ABSTRACT
A 10-year-old boy with acute lymphoblastic leukemia in second relapse received CD34+ purified allogeneic peripheral blood stem cell transplantation (PBSCT) from his HLA-haploidentical father. The patient developed grade II acute GVHD and received high-dose methyl-prednisolone starting on day + 13 posttransplant. Renal dysfunction followed by massive gastrointestinal bleeding was observed from day + 14. The laboratory findings including elevated serum LDH, increased RBC fragmentation, higher level of thrombomodulin and undetectable haptoglobin corresponded with the diagnosis of thrombotic microangiopathy (TMA). In spite of various treatments, the patient died of multiple organ failure on day + 93. Post-mortem examination revealed systemic adenovirus infection without histological findings of TMA. Severe adenovirus infection may be confused with TMA, and should be distinguished by rapid virological assay.
Subject(s)
Adenoviridae Infections/diagnosis , Antigens, CD34/immunology , Hematopoietic Stem Cell Transplantation , Vascular Diseases/diagnosis , Adenoviridae Infections/pathology , Adenoviridae Infections/virology , Autopsy , Child , Epithelial Cells/immunology , Epithelial Cells/pathology , Epithelial Cells/virology , Fatal Outcome , Graft vs Host Disease , Humans , Intestines/immunology , Intestines/pathology , Intestines/virology , Male , Necrosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/surgery , Precursor Cell Lymphoblastic Leukemia-Lymphoma/virology , Transplantation, Homologous , Treatment Failure , Vascular Diseases/pathologyABSTRACT
Gaucher disease has been treated by allogeneic bone marrow transplantation (BMT), however, severe bone involvement that is probably the most disabling aspect of this disease is difficult to reverse. Other problem of BMT is the use of intensive preconditioning that adversely affects growth and development of the patients. In this study, a patient with type I Gaucher disease was treated by allogeneic BMT from HLA-matched sibling donor. However, the treatment resulted in late graft failure and the patient developed severe bone involvement. Fifty months after the first BMT, the patient was treated by allogeneic peripheral blood stem cell (PBSC) transplantation without preconditioning. Recombinant human granulocyte-colony stimulating factor (rhG-CSF) was used to mobilize PBSC. Cyclosporine A (CyA) was administered for the prophylaxis of graft-versushost disease (GVHD). Full donor-derived hematopoiesis was obtained, and clinical symptoms including severe bone involvement improved completely with increased glucocerebrosidase activity. It was shown that an engraftment could be obtained without intensive preconditioning when a recipient receives an rhG-CSF-mobilized PBSCs infusion as a secondary transplant. Another important finding of this study is the complete reversal of severe bone involvement by the supply of abundant glucocerebrosidase from high proliferating PBSC graft.
Subject(s)
Gaucher Disease/complications , Gaucher Disease/surgery , Granulocyte Colony-Stimulating Factor/pharmacology , Hematopoietic Stem Cell Mobilization , Peripheral Blood Stem Cell Transplantation/methods , Shoulder Fractures/complications , Bone Marrow Transplantation , Child, Preschool , Female , Gaucher Disease/diagnostic imaging , Glucosylceramidase/metabolism , Humans , Radiography , Shoulder Fractures/diagnostic imaging , Transplantation Conditioning , Transplantation, HomologousABSTRACT
Fetomaternal microchimerism has been demonstrated, and immunologic tolerance to unshared HLA antigens between mother and offspring may be suggested. We used T-cell-repleted bone marrow transplantation (BMT) from their HLA-haploidentical mothers to treat 6 patients with fatal nonmalignant diseases. The number of mismatched HLA loci in the graft-versus-host disease (GVHD) direction was 3 in 4 patients and 2 in 2 patients. The number in the host-versus-graft direction was 3 in 4 patients, 2 in 1 patient, and 1 in 1 patient. Microchimerism of inherited paternal antigens was demonstrated in 5 donors, and microchimerism of noninherited maternal antigens was detected in 3 recipients. GVHD prophylaxis consisted of short-course methotrexate, tacrolimus, and mycophenolate mofetil (3 patients) or short-course methotrexate, tacrolimus, and methylprednisolone (1 patient). Engraftment was achieved in 5 patients who had received preconditioning, and T-cell engraftment was confirmed in 1 patient with severe combined immunodeficiency. Acute GVHD developed in 3 patients: grade 1 in 2 patients and grade 2 in 1 patient. Chronic GVHD was observed in 5 patients: localized type in 3 patients and extended type in 2 patients. Five patients were alive 11 to 30 months after BMT and 1 patient died of chronic GVHD. Unmanipulated haploidentical BMT from a maternal donor may be the treatment of choice of poor-prognosis nonmalignant diseases.
