Phase I dose-escalation trial of clofarabine followed by escalating doses of fractionated cyclophosphamide in children with relapsed or refractory acute leukemias.

BACKGROUND: By inhibiting DNA repair, clofarabine (CLO) may augment cyclophosphamide (CY)-induced DNA damage and apoptosis. We performed a Phase I study for refractory and/or relapsed (R/R) leukemia in children to determine maximum-tolerated dose (MTD) of time-sequential CLO followed by CY. PROCEDURE: Thirteen patients with (R/R) ALL (n = 8) and AML (N = 5), median age 9 years (range: 2-12 years), were treated with escalating doses of CLO on days 1, 2, 3 and 8, 9, 10 and CY 200 mg/m(2) /day on days 0 and 1 then 400 mg/m(2) /day on days 2, 3, 8, 9, and 10. Ten patients were treated at dose level 1 (DL1) (CLO 20 mg/m(2) /day) and three patients at DL2 (CLO 30 mg/m(2) /day). The average number of prior chemotherapies was 8.9. DNA damage testing was performed before treatment on day 0, and 2 hours after CY on day 0, before sequential CLO, CY treatment on day 1, and 2 hours after CLO followed by CY on day 1. RESULTS: Two patients at DL2 had dose-limiting toxicities (DLTs) that included hypotension with cardio-respiratory failure (1) and hepato-renal failure (1). Complete remission (CR) was achieved in 2/11 (18.2%) and partial remission (PR) in 2/11 (18.2%) for an overall response (OR) of 36.4%. The use of CLO before CY augmented CY-induced DNA damage in leukemic blasts compared to CY alone. CONCLUSION: In pediatric patients with R/R leukemia, 20 mg/m(2) /day is the MTD for CLO in timed sequential combination with CY. Increased DNA damage with the use of this combination suggests a mechanism for the sequential timing of these two chemotherapeutic agents.

Causes of hospitalization in sickle cell diseased children in western region of Saudi Arabia. A single center study.

OBJECTIVES: To highlight the causes of hospitalization among sickle cell diseased (SCD) children in Al-Madinah Al-Munawarah, Saudi Arabia. METHODS: A retrospective study conducted at the Maternity and Children's Hospital, Al-Madinah Al-Munawarah, Saudi Arabia. A data of 739 SCD children admitted to the hematology/oncology unit between October 2010 and September 2015 were collected. The collected data were analyzed using an independent t test and a Chi square test as appropriate. RESULTS: Approximately 49% of the studied children were presented by acute painful crisis. Acute chest syndrome was reported in 20.9%. Infection was the cause of admission in 17.5%, and acute anemia was reported in 8.1% of the studied patients. No significant difference of the reported clinical manifestations by patients' gender. Children aged <12 years showed significantly high frequency of acute chest syndrome (ACS) (26.5%), while acute painful crisis (66.4%) was significantly more frequent among children aged ≥12 years. CONCLUSION: This study revealed high rate of hospitalization of SCD children because of acute painful crisis, ACS, infection, and anemia. These admissions causes could potentially be continuously assessed to minimize the rate of hospitalization.