恶性淋巴瘤心脏侵犯的临床病理研究

已有报道恶性淋巴瘤心脏转移,占整个恶性肿瘤的9%以上,而死于淋巴瘤的病人有20%发现心脏侵犯。由于心肌被肿瘤浸润的程度,心脏功能障碍的临床症状和体征可能不典型,而且心脏受侵犯在死前不易被发现。因此,对恶性淋巴瘤心脏侵犯的知识,大部分从尸体解剖中得来。本文报道1960～1980年150例经尸解的何杰金氏病(53例)或非何杰金氏淋巴瘤(97例),其中13例(8.7%)有淋巴瘤心脏或心包壁侵犯的组织学证据。     

淋巴瘤与白血病患者血清铁蛋白水平及其临床意义

1999年 4月～ 2 0 0 1年 4月 ,我们对 35例淋巴瘤白血病患者和 84例白血病患者进行血清铁蛋白测定 ,以探讨其在治疗过程中的变化及其临床意义。现报告如下。临床资料 :35例淋巴瘤患者中 ,男 2 5例、女 10例 ,年龄 13～76岁。其中非何杰金氏淋巴瘤 (NHL) 2 6例 ,何杰金氏淋巴瘤(HD) 9例 ;进展期 2 1例 ,缓解期 14例 ,均符合 Annbor分类法。84例白血病中 ,男 4 8例、女 36例 ,年龄 2～ 6 4岁。其中 M2 4例 ,M32 4例 ,M4 3例 ,M52 1例 ;CGL6例 ,AL L2 6例 (L1 型 15例 ,L2 型11例 ) ;未缓解 4 8例 ,缓解期 36例。以上患者的诊断均符合…     

用DIFA 检测肿瘤患者的弓形虫抗体

目的: 为了解湖北肿瘤患者弓形虫感染概况并探索新技术直接免疫固相凝集试验(DIFA)等3项试验联合筛选诊断弓形虫感染的意义。方法: 使用DIFA检测100 例肿瘤患者的弓形虫IgG 抗体, 阳性者用IgG-IFAT 复查, 再用Toxo-IgG/IgA/IgM-ISAGA 检测。结果: DIFA 检测阳性率为12% (12/100), IgG-IFAT 检测符合率为100%; IgA 可疑1 例; IgM 抗体阳性4 例, 可疑1 例, 其中2 例提示为活动性感染。合并弓形虫感染的12 例分布于肺癌、非何杰金氏淋巴瘤和乳腺癌患者中, 其感染率分别为受检人数的22.2% (6/27)、19.3% (5/26) 及7.1% (1/14)。结论: DIFA 的敏感性和特异性均较佳, 3 种方法的联合应用适宜作弓形虫感染的常规筛选诊断。提示免疫功能降低的肿瘤患者, 特别是肺癌和非何杰金氏淋巴瘤患者容易感染弓形虫病或促使潜伏的弓形虫病活动。     

恶性血液病浆膜腔积液12例临床及细胞学分析

我科1987年3月至1990年10月共收治恶性血液病合并浆膜腔积液患者12例,现将其临床及细胞学检查报道如下.1 临床资料本组患者男7例,女5例,年龄26～66岁.原发病包括急性淋巴细胞性白血病(ALL)2例,急性早幼粒细胞白血病(APL)1例,慢性粒细胞白血病(CML)急变3例,非何杰金淋巴瘤(NHL)3例(包括NHL 白血病期2例),何杰金氏病(HD)1例,恶     

恶性胸腔积液治疗指南摘要

发病率、病因与发病机制恶性胸腔积液 (MPE)在肿瘤患者中较为常见。因恶性肿瘤而死亡的患者中 ,15 %发生 MPE。MPE在渗出性积液中 4 2 %至 77%是由恶性疾病引起。几乎所有肿瘤均可侵犯胸膜腔 ,肺癌最常见 ,约占 MPE的1/ 3。乳癌居第二位。淋巴瘤 ,包括何杰金氏病和非何杰金氏淋巴瘤 ,卵巢和胃肠道的肿瘤较少引起 MPE。约 5 %～ 10 %的MPE找不到原发肿瘤。胸膜间皮瘤的发病与地域有关。尸检显示 ,多数胸膜腔转移来源于肿瘤栓子种植于脏层胸膜 ,其次种植于壁层胸膜。其他可能的转移机制包括肿瘤直接侵犯 (肺癌、乳癌、胸壁恶性肿瘤 )…     

小儿恶性淋巴瘤的病理与临床特点

为了探讨小儿ML的病理与临床特点,我们根据1985年成都会议关于非何杰金淋巴瘤(NHL)工作分类方案及Rye会议关于何杰金氏病(HD)分型方法,对258例小儿恶性淋巴瘤进行了回顾性研究。一、材料与方法:资料为山东医科大学病     

副肿瘤肾综合征

副肿瘤肾综合征(Paraneoplastic renal syndrome)是指肿瘤伴有肾脏病变而非肿瘤的肾转移,无肾静脉血栓形成和肾淀粉样变性者。Lee谓癌症患者伴有肾病综合征(NS)并非巧合。并谓恶性肿瘤中11%患者有肾病综合征。Plager复习1,643例NS而有恶性肿瘤者6例,600例何杰金氏病者中发生NS者4例。1977年Eagen等报告171例肿瘤并发肾小球病变,其中79例属淋巴系统恶性肿瘤,包括何杰金氏病63例,尚有非何杰金性恶性淋巴瘤,白血病,多发性骨髓瘤,及巨球蛋白血症;171例中67例系各种癌症,包括肺癌28例,结肠直肠癌7例,其他如胃癌,肾,宫颈,乳房,甲状     

恶性淋巴瘤患儿糖皮质激素受体测定的临床意义

本文应用放射配基结合分析法对12例恶性淋巴瘤患儿及41例正常小儿完整淋巴细胞进行糖皮质激素受体(GCR)测定。探讨了GCR水平与化疗效果及疾病预后的关系。结果提示非何杰金氏淋巴瘤(NHL)患儿淋巴细胞GCR数量可用于指导化疗及预测预后,并且NHL患儿GCR水平与病理类型有关。     

淋巴瘤患者治疗前后的甲状腺激素水平变化

1992～ 1997年 ,我们收治 2 0例淋巴瘤患者 ,并在其治疗前后进行血清 T3 、T4 检测。现报告如下。临床资料 :本组 (观察组 ) 2 0例 ,男 14例 ,女 6例 ;年龄 8～ 6 3岁 ,平均 35.5岁。其中何杰金氏病 (HD) 3例 ,非何杰金氏淋巴瘤 (NHL) 17例。临床分期 : 期 4例 , 期 7例 , 期 9例。患者确诊后均采用 COP方案治疗 (环磷酰胺 0 .4 g)长春新碱 2 mg,第 1、8、15天静滴 ;强的松 4 5mg口服 ,1天 3次。化疗 3周后 ,间歇 2周为 1疗程 )。另取对照组 2 0例 (均为健康查体者 ) ,其中男 8例 ,女 12例 ,年龄 17～ 6 0岁 ,平均 38.5岁。方法 :观察组…     

吡喃阿霉素治疗淋巴瘤100例临床观察

1997年 4月～ 2 0 0 0年 8月 ,我们应用吡喃阿霉素 (THP)治疗 10 0例淋巴瘤患者 ,取得了较好的临床效果。现报告如下。一般资料 :10 0例淋巴瘤均经活检或细胞学确诊。男 76例 ,女 2 4例 ;年龄 12～ 75岁 ,平均 42岁。初治 6 6例 ,复治 34例。何杰金氏病 (HD) 2 2例 ,其中 期 10例、 期 5例、 期 7例 ;非何杰金氏淋巴瘤 (NHL) 78例 ,其中 期 11例、 期 2 3例、 期 2 4例、 期 18例。治疗方法 :THP、环磷酰胺 (CTX)、长春新碱 (VCR)、强的松 (Pred)组成 CHOP方案。THP30～ 40 mg/m2、CTX40 0～6 0 0 m g/m2 、 VCR1.4m g/m2 静…     

Analysis of factors affecting hematopoietic recovery after autologous bone marrow transplantation for lymphoma

Thirty patients with relapsed lymphoma (14 Hodgkin's disease, 16 non-Hodgkin's lymphoma) who underwent autologous bone marrow transplantation (ABMT) were assessed for the effect of different parameters on the rate of hematologic recovery post-ABMT. There was no correlation between nucleated cells count or numbers of CFU-GM or BFU-E in the infused marrow on either neutrophil or platelet recovery times. Patients with lymphoma who received more salvage chemotherapy (greater than six cycles) prior to marrow harvest took significantly longer to recover neutrophils to greater than 0.5 x 10(9)/l (p = 0.0229) and platelets to greater than 20 x 10(9)/l (p = 0.0007) than patients who received less than five cycles of salvage chemotherapy prior to harvest. There was no significant correlation between underlying disease, use of total body irradiation or status of cytomegalovirus serology and recovery times post-ABMT. The results suggest that extensive salvage chemotherapy may result in considerable stem cell damage to marrow, and that potential ABMT candidates with lymphoma should undergo harvest of tumor-free bone marrow as soon as possible following first relapse.     

Intensive cytotoxic therapy followed by autologous bone marrow transplantation for non-Hodgkin's lymphoma of high-grade malignancy

Fourteen patients with non-Hodgkin's lymphoma (NHL) of high-grade malignancy were treated with cyclophosphamide and total body irradiation followed by autologous bone marrow transplantation (ABMT). All patients were pretreated with conventional chemotherapy. Three of four patients with drug-resistant disease achieved complete remission (CR), but relapse occurred within six months. Four patients in partial remission (PR) achieved CR; one died because of sepsis, two relapsed within six months, and one is still in CR 28+ months later. Six were treated in CR, five in first CR, and one in second CR. From these six patients (who received this treatment as consolidation therapy), five are in unmaintained CR seven to 31+ months after ABMT (one patient died of a secondary illness). There were two therapy-related deaths, both in patients with a poor clinical condition. Toxicity of this treatment was mild for those receiving transplants who were in better condition. These preliminary results suggest that intensive cytoreductive therapy followed by ABMT may improve disease-free survival in patients in NHL of high-grade malignancy in CR.     

Autologous bone marrow transplantation in 69 patients with a history of low-grade B-cell non-Hodgkin's lymphoma

Sixty-nine patients with a history of low-grade B-cell non-Hodgkin's lymphoma (NHL) in sensitive relapse or incomplete first remission underwent high-dose chemoradiotherapy and anti-B-cell monoclonal antibody (MoAb)-treated autologous bone marrow transplantation (ABMT). At ABMT, 51 patients had low-grade histology and 18 patients had a history of low-grade NHL that had undergone histologic transformation to a higher-grade NHL. Before ABMT, only 20 of the 51 low-grade patients and 10 of the 18 patients with transformed histologies were in complete remission. Moreover, at the time of marrow harvest, 24 of the low-grade and eight of the transformed histology patients had histologic evidence of lymphoma cells infiltrating the marrow. Following high-dose therapy, only one acute, in-hospital death was observed. There was no significant difference in the disease-free survival (DFS) between patients with low-grade and patients with transformed histologies. Among patients with low-grade NHL, the patients in complete remission before ABMT experienced significantly longer DFS than those in partial remission (P less than .05). This preliminary study suggests that some patients with relapsed low-grade NHL may experience prolonged DFS following high-dose ablative therapy.     

Significance of detection of occult non-Hodgkin's lymphoma in histologically uninvolved bone marrow by a culture technique.

Prolonged disease-free survival of patients with recurrent or resistant non-Hodgkin's lymphoma (NHL) has been achieved with high-dose therapy followed by autologous bone marrow transplantation (ABMT). A concern with the use of ABMT is that the marrow that is reinfused may contain undetected NHL cells with the potential to reestablish metastatic disease in the recipient. Using a culture technique that is sensitive for detecting occult lymphoma cells in BM, we analyzed histologically normal marrow harvests from 59 consecutive patients with intermediate- or high-grade NHL who were candidates for high-dose therapy and ABMT. The culture results indicated that 22 of the patients had occult lymphoma in their marrow. Forty-three patients underwent high-dose therapy followed by ABMT. Twenty-four achieved a complete clinical remission. Those with occult lymphoma in their harvests (11 patients) continued to relapse for up to 3 years, whereas no relapses were observed beyond 8 months in 13 patients receiving marrow that did not contain detectable lymphoma cells using the culture technique. The relapses in the patients who achieved a complete remission occurred at sites of prior bulky disease rather than at new sites, suggesting that the ability to detect occult lymphoma cells in marrow is a marker of biologic aggressiveness and/or resistance to therapy, or that the reinfused cells could only grow in previously involved sites. The detection of lymphoma cells in marrow used for ABMT is an important adverse prognostic factor, and appears to be independent of other clinical predictors of outcome such as sensitivity or resistance of disease to prior chemotherapy.     

Induction of cutaneous graft-versus-host disease by administration of cyclosporine to patients undergoing autologous bone marrow transplantation for acute myeloid leukemia.

Cutaneous graft-versus-host disease (GVHD) has been reported after administration of cyclosporine (CSP) after autologous bone marrow transplantation (ABMT) with unpurged marrow in patients with lymphoma. To determine whether GVHD can be induced after ABMT with chemopurged marrow in acute myeloid leukemia (AML), we administered intravenous CSP for 28 days (beginning on the day of ABMT) to 19 patients with AML (12 in first remission [CR1], six in CR2, and one in CR3) who received busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg) and ABMT with 4-hydroperoxycyclophosphamide (4HC)-treated marrow. In this dose-escalation trial, CSP daily doses were 1 mg/kg in seven patients, 2.5 mg/kg in eight patients, or 3.75 mg/kg in four patients. Skin biopsies were obtained weekly after ABMT or on appearance of rash and were graded for GVH changes. Overall, 15 of 19 patients (79%) had cutaneous histopathologic grade 2 GVHD at a median of 33 days (range, 14 to 49) after ABMT; in 10, cutaneous manifestations were present at time of positive biopsy. The frequency, time to onset, and duration of GVHD were similar among the three CSP dosage groups. No patients had hepatic or gastrointestinal dysfunction attributable to GVHD or required specific therapy for GVHD. Positive biopsies for GVHD were seen in seven of eight patients who received full-course, full-dose CSP and 8 of 11 patients who had CSP discontinued or dosage reduced because of renal insufficiency. Three patients (one with positive biopsy) died with ABMT-related complications. Seven patients (four CR1, three CR2) relapsed with AML at a median of 411 days (range, 178 to 549) after ABMT; six of seven had positive biopsies for cutaneous GVHD. Nine patients (seven CR1, one CR2, and one CR3) are alive without relapse at a median of 501+ days (range, 252+ to 811+) after ABMT; eight of nine had cutaneous GVHD. Short-course CSP can induce autologous GVHD in recipients of chemopurged marrow autografts for AML, but randomized prospective trials are needed to determine whether this immunologic reaction is associated with alterations in leukemic relapse rate and disease-free survival after ABMT in AML.     

Eradication of polymerase chain reaction detectable immunoglobulin gene rearrangement in non-Hodgkin's lymphoma is associated with decreased relapse after autologous bone marrow transplantation

In B-cell non-Hodgkin's lymphoma (NHL), as in other B-cell malignancies, clonal rearrangement of the third complementarity determining region (CDR III) of the immunoglobulin heavy chain gene (IgH) provides a useful marker for the detection of minimal residual disease (MRD) after treatment. To determine the clinical utility of IgH polymerase chain reaction (PCR), we analyzed peripheral blood (PB) and bone marrow (BM) samples from 25 patients with NHL with no PCR detectable chromosomal rearrangement who have undergone autologous bone marrow transplantation (ABMT). Patients with histologic bone marrow infiltration at the time of bone marrow harvest were selected for study since this provided us with diagnostic tissue samples. As an initial strategy DNA was amplified using consensus variable (VH) and joining (JH) region primers. In those cases failing to amplify using consensus region primers, PCR was performed using a panel of VH family-specific framework region 1 (FR1) primers. The clonal products were directly sequenced. From the V-N-D region nucleotide sequences, clone specific probes were constructed and used for subsequent detection of MRD. A clonal PCR product could be PCR amplified and directly sequenced in 18 (72%, 90% confidence intervals 54%-86%) of these 25 patients, 8 with diffuse and 10 with follicular NHL. Eight of these 18 patients have relapsed after ABMT. All had detectable lymphoma cells before relapse and the sequence of the CDR III region at the time of relapse was identical to that obtained at the time of ABMT. All 10 patients who remain in complete remission from 18 to 36 months after ABMT had eradication of PCR detectable lymphoma cells after ABMT, although in three patients PCR detectable MRD was detected early after ABMT. We conclude that sequencing and the use of patient specific IgH CDR III oligonucleotides probes provides a simple and highly reliable method to determine the specificity of the IgH PCR technique. The clinical utility of this technique is demonstrated by the finding that eradication of PCR detectable lymphoma cells in these patients is associated with decreased relapse after ABMT (P = .0002).     

High-dose vincristine, fractionated total-body irradiation and cyclophosphamide as conditioning regimen in allogeneic and autologous bone marrow transplantation for childhood acute lymphoblastic leukaemia in second remission: a 7-year Italian multicentre study

We investigated the feasibility and efficacy of high-dose vincristine (4 mg/m² over 4 d) combined with fractionated total body irradiation (F-TBI) (200 cGyx2 over 3 d) and cyclophosphamide (60 mg/kg for 2 d) as a preparative regimen in allogeneic (AlloBMT) and autologous (ABMT) bone marrow transplantation for 75 consecutive children (median age at transplant 8-5 years) with acute lymphoblastic leukaemia in second complete remission (CR). Median duration of first CR was 26 and 25 months in the AlloBMT and ABMT group, respectively. Of the 46 patients who underwent AlloBMT, 33 had isolated or combined marrow relapse and 13 isolated extramedullary relapse. Of the 29 patients given ABMT, 23 had preBMT isolated or combined marrow relapse and six isolated extramedullary relapse. 44/75 patients are alive and in CR at a median follow-up of 35 months (range 10-90 months). Seven children given AlloBMT (15.8%) and two given ABMT (7%) died from transplant-related causes. No major early organ toxicity, including vincristine-related toxicity, was recorded. The overall 3-year EFS estimate (95% CL) was 53.8% (42-66%): in particular, 58.2% (40-76%) for AlloBMT and 27.6% (9-46%) for ABMT patients who experienced a marrow relapse before transplant. The overall 3-year relapse rate estimate (95% CL) was 39.2% (27-51%): in particular, 30.1% (12-49%) in the AlloBMT group and 72% (54-91%) in the ABMT group ( P < 0.01) who presented a preBMT isolated or combined marrow relapse. We conclude that the conditioning regimen with high-dose vincristine combined with cyclophosphamide and F-TBI is feasible and promising, although its therapeutic advantage should be tested in larger series of patients enrolled in randomized studies.     

Allogeneic peripheral blood stem cell transplantation using a fludarabine-based low intensity conditioning regimen for malignant lymphoma

Relapse is a serious complication following high-dose therapy and autologous bone marrow transplantation (ABMT) for malignant lymphoma (ML). Allogeneic transplantation (alloSCT) is a therapeutic option. However, it is associated with a high incidence of transplant-related organ toxicity and mortality. We recently reported fast engraftment and minimal transplant-related toxicity, using fludarabine-based conditioning with reduced amounts of chemotoxic drugs prior to alloSCT. We now present our experience with 23 heavily treated high risk ML patients who underwent matched alloSCT following the same low intensity conditioning. The patients (20 male, three female) were aged 13-63 years. Nineteen had NHL and four HD (resistant disease 12, partial remission 11). Five were post ABMT. Twenty-two patients had fully matched sibling donors, and one a fully matched unrelated donor. Engraftment was fast. There was no rejection or non-engraftment. Organ toxicity was moderate with no liver or renal toxicity >grade II. Four patients developed >grade II graft-versus-host disease (GVHD). Seven patients died - four of grade III-IV GVHD and severe infections, two of bacterial sepsis, one of pulmonary failure. Ten patients are alive after 22.5 (15-37) months. Survival and disease-free survival at 37 months are both 40%. Probability of relapse is 26%. These encouraging results suggest that alloSCT following fludarabine-based low intensity conditioning in high-risk patients merits further evaluation. Bone Marrow Transplantation (2000).     

Long-term observations of autoimmune-prone mice treated for autoimmune disease by allogeneic bone marrow transplantation.

Long-term effects of allogeneic bone marrow transplantation (ABMT) across major histocompatibility complex barriers were studied in (NZB x NZW)F1 (B/W), BXSB, and MRL/Mr-lpr-lpr (MRL/lpr) mice with established autoimmune disease at the time of ABMT. In the BXSB or B/W mice, ABMT cured all aspects of autoimmune disease. Glomerular damage, revealed by histological study was dramatically improved. Serological abnormalities and immunologic functions also were normalized. Correction of autoimmune disease and advanced renal disease in BXSB and B/W mice regularly lasted greater than 5-6 mo and even 1 yr after ABMT. In the MRL/lpr mice, however, autoimmune and renal disease at first improved but then recurred after ABMT, apparently because of intolerance of mice for high doses of irradiation and a high degree of resistance of recipient stem cells to irradiation. In this model, H-2 typing revealed that by the time of relapse, immunocompetent cells of the chimeric mice had been replaced by host (MRL/lpr; H-2k) cells. B220+ Ly-1+ cells, present in increased numbers in untreated MRL/lpr mice, initially returned to normal levels after ABMT but then reappeared in the MRL/lpr mice that had received marrow from donors having few such lymphocytes. Thus, our results show that MRL/lpr mice possess abnormal radioresistant stem cells and provide impressive evidence that the origin of autoimmune diseases in this strain, as in the several other strains studied, residues in abnormalities present in stem cells.     

Long-term follow-up of autologous bone marrow transplantation in patients with relapsed follicular lymphoma.

We report the results of high-dose chemoradiotherapy and anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation (ABMT) in patients with relapsed indolent follicular lymphoma. Between March 1985 and May 1995, 153 patients underwent ABMT using a uniform ablative regimen with cyclophosphamide and total body irradiation and bone marrow (BM) purging. All patients received multiple chemotherapy regimens before ABMT. At BM harvest, only 30% of patients were in complete remission, and overt BM infiltration was present in 47%. The disease-free survival (DFS) and overall survival (OS) are estimated to be 42% and 66% at 8 years, respectively. Patients whose BM was negative by polymerase chain reaction (PCR) for bcl2/IgH rearrangement after purging experienced longer freedom from recurrence than those whose BM remained PCR positive (P <.0001). Continued PCR negativity in follow-up BM samples was also strongly predictive of continued complete remission (CR). The 12-year survival from diagnosis for these 153 patients is 69%. Considering that the median survival from diagnosis and first recurrence of patients with advanced follicular lymphoma are 8 and 5 years, respectively, our results provide evidence that myeloablative therapy and ABMT may prolong overall survival.