高压氧治疗异基因造血干细胞移植后迟发性出血性膀胱炎1例

患者女性,27岁,因“乏力、活动耐力下降3个月”就诊于青岛大学附属医院,2020年5月27日病理检查（骨髓活检）示：骨髓细胞容积约70%,粒红比例明显升高,粒系细胞各阶段可见,偏幼稚阶段细胞易见,比例升高,嗜酸性粒细胞易见,红系少见,巨核细胞可见,数目偏少,查见3个巨核细胞,呈分叶核;诊断为急性髓系白血病。完善检查后予...     

MRI在慢性粒细胞白血病病情监测中的应用

目的探讨骨髓MRI在慢性粒细胞白血病(chronic myeloid leukemia,CML)病情监测中的应用价值。方法对12例CML患者在不同时间进行2次MRI检查,与同期血常规及骨髓穿刺结果对照,分析MRI的变化与病情发展演变的关系。结果患者骨髓MRI表现随病情进展而发生相应的变化,其中2例随病情好转,骨髓信号增高,4例病情进展,骨髓信号减低,6例病情稳定,骨髓信号不变。结论骨髓MRI能反映CML患者的病情变化,对监测病情发展有重要价值。     

难治性贫血与巨幼细胞性贫血细胞形态学鉴别分析

目的 探讨难治性贫血（MDS—RA）与巨幼细胞性贫血（MA）形态学特征。方法回顾分析40例RA,48例MA血象、骨髓象及骨髓细胞铁染色检查的特点。结果RA与MA血象均以全血细胞减少为主,MCV〉100fl,血片中可见到幼红细胞及幼稚粒细胞;红系巨变,骨髓细胞内外铁增加。RA骨髓象中红系以中晚幼红细胞增生为主,MA骨髓象中红系以巨早、中幼红细胞为主;RA病态遗血表现为粒系核浆发育不平衡、双核、环状核粒细胞,红系巨大,巨系出现小巨核、淋巴样巨核等。MA骨髓象表现为巨晚幼粒、杆状核粒细胞及分叶过多的粒细胞;红系早、中幼阶段巨幼变;分多个小核巨核细胞。结论RA与MA细胞形态学既具有相似性,又具有各自不同特征,这些特征可为这两种疾病的诊断和鉴别诊断提供线索和依据。     

重组人白细胞介素-1β对小鼠骨髓粒系细胞和红系细胞的正负调节作用

为阐明IL-1对粒系细胞和红系细胞的作用,我们通过对小鼠骨髓及外周血的研究探讨了IL-1对粒系和红系造血细胞的调节作用.结果表明:IL-1单剂量腹腔注射后第7天红系造血细胞明显减少,外周血网织红细胞在第8天显著下降.在5～10万U/kg剂量范围内IL-1明显促进粒系细胞的增殖.应用流式细胞仪对DNA分析显示IL-1并不引起全骨髓细胞DNA的变化,但大体积细胞在注射IL-1后第3天S期细胞明显增多.我们的结果表明IL-1抑制红系造血细胞的分化增殖,在适当的剂量范围内促进粒系细胞的增殖和分化成熟.其作用的分子基础是诱导造血细胞的细胞周期变化.     

格列卫治疗慢性粒细胞白血病急变期患者的临床疗效及毒性反应观察

目的评价格列卫治疗慢性粒细胞白血病急变期患者的疗效及毒性反应。方法36例患者中31例患者单用格列卫治疗,有5例加用亚砷酸治疗,根据患者耐受情况调整格列卫剂量。开始每2天复查外周血涂片、血常规,每周复查肝肾功能,1个月后每周复查外周血涂片、血常规,每2周复查肝肾功能,每1个月进行骨髓细胞形态学检查,每3个月进行细胞遗传学检查,记录治疗过程中的不良反应。结果1个月时血液学缓解率（包括CHRT和NEL）66.7%,服用格列卫3个月后进行细胞遗传学检查,5例附加染色体异常消失,其中部分细胞遗传学缓解3例,完全细胞遗传学缓解2例。血液学不良反应以白细胞、血小板减少多见,非血液学不良反应以恶心、呕吐、水肿多见,其次为骨骼肌酸痛、乏力、头昏常见,而胸腔积液、头痛、皮疹等少见。结论尽管格列卫是一种较安全的药物,其治疗慢粒急变期患者近期疗效明显,但远期疗效并不理想。     

间充质干细胞治疗急性骨髓型放射病的实验研究

目的研究骨髓间充质干细胞(MSCs)在治疗急性骨髓型放射病中的作用,并对其机理做初步的探索。方法BALBc雌性小鼠分成MSCs组和照射对照组,MSCs组经5.5Gy60Coγ射线照射,2h内尾静脉输注C57BL6雄性小鼠的MSCs,照射对照组照射后不作处理。观察各组外周血象变化、骨髓细胞凋亡、细胞增殖周期、骨髓病理变化、骨髓造血粒系祖细胞集落(CFUGM)以及基质细胞集落(CFU-F)计数。结果与对照组相比,MSCs组的三系血细胞下降慢,最低值抬高,并且造血恢复更迅速,尤其白细胞、血小板变化更明显。骨髓细胞凋亡率和P53蛋白表达量少于对照组。照后2d,MSCs组G0G1期比值较对照组明显下降(P<0.01),G2M期比值及S期计数较对照组显著升高(P<0.01)。照后4dMSCs组胸骨骨髓增生活跃,对照组增生减低,照后20dMS-Cs组新生造血灶多于对照。CFU-GM、CFUF计数在照后初期、极期、恢复期均高于对照。结论MSCs对急性放射病治疗有良好的治疗作用,其机制可能与MSCs减少细胞凋亡、改善造血微环境、促进干细胞增殖分化有关。     

芥子气中毒致外周血细胞和骨髓细胞形态学损伤的研究

目的 观察血细胞及骨髓细胞形态学指标在芥子气中毒人员的治疗过程中的变化与中毒严重程度的相关性。方法 对芥子气中毒人员进行外周血及骨髓细胞形态学分析。结果 44名芥子气中毒患者白细胞总数均进行性降低,有10名患者出现中性粒细胞减少症或中性粒细胞缺乏症,芥子气中毒早期嗜酸性粒细胞损伤较严重,淋巴细胞百分比及绝对值在早期显著降低,芥子气中毒对外周血的血小板总数影响不大,红细胞和血红蛋白在最初因血液浓缩而升高。血细胞及骨髓细胞形态改变明显,白细胞胞体肿大,胞质可见中毒颗粒、空泡等,所有中毒者均出现异型淋巴细胞,以幼稚型异型淋巴细胞为主,血小板形态改变不明显。芥子气中毒早期骨髓造血细胞损害严重。结论 检查血象和骨髓象是判断芥子气中毒患者中毒程度及预后的一项重要指标,淋巴细胞绝对值减少程度和恢复正常值的时间长短及骨髓细胞增生受抑制的程度与中毒严重程度有关。     

巨核细胞、血小板动态变化对急性白血病疗效和预后的意义150例分析与文献复习

目的　探讨急性白血病患者骨髓巨核细胞数量及质量 ,血小板数量及分布在治疗过程中的动态变化对判断疗效和预后的意义。方法　采集骨髓 ,常规涂片 ,瑞氏染色 ,标准化计数。结果　 15 0例初发急性白血病巨核细胞数量以减少者为主 ,形态以颗粒型巨核细胞、裸核型巨核细胞为主 ;血小板计数减低 ,血小板少见。治疗缓解后巨核细胞数量明显增加 ,以裸核型巨核细胞最为明显 ;血小板计数升高 ,血小板由少见向成堆分布。所需缓解天数 :减少组 <正常组 <增高组 ,正常巨核细胞组 <病态巨核细胞组 ,急性淋巴细胞性白血病<急性非淋巴细胞性白血病。血小板数量及分布与缓解时间无明显关系。结论　对急性白血病患者骨髓中巨核细胞、血小板的动态观察在临床上具有一定的判断疗效和预后意义。     

全身垂直振动对去卵巢骨质疏松大鼠骨髓细胞分化的调节作用

目的:观察全身垂直振动对去卵巢骨质疏松大鼠骨髓细胞分化的调节作用.方法:将36只3月龄雌性未孕SD大鼠按体重分层后随机分为假手术、去卵巢静止和去卵巢振动3个组.去卵巢手术后10周,去卵巢振动组大鼠经过1周适应振动治疗后,开始接受正式全身垂直振动治疗,每次振动15 min、频率为90 Hz,每天振动2次,每周7次.治疗7周时,用721分光光度计检测血清碱性磷酸酶和甘油三酯水平;常规HE染色观察左侧胫骨组织形态学;收集右侧股骨和胫骨骨髓细胞,一部分细胞用作碱性磷酸酶和油红O染色,另一部分细胞用作尼罗红(Nile Red)染色.结果:与假手术组比较,去卵巢静止组骨髓细胞碱性磷酸酶阳性染色细胞数目显著降低,而骨髓细胞Nile Red阳性染色细胞百分比和胫骨骨髓脂肪空泡数目显著增加;与去卵巢静止组比较,去卵巢振动组骨髓细胞碱性磷酸酶阳性染色细胞数目显著增加,而骨髓细胞Nile Red阳性染色细胞百分比和胫骨骨髓脂肪空泡数目显著下降.结论:全身垂直振动不仅增加去卵巢骨质疏松大鼠骨髓细胞的成骨分化能力,而且降低去卵巢骨质疏松大鼠骨髓细胞的成脂分化能力.     

重组人粒－巨噬细胞集落刺激因子对6．5Gy不均匀照射犬造血功能的影响

重组人粒－巨噬细胞集落刺激因子（ｒｈＧＭ－ＣＳＦ）在白血病及肿瘤病人大剂量放化疗白细胞减少性疾病的治疗中显示出了良好的前景。ｒｈＧＭ－ＣＳＦ可明显改善屏蔽全骨盆后６．５Ｇｙ６０Ｃｏｒ线照射犬的临床症状，加速外周血白细胞的恢复，提高白细胞的最低值，缩短白细胞减少的持续时间。可明显增加照射犬骨髓有核细胞数及骨髓细胞数，促进骨髓ＣＦＵ－ＧＭ的增殖，提高骨髓细胞的粒／红比值。可应用于事故性骨髓型急性放射病病人的临床治疗。     

骨髓检查和常规血液学参数在骨髓转移癌诊断中的意义

恶性肿瘤患者51例(男38例,女13例),骨髓穿刺涂片镜检发现瘤细胞者21例。在骨髓涂片瘤细胞阳性患者中,多数有贫血、血小板减少和外周血中出现幼粒、幼红细胞,并有硷性磷酸酶、乳酸脱氢酶及红细胞沉降率增高。结果表明,骨髓检查和一些血液学指标在骨髓转移癌的诊断中是有价值的。如必要时,作骨髓凝块切片、骨髓活检、X线骨照片和骨扫描检查以明确诊断。     

MR imaging of therapy-induced changes of bone marrow

MR imaging of bone marrow infiltration by hematologic malignancies provides non-invasive assays of bone marrow cellularity and vascularity to supplement the information provided by bone marrow biopsies. This article will review the MR imaging findings of bone marrow infiltration by hematologic malignancies with special focus on treatment effects. MR imaging findings of the bone marrow after radiation therapy and chemotherapy will be described. In addition, changes in bone marrow microcirculation and metabolism after anti-angiogenesis treatment will be reviewed. Finally, new specific imaging techniques for the depiction of regulatory events that control blood vessel growth and cell proliferation will be discussed. Future developments are directed to yield comprehensive information about bone marrow structure, function and microenvironment.     

右归丸对骨髓抑制小鼠骨髓细胞周期和凋亡的影响

目的观察右归丸对骨髓抑制小鼠外周血、骨髓细胞周期和凋亡的影响,探讨其可能造血调控作用机制。方法用全自动血细胞分析仪、白细胞计数法和流式细胞术（FCM）分别检测右归丸对骨髓抑制小鼠外周血、骨髓有核细胞数以及骨髓细胞周期和调亡的影响。结果右归丸中、高剂量均能明显升高外周血红细胞（RBC）、血红蛋白（Hb）、骨髓有核细胞（BMC）数,右归丸高剂量对血小板（PLT）和白细胞（WBC）有明显升高作用。右归丸低、高剂量组均能促进骨髓GO／G1期细胞向S期细胞以及S期细胞向G2／M期细胞的转化,从而导致G2／M期细胞比例明显升高,增殖指数（PI）也明显升高。中、低剂量组右归丸的骨髓细胞凋亡比例显著下降。结论右归丸可能通过促进骨髓细胞修复受损的DNA,加速通过GI／S和S期监测点,进行增殖和分化;抑制造血细胞的凋亡;调节造血细胞增殖与凋亡之间的平衡等机制,从而促进损伤骨髓造血功能恢复。     

Bone marrow in leukemia and aplastic anemia: MR imaging before, during, and after treatment

Serial magnetic resonance (MR) studies of the cervical bone marrow were performed in five patients undergoing bone marrow transplantation for chronic granulocytic leukemia and in four patients with aplastic anemia who were treated with antilymphocytic globulin. Findings were compared with those from a group of healthy volunteers. Chemical shift imaging techniques were used to exploit the presence of protons in fat and water in the red marrow. Characteristic changes were seen in aplastic anemia before treatment, but derivation of images representing fat and water fractions was necessary to distinguish leukemic marrow. Acute changes during the treatment of leukemia may reflect the effects of chemotherapy and radiation therapy, whereas changes in the chronic phase of both diseases may prove useful in predicting treatment outcome. MR studies are likely to be useful in the assessment and treatment of hematologic disorders.     

Initial experience with dynamic MR imaging in evaluation of normal bone marrow versus malignant bone marrow infiltrations in humans

The purpose of this study was (a) evaluation of dynamic contrast-enhanced MR imaging of normal bone marrow versus malignant bone marrow infiltrations in patients with proven B-cell-type chronic lymphocytic leukemia (B-CLL) and (b) correlation with the clinical stage according to Binet (stages A, B, C) and response to therapy. Bone marrow imaging of the lumbar spine, pelvis, and proximal femurs was performed at 1.5 T in 45 patients without known malignancy and in 30 patients with B-CLL. The differences between opposed-phase and in-phase dynamic gradient-echo sequences before and up to 10 minutes after intravenous application of .1 mmol/kg body weight of gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) were evaluated in normal bone marrow. The contrast-enhancement patterns of normal and malignant bone marrow were compared using the opposed-phase dynamic gradient-echo sequence. Ten of the patients with bone marrow infiltrations (Binet stage C) additionally underwent MR imaging follow-up during therapy. Opposed-phase gradient echo sequences demonstrated a signal decrease of normal bone marrow, and in-phase gradient echo sequences demonstrated a signal increase of normal bone marrow after administration of Gd-DTPA. The dynamic signal intensity time courses differed significantly (P < .05) between Binet stages B and C and controls as well as among the three Binet stages of B-CLL. In the 10 patients followed during therapy, MR imaging sensitively demonstrated response (n = 6), nonresponse (n = 2), or relapse after initial response (n = 2). In out-of-phase imaging, both normal bone marrow and initial bone marrow infiltration in CLL stage Binet A show signal decrease after administration of contrast agent, whereas there is increase in signal intensity in higher-grade bone marrow infiltration in Binet stage B or C disease. The signal loss of normal bone marrow in out-of-phase imaging is a phase effect rather than a T2* effect. The differentiation of initial from higher-grade bone marrow infiltration on out-of-phase images relies solely on a shift in the fat/water ratio.     

Multiple cranial nerve palsies revealing blast crisis in patient with chronic myeloid leukemia in the accelerated phase under nilotinib during severe infection with SARS-COV-19 virus: Case report and review of literature

Since the introduction of tyrosine kinase inhibitors as primary therapy for patients with chronic myeloid leukemia (CML), the prognosis of these patients has improved significantly, and the number of patients who progress to the blast phase has decreased considerably. We report the case of a 35 year-old CML patient in accelerated phase treated with nilotinib, who presents a severe COVID-19 infection requiring non-invasive ventilation, and who subsequently presents a multiple cranial nerve palsy revealing a blast crisis of his CML. Multiple cranial nerve palsy is a sign of neurological involvement of CML in its blast phase. The blast crisis represents a real challenge for the clinician, especially during COVID-19 infection. The treatment remains the association of a tyrosine kinase inhibitors with a chemotherapy protocol, as well as the administration of methotrexate and cytarabine by intrathecal and intravenous infusion in high doses. Despite the importance of the association of CML with COVID-19 infection, there is not yet enough data to know the true impact of this infection on the evolution of this hemopathy.     

Detection of K-ras and p-53 oncogene mutations in a patient with acute lymphoblastic leukemia before and after bone marrow transplantation]

We present a case of 22 years old male patient, who was submitted to singenic transplantation of hematopoietic cells originating from the bone marrow in the remission phase of the diagnosed acute lymphoblastic leukemia (ALL). The bone marrow sample was donated by his healthy twin brother. The pretransplantation and transplantation phases were regular. We analyzed the presence of K-ras and p-53 point mutations in our patient with ALL and for the first time we had the opportunity to analyze the samples from two monozygotic twins. DNA was isolated from the peripheral blood mononuclear cells (PBMNC) by the standard procedure, of the patient with ALL before and after bone marrow (BM) transplantation and of his clinically healthy twin brother. Samples were subjected to PCR amplification of K-ras exons 1 and 2 and p-53 exons 5, 6, 7 and 8. In PBMNC of the patient with ALL before BM transplantation, mutations were observed in exon 1 of K-ras and exon 8 of p-53 gene. These mutations were found neither in PBMNC sample of his twin brother, nor in PBMNC of the patient with ALL after BM transplantation. In the p-53 exons 5, 6 and 7 and exon 2 of K-ras, there were no mutations in any analyzed samples. Detected mutations in K-ras and p-53 genes could be a part of larger genetic abnormalities and the obtained results had shown the possibility of using DNA mutational changes in the follow-up of the success of BM transplantation. The molecular disease marker that was found by this method was also significant for the detection of minimal residual disease at the molecular level.     

Prospective study of bone marrow infiltration in aggressive lymphoma by three independent methods: whole-body MRI, PET/CT and bone marrow biopsy

PURPOSE: Initial lymphoma staging requires bone marrow assessment in aggressive lymphomas. Bone marrow lymphoma infiltration is routinely assessed by bone marrow biopsy (BMB), considered as the "gold standard". The aim of this study was to compare the performance of BMB, whole-body MRI and PET/CT for evaluation of BM infiltration. METHODS: Patients with newly diagnosed aggressive lymphoma were evaluated by BMB, MRI and PET/CT. Two radiologists, two nuclear medicine physicians and one pathologist independently assessed the results of the three modalities. Bone was considered as involved if BM was positive or if PET/CT or MRI was positive and if there was a resolution of the abnormal image shown on PET/CT or MRI halfway or at the end of therapy. RESULTS: Both MRI and PET/CT detected bone marrow lesions in the 9/43 patients, but two patients with multiple lesions had more lesions detected by PET/CT compared to MRI. Among these nine patients, two with an iliac crest lesion detected by both MRI and PET/CT had bone marrow involvement with large-cell lymphoma on histological examination. The other seven patients had focal MRI and PET/CT lesions in areas other than the iliac crest, where the blind BMB was done. The other patients had bone marrow without large-cell lymphoma involvement. In all cases, after lymphoma therapy bone marrow involvement regressed on histological examination, PET and MRI. CONCLUSION: These preliminary results suggest that non-invasive morphological procedures could be superior to BMB for bone marrow assessment in aggressive lymphomas. Ongoing study is underway to validate these results.     

Use of bone marrow stromal cells for tendon graft-to-bone healing: histological and immunohistochemical studies in a rabbit model

BACKGROUND: Despite increasing attention on the issue of tendon-to-bone integration, there has been no animal study on the use of cell therapy for promoting the insertion healing of tendon to bone. PURPOSE: To determine the efficacy of using a large number of bone marrow stromal cells (bMSCs) to enhance tendon-to-bone healing. STUDY DESIGN: Controlled laboratory study. METHODS: The hallucis longus tendons were translated into 2.5-mm diameter calcaneal bone tunnels in a New Zealand white rabbit model. The bone tunnels were treated with or without bMSCs. Three specimens from each group were harvested at 2, 4, and 6 weeks postoperatively and evaluated by conventional histological and immunohistochemical methods. RESULTS: At 4 weeks, the specimens with bMSCs exhibited more perpendicular collagen fiber formation and increased proliferation of cartilage-like cells, which was indicated by positive collagen type-II immuno-staining of the tendon-bone interface. In contrast, the specimens without bMSCs demonstrated progressive maturation and reorganization of fibrous tissue aligned along the load axis. CONCLUSION: Introduction of a large number of bone marrow stromal cells to the bone tunnel have shown to improve the insertion healing of tendon to bone in a rabbit model through formation of fibrocartilagenous attachment at early time points.