Improving the safety of high‐dose methotrexate for children with hematologic cancers in settings without access to MTX levels using extended hydration and additional leucovorin

• Published in: Pediatric blood & cancer 2018-12, Vol.65 (12), p.e27241-n/a
• Main Authors: Vaishnavi, Kalthi, Bansal, Deepak, Trehan, Amita, Jain, Richa, Attri, Savita Verma
• Format: Article
• Language: English
• Subjects: Acute lymphoblastic leukemia; Blood cancer; Cancer; Children; Creatinine; Dengue hemorrhagic fever; Dextrose; Diarrhea; folinic acid; Hematology; high‐dose methotrexate; Hydration; Leukemia; low–middle income country; Lymphatic leukemia; Lymphocytes B; Lymphocytes T; Lymphoma; Methotrexate; Mucositis; Neutropenia; Oncology; Pediatrics; pH effects; Potassium; Potassium chloride; renal toxicity; Sodium; Sodium bicarbonate; Sodium chloride; Toxicity; Underweight; Urine; Vector-borne diseases
• ISSN: 1545-5009; 1545-5017
• DOI: 10.1002/pbc.27241

Background A lack of access to methotrexate levels is common in low‐ and middle‐income countries (LMIC), relevant for 80% of children with cancer worldwide. We evaluated whether high‐dose methotrexate (HD‐MTX) can be administered safely with extended hydration and leucovorin rescue, with monitoring of serum creatinine and urine pH. Methods The prospective study was conducted at a single centre in Chandigarh, India in 2015. Patients with B‐cell acute lymphoblastic leukemia (ALL) or with T‐cell ALL or non‐Hodgkin lymphoma (T‐NHL) were administered 3 and 5 gm/m2 of MTX (24 hr infusion), respectively. Six doses of leucovorin (15 mg/m2/dose), instead of recommended three (for optimally reduced levels) at standard timing (42 hr from start of HD‐MTX) were administered. Hydration (125 ml/m2/hr) was continued for 72 hr, instead of the recommended 30 hr. Hydration fluid consisted of 0.45% sodium chloride, 5% dextrose, 7.5% sodium bicarbonate (50 mmol/l) and potassium chloride (20 mmol/l). Serum creatinine and urine pH were measured at baseline, 24 and 48 hr. The volume of hydration was increased (200 ml/m2/hr) for a serum creatinine > 1.25 times the baseline. Results The study included 100 cycles of HD‐MTX in 53 patients: B‐ALL 25 patients (51 cycles), T‐ALL 16 patients (28 cycles), T‐NHL 10 patients (18 cycles), and relapsed ALL 2 patients (3 cycles). The mean age was 6.8 ± 3.2 years. Patients were underweight in 15 (15%) cycles. Patients in 23% of cycles had a rise in creatinine to >1.25 times the baseline. Toxicities (NCI CTCAE v4.0) included mucositis (32%), diarrhoea (10%), and febrile neutropenia (9%). One patient died from dengue shock syndrome. Conclusions It is safe to administer 3 or 5 gm/m2 of MTX (24 hr infusion) without measuring MTX levels, with extended hydration, additional doses of leucovorin, and monitoring of serum creatinine and urine pH.