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1.
Lancet ; 371(9610): 395-403, 2008 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-18242413

RESUMEN

BACKGROUND: Chronic immune thrombocytopenic purpura (ITP) is characterised by accelerated platelet destruction and decreased platelet production. Short-term administration of the thrombopoiesis-stimulating protein, romiplostim, has been shown to increase platelet counts in most patients with chronic ITP. We assessed the long-term administration of romiplostim in splenectomised and non-splenectomised patients with ITP. METHODS: In two parallel trials, 63 splenectomised and 62 non-splenectomised patients with ITP and a mean of three platelet counts 30x10(9)/L or less were randomly assigned 2:1 to subcutaneous injections of romiplostim (n=42 in splenectomised study and n=41 in non-splenectomised study) or placebo (n=21 in both studies) every week for 24 weeks. Doses of study drug were adjusted to maintain platelet counts of 50x10(9)/L to 200x10(9)/L. The primary objectives were to assess the efficacy of romiplostim as measured by a durable platelet response (platelet count > or =50x10(9)/L during 6 or more of the last 8 weeks of treatment) and treatment safety. Analysis was per protocol. These studies are registered with ClinicalTrials.gov, numbers NCT00102323 and NCT00102336. FINDINGS: A durable platelet response was achieved by 16 of 42 splenectomised patients given romplostim versus none of 21 given placebo (difference in proportion of patients responding 38% [95% CI 23.4-52.8], p=0.0013), and by 25 of 41 non-splenectomised patients given romplostim versus one of 21 given placebo (56% [38.7-73.7], p<0.0001). The overall platelet response rate (either durable or transient platelet response) was noted in 88% (36/41) of non-splenectomised and 79% (33/42) of splenectomised patients given romiplostim compared with 14% (three of 21) of non-splenectomised and no splenectomised patients given placebo (p<0.0001). Patients given romiplostim achieved platelet counts of 50x10(9)/L or more on a mean of 13.8 (SE 0.9) weeks (mean 12.3 [1.2] weeks in splenectomised group vs 15.2 [1.2] weeks in non-splenectomised group) compared with 0.8 (0.4) weeks for those given placebo (0.2 [0.1] weeks vs 1.3 [0.8] weeks). 87% (20/23) of patients given romiplostim (12/12 splenectomised and eight of 11 non-splenectomised patients) reduced or discontinued concurrent therapy compared with 38% (six of 16) of those given placebo (one of six splenectomised and five of ten non-splenectomised patients). Adverse events were much the same in patients given romiplostim and placebo. No antibodies against romiplostim or thrombopoietin were detected. INTERPRETATION: Romiplostim was well tolerated, and increased and maintained platelet counts in splenectomised and non-splenectomised patients with ITP. Many patients were able to reduce or discontinue other ITP medications. Stimulation of platelet production by romiplostim may provide a new therapeutic option for patients with ITP.


Asunto(s)
Proteínas Portadoras/uso terapéutico , Púrpura Trombocitopénica Trombótica/tratamiento farmacológico , Receptores Fc/uso terapéutico , Adulto , Anciano , Proteínas Portadoras/administración & dosificación , Proteínas Portadoras/efectos adversos , Enfermedad Crónica/tratamiento farmacológico , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Púrpura Trombocitopénica Trombótica/sangre , Púrpura Trombocitopénica Trombótica/inmunología , Receptores Fc/administración & dosificación , Proteínas Recombinantes de Fusión , Esplenectomía , Trombopoyetina , Resultado del Tratamiento
2.
Am Surg ; 70(1): 71-4, 2004 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-14964553

RESUMEN

There are few cases of splenic infarction associated with antiphospholipid antibody reported in the literature. We present two cases of splenic infarction associated with anticardiolipin antibody, one complicated by the development of a splenic pseudocyst. Clinical diagnostic features of splenic infarction are described. In addition, a review of the literature on thrombotic manifestations of antiphospholipid syndrome is presented.


Asunto(s)
Anticuerpos Anticardiolipina/inmunología , Infarto del Bazo/inmunología , Adulto , Quistes/complicaciones , Quistes/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esplenectomía , Enfermedades del Bazo/complicaciones , Enfermedades del Bazo/cirugía , Infarto del Bazo/complicaciones , Infarto del Bazo/cirugía
3.
J Hematol Oncol ; 6(1): 81, 2013 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-24283202

RESUMEN

BACKGROUND: Ruxolitinib, a Janus kinase 1 and 2 inhibitor, demonstrated improvements in spleen volume, symptoms, and survival over placebo and best available therapy in intermediate-2 or high-risk myelofibrosis patients with baseline platelet counts ≥100 × 109/L in phase III studies. The most common adverse events were dose-dependent anemia and thrombocytopenia, which were anticipated because thrombopoietin and erythropoietin signal through JAK2. These events were manageable, rarely leading to treatment discontinuation. Because approximately one-quarter of MF patients have platelet counts <100 × 109/L consequent to their disease, ruxolitinib was evaluated in this subset of patients using lower initial doses. Interim results of a phase II study of ruxolitinib in myelofibrosis patients with baseline platelet counts of 50-100 × 109/L are reported. METHODS: Ruxolitinib was initiated at a dose of 5 mg twice daily (BID), and doses could be increased by 5 mg once daily every 4 weeks to 10 mg BID if platelet counts remained adequate. Additional dosage increases required evidence of suboptimal efficacy. Assessments included measurement of spleen volume by MRI, MF symptoms by MF Symptom Assessment Form v2.0 Total Symptom Score [TSS]), Patient Global Impression of Change (PGIC); EORTC QLQ-C30, and safety/tolerability. RESULTS: By week 24, 62% of patients achieved stable doses ≥10 mg BID. Median reductions in spleen volume and TSS were 24.2% and 43.8%, respectively. Thrombocytopenia necessitating dose reductions and dose interruptions occurred in 12 and 8 patients, respectively, and occurred mainly in patients with baseline platelet counts ≤75 × 109/L. Seven patients experienced platelet count increases ≥15 × 109/L. Mean hemoglobin levels remained stable over the treatment period. Two patients discontinued for adverse events: 1 for grade 4 retroperitoneal hemorrhage secondary to multiple and suspected pre-existing renal artery aneurysms and 1 for grade 4 thrombocytopenia. CONCLUSIONS: Results suggest that a low starting dose of ruxolitinib with escalation to 10 mg BID may be appropriate in myelofibrosis patients with low platelet counts.


Asunto(s)
Plaquetas/patología , Mielofibrosis Primaria/sangre , Mielofibrosis Primaria/tratamiento farmacológico , Pirazoles/efectos adversos , Pirazoles/uso terapéutico , Anciano , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Quinasas Janus/antagonistas & inhibidores , Masculino , Nitrilos , Recuento de Plaquetas , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas , Resultado del Tratamiento
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