Favorable outcomes in patients with high donor-derived T cell count after in vivo T cell-depleted reduced-intensity allogeneic stem cell transplantation.

Patients with hematologic malignancies were conditioned using a rabbit antithymocyte globulin-based reduced-intensity conditioning regimen for allogeneic stem cell transplantation. Donor-derived CD3(+) cell count (ddCD3), a product of CD3(+) cell chimerism and absolute CD3(+) cell count, when <110/µL at 8 weeks post-stem cell transplantation predicted a high risk of sustained mixed chimerism and relapse. Alternatively, patients with a higher ddCD3 developed graft-versus-host disease more frequently, and when partially chimeric, had higher rates of conversion to full donor chimerism after withdrawal of immunosuppression. Early data from our small cohort of patients indicate that ddCD3 at 8 weeks may be used to guide decisions regarding withdrawal of immunosuppression and administration of donor lymphocyte infusion in partially T cell-depleted reduced-intensity regimens.

Ipilimumab: a novel treatment for metastatic melanoma.

OBJECTIVE: To review the mechanism of action, pharmacokinetics, efficacy, safety, drug interactions, dosing, and economic considerations of ipilimumab. DATA SOURCES: A literature search using MEDLINE (1966-November 2010) was performed using the terms ipilimumab, metastatic melanoma, MDX-010, and MDX-101. Additional data were obtained from meeting abstracts, bibliographies, and media releases. STUDY SELECTION AND DATA EXTRACTION: English-language articles identified from the data sources were reviewed. Selected studies evaluated the pharmacology, pharmacokinetics, efficacy, and safety of ipilimumab for the treatment of metastatic melanoma. DATA SYNTHESIS: The incidence of melanoma in the US is increasing faster than any other type of cancer in men and more than any other type of cancer, except lung cancer, in women. For patients with metastatic melanoma, systemic therapies are limited by low response rates, short durations of response, and a 5-year survival rate <10%. Ipilimumab, a novel CTLA-4 inhibitor, is under investigation for the treatment of metastatic melanoma. Results of a randomized, controlled Phase 3 trial showed a first-ever overall survival benefit for patients with previously treated metastatic melanoma who received ipilimumab compared with the controls. The majority of adverse events reported with ipilimumab administration are considered to be low-grade immune-related events involving the skin and intestine and can be managed medically. Nonetheless, 10-17% of patients have immune-related adverse events of grade 3 or higher severity, with 2-3% of these events resulting in death. CONCLUSIONS: Ipilimumab is a novel CTLA-4 inhibitor that has been evaluated for the treatment of metastatic melanoma. On March 25, 2011, the Food and Drug Administration approved ipilimumab, making it the first agent indicated for unresectable or metastatic melanoma in more than a decade.

Plerixafor: a peripheral blood stem cell mobilizer.

Autologous hematopoietic stem cell (HSC) transplantation is a treatment strategy for restoring normal hematopoietic function in patients with select hematologic malignancies. The number of CD34(+) cells available for transplantation has been reported to be the strongest predictor of transplantation success, as measured by rapid and durable hematopoietic recovery. Currently, granulocyte colony-stimulating factor (G-CSF) alone or G-CSF plus chemotherapy are the most commonly used methods for stem cell mobilization. Unfortunately, 5-30% of patients do not respond to these agents. Plerixafor is a new HSC mobilizing drug that antagonizes the binding of chemokine stromal-cell-derived factor-1alpha (SDF-1alpha) to CXC chemokine receptor 4 (CXCR4). It is indicated in combination with G-CSF to mobilize HSC to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). Results of clinical trials have shown that plerixafor plus G-CSF allow for the collection of a high yield of HSC with fewer apheresis sessions in patients with NHL and MM. Plerixafor has also shown promising results in small studies enrolling patients with Hodgkin's lymphoma. Moreover, for patients who fail G-CSF mobilization alone, plerixafor with G-CSF may be useful as a salvage mobilization strategy. Overall, plerixafor has been generally well tolerated with adverse effects classified as mild to moderate. The most common adverse effects reported in randomized clinical trials were injection site reactions and diarrhea, with approximately 33% of patients experiencing these effects. To our knowledge, clinical trials comparing G-CSF plus plerixafor with G-CSF plus chemotherapy and cost-effectiveness analyses have not been published; therefore, questions remain regarding the optimal role of plerixafor in the clinical practice setting.