sodium-bicarbonate and Hematologic-Diseases

The aim of this study was to evaluate and compare the clinical characteristics of the B-cell non-Hodgkin lymphoma (NHL) patients and therapeutic efficacy of modified NHL BFM-90 and NHL BFM-95 protocols in the authors' center. From January 1993 to December 2003, 61 newly diagnosed children with B-NHL were enrolled to the study. The patients were stratified by risk factors and treated either with a modified B-NHL BFM-90 or BFM-95 protocols. The use of 1 or 3 g/m2 of methotrexate instead of 5 g/m2/24 h was the only important modification in BFM-90 protocol. Sixty-one children (12 girls, 49 boys) with a median age of 6.5 years (range: 2.5-16) were treated in the center. There were 14 patients in stage II, 28 in stage III, and 19 in stage IV. The most common initial primary tumor sites were abdomen, head, and neck. Forty-five patients were treated with modified B-cell BFM-90 and 16 patients were treated with B-cell BFM-95 regimens. The 5-year overall survival (OS) for all patients was 85.8%, and event-free survival (EFS) was 82.8%. The 5-year OS rates in modified BFM-90 and in BFM-95 protocols were 85.2 and 87.5%; the 5-year EFS rates in these 2 protocols were 84.6 and 70%, respectively (p >.05). Factors associated with lower EFS by univariate analysis were bulky disease, risk groups, and LDH level > or = 500 IU/L. By multivariate analysis only LDH level was significant. In conclusion, the treatment results in this study were similar to those of BFM group.

Topics: Adolescent; Allopurinol; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Disease-Free Survival; Diuretics; Female; Fluid Therapy; Hematologic Diseases; Humans; Kaplan-Meier Estimate; L-Lactate Dehydrogenase; Leucovorin; Lymphoma, B-Cell; Male; Methotrexate; Mucositis; Neoplasm Proteins; Risk Assessment; Sodium Bicarbonate; Survival Analysis; Survival Rate; Treatment Outcome; Tumor Burden; Tumor Lysis Syndrome; Turkey; Vincristine

HMBA is a potent differentiating agent capable of causing > 95% morphological differentiation in cell lines in vitro. The induction of differentiation is dependent on both the concentration of and the duration of exposure to HMBA. However, acute toxicities (neurotoxicity and acidosis) have limited the maximal HMBA css value to < 2 mM, which is at the lower limit of effective in vitro concentrations. When HMBA css values have been maintained at 1-2 mM, thrombocytopenia has limited the duration of HMBA infusion to < or = 10 days. The present studies were performed to determine whether exposure to HMBA could be individualized and maximized without resulting in intolerable toxicity to patients and to determine which factors would predispose a patient to the development of acute toxicity during treatment with HMBA. For these investigations, patients were given HMBA at a target css using an adaptive-feedback-control method rather than at a set dose. Because HMBA administration produces large anion gaps, a simple maneuver such as alkalinization might enable the escalation of plasma HMBA css values to > 2 mM. HMBA was given as a 5-day CI to 14 patients (26 courses) at 2 target HMBA css levels near the maximal tolerated value in the presence or absence of concurrent alkalinization with sodium bicarbonate. Symptomatic acidosis occurred in one patient who did not receive bicarbonate. Neurotoxicity proved to be dose-limiting at the target HMBA css value of 1.5-2.0 mM in the absence of concurrent alkalinization and at a css level of > 2 mM, regardless of alkalinization. No neurotoxicity was seen at target HMBA css values of 1.5-2.0 mM in patients who did receive concurrent alkalinization. Alkalinization was not associated with any detectable changes in plasma HMBA metabolites. With the maximal tolerable 5-day HMBA css having thus been defined at 1.5-2.0 mM, we attempted to maximize exposure to HMBA by defining a tolerable duration of infusion. Individualization of the duration of HMBA infusion to a target nadir PLT was performed in patients who had received an initial 5-day CI of HMBA at a css 1.5-2.0 mM along with concurrent alkalinization. The AUC achieved and the thrombocytopenia produced during this first course were used to predict the duration of infusion that each patient would subsequently tolerate (at an HMBA css of 1-2 mM) to achieve a nadir PLT of 75,000-100,000/microliters.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Acetamides; Acidosis; Adult; Aged; Bicarbonates; Clinical Trials, Phase I as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Hematinics; Hematologic Diseases; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Models, Biological; Neoplasms; Nervous System Diseases; Sodium; Sodium Bicarbonate