Hydroxycarbamide treatment in sickle cell disease: estimates of possible leukaemia risk and of hospitalization survival benefit

Abstract

SummaryUsing health insurance claims databases we compared the frequency/ incidence of acute myeloid leukaemia (AML) and inpatient mortality in sickle cell disease (SCD) subjects taking (n = 1051), or not taking (n = 9203) hydroxycarbamide (HC). Patients taking HC were older (median 19 vs. 17 years of age), had a higher proportion of males (53% vs. 38%), and their median hospitalizations per year was five times greater than in SCD patients not on HC (all P < 0Á001). No new AML cases occurred in HC-treated paediatric SCD patients. For adults, the new AML incidence with HC exposure was 10Á7/10 000 patient years, vs. 4Á0/10 000 patient years in subjects not on HC (P = 0Á2), a possible AML risk ratio of 3Á18. Adjustment for a probable database bias for AML diagnosis/ascertainment lowered the risk ratio to 0Á94 (95% confidence interval = 0Á16-5Á47). Despite their greater disease severity, the inpatient mortality in SCD adults prescribed HC (0Á29%) was lower than that of patients not taking the drug (0Á42%, P = 0Á032). In this SCD population we find no increased risk for AML with HC treatment. If such a risk is eventually proven, it will probably be lower than that for drugs with known AML association. By contrast, HC treatment appears to confer a survival benefit.

Myelodysplastic syndrome with clonal cytogenetic abnormalities followed by fatal erythroid leukemia after 14 years of exposure to hydroxyurea for sickle cell anemia

“…The main adverse hematologic effect of HU is usually mild myelosuppression. Regarding the hematologic side effects of HU exposure, no case of malignancy was reported in large series of SCD patients [3][4][5]. Very few cases of myelodysplastic syndrome or acute leukemia after HU in patients suffering from SCD have been reported [6][7][8][9].…”

“…The current risk-benefit balance is in favor of using HU therapy in severe SCD [3,5]. Despite the favorable safety profile of HU, the very long-term adverse effect of HU administered to young patients and continued for decades remains to be determined.…”

Do not leave for tomorrow what you can do today

“…Multiple, independent lines of evidence indicate that hydroxyurea therapy decreases mortality in both children and adults with sickle cell anemia (hydroxyurea has not been studied well in other SCD genotypes) . Well before this survival benefit was recently documented, we have had ample evidence that hydroxyurea decreases morbidity and improves quality of life.…”

“…Multiple, independent lines of evidence indicate that hydroxyurea therapy decreases mortality in both children and adults with sickle cell anemia (hydroxyurea has not been studied well in other SCD genotypes). [7][8][9][10] Well before this survival benefit was recently documented, we have had ample evidence that hydroxyurea decreases morbidity and improves quality of life. Unfortunately, many clinicians, patients, and parents still avoid or delay the initiation of hydroxyurea out of inordinate fear of toxicity or a preference to wait for some inevitable complication of a serious disease to occur first, rather than try to prevent it in the first place.…”

Risk of thrombosis in patients with myeloproliferative neoplasms and elevated platelet counts

“…Fear of carcinogenic effects of hydroxyurea has hampered the use of this drug, but the risk seems to be very small. Several thousand children and adolescents with sickle cell anemia have been treated with hydroxyurea for many years without any evidence of increased risk of acute leukemia .…”