Chemotherapy dose and dose intensity: analyzing data to guide therapeutic decisions.

PURPOSE/OBJECTIVES: To provide key examples from the oncology literature related to chemotherapy dose/dose intensity to guide nurses in evidence-based decision making. DATA SOURCES: Published articles and abstracts of scientific findings and clinical trials. DATA SYNTHESIS: Understanding tumor biology and growth kinetics is essential in determining optimal approaches to cancer treatment and goal setting in cancer care. CONCLUSIONS: Therapeutic decision making ideally should be data driven. Dose and dose intensity can make a difference in therapeutic outcomes. Additional research with well-designed clinical trials, incorporating recent advances in cancer biology, is needed to define more distinctly the role of dose/dose intensity related to specific tumor types. IMPLICATIONS FOR NURSING PRACTICE: Establish therapeutic goals at initiation of therapy, and communicate them clearly with patients, families, and the rest of the healthcare team.

Hematopoietic response to lineage-non-specific (rrIL-3) and lineage-specific (rhG-CSF, rhEpo, rhTpo) cytokine administration in SIV-infected rhesus macaques is related to stage of infection.

The present study reports the hematopoietic response to the exogenous administration of recombinant rhesus interleukin-3 (rrIL-3) or a combination of recombinant human granulocyte colony-stimulating factor (rhG-CSF)/erythropoietin (Epo)/thrombopoietin (Tpo) at two different stages of SIV infection: Early-stage (n = 6, CD4 + > 1000/microl and mild splenomegaly) and late-stage (n = 6, CD4 + < 500/microl, progressive hepatosplenomegaly and/or weight loss). SIV-infected animals exhibited significantly impaired bone marrow (BM) and peripheral blood (PB) responses to both rrIL-3 and rhG-CSF/Epo/Tpo administration, as compared to historic controls. In addition, compared to early-stage SIV-infected animals, late-stage SIV-infected macaques demonstrated a more marked dysfunction, as assessed by PB and BM CD34 + content and clonogenic progenitors (colony-forming unit). Neither rrIL-3 nor rhG-CSF/Epo/Tpo administration during either early-stage or late-stage SIV infection increased the viral load, as assessed by bDNA assay. These data suggest that hematopoietic reserve and the response to various cytokines is decreased even in early-stage SIV infection, with the hematopoietic dysfunction progressing in parallel to SIV infection.

Recombinant human CD40 ligand inhibits simian immunodeficiency virus replication: a role for interleukin- 16.

CD40 ligand (CD40L), expressed on activated T cells, binds its receptor, CD40, on dendritic cells, B cells, and monocytes/ macrophages. Human immunodeficiency virus (HIV)-infected individuals exhibit normal B-cell CD40 expression but diminished expression of CD40L on CD4 + T cells. Thus, we studied recombinant human CD40L (huCD40L) in an in vitro rhesus macaque model of acquired immunodeficiency syndrome (AIDS). huCD40L induced peripheral blood mononuclear cell (PBMC) proliferation independent of mitogenic cytokines and led to a 70% reduction in p27 production by simian immunodeficiency virus (SIV) mac239 infected PBMCs (P < 0.05). Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed reduced expression of SIV gag and increased expression of interleukin (IL)-16 mRNA. Supernatants from huCD40L-stimulated PBMC and control cultures contained similar amounts of IL-16, suggesting an intracellular antiviral effect by IL-16. Phytohemagglutinin (PHA)-stimulated PBMCs similarly cultured with huCD40L showed only slight increases in chemokine production (P > 0.05). These results suggest that huCD40L inhibits replication (antigen and mRNA production) of SIVmac239. This response involves huCD40L induction of IL16 mRNA expression and appears to be independent of beta-chemokines.

Peripheral blood progenitor cells for marrow reconstitution: mobilization and collection strategies.

Previous studies of PBPC BMR have found evidence supporting its safety, feasibility, and efficacy when used in a wide range of patients. Although the optimal regimen for mobilization remains a focus of debate, data from the use of combinations of chemotherapy and cytokines suggest that there is more rapid white cell and platelet engraftment than with BMT, which leads to decreased transfusion requirements and, possibly, reduced patient care costs. Recent advances in the field include allogeneic PBPC BMR, negative selection of tumor cells to reduce contamination, and positive selection of CD34+ cells. These new strategies are anticipated to enhance the therapeutic effectiveness of PBPC BMR while minimizing toxicity. Still, the ultimate comparison of PBSC BMR and medullary BMT will depend on the results of well-designed, randomized, controlled clinical trials with long-term outcome analysis. However, the refinement and improvement of mobilization and collection techniques for PBPC BMR continue to add to the armamentarium of current therapeutic approaches for cancer and related nonmalignant conditions and will enable future strategies for ex vivo expansion of progenitor cells and use in gene transfer studies.