ABSTRACT
ABSTRACT The addition of the new protease inhibitors (PIs) to peg-interferon (IFN) and ribavirin (RBV), approved for chronic hepatitis C, has clearly improved sustained virological response (SVR) rates although several adverse events have been reported with this regimens, including mild hematological toxicity. Moreover, severe pancytopenia and aplastic anemia during triple therapy with telaprevir has recently been described in seven patients. We report here two cases of severe agranulocytosis/aplastic anemia using boceprevir or simeprevir in interferon-based combination and 2 additional cases of severe myelosupression in IFN-free therapy with sofosbuvir and simeprevir plus RBV. Our observations suggest that PIs could have a sort of class-effect in developing severe hematologic toxicity or, at least, an additive interaction with other potentially myelotoxic agents such as IFN or RBV that are used in the classical regimens against HCV. Unfortunately, the mechanisms behind this phenomenon are currently unknown. In conclusion, given the lifethreatening character of these complications, close monitoring is mandatory in patients under PIs based therapy to promptly detect serious hematological toxicities and to carefully evaluate treatment discontinuation. Prospective studies assessing the usefulness of RBV in the era of new IFN-free combinations are needed.
Subject(s)
Humans , Protease Inhibitors/adverse effects , Bone Marrow Diseases/chemically induced , Bone Marrow Diseases/therapy , Proline/analogs & derivatives , Hepatitis C/drug therapy , Simeprevir/adverse effects , Anemia, Aplastic/chemically induced , Anemia, Aplastic/therapy , Severity of Illness Index , Bone Marrow Examination , Proline/adverse effects , Predictive Value of Tests , Risk Factors , Treatment Outcome , Hepatitis C/diagnosis , Fatal Outcome , Drug Therapy, CombinationABSTRACT
Background. We analysed the results of allogeneic haematopoietic stem cell transplantation (HSCT) in various genetic disorders, bone marrow failures and haematological malignancies done from 2002 to 2010 at the Army Hospital, Research and Referral, Delhi. Methods. A total of 119 matched-related allogeneic- HSCTs (allo-HSCTs) were done in 114 patients (men 76, women 38) aged between 2 and 60 years. Peripheral blood stem cells (n=75) and bone marrow (n=43) were used as the source of stem cells. Results. The overall survival was 62.3% (71/114) at a median follow-up of 34 months. Graft versus host disease (GVHD) was seen in 42 (36.8%) patients; grade III/IV acute GVHD in 17 (15%) and chronic GVHD in 24 (21%) patients. There were 4 (3.5%) graft rejections and one nonengraftment. The overall mortality was 37.7% (n=43) and the main causes of death were GVHD (32%), infections (26%), relapse (23%) and regimen-related toxicity (11%). Conclusion. Our results are comparable to published data in most disease conditions. With improvements in GVHD prophylaxis and better supportive care, we need to further reduce our mortality and morbidity.
Subject(s)
Adolescent , Adult , Bone Marrow Diseases/therapy , Child , Child, Preschool , Female , Genetic Diseases, Inborn/therapy , Graft Rejection/etiology , Graft vs Host Disease/etiology , Hematologic Neoplasms/therapy , Hospitals, Military , Humans , India , Kaplan-Meier Estimate , Male , Middle Aged , Survival Rate , Transplantation, Homologous , Young AdultABSTRACT
La insuficiencia medular es un síndrome hematológico; de pronóstico siempre reservado; que reconoce dos mecanismos etiopatogénicos: la aplasia medular y la mieloptisis. La primera es de naturaleza benigna y recuperable (50 por ciento) y la segunda maligna. Ambas se manifiestan clínicamente por una pancitopenia de la sangre periférica, la que se traduce por la asociación de un síndrome anémico normocítico y normocrómico arregenerativo, uno infeccioso febril y uno purpúrico. El diagnóstico clínico de insuficiencia medular es fácil, no así su tratamiento, especialmente en las mieloptisis.
Subject(s)
Humans , Bone Marrow Diseases/diagnosis , Bone Marrow Diseases/therapy , Leukopenia/therapy , Neutropenia/therapy , Hematologic Diseases/diagnosis , Hematologic Diseases/therapy , Hematopoiesis , Myelopoiesis , PancytopeniaSubject(s)
Humans , Male , Female , Infant, Newborn , Infant , Anemia, Aplastic/genetics , Bone Marrow Transplantation , Bone Marrow Diseases/physiopathology , Bone Marrow Diseases/therapy , Hematopoietic Cell Growth Factors/therapeutic use , Fanconi Anemia , Fanconi Anemia/genetics , Fanconi Anemia/physiopathology , Fanconi Anemia/therapyABSTRACT
Se reportan dos casos de aplasia medular jsevera adquirida, evaluados en el servicio de Pediatría que respondieron satisfactoriamente a la terapia con dosis altas de metilprednisolona, administrado en bolos intravenosos, iniciándose con 25 mg/kg/día disminuyéndolo en un período de cinco semanas. El tratamiento fue bien tolerado por ambos pacientes y no presentaron efectos adversos significativos. En nuestro medio que no contamos con la posibilidad del transplante de médula ósea y de la globulina antilinfocítica, debe considerarse la metilprednisolona como una alternativa terapéutica en los casos de aplasia medular severa.