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1.
E Alyea D Neuberg P Mauch K Marcus A Freedman I Webb K Anderson R Schlossman D Fisher J Gribben J Ritz R Soiffer 《Biology of blood and marrow transplantation》2002,8(3):139-144
Prior studies of non-T-cell-depleted (TCD) transplantation have demonstrated a reduction in relapse in patients receiving escalated doses of TBI; however, overall survival in these studies was not significantly improved due to increased treatment-related toxicity seen at the higher doses of irradiation. Toxicity was in part related to an increased incidence of GVHD. Because T-cell depletion of donor bone marrow reduces the incidence of GVHD and other treatment-related complications after allogeneic bone marrow transplantation, it was postulated that TBI dose may be safely escalated in this setting and may decrease the risk of relapse following TCD BMT. Herein, we report the results of a trial assessing the safety and impact of escalated doses of TBI after TCD BMT. Two hundred adults with hematologic malignancies were treated in consecutive cohorts defined by increasing doses of TBI (1400, 1480, and 1560 cGy) in combination with cyclophosphamide. In vitro T-cell depletion using anti-CD6 monoclonal antibody was used for GVHD prophylaxis. The incidence of grade II or greater acute GVHD in patients receiving 1560 cGy (36%) was significantly higher than in patients receiving 1400 cGy (18%) (P = .04) or 1480 cGy (13%) (P = .01). Two-year treatment-related mortality was significantly higher in patients who received 1560 cGy of TBI (33%) than in those who received 1400 cGy (20%) (P = .04) or 1480 cGy (19%) (P = .05). The increased dose of TBI did not reduce the rates of relapse, with the estimated 2-year risk of relapse being 24% (1400 cGy), 24% (1480 cGy), and 31% (1560 cGy) for the 3 cohorts of patients. Overall survival at 2 years was inferior for patients receiving 1560 cGy of TBI (36%) compared with those who received 1400 cGy (55%) or 1480 cGy (58%) (P = .01). We conclude that dose escalation of TBI is associated with increased GVHD and inferior survival following TCD BMT. Future efforts to reduce the risk of relapse after TCD BMT should focus on immunologic methods to induce the graft-versus-leukemia effect after BMT rather than intensification of the ablative regimen by escalation of irradiation dose. 相似文献
2.
Successful allogeneic transplantation of T-cell-depleted bone marrow from closely HLA-matched unrelated donors 总被引:8,自引:0,他引:8
R C Ash J T Casper C R Chitambar R Hansen N Bunin R L Truitt C Lawton K Murray J Hunter L A Baxter-Lowe 《The New England journal of medicine》1990,322(8):485-494
We describe a four-year experience with bone marrow transplantation involving closely HLA-matched unrelated donors and 55 consecutive patients with hematologic disease who were seven months to 48.6 years old (median, 18 years). An intensive pretransplantation conditioning regimen and graft-versus-host disease (GVHD) prophylaxis with CD3-directed T-cell depletion and cyclosporine were employed. Durable engraftment was achieved in 50 of 53 patients who could be evaluated (94 percent; 95 percent confidence interval, 83 to 98 percent). Acute GVHD of Grade II to IV developed in 46 percent of the patients (confidence interval, 27 to 66 percent). The incidence and severity of acute GVHD were increased in recipients of HLA-mismatched marrow as compared with recipients of phenotypically matched marrow (incidence of 53 percent [confidence interval, 37 to 68 percent] vs. 17 percent [confidence interval, 5 to 45 percent]; P less than 0.05). Extensive chronic GVHD and deaths not due to relapse also tended to be more frequent when HLA-mismatched marrow was used, but not significantly so. With a median follow-up of more than 19 months (range, greater than 9 to greater than 39), the actuarial disease-free survival of transplant recipients with leukemia and a relatively good prognosis (acute leukemia in first remission and chronic myelogenous leukemia in chronic phase) was 48 percent (confidence interval, 24 to 73 percent), and that of recipients with more aggressive leukemia was 32 percent (confidence interval, 18 to 51 percent); the actuarial survival of recipients with non-neoplastic disease was 63 percent (confidence interval, 31 to 86 percent). We conclude that marrow transplantation with closely HLA-matched unrelated donors can be effective treatment for neoplastic and non-neoplastic diseases. Although transplants from phenotypically HLA-matched unrelated donors appear to be most effective, transplants with limited HLA disparity can also be successful in some patients. 相似文献
3.
Regeneration of humoral immunity to herpes simplex virus following T-cell-depleted allogeneic bone marrow transplantation 总被引:1,自引:0,他引:1
J Z Wimperis N J Berry H G Prentice A Lever P D Griffiths M K Brenner 《Journal of medical virology》1987,23(1):93-99
We investigated the adoptive transfer of immunity to herpes simplex virus (HSV) in 61 recipients of T-cell-depleted marrow allografts. Up to 3 months after bone marrow transplantation (BMT), high titres of HSV antibody (Ab) are passively acquired from blood products. This antibody has a half-life of 40.3 days, so that determination of recipient immunity to HSV cannot be made during the early post-transplant period. By 4 months after the allograft, seronegative recipients of seronegative donors had near-background levels of HSV Ab. Seropositive recipients, whether they were excreting virus or not, had high titres of HSV Ab regardless of donor status. Surprisingly, the seronegative recipients of HSV seropositive donors remained seronegative, a result at variance with observations made in the recipients allografts from which T-cells had not been removed. Thus, T-cell depletion modifies the adoptive transfer of humoral immunity to HSV, and an immune donor alone no longer ensures continued antibody production in the recipient. 相似文献
4.
N J Chao 《Current opinion in immunology》1992,4(5):571-576
Graft versus host disease is a major barrier in allogeneic bone marrow transplantation. The associated morbidity and mortality need to be understood and prevented if possible, as the potential indications for bone marrow transplantation continue to broaden. Areas of investigation include the cellular effector arm as well as the cytokines associated with the expression of the disease. 相似文献
5.
Histopathology of bone marrow reconstitution after allogeneic bone marrow transplantation 总被引:3,自引:0,他引:3
In order to study haematopoietic reconstitution in allogeneic bone marrow transplantation we investigated bone marrow histology in 61 biopsies of 37 patients, treated with HLA-compatible bone marrow grafts for leukaemia or severe aplastic anaemia. The biopsies were taken from the day of transplantation until 100 d after transplantation. Stromal changes, in particular oedema, fibrosis and granulomas, were found during the whole period of observation. These changes were more prominent in biopsies from leukaemia patients than from patients with aplastic anaemia. The cellularity in the biopsies increased until 28 d after bone marrow transplantation and was stable thereafter. Initially, only clusters of cells belonging to a single cell lineage were seen, suggesting that the first outgrowth of haematopoietic cells is by proliferation of committed precursor cells. Long-lasting abnormalities in localization of haematopoietic cells in the bone marrow space and of the myeloid: erythroid ratio were seen; dyserythropoiesis was common. 相似文献
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Heinonen H Volin L Zevon MA Uutela A Barrick C Ruutu T 《Patient education and counseling》2005,56(1):62-71
BMT (bone marrow transplantation) is acknowledged as one of the most stressful treatments in modern cancer care. When investigating the impact of BMT on patients it is crucial that the analytic method employed captures direct patient perceptions, allowing the patient to define the domains under investigation. In this study, a multivariate analytic method, concept mapping (CM), was used to identify perceived stressors among 109 allogeneic BMT recipients. CM employs multidimensional scaling and hierarchical cluster analyses to empirically identify the structure underlying the investigated conceptual domain. The analyses of the BMT stress data resulted in an eight-cluster solution. The stress clusters, ranked from the most severe to the least severe, were identified as: Change of life and impact of long-lasting treatment; Side-effects; Distress related to treatment outcome and physiological status; Family-related stress; Fear of death and depressive thoughts; Other concerns; Negative social support; and Stress related to lack of information and the medical staff. A number of stressors generated by the patients were quite novel, and identified important information likely to be useful in clinical settings as well as subsequent research with this high-risk population. 相似文献
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Engraftment after bone marrow transplantation (BMT) can be monitored with genetic markers. Cytogenetic markers are the ones that can be studied earliest. Of 27 patients studied, 16 had a sex-mismatched donor, and in 8 cases, there were discriminative markers identified with regular Giemsa and Q-banding. In one case, there was a rather slight polymorphism of the C-bands of chromosomes #9. Thus, donors' cells were identifiable in 25 of 27 cases (93%). The markers studied easiest are the sex chromosomes in sex-mismatched BMT. Different fluorescence of the centromeric regions of chromosomes #3 and characteristic satellites of acrocentric chromosomes are rather frequent and also well suited to discriminate donors' from patients' cells. Nonprominent variabilities (fluorescence of the centromeric regions of chromosomes #4 and #6 after Q-banding), rare polymorphisms (pericentric inversions of chromosomes #1 and #9), and difficult to evaluate polymorphisms (heterochromatic regions of chromosomes #1, #9, and #16) are not very practical for the routine monitoring of engraftment after BMT. 相似文献
12.
Protection of killer antiidiotypic antibodies against early invasive aspergillosis in a murine model of allogeneic T-cell-depleted bone marrow transplantation 总被引:5,自引:0,他引:5 下载免费PDF全文
Cenci E Mencacci A Spreca A Montagnoli C Bacci A Perruccio K Velardi A Magliani W Conti S Polonelli L Romani L 《Infection and immunity》2002,70(5):2375-2382
Antiidiotypic monoclonal antibodies (MAbs) representing the internal image of a yeast killer toxin (KT) have therapeutic potential against several fungal infections. The efficacy of KT MAbs against Aspergillus fumigatus was investigated in a mouse model of T-cell-depleted allogeneic bone marrow transplantation (BMT) with invasive pulmonary aspergillosis. Mice were highly susceptible to infection at 3 days post-BMT, when profound neutropenia was observed both in the periphery and in the lungs. Treatment with KT MAbs protected the mice from infection, as judged by the long-term survival and decreased pathology associated with inhibition of fungal growth and hyphal development in the lungs. In vitro, similar to polymorphonuclear neutrophils, KT MAbs significantly inhibited the hyphal development and metabolic activity of germinated Aspergillus conidia. These results indicate that mimicking the action of neutrophils could be a strategy through which KT MAbs exert therapeutic efficacy in A. fumigatus infections. 相似文献
13.
Transfer of allergen-specific IgE-mediated hypersensitivity with allogeneic bone marrow transplantation 总被引:4,自引:0,他引:4
J M Agosti J D Sprenger L G Lum R P Witherspoon L D Fisher R Storb W R Henderson 《The New England journal of medicine》1988,319(25):1623-1628
We investigated whether allergen-specific IgE-mediated hypersensitivity is transferred by bone marrow transplantation. Twelve patients, 14 to 47 years of age, undergoing allogeneic bone marrow transplantation for the treatment of hematologic cancer were selected, along with their donors, by a screening questionnaire for a history of atopy in the donor. We evaluated these donor-recipient pairs before transplantation and at several points afterward for immediate skin-test reactivity to 17 allergens. For allergens for which pretransplantation skin tests had been positive in the donors and negative in the recipients, 20 of 46 post-transplantation skin tests were positive in 8 of the 11 recipients who survived for more than one year after transplantation. For allergens for which both donors and recipients had had negative skin tests before transplantation, only 6 of 256 tests (2.3 percent) were positive in the recipients after transplantation. Long-term transfer of donor-derived mite-specific IgE was demonstrated by radioallergosorbent testing in two recipients. Seven recipients either acquired or had an exacerbation of allergic rhinitis, and two recipients without a history of asthma had asthma one year after transplantation. We conclude that allergen-specific IgE-mediated hypersensitivity is adoptively transferred by bone marrow transplantation from donor to recipient by B cells with allergen-specific memory. 相似文献
14.
R J Cuthbert A Iqbal A Gates P J Toghill N H Russell 《Journal of clinical pathology》1995,48(3):257-259
AIMS--To investigate the incidence of functional hyposplenism in a group of patients who had undergone allogeneic bone marrow transplantation (BMT). METHODS--Splenic function was assessed by counting the number of gluteraldehyde fixed red blood cells containing pits or indentations as examined by interference phase microscopy. Normal values are < 2% whereas splenectomy patients have values of 25 to 40%. RESULTS--Twenty eight BMT recipients (17 men, 11 women) were studied at varying periods post-transplant and the results compared with 20 healthy volunteers and 10 patients who had undergone splenectomy or had splenic atrophy because of haematological conditions. Of the 28 BMT recipients, one had undergone a prior splenectomy; of the remaining 27 patients, four (15%) had evidence of functional hyposplenism with between 5.0 and 34.0% pitted cells. Of these four patients, one had active extensive chronic graft versus host disease (GvHD) which has been previously reported to be associated with functional hyposplenism following transplantation. Only one of the four patients had peripheral blood red cell changes typical of hyposplenism. CONCLUSION--These results confirm that extensive chronic GvHD is associated with hyposplenism. Intermediate degrees of functional hyposplenism may also occur following BMT in the absence of chronic GvHD and in the absence of haematological features of hyposplenism on routine blood films. This may be of significance in mediating the susceptibility to infection with encapsulating bacteria seen following allogeneic BMT. 相似文献
15.
C. Müller P. Ostendorf P. Wernet K. Schüch H. Wahl H. D. Waller 《Journal of molecular medicine (Berlin, Germany)》1984,62(14):675-688
Summary Skin biopsies of 26 patients with leukemia and seven patients with aplastic anemia were investigated before and at different stages after allogeneic bone marrow transplantation (BMT) to establish the immunological criteria which distinguish skin alterations during normal reconstitution from dermal lesions mediated by graft-versushost disease (GvHD). Of the 33 patients studied 27 presented with clinically diagnosed acute and/or chronic GvHD, one patient died of bone marrow rejection. Immunohistological analysis of the respective skin biopsies with selected monoclonal antibodies against human leukocyte antigens (HLA) and differentiation antigens of the lympho-hematopoietic cells revealed low dermal mononuclear cell counts with phenotypically normal constituents in five cases with uncomplicated reconstitution post-grafting. In contrast, increased dermal cellular infiltrates predominantly consisting of Lyt 3+, OKT 8+ T-lymphocytes, as well as of a large number of Ia-like (immune response associated = HLA-D) determinant+ monocytes/macrophages were observed in all patients with active acute/chronic GvH reactivity. As sign of activation simultaneous expression of HLA-D region products was also found on a subset of the invading OKT 8+ T-lymphocytes. Progression of GvHD was associated with additional surface staining of keratinocytes for Ia-like determinants. Loss of Ia-like determinant+, OKT 6+ dentritic epithelial cells in all leukemic patients, as well as in patients with aplastic anemia with or without GvHD suggested damage of Langerhans cells due to the previous radiotherapy and/or specific immunological destruction. In patients with fatal outcome of GvHD prolonged reduction of these dentritic epithelial cells seemed to be indicative of impaired immune reconstitution or bone marrow dysfunction. Thus immunopathological features of skin GvHR may enable early recognition and prognostic evaluation of this disease possibly allowing more effective therapy.Abbreviations GvHD
graft-versus-host disease
- GvHR
graft-versus-host reactivity
- SAA
severe aplastic anemia
- TBI
total body irradiation
- BMT
bone marrow transplantation
- HLA
human leukocyte antigens
- Ia-like antigens
Immune-response-associated antigens
- PBS
phosphate buffered saline
- FITC
fluorescein isothiocyanate
- TRITC
tetramethylrhodamine isothiocyanate
Supported by DFG Sonderforschungsbereich 120, Projekt A 2 and B 1Dedicated to Prof. Dr. Dr. h.c. H.E. Bock on the occasion of his 80th birthday 相似文献
16.
Etienne Roux Claudine Helg Bernard Chapuis Michel Jeannet Eddy Roosnek 《Human immunology》1996,48(1-2):135-138
We analyzed the T-cell repertoire in patients transplanted with bone marrow from an HLA identical sibling by determining the TCR diversity through Vβ-CDR3-size spectratyping with Vβ/Cβ- and Vβ/Jβspecific primers. Using the Vβ/Cβ primers, we observed limited TCR diversity only in recipients of a T-celldepleted graft, whereas the TCR diversity of patients transplanted with an unmanipulated graft seemed to be indistinguishable from the one of a normal individual. However, with Vβ/Jβ-specific primers, increase of the resolution by approximately 10-fold also allowed the detection of imbalances in the TCR repertoire of recipients of an unmanipulated graft. This demonstrates that when high numbers of T cells are cotransfused with marrow, the TCR repertoire is more complete but still not as complete as in normal individuals, thereby emphasizing the important role of coinfused mature T cells in the restoration of the T-cell compartment after bone marrow transplantation. 相似文献
17.
Molecular matching in allogeneic bone marrow transplantation. 总被引:2,自引:0,他引:2
18.
Hemorrhagic cystitis after allogeneic bone marrow transplantation in children: clinical characteristics and outcome. 总被引:8,自引:0,他引:8
G A Hale R J Rochester H E Heslop R A Krance J R Gingrich E Benaim E M Horwitz J M Cunningham X Tong D K Srivastava W H Leung P Woodard L C Bowman R Handgretinger 《Biology of blood and marrow transplantation》2003,9(11):698-705
Hemorrhagic cystitis (HC) is a well-documented adverse event experienced by patients undergoing hematopoietic stem cell transplantation. When severe, HC causes significant morbidity, leads to renal complications, prolongs hospitalization, increases health-care costs, and occasionally contributes to death. We retrospectively studied the medical records of 245 children undergoing an initial allogeneic bone marrow transplantation for malignant disease at St. Jude Children's Research Hospital between 1992 and 1999 to describe the clinical course of HC in all patients and to identify the risk factors for HC in this cohort. Conditioning regimens included cyclophosphamide, cytarabine, and total body irradiation. Grafts from unrelated or mismatched related donors were depleted of T lymphocytes, whereas matched sibling grafts were unmanipulated. All patients received cyclosporine as prophylaxis for graft-versus-host disease. Recipients of grafts from matched siblings also received pentoxifylline or short-course methotrexate. Severe HC developed in 27 patients (11.0%). The median duration of HC was 73 days (range, 5-619 days); 12 patients had ongoing HC at the time of death. In univariate analyses, patients were at increased risk of severe HC if they were male (P =.021) or had received T cell-depleted grafts (P =.017), grafts from unrelated donors (P =.021), a lower total nucleated cell dose (P =.032), or antithymocyte globulin (P =.0446). Multiple regression analysis revealed male sex (beta =.97; P =.027) and unrelated donor graft recipients (beta =.83; P =.039) to be significant factors. 相似文献
19.
I. Quinti A. Velardi S. Le Moli E. Guerra R. D'Amelio P. Mastrantonio M. F. Martelli F. Aiuti 《Journal of clinical immunology》1990,10(3):160-166
Allogeneic bone marrow-engrafted adults immunized with meningococcal types A and C and pneumococcal type 14 polysaccharide antigens showed only low antibody titers of the IgM class, no antibody titers of the IgG or IgA classes, and no bactericidial activityin vitro. The analytical isoelectrofocusing showed the appearance of a restricted pattern of clonotypes in a minority of subjects. These observations are consistent with the hypothesis that B cells in bone marrow transplant patients express some characteristics of neonatal B cells and suggest that polysaccharide-protein conjugates, rather than isolated polysaccharide, might be utilized in the setting of bone marrow transplantation. 相似文献