sodium-bicarbonate and Precursor-Cell-Lymphoblastic-Leukemia-Lymphoma

Hyperleukocytosis secondary to acute leukemia is a medical emergency. Intracranial hemorrhage often leads to death in this setting. Early efforts to prevent this serious complication have included emergent cranial irradiation, with its associated morbidity when used in the young child. Currently, exchange transfusion and/or leukapheresis are employed to acutely lower the peripheral leukocyte count.. We report three infants with acute leukemia and hyperleukocytosis in whom intravenous hydration, alkalinization, and allopurinol therapy alone produced rapid and dramatic decreases in the peripheral leukocyte count.. The maximal decrease in leukocyte count averaged 88% within 70 h of starting conservative management. A fall in leukocyte count to < 100 x 10(9)/L was noted at an average of 15 h following hospitalization. No patient developed complications.. When comparing this approach to exchange transfusion and leukapheresis we find it to be both safe and effective. Children with hyperleukocytosis in association with acute lymphocytic leukemia who present without life-threatening complications of an extremely high leukocyte count can be safely and effectively managed with intravenous hydration, alkalinization, and allopurinol therapy.

Topics: Allopurinol; Bicarbonates; Female; Fluid Therapy; Humans; Infant; Leukemia; Leukocytosis; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Sodium; Sodium Bicarbonate

National drug shortages of essential medications for childhood cancer have increasingly posed a challenge in the treatment of patients. The efficacy of standardized supportive care practices to avoid treatment-related toxicities may be limited during these drug shortages. High-dose methotrexate (HDMTX) plays a critical role in modern treatment protocols for acute lymphoblastic leukemia and requires stringent supportive care measures to mitigate toxicity. As the result of a national intravenous (IV) sodium bicarbonate shortage, institutional standard HDMTX supportive care guidelines had to be modified. We describe the unanticipated consequences on HDMTX clearance.. We performed a retrospective chart review assessing the impact of alternative compositions of IV fluids on the mean 24-h methotrexate levels (Cp. Patients receiving a higher total sodium dose demonstrated significantly lower Cp. Our report shows that in the setting of IV sodium bicarbonate shortage, the composition of hydration IV fluids may affect methotrexate clearance. Patient who received a higher sodium load had a lower 24-h methotrexate level. This demonstrates the potential for unanticipated outcomes resulting from national drug shortages.

Topics: Administration, Intravenous; Adolescent; Antimetabolites, Antineoplastic; Child; Child, Preschool; Female; Humans; Male; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Sodium; Sodium Bicarbonate

To determine the correlation between pH and bicarbonate of soda in blood and saliva in child and adolescent patients during the administration of 3 g/m2 of methotrexate.. A controlled clinical test was performed on 23 patients diagnosed with Acute Lymphoblastic Leukemia. Ages ranged from 4 to 18. The Spearman Correlation Coefficient was used to interpret the data.. No significant correlation was found between pH levels and seric and salivary sodium bicarbonate. However, there was a significant correlation between the levels of sodium bicarbonate in the body fluids evaluated (rs 0.2576, p=0.0354).. Changes modifying the microenvironment of the oral cavity probably do not allow saliva to be used to determine blood pH and seric bicarbonate.

Topics: Adolescent; Child; Child, Preschool; Humans; Hydrogen-Ion Concentration; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Saliva; Sodium Bicarbonate

To analyze the behavior of pH and sodium bicarbonate (NAHCO3) in the saliva of patients with leukemia during the administration protocol for Methotrexate (Mtx).. A controlled clinical essay was carried out on 23 patients between 4 and 18 years of age with high-risk Acute Lymphoblastic Leukemia. Sampling was carried out at To: basal condition; T1: 12 hours after intravenous administration of sodium bicarbonate, before administering Mtx and T2: 3 hours after administering Mtx, the time of maximum concentration. Chiron-Diagnostic 378 equipment was used to determine pH and sodium bicarbonate. The data was interpreted using Analysis of Variance at the 5% significance level.. The highest values of sodium bicarbonate were observed at T2, with salivary pH levels remaining within neutrality ranges, diminishing slightly in T1. CONCLUSION. In this study, the dose of sodium bicarbonate considered in the administration protocol of 3 g /m2 Mtx, kept sodium bicarbonate levels in saliva at normal levels and pH neutral.

Topics: Adolescent; Antimetabolites, Antineoplastic; Child; Child, Preschool; Clinical Protocols; Humans; Hydrogen-Ion Concentration; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Saliva; Sodium Bicarbonate

One of the major complications after high-dose methotrexate (HDMTX) infusions is renal damage. We investigated the occurrence of proteinuria after HDMTX administration in children with pediatric malignancies (acute lymphoid leukaemia, osteosarcoma Burkitt's lymphoma). In the period 1989-1990 we gave 52 HDMTX courses to 24 children. During this period, prehydration and extra urinary alkalisation were performed only if the urinary specific gravity was over 1010 or if the urinary pH fell below 7. Using this schedule the mean values obtained for protein extraction were: before the therapy, 0.12 +/- 0.03 g/m2; on day 1 after MTX treatment, 0.38 +/- 0.06 g/m2; and on day 2 after the MTX infusion, 0.39 +/- 0.11 g/m2 (P < 0.01). A significant increase in proteinuria (> 0.2 g/m2 post- vs pretreatment) was detectable in 54% of the patients. In the period 1991-1992 we modified the hydration-alkalisation schedule to include i.v. prehydration for 18-24 h at 3 l/m2/day with a 0.45% NaCl-5% glucose solution along with sodium bicarbonate and posthydration for 72 h with the same solution. On this protocol the mean values determined for the urinary protein content were all in the normal range (pretreatment, 0.03 g/m2/day; day 1, 0.05 g/m2/day; and day 2, 0.08 g/m2/day). These findings were significantly different from the previous results (P < 0.05).

Topics: Adolescent; Bone Neoplasms; Burkitt Lymphoma; Child; Female; Fluid Therapy; Glomerular Filtration Rate; Glucose; Humans; Male; Methotrexate; Neoplasms; Osteosarcoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Proteinuria; Sodium Bicarbonate

NaHCO3 activated the folylpolyglutamate synthetase (FPGS) from rat liver and the human leukemia cell lines K562 and CCRF-CEM by 1.7- to 2.0-fold. Optimal activation was achieved by 10 mM NaHCO3 in all cases; NaCl, sodium formate, sodium acetate, NaN3, and Na2SO3 at 10 mM did not cause activation. Activation could be masked if assay solutions which had extensively absorbed atmospheric CO2 were used. Activation of the human CCRF-CEM FPGS was examined in detail. Km and Vmax values for pteroyl substrates (aminopterin or methotrexate) and L-glutamate increased proportionally in the presence of NaHCO3; there was thus no apparent change in the catalytic efficiency (Vmax/Km) of the FPGS reaction with these substrates. However, NaHCO3 increased the efficiency of the reaction with respect to ATP by decreasing its apparent Km while increasing the Vmax of the reaction. NaHCO3 also activated FPGS activity when folic acid, dihydrofolic acid and tetrahydrofolic acid were substrates. The relative distribution of products synthesized from methotrexate or tetrahydrofolate by FPGS was not altered by addition of NaHCO3. The potency of 5,8-dideazapteroylornithine, an FPGS-specific inhibitor, was not changed by the presence of NaHCO3 (IC50 = 0.4 microM). These results suggest that FPGS activity with folates and classical antifolates may be activated at physiological concentrations of NaHCO3. In addition, inadvertent contamination of assay solutions with bicarbonate from atmospheric CO2 may cause artifacts in the determination of activity levels and kinetic constants of FPGS.

Topics: Animals; Bicarbonates; Enzyme Activation; Humans; Ornithine; Peptide Synthases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Rats; Sodium; Sodium Bicarbonate; Substrate Specificity; Tumor Cells, Cultured