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Background Repeated high-dose methotrexate (HDMTX) is a critical component of contemporary childhood acute lymphoblastic leukemia (ALL) treatment regimens. Serum albumin is considered a carrier of methotrexate (MTX) in the blood. Hypoalbuminemia is not a rare finding in children with leukemia. This study aimed to investigate the relationship between pre-infusion serum albumin and possible HDMTX toxicities. Methods Thirty Egyptian children with ALL were consecutively enrolled in the study between May 2018 and July 2020. They were prospectively followed up while receiving HDMTX during the consolidation phase of the TOTAL study XV protocol. HDMTX was administered intravenously as a 24-h infusion every 2 weeks. Doses of 2.5 g/m2 were used for low-risk patients and 5 g/m2 for standard/high-risk patients. The Common Terminology Criteria for Adverse Events (V.4.03) was used to report the observed toxicities after HDMTX cycles. Plasma MTX levels were estimated at 24 h (MTX24) from the beginning of HDMTX infusion in the first consolidation cycle. Serum albumin level was determined before HDMTX administration, and pre-infusion hypoalbuminemia was defined when serum albumin was <3.5 g/dL. Results The patients’ age ranged from 2.3 to 13.3 years at diagnosis, and most of them had B cell ALL (86.7%). Overall, 120 HDMTX cycles were analyzed, equally distributed between low and standard/high risk. Grade 3–4 anemia, grades 3–4 thrombocytopenia, febrile neutropenia, and oral mucositis were significantly more frequent in HDMTX cycles with pre-infusion hypoalbuminemia than those with normal pre-infusion albumin (p=0.003, p=0.007, p=0.006, and p=0.001, respectively). In addition, pre-infusion hypoalbuminemia was significantly associated with additional hospitalization due to HDMTX toxicity (p=0.031). Most HDMTX toxicities were comparable irrespective of the MTX dose. Oral mucositis was more frequently encountered in the 2.5 g/m2 than the 5 g/m2 HDMTX cycles (46.7 vs. 26.7%, p=0.023). A significantly longer hospitalization (due to HDMTX toxicity) was observed in the 5 g/m2 HDMTX cycles (median= 7 days vs. 4 days, p=0.012). Conclusions Serum albumin levels should be checked before starting HDMTX cycles, especially in resource-limited settings where malnutrition is common, and serum MTX monitoring may not be available. Optimizing serum albumin levels before HDMTX may help decrease the possibility of HDMTX toxicities.

Background β-thalassemia (βT) has a wide spectrum of clinical severity that may be attributed to the wide variations in βT gene mutations. β-Globin mutations with the Xmn-I site might be associated with elevated fetal hemoglobin levels, which in turn may affect the severity of βT phenotype. Aim To investigate the frequency of Xmn-I polymorphism (−158 C>T) among Egyptian children with βT, and to examine the relationship between Xmn-I polymorphism and βT phenotypes. Patients and methods This cross-sectional study was conducted on 112 βT patients (55 males and 57 females) with a mean age of 8.34±3.71 years (2–16 years). Laboratory investigations included complete blood count, hemoglobin electrophoresis, β-globin mutation, identification of Xmn-I polymorphism by two methods: PCR–restriction fragment length polymorphism and amplification refractory mutation system. Results All patients (76 with βT major and 36 with βT intermedia) were negative for the Xmn-I SNP whether in homozygous (+/+) or heterozygous (+/−) state. Conclusion This study demonstrated that Xmn-I polymorphism was not detected in the studied patients and this supports the low frequency of this polymorphism in other Egyptian studies.

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