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At least 19 recordsLinked to original sources

PubMed2001

Determination of optimal transport conditions for biopsies of human articular cartilage as well as for suspensions of cultured chondrocytes used in autologous transplantation.

Autologous transplantation of chondrocytes is currently being promoted as a novel approach for the treatment of deep cartilage lesions. Briefly, the method involves enzyme-mediated release of chondrocytes from cartilage biopsies, the expansion of cells by in vitro cultivation and their re-implantation into the defect. The success of this technique depends on many factors including transport conditions for both, cartilage biopsies from the operating hall to the laboratory and the return transport of final suspension of cultured chondrocytes. To determine the extent of cellular damage in biopsies, chondrocytes were enzymatically isolated following a few days of tissue preservation in different tissue culture media. The proportion of dead cells was assessed by Trypan blue staining and counting. The viability was not dependant of the type of the medium used and remained approximately 50% in all samples, even after 72 h. To develop optimal conditions for transport of final chondrocyte suspension, isolated cells were firstly grown in monolayer cultures. Cell suspensions in media with different additives were injected into special glass containers used for the transport and left at 4 degrees C or 25 degrees C for up to 3 days. During this period every 24 h the samples were taken and viability as well as apoptosis levels were assessed. Viability of cells in suspensions at 25 degrees C decreased significantly and became inadequate already after 48 h. In contrast to that, the proportion of viable cells at 4 degrees C remained above 80% even after 48 h. In the majority of the samples, culture medium containing serum and vitamin C provided the best conditions for long-term preservation of chondrocytes.

Apoptosis↗

PubMed2005

The current status of gene therapy in autologous transplantation.

Autologous hematopoietic cells have been used as targets of gene transfer, with applications in inherited disorders, cell therapy, and acquired immunodeficiency. The types of cells include hematopoietic progenitor cells, lymphocytes, and mesenchymal stem cells. The inherited disorders thus far approached in clinical trials include severe combined immunodeficiency, common variable gamma-chain immunodeficiency, chronic granulomatous disease, and Gaucher disease. Preclinical studies are vigorously under way in thalassemia, sickle cell anemia, Wiskott-Aldrich syndrome and Fanconi anemia. Clinical trials of immunological therapy with gene-modified lymphocytes are under study in the treatment of malignancies. Clinical trials using anti-viral strategies for HIV infection in combination with autologous transplantation have begun, with additional approaches being developed. Gene therapy vectors are being developed to eliminate tumor cells contaminating autologous stem cell products. However, the risk of insertional mutagenesis and the potential for development of leukemia was highlighted by the first gene therapy trials in inherited immunodeficiency syndromes that achieved a therapeutic effect. Despite the slow progress of the field to date, there is extraordinary promise for gene therapy in the future.

Animals↗

PubMed1994

Cell function studies in long-term bone marrow culture after cell concentration and cryopreservation for autologous transplantation.

Autologous bone marrow transplantation (ABMT) is frequently used in the treatment of neoplastic diseases. It involves several manipulations in vitro that can damage the stem cells responsible for grafting. Long-term bone marrow cultures (LTBMC) reproduce the bone marrow microenvironment and support haematopoiesis in vitro for several weeks. This technique provides information on the extent of the injury of stem cells during manipulations of bone marrow cells in vitro. We studied the effect of the usual process of bone marrow cells in vitro in autologous transplantation: cell concentration and cell cryopreservation. 28 bone marrows from healthy donors and 45 from patients who had undergone ABMT were assayed in LTBMC. The cultures were initiated after manual or automatic buffy coat cell separation or after density gradient or automatic mononucleated cells suspension. Bone marrows were studied pre- and post-cryopreservation. The results show that several manipulations can disturb normal cell behaviour in LTBMC. Following automatic mononucleated cell separation and after thawing, the development of adherent cell layer in LTBMC is anomalous. These manipulations led to a delay in covering 50% of the flask surface, absence of adypocytes in adherent cell layer and absence of haemopoietic precursors in the supernatant at the 4th week of culture. The results suggest that LTBMC can be used for control of the manipulations in vitro related with ABMT.

Bone Marrow Cells↗

PubMed1990

A simplified method for purification, concentration and freezing of bone marrow cells for autologous transplantation.

Autologous bone marrow (BM) transplantation is being increasingly applied in hematological and oncological patients. However, because of the need to purify and preserve BM requiring high technology, such treatments are virtually concentrated in the "developed" countries. This paper examines methods of BM purification and freezing that could make the technique potentially applicable in developing countries. Hemapheresis is routinely applied for BM purification in our Dutch Centre, where the buffy coats obtained from routine blood donations were utilised in experimental settings. Using DMSO as cryoprotectant, semi-purified white cells were frozen in liquid N2 (LN2), by mechanical freezer or snap-frozen at -55 degrees C. Different types of containers were compared including plastic tubes and ordinary blood bags. After thawing the results show that snap-freezing had a deleterious effect but the cell yields and viability were similar in LN2 or the mechanical freezer where the tubes and the bag were equally effective as containers (86% cell recovery with 90% viability). In the purification/concentration stage, reduction of the volume of the material by extra centrifugation, thus requiring less DMSO, produced better results--96% cell yield and 90% viability after thawing. This simplified method was applied in a general hospital in Sao Paulo where four oncology patients underwent BM collection. BM was purified and concentrated within a blood bank facility. Hydroxyethyl starch sedimentation and centrifugation of the material in plastic blood bags gave 80% BM cell harvest. After thawing from the mechanical freezer 1 x 10(8) BM cells/kg were available for reinfusion to patients. There was no immediate untoward reaction. Three of the patients showed signs of bone marrow regeneration by three weeks, but one patient died 16 days after transplantation, of septicemia. We conclude that certain high-technology procedures for ABMT can be adapted for existing facilities in developing countries.

Bone Marrow Transplantation↗

PubMed2003

Outcome of autologous transplantation for mantle cell lymphoma: a study by the European Blood and Bone Marrow Transplant and Autologous Blood and Marrow Transplant Registries.

Mantle cell lymphoma (MCL) has an aggressive clinical course with a median survival < 3 years and is incurable with conventional chemotherapy. A large multicentre study with adequate follow-up may clarify the role of significant factors affecting outcome in autologous stem cell transplantation for MCL. Patients receiving an autologous transplant for MCL between 1988 and 1998, and reported to the European Blood and bone Marrow Transplant (EBMT) registry or Autologous Blood and Marrow Transplant Registry (ABMTR), were included. Expert haematopathology review was required on all identified patients. Disease and transplant details were requested from the transplant centres, and the final cohort of patients with verified pathology, adequate clinical information and follow-up was analysed. One hundred and ninety-five patients were included in the analyses (149 EBMT, 46 ABMTR) with a median follow-up of 3.9 years. The 2 year and 5 year overall survival were 76% and 50%, and progression free survival was 55% and 33% respectively. Disease status at transplant was the most significant factor affecting survival: patients with chemosensitive disease but not in first complete remission (CR1) were 2.99 times (95% CI: 1.66-5.38, P < 0.001) more likely to die than patients transplanted in CR1. Autologous transplantation probably improves survival in patients with MCL especially if performed in first CR.

Adult↗

PubMed1991

[Future perspectives of bone marrow and stem cell activation for autologous transplantation].

Autologous bone marrow transplantation has gained an increasing role in modern oncology. The use of circulating progenitors from the peripheral blood as autografts might have some important advantages, since leukaphereses are better tolerable than a BM harvest, could be done immediately following chemotherapy, are possible in patients with previous irradiation to the pelvis and might be less contaminated with malignant progenitor cells. We have shown that monitoring transplants with the relatively simple in vitro assay for myeloid progenitor cells is predictive for hematopoietic recovery in animal models as well as in the clinical setting. Moreover, stem cells harvested during repeated leukapheresis were able to repopulate permanently the irradiated BM. Using recombinant human granulocyte/macrophage colony stimulating factor, large quantities of progenitor cells can be mobilized into the peripheral blood and collected for autotransplantation, in particular if used directly following chemotherapy. Cell separation studies showed that a bone marrow/blood barrier retains some subpopulations of progenitor cells which might lead to the preferential circulation of normal stem cells following chemotherapy. Methods are described to distinguish normal and leukemic progenitor cells which will help in the future to assay autografts both for their repopulating ability and their contamination with tumor cells.

Animals↗

PubMed1999

Unrelated donor stem cell transplantation after autologous transplantation: experience of a single center.

Patients who do not respond to autologous stem cell transplantation (ASCT) have a poor prognosis. Concerns about toxicity limit the use of unrelated donor stem cell transplantation (UDSCT), but the knowledge about outcome after UDSCT post-ASCT is limited. We carried out a retrospective analysis of the outcome in seven consecutive patients with leukemia (n = 5), myeloma (n = 1) and graft failure (n = 1) who underwent UDSCT after ASCT. Donors were matched for HLA-A, -B and -DR (n = 6) or had one class I antigen mismatch (n = 1). Tissue typing was performed by a high-resolution genomic technique for class II. Median patient age was 34 (11-54) years and time from ASCT to UDSCT was 16 (3-22) months. Patients with malignant diseases were given TBI and a CY preparatory regimen. In addition, all patients received T cell antibodies prior to UDSCT. Grade I acute GVHD developed in all seven patients, but there was no sign of more severe acute GVHD. Two of four evaluable patients developed limited chronic GVHD. Three died of transplant-related toxicity, all due to pulmonary complications. Four patients are alive at 1.1, 1.5, 3.1 and 4.9 years post-UDSCT. A closely matched UDSCT could be considered for selected patients who are not cured by an ASCT.

Adult↗

PubMed2004

Second autologous transplantation after failure of a first autologous transplant in 18 patients with non-Hodgkin's lymphoma.

High-dose chemotherapy and autologous marrow or peripheral stem cell support offers the best chance of cure in some subgroups of patients with non-Hodgkin's lymphoma (NHL). Less is known about the role of a second course of myeloablative chemotherapy in patients who relapse after a first autologous transplant. The aim of this retrospective study was to evaluate the disease outcome, morbidity and mortality associated with second autologous transplantation in patients with NHL. Between 1985 and 2001, 225 patients who had received autologous transplantation for NHL in two institutions in Lyon relapsed. Of these 225 patients 18 underwent a second autologous transplantation. The median age at second transplant was 41 years. There were six indolent lymphomas and 12 aggressive lymphomas. The median follow-up from the second transplant was 42 months. The OS rate at 2 and 5 years were 58 and 27%, respectively. The PFS rate at 2 and 5 years was 36%. Five patients are alive without disease 20 to 100 months after the second transplant. Seven patients died of disease recurrence. Four (22%) toxic deaths occurred: one of pulmonary fibrosis, one of fungal infection and cardiac failure and two of acute leukaemia. A minority of patients with NHL recurrence after a first transplant can be cured by a second course of myeloablative chemotherapy at the cost however of high-risk toxic death.

Adult↗

PubMed2003

Cryopreservation of human brain tissue allowing timely production of viable adult human brain cells for autologous transplantation.

BACKGROUND: Autologous transplantation is an attractive approach to treat some neurological diseases. A major obstacle is the capacity to produce cells for transplantation at the appropriate time. We describe a cryopreservation procedure for adult human brain tissue allowing the generation of cells in vitro. METHODS: Neurological resections were dissected to separate white and grey matter. Fractions were frozen in a specific cryopreservation medium containing a selected serum and stored in liquid nitrogen. Tissue was thawed, cells were mechanically dissociated, expanded in culture and characterized by immunochemistry. RESULTS: Adult human brain tissue cryopreserved for up to two years was successfully used to generate brain cells that could be maintained in culture for up to 100 days. Cells expressed a variety of neuroectodermal markers including GFAP, S100beta, and neurofilament. CONCLUSION: A successful procedure for cryopreservation of adult human brain tissue has been established that might facilitate future autologous transplantation strategies.

Adult↗

PubMed2000

Second allogeneic transplantation after failure of first autologous transplantation.

We evaluated the outcome of second allogeneic bone marrow transplantations (BMTs) in 59 patients aged 1-57 years who relapsed after initial autologous transplantation. Patients received a second transplantation for recurrent acute myeloid leukemia (AML) (n = 24), acute lymphoblastic leukemia (ALL) (n = 13), lymphoma (n = 18), multiple myeloma (n = 3), or chronic myelogenous leukemia (n = 1) from an HLA-matched related (n = 14), mismatched related (n = 25), or matched unrelated (n = 20) donor. The probabilities of nonrelapse mortality, relapse, and disease-free survival (DFS) 2 years after the second BMT were 51%, 26%, and 23%, respectively. The 2-year DFS estimates for AML, ALL, and lymphoma were 46%, 23%, and 0%. Univariate analysis demonstrated that superior DFS was associated with age < or =17 years at the time of the second transplantation, remission before the second transplantation, total-body irradiation-based preparative regimen for the second transplantation, and the diagnosis of AML. These data demonstrate that an allogeneic transplantation after a failed autologous transplantation can result in disease-free survivors, especially in the young. The outcomes after a second transplantation for patients aged >17 years and for those with lymphoma were especially grim. These data suggest that pediatric patients may be appropriate candidates for a second transplantation. In adults, however, the use of an allogeneic transplantation as salvage therapy after failure of the initial autologous transplantation is generally unsuccessful. Alternative experimental strategies, such as low-dose nonmyeloablative allogeneic minitransplantations, should be considered.

Adolescent↗

PubMed2001

A comparison of allogeneic bone marrow transplantation, autologous bone marrow transplantation, and aggressive chemotherapy in children with acute myeloid leukemia in remission.

Intensive, myelosuppressive therapy is necessary to maximize outcomes for patients with acute myeloid leukemia (AML). A comparison was made of 3 aggressive postremission approaches for children and adolescents with AML in a randomized trial, CCG-2891. A total of 652 children and adolescents with AML who achieved remission on 2 induction regimens using identical drugs and doses (standard and intensive timing) were eligible for allocation to allogeneic bone marrow transplantation (BMT) based on matched related donor status (n = 181) or randomization to autologous BMT (n = 177) or to aggressive high-dose cytarabine-based chemotherapy (n = 179). Only 115 patients (18%) refused to participate in the postremission phase of this study. Overall compliance with the 3 allocated regimens was 90%. At 8 years actuarial, 54% +/- 4% (95% confidence interval) of all remission patients remain alive. Survival by assigned regimen ("intent to treat") is as follows: allogeneic BMT, 60% +/- 9%; autologous BMT, 48% +/- 8%; and chemotherapy, 53% +/- 8%. Survival in the allogeneic BMT group is significantly superior to autologous BMT (P =.002) and chemotherapy (P =.05); differences between chemotherapy and autologous BMT are not significant (P =.21). No potential confounding factors affected results. Patients receiving intensive-timing induction therapy had superior long-term survival irrespective of postremission regimen received (allogeneic BMT, 70% +/- 9%; autologous BMT, 54% +/- 9%; chemotherapy, 57% +/- 10%). Allogeneic BMT remains the treatment of choice for children and adolescents with AML in remission, when a matched related donor is available. For all others, there is no advantage to autologous BMT; hence, aggressive nonablative chemotherapy should be used.

Actuarial Analysis↗

PubMed1993

Immune reconstitution following peripheral blood stem cell transplantation, autologous bone marrow transplantation and allogeneic bone marrow transplantation.

The rate and pattern of recovery of total lymphocytes, T cell subsets, B cells and NK cells were compared for 12 months following recovery phase peripheral blood stem cell (PBSC) autotransplantation (n = 49), autologous (n = 7) and allogeneic BMT (n = 11). The PBSC group had a significantly faster recovery of total lymphocyte count, total T cells (CD3+ cells), CD8 cells and CD4 cells than the allogeneic BMT group. The pattern of earlier recovery of CD8 cells than CD4 cells was the same for each type of transplant. Reconstitution following autologous BMT was intermediate between PBSC and allogeneic BMT. Multivariate analysis identified type of transplant, number of mononuclear cells transplanted and conditioning regimen as significantly influencing immune recovery.

B-Lymphocyte Subsets↗

PubMed2002

Successful unrelated cord blood transplantation for relapse after autologous transplantation in non-Hodgkin's lymphoma.

We report a 34-year-old male with relapsed non-Hodgkin's lymphoma (NHL) after autologous peripheral blood stem cell transplantation successfully treated with unrelated cord blood transplantation (CBT). The conditioning regimen included 12 Gy total body irradiation and cyclophosphamide. After the conditioning, a total of 3.14 x 10(7)/kg cord blood nucleated cells was infused on 14 February 2000. An absolute neutrophil count greater than 5 x 10(8)/l and a self-sustained platelet count greater than 50 x 10(9)/l were achieved on days 21 and 43, respectively. During the follow up period, grade I acute graft-versus-host disease (GVHD) and limited chronic GVHD occurred, but both were successfully treated with a dose modification of cyclosporine. After a follow-up period of 16 months, the patient is alive and free of disease. To our knowledge this is the first report of a successful unrelated CBT for an adult NHL patient who relapsed after autologous transplantation.

Adult↗

PubMed2001

Allogeneic stem cell transplantation reduces disease progression compared to autologous transplantation in patients with multiple myeloma.

This study compares the probability of disease progression, progression-free survival, and overall survival between patients undergoing an allogeneic or autologous transplant for multiple myeloma using an identical preparative regimen. Patients received a preparative regimen of TBI, busulfan, and cyclophosphamide followed by an allogeneic or autologous transplant. In the allogeneic group (n = 21), six patients received bone marrow and 15 received G-CSF mobilized PBSC; all autologous patients (n = 35) received PBSC mobilized with cyclophosphamide and G-CSF. Allogeneic donors were HLA-identical (n = 20) or one-antigen mismatched (n = 1) siblings. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus (n = 10), tacrolimus/methotrexate (n = 6), cyclosporine/methotrexate (n = 4), or cyclosporine (n = 1). The groups were evenly matched for gender, pretransplant therapy, disease status at time of transplant, myeloma subtype, and time from diagnosis to transplant. The median age was significantly lower in the allogeneic group (48 vs 55 years, P < 0.01). In the allogeneic group the probabilities of developing acute GVHD grade II-IV and chronic GVHD were 55% and 82%, respectively. The Kaplan-Meier probability of disease progression was significantly lower in the allogeneic group (11% vs 64%, P < 0.001) compared to the autologous group. Although progression-free (60% vs 30%, P = 0.19) and overall survival at 2 years (60% vs 42%, P = 0.39) favored the allogeneic group, this did not reach statistical significance. Within the allogeneic transplant group, patients age 50 years or under had a 3-year overall survival significantly higher when compared to older patients (79% vs 29%, P = 0.03). Using identical preparative regimens, allogeneic transplantation reduced disease progression compared to autologous transplantation for myeloma. This suggests that allogeneic transplantation induces a graft-versus-myeloma (GVM) effect.

Actuarial Analysis↗

PubMed2005

Allogeneic hematopoietic cell transplantation as consolidation immunotherapy of cancer after autologous transplantation.

Autologous and allogeneic hematopoietic cell transplantations (HCT) after high-dose conditioning are curative for many patients with hematologic malignancies. The major limitation of autologous HCT is disease recurrence, while the problem with allogeneic HCT is the restriction to relatively young and otherwise medically fit patients because of complications from high-dose therapy coupled with those from graft-versus-host disease (GVHD). The well-described benefits of graft-versus-tumor (GVT) effects have stimulated the development of conditioning regimens with attenuated doses of chemoradiotherapy that may provide both a degree of cytoreduction before allografting (reduced intensity) and facilitate allogeneic cell engraftment through immuno- suppression (nonmyeloablative). Both reduced-intensity and nonmyeloablative approaches seek to exploit GVT activity of donor cells to eradicate cancer. Because of intrinsic or acquired insensitivity of some malignancies to standard dose chemotherapy and the limitations of GVT effects in eradicating large tumor burdens, high-dose autologous HCT has been used before reduced-intensity and nonmyeloablative allogeneic HCT. This approach appears to improve response rates for malignancies such as multiple myeloma and lymphoma, while avoiding morbidity and mortality of high-dose allogeneic HCT. This review details the rationale, benefits and limitations of this approach.

Disease-Free Survival↗

PubMed1997

Bone marrow transplantation after failure of autologous transplant for non-Hodgkin's lymphoma.

We evaluated the response to and toxicity of allogeneic or autologous bone marrow transplantation (BMT) for patients with non-Hodgkin's lymphoma (NHL) who relapsed after autologous BMT. Since 1990, 172 patients have received autologous BMTs in NHL at the MD Anderson Cancer Center and 75 have relapsed. Twelve patients (median age, 42 years), with disease recurrence underwent either allogeneic BMT (eight patients) or a second autologous BMT (four patients). Ten patients received thiotepa, busulfan and cyclophosphamide as conditioning, one patient received cyclophosphamide and total body irradiation and one received BCNU, etoposide, Ara-c and melphalan. The median interval between the first and second transplants was 23.5 months (range 5-80 months). Three patients who underwent allogeneic BMT had refractory relapses, three had a responsive relapse and two were in complete response (CR) at the time of BMT. Five patients received peripheral blood stem cells and three patients, allogeneic bone marrow. Three patients are alive and disease-free at 25, 22 and 7 months after allogeneic BMT. Four patients died of treatment-related causes and one from disease recurrence. All four patients undergoing autologous BMT had responsive relapses. Three patients received peripheral blood stem cells and one patient bone marrow. Two patients are alive and disease-free at 12 and 30 months after autologous transplants. There were no treatment-related deaths; two patients died of disease recurrence. This retrospective study shows that in selected patients, allogeneic or autologous BMT is an effective salvage therapy for NHL which recurs after autologous BMT.

Adult↗

PubMed2005

Therapeutic options for patients with Hodgkin's disease and non-Hodgkin's lymphoma who relapse after autologous transplant.

Although autologous stem cell transplantation for Hodgkin's disease and non-Hodgkin's lymphoma has become a safe and effective therapy, relapses after transplant are common. Emerging data indicate that an increasing number of patients can be re-induced into durable complete remission. Conventional dose- salvage chemotherapy and single-agent monoclonal antibody treatment provided limited success, but combination chemotherapy-monoclonal antibody treatments, second autografts, and reduced-intensity conditioning allografts provide encouraging results. For some patients, the best strategy may consist of participation in phase I to II studies of novel agents. New strategies designed to prevent relapse after autograft include cytokine therapy such as interleukin-2 in combination with monoclonal antibodies and the use of autologous antilymphoma vaccines.

Clinical Trials as Topic↗

PubMed1992

[Methods for preserving bone marrow for autologous transplantation].

For Autologous Bone Marrow Transplantation (ABMT) the patient's own marrow is harvested before myelotoxic high-dose radio-chemotherapy and later returned to promote hemopoietic reconstitution. Between harvest and return the bone marrow must be preserved. The time elapsed between harvest and return depends on the intended therapy. Although--bone marrow may keep its hematopoietic potential for a few days without freezing, preservation for longer periods imposes the need for cryopreservation. Some of the current methods for marrow preservation are reviewed, with special emphasis given to cryopreservation. Hospital de Santa Maria Bone Marrow Transplant Unit cryopreservation method is described.

Adolescent↗