1/106. Successful one antigen mismatched bone marrow transplant for chronic myeloid leukemia (CML) after two failed syngeneic transplants.In May 1989, a 43-year-old woman with chronic myelocytic leukemia diagnosed in 1988 underwent a syngeneic bone marrow transplant (BMT), conditioned with cyclophosphamide-TBI while in chronic phase. Three years later, because of both cytogenetic and hematological relapse, she was treated with interferon-alpha (IFN-alpha) and hydroxyurea (HU) for 3 years. In 1994 while still in chronic phase, she was conditioned with busulfan-cyclophosphamide (BU-CY) and underwent a second syngeneic BMT. In 1996, following a further cytogenetic and hematological relapse, she was again placed on IFN-alpha and HU therapy for 13 months, when she was referred to our hospital in accelerated phase. In October 1997 following thiotepa, CY and anti-thymocyte globulin conditioning, she underwent an allogeneic BMT from her 1-Ag mismatched brother. She became Ph1 negative with full chimerism and normal hematological parameters; acute graft-versus-host disease (GVHD) grade 3 of the skin and chronic GVHD of the liver occurred. At 11 months follow-up she is in good clinical condition and with a Karnofsky score of 90%. The role of a graft-versus-leukemia (GVL) effect in securing and maintaining the complete remission is discussed.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
2/106. Unusual presentation of graft-versus-host disease in pediatric liver transplant recipients: evidence of late and recurrent disease.Graft-versus-host disease (GvHD) is a multi-organ disease caused by mature donor T cells that are activated by alloantigens expressed by the host antigen-presenting cells. GvHD has been reported after solid organ transplantation with two principal presentations: humoral and cellular. In the cellular type of GvHD after liver transplantation the symptoms are identical to the GvHD after bone marrow transplant, except that the liver is spared because it lacks host antigens. We have described three cases of intestinal GvHD after pediatric liver transplant with an unusual recurrent late presentation in two patients. Two patients were female, and their age at the time of transplant was 8 and 9 months, respectively, and one was an 8-month-old male. They all received reduced liver allografts of identical blood type from three different donors. One patient received two doses of donor bone marrow cell infusion. Two patients received double immunosuppressive therapy constituted by tacrolimus at a dose of 0.05 mg/kg p.o. b.i.d. and steroids 10 mg p.o. daily. One patient received a triple drug immunosuppression with tacrolimus (0.05 mg/kg p.o. b.i.d.), steroids (10 mg p.o. daily) and mycophenolate mofetil (125 mg p.o. b.i.d.). diagnosis of intestinal GvHD was confirmed histologically on intestinal biopsies performed at the time of presentation of the clinical symptoms or at autopsy.- - - - - - - - - - ranking = 0.75keywords = antigen (Clic here for more details about this article) |
3/106. Ultraviolet B irradiation: a new therapeutic concept for the management of oral manifestations of graft-versus-host disease.Ultraviolet irradiation inhibits the proliferative responses of lymphoid cells to mitogens and alloantigens by inactivation of T lymphocytes and antigen-presenting cells. Its immunosuppressive capacity led to the introduction of UV irradiation into clinical practice for the treatment of dermatologic manifestations of chronic graft-versus-host disease. The cumulative experience with psoralen-UV-A rays in the treatment of cutaneous and oral graft-versus-host disease was the incentive for the application of oral UV-B rays in 2 patients with oral graft-versus-host disease signs and symptoms after allogeneic marrow transplantation. Intraoral UV-B irradiation (0.02 mJ/cm(2)) was administered 2 or 3 times per week on an ambulatory basis; the dose was increased by 0. 02 mJ/cm(2) every fourth session. Both patients responded early and satisfactorily, displaying only minimal side effects at a relatively low cumulative dose. Intraoral UV-B proved a valuable modality in the treatment of resistant chronic oral graft-versus-host disease.- - - - - - - - - - ranking = 0.5keywords = antigen (Clic here for more details about this article) |
4/106. Severe acute graft-versus-host disease occurring after syngeneic BMT for AML in a patient not given prior cyclosporin A therapy.A syndrome akin to graft-versus-host disease in the recipient of syngeneic stem cells is hitherto described as being milder, self-limiting and confined to the skin. It is enhanced by prior cyclosporin A therapy. We describe here a recipient of a syngeneic marrow transplant who did not receive priming with cyclosporin A and yet developed severe and progressive graft-versus-host disease which necessitated and responded to high-dose immunosuppressive therapy. We believe that this is because the conditioning regimen in stem cell transplant acts to reset the immune system enabling it to recognise 'self' antigens. bone marrow transplantation (2000) 25, 205-207.- - - - - - - - - - ranking = 0.25keywords = antigen (Clic here for more details about this article) |
5/106. Graft-versus-host disease after liver transplantation: documentation by fluorescent in situ hybridisation and human leucocyte antigen typing.Graft-versus-host disease (GVHD) after liver transplantation is uncommon and the outcome is often fatal. A firm diagnosis of GVHD is difficult because the clinical triad of skin rash, marrow failure and diarrhoea can be indistinguishable from drug reaction or viral infection, and the presence of donor lymphocyte chimerism is not specific. We describe a case of severe GVHD in a female patient after liver transplantation from a male cadaveric donor. skin biopsy showed characteristic changes of GVHD. Using Y-chromosome-specific fluorescent in situ hybridisation (FISH), male lymphocytes were demonstrated in 10% of marrow cells and in 90% of lymphocytes infiltrating the dermal epidermal junction. Donor human leucocyte antigens (HLAs) were detected in the peripheral blood, buccal mucosa and skin by polymerase chain reaction. The GVHD subsided with steroid and anti-thymocyte globulin, but recurred on tailing off of treatment. Despite maximum supportive therapy, including random donor leucocyte infusion, and marrow infusion from a HLA-identical sibling, the patient succumbed to sepsis. Our results showed the utility of combining morphological features with molecular techniques using FISH and HLA typing in confirming a diagnosis of GVHD.- - - - - - - - - - ranking = 1.25keywords = antigen (Clic here for more details about this article) |
6/106. Transplantation of autologous and allogeneic bone marrow with liver from a cadaveric donor for primary liver cancer.BACKGROUND: In histocompatibility mismatched experimental animals, a combination of T-cell-depleted autologous and allogeneic marrow may induce mixed chimerism and tolerance. patients with large primary liver tumors have a poor outcome. We investigated whether it were possible to induce mixed chimerism and obtain an antitumor effect in a patient with a large primary liver cancer after combined liver and bone marrow transplantation (BMT). methods: A 46-year-old female with a primary non resectable liver cancer received a liver transplant from a cadaveric donor. Subsequently, she was conditioned with 4x2 Gy of total lymphoid irradiation, 120 mg/kg cyclophosphamide, and 7.5 Gy total body irradiation. Twelve days after liver transplantation, she received T-cell-depleted autologous:cadaveric 5/6 antigen HLA-mismatched marrow in a proportion of CD34 cells of 0.5:3.0x10(6)/kg. chimerism status was determined with polymerase chain reaction amplification of variable number tandem repeats from dna obtained from CD3 , CD19 , and CD45 magnetic-bead-separated cells. RESULTS: The early posttransplant period was uneventful; liver function was normal and the hematopoietic engraftment of donor and recipient origin was prompt. Alpha-fetoprotein levels dropped from 440 to 35 microg/l. One month after marrow transplantation, donor T-cells decreased markedly. Monoclonal antibody OKT-3 and 10(5)/kg donor T-cells were given. One month later, the patient developed diarrhea and abdominal pain. A colonoscopy showed moderate gastrointestinal acute graft-versus-host disease and a cryptosporidium infection. Three months after BMT, she became a complete donor chimera. chimera cells showed little, if any, reactivity in mixed lymphocyte cultures to recipient and donor cells, but reacted to third party. Five months after BMT, she developed progressive aspergillus fumigatus pneumonia and died. No tumor was found at the autopsy. CONCLUSION: We obtained mixed donor-recipient hematopoietic chimerism without severe acute graft-versus-host-disease, after combined T-cell depleted autologous and allogeneic BMT and a transplantation of a liver from an HLA-mismatched cadaveric donor. Additional donor T-cells enhanced donor bone marrow engraftment, but rejected the autograft. On the basis of this first attempt, further clinical studies are warranted.- - - - - - - - - - ranking = 0.25keywords = antigen (Clic here for more details about this article) |
7/106. Graft vs autoimmunity following allogeneic non-myeloablative blood stem cell transplantation in a patient with chronic myelogenous leukemia and severe systemic psoriasis and psoriatic polyarthritis.OBJECTIVE: No specific therapy exists for autoimmune diseases caused by self-reactive lymphocytes. As shown in experimental animals, which led to pilot clinical studies, elimination of self-reactive lymphocytes can be accomplished with high-dose chemoradiotherapy, followed by autologous stem cell transplantation, by re-establishment of unresponsiveness to self antigens of newly generated lymphocytes, due to a mechanism of central clonal deletion. We hypothesized that self-reactive lymphocytes causing autoimmune disease may be successfully eliminated by highly immunosuppressive yet not necessarily myeloablative conditioning in conjunction with allogeneic blood stem cell transplantation, since immunocompetent alloreactive lymphocytes of donor origin can effectively eliminate residual host-type hematopoietic cells, self-reactive lymphocytes included, by a mechanism that resembles graft-vs-leukemia (GVL) effects. The present report is an attempt to confirm the existence of graft-vs-autoimmunity (GVA) effects in parallel with amplification of the alloreactive potential of donor lymphocytes following allogeneic non-myeloablative stem cell transplantation (NST). methods: We identified a patient with severe psoriatic arthritis who also had philadelphia (bcr/abl) positive chronic myelogenous leukemia and therefore was fully eligible for NST. Both diseases responded initially to non-myeloablative conditioning involving fludarabine 30 mg/m2 x 6, anti-T-lymphocyte globulin 10 mg/kg X 4, and busulfan 4 mg/kg x 2. RESULTS: The initial NST procedure was uneventful and resulted in elimination of all signs of autoimmunity (psoriasis and arthritis). recurrence of polyarthritis and exacerbation of psoriasis were observed in parallel with a significant increase in the proportion of male (host) dna, and 5% of the mitoses were bcr/abl positive, indicating an increase in the clone of CML. Both bcr/abl-positive cells identified by RT-PCR and psoriatic arthritis were successfully eliminated following discontinuation of anti-GVHD prophylaxis with cyclosporine A (CSA), which resulted in activation of the alloreactive potential of donor T cells, accompanied by graft-vs-host disease (GVHD), suggesting the existence of GVA effects. RT-PCR for bcr/abl remains consistently negative for nearly 3 years, and all dna remains donor type. CONCLUSIONS: The response of autoimmune disease manifestations to GVA effects in parallel with elimination of all host-derived hematopoietic cells supports our working hypothesis that autoimmune diseases caused by self-reactive lymphocytes may be effectively treated by elimination of alloreactive self-reactive lymphocytes following induction of host-vs-graft tolerance, in analogy with replacement of malignant or genetically abnormal host cells following DLI. It is therefore suggested that intentional GVA effects may be inducible by DLI following a conventional or preferably safer non-myeloablative regimen in recipients with life-threatening autoimmune diseases resistant to conventional modalities. Adoptive immunotherapy of autoimmunity may thus involve a two-step procedure: first, inducing host-vs-graft and graft-vs-host transplantation tolerance through a transient stage of mixed chimerism; second, inducing controlled GVA effects, initially by discontinuation of CSA and then, if indicated, by late outpatient DLI to eradicate residual hematopoietic cells of host origin.- - - - - - - - - - ranking = 0.25keywords = antigen (Clic here for more details about this article) |
8/106. Infiltrating T cells during liver graft-versus-host disease show a restricted T-cell repertoire.Data from animal models have shown that hepatic graft-versus-host disease (GVHD) may be mediated by donor T cells interacting with liver adhesion molecules, other minor histocompatibility antigens, or both. We hypothesized that T-cell infiltrates within a liver biopsy during clinical GVHD would show a restricted T-cell response because the T cells would be responding to a limited number of antigens. We studied the peripheral T-cell repertoire and the liver-infiltrating T-cell repertoire of a patient who developed skin GVHD and subsequent liver GVHD after a matched sibling bone marrow transplantation for acute myeloid leukemia. Spectratype analysis of peripheral blood at the time of liver GVHD revealed that the patient had reconstituted a complex peripheral T-cell repertoire as evidenced by the presence of complementarity-determining region 3 (CDR3) length heterogeneity in most of the T-cell families. The repertoire complexity was skewed in variable gene beta (VB) 5.3, VB4, VB7, VB8, and VB15. Spectratype analysis on the liver biopsy sample revealed a limited infiltrate with an oligoclonal expansion in VBs 4, 7, and 8. We evaluated the T-cell infiltrate in more detail by sequencing the relevant expansions noted by spectratype and developing probes for the predominant CDR3 sequences. These clonotype probes were hybridized to peripheral blood and liver samples from the patient, a T-cell line developed from the patient's peripheral blood at the time of the initial skin GVHD, the donor's blood and marrow, and control samples. The results showed that the T-cell infiltrate during liver GVHD is mediated by a limited number of T cells, and that those cells are mostly different from the ones expanded from the peripheral blood during an acute skin GVHD reaction. These data support the concept that liver GVHD is a response to tissue-specific minor histocompatibility antigens.- - - - - - - - - - ranking = 0.75keywords = antigen (Clic here for more details about this article) |
9/106. Allogeneic peripheral blood stem cell transplantation for severe aplastic anemia.Allogeneic peripheral blood stem cell transplantation (PBSCT) is rarely applied for the treatment of severe aplastic anemia (SAA) because of questionable durability of engraftment and increased risk of graft versus host disease (GVHD). We performed allogeneic PBSCT in 3 SAA patients from their human leukocyte antigen (HLA)-identical siblings. One received bone marrow after conditioning with cyclophoshamide (Cy) plus antithymocyte globulin. He had a second transplant with peripheral blood stem cells from the original donor because of a graft failure (GF). Two other patients received PBSCT as a first option, with Cy as the only conditioning drug. The 3 patients received short-term methotrexate and cyclosporine as a postgrafting immunosupression. In the latter 2 cases, no GF has been observed, and a successful and complete hematological recovery was achieved and maintained for 28 and 25 months, respectively. In conclusion, PBSCT provides a quick and complete hematological recovery in SAA patients.- - - - - - - - - - ranking = 0.25keywords = antigen (Clic here for more details about this article) |
10/106. Epstein-Barr virus-associated post-transplant lymphoproliferative disease after bone marrow transplantation mimicking graft-versus-host disease.In contrast to solid organ transplantation (Tx), the incidence of post-transplant lymphoproliferative disease (PTLD) after hematopoietic stem cell Tx (HSCT) is generally low. This risk, however, is significantly elevated in patients receiving human leukocyte antigen (HLA) mis-matched or T-cell-depleted grafts, or after treatment for severe graft-versus-host disease (GvHD). An 18-yr-old patient with positive Epstein-Barr virus (EBV) serology received a fully matched, unmanipulated bone marrow graft from an unrelated EBV-positive donor for treatment of acute myeloid leukemia (AML) in second complete remission. GvHD prophylaxis was performed with cyclosporin A (CsA) and a short course of methotrexate. Four months after Tx, the patient developed ulcerative tonsillitis that was unresponsive to antibiotic treatment. diarrhea appearing simultaneously was interpreted as gastrointestinal GvHD and steroids were added to CsA. A few days later the patient was admitted to hospital because of generalized seizure and pneumonia. Despite reduction of immunosuppression, intensification of anti-viral treatment, and subsequent mechanical ventilation, the patient died of acute respiratory distress 6 days later. autopsy demonstrated disseminated EBV-induced, multi-nodular lymphoma infiltration of the entire colon but no signs of GvHD. Moreover, both lungs, paratracheal lymph nodes, kidneys, thyroid gland, and liver were infiltrated with large B-cell non-Hodgkin's lymphomas. This case underlines the rapid and aggressive course of EBV-induced disseminated PTLD after HSCT, initially mimicking intestinal GvHD because of massive colonic lymphoma infiltration. Tissue biopsies should be performed early for establishing correct diagnosis, thus enabling specific therapy, e.g. infusion of donor leukocytes with cytotoxic t-lymphocytes.- - - - - - - - - - ranking = 0.25keywords = antigen (Clic here for more details about this article) |
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