Pegfilgrastim use during chemotherapy: current and future applications.

Chemotherapy-induced myelosuppression is the most common dose-limiting side effect of cancer chemotherapy. Neutropenia is a serious risk with chemotherapy, associated with infectious complications, use of intravenous antibiotics, hospitalization, and even death. The occurrence of febrile neutropenia can lead to dose reductions and delay in subsequent cycles of chemotherapy that may have a detrimental affect on overall survival and disease-free survival. Granulocyte colony-stimulating factors (G-CSF) can reduce the duration of severe neutropenia, the incidence of febrile neutropenia, and allow planned dosing and timing of chemotherapy. Filgrastim is a G-CSF that has demonstrated benefit for the treatment and prophylaxis of chemotherapy-induced neutropenia (CIN), but its short half-life requires repeated daily subcutaneous injection. Pegfilgrastim is a recombinant G-CSF created by attaching a polyethylene glycol (PEG) molecule to the filgrastim protein. Once-per-cycle dosing of pegfilgrastim has been evaluated in clinical trials using myelosuppressive chemotherapy in breast cancer, Hodgkin's lymphoma, and non-Hodgkin's lymphoma. Trials have demonstrated that pegfilgrastim is comparable in safety and efficacy to filgrastim for decreasing the duration of severe neutropenia after chemotherapy in patients with nonmyeloid malignancy. This review will summarize recent clinical trial results and novel uses of pegfilgrastim.

Gentle Massage Improves Disease- and Treatment-Related Symptoms in Patients with Acute Myelogenous Leukemia.

OBJECTIVE: Cancer treatment is reported to be stressful, and patients diagnosed with hematologic cancers often exhibit higher levels of anxiety and emotional distress than individuals with other malignancies. Management of these symptoms in patients with hematologic cancer presents significant challenges, as many of them are in and out of the hospital while undergoing high dose chemotherapy. Oncology patients use complementary modalities such as therapeutic massage in an attempt to alleviate disease and treatment-related symptoms, including anxiety and emotional distress. In the current study, the feasibility of a novel massage intervention delivered over the continuum of care, as well as assessment of the immediate and cumulative effects of massage, was examined in patients with acute myelogenous leukemia. METHODS: A mixed-methods, unmasked, prospective, randomized study was conducted with two groups: a usual care alone control group and a massage therapy intervention plus usual care group. RESULTS: Significant improvements in levels of stress and health-related quality of life were observed in the massage therapy group versus the usual care alone group, after adjusting for anxiety level, including both immediate and cumulative effects of massage. CONCLUSIONS: While the findings of the current study regarding acceptability, feasibility, and potential efficacy of therapeutic massage as a complementary health-enhancing intervention in patients diagnosed with acute myelogenous leukemia are very promising, the relatively small size of the study sample limits generalizability.

Treatment strategies for relapsed and refractory aggressive non-Hodgkin's lymphoma.

The aggressive non-Hodgkin's lymphomas (NHL) are a clinically heterogeneous group of lymphomas with disparate responses to standard chemotherapy regimens. Aggressive NHL includes diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL) and peripheral T-cell lymphomas (PTCL), among others. Significant advances have been made in the last decade in the initial treatment of DLBCL and MCL, but the treatment of relapsed or refractory disease remains difficult. The addition of rituximab to the treatment of DLBCL and MCL has improved clinical outcomes and is now a critical component of initial therapy and treatment of relapsed disease. The PTCLs, not having a similar agent to significantly change the treatment approach to these diseases, remain a difficult therapeutic problem. This review examines recent advances in the treatment of relapsed or refractory aggressive NHL and discusses novel approaches currently under investigation.

Thrice-weekly low-dose rituximab decreases CD20 loss via shaving and promotes enhanced targeting in chronic lymphocytic leukemia.

Treatment of chronic lymphocytic leukemia (CLL) patients with standard dose infusion of rituximab (RTX), 375 mg/m2, induces clearance of malignant cells from peripheral blood after infusion of 30 mg of RTX. After completion of the full RTX infusion, substantial recrudescence of CLL cells occurs, and these cells have lost > 90% of CD20. To gain insight into mechanism(s) of CD20 loss, we investigated the hypothesis that thrice-weekly low-dose RTX (20 or 60 mg/m2) treatment for CLL over 4 wk would preserve CD20 and enhance leukemic cell clearance. During initial infusions in all 12 patients, the first 30 mg of RTX promoted clearance of > 75% leukemic cells. Four of six patients receiving 20 mg/m2 RTX retained > or = 50% CD20, and additional RTX infusions promoted further cell clearance. However, four of six patients receiving 60 mg/m2 had CD20 levels < 20% baseline 2 days after initial infusions, and additional RTX infusions were less effective, presumably due to epitope loss. Our results suggest that when a threshold RTX dose is exceeded, recrudesced RTX-opsonized cells are not cleared, due to saturation of the mononuclear phagocytic system, but instead are shaved of RTX-CD20 complexes by acceptor cells. Thrice-weekly low-dose RTX may promote enhanced clearance of circulating CLL cells by preserving CD20.

Phase II trial of idiotype vaccination in previously treated patients with indolent non-Hodgkin's lymphoma resulting in durable clinical responses.

PURPOSE: To evaluate idiotype (Id) vaccination as a single agent in previously treated patients with indolent non-Hodgkin's lymphoma. PATIENTS AND METHODS: Patients underwent biopsy for determination of their lymphoma-specific Id sequence. Recombinant Id protein was manufactured and covalently linked with keyhole limpet hemocyanin (KLH) to generate Id/KLH. Patients received Id/KLH 1 mg on day 1 subcutaneously, with granulocyte-macrophage colony-stimulating factor 250 mug on days 1 to 4, monthly for 6 months. Booster injections were administered until progression. Both clinical and immune responses were evaluated. RESULTS: Thirty-two previously treated patients received at least one injection of Id/KLH, and 31 were assessed for efficacy. Responses were observed in four patients (one complete response and three partial responses). Median time to onset of response was 5.9 months (range, 2.3 to 14.1 months). Median duration of response has not been reached but should be at least 19.4 months (range, 10.4 to 27.2+ months). Median time to progression is 13.5 months. The most common adverse events were mild to moderate injection site reactions. Six (67%) of nine patients tested demonstrated a cellular immune response, and four (20%) of 20 patients demonstrated an antibody response against their Id. CONCLUSION: This trial demonstrates that Id/KLH alone can induce tumor regression and durable objective responses. Further study of Id/KLH is recommended in other settings where efficacy may be further enhanced as in first-line therapy or after cytoreductive therapy.

Biology and therapy of mantle cell lymphoma.

PURPOSE OF REVIEW: Mantle cell lymphoma is an aggressive non-Hodgkin's lymphoma characterized by the t(11;14) chromosomal translocation and overexpression of cyclin D1. Constituting approximately 5 to 8% of all non-Hodgkin's lymphomas, it carries the poorest prognosis among non-Hodgkin's lymphoma subtypes. Standard and effective treatment approaches have yet to be established. RECENT FINDINGS: Several recent insights regarding the molecular pathogenesis and prognostic biomarkers have been realized by way of comparative genomic hybridization, cDNA microarray, and proteomic analysis. Clinical trials using chemotherapy plus rituximab have shown improved response rates, including complete remissions, but without cure in most cases, indicating a clear need for new treatment approaches. Novel therapies for relapsed disease using the proteasome inhibitor bortezomib, thalidomide plus rituximab, the cyclin inhibitor flavopiridol, or inhibitors of the mammalian target of rapamycin (mTOR) have shown encouraging clinical responses. Stem cell transplantation, including nonmyeloablative approaches, are being incorporated into therapeutic regimens and show promise in both the front-line and relapsed/refractory settings. SUMMARY: This review summarizes recent advances in the biology, pathogenesis, and therapy of mantle cell lymphoma and identifies ongoing areas of clinical investigation and new treatment approaches.

Hematologic disorders in the athlete.

Optimal athletic performance depends on proper function of many organs, including the blood. This is underscored by the focus of endurance athletes on increased hemoglobin through training at altitude or exogenous erythropoietin. Several other aspects of the hematologic system can also affect or be influenced by physical activity. In this article, the authors briefly discuss inherited abnormalities of the blood that can manifest themselves in athletes. We then discuss the effects of exercise on the blood, and acquired abnormalities of blood cells or coagulation parameters that occur in athletes, and that can influence performance or cause other symptoms.

Mantle cell lymphoma.

Mantle cell lymphoma is an aggressive non-Hodgkin's lymphoma that remains incurable with current chemotherapeutic approaches. Despite response rates to many regimens of 50% to 70%, the disease typically progresses after chemotherapy with a median survival time of approximately 3 years. There is no clear standard approach for treating mantle cell lymphoma, making it critical that appropriate patients be enrolled in clinical trials. Off protocol, chemotherapy with chlorambucil, CVP (cyclophosphamide, vincristine, and prednisone), or CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) can be used in patients who are not candidates for aggressive therapy. Intensive combination chemotherapy regimens have high response rates and may prolong time to progressive disease. High-dose therapy with autologous stem cell transplantation may, but does not appear to, provide longer time to progression, although it may improve survival. For young patients with matched donors, allogeneic transplant is promising in the limited numbers of patients treated. Other agents, including rituximab, fludarabine, and cladribine, have demonstrated activity, but these agents do not appear to offer survival advantages over combination chemotherapy.

Rituximab infusion promotes rapid complement depletion and acute CD20 loss in chronic lymphocytic leukemia.

Complement plays an important role in the immunotherapeutic action of the anti-CD20 mAb rituximab, and therefore we investigated whether complement might be the limiting factor in rituximab therapy. Our in vitro studies indicate that at high cell densities, binding of rituximab to human CD20(+) cells leads to loss of complement activity and consumption of component C2. Infusion of rituximab in chronic lymphocytic leukemia patients also depletes complement; sera of treated patients have reduced capacity to C3b opsonize and kill CD20(+) cells unless supplemented with normal serum or component C2. Initiation of rituximab infusion in chronic lymphocytic leukemia patients leads to rapid clearance of CD20(+) cells. However, substantial numbers of B cells, with significantly reduced levels of CD20, return to the bloodstream immediately after rituximab infusion. In addition, a mAb specific for the Fc region of rituximab does not bind to these recirculating cells, suggesting that the rituximab-opsonized cells were temporarily sequestered by the mononuclear phagocytic system, and then released back into the circulation after the rituximab-CD20 complexes were removed by phagocytic cells. Western blots provide additional evidence for this escape mechanism that appears to occur as a consequence of CD20 loss. Treatment paradigms to prevent this escape, such as use of engineered or alternative anti-CD20 mAbs, may allow for more effective immunotherapy of chronic lymphocytic leukemia.