Rituximab maintenance after autologous stem cell transplantation prolongs response duration in non-naive rituximab follicular lymphoma patients: a single institution experience.

We retrospectively evaluated the role of rituximab (R) in maintenance treatment after autologous stem cell transplantation performed in patients with relapsed follicular lymphoma. We compared the outcome of 67 follicular lymphoma (FL) patients according to the use of rituximab maintenance (RM) or not. All patients received rituximab plus chemotherapy before autologous stem-cell transplantation (ASCT). Patients received median of two lines of prior therapy. The RM schedule was one injection of rituximab every 3 months for 2 years. Median follow-up is 4.6 years. The 3-year progression-free survival (PFS) after ASCT was 86 % with RM vs. 46 % without (p = 0.0045). Median is not reached in the RM arm vs. 31 months in non-RM arm. The 3-year OS was 96 % with RM vs. 78 % without (p = 0.059). The present monocentric study shows that 2 years of RM after ASCT significantly increases response duration for non-naive rituximab relapsed FL patients compared with observation.

Upfront allogeneic stem-cell transplantation for patients with nonlocalized untreated peripheral T-cell lymphoma: an intention-to-treat analysis from a single center.

BACKGROUND: Peripheral T-cell lymphomas (PTCLs) are rare and heterogeneous diseases with dismal outcome when treated with chemotherapy alone. Because allogeneic stem-cell transplantation (allo-SCT) can cure relapse/refractory patients, we hypothesized that upfront allo-SCT may provide a better outcome. Therefore, all patients that presented with advanced PTCL in our institution at diagnosis were scheduled to undergo upfront allo-SCT after induction chemotherapy. PATIENTS AND METHODS: The aim of the present work was to assess the feasibility and toxicity of upfront allo-SCT. From 2004 to 2012, 49 newly diagnosed PTCL patients were scheduled to receive upfront allo-SCT. A human leukocyte antigen-matched donor was found for 42 patients: related to the patient in 15 cases, unrelated in 20 cases, and suitable cord blood units were used in 7 cases. RESULTS: After induction chemotherapy, 17 patients reached complete remission and 29 (60%) proceeded to upfront allo-SCT. For all patients, the 1 and 2-year overall survival (OS) rates were 59% [95% confidence interval (CI) 47-75] and 55% (95% CI 43-71), respectively. The most frequent reason we did not proceed to allo-SCT was disease progression or insufficient response after induction. For transplanted patients, the 1- and 2-year OS were 76% (95% CI 62-93) and 72.5% (95% CI 58-91), respectively. Toxicity-related mortality (TRM) 1 year after allo-SCT was only 8.2% (95% CI 0-18.5). The 2-year progression-free survival (PFS) rate of patients who did not proceed to allo-SCT (n = 20) was below 30%. The disease status at the time of transplantation was a strong predictive marker for both PFS and OS in transplant patients. CONCLUSIONS: Upfront allo-SCT in PTCLs is feasible with low TRM, and it provides long-term disease control. However, one-third of patients remain chemo-refractory and, thus, new therapeutic approaches are warranted. The role of upfront allo-SCT compared with other therapeutic approaches in PTCLs requires investigation in randomized studies.

18F-fluorodeoxyglucose-positron emission tomography before, during and after treatment in mature T/NK lymphomas: a study from the GOELAMS group.

BACKGROUND: In non-cutaneous T-cell/natural killer (T/NK) lymphomas, the prognostic value of (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) during or after therapy is unknown. PATIENTS AND METHODS: In this retrospective study, 54 T/NK lymphoma patients were assessed using FDG-PET before (n = 40), during (n = 44) and/or after therapy (n = 31). RESULTS: FDG-PET showed an abnormal FDG uptake in all cases. Interim FDG-PET was negative in 25 of 44 cases. After completion of therapy, 19 of 31 patients reached complete remission with negative FDG-PET. In ALK+ anaplastic large cell lymphomas, the 4-year progression-free survival (PFS) was 80% and the negative predictive value of post-therapy FDG-PET was 83% (n = 9). In ALK- T/NK lymphomas, the 4-year PFS was 59% for patients with a negative interim FDG-PET versus 46% for patients with a positive interim FDG-PET (P = 0.28, n = 35). Similarly, there was no statistical difference in 4-year PFS between negative and positive post-therapy FDG-PET in these lymphomas (51% and 67%, respectively, P = 0.96). The 4-year cumulative incidence of relapse from a negative post-therapy FDG-PET was 53% in ALK- T/NK lymphomas. CONCLUSIONS: Although T/NK lymphomas are FDG-avid at diagnosis, a negative interim or post-therapy FDG-PET does not translate into an improved PFS in ALK- T/NK lymphomas.

High incidence of translocations t(11;14)(q13;q32) and t(4;14)(p16;q32) in patients with plasma cell malignancies.

Abnormalities involving the 14q32 region are recurrent chromosomal changes in plasma cell malignancies. Recent preliminary molecular analyses found IGH rearrangements in almost 100% of human myeloma cell lines and in 75% of patients. However, no systematic study analyzing the nature of the partner chromosomal regions have been reported thus far. To define the exact incidence of illegitimate IGH rearrangements and the respective incidence of partner genes cloned to date, we analyzed 141 patients with either multiple myeloma (MM, n = 127) or primary plasma cell leukemia (PCL, n = 14) using fluorescence in situ hybridization. The overall incidence of illegitimate recombinations was 57% (80 of 141 patients). Analysis of this incidence according to Durie and Salmon stage, patients' status, i.e., MM versus primary PCL and diagnosis versus relapse, immunoglobulin type and subtype, and beta2-microglobulin value, did not show any correlation. To analyze the nature of the partner chromosomal region, we selected probes specific for the following genes: FGFR3 (4p16), MYC (8q24), CCND1 (11q13), MAF (16q23), and BCL2 (18q21). These probes, combined with differentially labeled 14q32 probes, were used for dual-color fluorescence in situ hybridization on interphase plasma cells. Among the 80 patients with illegitimate IGH rearrangement, we identified 23 IGH-CCND1 fusion cases [i.e., t(11;14)], 17 IGH-FGFR3 fusion cases [i.e., t(4;14)], 3 IGH-MYC fusion cases [i.e., t(8;14)], and only one IGH-MAF fusion case. No IGH-BCL2 fusion case was detected. In 37 of 80 patients, none of these partner genes was involved. Analysis of cases with specific translocations according to their bioclinical features at diagnosis did not show any correlation. This study demonstrated that CCND1 and FGFR3 genes are involved together in about 50% of MM and primary PCL patients with illegitimate IGH rearrangements.

Lack of benefit of CD34+ cell selected over non-selected peripheral blood stem cell transplantation in multiple myeloma: results of a single center study.

In order to determine the clinical impact of CD34+ cell selected autologous transplantation in multiple myeloma (MM), we have performed a retrospective case-controlled analysis comparing 21 MM patients receiving high-dose melphalan and autologous transplantation with CD34+ peripheral blood stem cells (PBSC) as front-line therapy to 21 control patients receiving unselected products. Case matching was performed using the following criteria: age and beta2-microglobulin at diagnosis and disease status at the time of transplantation. Both cohorts were homogeneous in term of induction treatment and conditioning regimen. Patients were collected for CD34+ selection after priming with G-CSF alone. Significantly fewer CD34+ cells/kg were infused to patients in the selected group as compared to patients in the control group: 2.2 (range 0.5-14.3) vs 9.4 (range 1.1-15) (P < 0.001). The median time to neutrophil recovery > or =0.05 x 10(9)/l was 10 days for the CD34+ group and 9.5 days for the control group (P = 0.357). The median time to platelet recovery > or = 20 x 10(9)/l was 9 days for the CD34+ group and 4.5 days for the control group (P = 0.005). Response rates were comparable in both groups (85.7% in the CD34+ group vs 90.4% in the control group). At 3 years, event-free survival (32% in the CD34+ group vs 39% in the control group) and overall survival (85% in the CD34+ group vs 79% in the control group) were not significantly different. Finally, use of unselected products dramatically reduced the cost of the transplantation procedure. This study shows that CD34+ cell selected autologous transplantation is more expensive than transplantation with unselected products and does not improve the clinical outcome of patients with MM.

Long-term results (12 years) of high-dose therapy in 127 patients with de novo multiple myeloma.

This report describes the long-term outcome of a cohort of 127 de novo multiple myeloma patients treated with at least one course of high-dose therapy (HDT) in a single institution between June 1985 and December 1995, for whom the minimum follow-up duration for survivors is 6 years. The 12-year overall survival (OS) and event-free survival (EFS) rates are 24.9% and 3.1%, respectively, and the median survival and EFS are 49 and 17 months, respectively. Only four patients are alive and disease-free 79, 90, 132 and 153 after the first HDT, respectively. Three of them received a subsequent allogeneic bone marrow transplantation. Three factors significantly influence OS in this series: B2M at diagnosis, age, and the completion of a second HDT. The 10-year survival is 18.9% for the group of patients with B2M level >3 mg/l at diagnosis as compared with 41% for patients with B2M < or =3, with a median survival of 31 months vs 73 (P = 0.01). The 10-year survival is 23.4% for the group of patients aged >55 years as compared with 36.5% for patients aged <55 years, with a median survival of 34.5 months vs 70.5 (P = 0.04). The 10-year survival is 20.4% for the group of patients who did not receive a second HDT as compared with 35.2% for patients who completed a second HDT, with a median survival of 29 months vs 70 (P = 0.02). In this study we show that some patients treated with HDT experience durable remission and prolonged survival. This survival is significantly influenced by age (< or =55 years), B2M at diagnosis (< or =3 mg/l) and by the completion of two cycles of HDT.

Differential expression of Bcl-2 in human plasma cell disorders according to proliferation status and malignancy.

Multiple myeloma (MM) is a malignancy characterized by a very slow proliferation of malignant plasma cells leading to their accumulation within the bone marrow. This suggests that resistance to apoptosis may play a critical role both in the pathogenesis and resistance to treatment of MM. Bcl-2 is a key protein for the regulation of apoptosis. However, it has been shown that this protein also regulates the state of proliferation. In the current study, we show that malignant plasma cells from both the bone marrow and peripheral blood express high levels of Bcl-2 and are slowly proliferating cells. In contrast, myeloma cells from extramedullary sites (ie pleural effusion, ascitis, mammary and gastric plasmacytoma) express Bcl-2 weakly while being highly proliferative. Normal non-dividing bone marrow plasma cells express high levels of Bcl-2 protein. In contrast, four highly proliferative reactive plasmacytosis express weak levels of Bcl-2. We conclude that there is an inverse correlation between Bcl-2 expression and the proliferation rate of both normal and malignant plasma cells. These data may be explained by the double function of Bcl-2, ie its well known function as an anti-apoptotic molecule and its intriguing function as an inhibitory molecule of cell proliferation.

Immunoglobulins D and M multiple myeloma variants are heavily mutated.

Multiple myeloma (MM) is a B-cell malignancy characterized by the expansion of malignant plasma cells within the bone marrow. Previous studies that have examined the Ig VH genes of IgG and IgA MMs have shown the presence of somatic mutations, suggesting that in these cases, the myeloma precursor cell passed through the phase of antigenic selection within the germinal center but is no longer exposed to the somatic mutation process. However, no information about this matter is available in the rare IgD and IgM MM variants. Therefore, we have analyzed the Ig VH genes of three IgD, one IgM, and one biclonal (IgG and IgM) MM for the presence of somatic mutations. Our study demonstrates that all of these myeloma clones have accumulated a high number of somatic mutations within their Ig VH genes but show no intraclonal variation. Moreover, proof that the clone sustained a strong antigenic selection pressure could be provided in three cases (one IgD and two IgMs). Therefore, this study strongly implies that IgD and IgM MMs emerge from a postgerminal center preswitched B cell that is no longer exposed to the somatic mutation process or able to undergo further isotype switching in vivo.

PCR detection of residual Bcl-2/IgH-positive cells after high-dose therapy with autologous stem cell transplantation is a prognostic factor for event-free survival in patients with low-grade follicular non-Hodgkin's lymphoma.

This study was designed to evaluate the results of high-dose therapy followed by purged autologous stem cell transplantation (ASCT) for patients with low-grade follicular non Hodgkin's lymphoma (LGFL), and the prognostic significance of PCR detection of residual Bcl-2/IgH-positive cells after ASCT. Between 1992 and 1998, 49 patients with LGFL received total body irradiation and high-dose cyclophosphamide followed by purged ASCT. PCR amplification of the Bcl-2/IgH rearrangement was performed at diagnosis, on stem cell collections before and after purging and on bone marrow and blood samples after ASCT. With a median follow-up of 76 months (37-103) 34 patients remain alive and event-free. A total of 20 patients had disease recurrence, three patients developed secondary myelodysplastic syndrome (MDS). In all, 11 patients died; 10 deaths were because of recurrent disease, one because of MDS. Kaplan-Meier estimates of event-free survival (EFS) and overall survival (OS) at 5 years were 65% (+/-7%) and 77% (+/-6%), respectively. Patients who achieved a sustained molecular complete response (CR) had a lower risk of disease recurrence and experienced significantly longer EFS (93% (+/-6%) vs 11% (+/-7%) P=0.0008) and OS (100 vs 55% (+/-12%) P=0.0057). In conclusion, myeloablative therapy followed by purged ASCT may induce long EFS in patients with LGFL. The achievement of sustained molecular CR after ASCT improves EFS and OS.

High-dose therapy with stem cell transplantation for mantle cell lymphoma: results and prognostic factors, a single center experience.

From 1991 to 1997 18 consecutive patients with well-defined mantle cell lymphoma (MCL) underwent high-dose therapy with unpurged autologous (17 patients) or allogeneic (one patient) stem cell transplantation. Tissue sections were reviewed for morphology, immunophenotype, cyclin D1 and P53 expression as well as proliferation index (PI). Median age of patients was 47 years (range 40-60). Sixteen had stage IV disease with bone marrow involvement in 12 and performance status was > or =1 in 12 patients. At the time of high-dose therapy 10 patients were in first partial response (PR), one was in second complete remission (CR), four were in second PR and three were refractory to conventional anthracycline-containing chemotherapy. The conditioning regimen consisted of TBI plus chemotherapy in 13 patients and chemotherapy only (BEAM) in five patients. No treatment-related deaths were observed. With a median follow-up of 36 months (range 13-80) after transplant, disease-free survival (DFS) and overall survival (OS) are estimated to be 48 and 80% at 4 years, respectively. Significantly better results are achieved for patients transplanted after a TBI containing regimen with a 4 year OS and DFS estimated at 89 and 71%, respectively compared to 60 and 0% respectively for patients who were conditioned without TBI (P = 0.07 for OS and P < 0.0001 for DFS). There is a trend towards better DFS when the transplant is performed in PR1 (4 year DFS: 80% with eight patients out of 10 in continuous CR 13 to 80 months, median 36 months after transplant) compared to more advanced stages (4 year DFS: 18% with only three patients out of eight in continuous CR 16, 17 and 58 months after transplant). Blastic histology and P53 overexpression are also associated with a trend towards a worst prognosis.

Front-line high-dose therapy with autologous stem cell transplantation for high risk Hodgkin's disease: comparison with combined-modality therapy.

This retrospective study compares high-dose therapy (HDT) with autologous stem cell transplantation and combined-modality treatment (CT) as a first-line therapy for Hodgkin's disease (HD) for patients with both a clinical stage (CS) IV and/or a mediastinal mass > or =0.45 of the thoracic diameter (MM > or =0.45) at diagnosis, and an incomplete response after the first-line chemotherapy. Data on 42 grafted patients (GP) in Nantes Hospital, France and on 108 combined-modality treated patients (CTP) from two protocols of the GOELAMS group, France (POF 81 and H90) was analyzed. Both groups were comparable except for pulmonary disease in excess in the grafted group (P = 0.01). Among GP, 95% were in complete response at the end of first-line treatment and 77% among CTP. Median follow-up was 53 months (range, 7 to 128 months) for GP and 88 months (range, 25 to 181 months) for CTP. The 5-year freedom from progression (FFP) and event-free survival (EFS) rates were better for GP (87% vs 55% for FFP: P = 0.0004 and 81% vs 51% for EFS: P = 0.0004) whereas the overall survival (OS) rates did not differ significantly (85% for GP vs 71% for CTP: P = 0.06). Similar results were obtained for the groups with a response > or =50% after initial chemotherapy: 91% vs 65% for FFP, P = 0.01; 87% vs 61% for EFS, P = 0.02; and 92% vs 77% for OS, P = 0.2; and for the groups with a response <50%: 80% vs 22% for FFP, P = 0.0003; 72% vs 13% for EFS, P = 0.0001; and 76% vs 46% for OS, P = 0.04. This study shows a better control of the disease with HDT.

Melphalan 220 mg/m2 followed by peripheral blood stem cell transplantation in 27 patients with advanced multiple myeloma.

Twenty-seven patients with advanced multiple myeloma received high-dose therapy with 220 mg/m2 i.v. melphalan (HDM220) followed by autologous stem cell transplantation. At the time of HDM220, nine patients had primary refractory disease and 18 were in relapse after having responded to prior high-dose therapy. No toxic deaths were observed. The major adverse side-effect was grade 4 mucositis in 63% of patients. Two patients experienced reversible paroxysmal atrial fibrillation after HDM220. For the whole group of patients, the actuarial 3-year overall survival (OS) and event-free survival (EFS) are 36.1 and 16.9%, respectively. The probability of OS and EFS was significantly lower in patients treated for refractory relapse (22.9 and 0% at 2 years, respectively) as compared to primary refractory patients (66.7 and 64.3% at 2 years, respectively) or patients treated for chemosensitive relapse (42.9% at 2 years) (P = 0.0001). Low beta2-microglobulin and CRP levels at the time of HDM220 were associated with a better OS and EFS. Our data suggest that HDM220 followed by ASCT should be considered in patients with primary refractory disease or chemosensitive disease relapsing after prior intensive therapy.

Peripheral blood stem cell transplantation as front-line therapy in patients aged 61 to 65 years: a pilot study.

The aim of the present trial was to investigate the feasibility of high-dose therapy followed by autologous peripheral blood stem cell transplantation (PBSCT) as a component of front-line treatment in patients with disseminated intermediate- and high-grade non-Hodgkin's lymphoma (NHL) aged 61-65 years. From October 1993 to June 1996, 14 consecutive patients entered this single-center prospective pilot trial. Patients were five males and nine females, median age 63 (range 61-65). The first-line treatment consisted of three courses of CHOP therapy. Patients achieving either a partial response (PR) or a complete response (CR) after initial therapy were eligible for PBSCT, while those with refractory or progressive disease were not autografted but included in the feasibility study in an intent-to-treat analysis. Of the 14 patients, 11 achieved either a CR (one) or a PR (10) after three courses of CHOP while the three patients with no response were not autografted and subsequently died of progressive disease. PBSC collection was feasible in responding patients after G-CSF priming (10 microg/kg/day for 6 days). Conditioning therapy was the BEAM protocol. All patients engrafted after PBSCT. The median time to granulocyte (>0.5 x 10(9)/l) and platelet recovery (>25 x 10(9)/l) was 12 (range 9-18) and 13 days (range 7-22), respectively. No toxic deaths VOD or IP were observed. Four of the 11 responding patients relapsed 2, 7, 9 and 12 months after PBSCT, respectively, and all died from progressive disease. Overall, 7/14 patients are alive and free from disease, 16-43 months after initial diagnosis (median 28). The actuarial overall survival is 45.7 %, and the actuarial event-free survival is 50% at 3.5 years. This study shows the feasibility of high-dose therapy and PBSCT in patients with intermediate- or high-grade disseminated NHL aged 61-65 years. Such patients should not be excluded from trials evaluating the role of ASCT as part of initial treatment for disseminated and histologically aggressive NHL.

The retinoblastoma susceptibility gene RB-1 in multiple myeloma.

Genetic mechanisms leading to the development of multiple myeloma (MM) remain poorly understood. Given the frequency of chromosome 13 deletion in MM and the localization in 13q14 of the retinoblastoma susceptibility gene RB-1, an involvement of RB-1 in MM pathogenesis has been proposed. Moreover, interleukin-6 (IL-6) has been shown to be the main growth factor for MM in vitro and in vivo. The product of the RB-1 gene (pRB) can down-regulate IL-6 gene expression. Absence of pRB may then induce an autocrine IL-6 expression in myeloma cells and contribute to the autonomous growth of MM. As assessed in this review, heterozygous deletion of RB-1 is very common in MM but does not alter gene transcription and protein expression. Nevertheless, homozygous deletion of RB-1 has been identified in some MM patients with advanced disease and in the IL-6-autocrine human myeloma cell line U266. Thus, even if inactivation of RB-1 appears to be only a rare and late oncogenic event in MM and is not likely to represent the main mechanism involved in IL-6 up-regulation in MM, definitive assessment of the actual role played by RB-1 in MM pathogenesis still needs further investigation particularly the examination of pRB function.

Early intensive therapy with autologous stem cell transplantation in high-risk Hodgkin's disease: long-term follow-up in 35 cases.

Thirty-five adult patients with high-risk HD (HD) defined by (1) Ann Arbor stage IV or bulky nodal disease (tumor/thorax ratio > 0.45) and (2) no or partial response (PR) (< 75%) to the initial 3 courses of ABVD, received an early intensive therapy with autologous stem cell transplantation (ASCT). Thirty patients were considered as partial responders and 5 as refractory to initial chemotherapy. Conditioning regimen consisted of chemotherapy alone (CBV in 11 patients before 1993, BEAM in 13 patients since 1993) followed by adjuvant radiotherapy: 40 Gy) on the initial sites of bulky disease, or 12 Gy total body irradiation plus 120 mg/kg cyclophosphamide in 11 patients with disseminated extra-nodal disease. All 30 patients in PR at the time of ASCT experienced prolonged complete remission (CR). One patient died in CR from an acute myocardial infarction 48 months after ASCT. Four out of the 5 patients with refractory disease at the time of ASCT experienced rapid progression of HD leading to death in 3 cases. After 6 years of CR post-ASCT, the last refractory patient died of myelodysplastic syndrome diagnosed 2 years after intensive therapy. With a median follow-up for surviving patients of 51 months (range: 11-111), the cumulative probability of 8-year overall survival is 75.6% for the entire group of patients, 94.1% for the chemosensitive ones, and 0% for the primary refractory (P < .0001). The cumulative probability of 8-year event-free survival is 79.9% for the entire group of patients, 94.1% for the chemosensitive ones, and 0% for the primary refractory (P < .0001). We conclude that early intensive therapy with ASCT is feasible in patients with high-risk HD and induces a high cure rate in chemosensitive patients. In primary refractory patients, new therapeutic approaches are warranted.

Detection of minimal residual disease in multiple myeloma and acute leukaemia.

The importance of minimal residual disease detection has increased due to the advanced therapeutic protocols available for multiple myeloma and acute leukaemia. High-dose chemotherapy, followed by stem cell transplantation is often used in patients with multiple myeloma. But despite a longer disease-free period and overall survival, all patients relapse. In the treatment of acute leukaemia, there are similar problems. The present strategy is to give continuous chemotherapy to eradicate minimal residual disease. In this review, we consider the methods used to detect and quantify minimal residual disease. At present, the most effective seem to be those based on the use of polymerase chain reactions to detect the malignant cells.

[Pseudallescheria boydii osteoarthritis in a patient with acute lymphoblastic leukemia: a case report]. / Ostéoarthrite à Pseudallescheria boydii chez un patient porteur de leucémie aiguë lymphoblastique: à propos d'un cas.

INTRODUCTION: The outcome of neutropenic patients with Pseudallescheria boydii infection is poor. EXEGESIS: We report the first case of Pseudallescheria boydii hip arthritis in a patient treated for acute lymphoblastic leukemia. In vitro susceptibility testing showed that the strain was resistant to amphotericin B, fluorocytosine and nystatin, but susceptible to itraconazole. The patient received oral itraconazole (600 mg/day) and clinical symptoms initially resolved. Two months later, after a course of chemotherapy and high-dose steroids while receiving oral itraconazole treatment, the patient developed fever, skin lesions and disseminated lung infiltrates due to Pseudallescheria boydii and finally died. CONCLUSION: This case illustrates the severity of fungal infections due to Pseudallescheria boydii despite a presumably well-conducted antifungal therapy.

Efficacy of bendamustine in relapsed/refractory myeloma patients: results from the French compassionate use program.

One hundred and ten patients with multiple myeloma were treated with bendamustine as part of a French compassionate use program. To receive bendamustine, patients had to present with relapsed or refractory disease after prior therapies that had to include alkylators, steroids, IMiDs and bortezomib. The median number of bendamustine cycles administered was 4 (1-13). The overall response rate (≥ partial response) was 30%, including 2% complete responses. The median progression-free and overall survival for the entire cohort were 9.3 and 12.4 months, respectively. In this series of patients with advanced disease, both the response rate and the duration of response are encouraging and indicate that bendamustine presents a feasible option, which should be considered for the treatment of relapsed/refractory patients.

Impact of high-dose chemotherapy followed by auto-SCT for positive interim [18F] FDG-PET diffuse large B-cell lymphoma patients.

[(18)F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) is increasingly used for response assessment in diffuse large B-cell lymphoma (DLBCL). A positive interim FDG-PET was shown to be associated with an unfavorable outcome in high-grade non-Hodgkin's lymphomas. For positive interim FDG-PET patients, the question of increasing the intensity of treatment using high-dose chemotherapy followed by auto-SCT (HDC-ASCT) remains unanswered. We retrospectively analyzed the prognostic value of FDG-PET in 42 DLBCL patients who were systematically evaluated at time of diagnosis, before and after HDC-ASCT. Of note, HDC-ASCT was part of the initial treatment strategy, while FDG-PET results did not influence the treatment approach. Results and outcome were analyzed according to FDG-PET results before and after HDC-ASCT. Patients were classified into three groups according to FDG-PET results before and after HDC-ASCT: those who were negative before and after (-/-; n=25), positive before and negative after (+/-; n=9) or positive before and after (+/+; n=8). The median follow-up was 34.5 (range, 19-74) months. The median EFS was significantly lower for the +/+ group (27.4 months) as compared with other groups (median not reached; P=0.0001). More importantly, there was no difference in term of EFS between the -/- group compared with the +/- group. These results suggest that HDC-ASCT can significantly improve the bad prognosis, otherwise indicated by a positive interim FDG-PET.

A combination of anti-interleukin 6 murine monoclonal antibody with dexamethasone and high-dose melphalan induces high complete response rates in advanced multiple myeloma.

To improve the complete response (CR) rate in advanced multiple myeloma (MM) without increasing the toxicity of high-dose therapy, we have used a new conditioning regimen. A combination of BE-8 [an anti-interleukin 6 (IL-6) murine monoclonal antibody] and dexamethasone followed by high-dose melphalan (220 mg/m2) and autologous stem cell transplantation was used to treat a series of 16 patients with advanced multiple myeloma. A strong inhibition of IL-6 activity evaluated by quantification of C-reactive protein was observed in all patients and was correlated with the high CR rate achieved with this combination therapy.