儿童急性淋巴细胞白血病化疗后的不良反应

目的 分析儿童急性淋巴细胞白血病化疗后不良反应发生的特点及规律, 实施个体化给药避免或减少严重的药品不良反应 (ADR) 的发生.方法 收集2014年3月至2015年2月新发儿童急性淋巴细胞白血病化疗后不良反应184 3例, 对患者性别, 年龄, 危险度、药物、ADR累及器官或系统等方面进行研究分析.结果儿童急性淋巴细胞白血病化疗后不良反应涉及高危组患者居多;涉及药物以左旋门冬酰胺酶、长春新碱、阿糖胞苷居前3位;不良反应累及的系统或器官以血液系统最为常见;骨髓抑制并发感染与危险度及患儿年龄差异有统计学意义 (P<0.01) , 与性别无统计学差异 (P>0.05) .结论 儿童急性淋巴细胞白血病化疗后ADR以骨髓抑制最为常见, 其中以骨髓抑制及并发感染对患儿生活质量及治疗效果的影响最大.     

Hematopoietic stem cell transplantation for beta-thalassemia major]

OBJECTIVE: To discuss the feasibility of hematopoietic stem cell transplantation for beta-thalassemia major. METHODS: Bone marrow or cord blood of sibling was transplanted to 4 children with thalassemia, whose type of gene mutations was homozygous. All of them were diagnosed as beta-thalassemia major. HLA type was matched in 2 cases, and mismatched with 1 locus in the other 2. RBC type was mismatched in 1 cases. Pretransplant condition including busulfan (BU) 16 mg/kg, cyclophosphamide (CY) 200 mg/kg and anti-thymocyte globulin (ATG) 90 mg/kg. Graft-versus-host disease (GVHD) prophylaxis was cyclosporine-A (Cs-A) and methotrexate (MTX). RESULTS: Two Children had "serum sickness" during pretransplant condition; two children had grade II acute GVHD and 1 developed chronic GVHD, 1 case veno-occlusive disease (VOD), 1 case cytomegalovirus (CMV) interstitial pneumonia and 1 case fungemia post-transplant, which had been cured. The average time for peripheral WBC recovery > 1.0 x 10(9)/L was 16 days, 18 days for neutrophile granulocyte > 0.5 x 10(9)/L, 59 days for Plt > 50 x 10(9)/L and 39 days for Hb > 100 g/L. The average time for WBC recovery to normal was at day 24. The average time of last blood transfusion for patients was 29 days. The patients had to receive about 100 ml blood infusion per 2 months pretransplant, while not infused for 7 approximately 15 months up to now with Hb > 100 g/L. Gene mutation type of patients had changed to donor's. CONCLUSION: We report a successful transplantation of bone marrow and cord blood stem cells for thalassemia major in China. This will give a new strategy for treatment of the disease and further expand the use of stem cells transplantation.     

益肾升白贴联合穴位注射治疗放化疗所致骨髓抑制的疗效观察

目的 观察益肾升白贴联合穴位注射地塞米松治疗恶性肿瘤放化疗所致骨髓抑制的疗效及副作用。方法 将101例恶性肿瘤放化疗后发生骨髓抑制的病人随机分成3组，35例采用益肾升白贴联合穴位注射地塞米松治疗，35例仅采用穴位注射地塞米松治疗作为对照组1组，31例以重组人粒细胞集落刺激因子皮下注射治疗作为对照组2组。观察骨髓功能恢复情况及用药的不良反应。结果 3组病人骨髓功能恢复时间及总有效率无统计学差异(P＞0.05)，3组病人经治疗后再程放化疗，骨髓功能分级有统计学意义(P＜0.05)，益肾升白贴联合穴位注射地塞米松治疗组再程放化期间，仍对骨髓功能有显著保护作用。3组病人均无特殊不良反应。结论 益肾升白贴联合穴位注射地塞米松治疗恶性肿瘤放化疗后骨髓抑制安全、有效，且对骨髓功能保护时间长，无明显不良反应，值得临床推广使用。     

儿童急性白血病化疗后骨髓抑制期感染的临床分析

目的：分析急性白血病（AL）患儿化疗后骨髓抑制期感染的临床特点及血培养刚性细菌对抗生素的敏感性,探讨其防治措施。方法：回顾性分析住院AL患儿化疗后进入骨髓抑制期其感染的发生率;血培养刚性细菌对抗生素的耐药性及敏感性;血培养阳性与血培养阴性患儿在骨髓抑制期的时间及抗生素使用时间的差异。结果：札患儿骨髓抑制期感染的发生率为75．8％（72／95）,其中血培养阳性率为26．4％（19／72）。血培养阳性组以肠道感染较多（47．6％）,其主要病原茵为大肠埃希茵、铜绿假单胞茵、葡萄球菌属。三种病原茵对青霉素类、头孢三代抗生素、红霉素的耐药率均较高,葡萄球菌属对万古霉素和利奈唑烷相对较敏感,大肠埃希茵对碳青霉烯类抗生素敏感性较高。铜绿假单胞茵对碳青霉烯类抗生素和哌拉西林／他巴唑较敏感,对复方新诺明耐约者较多。血培养刚性组患儿在中性粒细胞缺乏持续时间为（9．37±5．20）d。抗生素使用时间为（16．53±6．29）d,两项指标在血培养刚性组与阴性组之间的差异有显著性。结论：AL患儿骨髓抑制期易发生感染,如考虑革兰阴性茵感染可选择碳青霉烯类,如考虑革兰阳性茵感染可选择万古霉素及利奈唑烷,必要时根据细菌药物敏感试验调整抗生素。     

异基因外周造血干细胞移植治疗儿童重型再生障碍性贫血

目的探讨异基因外周血造血干细胞移植(allo—PBSCT)对儿童重型再生障碍性贫血(SAA)的疗效。方法8例接受allo—PBSCT治疗的SAA 患儿均为血缘供体移植,男6例,女2例,7～14岁,中位年龄为11岁。4例患儿为急性SAA I型,其中2例移植前合并重型感染且未能完全控制;另4例患儿为SAA Ⅱ型,患儿移植前大多经包括环孢菌素A(CSA)在内的多种治疗无效。诊断至移植的时间为1～45个月,中位时间为13个月。预处理方案由低剂量环磷酰胺（CTX）和抗淋巴细胞球蛋白（ALG）或抗胸腺细胞球蛋白（ATG）组成,采用CsA+短程甲氨蝶呤(MTX)方案预防移植物抗宿主病(GVHD)。以DNA短串联重复序列多态性分析(STR PCR)检测学植入依据。结果患者移植后均获造血重建,中性粒细胞绝对值≥0.5×109／L和血小板计数≥20×109／L的中位时间分别为移植后+12.75d(+10～+15d)和+19.88d(+15～+32d)。8例患儿均为完全供体型植入,其中1例移植后10个月出现外周血白细胞、红细胞、血小板计数逐渐下降,STR PCR显示移植排斥,经ATG、CsA 等药物治疗逐渐恢复自身造血。1例患儿出现Ⅱ度急性GVHD,1例出现局限性慢性GVHD。随访15～50个月,中位数为29个月,8例SAA患儿均存活。结论采用以免疫抑制为主的ATG/ALG+CTX预处理方案进行allo—PBSCT能够有效治疗儿童SAA,移植相关并发症少,值得临床推广应用。     

甲磺酸伊马替尼治疗3例Ph阳性慢性髓性白血病达细胞遗传学缓解后的疾病转化

目的:观察Ph阳性慢性髓性白血病(Philadelphia chromosome-positive chronic myelogenous leukemia, Ph CML)患者在甲磺酸伊马替尼治疗达细胞遗传学缓解后的疾病进展. 方法:对3例伊马替尼单药治疗有效的Ph CML患者,包括第1次慢性期(例1)、第2次慢性期(例2)和加速期(例3)各1例,在治疗前及持续治疗后定期监测其血液学和细胞遗传学(G显带方法)变化. 结果:例1、例2和例3分别在伊马替尼治疗4个月、3个月和6个月时获得完全细胞遗传学缓解(complete cytogenetic remission, CCyR),但在随后的12个月、6个月和0个月(即服药的第16个月、9个月和6个月)时,分别发生了急性淋巴细胞白血病、急性髓性白血病和皮肤软组织髓外急变,同期骨髓染色体检查显示:例1和例3未检出Ph 细胞,呈完全正常核型,例2 Ph 细胞仅占20%. 结论:伊马替尼治疗Ph CML获得CCyR后,患者仍可发生Ph阴性(Philadelphia chromosome-negative, Ph-)或Ph-为主的急性白血病或髓外急变.     

VDD（P）＋M强化诱导治疗成人急性淋巴细胞白血病的临床观察

报告了用VDD(P)+M强化诱导治疗成人急性淋巴细胞白血病(ALL)18例的结果。完全缓解(CR)13例(72％),接受CR后强化巩固和高(中)剂量Ara-C或MTX者,中位持续CR期5.5月,中位生存期21月。主要毒副作用为骨髓造血严重受抑,半数患者并发感染,强调同时强力支持及对症治疗的必要性。     

The morbidity and mortality of right hemicolectomy for complicated intussusception in infants

Infants with intussusception in tropical Africa frequently present late. Intestinal resection for gangrene or perforation may warrant a right hemicolectomy. Over a period of 11 year, 15 (45.5%) of 33 infants with intussusception required bowel resection, 10 of which were right hemicolectomies. The age range of those who had right hemicolectomy was 3-9 months (median 6 months) and duration of symptoms 3-8 days (median 6 days). In addition to features of intussusception, seven (78%) infants were dehydrated and one was anaemic. Six (67%) of 9 infants developed procedure related complications postoperatively. Four (44%) had anastomotic dehiscence, associated with abdominal wound dehiscence in 2. In 3 of the patients, the anastomosis leaked again following repeat resection and anastomosis, necessitating relaparotomy and stoma formation. One (11%) patient each had wound infection and prolonged ileus respectively. Six (67%) patients died, including the 4 who had anastomotic dehiscence. The cause of death was overwhelming infection in 4 patients and aspiration of vomitus in two patients. Recommendations are made to minimize morbidity and mortality in these infants.     

Multiple myeloma in Mexico: a 20-year experience at a single institution

BACKGROUND: In a 20-year period at a single institution, 66 cases of multiple myeloma (MM) were identified. The disease was less frequent in Mexico because in a multicenter study it represented 4.2% of all hematologic malignancies, whereas during this experience it was found to represent 7.7%. These figures contrast with those reported in Caucasians-10-15%. METHODS: There were two patients <40 years of age; median age was 66 years. Bone pain was present in 54%, fatigue in 66%, and weight loss in 47%. Anemia was present in 75% of females and in 96% of males at diagnosis; median hemoglobin was 10.2 g/dL; abnormal monoclonal spike had a median of 2.87 g/dL (range 0-9.9). Four cases (6%) of nonsecretory myelomas were identified. Bence Jones proteinuria was present in 51 cases (77%). Forty six individuals were followed for >3 months (97-7,054 days, median 2,371 days). RESULTS: Their survival (SV) was 51% at 540 days. Patients treated with melphalan/prednisone had a median SV of 33 months with a 72-month SV of 30%. Patients treated with vincristine/adriamycin/dexamethasone had an SV of 40% at 42 months, whereas those given high-dose chemotherapy and autologous stem cell rescue had an SV of 80% at 22 months. CONCLUSIONS: Clinical features of Mexican patients with MM were not significantly different from those reported for other populations; best results from treatment were observed in patients administered autologous stem cell transplantation.     

托泊替康联合顺铂治疗晚期肺及头颈部鳞癌的临床研究

目的 观察托泊替康联合顺铂治疗晚期肺及头颈部鳞癌的疗效及毒副反应.方法 126例经病理或细胞学证实为肺鳞癌和头颈部鳞癌患者予托泊替康0.75～1.2mg/m<2,静脉滴注30min,d1～d5;顺铂25-30mg/m2,静脉滴注,d1～d3.21 d为1周期.2周期为一疗程.结果 全组无完全缓解病例,部分缓解61例,稳定53例,进展12例,总有效率48.4%,中位生存期10.1个月.1年生存率36.7%.毒副反应:主要为骨髓抑制和脱发.结论 托泊替康联合顺铂治疗晚期肺及头颈部鳞癌疗效较好.毒副反应可耐受,无蓄积.     

慢性髓性白血病骨髓细胞体外培养净化的实验研究

目的 :探讨慢性髓性白血病 (CML)骨髓细胞体外培养对自体骨髓移植物的净化作用。方法 :分离 10例初诊的慢性期Ph+ CML患者骨髓单个核细胞 (MNC) ,体外培养 10天 ,利用染色体分析法检测培养前后Ph+ 中期细胞比例 ;通过流式细胞术检测培养前后MNC中CD+ 3 4干 /祖细胞比例。结果 :培养后Ph+ 中期细胞比例下降明显 (5 7%±6 92 % )vs(88.2 %± 7.97% ) ,P <0 .0 5 ;培养体系MNC中CD+ 3 4干 /祖细胞数量减少无显著性 (2 .78± 1.6 7)× 10 5 vs(3 2 7± 2 .2 5 )× 10 5 ,P >0 .0 5。结论 :CML骨髓细胞经体外培养 ,Ph+ 细胞比例下降 ,而CD+ 3 4干 /祖细胞数量无明显变化 ,提示该法对CML骨髓细胞具有一定程度净化作用。     

生物型APC重建股骨近端瘤性骨缺损的保肢技术及疗效分析

目的 探讨生物型同种异体骨-假体复合物（allograft-prosthetic composite,APC）重建股骨近端肿瘤切除后骨缺损的手术方法和中期疗效。 方法 收集2007~2011年在我科接受股骨近端肿瘤切除、生物型APC重建的15例患者资料及病理结果;术后第1、3、6、9、12月及之后每半年对患者进行影像学检查及功能随访评估。影像学评估主要包括骨-骨界面愈合情况及大转子骨吸收情况;采用骨与软组织肿瘤协会评分（MSTS）及Harris髋关节评分（HHS）评估患者关节功能,采用查体评估患者外展肌肌力。结果 本组15例患者中,男7例,女8例,平均年龄25.1岁（17~56岁）;平均随访时间32.8月（18~48月）;病理学诊断:骨巨细胞瘤4例,骨肉瘤3例,软骨肉瘤3例,恶性纤维组织细胞肿瘤2例,骨母细胞瘤2例,尤文氏肉瘤1例。15例患者异体骨-宿主骨界面均获骨性愈合,愈合时间为5~9月;至末次随访时,未出现感染、异体骨-宿主骨愈合处骨吸收、髋关节脱位、异体骨超敏反应、髋臼磨损及肿瘤复发和转移等并发症。3例患者术中出现假体周围骨折,以钢丝环扎术固定。术后6例患者出现大转子骨吸收。15例患者平均MSTS评分和HHS评分,术前为11.3分（7~15分）和47.3分（40.3~58.5分）,末次随访时为26.1分（24~29分）和80.1分（66.2~92.7分）。结论 生物型APC应适用于年龄轻、预期生存时间长及术后功能要求高的股骨近端骨肿瘤患者。     

Hairy cell leukaemia with advanced treatment - a case report

A case of hairy cell leukaemia (HCL), a rare leukaemia, is reported here. The patient was presented with high grade continuous fever with left upper abdominal discomfort for 6 days. He was moderately anaemic, had no peripheral lymphadenopathy with mild hepatosplenomegaly. He was anaemic (Hb-7.8 gm/dl), total leukocyte count was 20 x 109/L. Peripheral blood film showed lymphocytosis (92%) with neutropenia (8%) and absolute neutophil count (ANC) was 1 x 109/L. On review, 88% of the peripheral cells had peripheral hairy projections resembling hairy cell (HC). Bone marrow examination was consistent with HCL (morrow hairy cell = 52%) including marker studies. Tartrate resistant acid phosphatase test (TRAP) was also positive. He had opportunistic mycobecterial infection giving a positive bronchial lavage for acid fast bacilli. After controlling the infection he was advised a single dose chemotherapy of 2-chlorodeoxyadenosine (2-CDA). After that he was in partial remission and after 25 months clinical and pathological relapses occurred and a second dose of 2-CDA was given and the patient went into complete remission.     

Application of autologous peripheral blood stem cell transplantation in children with malignant tumor

Objective To investigate if low dose total body irradiation (TBI, 6.0-9.0 Gy) combined with intensified chemotherapy followed by autologous peripheral blood stem cell transplantation results in better survival in children with refractory leukemia or solid tumors. Methods Twenty-one children with malignant tumors were included in this study.There w ere 14 males and 7 females aged 3.5-12 years.Underlying disease included high -risk acute lymphoblastic leukemia (ALL, CR(1) in 3 children and CR(2) in 5 ch ildren), acute myeloblastic leukemia (AML, 9 children), non-Hodgkin’s lymphoma stage Ⅳ ( 2 children), and neuroblastoma stage Ⅳ (2 children).The peripheral hematopoi etic stem cells were collected six to eleven months after complete response, mob ilized with high dose chemotherapy alone or combined with GM-CSF or G-CSF.Th e conditioning regimen consisted of chemotherapy with two to three combinations of the following drugs: cyclophosphamide, arabinosylcytosine, McNU, etopside, an d Idarubicin on the basis ofTBI (6.0-9.0 Gy).A mean of (1.8±0.5) ×10(8)/kg autologous mononuclear cells were transplanted.The patients were followed up after transplantation. Results Severe bone marrow suppression occurred in all patients around day +7.Peripher al white blood cell count decreased to 0 in all patients at day +4.8±2.9, and platelet count decreased to less than 20×10(9)/L at day +9.0±2.6.Succ essful engraftment was achieved in 21 patients, but four died of infection at da y +17, +20, +31 and +67, respectively.Recovery of white blood cell (WBC) to 10×10(9)/L, absolute neutrophil count to 0.5×10(9)/L, platelet count to 20 ×10(9)/L occurred on 21±12, 26±13, and 27±10 days, respectively.During the follow up period, three patients relapsed at +5 months, +1.5 years, and +2 yea rs 10 months, respectively.One patient died of intracranial hemorrhage at +8 m onths.Thirteen patients had event-free survival for 2-12 years, with a mean o f 6.7±3.4 years.Conclusion Our preliminary data suggest that myeloablative therapy with low dose TBI (6.0 -9.0 Gy) combined with intensified chemotherapy followed by autologous periphe ral blood stem cell transplantation might be associated with favorable results i n children with refractory leukemia or solid tumors.     

A study of haematological and bone marrow changes in symptomatic patients with human immune deficiency virus infection with special mention of functional iron deficiency,anaemia of critically ill and haemophagocytic lymphohistiocytosis

Background

Haematological abnormalities are among the most common complications of HIV. These involve all lineages of blood cells. Bone marrow studies form integral part of complete workup of the HIV positive patients specially when they present as case of pyrexia of unknown origin (PUO), refractory anaemia and pancytopenia.

Method

55 HIV infected symptomatic patient requiring bone marrow examination were included in the study. Relevant clinical history, baseline haematological investigations including full blood count, CD4 cell counts using flow cytometry were recorded.

Results

Median ANC values in males were found to be significantly lower than females (p = 0.046). CD4 cell count statistically significantly correlated with age, TLC, ANC & platelet count. Anaemia was present in 45 patients and out of which 66.66% patients had normocytic normochromic anaemia. Iron deficiency anaemia was present in (37.77%) patients and anaemia of chronic disease in (62.22%) patients. 2 patients had anaemia of the critically ill.Two patients had non-Hodgkin's lymphoma (NHL) and showed lymphoma deposit in the bone marrow. Gelatinous degeneration was seen in 3 patients. Ill formed epithelioid cell granulomas were seen in 7 cases, and 2 cases were positive for acid fast bacilli (AFB). Haemophagocytosis was seen in 8 cases; two cases later diagnosed as a case of infection induced HLH. Leishmania donovani (LD) bodies seen in 2 cases.

Conclusions

Bone marrow study is an important investigation in HIV infected symptomatic patients with peripheral haematological abnormalities.     

急性白血病完全缓解期检测微小残留病的临床意义

目的探讨急性白血病(acute leukemia,AL)获得完全缓解(complete remission,CR)后检测微小残留病(minimal residual disease,MRD)的临床意义。方法所有患者初诊时均进行骨髓免疫分型检测,从首次诱导缓解治疗结束后第14天开始,每3个月检测一次MRD,并动态监测,同时进行骨髓形态学检查。结果MRD<10-4复发率为22.2%,MRD>10-3复发率为77.8%,MRD>10-2复发率为100%。结论经过20例患者的MRD检测显示:MRD<10-4的复发率低,MRD﹥10-3的复发率高,MRD﹥10-2提示近期复发。因此,MRD对早期复发的判断、及早干预治疗和治疗方案的选择有着明显的指导意义。     

系统性肥大细胞增生症的骨髓病理学特点与鉴别

目的探讨系统性肥大细胞增生症（SM）的病理学特点、诊断与鉴别诊断。方法回顾性分析了2例SM的骨髓病理形态学观察、免疫表型和特殊染色检测。结果1例为男性,73岁,以皮肤瘙痒7年伴乏力2月就诊。查体示脾肿大,浅表淋巴结及肝脏均不大;另1例女性,57岁,以面苍、乏力、发热5月余就诊。查体示双下肢、背部少量出血点。外周血检查示1例为全血细胞减少,另1例贫血、白细胞少。骨髓涂片示2例均出现肥大细胞增多,分别为15．5％、6．5％。骨髓活检示2例骨髓中异常肥大细胞多灶性增生,伴有淋巴细胞、嗜酸粒细胞、纤维母细胞增生。甲苯胺蓝染色细胞胞质内见紫红色颗粒。免疫组化示异常细胞为CDll7（＋）、CD25（＋）、CD2（-）、MPO（-）、lysozyme（-）,CD20（-）、CD3（-）。结论SM的骨髓病理学改变具有特征性,骨髓活检病理形态学、特殊染色和免疫组化对于SM的诊断十分重要。     

Chlorpropamide-induced granulomas. A probable hypersensitivity reaction in liver and bone marrow.

Anicteric hepatitis, associated with fever and exfoliative dermatitis, developed in a diabetic patient two weeks after intake of a long-acting sulfonylurea, chlorpropamide (Diabinese). Granulomas showing heavy infiltration with eosinophils were found in the liver and bone marrow. These were interpreted as manifestations of an allergic reaction. The clinical signs, abnormal laboratory findings, and hepatic lesions subsided spontaneously on withdrawal of the drug. Bone marrow changes, however, persisted seven months after cessation of the drug. To our knowledge, this is the first report of a patient with liver and bone marrow inflammation characterized by granulomas with eosinophilic infiltration following intake of chlorpropamide.     

自体骨髓经皮注射治疗四肢骨折不愈合

目的：探讨经皮自体骨髓注射移植治疗四肢骨折不愈合的疗效。方法：于骨折不愈合部位注入自髂骨抽取的骨髓。结果：经注射１～３次,历时４～９个月,平均６个月达到骨性愈合。结论：经皮自体骨髓注射移植治疗四肢骨折不愈合简单有效。