Favorable outcome of patients with relapsed or refractory Hodgkin's disease treated with high-dose chemotherapy and stem cell rescue at the time of maximal response to conventional salvage therapy (Dexa-BEAM)

Background: Disease status before high-dose chemotherapy with autologous bone marrow transplantation (ABMT) or peripheral blood stem cell transplantation (PBSCT) is an important predictor of transplantation-related toxicity and event-free survival (EFS) for patients with relapsed or refractory Hodgkin's disease (HD). We performed a phase II study in patients with relapsed or refractory HD to evaluate the feasibility of four cycles of Dexa-BEAM followed by high-dose chemotherapy with ABMT or PBSCT.Patients and methods: Twenty-six patients (median age 30, range 20–40 years) were treated with 2–4 courses of dexamethasone, carmustine, etoposide, cytarabine and melphalan (Dexa-BEAM) as salvage chemotherapy in order to attain maximal response. Patients achieving complete response (CR) or partial response (PR) received high-dose chemotherapy with ABMT or PBSCT. The conditioning regimen used was CVB (cyclophosphamide, carmustine, etoposide).Results: Eighteen patients responded to Dexa-BEAM, resulting in a response rate of 69%. At the time of transplant 16 patients were in CR two patients in PR. At present 14 patients transplanted are in continous CR (median follow-up 40 months, range 14–60 months). Two patients with PR after four courses of Dexa-BEAM relapsed and died three months posttransplantation. Two patients with CR at the time of transplant relapsed after nine and 13 months respectively. Eight patients had rapid progressive disease after 2–4 cycles of Dexa-BEAM. One patient with progressive disease died in gram-negative sepsis after four cycles of Dexa-BEAM. There was no transplantation-related death.Conclusion: These data suggests the use of high-dose chemotherapy followed by stem cell transplantation at the time of maximal response.     

Low doses of rIL2 after autologous bone marrow transplantation induce a “prolonged” immunostimulation of NK compartment in high-grade non-Hodgkin's lymphomas

Ten patients with high-grade non-HodgKin's lymphoma (HG-NHL) entered a subcutaneous (s.c.) recombinant interleukin 2 (rIL2) trial within 2 months of undergoing autologous bone marrow transplantation (ABMT). Immunological studies, consisting in T- and natural killer (NK)-cell subset assessment, together with functional assays, such as NK activity and CD16-mediated redirected killing assay, were performed before therapy, after 2 weeks, and then monthly. Phenotypic analysis showed a significant increase (p=0.01) of CD16 and CD56 NK cells, from 12% to 28% and from 17% to 37%, respectively. In particular, the CD56^bright NK cell population showed a tenfold increase, while CD56^dim NK cells remained unmodified compared with pretreatment values. The expression of IL2 receptors was also studied, and a significant increase (p=0.01) of CD122 (p75)-positive cells from 8% to 30% was found, while no significant increase was observed in CD25 (p55)-positive cells. Furthermore, rIL2 administration led to an increase of NK activity even at the lowest effectors: target ratio and to an increase of CD16-mediated redirected killing assay. These phenotypic and functional modifications lasted throughout the duration of rIL2 therapy and remained after completion of therapy. In addition, none of the ten patients relapsed, and two of them who started IL2 treatment while still showing residual disease experienced a complete disappearance of the disease after 10 and 7 months of therapy, respectively. Our data suggest that infusion of rIL2 s.c. after ABMT is safe, can selectively increase NK cell number and function, and may have a beneficial effect on the minimal residual disease.This work sas supported in part by CNR PF ACRO: 94.01214.PF39.     

Flow cytometry for CD34 determination in hematopoietic grafts

CD34 is a type I transmembrane protein that is expressed on lympho-hematopoietic progenitor and endothelial cells and has a potential adhesion function. Various monoclonal antibodies, whether characterized by glycosylated epitopes or not, are utilized to recognize different subsets of hematopoietic progenitors. Coexpression of membrane markers involving CD34 is an approach to the definition of those subpopulations of cells previously characterized by using in vitro cultures. Thus, in the autologous transplantation procedure, flow cytometry determination of CD34+ cells in the grafts themselves, especially as concerns cytapheresis products, was enhanced with CFU-GM enumeration. This methodology required a standardized protocol with regard to the choice of the monoclonal antibody, had to be to data acquisition and to computer analysis. Within the framework of a multicentric trial, various strategies had to be evaluated. Special attention was paid to obtaining a sensitivity level of 0.1 %. New, standardized approaches are currently in the planning stage, in particular with a view to determining absolute count on the basis of readings generated by the flow-cytometer.     

Monoclonal gammopathy (IgA:λ) after autologous T-cell-depleted bone marrow transplantation in a patient with non-Hodgkin's lymphoma

Summary We report a case study of a patient suffering from T-lymphoblastic lymphoma, for whom autologous T-cell-depleted bone marrow transplantation was carried out. Low-dose cyclosporin A (CsA) was administered just after autologous bone marrow transplantation (ABMT) for induction of autologous graft-versus-host disease. Three months later, the lymphoma relapsed with marked monoclonal gammopathy of the immunoglobulin A type, which had not been seen before ABMT. It is suggested that the regrowth of the lymphoma cells was related to the maturation of B cells or the secretion of immunoglobulins from plasma cells, associated with some cytokines produced under the condition of an abnormal immunological circumstance after ABMT plus CsA.     

大剂量马法兰或加足叶乙甙/全身放疗预处理进行自体骨髓移植治疗恶性淋巴瘤

报告7例有预后不良因素的恶性淋巴瘤患者,经大剂量马法兰或加足叶乙甙和全身放疗预处理行自体骨髓移植的治疗结果.采髓后54小时内回输非净化非冷冻的自体骨髓.上述方案对骨髓产生毁灭性作用,但全部患者获造血重建,取得了满意的近期疗效.无相关死亡.     

IL-2/同种异体LAK细胞疗法用于自体骨髓移植后治疗急性白血病5例

５例急性白血病患者，行自体骨髓移植获得造血重建后，以白细胞介素Ⅱ（ＩＬ－２）合并应用同种异体ＬＡＫ细胞做为免疫疗法，以清除体内微小残留疾病，采用ＩＬ－２剂量为４×１０４ｕ／ｄ～２×１０５ｕ／ｄ。同种异体ＬＡＫ细胞来源于脐带血及胎儿胸腺、脾脏，初步结果表明，该方法安全，有效，毒副作用小，未见ＧＶＨＤ发生。     

Cyclosporine-induced graft-versus-host disease after autologous bone marrow transplantation in hematological malignancies

Summary In the attempt to induce graft-vs-host disease (GVHD) in patients undergoing autologous bone marrow transplantation (ABMT) or blood stem cell transplantation (BSCT), 12 consecutive patients received cyclosporin A (CyA) post transplant. CyA was given at a dose of 1.5 mg/kg/day intravenously for 28 days, starting on the day of transplant. Histologically proven acute GVHD of the skin occurred in seven patients 9–14 days after ABMT and lasted 7–11 days. CyA-induced GVHD after ABMT resembles mild GVHD after allogeneic bone marrow transplantation (BMT). Although the preliminary data reported here show that it is possible to induce GVHD in patients undergoing ABMT, it is not yet known whether GVHD after ABMT will have an antitumor activity.     

免疫毒素清除人骨髓中克隆化白血病细胞的研究——Ⅰ.抗CD_7免疫毒素的制备及其细胞毒性质研究

本实验采用优化的方法通过SPDP交联抗CD_7单克隆抗体与蓖麻毒素制成免疫毒素。经MTT方法检测其对表达CD_7抗原的Molt-4及HPB-ALL细胞系均有显著特异性杀伤作用。克隆杀伤实验结果表明,该免疫毒素在10~(-10)mol/L浓度时达3个杀伤log(即清除99.9%的molt-4细胞),而在此浓度时,其只抑制21.6%的粗-单系造血祖细胞生长,从而初步证明其在自体骨髓移植中可用于清除骨髓中残留白血病细胞。     

影响自身骨髓移植疗效的多因素分析

本文采用单因素及ＣＯＸ多元回归分析了５９例急性白血病自身骨髓移植（ＡＢＭＴ）影响疗效的多种因素。结果表明，当采用单因素分析时发现移植时年龄＜４０岁与≥４０岁组，完全缓解（ＣＲ）至移植时间＜６月≥６组对缓解期无明显影响（Ｐ＞０．０５），ＣＲ１后移植者缓解期长于ＣＲ２后移植者，且复发率低，但两组未能得出统计学差异（Ｐ＞０．０５）。单用化疗作为预处理方案，疗效优于化疗合用放疗者（Ｐ＜０．０５）。当采用多因素分析时，则发现移植后中性粒细胞恢复所需时间及预处理方案对缓解时间有显著影响（Ｐ＜０．０５），单次移植后复发概率明显高于双次移植者。认为影响ＡＢＭＴ疗效的因素复杂，尚难得出肯定结论。     

Peripheral blood stem cell versus autologous bone marrow transplantation for Hodgkin's disease: equivalent survival outcome in a single-centre matched-pair analysis

A matched-pair retrospective analysis was used to compare 70 patients who had undergone peripheral blood stem cell transplantation (PBSCT) with 70 who had undergone autologous bone marrow transplantation (ABMT) for Hodgkin's disease. All transplants took place at a single centre using the same conditioning regimen (BEAM). Patients were matched for sex, previous chemotherapy and relapse status: factors which have previously been shown to have prognostic significance for transplant outcome in Hodgkin's disease at this centre. The two groups were also generally comparable for unmatched patient and disease characteristics. Toxic deaths and 90 d outcome were not different between the two groups. Three-year overall survival was 68.6% for the ABMT group and 78.2% for the PBSCT group (P = 0.078); progression-free survival was 59.4% for the ABMT group and 58.1% for the PBSCT group (P = 0.255), and relapse rates were 36.9% and 42.6% respectively (P = 0.30). Within the limitations of retrospective analysis, we conclude that there is no major overall or progression-free survival advantage for PBSCT compared to ABMT in Hodgkin's disease.