RESUMEN
Patients with severe aplastic anemia (SAA) may benefit from hematopoietic stem cell transplantation, but many of them lack a matched donor. Haploidentical transplantation is increasingly utilized for the treatment of nonmalignant disease where patients lack a matched donor. We report patients with aplastic anemia who experienced successful engraftments of haploidentical stem cells with post-transplantation cyclophosphamide (PTCy). Case series and review of the literature. We present two cases of pediatric patients with severe aplastic anemia who experienced successful engraftment of haploidentical related bone marrow. Both patients received conditioning consisting of rabbit ATG, cyclophosphamide, fludarabine, and total body irradiation pretransplant, with PTCy. The conditioning regimen was well tolerated by both patients, and they achieved full donor engraftment and were weaned off all immunosuppressants. Haploidentical stem cell transplantation in patients with severe aplastic anemia may be an effective alternative when fully matched donors are not available. PTCy can facilitate successful engraftment and therefore expand the pool of eligible donors for patients with aplastic anemia.
Asunto(s)
Anemia Aplásica/terapia , Trasplante de Médula Ósea/métodos , Ciclofosfamida/uso terapéutico , Rechazo de Injerto/prevención & control , Trasplante de Células Madre Hematopoyéticas/métodos , Inmunosupresores/uso terapéutico , Trasplante Haploidéntico , Adolescente , Esquema de Medicación , Femenino , Humanos , Masculino , Cuidados Posoperatorios/métodos , Acondicionamiento Pretrasplante , Adulto JovenRESUMEN
BACKGROUND: Haploidentical bone marrow transplant (haplo-BMT) offers near universal donor availability as a curative modality for individuals with severe sickle cell disease (SCD). However, the required intense immunodepletion is associated with increased infectious complications. A paucity of data exists on immune reconstitution following haplo-BMT for SCD. METHODS: A multi-institution learning collaborative was developed in the context of a phase II clinical trial of a non-myeloablative, related haplo-BMT with post-transplant cyclophosphamide for SCD. We report results from a cohort of 23 patients for whom immune reconstitution data up to one year were available. RESULTS: Median age was 14.8 years. Out of 23, 18 participants received pre-conditioning with azathioprine, hydroxyurea, and hypertransfusions. 70% (16/23) of participants had multiple indications for haplo-BMT. We observed excellent immune reconstitution of CD4, CD8, CD19, and CD56 cellular subsets by 6 months post transplant. Engraftment rate and event-free survival in this cohort were 100% and 96%, respectively. 70% (16/23) of patients had at least one viral reactivation or infection, including CMV 35% (8/23), HHV-6 22% (5/23), and polyoma virus 17% (4/23), with no cases of post-transplant lymphoproliferative disease. CONCLUSION: Further prospective studies are needed to better characterize immune reconstitution and the immunologic basis for increased viral reactivation following haplo-BMT with post-transplant cyclophosphamide for SCD.
Asunto(s)
Anemia de Células Falciformes/complicaciones , Trasplante de Médula Ósea/efectos adversos , Ciclofosfamida/administración & dosificación , Reconstitución Inmune , Inmunosupresores/administración & dosificación , Activación Viral , Adolescente , Adulto , Niño , Ensayos Clínicos Fase II como Asunto , Supervivencia sin Enfermedad , Enfermedad Injerto contra Huésped , Humanos , Estudios Prospectivos , Acondicionamiento Pretrasplante/efectos adversos , Trasplante Haploidéntico/efectos adversos , Adulto JovenRESUMEN
To date, there has been a lack of pediatric experience regarding the efficacy and tolerability of immune checkpoint inhibitors after haploidentical hematopoietic stem cell transplant (HSCT). We present the case of a 22-year-old female with multiple-relapsed Hodgkin lymphoma (HL) who presented with a new relapse after haploidentical (post-haplo) HSCT. Anti-PD-1 therapy with nivolumab resulted in significant objective disease response and clinical improvement without notable side effects, including the absence of a graft-versus-host disease (GVHD). This case report suggests that immune checkpoint inhibition may be safely tolerated even in the setting of haploidentical HSCT, without triggering overt GVHD.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Trasplante de Médula Ósea/efectos adversos , Enfermedad Injerto contra Huésped/prevención & control , Enfermedad de Hodgkin/tratamiento farmacológico , Tolerancia Inmunológica/inmunología , Linfocitos T/efectos de los fármacos , Adulto , Antineoplásicos/uso terapéutico , Femenino , Enfermedad Injerto contra Huésped/inmunología , Enfermedad de Hodgkin/terapia , Humanos , Depleción Linfocítica , Nivolumab , Pronóstico , Trasplante Homólogo , Adulto JovenRESUMEN
There are few therapeutic options for patients with T-cell acute lymphoblastic leukemia (T-ALL) who have recurrent disease after initial matched sibling hematopoietic stem cell transplantation. While a second hematopoietic stem cell transplant (HSCT) from a haploidentical donor offers the conceptual possibility of greater graft versus leukemia effect, there is minimal literature to describe the efficacy of this approach in recurrent pediatric T-ALL. We present the case of a now 9-year-old female in whom second haploidentical HSCT, followed by successive donor lymphocyte infusions in response to minimal residual disease reemergence, has led to 3+ years of ongoing disease control without graft versus host disease and excellent quality of life.