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This post-hoc subanalysis of the LYM-3002 phase 3 study assessed the efficacy and safety of substituting vincristine in rituximab, cyclophosphamide, doxorubicin and prednisone (R-CHOP; n = 42) for bortezomib (VR-CAP; n = 38) in a subgroup of 80 mantle cell lymphoma (MCL) patients aged <60 years who did not receive stem cell transplantation (SCT) despite medical eligibility. Complete response (CR)/unconfirmed CR (CRu) rates were 67 vs. 39% (odds ratio 3.69 [95% CI(confidence interval): 1.31, 10.41]; p = .012). After 40 months median follow-up, median progression-free survival by independent radiology committee with VR-CAP vs. R-CHOP was 32.6 vs. 12.0 months (hazard ratio (HR) 0.59 [95% CI: 0.31, 1.13]; p = .108); median overall survival was not reached vs. 47.3 months (HR 0.81 [95% CI: 0.33, 1.96]; p = .634). Adverse events included neutropenia (92/76%), thrombocytopenia (70/10%) and leukopenia (65/50%). VR-CAP represents a potential alternative to R-CHOP in combined and/or alternating regimens for younger, SCT-eligible MCL patients. [ABSTRACT FROM AUTHOR]

Although an activating mutation of Ras is commonly observed in myelodysplastic syndrome (MDS), the role of Ras in the natural history of MDS remains largely unknown. We prospectively studied efficiency and tolerance of lonafarnib, a compound able to inhibit Ras signalling pathway through an inhibition of farnesyl transferase, in patients with MDS or secondary acute myeloid leukaemia (sAML). Lonafarnib was administered orally at a dose of 200 mg twice daily for three courses of 4 weeks (separated by 1 to 4 weeks without treatment). Sixteen patients were included: FAB/RAEB ( n = 10), RAEB-T ( n = 2), sAML ( n = 2) and chronic myelomonocytic leukaemia (CMML; n = 2); WHO/RAEB-1 ( n = 4), RAEB-2 ( n = 5), AML ( n = 5), CMML ( n = 2). Median age was 70 (53–77) years. The karyotype was complex or intermediate in 11 patients, and the International Prognostic Scoring Systems (IPSS) risk groups were low in two patients, INT-1 in one patient, INT-2 in four patients and high in six patients (unknown or not applicable in three patients). Among the 14 patients tested, five had Ras mutations in codons 12, 13 or 61 of N-Ras, K-Ras or H-Ras. One patient was excluded of the analysis for protocol violation, and 15 patients were assessable for tolerance. Gastrointestinal toxicities (diarrhoea, nausea and anorexia) and myelosuppression were the major side effects. Other toxicities included infections, fatigue, increase of liver enzymes, arrhythmia and skin rash. One patient died of infection, and the treatment was stopped in one other who developed atrial fibrillation. Doses were reduced in all but one patient treated with more than one course of farnesyl transferase inhibitor. Responses were assessable in 12 patients. A partial response in one sAML patient and a very transient decrease of blast cell count with normalisation of karyotype in one MDS patient were observed. No relation between improvement of marrow parameters and detected Ras mutations was observed. Lonafarnib alone, administered following our schedule, has shown limited activity in patients with MDS or secondary AML. Gastrointestinal and haematological toxicities appear the limiting toxicity in this population of patients. [ABSTRACT FROM AUTHOR]

18F-Fluorodeoxyglucose-positron emission tomography (FDG-PET) plays an increasing role in the management of patients with lymphoma, for which it is successfully used for staging and treatment monitoring. We report seven patients with a history of lymphoma who presented a positive FDG-PET suggestive of lymphoma relapse and for which FDG-PET oriented biopsies revealed alternative diagnoses. Early in lymphoma follow-up, persistence of focal increased FDG activity corresponded to inflammatory or infectious lesions in two patients: one aspergillosis and one sarcoidosis. Later in the follow-up, five cases of secondary malignancies were identified (three lung cancers, one epidermoid carcinoma, and one villous tumor) in this particularly exposed population. The routine use of FDG PET to evaluate lymphoma significantly increases the probability of detecting unexpected diseases. These cases illustrate the potential pitfalls in PET follow-up. Because FDG is not lymphoma-specific, a relapse suspected only on FDG-PET imaging requires biopsy, as alternative diagnoses--infectious or malignant--are possible. Our data draws clinician's attention to potential false-positive FDG-PET findings, which may lead to therapeutic mistakes. Our data also suggests that FDG-PET might be a new imaging modality for long-term monitoring of late effects, especially second cancer occurrence. [ABSTRACT FROM AUTHOR]

The prognostic value of interim 18fluorodeoxyglucose positron emission tomography (i-PET) was investigated in 73 patients (median age 60 years) with diffuse large B-cell lymphoma (DLBCL). i-PET was analyzed using the Deauville score (DS) and change in maximum standardized uptake value (ΔSUVmax). Patients with a DS of 1-3 demonstrated a significantly ( p < 0.0001) better outcome (median follow-up 2.4 years) than patients with a score of 4 or 5 in terms of event-free survival (EFS) (79% vs. 36%), progression-free survival (PFS) (84% vs. 47%) and overall survival (OS) (91% vs. 51%). EFS (73% vs. 42%), PFS (78% vs. 50%) and OS (88% vs. 56%) were also significantly ( p = 0.023) different between patients with ΔSUVmax > 66% or ≤ 66%. Patients ( n = 33) combining a favorable age-adjusted International Prognostic Index (IPI) (0 or 1) and a negative i-PET either by DS or ΔSUVmax criteria showed a particularly good outcome (EFS: 85%, PFS: 88%, OS: 94%). Overall, i-PET was highly and independently predictive of any outcome, and its negative predictive value was improved by combination with IPI. [ABSTRACT FROM AUTHOR]

This international, multicentre phase II study was conducted to assess ofatumumab, a human anti- CD20 monoclonal antibody, in patients with relapsed/progressive diffuse large B-cell lymphoma ( DLBCL) who were ineligible for autologous stem cell transplantation ( TI) or who had relapse/progression after transplantation ( PT). Eighty-one patients received ofatumumab 300 mg intravenously ( IV) on Day 1, followed by seven weekly IV infusions of 1000 mg. Patients in the TI and PT groups had received a median of 3 (range, 1-7) and 5 (range, 2-7) prior therapies, respectively. One-third of patients did not respond to the last prior therapy, and 53% had failed two or more rituximab-containing therapies. Overall response rate was 13% for the TI group (seven partial responses) and 8% for the PT group (two complete responses). Median progression-free survival was 2·6 months, and median duration of response was 9·5 months. The most common Grade 3-4 adverse events were neutropenia (11%), leucopenia (6%), lymphopenia (6%) and thrombocytopenia (6%). Sixteen deaths have been reported, with disease progression as the most common cause of death. In conclusion, ofatumumab monotherapy was well tolerated and provided clinical benefit to some DLBCL patients in this study. This trial was registered at www.clinicaltrials.gov ( NCT00622388). [ABSTRACT FROM AUTHOR]

Elevated serum free light chains (FLCs) have been associated with an unfavorable prognosis in diffuse large B-cell lymphoma (DLBCL). The aim of this study was to determine the clinical relevance of a quantitative assessment of intact circulating immunoglobulin (Ig), using serum Ig heavy chain/light chain pair (HLC) measurements in patients with DLBCL. FLC and HLC were measured in 409 serum samples of patients with DLBCL included in the LNH03-B clinical trial program of the Groupe d'Etudes des Lymphomes de l'Adulte (GELA). Patients with an abnormal IgMκ/IgMλ ratio or an abnormal FLC ratio more frequently displayed adverse clinical characteristics. Patients with abnormal IgMκ/IgMλ ratios had inferior progression-free survival (PFS) and overall survival (OS) as compared to patients with a normal ratio in the overall cohort (5-year PFS 44.9% vs. 69.3%, p = 0.0003 and 5-year OS 50.8% vs. 78.1%, p = 0.0003) and in the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) cohort (5-year OS 43.5% vs. 70.3%, p = 0.003). In multivariate analysis, including elevated FLC/HLC and International Prognostic Index (IPI), an abnormal IgMκ/IgMλ ratio (hazard ratio [HR] = 1.54, 95% confidence interval [CI] 1.03-2.3, p = 0.03) remained predictive of shorter progression-free survival. Gene expression profile experiments and immunohistochemistry indicate that this measurement is at least partially related to tumor cell secretion. Both elevated serum FLCs and an abnormal IgMκ/IgMλ ratio are associated with unfavorable outcomes in patients with DLBCL treated by R-CHOP. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy-induced neutropenia (CIN) places patients at risk of life-threatening infections. While reduction of chemotherapy dose or delay of the subsequent treatment cycle and, consequently, reduction of relative dose intensity (RDI) may limit myelotoxicity, these actions can also impact adversely on treatment outcome and should be avoided in adjuvant settings.Patients and Methods: Based on data from 444 breast cancer patients in the INC-EU Prospective Observational European Neutropenia Study, we have evaluated patient-specific and treatment-specific factors that impact on the incidence of grade 4 CIN (absolute neutrophil count <0.5 × 10(9)/L), either during the first or in any cycle of (neo)adjuvant chemotherapy, across a range of regimens and doses.Results: Using multivariate logistic regression analysis, risk factors for grade 4 CIN were identified as older age, lower weight, higher planned dose intensity of doxorubicin, epirubicin, or docetaxel, higher number of planned cycles, vascular comorbidity, lower baseline white blood cell count, and higher baseline bilirubin. Use of colony-stimulating factor before a neutropenic event occurred, dose delays, and dose reductions were protective against grade 4 CIN.Conclusions: By identifying risk factors for grade 4 CIN, CSF prophylaxis may be appropriately targeted to prevent low RDI in patients treated with curative intent. [ABSTRACT FROM AUTHOR]

The article focuses on a research about the long-term results of the registered patients and their rate of histologic transformation (HT) rate to diffuse large B-cell lymphoma (DLBCL). It states that 164 patients with nodular, lymphocyte-predominant Hodgkin lymphoma (NLPHL) served as subjects of the study. Findings show that there was no significant difference in the overall survival rate after HT of patients who underwent autologous stem cell transplantation (ASCT) and the others.

Background: The use of chemotherapy regimens with moderate or high risk of febrile neutropenia (defined as having a FN incidence of 10% or more) and the respective incidence and clinical management of FN in breast cancer and NHL has not been studied in Belgium. The existence of a medical need for G-CSF primary and secondary prophylaxis with these regimens was investigated in a real-life setting. Methods: Nine oncologists and six hematologists from different Belgian general hospitals and university centers were surveyed to collect expert opinion and real-life data (year 2007) on the use of chemotherapy regimens with moderate or high risk of febrile neutropenia and the clinical management of FN in patients aged <65 years with breast cancer or NHL. Data were retrospectively obtained, over a 6-month observation period. Results: The most frequently used regimens in breast cancer patients (n = 161) were FEC (45%), FEC-T (37%) and docetaxel alone (6%). In NHL patients (n = 39), R-CHOP-21 (33%) and R-ACVBP-14 (15%) were mainly used. Without G-CSF primary prophylaxis (PP), FN occurred in 31% of breast cancer patients, and 13% had PSN. After G-CSF secondary prophylaxis (SP), 4% experienced further FN events. Only 1 breast cancer patient received PP, and did not experience a severe neutropenic event. Overall, 30% of chemotherapy cycles observed in breast cancer patients were protected by PP/SP. In 10 NHL patients receiving PP, 2 (20%) developed FN, whereas 13 (45%) of the 29 patients without PP developed FN and 3 (10%) PSN. Overall, 55% of chemotherapy cycles observed in NHL patients were protected by PP/SP. Impaired chemotherapy delivery (timing and/or dose) was reported in 40% (breast cancer) and 38% (NHL) of patients developing FN. Based on oncologist expert opinion, hospitalization rates for FN (average length of stay) without and with PP were, respectively, 48% (4.2 days) and 19% (1.5 days). Similar rates were obtained from hematologists. Conclusions: Despite the studied chemotherapy regimens being known to be associated with a moderate or high risk of FN, upfront G-CSF prophylaxis was rarely used. The observed incidence of severe neutropenic events without G-CSF prophylaxis was higher than generally reported in the literature. The impact on medical resources used is sizeable. [ABSTRACT FROM AUTHOR]

Myelosuppression, particularly febrile neutropenia (FN), are serious dose-limiting toxicities that occur frequently during the first cycle of chemotherapy. Identifying patients most at risk of developing FN might help physicians to target prophylactic treatment with colony-stimulating factor (CSF), in order to decrease the incidence, or duration, of myelosuppression and facilitate delivery of chemotherapy as planned. We present a risk model for FN occurrence in the first cycle of chemotherapy, based on a subgroup of 240 patients with non-Hodgkin lymphoma (NHL) enroled in our European prospective observational study. Eligible patients had an International Prognostic Index of 0–3, and were scheduled to receive a new myelosuppressive chemotherapy regimen with at least four cycles. Clinically relevant factors significantly associated with cycle 1 FN were older age, increasing planned cyclophosphamide dose, a history of previous chemotherapy, a history of recent infection, and low baseline albumin (<35 g/l). Prophylactic CSF use and higher weight were associated with a significant protective effect. The model had high sensitivity (81%) and specificity (80%). Our model, together with treatment guidelines, may rationalise the clinical decision of whether to support patients with CSF primary prophylaxis based on their risk factor profile. Further validation is required. [ABSTRACT FROM AUTHOR]

Goals Of Work: Neutropenia is a life-threatening, dose-limiting toxicity of many chemotherapy regimens. The goals of this study were to assess the incidence and risk of chemotherapy-induced neutropenia, febrile neutropenia (FN) and dose limitations in breast cancer and lymphoma patients undergoing chemotherapy in Europe.Patients and Methods: Four hundred forty-four breast cancer and 305 lymphoma patients undergoing chemotherapy at 66 practices in five European countries participated in this prospective, observational study. Predictors of impaired chemotherapy delivery were investigated using a logistic regression model.Main Results: In breast cancer, FN incidence was low (6%); however, grade 4 neutropenia was frequent (34%). Lymphoma patients experienced higher incidences of FN (non-Hodgkin lymphoma (NHL) 22%; Hodgkin lymphoma (HL) 15%) and grade 4 neutropenia (NHL 54%; HL 40%). For both diseases, FN and grade 4 neutropenia were associated with low relative dose intensity (RDI). Multivariate regression models indicated that first cycle FN, age > or = 65 years and Eastern Co-operative Oncology Group > 1 were associated with low RDI in breast cancer and lymphoma, while colony-stimulating factor (CSF) primary prophylaxis appeared to be protective in lymphoma only. Primary CSF prophylaxis was provided to 9% of breast cancer, 28% of NHL and 19% of HL patients.Conclusions: Neutropenia and low RDI remain serious problems in both breast cancer and lymphoma populations undergoing chemotherapy. Several risk factors which can trigger reduced chemotherapy delivery were identified. These results can support physicians in identifying patients most at risk of receiving impaired chemotherapy delivery who would benefit from suitable preventive measures. [ABSTRACT FROM AUTHOR]

Summary. Death during the induction phase of chemotherapy remains a common event in patients with aggressive non-Hodgkin's lymphoma (NHL). In a series of patients with aggressive NHL homogeneously treated with intensive induction chemotherapy [ACVB (doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone) regimen], we determined the clinical and biological parameters that were predictive of early death. Early death was defined as death, for whatever reason, occurring within 100 d of randomization. Predictive factors were identified by logistic regression and an index predictive for individual risk of early death was designed. Among the 2210 patients treated with ACVB, there were 162 (7·3%) early deaths. There was no significant reduction in the rate of early death between 1987 and 1998. In a multivariate analysis, age > 60 years, Eastern Cooperative Oncology Group performance status > 1, serum lactate dehydrogenase > normal, serum albumin < 30 g/l, leucocyte counts > 10 × 109 /l and haemoglobin levels < 8·5 g/dl were found to be independent predictive factors for early death. An early death index was designed, enabling the evaluation of the individual risk of early death in young (range 2–31% risk of early death) and elderly patients (range 5–53%). Clinical and biological parameters available at diagnosis can help physicians identify patients with aggressive lymphoma at low or high risk of early death. [ABSTRACT FROM AUTHOR]

A multi-center, open trial was conducted to determine the maximal tolerable dose of carboplatin in combination with conventional doses of both etoposide and an anthracycline for the treatment of previously untreated small cell lung cancer (SCLC) patients. Ninety-five patients [48 with limited disease (LD) and 47 with extensive disease (ED)¦ received a total of 376 courses of treatment. Carboplatin was given on day 1 at a dose of 250 mg m in 60 courses, 300 mg m in 69, 330 mg m in 236 and 350 mg m in 11, with 120 mg m etoposide on days 1, 3 and 5 and either 40 mg m adriamycin or 60 mg m epirubicin on day 1. Epirubicin was not administered before carboplatin reached the dose of 330 mg m. Courses were repeated every 3 weeks. The main toxicity was hematological. The first course of therapy induced a dose-dependent decrease of leucocyte, neutrophil and platelet counts: all patients, except one, who received 350 mg m carboplatin had a neutropenia below 200 μ and a thrombopenia below 100,000 μl. Three patients died of septicemia. Other toxicities were well tolerated. After three courses, patients were re-staged by performing a mandatory fiberoptic bronchoscopy and a thoracic computed axial tomography (CAT). The overall objective response rate for 86 evaluable patients was 91% (98% for LD) with 21% complete remissions (30% for LD). All 23 hepatic and six brain sites, evaluable after chemotherapy alone, responded. This new combination, in which the recommended dose of carboplatin is 330 mg m, should be evaluated in a prospective study for SCLC. [ABSTRACT FROM AUTHOR]

Background: Patients with lymphoma who have experienced a first relapse or progression and have disease deemed sensitive to salvage chemotherapy nevertheless have a high likelihood of having a second relapse. To decrease the likelihood of a second relapse after high-dose therapy (HDT) and autologous stem cell transplantation (ASCT), interferon (IFN) -2b was given in a prospective randomized international trial. Methods: In this trial, 221 patients with varying histologic diagnoses (8 small lymphocytic, 37 follicular, 9 mantle, 90 diffuse large B-cell,20peripheral T-cell,3high-grade B-cell non-Hodgkin lymphoma, and 54Hodgkinlymphoma)wererandomlyassigned to receivenofurthertreatment(armA:117patients) or IFN -2b, 3MUthree times weekly, for 18 months (arm B: 104 patients). Results: In arm B, 21 patients (20%) did not receive IFN -2b because of early progressionor absence of hematologic recovery, 29patients(28%)completedthe18monthsoftreatment, and54 patients (52%) interrupted treatment because of progression (23%) or toxicity (29%). Event-free survival and overall survival were not different between the two arms on an intent-to-treat analysis and also if analysis was restricted to patients who were aliveandhadnot experienced disease progression threemonths after transplantation. The study was not sufficiently powered to evaluate effects in histologic subtypes. Conclusion: In this trial, post-autograft IFN -2b did not improve outcomesin a heterogeneous group of patients withlymphoma. [ABSTRACT FROM AUTHOR]

Background: The use of chemotherapy regimens with moderate or high risk of febrile neutropenia (defined as having a FN incidence of 10% or more) and the respective incidence and clinical management of FN in breast cancer and NHL has not been studied in Belgium. The existence of a medical need for G-CSF primary and secondary prophylaxis with these regimens was investigated in a real-life setting.Methods: Nine oncologists and six hematologists from different Belgian general hospitals and university centers were surveyed to collect expert opinion and real-life data (year 2007) on the use of chemotherapy regimens with moderate or high risk of febrile neutropenia and the clinical management of FN in patients aged <65 years with breast cancer or NHL. Data were retrospectively obtained, over a 6-month observation period.Results: The most frequently used regimens in breast cancer patients (n = 161) were FEC (45%), FEC-T (37%) and docetaxel alone (6%). In NHL patients (n = 39), R-CHOP-21 (33%) and R-ACVBP-14 (15%) were mainly used. Without G-CSF primary prophylaxis (PP), FN occurred in 31% of breast cancer patients, and 13% had PSN. After G-CSF secondary prophylaxis (SP), 4% experienced further FN events. Only 1 breast cancer patient received PP, and did not experience a severe neutropenic event. Overall, 30% of chemotherapy cycles observed in breast cancer patients were protected by PP/SP. In 10 NHL patients receiving PP, 2 (20%) developed FN, whereas 13 (45%) of the 29 patients without PP developed FN and 3 (10%) PSN. Overall, 55% of chemotherapy cycles observed in NHL patients were protected by PP/SP. Impaired chemotherapy delivery (timing and/or dose) was reported in 40% (breast cancer) and 38% (NHL) of patients developing FN. Based on oncologist expert opinion, hospitalization rates for FN (average length of stay) without and with PP were, respectively, 48% (4.2 days) and 19% (1.5 days). Similar rates were obtained from hematologists.Conclusions: Despite the studied chemotherapy regimens being known to be associated with a moderate or high risk of FN, upfront G-CSF prophylaxis was rarely used. The observed incidence of severe neutropenic events without G-CSF prophylaxis was higher than generally reported in the literature. The impact on medical resources used is sizeable. [ABSTRACT FROM AUTHOR]