מתוך medicontext.co.il
By Faith Reidenbach
NEW YORK (Reuters Health) – In children with severe sickle cell anemia, the fetal hemoglobin (HbF) response to hydroxyurea therapy correlates with certain baseline blood values, treatment-associated changes, and the maximally tolerated dose, US researchers report. Even so, they warn, the HbF response cannot be predicted accurately.
Fetal hemoglobin "inhibits polymerization of sickle hemoglobin and thereby prevents the erythrocytes from changing into their characteristic sickled shape," Dr. Russell E. Ware, of Duke University, Durham, North Carolina, noted in an interview with Reuters Health. "The total amount of fetal hemoglobin (%HbF) is recognized as an important prognostic factor for patients with sickle cell anemia."
In HUG-KIDS, a recent phase I/II study of African-American children with severe sickle cell anemia, hydroxyurea was efficacious and well tolerated, Dr. Ware said. But as in adult trials, the increase in %HbF was highly variable, ranging from 0.1% to 26.4% over 12 months of therapy (median 9.6%).
To investigate what influences the HbF response, Dr. Ware and colleagues analyzed data on the 68 children (of 84 enrolled) in HUG-KIDS for whom a maximally tolerated dose was known. They used %HbF at the maximally tolerated dose (MTD) as the primary response variable.
Overall, the higher the baseline %HbF, the higher the MTD %HbF level, Dr. Ware's team reports in the January 1st issue of Blood. Baseline %HbF was the strongest predictor of the response (p < 0.001).
However, "even patients with a low baseline %HbF level occasionally had a substantial response to hydroxyurea therapy," the researchers advise.
Other predictors of a higher MTD %HbF level were a higher baseline reticulocyte count, a higher baseline white blood cell count, greater treatment-related positive changes in hemoglobin concentration and mean corpuscular volume, and greater treatment-related negative changes in reticulocyte and WBC counts.
"Taken together, these data demonstrate that almost all children with sickle cell anemia will respond to hydroxyurea therapy with increases in %HbF, but the response is complex and cannot be predicted accurately," the research team concludes.
"Currently, school-aged children who are severely affected by sickle cell disease, particularly those with recurrent acute vaso-occlusive events such as pain or acute chest syndrome, should be considered candidates for hydroxyurea therapy," Dr. Ware told Reuters Health. "Hydroxyurea should only be prescribed by a qualified pediatric hematologist who is experienced with its use and side effects," he cautioned.
"Hydroxyurea may also have efficacy for very young patients with sickle cell anemia," Dr. Ware added. "A recently completed pilot trial, HUSOFT, tested the feasibility of administering liquid hydroxyurea to a cohort of infants with sickle cell anemia. Hydroxyurea was well tolerated, had modest toxicity, and possibly reduced the onset of splenic dysfunction."
He said that because of these promising results, "a multicenter phase III trial will test the ability of hydroxyurea to prevent chronic organ damage in infants with sickle cell anemia."
תגובות רוצה להצטרף לדיון?
יש להתחבר כדי להגיב.
התחבראין תגובות עדיין. היה הראשון להגיב!