A combination of fludarabine (Flu) and daily IV busulfan (Bu) is well tolerated and effective in patients receiving allogeneic transplantation for acute myelogenous leukemia (AML). The addition of rabbit antithymocyte globulin (Thymoglobulin) may reduce morbidity and mortality from graft-versus-host disease but lead to more relapse. To compensate for this effect we added 400cGy total body irradiation to the Flu/Bu regimen in 89 patients and compared outcomes with those achieved in 90 patients receiving the drug combination alone. Non-relapse mortality (NRM) at 3 years did not differ between the groups, in contrast the inclusion of TBI significantly reduced relapse (Hazard ratio (HR) 0.29; 95% confidence interval (CI) 0.15-0.54), p=0.0001). Consequently both overall survival (HR 0.50; CI 0.3-0.84, p=0.009) and disease-free survival (HR 0.43; CI 0.26-0.72, p=0.001) were improved after TBI. This study confirms the importance of regimen intensity in allogeneic HSCT for AML. The combination of daily IV Bu, Flu, 400cGy TBI and Thymoglobulin provides a well-tolerated regimen with antileukemic activity in AML comparable with other conventional myeloablative regimens.

Based on the hypothesis that bortezomib may potentiate fludarabine activity by inhibiting DNA repair, we designed a phase I trial using this combination with rituximab in patients with relapsed and refractory indolent and mantle cell non-Hodgkin lymphoma. Twenty-four patients were enrolled. Non-Hodgkin lymphoma subtypes included 12 patients with follicular lymphoma, four with marginal zone lymphoma, three with lymphoplasmacytic lymphoma, three with mantle cell lymphoma and two with small lymphocytic/chronic lymphocytic leukaemia. Fludarabine and bortezomib were escalated in cohorts of three patients. Rituximab was added to the maximum tolerated dose of fludarabine and bortezomib and added significant dose-limiting myelosuppression. The maximum tolerated dose was fludarabine 25 mg/m(2) on days 1-3, bortezomib 1.3 mg/m(2) on days 1, 4, 8, 11, with rituximab 375 mg/m(2) on day 1 administered every 21 d. Clinical responses were observed in 11 patients, five of whom were refractory to their most recent treatment regimen. Six additional patients had stable disease for a median of 10 months (range 4-30+). Cumulative myelosuppression and neuropathy was observed. The combination of fludarabine, bortezomib, and rituximab appears to be an active regimen with manageable toxicity for relapsed NHL.

Lenalidomide gained Food and Drug Administration (FDA) approval for treatment of patients with relapsed or refractory multiple myeloma (MM) in combination with dexamethasone in June 2006. In April 2005, the FDA and patient advocacy groups requested an expanded access programme to both provide lenalidomide to patients likely to benefit and obtain additional safety information. Relapsed/refractory MM patients received lenalidomide 25 mg/d (days 1-21) and dexamethasone 40 mg/d (days 1-4, 9-12, and 17-20 of cycles 1-4; days 1-4 only from cycle 5 onwards), in 4-week cycles until disease progression, study drug discontinuation, or lenalidomide approval. Of the 1438 patients enrolled, approximately 60% were male, median age was 64 years, and 61.7% had Durie-Salmon stage III disease. Median time on study was 15.4 weeks (range: 0.1-49.1) and median dose was 25 mg. The most common adverse events (AEs) were haematological (49%), gastrointestinal (59%), and fatigue (55%). The most common grade >/=3 AEs were haematological (45%), fatigue (10%), and pneumonia (7%). The most common serious AEs were pneumonia (8%), pyrexia (4%), and deep-vein thrombosis (3%). Primary cause of death was disease progression (10%). Safety data confirmed known AEs of lenalidomide plus dexamethasone therapy in patients with relapsed/refractory MM.

Although lenalidomide and dexamethasone is effective therapy for patients with relapsed/refractory multiple myeloma (MM), the influence of high-risk cytogenetic abnormalities on outcomes is unknown. This sub-analysis of a large, open-label study investigated the effects of the most common unfavorable cytogenetic abnormalities detected by fluorescence in situ hybridization - del(13q), t(4;14), and del(17p13)- in 130 evaluable patients treated with this regimen. While patients with either del(13q) or t(4;14) experienced a median time to progression (TTP) and overall survival (OS) comparable to those without these cytogenetic abnormalities, patients with del(17p13) had a significantly worse outcomes with a median TTP = 2.22 months (HR 2.82; P =.0014) and median overall survival OS = 4.67 months (HR 3.23; P =.0013). Improved therapeutic strategies are required for this subgroup of patients. This study was registered in Clinicaltrials.gov under number NCT00179647.

PURPOSE/OBJECTIVES: To investigate the relationships among physiologic variables, fatigue, and quality of life (QOL) in patients with multiple myeloma. DESIGN: Cross-sectional, descriptive, exploratory. SETTING: Outpatient ambulatory care clinics at a tertiary oncology center. SAMPLE: 56 patients with multiple myeloma were accrued consecutively via nonprobability sampling strategy. METHODS: Study participants completed the European Organisation for Research and Treatment of Cancer QLQ-C30 and the Functional Assessment of Cancer Therapy-Fatigue. Physiologic variables and demographic data were collected from patient charts. MAIN RESEARCH VARIABLES: Hemoglobin (hgb), C-reactive protein (CRP), fatigue, and QOL. FINDINGS: Statistically significant correlations were found among hgb and two measures of fatigue and QOL, as well as among CRP and two measures of fatigue and QOL. Regression analysis revealed that as soon as the effect of CRP was removed, hgb was no longer a significant predictor of fatigue or QOL. CONCLUSIONS: Although significant relationships between hgb and fatigue and hgb and QOL were identified, CRP made a significant contribution to predicting the variance in fatigue and QOL, whereas hgb did not. The findings suggest that higher CRP is predictive of greater fatigue and lower QOL. IMPLICATIONS FOR NURSING: Nurses play an integral role in the assessment and management of cancer-related fatigue. Greater understanding of the pathophysiology of fatigue may lead to progress in assessment and intervention, with the ultimate goal of reducing cancer-related fatigue and improving QOL.

It is anticipated that the ultimate solution for the prevention and termination of autoimmune disorders will be based on somehow manipulating the cells of the immune system to attain antigen (ag) specific downregulation and termination. In the last few years we have developed a new vaccination technique that we call "modified vaccination technique"(MVT). It has with equal effectiveness both prevented and terminated autoimmune disease causing events in an experimental autoimmune kidney disease model. We expect that our technique will be similarly applicable to the specific treatment and cure of numerous other chronic disorders presently treated only by drugs. The vaccine is composed of two components, an ag and a specific antibody against it. When these are combined at slight ag excess they constitute a vaccine which is capable of treating chronic ailments by redirecting immune response outcomes in the vaccinated host. Both components, like drugs, will have to be produced ex vivo in order to maintain uniformity, safety, efficacy, and specificity.

We have reported a lower incidence of acute graft-versus-host disease (aGVHD) with a novel conditioning regimen using low-dose rabbit antithymocyte globulin (ATG; Thymoglobulin [TG]) with fludarabine and intravenous busulfan (FluBuTG). To assess further this single-center experience, we performed a retrospective matched-pair analysis comparing outcomes of adult patients transplanted using the FluBuTG conditioning regimen with matched controls from patients reported to the CIBMTR receiving a first allogeneic hematopoietic stem cell transplant (HCT) after standard oral busulfan and cyclophosphamide (BuCy). One hundred twenty cases and 215 matched controls were available for comparison. Patients receiving FluBuTG had significantly less treatment related mortality (TRM; 12% versus 34%, P <.001) and grades II-IV aGVHD (15% versus 34%, P <.001) compared to BuCy patients. The risk of relapse was higher in the FluBuTG patients (42% versus 20%, P <.001). The risks of chronic GVHD (cGVHD) and disease free survival (DFS) were similar in the cases and controls. These results suggest that the novel regimen FluBuTG decreases the risk of aGVHD and TRM after HLA-identical sibling HSCT, but is associated with an increased risk of relapse, resulting in similar DFS. Whether these conditioning regimens may be more suitable for specific patient populations based on relapse risk requires testing in prospective randomized trials.

Two hundred patients received hematopoietic stem cell transplantation (HSCT) from matched sibling donors (MSD) after myeloablative conditioning including fludarabine (Flu) and once-daily intravenous busulfan (Bu). Thymoglobulin (TG) was added to methotexate (MTX) and cyclosporine (CsA) as graft-versus-host disease (GVHD) prophylaxis. For low-risk (acute leukemia CR1/CR2, CML CP1) patients projected 5-year nonrelapse mortality (NRM) and overall survival (OS) were 4% and 76% for those <or=45 years old (n = 54) and 6% and 83% for those >45 (n = 31). For high-risk (HR) patients NRM was 6% versus 27%(18% at 1 year)(P =.04) and OS 64% versus 37%(P =.47) in younger (n = 40) and older (n = 75) patients, respectively. To correct for imbalance in HR diagnoses each of 17 younger HR patients were matched with 2 older HR (OHR) patients by diagnosis and details of stage, and thereafter for other risk factors. For the younger HR and OHR patients, respectively, OS was 70% versus 37%(P =.02) and NRM 0 versus 34%(P =.02). When outcomes of OHR patients were compared with the other 3 groups combined NRM was 27% versus 5%, respectively (P =.002). Incidence of acute graft-versus-host disease (aGVHD) grade II-IV, aGVHD grade III-IV, and chronic GVHD (cGVHD) was 23% versus 10%(P =.02), 4% versus 2%(P = ns), and 66% versus 41%(P =.001), respectively. Nine of 14 nonrelapse deaths in the OHR group were related to GVHD or its treatment compared with 3 of 6 in all others (P value for GVHD related death =.01). Multivariate analysis of OS and DFS correcting for potentially confounding pretransplant factors identified only the OHR patients as having significantly increased risk (relative risk [RR] 3.32, confidence interval [CI] 1.71-6.47, P <.0001, and RR 3.32, CI 1.71-6.43, P <.0001, respectively). The effect of age on NRM is only apparent in HR patients, and is not explained by heterogeneity in diagnoses. Older HR patients experience more GVHD and more GVHD-related death than others, but NRM is no higher than reported with many nonmyeloablative regimens.

Neither autoimmune disorders nor cancer can be prevented with treatment modalities that are currently available. These diseases are generally treated with immunosuppressive agents and cytotoxic drugs, both of which can cause numerous side effects. However, scientific evidence now exists to suggest that such endogenous antigen-derived ailments can be controlled and even terminated by immunological approaches. Both autoimmune disorders and cancer can progress into chronic, irreversible conditions because of the abnormal presentation of endogenous antigens to the cells of the immune system. By appropriate regulation of the autoimmune system, both types of ailments could be curable. This feature review describes various autoimmune events that may occur both to the benefit and the detriment of the host, and highlights a new vaccination technique against slowly progressive Heymann nephritis. This modified vaccination technique holds promise in the prevention and cure of autoimmune system-related disorders. The vaccination has been employed both against endogenous antigen-induced diseases (autoimmune disorders and cancer) and against exogenous antigens. In each study performed to date, the technique has been demonstrated to induce specific, predetermined immune response outcomes.