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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.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.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 (ANC1.0 × 10(9)/L and ANC0.5 × 10(9)/L), duration of thrombopenia (platelets50 × 10(9)/L and20 × 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.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) waseuro25,024 (SD 9,945). That in the filgrastim arm (n = 76) waseuro28,700 (SD 20,597). Pegfilgrastim strictly dominated filgrastim for days of febrile neutropenia avoided, days of neutropenia (ANC1.0 × 10(9)/L) avoided, days of thrombopenia (platelets20 × 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 ANC0.5 × 10(9)/L avoided and the number of days with platelets50.0 × 10(9)/L avoided. Taking uncertainty into account, the probabilities that pegfilgrastim strictly dominated filgrastim were 67 % for febrile neutropenia, 86 % for neutropenia (ANC1.0 × 10(9)/L), 59 % for thrombopenia (platelets20 × 10(9)/L), 86 % for temperature ≥38 °C, 32 % for neutropenia (ANC0.5 × 10(9)/L), and 43 % for thrombopenia (platelets50 × 10(9)/L). Conversely, the probability that filgrastim strictly dominated pegfilgrastim for neutropenia (ANC0.5 × 10(9)/L) is 5 %.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.

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 (P0.005). 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.

Patients receiving high-dose cyclophosphamide as a conditioning regimen for peripheral stem cell collection are subjected over a short period of time to significant exposure to reactive oxygen species (ROS). All these patients undergo profound leucopenia. Various other short-term toxicities are observed in a fraction of the patients, including febrile aplasia requiring hospitalization, thrombocytopenia and mucositis. Although stem cell collection is feasible in the majority of patients stimulated with haematopoietic growth factors, in some instances, graft collection cannot be performed because of insufficient concentrations of stem cells in peripheral blood. There is currently no predictive assay to determine which patients treated with high-dose cyclophosphamide have a high risk of febrile aplasia or will successfully undergo cytaphereses for stem cell collection. In order to identify such predictive factors, we analysed the level of expression before treatment of various ROS detoxification mechanisms in the peripheral blood of 37 patients receiving high-dose cyclophosphamide for lymphoproliferative diseases. Various parameters involved in the metabolism of ROS were measured in plasma and/or erythrocytes, including superoxide dismutase, glutathione, glutathione peroxidase, glutathione reductase and malondialdehyde. High levels of erythrocyte superoxide dismutase before cyclophosphamide therapy were correlated with an increased risk of hospitalization for febrile aplasia (65% vs. 29%, P = 0·013). High superoxide dismutase and low erythrocyte glutathione reductase were associated with lower CD34 yields. These data suggest that components of the ROS detoxification system modulate the degree of short-term toxicity of cyclophosphamide and could be used as predictive markers in individual patients.

Patients with nhl and two or three factors of the international prognostic index (ipi) have a poor prognosis. we performed a prospective trial of intensive induction therapy followed with high-dose consolidation in such patients to determine the feasibility of this approach, as well as the response rate and survival. untreated patients with aggressive lymphoma under the age of 60 with two or three adverse prognostic factors (disseminated stage, increased serum ldh, ecog performance status >1) were prospectively included between June 1995 and April 1998 in a trial evaluating intensive induction chemotherapy with the ACE regimen (adriamycin day 1; cyclophosphamide days 1–2; etoposide days 1–3), with G-CSF support. Patients in complete remission after induction received one course of intensification with stem cell support (BEAM regimen), whereas patients in partial response received two intensifications (BEAM, then ICE regimens). Thirty-three patients (median age 38 years) were included. All patients presented WHO grade 4 leukopenia and 84% grade 3–4 thrombocytopenia during induction. There was one toxic death during induction. Twenty-nine patients proceeded to high-dose consolidation, including 12 patients who received a second high-dose treatment. The overall response rate was 88% (95% CI 76–99%), both after induction therapy and treatment completion. Thirty-nine percent of the patients had achieved complete remission after induction, and 73% after treatment completion. With a median follow-up after treatment onset of 29 months, the projected 3-year overall survival was 71% (95% CI 64–78%) and the event-free survival 58% (95% CI 50–66%). Event-free survival was significantly shorter in patients who did not achieve CR after induction therapy or after treatment completion. Early therapeutic intensification after intensive induction chemotherapy is feasible in patients with poor prognosis aggressive NHL and shows promising response and survival rates.

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.

Between 1990 and 1997, 55 patients with high risk multiple myeloma underwent high-dose therapy with peripheral blood stem cell transplantation. Intensification consisted of high-dose L-PAM in 54 patients, and 15 patients underwent a second high-dose treatment. Thirty patients received total body irradiation. Twenty patients were more than 60 years old. Thirty-five patients were intensified during first response. The overall response rate was 78%. There were four toxic deaths. The median overall survivals after intensification and after first treatment of myeloma were greater than 48 months and 71 months, respectively. Conversely freedom from progression after intensification was short, with a median of 22 months. Freedom from progression was significantly shorter in patients older than 60 (12 months), and in patients who had received more than 75 mg/m2 of L-PAM before intensification (16 months). Although intensification is feasible in elderly patients the benefit appears to be reduced in this subgroup of patients. Prior therapy with high cumulative doses of L-PAM should be avoided in patients who will receive high-dose L-PAM for therapeutic intensification.

Identification of a rare e8a2 BCR-ABL fusion gene in three novel chronic myeloid leukemia patients treated with imatinib

Intensive therapy, mainly with purged autologous bone marrow transplantation (ABMT), has been proposed in recent years as consolidation treatment in young patients with follicular lymphoma. Reported experience with transplantation of peripheral blood progenitor cells (PBPC) is, so far, limited. The feasibility and the therapeutic efficacy of intensive therapy followed by unpurged autologous PBPC reinfusion were evaluated in 60 patients with poor-prognosis follicular lymphoma. Twelve patients were in first partial remission (PR), 34 were in second partial or complete remission (CR), and 14 were in subsequent progression. At the time of the procedure, 39 patients (65%) had persistent bone marrow involvement, 49 patients (82%) were in PR, and 16 patients had presented with a histologic transformation (HT). PBPC were collected after chemotherapy followed by granulocyte (G) colony-stimulating factor (CSF) or granulocyte-macrophage (GM)-CSF in 50 patients. Conditioning regimens included high-dose chemotherapy alone (14 patients); mainly the BCNU, etoposide, aracytine, melphalan [BEAM] regimen), or cyclophosphamide with or without etoposide plus total body irradiation (46 patients). The median time to reach a neutrophil count greater than 0.5 x 10(9)/L was 13 days. There were five treatment-related deaths, with four being associated with a delayed engraftment and all occurring in patients in third or subsequent progression. At a median follow-up of 21 months, 48 patients were still alive, 18 relapsed, and seven died of lymphomas progression. Estimated 2-year overall survival (OS) and failure-free survival (FFS) rates were 86% and 53%, respectively, without or plateau. Patients treated in PR1 or PR2/CR2 had a significantly longer rate of OS and FFS than those treated in subsequent progression (P = .002 and P = .001, respectively), whereas age, response to salvage treatment, presence or absence of residual bone marrow involvement, or conditioning regimen had no influence on outcome. Patients with HT tended to have a worse FFS rate (P = .04) without an OS difference. Along with an unusual rate of engraftment failure, the poor FFS observed in heavily pretreated patients suggests that intensive therapy should be performed early in the course of the disease. Given the high percentage of patients intensified in PR with residual bone marrow involvement, our results are comparable with those achieved with ABMT published to date. Prospective trials are warranted to compare this strategy with standard therapy in patients with relapsing or PR follicular lymphoma.

Described for the first time by Adachi et al. in 1994 [1], CD4+/CD56+ hematodermic neoplasm was thought to be of natural killer (NK) lineage due to expression of the NK-cell marker CD56 by the tumo...

Aim To evaluate in a multicentre randomised study the effect on duration of febrile neutropenia (FN), the safety and cost-effectiveness of a single subcutaneous pegfilgrastim injection compared with daily injections of filgrastim after peripheral blood stem cell transplantation in patients receiving high dose chemotherapy for myeloma and lymphoma. Methods Patients were randomly assigned to a single dose of pegfilgrastim at day 5 (D5) or daily filgrastim from D5 to the recovery of absolute neutrophil count (ANC) to 0.5 G/L. Duration of FN, of neutrophil and platelet recovery, transfusion and antibiotic requirements were the main end-points of the study. Costs were calculated from D0 until transplant unit discharge. The incremental cost-effectiveness ratio was expressed as the cost per day of FN prevented. Probabilistic sensitivity analysis was performed by non-parametric bootstrap methods. Results Between October 2008 and September 2009, 10 centres enrolled 151 patients: 80 patients with lymphoma and 71 patients with myeloma. The mean duration of FN was 3.07 days (standard deviation (SD) 1.96) in the pegfilgrastin arm and 3.29 (SD 2.54) in the filgrastim one. Mean total costs were 23,256 and 25,448 euros for pegfilgrastim and filgrastim patients, respectively. There was a 62% probability that pegfilgrastim strictly dominates filgrastim. Concluding statement Pegfilgrastim after PBSC transplantation in myeloma and lymphoma is safe, effective when compared with filgrastim and could represent a cost-effective alternative in this setting.

Background: Rituximab has demonstrated significant clinical efficacy in the treatment of NHL, particularly in combination with chemotherapy, and its use has dramatically changed the treatment and outcome of both indolent and aggressive B-cell NHL over the past decade. Furthermore, consistent toxicity data have been obtained with a safe and tolerable profile in a large majority of patients. Aim: The objective of this retrospective study is to evaluate the long-term efficacy of rituximab monotherapy (4 weekly infusion at induction followed by 4 infusion every 2 months as consolidation) used for patients with relapsed indolent NHL. Results: From May 1998 through January 2011, Among 919 patients with indolent NHL treated in our department, 488 (53%) relapsed and were treated with rituximab alone (first and later relapse). 126 (26%) responded and were still in response 2 years later. These 126 patients (68 (54%) males and 58 (46%) females with a median age of 61 y; range: 17-94) are the subject of our analysis. 24% were over 70 years old, 45% were in first relapsed and 25% in later relapsed. Only 16% of the population have more than one co-morbidities (cardiac and or renal respectively); 79% a normal PS (0-1) with only 4 patients having a PS >2; 80% no bulky disease but 72% a disseminated disease (73% stage III and IV). In this study, 60 (48%) patients had a follicular lymphoma with 50% at an intermediate risk group according to the FLIPI score ; 20 (16%) a marginal zone lymphoma, and 43 (34%) a small lymphocytic or lymphoplasmacytic lymphoma and 3 patients other characteristics of lymphoproliferative disorders. After rituximab monotherapy, 55% of the entire cohort was in complete response (CR) and 31% in CRu or partial response and 5% in stable disease. Among these 126 patients, 74% progressed later than 3 years (38% later than 5 years). With a median follow-up of 6.5 years, 4-year and 8-year PFS were 70% and 30%, respectively. 18% had transformation into Richter syndrome and 12 patients have died. Conclusion: Rituximab monotherapy is an effective therapy in selected relapsed indolent NHL and allows long-term response. This strategy could be used as “spare of chemotherapy” which is an important question today, especially in indolent not curable disease. Disclosures No relevant conflicts of interest to declare.

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 106/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. Cancer 2005. © 2005 American Cancer Society.

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.

The pathogenesis of thrombocytopenia occurring after autologous stem cell transplantation (ASCT) remains unclear. Six cases of classical peripheral thrombocytopenia that developed after ASCT for non-Hodgkin's lymphoma (NHL) are presented. Resolution of this complication was obtained by usual treatment such as steroids, splenectomy or progressively resolved without specific treatment. Five out of six patients have been followed for more than 5 years after hematopoietic transplantation and are still alive in complete remission despite poor prognostic factors at diagnosis. Several arguments suggest that this phenomenon represents autoimmune thrombocytopenia and may be the consequence of an altered immune balance. Consequently, development of autoimmune reactions after bone marrow transplantation might be associated with an antitumoral effect (graft-versus-lymphoma effect).

High-dose melphalan (HDM) has been adopted as standard therapy in the treatment of multiple myeloma. This treatment is associated with non-selective cytotoxicity, causing oral mucositis as the major non-hematological side-effect. Amifostine is a cytoprotector which prevents toxicity induced by anticancer therapy. We prospectively compared two groups of patients who either received (group A, n = 21) or did not receive (group B, n = 20) amifostine (740 mg/m(2)) before HDM (200 mg/m(2)) followed by autologous peripheral blood progenitor cell transplantation. The occurrence of severe oral mucositis was significantly decreased in group A in comparison to group B (33% vs 65%, P < 0.05). Six patients in group A required opioid analgesic therapy during a mean period of 4.8 days as compared to eight patients for 6.5 days in group B (P = NS). Delayed vomiting was less frequent in group A (43% vs 70%, P = 0.07) and significantly less severe in group A (grade 2-4) vomiting: two patients vs nine patients, P < 0.02). No difference was observed between the two groups in either hematological toxicity after HDM or in response rate. Grade I emesis was the only immediate side-effect observed after amifostine administration. We conclude that amifostine can reduce mucositis induced by HDM.

PURPOSE: We sought to describe the infections that occur after large-dose chemotherapy, which was followed by autologous peripheral blood progenitor cell transplantation, and to determine their risk factors. PATIENTS AND METHODS: We retrospectively analyzed the occurrence and the characteristics of infections in 277 consecutive patients who received intensive chemotherapy for non-Hodgkin's lymphoma (n = 207), Hodgkin's disease (n = 27), or multiple myeloma (n = 43) in a single institution. Conditioning regimens included total body irradiation in 47% of the cases. Infections occurring within the 30 days after transplant were defined as early infections, whereas infections after that time in patients who had achieved a neutrophil count greater than 1.0 × 10 9 /L (1,000 per μL) were considered as late infections. RESULTS: Within the first 30 days, 172 patients had unexplained fever (62%); infections were documented in 83 patients (30%), most commonly bacteremia (57 patients). Late infections occurred in 64 (26%) of 244 evaluable patients and consisted mainly of varicella zoster virus infections (n = 36) and pneumonia (n = 16). Administration of total body irradiation [odds ratio (OR) = 2.50; 95% confidence interval (CI) 1.4 to 4.5; P = 0.002) and previous use of fludarabine (OR 2.5; CI 1.2 to 5.2; P = 0.02) and a diagnosis of myeloma (OR 2.6; CI 1.2 to 5.6; P = 0.04) were significantly associated with late infections. CONCLUSIONS: This study confirms that infectious toxicity after peripheral blood progenitor cell transplantation is usually moderate, although bacteremia remains a serious problem. Late infections are encountered in about 25% of patients and are more common in those with myeloma, or those who received total body irradiation or fludarabine.

Abstract 3479 Objective: To assess the efficacy, safety, and cost-effectiveness of a single injection of Pegfilgrastim (P) 6mg given at D5 or Filgrastim (F) 5μg/kg/day subcutaneously from D5 to the end of neutropenia after reinjection of stem cells in patients with lymphoma or myeloma. Patients and methods: The PALM study was an open, multicentre randomized phase II trial. Patients had to be at least 18 years old, with a diagnosis of lymphoma or myeloma, a cryopreserved graft of at least 2.10 CD34/kg, must have had a conditioning regimen without irradiation and an intensive chemotherapy. Eligible pts were 1:1 randomly assigned to P 6mg subcutaneously at D5 or F 5μg/kg/day subcutaneously from D5 to the end of neutropenia (absolute neutrophil count (ANC) >0.5G/L). Randomization was stratified on underlying disease and center. The primary efficacy endpoint was the mean duration of febrile neutropenia (FN) defined as ANC 38°C. Assuming a mean duration of FN of 4 days (SD 3.7), sample size (75 pts per arm) was calculated in order to estimate, with a precision of 0.85 day, a two-sided 95% confidence interval on the mean duration of FN in P arm. No formal comparison between arms was planned for the primary endpoint. The randomization was intended to afford a substantial degree of re-assurance that the historical control value chosen to plan the sample size was appropriate. Key secondary objectives were to estimate, for each treatment regimen, the respective tolerance profile and to compare the cost-effectiveness of the two strategies. The time horizon of the clinical and cost-effectiveness analysis was 100 days. All analyses were performed in the intent-to-treat population, which included all randomly assigned patients. For the economic assessments, a microcosting approach from the hospital perspective was used. Costs (2009 Euros) between P and F were compared using a Mann-Whitney U nonparametric test. Probabilistic sensitivity analyses were conducted using 1000 non-parametric bootstrap replications. Results: From October 2008 to September 2009, 151 pts were randomized. Clinical and demographic data were similar in both groups except for older age in the P arm. No grade 3 or 4 adverse event related to the drugs was notified. Data suggested that patients receiving P had similar or slightly better clinical outcomes. Especially, mean duration of FN were 3.07 (SD 1.96) and 3.29 (SD 2.54) days in the P and the F arms, respectively. Conclusions: Our findings suggest that Pegfilgrastim, at least as efficient and safe than Filgrastim on clinical outcomes, strictly dominates Filgrastim in terms of economic outcomes, i.e. had better effectiveness and lower costs, on most common intermediate efficacy criteria. Therefore, Pegfilgrastim should be considered as a standard of care in patients with lymphoma and myeloma after high-dose chemotherapy and autologous stem cell transplantation. This study was partly supported by Amgen France S.A.S. Disclosures: No relevant conflicts of interest to declare.

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Most patients with chronic myeloid leukemia (CML) express the BCR-ABL transcript with the b2a2 (e13a2) or b3a2 (e14a2) junctions corresponding to the major BCR gene breakpoint cluster region (M-BCR). We and others have reported that a small proportion of CML patients (1–2%), which have breakpoints that fall outside of the M-BCR, giving rise to shortened BCR-ABL transcripts (m-BCR, e6a2, b2a3, b3a3) or longer BCR-ABL transcripts (μ-BCR). The clinical and hematologic features of 8 additional patients with e8a2 BCR-ABL fusions transcripts have been recently reviewed (Demehri et al, Leukemia 2005) and, according to the authors, could be associated with thrombocytosis and a worse prognosis than common M-BCR transcripts. Here, we report three additional CML patients with an e8a2 BCR-ABL fusion transcript treated with imatinib and who achieved hematologic, cytogenetic remission. Molecular studies allowed us to quantify this rare BCR-ABL fusion mRNA. All the patients showed a major molecular response with a reduction of at least 3 logs compared to initial samples at a median follow-up of 34 months (range 30–39). None of the cases (patients #1, 2 and 3) described here showed thrombocytosis at diagnosis. The diagnosis of chronic phase CML was based on typical peripheral blood findings and cytogenetics. In all cases, standard karyotyping demonstrated a t(9;22)(q34;q11), but further molecular analysis revealed an atypical e8a2 BCR-ABL fusion gene. In case #1, FISH using the LSI-bcr/abl ES probe (Vysis) showed a typical M-BCR picture which was different with the case previously described. Multiplex RT-PCR for BCR-ABL and sequencing showed a fusion between BCR exon e8 and ABL exon a2, with a 55 base pair (bp) insert, which perfectly matched an inverted sequence from ABL intron Ib. Most of the patients with an e8a2 BCR-ABL fusion transcript previously described seem to be associated with a worse prognosis because none of them treated with interferon achieved even a minor response. Here, all the patients are alive, achieved complete cytogenetic and major molecular responses with a prolonged follow up, confirming thus the efficacy of imatinib mesylate in patients with rare BCR-ABL transcripts. Of note, in cases #2 and #3, the major molecular response was obtained after increasing the dosage of imatinib (400 to 600 mg/day), suggesting that those patients may require higher doses of imatinib to achieve proper molecular response. The aggressive clinical course of these leukemias could be shrouded by appropriate targeted therapy. A longer follow-up and the analysis of a large cohort of patients with e8a2 BCR-ABL fusions are necessary to analyse the clinical outcome of these patients. The study of these unusual transcripts is essential to gain more insights of their molecular pathological function and a more comprehensive survey of the different functions of the BCR-ABL chimeric protein.

Epileptic seizures after autologous peripheral blood progenitor infusion in a patient treated with high-dose chemotherapy for myeloma

Five patients presenting extremely exaggerated chromatin clumping in leucocytes, associated with a loss of segmentation, are described. Peripheral cytopenia, a high percentage of circulating immature granulocytes (chiefly myelocytes) with variable leucocytosis, marrow hypercellularity with granulocytic hyperplasia and moderate dysplastic changes in erythroblastic and megakaryocytic lines, constitute, together with the granulocytic nuclear anomaly, the characteristic features of the studied cases. Cytogenetic analysis showed a clonal 12p anomaly in one of the three cases available for study. Survival was poor with a median of 15 months, bleeding and infections being responsible for the majority of deaths. All these findings point to abnormal chromatin clumping in leucocytes as the marker of a true entity with both myelodysplastic and myeloproliferative features. We propose that it take its place among myelodysplastic syndromes (MDS) beside chronic myelomonocytic leukaemia (CMML), with which it shares many similarities in clinical and biological behaviour.

Summary: 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

Unusual intracytoplasmic crystal-like inclusions within granulocytic precursor cells from a patient with acute myeloid leukemia (AML) are described. Based upon their cytochemical and immunochemical properties, the possible composition and origin of these inclusions are discussed. They represent a rare event in leukemic cell metabolism since, to our knowledge, only 1 case with identical characteristics has previously been reported.

Optimal numbers of CD34+ cells to be reinfused in patients undergoing peripheral blood progenitor cell (PBPC) transplantation after high-dose chemotherapy are still unknown. Hematologic reconstitution of 168 transplantations performed in patients with lymphoproliferative diseases was analyzed according to the number of CD34+ cells reinfused. The number of days from PBPC reinfusion until neutrophil recovery (>1.0 × 109/L) and unsustained platelet recovery (>50 × 109/L) were analyzed in three groups defined by the number of CD34+ cells reinfused: a low group with less than or equal to 2.5 × 106 CD34+ cells/kg, a high group with greater than 15 × 106 CD34+cells/kg, and an intermediate group to which the former two groups were compared. The 22 low-group patients had a significantly delayed neutrophil (P < .0001) and platelet recovery (P < .0001). The 41 high-group patients experienced significantly shorter engraftment compared with the intermediate group with a median of 11 (range, 8 to 16) versus 12 (range, 7 to 17) days for neutrophil recovery (P = .003), and a median of 11 (range, 7 to 24) versus 14 (range, 8 to 180+) days for platelet recovery (P< .0001). These patients required significantly less platelet transfusions (P = .002). In a multivariate analysis, the amount of CD34+ cells reinfused was the only variable showing significance for neutrophil and platelet recovery. High-group patients had a shorter hospital stay (P = .01) and tended to need fewer days of antibotic administration (P = .12). In conclusion, these results suggest that reinfusion of greater than 15 × 106 CD34+ cells/kg after high-dose chemotherapy for lymphoproliferative diseases further shortens hematopoietic reconstitution, reduces platelet requirements, and may improve patients' quality of life.

Between September 1998 and September 2003, 25 patients with Mantle Cell Lymphoma (MCL) were treated in our centres with a treatment combining rituximab + chemotherapy at induction with subsequent consolidation high-dose chemo/radiotherapy (HDT) and autologous PBSC-transplantation. Twenty-two (80%) patients received this treatment in first line therapy. Median age of patients was 53 (range: 41–65). All patients had a disseminated disease with a bone marrow (BM) involvement in 23 (92%) patients. Elevated LDH was present in 11 patients. All patients except one had a good performance status. IPI score was low in 5 patients, low-intermediate in 10 patients, high-intermediate in 7 patients and high in 3 patients. Chemotherapy induction regimens were: R-CHOP (n=7 pts), R-ACVB (n=4 pts), R-ESHAP (n=1 pts), R-DHAP (n=1pts), or sequential CHOP+DHAP/ESHAP+Rituximab (n=12pts) regimens. Rituximab was giving simultaneously with the chemotherapy in 13 patients or just before harvest in 12 patients. Number of rituximab injections was four in all patients except one that received 5 injections. PBSC harvest was done after cyclophosphamide or cyclophosphmide + etoposide followed by G-CSF and was successful in all patients with a median number of CD34+ cells at 6.44 106/kg. HDT included TBI in 21 patients. After induction therapy, all patients were in response: 16 (64%) reached a CR and 9 (36%) a PR because of persistence of a weak ( 0.5GI/L at 10 days. One patient died before neutrophil recovery because of undocumented pulmonary infection. No patient presented late neutropenia. In conclusion, combined induction chemotherapy with rituximab followed by HDT dramatically improved the overall survival and the progression free survival in MCL patients, without adding hematological toxicities and infectious complications. Figure Figure