Serum Creatinine Versus Plasma Methotrexate Levels to Predict Toxicities in Children Receiving High-dose Methotrexate.

Facilities for measuring methotrexate (MTX) levels are not available everywhere, potentially limiting administration of high-dose methotrexate (HDMTX). We hypothesized that serum creatinine alteration after HDMTX administration predicts MTX clearance. Overall, 122 cycles in 50 patients of non-Hodgkin lymphoma or acute lymphoblastic leukemia aged ≤18 years receiving HDMTX were enrolled prospectively. Plasma MTX levels were measured at 12, 24, 36, 48, 60, and 72 hours; serum creatinine was measured at baseline, 24, 48, and 72 hours. Correlation of plasma MTX levels with creatinine levels and changes in creatinine from baseline (Δ creatinine) were evaluated. Plasma MTX levels at 72 hours showed positive correlation with serum creatinine at 48 hours (P = .011) and 72 hours (P = .013) as also Δ creatinine at 48 hours (P = .042) and 72 hours (P = .045). However, cut-off value of either creatinine or Δ creatinine could not be established to reliably predict delayed MTX clearance. Greater than 50% Δ creatinine at 48 and 72 hours significantly predicted grade 3/4 leucopenia (P = .036 and P = .001, respectively) and thrombocytopenia (P = .012 and P = .009, respectively) but not mucositis (P = .827 and P = .910, respectively). Delayed MTX elimination did not predict any grade 3/4 toxicity. In spite of demonstration of significant correlation between serum creatinine and Δ creatinine with plasma MTX levels at 72 hours, cut-off value of either variable to predict MTX delay could not be established. Thus, either of these cannot be used as a surrogate for plasma MTX estimation. Interestingly, Δ creatinine effectively predicted hematological toxicities, which were not predicted by delayed MTX clearance.

Therapy and outcome of primitive neuroectodermal tumor of the jaw.

Data pertaining to outcomes in jaw primitive neuroectodermal tumor (PNET) are lacking. Eleven cases of jaw PNET (five maxillary and six mandibular) were treated at our cancer center with the same chemotherapeutic agents from June 2003 to January 2009. Four patients underwent surgery after neoadjuvant chemotherapy and all received local radiotherapy. At median follow-up of 56 months (range: 19-77 months), 7/11 patients are in sustained remission. There was no difference in outcome with respect to site of tumor, and whether surgery was performed or not. These results support the use of chemoradiation as initial modality of treatment rather than going for extensive and mutilating surgery.

Complications of "very high" leukocytosis in pediatric acute leukemia patients managed without rasburicase and leukopheresis.

The authors evaluated complications in pediatric acute leukemia with "very high" leukocytosis (VHL) prior to rasburicase availability and without leukopheresis. From Jun 2003 through Dec 2009, 45 out of 457 (10 %) pediatric acute leukemia patients had VHL. Median WBC for acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) patients was 296,500/mm3 (200,000-615,220) and 206,300/mm3 (106,100-541,900) respectively. Laboratory and clinical tumor-lysis-syndrome was seen in 37.7 % and 13.3 % patients respectively; none required dialysis; 6.6 % died due to CNS/pulmonary bleed. Thrombocytopenia <31,000/mm3 was associated with hypocalcemia (p = 0.04) and mortality (p = 0.04), and hypoalbuminemia with kidney dysfunction (p = 0.04). In resource-limited setting, VHL patients with thrombocytopenia may warrant rasburicase with or without leukopheresis, and aggressive platelet support.