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PubMed1994

Allogeneic marrow transplantation for myelodysplastic syndrome complicating autologous bone marrow transplantation.

A patient with refractory relapsed Hodgkin's disease underwent an autologous bone marrow transplant in July 1987 and achieved remission of Hodgkin's disease. He had complete hematological recovery but developed pancytopenia 3 years post bone marrow transplantation with morphological evidence of myelodysplasia. High-dose cyclophosphamide, 200 mg/kg, chemotherapy followed by an allogeneic bone marrow transplant from a HLA-matched sibling was performed in April 1991 with complete hematological recovery. Allogeneic bone marrow transplantation was thus used successfully to treat a potential complication of autologous bone marrow transplantation.

Adult↗
PubMed2006

CD8 T cells specific for a donor-derived, self-restricted transplant antigen are nonpathogenic bystanders after vascularized heart transplantation in mice.

CD8 T cell cross-priming, an established mechanism of protective antiviral immunity, was originally discovered during studies involving minor transplantation Ags. It is unclear whether or how cross-primed CD8 T cells, reactive to donor-derived, but recipient class I MHC-restricted epitopes, could injure a fully MHC-disparate, vascularized transplant. To address this question we studied host class I MHC-restricted, male transplantation Ag-reactive T cell responses in female recipients of fully MHC-disparate, male heart transplants. Cross-priming to the immune-dominant determinant HYUtyp occurred at low frequency after heart transplantation. CD8 T cell preactivation through immunization with HYUtyp mixed in CFA did not alter the kinetics of acute rejection. Furthermore, neither HYUtyp immunization nor adoptive transfer of HYUtyp-specific TCR-transgenic T cells affected outcome in 1) a model of chronic rejection in the absence of immunosuppression or 2) a model of allograft acceptance induced by costimulatory blockade. The results support the contention that CD8 T cells reactive to host-restricted, but donor-derived, Ags are highly specific and are nonpathogenic bystanders during rejection of MHC-disparate cardiac allografts.

Acute Disease↗
PubMed2000

Unrelated donor marrow transplantation: an update of the experience of the Italian Bone Marrow Transplant Group (GITMO).

Unrelated donor bone marrow transplant (UD-BMT) has become an attractive alternative source of hematopoietic cells for patients lacking a matched sibling. The aim of this paper was to report on results of the 696 UD BMTs performed in 31 Italian institutions during the first 10 years of activity of the Italian Bone Marrow Donor Registry (IBMDR). In 1989 the Italian Bone Marrow Transplant Group (GITMO) established the IBMDR to facilitate donor search and marrow procurement for patients lacking an HLA identical sibling. By end of December 1999, 260,000 HLA-A, B typed volunteer donors had been cumulatively registered and 2,620 searches had been activated for Italian patients. At least one HLA-A, B, DRB1 matched donor was found for 54% of the patients and 696 UD BMTs were performed. In 50% of cases the donor was found in the IBMDR and in 50% in 15 other Registries. The average time from search activation to transplant was 6 months for disease other than CML. For CML it was 14 months. Actuarial 12-month transplant-related mortality (TRM) was 68% in patients grafted between 1979 and 1992 and 44% for patients grafted after 1993. Twenty-eight per cent of patients developed grade III or IV acute GvHD and 24% developed extensive chronic GvHD. The rate of disease free survival at three years was 57% for patients with 1st chronic phase CML, 37% for patients with 1st or 2nd CR ALL, 31% for AML or MDS patients < or = 18 years of age and 54% for patients with inborn errors. We conclude that the IBMDR has benefited a substantial number of patients lacking a matched sibling and has facilitated the recruitment of UDs into the international donor pool. The long time required for the search is the major obstacle to the success of this programme. This suggests that early transplant and a decrease in TRM could further improve these encouraging results.

Bone Marrow Transplantation↗
PubMed2002

Unrelated bone marrow transplantation in thalassemia. The experience of the Italian Bone Marrow Transplant Group (GITMO).

BACKGROUND AND OBJECTIVES: Allogeneic bone marrow transplantation (BMT) is a widely accepted therapeutic approach in homozygous beta-thalassemia. However, the majority of patients do not have a genotypically identical donor within the family. This prompted us to conduct a pilot study to investigate the feasibility of matched unrelated bone marrow transplantation in thalassemia. The major drawback was the high risk of immunologic and transplant-related complications, mainly graft-versus-host disease (GvHD) and graft failure. DESIGN AND METHODS: Our aim was to reduce this risk through careful selection of donor/recipient pairs. HLA haplotypes that show a high linkage disequilibrium among their class I, class II and class III alleles are considered extended or ancestral haplotypes. RESULTS: These haplotypes are conserved and can be shared by apparently unrelated individuals. Our study shows that matching for these haplotypes significantly improves the outcome of unrelated bone marrow transplantation in thalassemia. In fact, results were comparable to those obtained in transplants using HLA-identifical family donors. INTERPRETATION AND CONCLUSIONS: Better results were obtained in patients with lesser iron overload and when the donor shared an identity for the DPB1 alleles.

Adolescent↗
PubMed2003

[Comparison of curative effect of autologous peripheral blood stem cell transplantation versus bone marrow transplantation for acute leukemia].

To compare the clinical outcome of autologous peripheral blood stem cell transplantation (APBSCT) and autologous bone marrow transplantation (ABMT) in treatment of patients with acute leukemia in first remission, 41 patients received APBSCT, 17 patients received unpurged ABMT and 30 patients received purged ABMT. The results showed that hematopoietic recovery was significantly earlier after APBSCT than that after purged or unpurged ABMT. The 3-year disease-free survival (DFS), relapse rate (RR) and transplant-related mortality (TRM) for all patients of 3 groups were 51.7%, 41.7% and 6.8%, respectively. DFS and RR were significantly influenced by disease types (ALL or AML) and intervals between diagnosis and CR(1) or CR(1) and transplant. The main causes of transplant-related death were infection and hemorrhage. After APBSCT, DFS, RR and TRM were 48.4%, 43.9% and 4.9%, respectively, and did not differ significantly from those found in unpurged ABMT (47.1%, 45.6% and 11.8%) or purged ABMT (66.5%, 29.6% and 6.7%). It is concluded that the clinical outcome of APBSCT is similar to unpurged or purged ABMT but APBSCT allows faster recovery of hematopoiesis and needs less transfusion support.

Acute Disease↗
PubMed1992

[The kinetics of vaccine antibodies against tetanus toxoid, diphtheria toxoid, measles virus, poliomyelitis virus and pneumococcus after allogeneic and autologous bone marrow transplantation and revaccination. 3: The kinetics of vaccine antibodies against tetanus toxoid and diphtheria toxoid after allogeneic and autologous bone marrow transplantation and combined revaccination against diphtheria and tetanus].

The 3rd part of the paper deals with the results of a combined revaccination against diphtheria and tetanus in a group of 25 children after allogeneic bone marrow transplantation (BMT) with and without graft versus host disease (GvHD) and after autologous transplantation. It can be shown that in the allogeneic transplanted groups with and without GvHD it is possible to build up a tetanus and diphtheria antitoxin titre in a safe protective cause by a 2nd basic immunisation consisting of 3 single vaccinations starting about 9 to 12 months later. For autologous transplanted children only 1 to 2 vaccinations at a later term than for the allogeneic transplanted children may possibly be sufficient.

Bone Marrow Transplantation↗
PubMed1996

Analysis of time to death after transplantation when transplants are only given to patients in remission.

The analysis in nonrandomized studies of the potential benefit to a patient which is derived from organ transplantation has been an important topic in survival analysis, having served as a key motivation for the development of such methods as the Mantel-Byar test and the Cox regression model with time-dependent covariates. This paper discusses an additional complication in the analysis of survival after transplantation that arises in cases when organ transplantation is only given to patients who are currently in remission from their illness after a first application of some other initial treatment. We show that the time-dependent covariates methods available in current survival analysis statistical programs are inadequate to properly handle the comparison of subsequent survival from transplant in this case, and propose a modification of the Mantel-Byar test specifically designed to deal with this difficulty. The proposed method is contrasted with other approaches using data from studies of bone marrow transplantation in the treatment of childhood cancer.

Biometry↗
PubMed1996

[Difference in costs of autologous transplantation of peripheral and bone marrow hematopoietic stem cells. A retrospective analysis over 1 year of transplantation in lymphoma, Hodgkin's disease and myeloma in a Center].

The study analysed the financial benefits of transplantation with peripheral blood stem-cells primed after chemotherapy and growth factor in comparison with bone marrow transplantation. Twenty-three consecutive transplantations were performed during one year: 14 peripheral blood stem-cell (CSC group) and 9 bone marrow transplantations (MO group). No differences in patients characteristics were seen between the two groups except for higher number of "BEAM" conditioning in CSC group. Were analyzed delay in neutrophil and platelet recovery, numbers of days in hospital, with fever, under antibiotics, costs of supportive therapy, stem-cell collection and cryopreservation. Difference was significant for duration of neutropenia with advantages in CSC group, but the number on days in hospital, with fever or under antibiotics were similar. Number of platelet transfusions was reduced in CFC group: this economical advantage was lost with the cost of growth factor used for priming stem-cells stem-cell collections and cryopreservations. In our retrospective study, financial advantages associated to peripheral blood stem-cell transplantation was not verified.

Adolescent↗
PubMed1997

Randomized trial of autologous filgrastim-primed bone marrow transplantation versus filgrastim-mobilized peripheral blood stem cell transplantation in lymphoma patients.

Although a large amount of data is available on the effects of filgrastim (granulocyte colony-stimulating factor [G-CSF]) on the mobilization of stem cells in the circulation, data concerning its effects on bone marrow (BM) harvesting is scarce and controversial. We have designed a randomized trial comparing filgrastim-mobilized peripheral blood stem cell (PBSC) transplantation with filgrastim-primed autologous bone marrow transplantation (ABMT). Fifty-five patients affected by non-Hodgkin's (n = 38) or Hodgkin's (n = 17) lymphoma, selected for autologous transplantation over a 12-month period in a single institution, were randomized 2:1 to undergo BM or PB harvest/collection after priming for 3 days with filgrastim, 16 microg/kg body weight daily subcutaneously. BM priming with G-CSF allowed the harvest of a significantly higher number of mononuclear cells (MNC) (0.53 x 10(8)/kg, range, 0.32 to 1.40), as compared with a historical control of unprimed BM harvests (0.43 x 10(8) MNC/kg, range, 0.15 to 0.72, P = .001). After high-dose ablative therapy, median time to neutrophil recovery above 0.5 x 10(9)/L was 12 days for BM and 11 days for PB (P = .219); median time to platelet recovery above 20 x 10(9)/L was 13 days for BM and 11 days for PB (P = .242). The same number of red blood cells, platelet transfusions, and posttransplant G-CSF doses were required in the two groups of patients. Less patients (50% v 70%) became febrile in the group transplanted with mobilized PB, but days of fever/patient and days on antibiotics were overlapping. The median time spent in the hospital after reinfusion was 16.5 and 15.5 days after primed BM and primed PB, respectively (P = .134). These data suggest that in patients with lymphoma submitted to autologous transplantation, the reinfusion of filgrastim-primed BM or filgrastim-mobilized PB leads to similar results, with an advantage of only 1 day in the neutrophil recovery and 1 day on the time spent in the hospital in favor of primed PB. Either option can be chosen on the basis of the availability of a surgery room or cell separator facilities and considering the patients' characteristics and wishes.

Bone Marrow Transplantation↗
PubMed1987

Patterns of angiogenesis in neural transplant models: I. Autonomic tissue transplants.

Functional vascular connections must form rapidly to prevent ischemic damage to grafted neural tissues. The temporal sequence by which transplant circulation is re-established provides information about the angiogenic capacity of either intact or damaged CNS blood vessels. This study compares the time course and mechanism of vascular reperfusion in allografts of superior cervical ganglia or adrenal medulla inserted either into the fourth ventricle or directly into the parietal cortex of perinatal rats. Tritiated thymidine was administered to recipients to determine angiogenic patterns at various postoperative time periods. After processing for light microscopic autoradiography, host and graft endothelial labelling indices were determined in order to establish the temporal sequence and location of vascular proliferation. Correlative electron microscopy depicted the morphological changes in transplant vasculature. Some recipients were prelabelled with 3H thymidine prior to transplantation to determine if host vessels invaded the grafts. Intraventricular graft vessels initially collapsed but sustained minimal ischemic damage and were completely reperfused by 24 hours postoperative. Adjacent intact host vessels attained peak 3H thymidine incorporation at 20 hours. Intrinsic graft vessels were radioactively labelled only after 48 hours. Intraparenchymal transplants surrounded by minimal trauma exhibited a similar temporal sequence of reperfusion and host endothelial proliferation. Intrinsic graft vessels in intraparenchymal grafts sustained more severe damage. With increased trauma, a concomitant delay in graft reperfusion time was observed. Grafts within prelabelled hosts rarely contained any labelled endothelium, indicating that anastomotic connections were made between original, intrinsic graft vessels and nearby host vascular sprouts. This study demonstrates that mature autonomic tissue stimulates the growth of adjacent host vessels when transplanted to undamaged brain surfaces. The anastomosis of nascent host vessels with pre-existing graft vessels is responsible for the rapid re-establishment of circulation within the transplants. A similar mechanism occurs within intraparenchymal grafts, although the rapidity of reperfusion appears to be predicated on the amount of trauma present at the graft site.

Adrenal Medulla↗
PubMed1981

A pseudogene homologous to mouse transplantation antigens: transplantation antigens are encoded by eight exons that correlate with protein domains.

We have isolated about 30 to 40 different BALB/c mouse sperm DNA genomic clones that hybridize to cDNA clones encoding proteins homologous to transplantation antigens. One of these clones (27.1) was selected for sequence because it was polymorphic in Southern blot analysis of the DNAs from BALB/c and CBA mice. A fragment of 5.7 kilobases of this clone was completely sequenced and found to contain a pseudogene whose sequence is highly homologous to the sequences of known transplantation antigens. Pseudogene 27.1 is split into eight exons that correlate with the structurally defined protein domains of transplantation antigens. Using Southern blot hybridization on the DNAs of different inbred mouse strains, we mapped the pseudogene to the Qa-2,3 region, a part of the Tla complex on chromosome 17 that is adjacent to the major histocompatibility complex. The Qa2,3 region encodes lymphoid differentiation antigens homologous to the transplantation antigens in size, in peptide map profiles and in their association with beta2-microglobulin. These mapping studies suggest that gene 27.1 may be a pseudogene for eigher a Qa antigen or an as yet undefined transplantation antigen. Accordingly, we may have isolate genes encoding lymphoid differentiation antigens of the Tla complex as well as those encoding transplantation antigens among the 30 to 40 different genomic clones isolated from our sperm library.

Base Sequence↗
PubMed1995

Multi-organ donor transmission of hepatitis C virus to five solid organ transplant recipients and lack of transmission to corneal transplant recipients.

BACKGROUND: A multi-organ donor seronegative for hepatitis C virus (HCV) by 1st generation enzyme immunoassay (EIA) supplied 5 solid organs and 2 corneas to 7 recipients. This donor was retrospectively shown to be 2nd generation HCV EIA-positive and polymerase chain reaction (PCR)-positive. All 5 solid organ recipients but none of the corneal recipients developed HCV infection. OBJECTIVES: To demonstrate the discordance between serological and PCR-based HCV detection in solid organ transplant recipients and the lack of transmission of HCV to the two corneal transplant recipients. STUDY DESIGN: All 5 solid organ recipients were retrospectively shown to be HCV PCR-negative and -seronegative pre-transplant and HCV PCR-positive post-transplant. Serial serum samples on 3 recipients were evaluated by 2nd generation EIA, a prototypic structural and non-structural dual bead assay (EIA-SA, Abbott), the Chiron Recombinant Immunoblot Assay, 2nd generation (RIBA-2), and the Chiron RIBA HCV Test System Strip Immunoblot Assay 3.0 (RIBA-3, Chiron). RESULTS: The dual bead EIA-SA and RIBA-3 were able to detect HCV seroconversion approximately 6 months earlier than the 2nd generation EIA in 2 recipients, and in 1 recipient only PCR detected infection within the first 10 months. There was no evidence of HCV transmission to the corneal recipients. CONCLUSIONS: Although third generation assays such as the RIBA-3 and EIA-SA narrowed the window of HCV seronegativity in transplant recipients compared with the 2nd generation EIA, PCR was the most sensitive method of detecting acute HCV infection. Despite transmission of HCV to all of the solid organ recipients HCV was not transmitted to the corneal transplant recipients.

Journal Article↗
PubMed2003

Development and gene expression of nuclear transplants generated by transplantation of cultured cell nuclei into non-enucleated eggs in the medaka Oryzias latipes.

To develop nuclear transplantation techniques for the medaka Oryzias latipes, nuclei of cultured cells from transgenic fish were transplanted into unfertilized eggs of the orange-red variety of O. latipes, without enucleation, in two experimental series. In the first experimental series, fibroblast cells cultured from the adult caudal fin were used as donors, which carried the green fluorescent protein (GFP) gene driven by the promoter of the medaka elongation factor 1alpha-A gene. Wild-type body color was another donor genetic marker used in this experimental series. In the second experimental series, cells cultured from 6-day-old embryos were used as donors, which carried the GFP genetic marker driven by the promoter of the medaka beta-actin gene. From more than 1000 eggs transplanted in each experiment, a considerable number of nuclear transplants developed to various embryonic stages showing stage- and tissue-specific expression of the donor genetic markers, although the expression was mosaic in many cases. Three and six of the transplanted eggs in the first and second experimental series (0.3 and 0.5%, respectively) hatched, and the hatchlings expressing the genetic markers survived for up to 3 weeks. The chromosome number varied among cells in a single transplant embryo. The results obtained in these experiments may help future cloning efforts in fish.

Animals↗
PubMed2000

Expression of GFP in nuclear transplants generated by transplantation of embryonic cell nuclei from GFP-transgenic fish into nonenucleated eggs of medaka, Oryzias latipes.

In order to investigate whether foreign genes can be used as genetic markers of donor nuclei in fish nuclear transplantation, expression of the GFP gene derived from donor nuclei was examined in nuclear transplants in medaka (Oryzias latipes). Embryonic nuclei were obtained from blastula embryos produced by crossing of transgenic fish of the wild-type strain heterozygous for the GFP gene with nontransgenic ones or by mutual crossing between transgenic fish. The GFP gene was driven by the promoter of the medaka elongation factor gene, EF-1alpha-A, which is known to induce GFP expression in many tissues except for the muscle in the transgenic fish. The nuclei were transplanted into nonenucleated unfertilized eggs of the orange-red strain. Adult nuclear transplants were successfully obtained at the rate of about 2% of the operated eggs. They were triploid and had no reproductive potential. The GFP gene was expressed in embryos, fry, and adults of nuclear transplants in a pattern similar to that in the transgenic fish. These results indicate that GFP is useful as a foreign genetic marker of donor nuclei in fish nuclear transplantation.

Animals↗
PubMed2004

Effect of post-transplant double filtration plasmapheresis on recurrent focal and segmental glomerulosclerosis in renal transplant recipients.

In the present study, we reviewed the effect of post-transplant double filtration plasmapheresis (DFPP) on recurrent focal segmental glomerulosclerosis (FSGS) in the transplanted kidney allograft. Sixteen patients with post-transplant recurrent FSGS were enrolled in this study. Out of 16 patients with recurrent FSGS after transplantation, five did not receive DFPP and lost their grafts, while 11 did receive DFPP and four of these patients lost their grafts. Seven patients were able to maintain normal renal function for an average observation period of 57.1 +/- 40.7 months (range 7-125 months). In five patients who had a significant reduction in urinary protein after DFPP, the urinary protein level decreased from 26.60 +/- 23.05 g/day (range 3.34-62.6 g/day) to 2.95 +/- 3.42 g/day (range 0.02-8.64 g/day) and renal function was maintained. The beneficial effects of DFPP on graft outcome were more likely to occur if the patients experienced a marked drop in urinary excretion. Thus, post-transplant DFPP appears to be effective for reducing urinary protein levels and improving long-term graft survival. With the small numbers in this trial, however, none of the findings were statistically significant. We recommend the use of post-transplant DFPP to prevent the progression of recurrent FSGS.

Adolescent↗