RESUMEN
BACKGROUND: Activated phosphatidylinositol-3-OH kinase δ syndrome type 1 (APDS1) is a recently described primary immunodeficiency syndrome characterized by recurrent respiratory tract infections, lymphoid hyperplasia, and Herpesviridae infections caused by germline gain-of-function mutations of PIK3CD. Hematopoietic stem cell transplantation (HSCT) can be considered to ameliorate progressive immunodeficiency and associated malignancy, but appropriate indications, methods, and outcomes of HSCT for APDS1 remain undefined. OBJECTIVE: Our objective was to analyze the clinical manifestations, laboratory findings, prognosis, and treatment of APDS1 and explore appropriate indications and methods of HSCT. METHODS: We reviewed retrospectively the medical records of cohorts undergoing HSCT at collaborating facilities. RESULTS: Thirty-year overall survival was 86.1%, but event-free survival was 39.6%. Life-threatening events, such as severe infections or lymphoproliferation, were frequent in childhood and adolescence and were common indications for HSCT. Nine patients underwent HSCT with fludarabine-based reduced-intensity conditioning. Seven patients survived after frequent adverse complications and engraftment failure. Most symptoms improved after HSCT. CONCLUSION: Patients with APDS1 showed variable clinical manifestations. Life-threatening progressive combined immunodeficiency and massive lymphoproliferation were common indications for HSCT. Fludarabine-based reduced-intensity conditioning-HSCT ameliorated clinical symptoms, but transplantation-related complications were frequent, including graft failure.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Síndromes de Inmunodeficiencia , Trastornos Linfoproliferativos , Adolescente , Adulto , Aloinjertos , Niño , Preescolar , Fosfatidilinositol 3-Quinasa Clase I/inmunología , Supervivencia sin Enfermedad , Femenino , Humanos , Síndromes de Inmunodeficiencia/inmunología , Síndromes de Inmunodeficiencia/mortalidad , Síndromes de Inmunodeficiencia/patología , Síndromes de Inmunodeficiencia/terapia , Trastornos Linfoproliferativos/inmunología , Trastornos Linfoproliferativos/mortalidad , Trastornos Linfoproliferativos/patología , Trastornos Linfoproliferativos/terapia , Masculino , Enfermedades de Inmunodeficiencia Primaria , Tasa de SupervivenciaRESUMEN
Chronic Epstein-Barr virus-associated T/natural killer cell lymphoproliferative diseases represented by chronic active Epstein-Barr virus infection are lethal but are curable with several courses of chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). Recently, we reported that reduced-intensity conditioning (RIC) provided better outcomes than myeloablative conditioning because RIC was less toxic. However, it was unclear whether cord blood transplantation (CBT) works in the context of RIC. We retrospectively analyzed 17 patients who underwent RIC followed by bone marrow transplantation (RIC-BMT) and 15 patients who underwent RIC followed by CBT (RIC-CBT). The representative regimen was fludarabine and melphalan based. The overall survival rates with RIC-BMT and RIC-CBT were 92.9% ± 6.9% and 93.3% ± 6.4%, respectively (P = .87). One patient died of lung graft-versus-host disease after RIC-BMT, and 1 patient died of multiple viral infections after RIC-CBT. Although cytotoxic chemotherapy was also immunosuppressive and might contribute to better donor cell engraftment after RIC-HSCT, the rate of engraftment failure after RIC-CBT was still higher than that after RIC-BMT (not significant); however, patients who had experienced graft failure were successfully rescued with a second HSCT. Unrelated cord blood can be an alternative source for RIC-HSCT if a patient has no family donor.
Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Trasplante de Células Madre Hematopoyéticas/métodos , Trastornos Linfoproliferativos/terapia , Acondicionamiento Pretrasplante/métodos , Trasplante Autólogo/métodos , Adolescente , Adulto , Niño , Preescolar , Enfermedad Crónica , Infecciones por Virus de Epstein-Barr/virología , Femenino , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Lactante , Recién Nacido , Células Asesinas Naturales , Masculino , Adulto JovenRESUMEN
We present the case of a 1-year-old female with stage-4 neuroblastoma with MYCN amplification; she was treated with five chemotherapy courses, resulting in normalization of elevated serum levels of tumor markers. Complete remission was achieved after allogeneic hematopoietic stem-cell transplantation with reduced-intensity conditioning. Nine months later, however, the tumor relapsed in the central nervous system (CNS). The serum and cerebrospinal fluid (CSF) levels of the tumor markers were normal, but the MYCN copy number was high only in the CSF DNA, suggesting an isolated CNS recurrence. The MYCN copy number in the CSF DNA was reflective of response to treatment.