RESUMEN
Hematopoietic stem cell transplantation (HSCT) is the treatment of choice for Wiskott-Aldrich syndrome (WAS). The aim of this retrospective study is to report the effect of the conditioning regimen and donor source on disease-free survival (DFS) in children undergoing HSCT for WAS. Fourteen children who underwent HSCT at 4 Israeli centers from 1996 to 2011 were included in this study. Five children were transplanted from matched related donors (4/5 siblings, 1/5 fully matched uncle) and other donors were used in 9 children. Six patients were conditioned with full dose busulfan/cyclophosphamide (Bu/Cy) whereas 8 patients were conditioned with other regimens. Thirteen of 14 patients (92.8%) are alive with a median follow-up of 3.4 years (range, 5 mo to 12.5 y). Nine patients (64.3%) survive with complete clinical, immunologic, and hematologic recovery. Children conditioned with full dose Bu/Cy had a 100% DFS, compared with children conditioned with other regimens, 25%±19% (P=0.022). Donor source was not associated with DFS. Graft failure was related to the use of conditioning regimens other than full dose Bu/Cy and not to the donor source. Further studies are required to determine the best conditioning regimen and optimal donor source for children with WAS.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Acondicionamiento Pretrasplante/métodos , Síndrome de Wiskott-Aldrich/cirugía , Niño , Preescolar , Supervivencia sin Enfermedad , Supervivencia de Injerto , Humanos , Lactante , Estimación de Kaplan-Meier , Estudios Retrospectivos , Trasplante Homólogo/mortalidad , Síndrome de Wiskott-Aldrich/mortalidadRESUMEN
Gemtuzumab ozogamicin (GO) is a humanized anti-CD33 antibody used for treating patients with CD33+ acute myeloid leukemia (AML). We report three young children (two infants and one toddler) with AML treated with GO 9 mg/m(2). Two received two doses at diagnosis alone with conventional chemotherapy and one received one dose after relapse. GO was well tolerated and all three achieved remission. All were transplanted: one relapsed after 5 months and died of disease, one died a toxic death in remission due to pulmonary fibrosis, and one survived (41 months from diagnosis). In conclusion, GO was well tolerated in these young patients with evidence for efficacy.
Asunto(s)
Aminoglicósidos/inmunología , Aminoglicósidos/uso terapéutico , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/uso terapéutico , Antígenos CD/inmunología , Antígenos de Diferenciación Mielomonocítica/inmunología , Leucemia Mieloide Aguda/terapia , Aminoglicósidos/efectos adversos , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Reacciones Antígeno-Anticuerpo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resultado Fatal , Femenino , Gemtuzumab , Humanos , Lactante , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/inmunología , Recurrencia , Lectina 3 Similar a Ig de Unión al Ácido SiálicoRESUMEN
BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is a member of the CC chemokines. MCP-1 has been previously shown to have a major role in the migration of monocytes towards human leukemic cells, yet it cannot increase cytotoxic effects of monocytes on human leukemic cells. AIM: To determine levels of MCP-1 in the CSF of children during various stages of acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: A 19 children with ALL and without known CNS involvement were enrolled in the study. CSF samples were aliquoted at different stages of therapy (diagnosis, induction, and maintenance) and were frozen at -70 degrees C until use. MCP-1 was measured with a sandwich enzyme-linked immunoabsorbent assay. RESULTS: Mean MCP-1 levels in the CSF were 1762.38 pg/ml (range 522-5000 pg/ml). In children without CNS involvement at diagnosis, CSF MCP1 levels did not change over time and remained within this range throughout the diagnosis and treatment stages. CNS involvement was associated with an increased MCP-1 level following chemotherapy, in patients with CNS involvement from 840 to 3990 pg/ml (P<0.0001), and in patients without CNS involvement from 1134 to 1943 pg/ml (P-value of 0.0322). White blood cells found in the CSF at diagnosis have vanished after induction. CONCLUSIONS: CNS involvement in ALL is associated with significantly higher levels of MCP1 during therapy. This significant rise in MCP-1 levels might be one of the mechanisms involved in the regulation of CNS leukemia. Since chemokines target specific leukocyte subsets, inhibition of a single Chemokine ligand or receptor may have a circumscribed effect, endowing the inhibitor with a limited side effect profile. Chemokines should be considered as possible targets for therapeutic intervention.
Asunto(s)
Quimiocina CCL2/líquido cefalorraquídeo , Leucemia-Linfoma Linfoblástico de Células Precursoras/líquido cefalorraquídeo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Biomarcadores de Tumor/líquido cefalorraquídeo , Enfermedades del Sistema Nervioso Central/líquido cefalorraquídeo , Enfermedades del Sistema Nervioso Central/epidemiología , Niño , Preescolar , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Estadificación de Neoplasias , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologíaRESUMEN
Mutations in both of the recombination activating genes (RAG)1 and RAG2 can lead to either T-B-severe combined immune deficiency (SCID) or Omenn syndrome (OS), two diseases presenting with totally different clinical and laboratory manifestations. The fact that the same mutations can cause either T-B- SCID or OS, even within the same family, lends credibility to the hypothesis that an additional factor (autoantigen or exoantigen) is required in certain circumstances for the development of OS phenotype. We investigated three patients from the same extended family who presented as T-B- SCID due to a homozygous mutation (G1305T) in the RAG2 gene. Our data support the notion that mutated RAG proteins may not always be sufficient to cause OS phenotype, and show evolution from a T-B- SCID into a typical OS phenotype subsequent to parainfluenza 3 virus infection.