Preparative regimen dosing for hematopoietic stem cell transplantation in patients with chronic kidney disease: analysis of the literature and recommendations.

Hematopoietic stem cell transplantation (HSCT) is a potentially life-saving therapy that has traditionally been associated with high treatment-related mortality due to direct regimen toxicity and a high incidence of graft-versus-host disease. Historically, pre-existing renal insufficiency has been considered an exclusion criterion for transplantation. The advent of nonmyeloablative conditioning regimens as a less toxic modality for treatment has made HSCT more accessible to elderly patients and patients with comorbidities, such as renal impairment. However, there is no clear standard for how to dose preparative regimens for patients with chronic renal impairment who undergo HSCT. This article serves as a review of the current literature to provide dosing recommendations for commonly used preparative agents in the setting of chronic kidney disease, with the aim of providing optimal dosing for this patient population.

Preparative regimen dosing for hematopoietic stem cell transplantation in patients with chronic hepatic impairment: analysis of the literature and recommendations.

Hematopoietic stem cell transplantation (HSCT) is a potentially life-saving therapy for patients with malignant and nonmalignant disease states. Transplant has been associated with high treatment-related morbidity and mortality, therefore limiting its usefulness in patients with baseline liver dysfunction. In the event that a patient with hepatic insufficiency is selected for HSCT, dosage adjustments may be considered; however, no reliable endogenous biomarkers can serve as a guide for adjustments. There is no clear standard or guideline for how to approach these patients, and most adjustments are made empirically on the basis of expert opinion. This article offers practical advice and outlines our personal approaches to provide dosing recommendations for commonly-used preparative agents in the setting of hepatic impairment with the aim to optimize dosing for this patient population.

Safety and efficacy of aprepitant for chemotherapy-induced nausea and vomiting in pediatric patients: a prospective, observational study.

Pediatric patients between the ages of 12 months and 17 years with a confirmed malignancy who were scheduled to receive aprepitant as part of triple therapy antiemetic prophylaxis for a cycle of moderately- or highly emetogenic chemotherapy were eligible for enrollment. Patients were evaluated for the incidence of nausea, episodes of emesis, interference with activities of daily living (ADLs), and appetite through utilization of a patient survey. Eleven patients were enrolled for a total of 20 patient encounters, mean age 9.55 ± 4.85 (range, 12 months-17 years). Aprepitant was well-tolerated and complete response (CR) rate was 38.9%.

Erythematous rash following romiplostim administration in a patient with autoimmune lymphoproliferative syndrome.

OBJECTIVE: To report a case of erythematous rash induced by romiplostim administration in a patient with autoimmune lymphoproliferative syndrome (ALPS). CASE SUMMARY: A 19-year-old female with ALPS-related thrombocytopenia (platelet count 4 × 10(3)/µL) successfully treated with romiplostim 500 µg weekly for 9 months presented with a grade 3 maculopapular rash. Symptoms on presentation included purpuric, erythematous pustules confined to the trunk following romiplostim administration the previous day. A punch biopsy of skin from the patient's right lower abdomen revealed perivascular chronic inflammation with numerous eosinophils consistent with drug reaction. The patient had received romiplostim 500 µg weekly with no other reports of rash until this time. Romiplostim was discontinued, the patient was monitored, and the rash resolved within 1 week. Romiplostim was then restarted at 200 µg weekly. The patient has achieved platelet normalization at a current romiplostim dose of 250 µg weekly with no further adverse reactions. DISCUSSION: ALPS is a rare autoimmune disorder with approximately 500 known cases worldwide. Pharmacotherapy for ALPS patients generally targets autoimmune cytopenias associated with the disorder. When standard therapies for ALPS-related cytopenias fail, clinicians are often forced to consider novel treatment options. Our patient had ALPS-related thrombocytopenia that was treated with romiplostim, which resulted in grade 3 maculopapular rash after almost 1 year of treatment. The likelihood that this patient's erythematous rash was due to romiplostim administration was determined to be possible based on the Naranjo probability scale. The reaction was reported to the drug manufacturer and to the Food and Drug Administration's MedWatch program. CONCLUSIONS: This is the first documented case, to our knowledge, of severe maculopapular rash occurring less than 24 hours after romiplostim administration for treatment of ALPS-related chronic thrombocytopenia. Rash has been reported as an adverse event of romiplostim therapy at higher doses (750 µg), but not at a dose of 500 µg. This report also describes successful rechallenge of romiplostim after resolution of the rash.

Profile of belinostat for the treatment of relapsed or refractory peripheral T-cell lymphoma.

The peripheral T-cell lymphomas are a rare and heterogeneous group of mature T-cell lymphomas with limited available therapies. The outcome of frontline chemotherapy regimens has been disappointing, with a long-term survival of only 20%-30%. There is an urgent need to optimize induction therapy by incorporating novel agents that target the dysregulated pathways. Histone deacetylase inhibitors that induce acetylation of histones and enhance apoptosis have shown promising activity. In this article, we summarize the role of histone deacetylase inhibitors and specifically discuss pharmacokinetics, efficacy, and toxicity of the recently US Food and Drug Administration-approved agent belinostat for its use in patients with relapsed/refractory peripheral T-cell lymphoma.