Sherry Mathew

Intensified Mycophenolate Mofetil Dosing and Higher Mycophenolic Acid Trough Levels Reduce Severe Acute Graft-versus-Host Disease after Double-Unit Cord Blood Transplantation.

Although mycophenolate mofetil (MMF) has replaced corticosteroids as immunosuppression in cord blood transplantation (CBT), optimal MMF dosing has yet to be established. We intensified MMF dosing from every 12 to every 8 hours to augment graft-versus-host disease (GVHD) prophylaxis in double-unit cord blood transplantation (dCBT) and evaluated outcomes according to the total daily MMF dose/kg in 174 dCBT recipients (median age, 39 years; range, 1 to 71) who underwent transplantation for hematologic malignancies. Recipients of an MMF dose ≤ the median (36 mg/kg/day) had an increased day 100 grade III and IV acute GVHD (aGVHD) incidence compared with patients who received >36 mg/kg/day (24% versus 8%, P = .008). Recipients of ≤ the median dose who had highly HLA allele (1 to 3 of 6) mismatched dominant units had the highest day 100 grade III and IV aGVHD incidence of 37% (P = .009). This finding was confirmed in multivariate analysis (P = .053). In 83 patients evaluated for mycophenolic acid (MPA) troughs, those with a mean week 1 and 2 trough < .5 μg/mL had an increased day 100 grade III and IV aGVHD of 26% versus 9% (P = .063), and those who received a low total daily MMF dose and had a low mean week 1 and 2 MPA trough had a 40% incidence (P = .008). Higher MMF dosing or MPA troughs had no impact on engraftment after myeloablation. This analysis supports intensified MMF dosing in milligram per kilogram per day and MPA trough level monitoring early after transplantation in dCBT recipients.

Retrospective comparison of the effects of filgrastim and pegfilgrastim on the pace of engraftment in auto-SCT patients

The high doses of chemotherapy used for the preparatory regimens before autologous blood or marrow stem cell transplantation leave patients at risk for neutropenic complications. The administration of filgrastim post transplant reduces the time to neutrophil recovery and therefore has become a standard practice at many institutions. In 2006, we implemented a practice change from filgrastim to pegfilgrastim. We present data on 164 consecutive patients (82 patients who received filgrastim compared with 82 patients who received pegfilgrastim) who received an auto-SCT between January 2006 and November 2007. Patients who received pegfilgrastim had faster engraftment (9.6 days compared with 10.9 days, P<0.0001), a lower incidence of febrile neutropenia (59% compared with 78%, P=0.015), as well as shorter hospital stay, fewer days of treatment with i.v. antibiotics (6.3 days compared with 9.6 days, P=0.006), and fewer radiographic tests, which translated to an estimated total cost savings of over

Retrospective Evaluation of Palifermin Use in Nonhematopoietic Stem Cell Transplant Pediatric Patients

8000 per patient. Overall, there were no differences in toxicity with these two agents. We conclude that a single dose of pegfilgrastim is a safe and efficacious alternative to daily injections of filgrastim and can be a cost-effective approach in auto-SCT patients.

Retrospective Analysis of Posaconazole Suspension Dosing Strategies in a Pediatric Oncology Population: Single-Center Experience

Background: Palifermin has been proven to decrease the frequency of severe oral mucositis in adult patients with sarcoma and metastatic colorectal cancer receiving chemotherapy. The impact of palifermin on the incidence of mucositis in nonhematopoietic stem cell transplantation (HSCT) pediatric population receiving chemotherapy has never been reported to date. Patients and Methods: This is a retrospective analysis of pediatric patients who received palifermin as secondary prophylaxis to prevent chemotherapy-induced mucositis at Memorial Sloan Kettering Cancer Center from January 1, 2008 to 2014. Data from electronic medical records on days to mucositis resolution, use of opioids, use of total parenteral nutrition, duration of hospitalization, and antibiotics are collected and presented here. Results: A total of 18 patients received palifermin for secondary prophylaxis after developing mucositis from the prior chemotherapy cycle. Mucositis did not reoccur in the subsequent cycle for 13 of the 18 patients. The majority of patients who received palifermin prophylaxis had decreased opioids and antibiotics use and decreased duration of hospitalization. Six of the 7 patients previously requiring total parenteral nutrition due to mucositis had decreased supplemental nutritional needs following the use of palifermin. Conclusion: Palifermin may provide benefit as secondary prophylaxis in pediatric patients to prevent chemotherapy-induced mucositis.

Management of Patients with Acute Methotrexate Nephrotoxicity with High‐Dose Leucovorin

Limited data on optimal posaconazole dosing strategies for pediatric patients exist. In this study, we found that the median initial dose in patients who achieved a posaconazole plasma concentration of 0.7 μg/mL was 22.8 mg/kg per day whereas the median initial dose in those who did not reach the target concentration was 15.8 mg/kg per day; this result suggests that higher initial doses might be warranted.

Spotlight on nilotinib in the treatment of chronic myelogenous leukemia

Acute kidney injury complicating high‐dose methotrexate (HDMTX) therapy increases the risk for severe mucositis, myelosuppression, and death. It is unclear whether high‐dose leucovorin and supportive therapy without the use of glucarpidase can reduce toxicity from HDMTX.

Retrospective Evaluation of Palivizumab Efficacy and Safety for RSV Prophylaxis in Pediatric Hematopoietic Stem Cell Transplant Patients: A Single Center Experience

Nowhere has targeted therapy been more successful in the hematologic malignancy arena than chronic myelogenous leukemia (CML). By targeting the BCR-ABL fusion oncogene, the introduction of tyrosine-kinase inhibitors (TKIs) has dramatically improved the outcomes of this disease. Nilotinib is a second-generation TKI that initially gained approval for the treat- ment of imatinib-resistant or -intolerant disease for patients with chronic or accelerated-phase CML. Investigation in the first-line setting also demonstrated efficacy, and expanded nilotinibs approval to include therapy for patients with treatment-naive chronic-phase CML. Data also exist for blast-phase disease, which allows nilotinib to be an option for all phases. Nilotinibs place in therapy is continuously being expanded by research in novel areas, such as post-hematopoietic stem cell transplants for prevention of relapse and in the pediatric arena. With multiple TKIs now approved for the treatment of CML, delineating the pharmacologic distinctions of nilotinib is an asset when determining therapy. By understanding the pharmacokinetics and dependence on hepatic metabolism of nilotinib, the clinician can manage the potential toxicities, interactions, and unique dosing of this drug. The recognition of mechanisms of resistance, patient adherence, and cost-effectiveness are similarly significant considerations. Actively integrating these various specifics will allow clinicians to optimize nilotinib therapy for the CML patient.