RESUMO
We analyzed the outcomes of 214 HLA non-identical T-cell-depleted bone marrow transplantations (BMTs), performed in 178 consecutive patients for treatment of severe combined immunodeficiencies (SCID). Patients were treated in 18 European centers between 1981 and March 1995. SCID variants, that is, absence of T and B lymphocytes (B-) or absence of T cells with presence of B lymphocytes (B+) were found to have a major influence on outcome. The disease-free survival was significantly better for patients with B+ SCID (60%) as compared with patients with B- SCID (35%) (P =.002), with a median follow-up of 57 months and 52 months, respectively. Other factors associated with a poor prognosis were the presence of a lung infection before BMT (odds ratio = 2.47 [1.99-2.94]) and the use of monoclonal antibodies for T-cell depletion of the graft (odds ratio = 1.67 [1. 18-2.15]). Additional factors influencing outcome were age at BMT (<6 months) and period during which BMT was performed. Better results were achieved after 1991. Reduced survival of patients with B- SCID was associated with a higher incidence of early deaths from infection, a diminished rate of marrow engraftment, a trend to a higher incidence of chronic graft-versus-host disease, and slower kinetics of T/B immune function development. In both groups of patients, the use of busulfan (8 mg/kg total dose) and cyclophosphamide (200 mg/kg total dose) as a conditioning regimen provided the best cure rate (74% for patients with B+ SCID and 43% for patients with B- SCID, respectively), although results were not statistically significantly different from other regimens. This retrospective analysis should lead to the design of adapted measures to the performance of HLA non-identical BMT in patients with distinct SCID conditions.
Assuntos
Transplante de Medula Óssea/métodos , Imunodeficiência Combinada Severa/terapia , Fatores Etários , Linfócitos B/imunologia , Transplante de Medula Óssea/imunologia , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/complicações , Teste de Histocompatibilidade , Humanos , Lactente , Masculino , Razão de Chances , Fenótipo , Prognóstico , Infecções Respiratórias/complicações , Estudos Retrospectivos , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/genética , Linfócitos T/imunologia , Imunologia de Transplantes , Resultado do TratamentoAssuntos
Transplante de Medula Óssea , Gônadas/fisiologia , Leucemia/terapia , Doença Aguda , Adolescente , Adulto , Feminino , Humanos , Leucemia/radioterapia , MasculinoRESUMO
AIM: To analyze final height and hormonal function in long-term survivors of bone marrow transplantation (BMT). PATIENTS: Group 1 consisted of 16 patients (10 boys) with a hematologic malignancy, mostly leukemia, conditioned for BMT with total body irradiation (TBI), 7.5 to 12 Gy, and cyclophosphamide. Group 2 consisted of 14 patients (9 boys) with severe aplastic anemia, conditioned with chemotherapy only. RESULTS: In group 1, patients achieved a reduced final height after BMT. The difference between the height standard deviation score (SDS) at BMT and the height SDS at final height was -1.96 (0.82) SDS in boys and -0.92 (0.71) SDS in girls (p = 0.0001, and p = 0.02 respectively). Final height was also lower than target height (boys, p = 0.01; girls, p = 0.03). Prepubertal growth in the first 3 years after BMT was normal but pubertal height gain was decreased. The patients in group 2 achieved normal height. Thyroid function and adrenal function were normal in all patients, and no growth hormone deficiency was detected. Serum follicle-stimulating hormone values after BMT were increased in all group 1 patients, with return to normal in two patients. Serum luteinizing hormone values were increased in all group 1 girls, with recovery in one girl. Normal serum luteinizing hormone values and spontaneous puberty were found in all group 1 boys. In group 2, disturbances in gonadotropins were seen only in three boys and two girls. CONCLUSION: In patients treated in childhood with BMT after chemotherapy and TBI with 7.5 Gy or more, final height is compromised because of blunted growth in puberty. Patients who had not received TBI suffered no height loss. In the majority of patients, the combination of chemotherapy and TBI also resulted in irreversible disturbances of gonadal function.
Assuntos
Estatura , Transplante de Medula Óssea , Hormônios Adeno-Hipofisários/sangue , Condicionamento Pré-Transplante/métodos , Adolescente , Anemia Aplástica/terapia , Ciclofosfamida/uso terapêutico , Feminino , Hormônio Foliculoestimulante/sangue , Neoplasias Hematológicas/terapia , Hormônio do Crescimento Humano/sangue , Humanos , Hormônio Luteinizante/sangue , Masculino , Estudos Retrospectivos , Sobreviventes , Irradiação Corporal TotalRESUMO
The outcomes of 69 patients who received allogeneic bone marrow grafts for autosomal recessive osteopetrosis in the period between 1976 and 1994 were analyzed retrospectively. Four patients received bone marrow transplants (BMT) without prior myeloablative conditioning; transient osteoclast function was demonstrated in one of them. Sixty-five patients received myeloablative pretreatment. Recipients of a genotypically human leukocyte antigen (HLA)-identical BMT had an actuarial probability for 5-year survival, with osteoclast function, of 79%; recipients of a phenotypically HLA-identical bone marrow graft from a related or unrelated donor, or one HLA-mismatched graft from a related donor, had an actuarial probability for 5-year survival, with osteoclast function, of 38%; patients who received a graft from an HLA-haplotype mismatched related donor had a probability for 5-year survival of only 13%. The main problems in haplotype-nonidentical BMT were graft failure and BMT-related complications such as sepsis, bleeding, and interstitial pneumonia. Osteoclast function developed in all patients with full engraftment. Recovery of osteoclast function was associated with severe hypercalcemia in 24% of the patients with engraftment, especially those older than 2 years of age. At the time of BMT, severe visual impairment was present in 35% of the patients; of the 15 patients who had visual impairment at the time that a successful BMT was performed, two had improvement after BMT (13%). Within the total group, one patient had neurodegeneration. Engraftment of healthy donor cells had no influence on the progression of that abnormality and BMT thus had no beneficial effect on this phenotype of osteopetrosis. In general, however, early BMT remains the only curative treatment for autosomal recessive osteopetrosis.