bcr/abl融合基因阳性急性淋巴细胞白血病的临床特点

目的总结bcr/abl融合基因阳性急性淋巴细胞白血病(ALL)患儿临床特点,探讨其治疗及预后的相关因素。方法对经巢式逆转录聚合酶链反应(RT-PCR)方法检测bcr/abl融合基因阳性ALL患儿临床表现、治疗、预后进行回顾性分析。结果bcr/abl融合基因阳性ALL患儿20例。中位年龄9岁,普通B细胞型ALL 19例(95%);治疗d33骨髓完全缓解率为66.7%,16例中7例复发(45%),持续缓解时间2年以上6例;5例接受造血干细胞移植(HSCT),均骨髓复发;6例存活患者中均为单纯化疗,bcr/abl融合基因已转阴。1例T细胞表型患儿于化疗缓解3个月骨髓复发,接受移植术后1个月骨髓再次复发。结论bcr/abl融合基因阳性ALL患儿化疗效果差,难缓解,复发率高,预后差,T细胞表型预后更差。部分对化疗敏感的患儿bcr/abl融合基因持续阴性。异基因HSCT复发率也较高。     

盐酸吉西他滨对K562细胞增殖、凋亡及bcr/abl mRNA表达的影响

目的 观察盐酸吉西他滨对K562细胞增殖、凋亡及bcr/abl基因表达的影响,探讨盐酸吉西他滨用于慢性粒细胞白血病急变期治疗的可行性. 方法 采用水溶性四甲基偶氮唑盐(MTT)比色法检测盐酸吉西他滨对K562细胞增殖的影响,采用凋亡的原位酶标记检测(TUNEL)法检测盐酸吉西他滨对K562细胞凋亡的影响,采用半定量RT-PCR技术检测盐酸吉西他滨作用于K562细胞后bcr/abl融合基因mRNA表达变化. 结果 0.1 mg/L、1.0 mg/L 、10.0 mg/L盐酸吉西他滨分别作用K562细胞12 h、24 h、48 h、72 h 后,K562细胞增殖受到抑制,抑制作用随质量浓度及时间增加而增强,但48 h和72 h比较无显著性差异,10.0 mg/L吉西他滨组作用K562细胞48 h抑制率达(29.3±0.008)%.吉西他滨组对K562细胞的抑制作用明显强于同质量浓度同时间的阿糖胞苷组,二者比较有显著性差异(P<0.01).TUNEL实验结果 显示10.0 mg/L吉西他滨作用于K562细胞48 h,凋亡率为15.3%,明显高于阿糖胞苷组 3.7%(P<0.05)和空白对照组2.0%(P<0.05).RT-PCR结果 显示10 mg/L吉西他滨作用48 h对K562细胞bcr/abl融合基因mRNA的表达有明显抑制作用,与同剂量阿糖胞苷组比较无显著性差异.结论 盐酸吉西他滨对K562细胞有一定的增殖抑制及促凋亡作用,且具有剂量和时间依赖性.10 mg/L吉西他滨能够明显下调慢性粒细胞白血病bcr/abl融合基因mRNA表达,有望联合应用于慢性粒细胞白血病急变期的治疗.     

Simultaneously occurring alopecia areata and Hodgkin's lymphoma: Complete remission of both diseases with MOPP/ABV chemotherapy

A 43-year-old man presented with simultaneously occurring alopecia areata and stage IIIB nodular sclerosing Hodgkin's disease. Systemic symptoms of Hodgkin's disease were present for 6 months, and rapidly developing patchy hair loss of the scalp was present for 2 weeks prior to presentation. The patient was treated with eight cycles of MOPP-ABV chemotherapy that resulted in complete remission of Hodgkin's disease. Four months after the completion of chemotherapy, the patient had normal hair regrowth with no evidence of alopecia areata. Alopecia areata may be an autoimmune disease and may respond to chemotherapy. © 1992 Wiley-Liss, Inc.     

Simultaneously occurring alopecia areata and Hodgkin's lymphoma: complete remission of both diseases with MOPP/ABV chemotherapy.

A 43-year-old man presented with simultaneously occurring alopecia areata and stage IIIB nodular sclerosing Hodgkin's disease. Systemic symptoms of Hodgkin's disease were present for 6 months, and rapidly developing patchy hair loss of the scalp was present for 2 weeks prior to presentation. The patient was treated with eight cycles of MOPP-ABV chemotherapy that resulted in complete remission of Hodgkin's-disease. Four months after the completion of chemotherapy, the patient had normal hair regrowth with no evidence of alopecia areata. Alopecia areata may be an autoimmune disease and may respond to chemotherapy.     

Small cell carcinoma of the pancreas in association with a choledochal cyst: immunohistochemical characterization and complete response to combination chemotherapy

Carcinomas arising in choledochal cysts are well recognized; however, small cell carcinomas have not been reported to arise in choledochal cysts. Extrapulmonary small cell carcinomas have been recognized as unique clinicopathologic entities for decades, and have been found arising in numerous sites. Recently there have been several reviews of the subject (Remick et al.: Medicine 66:457-71, 1987; Richardson and Weiland: Seminars in Oncology 9:484-496, 1982; Levenson et al.: Journal of the National Cancer Institute 67:607-612, 1981). Small cell carcinoma of the pancreas has only rarely been described (Reyes and Wang: Cancer 47:2500-2502, 1981; Corrin et al.: Cancer 31:1523-1527, 1973). These tumors must be distinguished from carcinoid tumors and islet cell tumors, which can often lead to histochemical and histologic confusion (Richardson and Weiland: Seminars in Oncology 9:484-496, 1982). Their response to therapy has not been well documented. We report here a small cell carcinoma of the pancreas that arose within a choledochal cyst and that had immunohistochemical characteristics supporting a neuroendocrine origin but that lacked evidence of islet cell differentiation. A complete response to chemotherapy is also described.     

Treatment of small cell lung cancer: intensive remission induction, radiation therapy, and maintenance chemotherapy

Forty-eight patients with small cell lung cancer were treated with an intensive therapy regimen which included induction chemotherapy with vincristine, adriamycin, procarbazine, and methotrexate. This was followed by radiation therapy given to areas of residual disease after restaging. Maintenance chemotherapy with cyclophosphamide, methotrexate, and procarbazine was then given to patients who had entered complete remission (CR). Fifteen out of 17 patients with limited disease (88%) achieved complete remission. Remission rates for patients with extrathoracic metastases were somewhat lower. Seven of 11 patients (64%) of patients with a single extrathoracic metastatic site achieved CR, while only 6/20 (30%) with multiple extrathoracic metastases went into remission. Median survival for patients who achieved complete remission was 17 months.     

Multiple mucosal neuromas,pheochromocytoma, medullary carcinoma of the thyroid and marfanoid body build with muscle wasting

The autosomal dominantly inherited syndrome of multiple mucosal neuromas, pheochromocytoma, medullary carcinoma of the thyroid and marfanoid body build with muscle wasting is conceived as one of hyperplasia and/or neoplasia of neural crest derivatives. The authors hypothesize that the syndrome may arise when a repressor gene for APUD (amine precursor utilization and decarboxylation) cells is defective.This investigation supported by U.S.P.H.S. Grants GM 15477 from the Pharmacology-Toxicology Program and GM 01998 from the Clinical Pharmacology Program of the NIGMS and U.S.P.H.S. DE 1770 Program Grant in Oral Pathology.     

Complete response to carboplatin, gemcitabine, and paclitaxel in a patient with advanced metastatic renal medullary carcinoma

Renal medullary carcinoma (RMC) is a rare and aggressive malignancy seen primarily in patients with sickle-cell trait. We report a complete response to carboplatin, paclitaxel, and gemcitabine in a patient with advanced metastatic RMC.     

Renal cell carcinoma in children: histology, immunohistochemistry, and follow-up of 10 cases.

Ten renal cell carcinomas in children under 15 years were investigated. The average age was 122.5 months and the girls predominated in our cases (7 girls, 3 boys). By using the classification of Thoenes et al., Pathol Res Pract 181: 125-143, 1986 a predominance of clear cell-eosinophilic tumor cell type and of the tubulopapillary growth pattern was found. Immunohistochemistry revealed a heterogeneity of cytokeratin expression. By using the monoclonal antibodies Cam 5.2 and KL 1, cytokeratins were found in 7 cases each. The other 4 cytokeratin antibodies used were less sensitive. The expression of cytokeratin 13 in 3 cases suggested a more complex histogenesis than assumed. Vimentin was found in 3 tumors, but an association to a higher grade (G) of malignancy was not found in these cases. One tumor expressed the Tamm-Horsfall-protein, which is predominantly found in the distal tubule of the normal kidney. In summary the results of immunohistochemistry characterized the great heterogeneity of these tumors. Follow-up information was available in 9 cases. All patients with G I- and G II-tumors were free of disease after an average time of 39.6 months (mean 27 months). Two of the 3 cases with G III-tumors died after 9 and 15 months, despite additional chemo- or radiotherapy. Therefore tumors of grade I and II of the Thoenes classification seem to have a good prognosis.     

Persistent elastase/proteinase inhibitor imbalance during prolonged ventilation of infants with bronchopulmonary dysplasia: evidence for the role of nosocomial infections

Acute imbalance between elastase and alpha-1-proteinase inhibitor (alpha 1Pi) may contribute to the development of bronchopulmonary dysplasia (BPD). The question of whether such an imbalance persists in BPD infants still requiring mechanical ventilation after 4 wk of life has not been previously addressed. We studied 14 infants still on mechanical ventilation at 4 wk of age: nine had BPD and five did not. Weekly (4 to 9 wk) serum and bronchoalveolar lavage (BAL) specimens were taken. alpha 1Pi and alpha-2-macroglobulin were measured in serum and BAL by immunoturbidimetric assay. BAL elastase activity was measured by cleavage of a synthetic substrate and expressed as ng of porcine pancreatic elastase equivalent. Infants with BPD had higher levels of serum alpha 1Pi and alpha-2-macroglobulin than those without BPD. In contrast, the corresponding BAL levels were either similar or even decreased (alpha 1Pi). Moreover, there was a 3-fold increase in elastase-1Pi imbalance expressed as the BAL ng of porcine pancreatic elastase equivalent/2 alpha 1Pi ratio. The role of nosocomial infections was evident in a subgroup of 11 infected BAL aspirates in BPD infants. In such cases we found a 3-fold increase in the BAL ng of porcine pancreatic elastase equivalent/alpha 1Pi ratio as compared to 35 noninfected BAL in BPD infants. These data suggest a persistent alveolitis with imbalance between elastase and proteinase inhibitors in prolonged severe BPD. Such an imbalance is, in part, explained by a local destruction and/or inactivation of alpha 1Pi. Our results also emphasize the increase in proteolysis with nosocomial pneumonia.     

Prolonged survival of a patient with sickle cell trait and metastatic renal medullary carcinoma

PURPOSE: The treatment and outcome of a patient with sickle cell trait and metastatic renal medullary carcinoma is described. PATIENT AND METHODS: A 12-year-old boy with sickle cell trait had metastatic renal medullary carcinoma. After surgical resection of the primary tumor, he received chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin. The carcinoma progressed after a 6-month period of stable disease. At that time, he received chemotherapy including ifosfamide, etoposide, carboplatin, and topotecan. RESULTS: The patient died of progressive disease 15 months from diagnosis. The patient's tumor in this report showed no progression while he was receiving methotrexate, vinblastine, doxorubicin, and cisplatin, but eventually became refractory to these and other cytotoxic agents. CONCLUSION: Renal medullary carcinoma is a highly chemotherapy-resistant tumor. Average survival after diagnosis is 15 weeks; the longest survival reported in the literature is 12 months from diagnosis. The patient in this report survived longer than the previously described patients before dying from progressive disease.     

Leukemic iris infiltration as the only site of relapse in a child with acute lymphoblastic leukemia: temporary remission with high-dose chemotherapy

A 12-year-old Caucasian boy developed leukemic hyphema with iris infiltration as the only relapse site during the third complete remission of his acute lymphoblastic leukemia. With high-dose methotrexate, high-dose cytosine-arabinoside plus teniposide, and a 5-week course of vincristine, prednisolone, and L-asparaginase, a complete remission could be achieved. Maintenance treatment was reinstituted for 1 year. However, after stopping the treatment, the iris infiltrate reappeared, and this time the eye was irradiated after chemotherapeutic reinduction. Seven months later, the boy remains in complete remission. The pathogenesis of leukemic iris infiltration is discussed briefly.     

Spindle cell sarcoma of the heart in childhood: light microscopic, ultrastructural, and immunohistochemical evidence for smooth muscle, endothelial, and fibroblastic differentiation

We describe the clinical presentation and pathological features of a cardiac sarcoma that occurred within the right atrial cavity of a 14-year-old boy. The patient presented with a 2-month history of increasingly severe heart failure. Tumor tissue obtained by biopsy showed light microscopic features of leiomyosarcoma. Immunohistochemical reactions and ultrastructural studies provided evidence of tumor cell differentiation along three cell lines--smooth muscle, fibroblastic, and endothelial--suggestive of origin from a multipotent subendothelial reserve cell. Postmortem examination disclosed a large necrotic tumor filling the right atrial chamber. Implants were present on the pericardium, but there were no other metastatic lesions. The difficulty of making a diagnosis of these rare neoplasms when the tumor is small and potentially curable results in a grim prognosis.     

Antibody production following immunization with diphtheria and tetanus toxoids in children receiving chemotherapy during remission of malignant disease

Twenty-seven children with various childhood malignancies who were in clinical remission and receiving maintenance chemotherapy were given diphtheria-pertussis-tetanus (DPT) immunizations. Antidiphtheria and antitetanus titers were drawn before and 1 month after immunization. Only one child had no antibody response to either antigen. Two other children failed to develop any detectable antitetanus antibody titer but did mount a normal antibody response to inactivated diphtheria antigen. In fact, most children made good antibody responses to both immunizing antigens, irrespective of the nature of their disease or of the treatment given. These results show that children receiving long-term chemotherapy should not be denied the protection afforded by immunization with nonliving vaccines.