Epstein-Barr virus-induced lymphoproliferative disorder after rituximab combined with CHOP therapy.

We present the case of a 35-year-old woman with follicular lymphoma who developed an Epstein-Barr virus (EBV)-induced B-cell lymphoproliferation with secondary viral-induced hemophagocytosis 13 months after treatment with rituximab and CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy. The EBV-induced lymphoproliferation was successfully treated with single-agent rituximab. To our knowledge, this is the first such case reported in the literature. Herein, we briefly review the spectrum of immunodeficiency-associated lymphoproliferative disorders (LPDs), discuss the immune deficit induced by rituximab, and speculate on its possible association with EBV reactivation in this patient.

Efficacy of granulocyte and granulocyte-macrophage colony-stimulating factors in the induction treatment of adult acute lymphoblastic leukemia: a multicenter randomized study.

In all, 236 adults with newly diagnosed acute lymphoblastic leukemia (ALL) were randomly assigned to receive either granulocyte colony-stimulating factor (G-CSF), or granulocyte-macrophage CSF (GM-CSF), or no CSF during a 4-week 4-drugs induction chemotherapy. Two successive trials were performed. CSFs were given from the last infusion of anthracycline in Trial 1 or from day 4 of induction therapy in Trial 2 until neutrophil recovery. A total of 95 patients were included in the G-CSF group, 67 in the GM-CSF group, and 74 in the control group. Overall, CSFs showed a trend for a reduced incidence of severe infections and of days with antibiotics. Median time for neutrophil recovery was 17 days with G-CSF, 18 days with GM-CSF, and 21 days without CSF. In Trial 2, duration of hospitalization was significantly lower in the G-CSF group than in the other groups (P < 0.05). Time to neutrophil recovery was also significantly shorter (P < 0.05) and severe infections were lower in the G-CSF group (P = 0.01). CR rate was higher in the GM-CSF group as compared to the control group. This tended to be confirmed for the most aggressive ALL and was statistically significant for Philadelphia-positive ALL after salvage therapy (P = 0.04). There were no significant differences between the three groups in terms of disease-free survival.

Outcome in relation to treatment modalities in 48 patients with localized gastric MALT lymphoma: a retrospective study of patients treated during 1976-2001.

The aim of this study was to retrospectively analyze survival and tumor response data in patients with localized gastric MALT lymphoma treated by different treatment modalities other than anti-Helicobacter pylori treatment (diagnosis made before 1993, or after failure of antibiotics + anti-acid), including surgery, chemotherapy or combined treatment. Here we studied a series of 48 patients with stage IE or IIE disease treated during the past 11 years. These patients received different treatments: chemotherapy was proposed to 19 (40%) patients; gastric surgery to 21 (43%) patients, consisting of partial gastrectomy of 7 patients and total gastrectomy in 14 patients; combined treatment to 8 (17%) patients, consisting of surgery + chemotherapy in 7 patients and surgery + chemotherapy + radiotherapy in 1 patient. At diagnosis, 85% of the patients had good PS and no B symptoms. Complete response after treatment was reached in 45 (94%) patients (chemotherapy: 84% of the patients; surgery alone: 95%; combined treatment: 100%). Progression was observed in 16 (33%) patients. No statistical difference in the survival was found among the different therapeutic modalities: 5-year overall survival year FFP survival was 81% for chemotherapy, 86% for surgery alone and 95% for combined treatment. Prognostic factors for survival were age, performance status and hemoglobin level at diagnosis. Considering the natural bias of a retrospective analysis, surgery or chemotherapy was associated with a similar outcome in patients with MALT lymphoma after antibiotics failure.

Maintenance therapy with a monthly injection of alemtuzumab prolongs response duration in patients with refractory B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL).

Alemtuzumab, the monoclonal anti-CD52 antibody, has clinical activity in B-cell and T-cell malignancies at the dose of 30 mg three times weekly for 9-12 weeks. This standard regimen induced responses usually shorter than 6 months. To prolong time to progression, we initialized a phase II study with an identical initial scheme until partial response, followed by a maintenance therapy lasting at least 4 months. Eleven heavily pretreated patients (8 with B-chronic lymhocytic leukemia (B-CLL) and 3 with small lymphoctyic lymphoma (SLL)) have been treated with this maintenance regimen (MR patients) and were retrospectively compared to 5 patients (3 B-CLL and 2 SLL) treated with the standard regimen (SR patients). Patients characteristics before treatment were identical in both groups. Objective response was reached by 9 (82%) MR patients and 3 (60%) SR patients (p NS). After the treatment, 8 (73%) MR patients and all SR patients progressed with a median time at 12.2 months and 3 months respectively. Survival time from alemtuzumab was significatively different (P < 0.005). None of the patients died in the MR group with a median follow-up at 16 months. In the SR group, the median survival from alemtuzumab was 5.9 months. We did not observe any differences in terms of hematological toxicites and infections between the two groups. In conclusion, maintenance alemtuzumab therapy seems to increase the time to progression and the survival, without adding hematological toxicities and infectious complications. More patients are needed to confirm this observation.

Cost effectiveness of pegfilgrastim versus filgrastim after high-dose chemotherapy and autologous stem cell transplantation in patients with lymphoma and myeloma: an economic evaluation of the PALM Trial.

BACKGROUND: Use of the recombinant human granulocyte colony-stimulating factor (rhG-CSF) filgrastim accelerates neutrophil recovery following myelosuppressive chemotherapy. Since filgrastim requires multiple daily administrations, forms of rhG-CSF with a longer half life, including pegfilgrastim, have been developed. Pegfilgrastim is safe and effective in supporting neutrophil recovery and reducing febrile neutropenia after conventional chemotherapy. Pegfilgrastim has also been successfully used to support patients undergoing peripheral blood stem cell (PBSC) transplantation for haematological malignancies. To our knowledge, no cost-effectiveness analysis (CEA) of pegfilgrastim in this setting has been published yet. OBJECTIVE: We undertook a CEA to compare a single injection of pegfilgrastim versus repeated administrations of filgrastim in patients who had undergone PBSC transplantation for lymphoma or myeloma. The CEA was set in France and covered a period of 100 ± 10 days from transplant. METHODS: The CEA was designed as part of an open-label, multicentre, randomized phase II trial. Costs were assessed from the hospital's point of view and are expressed in 2009 euros. Costs computation focused on inpatient, outpatient, and home care. Costs in the two arms of the study were compared using the Mann-Whitney test. When differences were statistically significant, multiple regression analyses were performed in order to identify cost drivers. Incremental cost-effectiveness ratios (ICER) were calculated for the major endpoints of the trial; i.e., duration of febrile neutropenia (absolute neutrophil count [ANC] <0.5 × 10(9)/L and temperature ≥38 °C), duration of neutropenia (ANC <1.0 × 10(9)/L and ANC <0.5 × 10(9)/L), duration of thrombopenia (platelets <50 × 10(9)/L and <20 × 10(9)/L), and days with a temperature ≥38 °C). Uncertainty around the ICER was captured by a probabilistic analysis using a non-parametric bootstrap method. RESULTS: 151 patients were enrolled at ten French centres from October 2008 to September 2009. The mean total cost in the pegfilgrastim arm of the study (n = 74) was 25,024 (SD 9,945). That in the filgrastim arm (n = 76) was 28,700 (SD 20,597). Pegfilgrastim strictly dominated filgrastim for days of febrile neutropenia avoided, days of neutropenia (ANC <1.0 × 10(9)/L) avoided, days of thrombopenia (platelets <20 × 10(9)/L) avoided, and days with temperature ≥38 °C) avoided. Pegfilgrastim was less costly and less effective than filgrastim for the number of days with ANC <0.5 × 10(9)/L avoided and the number of days with platelets <50.0 × 10(9)/L avoided. Taking uncertainty into account, the probabilities that pegfilgrastim strictly dominated filgrastim were 67 % for febrile neutropenia, 86 % for neutropenia (ANC <1.0 × 10(9)/L), 59 % for thrombopenia (platelets <20 × 10(9)/L), 86 % for temperature ≥38 °C, 32 % for neutropenia (ANC <0.5 × 10(9)/L), and 43 % for thrombopenia (platelets <50 × 10(9)/L). Conversely, the probability that filgrastim strictly dominated pegfilgrastim for neutropenia (ANC <0.5 × 10(9)/L) is 5 %. CONCLUSION: This study found no evidence that the use of pegfilgrastim is associated with greater cost in lymphoma and myeloma patients after high-dose chemotherapy and PBSC transplantation.

Groshong or implanted catheter infections in ambulatory haematological patients.

Incidence rates of bacteraemia and catheter-related infections were measured prospectively amongst haematological patients having long-term catheters and hospitalised in the ambulatory care unit between November 2005 and October 2006. The following risk factors were collected: age, sex, catheter type, follow-up duration, level of personal hygiene, pathology, number of lines of treatment, autograft and erythropoietin treatment. 340 patients were included, having 353 catheters (100 of the Groshong-type, followed during 17,621 days, and 253 of the type with implantable ports, followed during 51,049 days). 0.13 catheter-related infections and 0.07 bacteraemia per 100 catheter days were observed with the Groshong-type catheter, whereas 0.05 (P<10(-5)) catheter-related infections and 0.05 (P=0.048) bacteraemia were observed amongst patients with implantable ports. A multivariate analysis (Cox method taking into account the length of follow-up) on risk factors highlighted a significant effect of the type of catheter on catheter-related infections (Groshong versus implantable port OR=5.74, P<10(-3)), and of several factors on bacteraemia (lymphoma versus other pathologies OR=3.19, P=0.041; erythropoietin treatment OR=2.88, P=0.009; autograft OR=3.35, P=0.011; number of lines of treatment OR=0.68, P=0.047). It was not possible to determine if poor levels of personal hygiene had a significant impact, due to large numbers of missing data. These results, consistent with other studies, are not only useful in validating prevention policy but also in demonstrating lack of catheter traceability.

Chemotherapy with rituximab followed by high-dose therapy and autologous stem cell transplantation in patients with mantle cell lymphoma.

BACKGROUND: The authors evaluated the efficacy of chemotherapy combined with rituximab followed by high-dose therapy (HDT) plus autologous stem cell transplantation in patients with mantle cell lymphoma (MCL). METHODS: This was a retrospective analysis of 34 patients who were treated in 2 departments of hematology, including 29 patients (85%) who received first-line treatment. Rituximab was administered as 4 injections just before harvest in 25 patients (73%) or simultaneously with chemotherapy in 9 patients (27%). HDT included total body irradiation in 26 patients (77%). RESULTS: After induction therapy, all patients except one reached a response: There were 14 (41%) complete responses (CR) and 19 (56%) partial responses (PR). Stem cell harvest was successful in all patients but 2, with a median number of 5.9 CD34-positive cells per 10(6)/kg. Three months after transplantation, 24 patients (71%) were in CR, and 7 patients (21%) were in PR. At 3 years from the day of transplantation, the estimated overall survival was 87%. With a median follow-up at 2.6 years, the estimated median time to disease progression was 3.4 years. Rituximab treatment before harvest did not delay hematopoietic reconstitution: The median time it took patients to recover absolute neutrophil count to > 0.5 G/L was 10 days. CONCLUSIONS: Chemotherapy combined with rituximab followed by HDT improved the overall survival and progression-free survival in patients MCL without adding toxicities.

Profiles and prognostic values of serum LDH isoenzymes in patients with haematopoietic malignancies.

Serum lacticodehydrogenase (LDH) is commonly increased in patients with haematopoietic malignancies and has been shown to be a prognostic factor in patients with non-Hodgkin's lymphoma (NHL) and myeloma. We have examined the LDH isoenzyme content in serum of 326 patients, including 252 patients with NHL (202 at diagnosis and 50 at relapse), 28 patients with Hodgkin's disease, 17 patients with CLL, 16 patients with myeloproliferative syndromes and 13 patients with multiple myeloma. Among these, 160 pts (49%) had increased serum LDH. The analysis of LDH isoenzyme profiles in all patients showed increased percentages of isoenzyme 2 in patients with NHL, CLL and myeloproliferative syndromes, but not in samples from patients with myeloma or Hodgkin's disease. Isoenzyme alterations were then analyzed for their prognostic value in patients with NHL. In univariate analyses, increased isoenzyme 2 percentages, increased isoenzyme 3 values, total serum LDH, performance status, stage and tumour aggressiveness were prognostic variables for survival. In a multivariate analysis increased LDH isoenzyme 3 values, high isoenzyme 2 percentages and the performance status, but not total serum LDH, were independent prognostic factor for survival. High isoenzyme 3 values were predictive of early death in NHL patients. In patients with relapsing NHL, the overall survival was 12 months in patients with normal isoenzyme 3 but only 2 months in patients with increased isoenzyme 3 values. We conclude that there are characteristic alterations in serum LDH profiles in patients with haematopoietic malignancies and that some of these may be more interesting in terms of prognostic value than total serum LDH.