Cases reported "Acute Disease"

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1/13. Detailed monitoring of hematopoietic chimerism in a child treated by adoptive immunotherapy for high risk of relapse after BMT for acute myeloid leukemia.

    We report a case of a 13-year-old boy who was transplanted for relapse of acute myeloid leukemia (AML). A detailed study of hematopoietic chimerism was performed using polymerase chain reaction (PCR) of variable number of tandem repeats (VNTR) at very short time intervals. We used discontinuation of post-transplant immunosuppression and donor lymphocyte infusions (DLI) in order to prevent leukemia relapse that was indicated by a progressive increase in autologous hematopoiesis. Despite the fact that the boy relapsed 10 months after BMT, we could see a significant influence of adoptive immunotherapy on the mixed chimerism status during the post-transplant period.
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2/13. Early allogeneic blood stem cell transplantation after modified conditioning therapy during marrow aplasia: stable remission in high-risk acute myeloid leukemia.

    Two patients with high-risk acute myeloid leukemia (AML) whose bone marrow aspirates showed more than 25% blasts between 2 and 4 weeks after the first induction chemotherapy immediately received modified conditioning therapy with intravenous busulfan at 50% of the usual dose and fludarabine, before hematologic recovery occurred. Unmanipulated G-CSF mobilized peripheral blood stem cells from an HLA-identical sibling donor were transfused and haematopoietic recovery was achieved in both recipients. Both of them are in continuing hematological remission with full donor chimerism 12 and 22 months after transplantation. Early treatment intensification with allogeneic cell therapy during marrow aplasia might cure high-risk AML patients who are unlikely to achieve remission with conventional chemotherapy protocols.
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keywords = chimerism
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3/13. Extramedullary relapse in the left proximal femur with philadelphia chromosome positive acute lymphoblastic leukemia after allogeneic bone marrow transplantation.

    We describe a rare presentation of extra-medullary relapse in an adolescent boy with philadelphia chromosome-positive acute lymphoblastic leukemia who had undergone allogeneic bone marrow transplantation after first remission. In spite of enduring bone marrow remission, the patient experienced a local relapse in the left proximal femur within 3 years of the transplant. The findings from radiography, bone scintigraphy, and chimerism analysis with short tandem repeats as well as bone marrow aspirates taken via the iliac crests were indeterminate. magnetic resonance imaging at the onset of hip pain was characterized by decreased signal intensity of the left proximal femur, a finding characteristic of bone marrow edema. Confirmation of extra-medullary relapse of the proximal femur was delayed until histologic proof of the computed tomography-guided biopsy samples was obtained. Overt bone marrow relapse was identified 14 months later. Reestablishment of normal donor hematopoiesis was achieved with reinduction chemotherapy.
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4/13. Successful immunotherapy in early relapse of acute myeloid leukemia after nonmyeloablative allogeneic stem cell transplantation.

    We report on a 35-year-old woman who underwent allogeneic stem cell transplantation (SCT) in second complete remission (CR) of acute myeloid leukemia (AML) after reduced-intensity conditioning with fludarabine and 2 Gy of total body irradiation. For graft-versus-host disease (GVHD) prophylaxis, cyclosporin A (CsA) and mycophenolate mofetil (MMF) were given. On day 27 after SCT complete hematological remission and donor chimerism was documented. However, in CD34( ) bone marrow cells 28% of recipient hematopoiesis persisted. On day 59 leukemic relapse occurred. After discontinuation of CsA and onset of GVHD, complete donor chimerism and hematological CR were achieved which has been maintained for 14 months.
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5/13. Successful reduced-intensity stem cell transplantation from an HLA haploidentical 3-loci-mismatched donor on the basis of fetomaternal microchimerism in a patient with advanced acute myeloid leukemia.

    A 31-year-old woman with advanced acute myeloid leukemia underwent non-T-cell-depleted (TCD) peripheral blood stem cell transplantation (PBSCT) with a reduced-intensity conditioning regimen. The donor was an HLA haploidentical 3-loci-mismatched complementary sibling who had not inherited maternal hla antigens. Long-term fetomaternal microchimerism was detected by nested polymerase chain reaction with specific primer typing. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus with minidose methotrexate. Durable engraftment was achieved without severe acute GVHD, and complete remission was obtained. Thus non-TCD HLA haploidentical reduced-intensity PBSCT based on fetomaternal immunological tolerance appears to be feasible. Our results have important implications in the selection of alternative donors and conditioning regimens for allogeneic hematopoietic stem cell transplantation.
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keywords = chimerism
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6/13. Acute graft-versus-host disease of the heart.

    Graft-versus-host disease (GVHD) is a frequent cause of morbidity and mortality after bone marrow transplantation. Acute GVHD most commonly involves the skin, gastrointestinal tract, and liver. Involvement of other organ systems is rare and remains controversial. We report a patient with GVHD who suffered a fatal ventricular arrhythmia shortly after bone marrow transplantation. autopsy of the heart showed lymphocyte infiltration. Investigations for cardiotrophic viruses were negative, and chimerism analysis of the heart showed both donor and recipient dna. We conclude that the cause of death was possibly graft-versus-host disease of the heart. A review of the literature revealed a total of 14 cases of possible cardiac GVHD. All but one of the reported cases have occurred in pediatric patients and six of those patients died, suggesting that this may be a rare but frequently fatal complication of pediatric allogeneic stem cell transplant.
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7/13. Acute graft-versus-host disease in pancreas transplantation: a comparison of two case presentations and a review of the literature.

    As a complication of solid organ transplantation, acute graft-versus-host disease (GVHD) is most associated with small bowel and liver transplants. We present two cases of acute GVHD following pancreas transplantation. Case 1 was a 27-year-old female who underwent cadaveric pancreas transplant 9 months after a successful live donor kidney transplant. Case 2 was a 38-year-old male who received a simultaneous cadaveric pancreas and live donor kidney transplant. Both patients presented within 30 days of transplant with nonspecific symptoms. Rejection and infection were ruled out. Both subjects had progressive decline in mentation associated with pancytopenia and hyperbilirubinemia. Rash was not present until late in their hospital course. skin biopsies demonstrated mixed chimerism with pancreas donor dna diagnostic of GVHD. Acute GVHD is a rare, often fatal, complication of pancreas transplantation, and its presentation appears to differ from acute GVHD associated with stem cell transplantation.
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keywords = chimerism
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8/13. Clonal karyotype evolution involving ring chromosome 1 with myelodysplastic syndrome subtype RAEB-t progressing into acute leukemia.

    Karyotypic evolution is a well-known phenomenon in patients with malignant hematological disorders during disease progression. We describe a 50-year-old male patient who had originally presented with pancytopenia in October 1992. The diagnosis of a myelodysplastic syndrome (MDS) FAB subtype RAEB-t was established in April 1993 by histological bone marrow (BM) examination, and therapy with low-dose cytosine arabinoside was initiated. In a phase of partial hematological remission, cytogenetic assessment in August 1993 revealed a ring chromosome 1 in 13 of 21 metaphases beside BM cells with normal karyotypes [46,XY,r(1)(p35q31)/46,XY]. One month later, the patient progressed to an acute myeloid leukemia (AML), subtype M4 with 40% BM blasts and cytogenetic examination showed clonal evolution by the appearance of additional numerical aberrations in addition to the ring chromosome [46,XY,r(1), 8,-21/45,XY,r(1), 8,-21,-22/46, XY]. Intensive chemotherapy and radiotherapy was applied to induce remission in preparation for allogeneic bone marrow transplantation (BMT) from the patient's HLA-compatible son. After BMT, complete remission was clinically, hematologically and cytogenetically (normal male karyotype) confirmed. A complete hematopoietic chimerism was demonstrated. A relapse in January 1997 was successfully treated using donor lymphocyte infusion and donor peripheral blood stem cells (PB-SC) in combination with GM-CSF as immunostimulating agent in April 1997, and the patient's clinical condition remained stable as of January 2005. This is an interesting case of a patient with AML secondary to MDS. With the ring chromosome 1 we also describe a rare cytogenetic abnormality that predicted the poor prognosis of the patient, but the patient could be cured by adoptive immunotherapy and the application of donor's PB-SC. This case confirms the value of cytogenetic analysis in characterizing the malignant clone in hematological neoplasias, the importance of controlling the quality of an induced remission and of the detection of a progress of the disease.
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9/13. Acute graft-versus-host disease after liver transplantation diagnosed by fluorescent in situ hybridization testing of skin biopsy specimens.

    Acute graft-versus-host disease after orthotopic liver transplantation is an underrecognized entity with a guarded prognosis. We describe a patient who underwent orthotopic liver transplantation with an HLA-matched donor liver. She had an uneventful recovery from operation up until day 36 posttransplantation, when she developed a generalized, erythematous, mostly macular eruption, accompanied by ascites, diarrhea, and fever. The diagnosis of graft-versus-host disease was considered but a drug rash could not be excluded. A polymerase chain reaction-based chimerism assay failed to identify donor dna in peripheral blood. A confirmatory fluorescent in situ hybridization analysis revealed significant numbers of donor lymphocytes in biopsied skin, with lesser amounts in biopsy specimens from the stomach and colon. Despite immunosuppressive treatment, the patient died of overwhelming sepsis 18 weeks after transplantation. We conclude that early testing of skin biopsy specimens using fluorescent in situ hybridization in sex-mismatched patients with orthotopic liver transplantation can serve as an early diagnostic tool for graft-versus-host disease.
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ranking = 0.16666666666667
keywords = chimerism
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10/13. Fetal liver transplantation in 2 patients with acute leukaemia after total body irradiation.

    2 patients with acute leukaemia in relapse were transplanted with fetal liver cells following a conditioning regimen of cyclophosphamide (120 mg/kg) and total body irradiation (1000 r). Each patient achieved a remission with haematopoietic recovery that was rapid in one case and delayed in the other. In one case there was evidence of chimerism as demonstrated by the presence of the xyy karyotype of the donor fetus in 20% of marrow metaphases, by the presence of double Y bodies in the peripheral blood, by the appearance of new HLA-antigens, and by red cell isoenzyme phenotypes of donor origin. In the second case there was prompt haematopoietic recovery and the appearance of red cell isoenzyme phenotype of donor origin. survival was 153 and 30 d, respectively, and both patients died of interstitial pneumonia without evidence of graft versus host disease.
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