RESUMO
Chédiak-Higashi syndrome (CHS) is one of the primary immunodeficiency syndromes accompanied by oculocutaneous albinism. It is characterized by existence of giant granule of neutrophils, and development of symptoms of hemophagocytic lymphohistiocytosis. CHS is a rare disorder and recognition of the disease is indispensable for its diagnosis. In our case, a four-month-old boy, virus-associated hemophagocytic syndrome (VAHS) was suspected from generation of fever, hepatosplenomegaly, and existence of atypical lymphocytes on admission. However, elevation of serum AST, LDH and ferritin were quite slight as VAHS, and rapid exacerbation of the findings was not seen. Associated virus was undetected. He was finally diagnosed as CHS developing hemophagocyctic lymphohistiocytosis based on the existence of a giant granule of neutrophils in the peripheral blood smear and oculocutaneous albisum and laboratory findings. Clinical outcome was successful after receiving HLA-matched unrelated bone marrow transplantation.
Assuntos
Síndrome de Chediak-Higashi/complicações , Linfo-Histiocitose Hemofagocítica/etiologia , Humanos , Lactente , Linfo-Histiocitose Hemofagocítica/diagnóstico , MasculinoRESUMO
Early T-cell precursor acute lymphoblastic leukaemia (ETP-ALL) is a recently identified subtype of T-ALL with distinctive gene expression and cell marker profiles, poor response to chemotherapy and a very high risk of relapse. We determined the reliability of restricted panel of cell markers to identify EPT-ALL using a previously classified cohort. Then, we applied the cell marker profile that best discriminated ETP-ALL to a cohort of 91 patients with T-ALL enrolled in the Tokyo Children's Cancer Study Group L99-15 study, which included allogeneic stem cell transplantation (allo-SCT) for patients with poor prednisone response. Five of the 91 patients (5·5%) met the ETP-ALL criteria. There were no significant differences in presenting clinical features between these and the remaining 86 patients. Response to early remission induction therapy was inferior in ETP-ALL as compared with T-ALL. The ETP-ALL subgroup showed a significantly poorer event-free survival (4-year rate; 40%) than the T-ALL subgroup (70%, P=0·014). Of note, three of four relapsed ETP-ALL patients survived after allo-SCT, indicating that allo-SCT can be effective for this drug-resistant subtype of T-ALL.
Assuntos
Leucemia-Linfoma Linfoblástico de Células T Precursoras/epidemiologia , Adolescente , Antígenos CD/análise , Antígenos de Neoplasias/análise , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Imunofenotipagem , Lactente , Japão/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Leucemia-Linfoma Linfoblástico de Células T Precursoras/classificação , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/cirurgia , Prednisona/administração & dosagem , Indução de Remissão , Transplante de Células-Tronco , Transplante Homólogo , Resultado do TratamentoRESUMO
We conducted a multicenter postmarketing study to investigate the efficacy and safety of reinduction therapy with a high-dose cytarabine-containing regimen for pediatric patients with relapsed or refractory acute leukemia. Seven of 13 patients (53.8%) with ALL achieved complete or partial remission, and only 1 of 6 patients (16.7%) with AML achieved partial remission. The frequent non-hematologic adverse events were gastrointestinal toxicities, such as vomiting, diarrhea and abdominal pain, as well as pyrexia and headache. Infection appeared in 9 of 20 (45%) patients. There were two death during reinduction therapy. One died of invasive bronchopulmonary aspergillosis, and the other died of intracranial hemorrhage and renal failure. These results indicated that a high-dose cytarabine regimen is effective as reinduction therapy in pediatric patients with relapsed ALL, and supportive care is essential to prevent or control treatment-related adverse events, such as infection.
Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Citarabina/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Antimetabólitos Antineoplásicos/efeitos adversos , Criança , Pré-Escolar , Citarabina/efeitos adversos , Feminino , Humanos , Lactente , Aspergilose Pulmonar Invasiva/etiologia , Aspergilose Pulmonar Invasiva/prevenção & controle , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Pulsoterapia , Recidiva , Indução de Remissão , Resultado do TratamentoRESUMO
BACKGROUND: Treatment response has become one of the most important prognostic factors in childhood acute lymphoblastic leukemia. We evaluated the significance of the complete clearance of peripheral leukemic blasts on survival in children with acute lymphoblastic leukemia. DESIGN AND METHODS: Seven hundred and fifty-four children diagnosed with acute lymphoblastic leukemia, consecutively enrolled from 1999 to 2003 in the TCCSG L99-15 study, were eligible for analysis. Patients were stratified into three risk groups based on presenting features, such as age and the leukocyte count before starting the treatment, followed by reclassification into three categories 7 days after prednisolone monotherapy based on the peripheral blast count; 0/microL (Day8NoBlasts), 1-999/microL and >or= 1,000/microL. RESULTS: After 7 days of prednisolone monotherapy, 249 patients (33%) were classified as Day8NoBlasts, 392 patients (52%) had blast counts of 1-999/microL, and 113 patients (15%) had blast counts >or= 1,000/microL. The event-free survival for all patients was 79.6+/-1.6 (SE)% at 4 years, whereas that for patients with Day8NoBlasts was 90.4+/-2.0% (n=249) and the event-free survival for the other patients was 74.2+/-2.2% (n=504) (log rank p<0.001). The event-free survival for Day8NoBlasts patients with B-lineage acute lymphoblastic leukemia and T-cell acute lymphoblastic leukemia was 89.8+/-2.1% (n=226) and 95.7+/-4.3% (n=23), respectively. In a multivariate analysis, age at diagnosis, the initial white blood cell count, immunophenotype, and gender did not remain as independent risk factors for treatment failure, whereas Day8NoBlasts and marked hyperdiploidy (more than 50 chromosomes) became statistically significant. CONCLUSIONS: Children with Day8NoBlasts constituted one third of all the cases with childhood acute lymphoblastic leukemia with an excellent outcome, and should be candidates for curative management with less intensive treatment.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Crise Blástica/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prednisolona/uso terapêutico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/classificação , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Estudos Retrospectivos , TóquioRESUMO
We retrospectively evaluated early and long-term complications of an intensified conditioning regimen consisting of busulfan and etoposide in combination with either nimustine hydrochloride (ACNU) (BVA regimen, n = 18) or melphalan (BVL regimen, n = 34) in 52 children with acute leukemia or non-Hodgkin's lymphoma. With a median follow-up of 13.2 years after the BVA regimen and 8.1 years after the BVL regimen, 61% and 76% of patients, respectively, are in continuous complete remission. Transplantation-related mortality was 17% and 6% after the BVA and BVL regimens, respectively, and the corresponding relapse rates were 17% and 15%. The most common and severe toxicity was pulmonary complication in the BVA regimen, which was seen in 67% of patients and was life-threatening in 20%. Thirty-three percent of patients after the BVA regimen and 24% after BVL died of relapse or disease progression (n = 9), interstitial pneumonia (n = 2), fungal pneumonia (n = 1), or chronic graft-versus-host disease (n = 2). One of the long-term survivors developed secondary leukemia. A significant decrease in the height standard deviation score of more than 2 SD from diagnosis to the last follow-up was seen in 17% of the patients, with hypothyroidism in 15%, and alopecia in 42%. Because our experience is limited to a small heterogeneous population of patients who mainly underwent transplantation in the first remission, we cannot draw conclusions on the treatment's effectiveness. The BVL regimen is tolerable, however, because no regimen-related death was observed, whereas the BVA regimen is not recommended because of the high incidence of pulmonary complications. The effectiveness of the BVL regimen requires further study.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Leucemia/mortalidade , Linfoma não Hodgkin/mortalidade , Transplante de Células-Tronco , Condicionamento Pré-Transplante , Doença Aguda , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Criança , Pré-Escolar , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Seguimentos , Humanos , Lactente , Leucemia/terapia , Linfoma , Linfoma não Hodgkin/terapia , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Nimustina/administração & dosagem , Nimustina/efeitos adversos , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , Transplante HomólogoRESUMO
BACKGROUND: Long-term survivors of childhood acute lymphoblastic leukemia (ALL) sometimes suffer from adverse long-term sequelae. We analyzed the incidence, clinical course and prognosis of moyamoya syndrome (MoS) following childhood ALL. PROCEDURE: A total of 1,846 ALL patients were treated with four consecutive TCCSG ALL protocols (L84-11, L89-12, L92-13, and L95-14) between 1984 and 1999. We surveyed the MoS cases among these patients in the follow-up studies. RESULTS: Six patients with MoS were identified: four boys and two girls whose ages ranged from 2 years and 1 month (abbreviated as "2y1m") to 14y 1 m at diagnosis of ALL. None of the patients had central nervous system (CNS) leukemia. All six patients received prophylactic cranial irradiation with a dosage of 18 or 24 Gy. Although one patient died of brain infarction due to MoS, no leukemic relapse was observed in the group. The cumulative incidence of MoS in our series was 0.46 +/- 0.02% at 8 years. Among several clinical characteristics, use of cranial irradiation was the only factor that appeared to be significantly related to the development of MoS. CONCLUSIONS: MoS occurs with increased frequency in children treated for ALL, and might be associated with cranial irradiation. Prophylactic cranial irradiation should be used cautiously in ALL patients who can be cured by other CNS-directed therapies.
Assuntos
Irradiação Craniana/efeitos adversos , Doença de Moyamoya/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Adolescente , Antraciclinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Asparaginase/administração & dosagem , Infarto Cerebral/etiologia , Criança , Pré-Escolar , Terapia Combinada , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Suscetibilidade a Doenças , Feminino , Seguimentos , Humanos , Incidência , Japão/epidemiologia , Masculino , Doença de Moyamoya/diagnóstico , Doença de Moyamoya/epidemiologia , Doença de Moyamoya/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Prednisolona/administração & dosagem , Qualidade de Vida , Indução de Remissão , Vincristina/administração & dosagemRESUMO
We report the clinical courses of two cases with relapsed acute lymphoblastic leukemia (ALL) after allogeneic bone marrow transplantation (BMT). After reinduction chemotherapy, the patients received reduced-intensity stem cell transplantation using allogeneic peripheral blood stem cells harvested from their previous BMT donors. The conditioning regimen used consisted of fludarabine and melphalan. Graft-versus-host disease (GVHD) prophylaxis was performed with low dose cyclosporin A (CsA, 1 mg/kg/day d.i.v.) on its own. The regimen related toxicity was minimal, and stable engraftment was achieved. Since acute GVHD had not developed by day 30, CsA was stopped abruptly in both cases. After CsA withdrawal, acute GVHD developed, and subsequent chronic GVHD. One of two cases is alive without any relapse of the leukemia 40 months after the peripheral blood stem cell transplantation (PBSCT). In the other case, ALL relapsed 15 months after the PBSCT, however, complete remission was again induced concomitantly with reactivated GVHD. In both these cases, the results suggest that using PBSC as a stem cell source and abrupt cessation of GVHD prophylaxis provided a potent graft-versus-leukemia effect.
Assuntos
Transplante de Medula Óssea , Transplante de Células-Tronco de Sangue Periférico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Doadores de Tecidos , Condicionamento Pré-Transplante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pré-Escolar , Ciclosporina/administração & dosagem , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Lactente , Masculino , Melfalan/administração & dosagem , Recidiva , Vidarabina/administração & dosagem , Vidarabina/análogos & derivadosRESUMO
A 9-year-old female patient with relapsed leukemia that was refractory to conventional reinduction chemotherapy was successfully treated with double allogeneic peripheral blood stem cell transplantation. The conditioning regimen for the first transplantation consisted of busulfan, etoposide, and melphalan, and that for the second transplantation was total body irradiation and thiotepa. Neither severe regimen-related toxicity nor graft-versus-host disease was observed. The patient is in complete remission without major complications for 5 years. Double transplantation should be considered as one of the possible treatments for refractory acute lymphoblastic leukemia.
Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Terapia de Salvação/métodos , Criança , Intervalo Livre de Doença , Humanos , Transplante de Células-Tronco de Sangue Periférico , Recidiva , Indução de Remissão/métodos , Tiotepa/uso terapêutico , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Falha de Tratamento , Irradiação Corporal TotalRESUMO
Persistent infection with human parvovirus B19 (B19) is primarily associated with chronic bone marrow failure in immunocompromised patients, but occasionally this organism may also affect immunocompetent hosts. B19 is also suggested as a causative agent of organ failure during bone marrow transplantation (BMT). We herein report the case of a 9-year-old girl with no previous history of immunodeficiency who developed severe aplastic anemia concurrent with B19 persistent infection. Both immunoglobulin (Ig)M antibody to B19 and B19 DNA identified by real-time polymerase chain reaction were found in the patient's serum at time of diagnosis of aplastic anemia. No giant proerythroblasts were found in her bone marrow at diagnosis. Although intravenous administration of Ig (IVIg) reduced serum B19 DNA, the aplastic status of her bone marrow did not improve. Both aplastic anemia and persistent B19 viremia were successfully treated by BMT from an HLA-identical sibling donor. Serum B19 DNA increased temporarily after BMT; however, neither organ nor marrow failure was observed. B19 DNA disappeared from the serum 2 months after BMT, suggesting that a normal immune response was restored by BMT and terminated the B19 viremia. During BMT, use of high-titer IVIg for B19 might prevent B19-associated organ failure.
Assuntos
Anemia Aplástica/complicações , Anemia Aplástica/terapia , Transplante de Medula Óssea , Infecções por Parvoviridae/complicações , Medula Óssea/patologia , Criança , Doença Crônica , Feminino , Humanos , Insuficiência de Múltiplos Órgãos/prevenção & controle , Infecções por Parvoviridae/diagnóstico , Parvovirus B19 Humano , Irmãos , Resultado do TratamentoRESUMO
The role of reactive oxygen species (ROS) in the cytotoxicity of N-(4-hydroxyphenyl)retinamide (4-HPR) was studied with use of the B-precursor lymphoblastic leukemia cell line YCUB-2. The increase in intracellular ROS measured with 2'-7'-dichlorodihydrofluorescein diacetate after 3 hours' incubation was 3.7-fold with 1 microM 4-HPR and 5.8-fold with 5 microM 4-HPR. The rate of apoptosis after 48 hours' incubation was 9.8% and 56.4% in comparison with untreated cells. Hydroethidine, which is a more specific indicator of superoxide anion radical level, did not effectively detect 4-HPR-induced ROS. The antioxidant 3-methyl-1-phenyl-2-pyrazolin-5-one suppressed 4-HPR-induced ROS production and apoptosis. The cytotoxicity of 4-HPR was analyzed in 4 other leukemia/lymphoma lines (CCRF-HSB2, Molt-4, KG-1, HL-60). We found that the cytotoxicity of 4-HPR correlated with the amount of ROS produced in cell lines, except in HL-60 cells. The intracellular glutathione level varied among the 5 cell lines, the highest levels occurring in Molt-4 and KG-1, which were less sensitive to 4-HPR. Suppression of glutathione by buthionine sulfoximine enhanced the level of 4-HPR-induced ROS production and apoptosis in Molt-4. Our findings suggest that ROS play a significant role in the antileukemia effect of 4-HPR and that the glutathione level in leukemias may be associated the sensitivity of the cells to 4-HPR.
Assuntos
Apoptose/efeitos dos fármacos , Fenretinida/farmacologia , Leucemia/patologia , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos/farmacologia , Butionina Sulfoximina/farmacologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Glutationa/análise , Glutationa/antagonistas & inibidores , Humanos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/análiseRESUMO
BACKGROUND: The Kanagawa Cord Blood Bank (KCBB) reports the treatment of 12 patients who received umbilical cord blood transplantation (CBT) from unrelated donors as their second hemopoietic stem cell transplantation (HSCT). METHODS: Provided by the KCBB, between February 1997 and September 2000, 12 patients had unrelated CBT as a second HSCT. Six patients were male and six female; nine patients were in malignant, and three were in non-malignant conditions. The median age of the patients was 7.9 years (range, 2.2-28.0), and the median bodyweight was 22.5 kg (12.0-55.0). The HLA-A and -B serological and DR genotypical disparities between the patients and CBT donors were as follows: one patient was a 0-mismatch, six were 1-mismatches, and five were 2-mismatches. RESULTS: The median time between first and second HSCT was 14.0 months (1.0-47.0). The overall survival rate was 25.0%, three years after CBT (Kaplan-Meier estimate). Mortality after CBT as a second HSCT accounted for nine cases, six from infection and three from treatment-related mortality other than infection. CONCLUSION: Cord blood transplantation offers the advantage of rapid availability, absence of donor risk, and possibly less HLA restriction. In these contexts, unrelated CBT should be considered as a source of HSCT for a second transplant.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Adrenoleucodistrofia/terapia , Adulto , Criança , Pré-Escolar , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/mortalidade , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Leucemia/terapia , Masculino , Mucopolissacaridose II/terapia , Purina-Núcleosídeo Fosforilase/deficiência , Recidiva , RetratamentoRESUMO
BACKGROUND: Familial hemophagocytic lymphohistiocytosis HLH (FHL) is fatal, unless patients are rescued with hematopoietic stem cell transplantation (SCT). Although the molecular identification of FHL now is possible at least in part from perforin gene study, many cases escape detection or never are tested due to the lack of specific hallmarks, making diagnosis difficult. To the authors' knowledge, it remains to be determined whether persistently low natural killer cell (NK) activity and a high incidence of central nervous system (CNS) disease increase the probability of FHL. METHODS: The authors analyzed 42 HLH patients age < 2 years, 13 of whom developed overt CNS disease and 5 of whom demonstrated persistently deficient NK activity (Group 1). The remaining 24 patients had no CNS disease and had NK activity of moderate decrease to within the normal range (Group 2). RESULTS: In Group 1, CNS symptoms were detected in 6 cases within 1 month and between 4.5-9 months in 6 other patients. In these cases, spotty lesions demonstrating a high T2 signal in the white matter were noted on brain magnetic resonance imaging. The survival was significantly poor for patients in Group 1 unless they were rescued with SCT, which was performed in 5 of the 13 patients with CNS disease and in all 5 patients with persistent NK activity deficiency. SCT was successful in 9 patients, with no CNS sequelae reported after the transplantation. Conversely, the prognosis of the 24 patients in Group 2 was better and only 1 patient required SCT. CONCLUSIONS: Very young HLH patients (age < 2 years) who are at high risk of fatal FHL with persistently deficient NK activity and/or overt CNS disease require appropriate SCT to reverse CNS disease and achieve a complete cure.
Assuntos
Encefalopatias/diagnóstico , Histiocitose de Células não Langerhans/diagnóstico , Células Matadoras Naturais/patologia , Idade de Início , Encéfalo/diagnóstico por imagem , Encefalopatias/complicações , Encefalopatias/imunologia , Pré-Escolar , Diagnóstico Diferencial , Tratamento Farmacológico , Infecções por Vírus Epstein-Barr/complicações , Feminino , Histiocitose de Células não Langerhans/etiologia , Histiocitose de Células não Langerhans/imunologia , Humanos , Imunoterapia , Lactente , Recém-Nascido , Células Matadoras Naturais/imunologia , Imageamento por Ressonância Magnética , Masculino , Prognóstico , Radiografia , Fatores de RiscoRESUMO
Long-term survivors of acquired aplastic anemia (AA) have an increased risk of developing myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) after immunosuppressive therapy (IST). It is uncertain whether the increased survival time simply discloses the natural history of AA as a premalignant disease or whether secondary disease is related to the therapy itself. Between November 1992 and September 1997, 113 AA children with normal cytogenetics at diagnosis were treated with IST using antithymocyte globulin, cyclosporin, and danazol with or without granulocyte colony-stimulating factor (G-CSF). We assessed risk factors for developing MDS/AML by Cox proportional hazards models. Twelve of 113 patients developed MDS between 9 and 81 months following the time of diagnosis, giving a cumulative incidence of 13.7 +/- 3.9%. The following cytogenetic abnormalities were observed at the time of diagnosis of MDS: monosomy 7 (6 patients), monosomy7/trisomy21 (1 patient), trisomy 11 (1 patient), del (11) (9?:14) (1 patient), add (9q) (1 patient), add 7 (q 32) (1 patient), and trisomy 9 (1 patient). The number of days of G-CSF therapy and nonresponse to therapy at 6 months were statistically significant risk factors by multivariate analysis. The present study suggests a close relationship between long-term use of G-CSF and secondary MDS in nonresponders to IST.
Assuntos
Anemia Aplástica/patologia , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Imunossupressores/efeitos adversos , Leucemia Mieloide/induzido quimicamente , Síndromes Mielodisplásicas/induzido quimicamente , Doença Aguda , Adolescente , Adulto , Anemia Aplástica/tratamento farmacológico , Anemia Aplástica/genética , Criança , Pré-Escolar , Cromossomos Humanos Par 7 , Feminino , Seguimentos , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Incidência , Lactente , Cariotipagem , Leucemia Mieloide/etiologia , Leucemia Mieloide/genética , Masculino , Monossomia , Síndromes Mielodisplásicas/etiologia , Síndromes Mielodisplásicas/genética , Estudos Prospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
We retrospectively analyzed results for 154 patients with acquired severe aplastic anemia who received bone marrow transplants between 1993 and 2000 from unrelated donors identified through the Japan Marrow Donor Program. Patients were aged between 1 and 46 years (median, 17 years). Seventy-nine donor-patient pairs matched at HLA-A, -B, and -DRB1 loci, as shown by DNA typing. Among the 75 mismatched pairs, DNA typing of 63 pairs showed that 51 were mismatched at 1 HLA locus (18 HLA-A, 11 HLA-B, 22 HLA-DRB1) and 12 were mismatched at 2 or more loci. Seventeen patients (11%) experienced either early or late graft rejection. The incidence of grade III/IV acute graft versus host disease and chronic graft versus host disease was 20% (range, 7%-33%) and 30% (range, 12%-48%), respectively. Currently, 99 patients are alive, having survived for 3 to 82 months (median, 29 months) after their transplantations. The probability of overall survival at 5 years was 56% (95% confidence interval, 34%-78%). Multivariate analysis revealed the following unfavorable factors: transplantation more than 3 years after diagnosis (relative risk [RR], 1.86; P =.02), patients older than 20 years (RR, 2.27; P =.03), preconditioning regimen without antithymocyte globulin (RR 2.28; P =.04), and HLA-A or -B locus mismatching as determined by DNA typing. Matching of HLA class I alleles and improvement of preparative regimens should result in improved outcomes in patients with severe aplastic anemia who receive transplants from unrelated donors.