Changes of immunological markers after autologous peripheral blood stem cell transplantation

PURPOSE: Recently high-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) has become an important treatment for hematological and solid tumors. METHODS: Immunological parameters were examined before and after PBSCT in 9 patients with lung cancer and 13 patients with malignant lymphoma. Findings were compared with those for bone marrow transplantation (BMT). Peripheral blood cells were analyzed for phenotype and the levels of cytokines and soluble factors were measured. RESULTS: After PBSCT, activated T cells (CD3+HLA-DR+ cells, CD8+HLA-DR+ cells) and suppressor/cytotoxic T cells (CD8+CD11b- cells) were significantly higher in the patients with lung cancer than in those with malignant lymphoma. Serum levels of interleukin-4 and soluble interleukin-2 receptor were also significantly higher in the patients with lung cancer than in those with lymphoma. On the other hand, the serum levels of interferon gamma, tumor necrosis factor alpha, interleukin-6, soluble human leukocyte antigen class 1, and soluble thrombomodulin were significantly increased after bone marrow transplantation. The transfused peripheral stem cells of lung cancer and lymphoma patients had a similar number of granulocyte/macrophage-colony-forming units, but lung cancer patients had significantly more CD34-positive cells. CONCLUSION: By reinfusing large numbers of autologous immune cells, PBSCT may accelerate immune reconstitution, with T cells being likely to have a marked therapeutic potential. The changes after PBSCT were greater in patients with lung cancer than in lymphoma patients. These blood cells are potent mediators of anticancer activity and could play an important role in the elimination of autologous malignant cells.     

Autologous peripheral blood stem cell transplantation for malignant lymphoma

Autologous peripheral blood stem cell transplantation (PBSCT) for patients with malignant lymphoma has been extensively performed in Japan for several years. Some of the disease states of lymphoma are considered to be a good candidate for auto-PBSCT application. Sensitive relapsers in non Hodgkin's lymphoma should be treated with a combination of salvage therapy and high dose chemo(radio)-therapy with stem cell support, and up-front PBSCT is recommended for poor risk aggressive lymphoma. The clinical results and indications for auto-PBSCT including other types of lymphoma such as lymphoblastic lymphoma, mantle cell lymphoma, low-grade lymphoma and Hodgkin's disease will be reviewed in this paper.     

Use of ondansetron in the control of emesis in autologous peripheral blood stem cell transplant (APBSCT) for solid tumours

The authors describe several case-records where Garamycin Schwamm was used primarily to prevent infection in recent injuries of the hand. They mention also the possibility to administer it secondarily in the treatment of chronic infection. The high local gentamycin concentration, the haemostatic effect of the collagen carrier and its favourable influence on wound healing are found in particular in recent hand injuries with a highly contaminated wound. Secondarily Garamycin is used as a supplement of surgery in chronic infections of soft tissues or the skeleton. Treatment and prevention of infection in surgery of the hand is of major importance for the resulting function of the hand and minimalization of the number of reconstruction operations.     

High-dose chemotherapy with autologous peripheral blood stem cell transplantation for metastatic gastric leiomyosarcoma

We report a case of metastatic gastrointestinal leiomyosarcoma treated with high-dose combination chemotherapy and autologous peripheral blood stem cell transplantation. After incomplete surgical resection, enteral, peritoneal and hepatic involvement remained. Postoperatively, standard-dose chemotherapy with etoposide, ifosfamide, cisplatin and epirubicine, and high-dose chemotherapy with the same agents (carboplatin replacing cisplatin) was given. Treatment was well tolerated and the patient remains in complete remission at 36+ months. We conclude that high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation may be of use as treatment for inoperable residual disease after resection of the primary lesion in gastrointestinal and other soft tissue sarcomas.     

Allogeneic peripheral blood stem cell transplantation in 30 patients with hematologic disorders

Thirty patients (median age of 32 years; range, 6-61) with hematologic disorders received unmanipulated peripheral blood stem cell transplants from HLA-matched or one-antigen-mismatched related donors following myeloablative therapy for acute lymphoblastic leukemia (7), acute myelogenous leukemia (6), chronic myelogenous leukemia (8), myelodysplastic syndrome (3), or other disorders (6). Granulocyte colony stimulating factor (G-CSF) mobilized peripheral blood stem cells were collected from donors in 1 to 3 aphereses. The apheresis products contained mean counts of 11.3 x 10(8) (range, 3.8-17.2) nucleated cells/kg and 6.7 x 10(6) (range, 1.3-16.7) CD34+ cells/kg. Graft-versus-host-disease (GVHD) prophylaxis consisted of cyclosporin A plus methotrexate, or FK506 plus methotrexate. All patients received G-CSF following their transplant. Although 1 patient died of pneumonia 6 days after transplantation, the others demonstrated rapid engraftment. Median days to recovery to 500/microliter neutrophils and 20,000/microliter platelets were 13 (range, 8-21) and 14 (range, 1-23) days, respectively. The incidence of acute GVHD grade II-IV was 33%; chronic GVHD developed in 57% of the assessable patients. There were no episodes of graft failure or rejection. Nineteen patients (63%) were alive and in complete remission from 147 to 839 days following their transplant (median follow-up of 560 days). Further follow-up study will be required to assess the incidence of chronic GVHD and graft-versus-leukemia (GVL) effects.     

Busulfan and melphalan as conditioning regimen for autologous peripheral blood stem cell transplantation in multiple myeloma

Twenty-four patients with multiple myeloma (MM), three (12.5%) in complete remission (CR) and 21 (87.5%) in partial remission (PR) were treated with high-dose chemotherapy (HDCT) (busulfan 12 mg/kg+melphalan 140 mg/m2) as preparative regimen for autologous peripheral blood stem cell (PBSC) transplantation. These cells were previously collected by leukapheresis after mobilization by high-dose cyclophosphamide (HD Cy)+rhGM-CSF (18 patients) or rhG-CSF alone (six patients). Considering 23 evaluable patients following HDCT, the CR rate was 58% (14 patients) and the PR rate was 38% (nine patients). One transplant-related death occurred following this regimen (4%). With a median follow-up of 20 months (range 4-34) after transplantation, 21 patients are alive (87%). Disease progression after transplantation was observed in four patients. Overall and relapse-free actuarial survival at 24 months was 91% and 74%, respectively. 12 patients (50%) remain in CR 15 months (4-34) post transplant. The major toxicity was mucositis. Busulfan+melphalan is a safe and feasible conditioning regimen for APBSCT in MM with acceptable toxicity and a high objective response rate, which may result in prolonged survival.     

Remission of nonerosive polyarthritis associated with Sj?gren's syndrome after autologous hematopoietic stem cell transplantation for lymphoma

We describe a 50-year-old woman with seropositive rheumatoid arthritis and Sj?gren's syndrome who underwent autologous blood stem cell transplantation after relapse of associated non-Hodgkin's lymphoma. This resulted in complete remission not only of the lymphoma, but also the arthritis.     

Allogenic peripheral blood stem cell (PBSC) transplantation in two patients with graft failure

Allogenic peripheral blood stem cells (PBSC) were used for graft failure after BMT in two patients. These PBSC were mobilized by G-CSF in the same donors, harvested and given without reconditioning to the patients. In one patient, PBSC with a very high T cell number were given unprocessed, in the other patient, CD34+ cells were positively enriched due to a 2-antigen difference. None of the patients had hyperacute GVHD. Trilineage engraftment was seen after 13 days. Acute GVHD grade II to III developed on days +31 in patient 1 and +16 in patient 2, involving predominantly gut and liver, but sparing the skin. Thus, allogeneic PBSCT for graft failure did not cause hyperacute GVHD even with very high T cell numbers in patient 1, and graft failure with CD34 selected PBSC was successfully reversed even with a low number of T cells in patient 2.     

Antibody responses to tetanus toxoid and Haemophilus influenzae type b conjugate vaccines following autologous peripheral blood stem cell transplantation (PBSCT)

OBJECTIVE: Although there are many anecdotal reports that psychological intervention is effective in enhancing adjustment to spinal cord injury (SCI), there are little data to support this assertion. To date, reports of few longitudinal-based controlled trials that assessed psychological outcomes for SCI persons have been published. This study was conducted to determine long-term efficacy of cognitive behavior therapy during rehabilitation. DESIGN: The study employed a nonrandomized controlled trial, and measures were taken on three occasions: before, immediately after, and 12 months after treatment. SETTING, OUTCOME MEASURES, AND INTERVENTION: Anxiety, depressive mood, and self-esteem were assessed in 28 SCI persons consecutively selected on admission to hospital, who participated in specialized group cognitive behavior therapy (CBT) during rehabilitation. CONTROLS: The intervention group's responses on the measures were compared with a control group of 41 SCI persons who only received traditional rehabilitation services during their hospitalization. RESULTS: There were no overall group differences on anxiety, depressive mood, and self-esteem, although there was a trend for the treatment group to have greater levels of improvement in depression scores across time in comparison to the control group. However, those in the treatment group who reported high levels of depressive mood before the CBT treatment were significantly less depressed 1 year after injury, compared to similar persons in the control group. CONCLUSIONS: While it appears not everyone who experiences SCI needs CBT, at least in the hospital phase of their rehabilitation, those who report high levels of depressive mood benefited greatly from CBT.     

High dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) For advanced testicular cancer]

Social work for the elderly in a demographical ageing society is not justified per se, but has to prove its utility under the altering social conditions of the changing age-structure. In the field of practice, this has led to an increasing need for professional orientation and to searching for profiles of performance with greater attraction. As manifold as the target groups are the spectra of social work for the elderly is also manifold in its content and methods. Nevertheless, we are able to recognize some general orientations and strategies, which are conceptual adaptions from social work in general, cultural work and educational work--combined with fundamental supplies of social gerontological knowledge. In this sense, social work, for the elderly--in its most advanced realms--should be integrated into an ageing-policy concept, which is of relevance for the society as a whole.     

Successful treatment with high dose chemotherapy following peripheral blood stem cell transplantation for relapsed Burkitt''s lymphoma with central nervous system involvement

BACKGROUND: The family of uncoupling proteins is thought to play an important role in the regulation of energy metabolism by uncoupling the respiratory chain reactions from ATP synthesis. The recently discovered uncoupling protein 2 (UCP2) is upregulated in genetically obese rodent models and during long term high fat feeding. AIM: We have examined the UCP2 mRNA levels in liver, heart and white adipose tissue (WAT) of obese ventromedial hypothalamus (VMH)-lesioned rats, during the dynamic and the early stage of the static phase of obesity, before the appearance of most of the metabolic perturbations associated with long term established obesity. RESULTS: The amount of UCP2 mRNA was not increased in any tissue of VMH-lesioned rats relative to control animals during the dynamic phase nor during the early static phase of obesity. CONCLUSION: These results indicate that in the rat, obesity does not necessarily lead to an increase in UCP2 expression and suggest that the up-regulation of UCP2 described in other models may be secondary to metabolic perturbations, rather than to a direct adaptative response to the increased adipose tissue content of the organism.     

Autologous peripheral blood stem and progenitor (CD34+) cell transplantation for systemic lupus erythematosus complicated by Evans syndrome

Immunoablation followed by allogeneic stem cell (SC) transplantation has been shown to be capable of curing a large spectrum of experimental autoimmune disorders, hereditary and/or induced. Superimposable results, albeit with some exceptions, have been obtained in human patients affected by coincidental autoimmune and blood diseases. However, both because of encouragine experimental results and of the procedure's greater safety, autologous SC are being increasingly utilized worldwide. Case reports are being collected in the registry of the European Group for Blood and Marrow Transplantation (EBMT)/European League against Rheumatism (EULAR) Autoimmune Disease Stem Cell Project. Among the severe autoimmune diseases (SADs), which are the target of autologous transplantation, severe refractory systemic lupus erythematosus (SLE) is a condition which may benefit from this procedure. We report here the case of a 19 year old female patient with a six year history of SLE with secondary antiphospholipid syndrome (APS), who later developed refractory Evans syndrome. She was transplanted with autologous mobilized CD34+ SC and progenitor cells after conditioning with cyclosphosphamide, anti-T lymphocyte globulin and prednisone. Eight months after transplant, the patient is alive and well, with normal blood counts and persistent low-titre direct antiglobulin (DAT, Coombs) and anti-nuclear antibody (ANA) tests. Anti-double stranded DNA antibody (Anti-dsDNA), lupus anticoagulant tests and anti-cardiolipin antibody (ACA) test are negative.     

BEAM chemotherapy and autologous haemopoietic progenitor cell transplantation as front-line therapy for high-risk patients with diffuse large cell lymphoma

In two consecutive and unselected cohorts of diffuse large cell lymphoma (DLCL) patients with advanced stage disease (IIB or bulk or more) and aged < 60 years, we compared a standard (MACOP-B for 12 weeks, 60 patients) versus a high-dose chemotherapy programme (8 weeks of MACOP-B plus one or two cycles of intensification with mitoxanthrone, dexamethasone, high-dose Ara-C, and finally BEAM chemotherapy with autologous haemopoietic progenitor cell transplantation, 61 patients). 41 patients (68%) in the standard group and 51 (84%) in the high-dose chemotherapy group, achieved a complete remission (CR) or an uncertain complete remission (CRu) (P = 0.0491). With a median follow-up time of 28 months for the high-dose group and 63.5 months for the standard group, the actuarial estimate of event-free survival (EFS) at 2 years demonstrates a significant benefit (70% v 50%, P = 0.03) for patients treated with the intensive regimen. The analysis of subgroups of patients showed that only high-risk patients (two or three risk factors) benefitted from the high-dose chemotherapy programme. Nevertheless, the overall survival does not show a significant difference between the two treatment modalities. The treatment-related morbidity was similar and the mortality rate was 8% in the standard (MACOP-B) group and 3% in the high-dose chemotherapy programme. In conclusion, our results show that high-dose chemotherapy and autologous stem cell transplantation is a safe procedure which should be considered for the front-line treatment of non-Hodgkin lymphoma patients with poor prognostic features.     

High degree of occult tumor contamination in bone marrow and peripheral blood stem cells of patients undergoing autologous transplantation for non-Hodgkin''s lymphoma

Treatment of cultured bovine adrenal chromaffin cells with dbcAMP increased [3H]STX binding with an EC50 of 126 microM and a half-effective time of 12 h; dbcAMP (1 mM x 18 h) raised the Bmax approximately 1.5-fold without altering the Kd value. Forskolin (0.1 mM) or IBMX (0.3 mM) also increased [3H]STX binding, while dbcGMP had no effect. Effects of dbcAMP and forskolin were abolished by H-89, an inhibitor of cAMP-dependent protein kinase. Cycloheximide (10 microgram/ml) and actinomycin D (10 microgram/ml), inhibitors of protein synthesis, nullified the stimulatory effect of dbcAMP, whereas tunicamycin, an inhibitor of protein glycosylation, had no effect. Treatment with dbcAMP augmented veratridine-induced 22Na influx, 45Ca influx via voltage-dependent Ca channels and catecholamine secretion, while the same treatment did not alter 45Ca influx and catecholamine secretion caused by high K (a direct activation of voltage-dependent Ca channels) [25]. Na influx via single Na channel calculated from 22Na influx and [3H]STX binding was quantitatively similar between non-treated and dbcAMP-treated cells. Brevetoxin allosterically enhanced veratridine-induced 22Na influx approximately 3-fold in dbcAMP-treated cells as in non-treated cells. These results suggest that cAMP-dependent protein kinase is involved in the modulation of Na channel expression in adrenal medulla.     

Aerobic exercise in the rehabilitation of cancer patients after high dose chemotherapy and autologous peripheral stem cell transplantation

BACKGROUND: Fatigue and loss of physical performance are frequent problems of cancer patients. In a pilot study, the authors evaluated the feasibility and effects of aerobic training in the rehabilitation of cancer patients after completing high dose chemotherapy. METHODS: Sixteen patients participated in a specially designed rehabilitation program for 6 weeks. The patients entered the program, which consisted of walking on a treadmill, shortly after completing treatment. Sixteen patients who did not train served as controls. Physical performance (maximum speed on the treadmill test), cardiac function, and hemoglobin concentration were compared at the time of discharge from the hospital and 7 weeks later. At the second examination, fatigue and limitations in daily activities due to impaired endurance were assessed during personal interviews. RESULTS: At the time of discharge from the hospital, maximum physical performance (training group: 6.2 +/- 1.1 km/hour; controls: 6.2 +/- 1.3 km/hour) and hemoglobin concentration (training group: 10.1 +/- 1.4 g/dL; controls: 10.1 +/- 1.2 g/dL) were similar for both groups. After 7 weeks, improvement in maximum physical performance (training group: 8.3 +/- 1.6 km/hour; controls 7.5 +/- 1.3 km/hour) and hemoglobin concentration (training group: 13 +/- 1 g/dL controls: 12 +/- 1.4 g/dL) were significantly higher for the training group (P < 0.05). By the second examination, no patient in the training group but 4 controls (25%) reported fatigue and limitations in daily activities due to low physical performance. CONCLUSIONS: Aerobic exercise improves the physical performance of cancer patients recovering from high dose chemotherapy. To reduce fatigue, this group of patients should be counseled to increase physical activity rather than rest after treatment.     

Reduced progression-free survival in elderly patients receiving intensification with autologous peripheral blood stem cell reinfusion for multiple myeloma

The stability of cisatracurium besylate was studied. Cisatracurium (as besylate) 2 mg/mL in 5- and 10-mL unopened vials and 10 mg/mL in 20-mL unopened vials, as well as 3 mL of solution from additional 2-mg/mL vials, repackaged in 3-mL sealed plastic syringes, was stored at 4 and 23 degrees C in the dark and in normal fluorescent room light. Admixtures of cisatracurium (as besylate) 0.1, 2, or 5 mg/mL in polyvinyl chloride (PVC) minibags of 5% dextrose injection or 0.9% sodium chloride injection were stored at 4 and 23 degrees C in normal fluorescent room light. Triplicate samples for each storage condition were taken initially and at 1, 3, 5, 7, 14, 21, and 30 days; samples from vials were also removed at 45 and 90 days. Solutions were stored in sterile vials at -70 degrees C and then thawed at room temperature before analysis of chemical stability by high-performance liquid chromatography. Physical stability was assessed as well. Cisatracurium besylate was physically stable in all samples throughout the study. Cisatracurium (as besylate) 2 mg/mL exhibited drug losses at 23 degrees C in vials at 45 days and in syringes at 30 days. Cisatracurium (as besylate) 0.1, 2, and 5 mg/mL in 5% dextrose injection and in 0.9% sodium chloride injection was stable for at least 30 days at 4 degrees C, but substantial drug losses occurred at 23 degrees C. Admixtures prepared with cisatracurium (as besylate) 0.1 mg/mL and with 5% dextrose injection exhibited the greatest losses. Cisatracurium besylate was stable in most samples for at least 30 days at 4 and 23 degrees C; admixtures containing cisatracurium (as besylate) 0.1 or 2 mg/mL exhibited substantial drug loss at 23 degrees C.     

中剂量依托泊苷联合粒细胞集落刺激因子动员恶性淋巴瘤的外周血造血干/祖细胞

目的 观察中剂量依托泊苷(VP16)和粒细胞集落刺激因子(G-CSF)在恶性淋巴瘤患者动员采集自体外周血造血干/祖细胞的有效性和安全性.方法 31例恶性淋巴瘤患者(非霍奇金淋巴瘤30例,霍奇金淋巴瘤1例),VP16 1.2 g/m2分3 d静脉滴注,外周血白细胞降至最低点时给予G-CSF每天5μg/kg,分2次,皮下注射,直至采集结束.结果 VP16应用后12 d(10～15 d)开始采集外周血造血干/祖细胞,获得单个核细胞(MNC)7.8×108/kg[(5.2～11.3)×108/kg],CD+34细胞7.2×106/kg[(5.3～13.1)×106/kg] 18例患者采集1次,13例采集2次.所有患者移植后均恢复造血,外周血粒细胞＞0.5×109/L的中位时间为12 d(9～18 d),血小板＞20×109/L的中位时间为14d(10～21 d).患者无严重不良反应结论中剂量VP16和G-CSF动员恶性淋巴瘤患者外周血干/祖细胞有效、安全,可获得满意的动员采集效果.