Study On High Dose Methotrexate And Different Calcium Folinate Rescue For Treatment In Audlt Refractory And Relapsed Acute Lymphoblastic Leukemia

Objective: To explore the toxicity and efficacy of two different Calcium folinate rescue for high dose methotrexate used in adult refractory and relapsed acute lymphoblastic leukemia(ALL).Methods: 1: MTT assay analysis cytotoxicities in leukemia cells of 35 patients with refractory and relapsed ALL before treatment. 2: They were divided into two groups randomly treated with HDMTX (2.0g/m²)and VP regimen. Calcium folinate was administered intramuscularly either 15 mg An² every 6 hour for 8 times, beginning at hour 12 and hour 20 after the end of HDMTX respectively in ordinary group and controlled group. 3: MTX serum concentrations were determined by fluorescence polarization immunoassay in 6 patients of the controlled group at hour 0, hour 12,hour 24 and hour 48 after the end of HDMTX. 4: Observe drug-induced toxicity and the efficacy of HDMTX regimen.Result: 1:35 patients were divided into the sensitive group and insensitive group by MTT assay. Cytotoxicities( X ±S) in the sensitive group is(63%±6.2%) and(34%±8.5%) in the insensitive group, two groups have significant difference (p<0.05) . 2: At hour 24 after the end of HDMTX ,all serum MTX concentrations were less than that of drug-induced toxicity (1× 10^-6mol/L) . at hour 48 after the end of HDMTX , serum MTX concentrations of one patient was more than that of drug-induced toxicity (0.1 ×10^-6 mol/L) . 3: The drug-induced toxicity and their recovery time did not differ significantly between the two groups. 4: HD-MTX regimen demonstrated a CR rate of 42.9%. 7 patients achieved Completeremission(CR 35%)in ordinary group, as compared with 8 patients (CR 53.3%)in controlled group, two groups have no significant difference (p>0.05) .but there have been 4 patients relapse in ordinary group, as compared with 2 patients in controlled group. 5: There were (in vitro/in vivo, S: sensitivity, R: resistance) 13 S/S, 15 R/R, 5 S/R, 2 R/S, The general, positive and negative coincident rates of chemosensitivity in vitro with those of in vivo sensitivity were 80%, 72.2% ,88.2%, respectively. Sensitivity and specificity were 86.7% and 75%, respectively.Conclusion: 1: From this study, it is our impression that the MTT assay gives a good predictive value for high sensitivity and specificity.2: HD-MTX regimen is effective in treatment in adult acute refractory and relapsed lymphoblastic leukemia.In HD-MTX regimen ,a delayed calcium folinate rescue can improve the efficacy of HDMTX , without increasing drug-induced toxicity .it can be applied in hospital.