乳腺癌骨髓转移伴重度骨髓抑制治疗后长期生存一例并文献回顾

目的探讨乳腺癌骨髓转移的临床特点、诊治方法及预后。方法报告1例乳腺癌骨髓转移病例,分析其诊疗经过并复习相关文献。结果本例患者就诊时已有明显骨痛和中度贫血,经紫杉醇单药联合最佳支持治疗(BSC),症状明显缓解,至2011年10月已获生存期31个月。结论骨髓转移癌早期易被忽视,当有骨痛并突发原因不明的贫血和血小板减少时(而白细胞多正常),应考虑骨髓转移的可能,骨髓穿刺是简单而有效的确诊手段。在造血因子的支持下,化疗联合BSC能缓解症状,延长生存期。     

骨髓转移癌41例临床分析

目的：探讨骨髓转移癌的临床特点。方法：分析41例骨髓转移癌患者的临床特点，包括症状、实验室检查和影像学检查结果。结果：骨痛、发热、消瘦为最常见症状；常见的血象异常包括贫血、血小板减少、外周血出现幼红幼白细胞；68％的患者血清碱性磷酸酶异常升高；88％的患者骨扫描检查发现骨放射性异常。原发灶不明转移癌占46％，其次为肺癌、前列腺癌等。18例接受了抗肿瘤治疗，41例患者的中位生存期仅3．6个月。结论：临床出现骨痛、发热、消瘦伴血象异常、血清碱性磷酸酶升高、骨扫描检查发现骨病灶时应怀疑骨髓转移癌，骨髓穿刺是简单而有效的确诊手段，及早给予抗肿瘤治疗可以延缓病情进展。     

以骨髓转移为首发表现的不明原发部位肿瘤的临床及形态学分析

目的：研究骨髓转移瘤的临床和形态学特点。方法：分析总结21例骨髓转移瘤的临床及形态学资料。结果：临床表现以骨痛、贫血、血小板减少常见,易误诊为多发性骨髓瘤和其他血液病,多数未查到原发肿瘤部位。结论：骨髓穿刺和活检对骨髓转移瘤,特别是原发肿瘤不明确者具有重要的诊断价值。     

乳腺癌骨髓转移的临床特征和预后分析

目的 探讨乳腺癌骨髓转移患者的临床特征、治疗和预后.方法 回顾性分析23例乳腺癌骨髓转移患者的临床资料,其中5例患者接受对症治疗,1例患者接受内分泌治疗,14例患者接受化疗序贯内分泌治疗,3例患者接受化疗.分析23例乳腺癌骨髓转移患者的临床特征,包括相关症状、血常规、肝肾功能、碱性磷酸酶(ALP)和乳酸脱氢酶(LDH),以及患者的治疗和生存情况等.结果 23例乳腺癌骨髓转移患者中,12例在内分泌维持治疗期出现血常规中一系或三系降低;7例因骨转移,常规行骨穿刺检查;2例化疗后血小板(PLT)持续降低;2例出现不规则发热.Luminal A型2例,Luminal B型15例,三阴性5例,HER2过表达型1例.23例乳腺癌患者诊断骨髓转移时均伴有其他部位转移:骨23例,区域或远端淋巴结转移8例,肝和肺各7例,脑、胸膜和皮下各2例,对侧乳腺、卵巢和脑膜各1例.15例患者不同程度的贫血,10例患者不同程度的PLT下降,21例患者不同程度的LDH升高.23例乳腺癌骨髓转移患者的中位总生存期(OS)为0.92年.接受化疗的患者中位OS为1.78年,明显长于未接受化疗患者的0.08年,差异有统计学意义(χ2=23.427,P<0.01).多因素分析显示未接受化疗是乳腺癌骨髓转移预后的独立影响因素(P<0.05).结论 乳腺癌骨髓转移多见于Luminal B型,化疗可以明显改善患者的生存情况.     

胃癌骨髓转移的血液学特征和治疗方式探讨

目的 探讨胃癌骨髓转移患者的临床病理特征、治疗及预后.方法 回顾性分析9例胃癌骨髓转移患者的临床资料,总结其临床特点、诊断和治疗方法.结果 9例患者的年龄为18~68岁,中位年龄为51岁,病理均为低分化腺癌.患者均伴有其他部位转移,常见淋巴结和骨转移.骨痛、非感染性发热、红细胞和血小板二系下降、碱性磷酸酶和(或)乳酸脱氢酶不同程度升高、外周血涂片可见幼稚细胞是胃癌骨髓转移的常见表现.胃癌骨髓转移患者的中位生存期为34 d(11~266 d).结论 胃癌骨髓转移患者的预后差,熟悉胃癌骨髓转移的临床特点有利于早期诊断.     

衰竭期骨髓转移癌临床表现及其治疗对策

目的:探讨衰竭期骨髓转移癌（MCBM）的发病率、病史、临床表现、诊断要点和治疗方法。方法:对疑似病例行骨髓穿刺和（或）活检、PET-CT 检查,病理学确诊者中9 例行抢救性化疗联合最佳支持治疗（BSC）,另6 例仅给予BSC ,收集患者症状、体征、病史、体质状态评分（KPS 评分）、血常规、骨髓特点、合并症、缓解率、生存期等数据。结果:2 876 例患者中发现该病15例,临床表现为进行性加重的乏力,病史多不足3 个月,部分患者有实体瘤病史而另一部分患者疑似血液系统疾患而就诊,骨髓均增生低下有时可发现有分类不明的细胞或较为典型的转移瘤细胞,并有贫血,KPS 评分不足50分,14例伴血小板减少症,3 例合并弥散性血管内凝血（DIC）。 其中9 例接受了抢救性化疗及BSC ,临床受益率88.9%（8/9）,生存期20天至5 年7 个月;而仅接受BSC 者生存期仅为20天至3 个月。结论:衰竭期骨髓转移癌临床罕见,起病隐匿,病史多不足3 个月,临床表现为不明原因并进行性加重的贫血和血小板减少症,诊断亦较为困难,骨髓检查常显示骨髓增生低下有时可发现有分类不明的细胞或较为典型的转移瘤细胞,该病的治疗国内外尚无成功的经验和方法,减量的抢救性化疗联合BSC 可能有效,生存期明显延长,打破了该期患者不宜化疗的传统观念。      

多发性骨髓瘤肾损害10例临床分析

目的 :探讨多发性骨髓瘤 (multiplemyeloma ,MM)肾损害的误漏诊原因并提出避免误漏诊的要点。方法 :对 1989年 6月～ 1999年 6月住院的MM患者中 10例并肾损害者进行临床分析。结果 :首发症状缺乏特异性 ,误诊率 80 %。结论 :对于有原因不明的贫血、骨痛、蛋白尿、高球蛋白血症和骨折 ,应及时进行本周氏蛋白、免疫球蛋白及免疫电泳测定 ,多部位的骨髓穿刺和骨X线摄片 ,避免误漏诊。     

新辅助化疗对乳腺癌骨髓微转移的影响

目的探讨乳腺癌骨髓微转移的临床特点及新辅助化疗对骨髓微转移的影响。方法手术治疗的乳腺癌患者100例,采用免疫组化SP法,用EMA,CK19单克隆抗体检测其骨髓微转移情况,分析其临床特点,并以骨髓微转移为指标,评价新辅助化疗对阳性患者的影响。结果100例中,检出骨髓微转移31例,阳性率为31.0%。临床Ⅲ期患者骨髓微转移率明显高于Ⅰ～Ⅱ期患者,阳性患者接受新辅助化疗后,转阴率达67.7%。结论乳腺癌是1种全身性疾病,即使在临床早期也有相当比例微转移,新辅助化疗对抑制骨髓微转移有效,可以指导化疗方案的选择,并可能对预防术后复发和转移起重要作用。     

骨髓坏死6例临床分析

目的:探讨骨髓坏死(BMN)的原发病、发病机理、临床特点及预后。方法:对6例骨髓坏死的临床资料进行分析。结果:6例BMN均以骨髓坏死为首要表现,以骨痛和发热为主要表现。1例原发病不明,其余5例均为恶性疾病,其中急性粒单核细胞白血病1例,急性淋巴细胞白血病2例,骨髓转移瘤2例。2例经积极治疗原发病取得一定疗效。结论:骨髓坏死是一种罕见的临床综合征,诊断难度大,预后差,应积极治疗原发病。     

多发性骨髓瘤肾损害10例临床分析

目的：探讨多发性骨髓瘤（multiple myeloma,MM)肾损害的误漏诊原因并提出避免误漏诊的要点。方法：对1989年6月－1999年6月住院的MM患者中10例并肾损害者进行临床分析。结果：首发症状缺乏特异性，误诊率80％，结论：对于有原因不明的贫血，骨痛，蛋白尿，高球蛋白血症和骨折，应及时进行本周氏蛋白，免疫球蛋白及免疫电泳测定，多部位的骨髓穿刺和骨X线摄片，避免误漏诊。     

Bone marrow necrosis in a patient with metastatic breast cancer in chemotherapy with chlorambucil, methotrexate and prednisone

In this case report the clinical course of a female patient with metastatic breast cancer receiving a mild cytostatic regimen with chlorambucil, methotrexate and prednisone is described. She developed an unusual clinico-pathological syndrome with pancytopenia, fever and bone pain resulting from a bone marrow necrosis. The clinical course illustrates the great diagnostic difficulties and the potential benefit from rapid identification of this prognostically very poor event. Leading symptoms such as fever, bone pain, pancytopenia, an increase in the sedimentation rate, in lactate dehydrogenase and alkaline phosphatase in serum are often misinterpretated as tumor progression with bone or hepatic metastases and bone marrow carcinomatosis. An iliac crest aspirate and biopsy detects the diagnosis of a marrow necrosis. These symptoms should be kept in mind in order to avoid a diagnostic pitfall resulting from a misinterpretation of the morphological picture as necrotic metastasis in bone marrow or as an artefact. It is assumed that, in addition to the underlying malignant disease, cytostatic therapy with chlorambucil, methotrexate and prednisone triggers this event.     

Thrombotic thrombocytopenic purpura associated with bone marrow metastasis and secondary myelofibrosis in cancer

To examine the relationship between cancer and development of thrombotic microangiopathy (TM), the medical records of patients with known TM were examined in one institution from January 1981 to December 2002. Nine out of 93 patients with the established diagnosis of TM had active cancer. All nine of those patients had thrombotic thrombocytopenic purpura (TTP). Among those patients, two patients received chemotherapy prior to the development of TTP. Six of the seven patients who received no chemotherapy had extensive bone marrow metastasis and secondary myelofibrosis. There were two patients each with breast cancer, lung cancer, and stomach cancer. Severe anemia and thrombocytopenia with leukoerythroblastosis were prominent clinical features in all six patients. Four patients had neurological (mental) changes and three developed fever, but none had significant renal dysfunction. Upon establishing the diagnosis of TTP, four patients were treated with exchange plasmapheresis (EP) and two patients were treated with chemotherapy because there were no neurological changes. Three patients achieved complete remission of TTP, one with EP alone and two with chemotherapy. The one patient who achieved remission with EP alone was later treated with chemotherapy and survived for 2 1/2 years. The other three patients treated with EP alone died within 2 months after the diagnosis of TTP. Since TTP occurred in association with bone marrow metastasis and myelofibrosis in six patients among seven chemotherapy-untreated cancer patients, this marrow change was considered to be the possible cause of the development of TTP. It is recommended that all cancer patients with unexplained anemia and thrombocytopenia be evaluated for the coexistence of bone marrow metastasis and TTP.     

乳腺癌骨髓转移特点及治疗方法探讨

目的探讨乳腺癌患者骨髓转移临床表现的特殊性、转移规律及治疗策略。方法回顾性分析62例女性乳腺癌骨髓转移患者的临床及随访资料,包括乳腺癌骨髓转移发生时间、激素受体状况等及不同治疗策略对预后的影响。24例联合化疗,25例单药化疗,13例未接受化疗。生存率用Kaplan—Meier方法计算,用Log—rank方法进行生存曲线比较。结果62例患者中位年龄39岁（30～71岁）,中位病程21个月（1～49个月）。雌激素受体（ER）和（或）孕激素受体（PR）阳性患者30例（48．4％）,阴性19例（30．6％）。发热14例（22．6％）和（或）血象的一系或三系降低34例（62．9％）是乳腺癌骨髓转移的常见表现。联合化疗和单药化疗中位生存期分别为10个月和16个月（QPH=7．38,P=0．0335）,未接受化疗者中位生存期仅1个月。骨髓转移发生偏晚,一般有多处转移尤其是骨转移的背景。结论骨髓穿刺有利于早期发现骨髓转移;骨髓转移晚期体质较弱,单药化疗可能是有效的治疗策略之一,与联合化疗组的患者相比具有生存优势。     

Nasopharyngeal carcinoma with bone marrow metastasis

Five of 23 patients with recurrent nasopharyngeal carcinoma (NPC) were diagnosed to have bone marrow metastasis. They all had advanced local-regional disease, and were treated with neoadjuvant chemotherapy and definitive radiotherapy after the initial diagnosis. Bone marrow metastasis developed 4-24 months later. The clinical features were anemia (5 of 5), leukopenia (3 of 5), thrombocytopenia (4 of 5), sepsis (3 of 5), tenderness of the sternum (3 of 5), and fever (4 of 5). Patients frequently had elevation of serum lactic dehydrogenase (LDH), alkaline phosphatase (ALK-P), and IgG and IgA antibody titers to Epstein-Barr viral capsid antigen when bone marrow involvement was diagnosed. However, clinical manifestations and laboratory tests were not specific. It is important that three patients had normal bone scans. All five patients had a rapid downhill course; four patients died within 23 days, and the fifth 3 months after the diagnosis of bone marrow metastasis. We concluded that bone marrow was a common metastatic site in NPC patients. Bone marrow metastasis adversely affected patients' survival and required a high index of suspicion for diagnosis. We suggested that bone marrow biopsy should be considered as a routine staging procedure in NPC patients and indicated especially when patients presented with abnormal blood counts, sepsis, bone pain, or tenderness of the sternum. It may be positive in the face of a normal bone scan.     

Retrospective evaluation of the safety of pamidronate administration at the dose of 90 mg/day/month in Japanese breast cancer patients with bone metastasis

The Japanese Ministry of Health, Labor and Welfare approved the use of pamidronate in November 2004 at a dose of 90 mg/day/month especially for Japanese breast cancer patients with lytic bone metastasis. But no safety data have been shown for these Japanese patients thus far. Therefore, we evaluated the safety of pamidronate treatment for breast cancer patients with bone metastasis at the dose of 90 mg/day/month since July 1, 2004 until Dec 31, 2004, retrospectively, in our institute, the Shikoku Cancer Center. No definite severe side effects were detected in these patients, including renal dysfunction and thrombocytopenia. In addition, there were no definite alternations in hemoglobin titers, platelet counts, BUN, serum creatinine and potassium levels in one month and 3 months after beginning the treatment except for significant alternations in RBC counts in one month and in the serum calcium level 3 months later (p=0.03). Improvements of clinical symptoms or data due to bone metastases, i.e., bone pain or elevation of tumor markers, were obtained in 91% of patients. As a conclusion, pamidronate administration at the dose of 90 mg/day/month was safe for Japanese breast cancer patients with bone metastasis.     

Anti-RANKL antibody for treatment of patients with bone metastasis from breast cancer

Breast cancer is known to be associated with a high incidence of bone metastases. Recent advances in treatment for breast cancer have improved patient prognosis, including those with bone metastasis, highlighting the importance of treating bone metastasis to reduce incidence of skeletal complications and to improve patients' QOL. Currently, bisphosphonates(BP), which are recommended by domestic and international clinical practice guidelines, are commonly used for the treatment of bone metastasis. However, the outcomes of BP therapy leave room for improvement in regard to their efficacy, safety, and convenience. Prior studies have indicated that RANK ligand(RANKL), a cytokine mainly expressed in osteoblasts and bone marrow stromal cells, plays an important role in bone resorption by osteoclasts, which are key mediators in the formation and progression of bone metastasis. Denosumab is a fully human monoclonal anti-RANKL antibody which suppresses differentiation, activation, and survival of osteoclasts by inhibiting the binding of RANKL to its receptor, RANK. In a phase III clinical trial, denosumab significantly decreased the time-to-first and time-to-first-and-subsequent skeletal related events(SRE), compared with zoledronic acid in advanced breast cancer patients with bone metastases. Further more, denosumab was more effective than zoledronic acid in preventing the progression of bone pain and maintaining patients QOL. In the future, treatment of bone metastases for breast cancer patients is expected to evolve further with the introduction of denosumab, which is conveniently administered by subcutaneous injection.     

Clinical and radiologic characteristics of bone metastases in breast cancer

Metastatic bone disease was evaluated in 380 consecutive patients at the time of first metastasis of breast cancer. Studies included radiographic examination, radionuclide examination, and bone marrow biopsy. Radiographs of the skeleton demonstrated metastases in 120 patients (32%), and in 40 of these patients (13%) the bone was the only site of metastases. The diagnostic efficiency was 82% for bone scanning, 80% for pain evaluation, 59% for s-calcium analyses, and 77% for s-alkaline phosphatase analyses. Bone scanning is an effective method to exclude metastatic bone disease (sensitivity: 96%). A positive scan, however, requires radiologic confirmation (specificity: 66%). Bone scanning of the skeleton should be the initial staging procedure in all patients with recurrent breast cancer with no clinical or biochemical signs of bone metastases. Bilateral posterior iliac crest bone marrow aspirations and bone biopsies were positive in 82 out of the 320 patients who underwent biopsy. The frequency of positive bone marrow biopsy was significantly correlated with both the site of radiographic metastases and with the total number of involved bone regions. Routine bone marrow biopsies are indicated in patients with a positive bone scan, but a negative x-ray examination. In these cases biopsies should be performed bilaterally.