1.
Romiplostim in children with immune thrombocytopenia: a phase 3, randomized, double-blind, placebo-controlled study
Tarantino M, Bussel J, Blanchette V, Despotovic J, Bennett C, Raj A, Williams B, Beam D, Morales J, Rose M, et al
Haematologica. 2016;101((s1)):137.. p401.
2.
Eltrombopag treatment of childhood persistent and chronic immune thrombocytopenia: final results of the PETIT study (TRA108062), a phase 2, placebo-controlled clinical trial
Bussel JB, Garcia de Miguel P, Despotovic J, Grainger JD, Sevilla Navarro J, Blanchette V, Connor P, David M, Matthews D, Marcello L, et al
Haematologica. 2014;99((S1):):263.. Abstract No. S733.
3.
Anti-D (WinRho SD) treatment of children with chronic autoimmune thrombocytopenic purpura stimulates transient cytokine/chemokine production
Semple JW, Allen D, Rutherford M, Woloski M, David M, Wakefield C, Butchart S, Freedman J, Blanchette V, Canadian Children's Platelet Study Group
American Journal of Hematology. 2002;69((3):):225-7.
Abstract
Intravenous anti-D is often used in the treatment of autoimmune thrombocytopenic purpura (AITP), but little is known about its mechanisms of action. To investigate anti-D's potential in vivo mechanism(s) of action, a small group (N = 7) of children with chronic AITP was studied. The children initially received either 25 or 50 microg/kg of WinRho-SD in a four-cycle cross-over trial, and peripheral blood samples from the first and third cycles were assessed for cytokine levels at pre-treatment, 3 hr, 1 day, and 8 days post-treatment. Results showed that platelet counts significantly increased in all the children by day 8 post-treatment. Analysis of serum by ELISA showed that there was a significant but transient rise in both pro- and anti-inflammatory cytokine/chemokine levels (e.g., IL1RA, IL6, GM-CSF, MCP-1 alpha, TNF-alpha and MCP-1) by 3 hr post-treatment in both cycles which returned to baseline levels by 8 days post-treatment. These results suggest that anti-D administration may initially activate the RES in the form of cytokine/chemokine secretion, which is subsequently followed by an increase in platelet counts. It is possible that the induced cytokine/chemokine storm may have an effect on several physiological processes such as those mediating either adverse effects or potentially RES phagocytic activity.
4.
Randomised trial of intravenous immunoglobulin G, intravenous anti-D, and oral prednisone in childhood acute immune thrombocytopenic purpura
Blanchette V, Imbach P, Andrew M, Adams M, McMillan J, Wang E, Milner R, Ali K, Barnard D, Bernstein M,, et al
Lancet. 1994;344((8924):):703-7.
Abstract
The most serious complication of childhood acute immune thrombocytopenic purpura (ITP), intracranial haemorrhage, occurs in about 1% of children with platelet counts below 20 x 10(9)/L. We conducted a randomised study to explore three treatment options in this high-risk group. 146 children (> 6 months and < 18 years old) with typical acute ITP and platelet counts of 20 x 10(9)/L or lower were randomised to receive high-dose intravenous immunoglobulin G (IVIgG) 1 g/kg on 2 consecutive days (n = 34), 0.8 g/kg once (n = 35), intravenous anti-D 25 micrograms/kg on 2 consecutive days (n = 38), or oral prednisone 4 mg/kg per day with tapering and discontinuation of prednisone by day 21 (n = 39). The rate of response as reflected by the number of days with platelet counts at 20 x 10(9)/L or lower and the time taken to achieve a platelet count 50 x 10(9)/L or more was significantly faster for both IVIgG groups than for the anti-D group (p < 0.05); the difference between prednisone and IVIgG was significant (p < 0.05) only for the IVIgG 0.8 g/kg group, and responses to the two IgG groups were similar. These differences in response rates were reflected in the percentages of children with platelet counts of 20 x 10(9)/L or lower at 72 hours following the start of treatment: 3% (IVIgG 0.8 g/kg x 1), 6% (IVIgG 1 g/kg x 2), 18% (anti-D), and 21% (oral prednisone 4 mg/kg/day). Treatment-associated toxicities included a fall in haemoglobin with anti-D (to less than 100 g/L in 24% of cases); weight gain with oral prednisone; and fever, nausea, vomiting, and headache with IVIgG. On the basis of these results, intravenous anti-D cannot be recommended as initial therapy for children with acute ITP and platelet counts of 20 x 10(9)/L or lower. A single dose of 0.8 g/kg IVIgG offers the fastest recovery for the least treatment; additional IgG or oral prednisone can be reserved for the one-third of children who continue to have platelet counts of 20 x 10(9)/L or less at 48-72 hours after the start of treatment.