dosage of 15–27.7 μg/kg body weight (median 16.25) subcutaneously following high-dose chemotherapy, according to the disease-related protocols, whereas 2 children had PBMNCS to induce graft vs. leukemia (GvL)-reaction in the HLA-identical sibling suffering from relapsed chronic myelogeneous leukemia (CML: n = 1), or chronic myelomonocytic leukemia (CMML: n = 1) after allogeneic BMT. In all cases, the collecting procedure was performed after filling the cell separator with priming solution consisting of 2 U of irradiated and washed packed red cells, 250 ml human albumin, and 0.9% NaCl. In the 7 patients with solid tumors between 0.45 and 62.7 × 10⁶ CD-34 positive cells/kg body weight were separated; the patient who had the lowest yield was separated twice after another mobilizing course. Three patients (2 with neuroblastoma IV and 1 with multifocal Ewing's-sarcoma) underwent a double transplantation with 1–3 portions of the collected stem cells within a 5- to 6-week interval. Two children had a rapid engraftment on both peripheral blood stem cell transplantations (PBSCTs). The third child, who had the lowest yield and was separated twice had prompt engraftment at the first PBSCT but delayed and incomplete engraftment at the second PBSCT. One patient after adoptive immunotransfer with PBMNCs for relapsed CML is now 40 months in complete cytogenetic and molecular biological remission, whereas the other patient treated for relapsed CMML did not respond to the PBMNC-transfusion. The results indicate that PBSCS and PBMNCS can be performed in children with a body weight below 20 kg. Med. Pediatr. Oncol. 29:115–120, 1997. © 1997 Wiley-Liss, Inc.     

rhG-CSF在小儿ANLL强烈化疗中的应用

为探讨rhG-CSF对小儿ANLL强烈化疗后粒细胞缺乏的疗效，采用AAE方案（ADM、Ara-C、VP(16)或VM(26)），化疗后当WBC＜1×109/L或ANC＜0．5×109/L时，给予rhG-CSF200μg/m2·d（5～10μg/kg·d），皮下注射，一般连续5～10天。本文15例ANLL，用rhG-CSF30例次。用rhG-CSF前，WBC平均0．78×109/L、ANC0．15×109/L。用rhG-CSF后，平均6．5天WBC升至＞3×109/L、ANC升至＞1×109/L。粒细胞恢复时间与对照组相比明显缩短（P＜0．01）。骨髓复查未见原始细胞增多或复发。rhG-CSF有促进强烈化疗所致骨髓抑制和粒细胞缺乏的恢复，但未见骨髓原始细胞增多和白血病复发。     

Allogeneic peripheral blood stem cell transplant in children

Allogeneic peripheral blood stem cell (PBSC) transplant has recently been introduced for the treatment of hematological malignancies. As the data were limited mainly to adult patients, this study aimed to assess the feasibility and safety of this procedure in pediatric patients and donors. Eleven children aged 2–16 years received allogeneic PBSC transplant for acute lymphoblastic leukemia (n = 4), acute myeloid leukemia (n = 1), myelodysplastic syndrome (n = 1), severe aplastic anemia (n = 3), and thalassemia (n = 2). Nine donors were human leukocyte antigen (HLA)-identical siblings and the other two were one antigen mismatched family members. Eight donors were younger than 18 years old (10 months to 17 years). Donors were primed with granulocyte colony-stimulating factor (G-CSF) at 10–16 μg/kg for 4–5 days. Aphereses were performed on 1 or 2 consecutive days, and the patients received a mean of 14.4 × 10⁸/kg nucleated cells, 6.9 × 10⁶/kg CD34 cells, and 6.9 × 10⁸/kg T cells. All patients achieved neutrophil counts of >0.5 × 10⁹/l at a median of 16 days. Nine patients achieved platelet counts of >20 ×10⁹/l at a median of 13 days. Grade II acute graft vs. host disease (GVHD) occurred in only one patient. Chronic GVHD was not observed in the seven patients with follow-up of more than 3 months. Eight patients remained in continuous complete remission after transplant ranged from 2 to 26 months. Allogeneic PBSC transplant appears safe in pediatric patients and donors, and it seems not to be associated with increase of acute GVHD or chronic GVHD. Med. Pediatr. Oncol. 30:147–151, 1998. © 1998 Wiley-Liss, Inc.     

米托蒽醌治疗小儿难治复发的急性非淋巴细胞白血病的临床研究

为探讨小儿难治复发的急性非淋巴细胞白血病的治疗方法 ,临床上观察了 2 7例病人 ,经米托蒽酯 6mg/m2 × 3天 ,Ara c 1 50mg/m2 × 7天 ,VP166 0mg/m2 × 5天的联合化疗疗效。结果治疗后CR 37% ( 1 0 /2 7) ,PR 30 % ( 8/2 7) ,总有效率 6 7% ,化疗后骨髓造血功能抑制明显 ,感染发生率较高为 73% ,结果显示 :以米托蒽醌为主的化疗治疗小儿难治及复发的急性非淋巴细胞白血病有较好疗效。     

抗CD47抗体联合阿糖胞苷靶向治疗NOD/SCID小鼠单核细胞白血病的研究

目的：探讨CD47在急性髓细胞白血病NOD/SCID小鼠模型中的预后意义及靶向治疗的最佳策略。方法：将分选的CD34+CD38-白血病干细胞（leukemia stem cells, LSCs）移植入NOD/SCID小鼠体内,建立小鼠急性单核细胞白血病模型;抗人CD47单克隆抗体单独或联合阿糖胞苷治疗白血病小鼠7~14 d,并进行疗效分析。将LSCs与小鼠巨噬细胞在含抗CD47单克隆抗体的培养液中共培养,观察CD47对巨噬细胞吞噬LSCs能力的影响。结果：THP-1细胞中存在CD34+CD38- LSCs,比例约为0.12%±0.06%,将分选后的CD34+CD38- LSCs（比例高达97.0%±1.7%）移植入NOD/SCID小鼠后成功建立白血病模型。体内实验表明,阿糖胞苷（7 d）联合抗CD47单克隆抗体（14 d）治疗后,白血病小鼠外周血和骨髓中CD33+CD45+白血病细胞下降最明显（P<0.01）,生存时间明显长于其它各组。体外共培养2 h后,抗CD47单克隆抗体组吞噬指数（76.9%±12.2%）明显高于抗CD45单克隆抗体组（7.60%±2.4%,P<0.01）。结论：CD47高表达是急性髓细胞白血病的预后不良因素。阿糖胞苷联合抗CD47单克隆抗体可有效杀灭普通白血病细胞和白血病干细胞,对彻底治愈急性髓细胞白血病具有重要临床意义。     

Autologous bone marrow transplantation with 4-hydroperoxycyclophosphamide-purged marrow for acute lymphoblastic leukemia

Ten patients age 13–52 years with acute lymphoblastic leukemia (ALL) in first complete remission (CR) (1), second CR (6), or relapse (3) were treated with cyclophosphamide 50 mg/kg daily × 4 and total body irradiation 3 Gy daily × 4 followed by infusion of autologous marrow purged with 4-hydroperoxycyclophosphamide (4-HC) at 100–120 μg/mL. The patients transplanted in relapse also received 2 mg vincristine and corticosteroids. All marrows were harvested while patients were in CR. The nucleated marrow cell dose was 3.5 ± 0.7 × 10⁸/kg, and the CFU-GM content of the transplant was 0.4 ± 0.5 × 10³/kg after purging with 4-HC. Median time from transplantation is 48 months. The neutrophil count (ANC) exceeded 1.0 × 10⁹/L at a median of 26 days and platelets exceeded 50 × 10⁹/L at 34 days. All patients were in remission after transplantation (ABMT). Five patients relapsed 2–9 months after ABMT (actuarial rate 60%). Three patients are alive and in CR at 17+, 43 +, and 54+ months after ABMT. Purging marrow with 4-HC did not adversely affect engraftment, but it is not clear if the high relapse rate was due to incomplete ex vivo purging or inadequacy of the conditioning regimen.     

Marked increase of peripheral blood myeloblasts following G-CSF therapy in a patient with acute lymphoblastic leukemia

A 9 year old boy with acute lymphoblastic leukemia (ALL) received recombinant human granulocyte colony-stimulating factor (rhG-CSF) and showed a marked increment of myeloblasts in the peripheral blood. He was administered repeated courses of intermediate-dose cytosine arabinoside (Ara-C) therapy (1500 mg/m², days 1–5) for frequent central nervous system (CNS) relapse of ALL. The peripheral white blood cell nadir was less than 1000/μL, so he was treated with rhG-CSF. A marked increment of peripheral blood blasts was noted 3–5 days after rhG-CSF treatment. These cells decreased with the appearance of mature myeloid cells and disappeared about 2 weeks after the start of treatment. These findings suggested that the blasts might have the ability to differentiate into mature myeloid cells. A control patient with repeated CNS relapse of ALL showed no increment of peripheral blood blasts after similar repeated courses of Ara-C without rhG-CSF treatment. Cultured peripheral blood blasts obtained from the present patient showed differentiation into mature myeloid cells by morphological studies and surface marker analysis. These findings indicate that the peripheral blood blasts drawn by G-CSF were not leukemic blasts but normal myeloblasts.     

APPLICATION OF NITRIC OXIDE FOR A CASE OF VENO-OCCLUSIVE DISEASE AFTER PERIPHERAL BLOOD STEM CELL TRANSPLANTATION

A 5-year-old girl at high risk for acute lymphoblastic leukemia was treated with high-dose chemotherapy and autologous peripheral blood stem cell transplantation (PBSCT). However, her condition was complicated by veno-occlusive disease of the liver (VOD) after PBSCT. For treatment of VOD, transdermal isosorbide tape was applied as a nitric oxide (NO) donor. The signs of VOD improved immediately after NO treatment was initiated, and the patient showed no side effects from the transdermal isosorbide tape.     

Application of nitric oxide for a case of veno-occlusive disease after peripheral blood stem cell transplantation

A 5-year-old girl at high risk for acute lymphoblastic leukemia was treated with high-dose chemotherapy and autologous peripheral blood stem cell transplantation (PBSCT). However, her condition was complicated by veno-occlusive disease of the liver (VOD) after PBSCT. For treatment of VOD, transdermal isosorbide tape was applied as a nitric oxide (NO) donor. The signs of VOD improved immediately after NO treatment was initiated, and the patient showed no side effects from the transdermal isosorbide tape.