ABSTRACT
Infectious complications due to adenovirus are of increasing concern after allogeneic stem cell transplantation. Over the past 4 years, we have modified our conditioning regimens to use alemtuzumab in preference to anti-thymocyte globulin (ATG) for pediatric patients receiving stem cell transplants from alternate donors. Recent reports in adult studies implicate alemtuzumab as a risk factor for adenovirus infection. We therefore evaluated the incidence of adenovirus infection in pediatric patients receiving either ATG or alemtuzumab in their conditioning regimens. Of the 111 patients evaluated, a total of 54 patients received ATG and 57 patients received alemtuzumab. In total, 35/111 (32%) patients were infected by adenovirus, and 9/111 (8%) had adenovirus disease (AD). Adenovirus infection was greater in the alemtuzumab group than the ATG group (23/57 vs 12/54) (P=0.039) and disseminated AD was more frequent in the alemtuzumab group vs the ATG group (8/57 and 1/54 respectively) (P=0.032). The presence of Grade 3-4 graft-versus-host disease was a risk factor for adenovirus infection. Our findings highlight the fact that adenovirus infection is a frequent complication after stem cell transplantation from alternate donors in the pediatric population and that alemtuzumab increases the risk of infection compared to ATG. This work will help in identifying at-risk populations for our upcoming immunotherapy trial using adoptively transferred donor-derived adenovirus-specific cytotoxic T lymphocytes.
Subject(s)
Adenovirus Infections, Human/chemically induced , Antibodies, Monoclonal/administration & dosage , Antibodies, Neoplasm/administration & dosage , Antilymphocyte Serum/administration & dosage , Bone Marrow Transplantation/adverse effects , Adenovirus Infections, Human/etiology , Adolescent , Alemtuzumab , Antibodies, Monoclonal/toxicity , Antibodies, Monoclonal, Humanized , Antibodies, Neoplasm/toxicity , Bone Marrow Transplantation/methods , Child , Child, Preschool , Graft vs Host Disease/complications , Hematologic Diseases/complications , Hematologic Diseases/therapy , Humans , Incidence , Infant , Retrospective Studies , Risk Factors , Tissue Donors , Transplantation Conditioning/adverse effects , Transplantation Conditioning/methods , Transplantation, HomologousABSTRACT
Guillain-Barré syndrome is a rare complication in the setting of hematopoietic stem cell transplantation. We report three children with T cell lymphoma/leukemia in whom this syndrome developed soon after they received unrelated donor transplants. The rapid onset of symptoms raises the concern that the bone marrow transplant conditioning regimen (ie, total body irradiation, cyclophosphamide and cytosine arabinoside) might have precipitated the clinical syndrome of ascending polyneuropathy. Although central nervous system toxicity has been well described with high-dose cytosine arabinoside therapy, peripheral neuropathy of the Guillain-Barré type has been reported only infrequently. We review possible factors contributing to the development of this syndrome in these three patients.
Subject(s)
Guillain-Barre Syndrome/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Adolescent , Cyclophosphamide/adverse effects , Cyclophosphamide/therapeutic use , Cytarabine/adverse effects , Cytarabine/therapeutic use , Fatal Outcome , Guillain-Barre Syndrome/chemically induced , Guillain-Barre Syndrome/drug therapy , Guillain-Barre Syndrome/virology , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Leukemia, T-Cell/drug therapy , Leukemia, T-Cell/radiotherapy , Leukemia, T-Cell/surgery , Leukemia, T-Cell/virology , Lymphoma, T-Cell/drug therapy , Lymphoma, T-Cell/radiotherapy , Lymphoma, T-Cell/surgery , Male , Parainfluenza Virus 1, Human/immunology , Parainfluenza Virus 1, Human/isolation & purification , Respirovirus Infections/complications , Respirovirus Infections/diagnosis , Respirovirus Infections/drug therapy , Transplantation Conditioning/adverse effects , Transplantation Conditioning/methods , Transplantation, Homologous , Whole-Body Irradiation/adverse effects , Whole-Body Irradiation/methodsABSTRACT
The hematopoietic stem cell underlying acute myeloid leukemia (AML) is controversial. Flow cytometry and the DNA-binding dye Hoechst 33342 were previously used to identify a distinct subset of murine hematopoietic stem cells, termed the side population (SP), which rapidly expels Hoechst dye and can reconstitute the bone marrow of lethally irradiated mice. Here, the prevalence and pathogenic role of SP cells in human AML were investigated. Such cells were found in the bone marrow of more than 80% of 61 patients and had a predominant CD34(low/-) immunophenotype. Importantly, they carried cytogenetic markers of AML in all 11 cases of active disease examined and in 2 out of 5 cases in complete hematological remission. Comparison of daunorubicin and mitoxantrone fluorescence emission profiles revealed significantly higher drug efflux from leukemic SP cells than from non-SP cells. Three of 28 SP cell transplants generated overt AML-like disease in nonobese diabetic--severe combined immunodeficient mice. Low but persistent numbers of leukemic SP cells were detected by molecular and immunological assays in half of the remaining mice. Taken together, these findings indicate that SP cells are frequently involved in human AML and may be a target for leukemic transformation. They also suggest a mechanism by which SP cells could escape the effects of cytostatic drugs and might eventually contribute to leukemia relapse. (Blood. 2001;98:1166-1173)
Subject(s)
Leukemia, Myeloid/pathology , Stem Cells/pathology , Acute Disease , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Antibiotics, Antineoplastic/pharmacokinetics , Antineoplastic Agents/pharmacokinetics , Benzimidazoles/pharmacokinetics , Cell Separation , Child , Child, Preschool , Daunorubicin/pharmacokinetics , Drug Resistance , Female , Humans , Immunophenotyping , Infant , Leukemia, Myeloid/drug therapy , Leukocytes, Mononuclear , Male , Mice , Mice, Inbred NOD , Middle Aged , Mitoxantrone/pharmacokinetics , Myelodysplastic Syndromes/drug therapy , Myelodysplastic Syndromes/pathology , Neoplasm Transplantation , Neoplasms, Second Primary , Stem Cell Transplantation , Stem Cells/drug effects , Tumor Cells, Cultured/drug effects , Tumor Cells, Cultured/transplantationSubject(s)
Bone Marrow Transplantation/methods , Drug Resistance, Neoplasm/genetics , Genetic Therapy , Herpesvirus 4, Human/genetics , Hodgkin Disease/therapy , Neomycin/metabolism , T-Lymphocytes, Cytotoxic/metabolism , Cell Line , Feasibility Studies , Female , Herpesvirus 4, Human/immunology , Humans , Male , RecurrenceABSTRACT
After bone marrow transplantation (BMT) using T-cell-depleted marrow from an unrelated donor or HLA-mismatched related donor, the risk of developing lymphoproliferative disease associated with the Epstein-Barr virus (EBV) ranges from 1% to 25%. We have shown that administration of donor-derived EBV-specific cytotoxic T lymphocytes (CTL) is effective prophylaxis and treatment for this complication, and we routinely generate CTL for high-risk patients. However, EBV lymphoma can occur in recipients of matched-sibling transplants for whom CTL are unavailable or in patients for whom CTL administration is contraindicated. We report on 3 such patients, who were successfully and safely treated with rituximab, a CD20 monoclonal antibody. The patients remain disease free 7, 8, and 9 months, respectively, after therapy. We conclude that CD20 antibody may be a useful alternative treatment strategy in patients with EBV lymphoma after BMT. (Blood. 2000;95:1502-1505)
