R-CHOP appears to be the best first-line treatment for second primary diffuse large B cell lymphoma: a cancer registry study.

Second primary diffuse large B cell lymphoma (spDLBCL) is defined as a metachronous tumor occurring after a first primary cancer. To date, while R-CHOP is the standard first-line treatment for de novo DLBCL, no available data show that R-CHOP is the optimal treatment for spDLBCL. This exploratory study aimed to investigate treatment of spDLBCL. From 2008 to 2015, the Poitou-Charentes general cancer registry recorded 68 cases of spDLBCL ≤ 80 years old, having received a first-line treatment with either R-CHOP (78%) or other regimens (22%). Patients without R-CHOP have worse overall survival in univariate (HR 2.89 [1.33-6.24], P = 0.007) and multivariate (HR 2.98 [1.34-6.67], P = 0.008) analyses. Patients without R-CHOP more frequently had PS > 1 (67% vs. 28%, P = 0.007) and prior chemotherapy (60% vs. 26%, P = 0.02), which suggests that both of these factors influence a clinician's decision to not use R-CHOP. Prior chemotherapy had no prognostic impact in univariate and multivariate analyses; this result could call into question the risk-benefit balance of not using R-CHOP to prevent toxicity. In our study, one DLBCL out of ten occurred after a first primary cancer, and as regards de novo DLBCL, R-CHOP appeared to be the best first-line treatment. Larger series are needed to confirm these results.

Added Value of Spectroscopy to Perfusion MRI in the Differential Diagnostic Performance of Common Malignant Brain Tumors.

BACKGROUND AND PURPOSE: Perfusion and spectroscopic MR imaging provide noninvasive physiologic and metabolic characterization of tissues, which can help in differentiating brain tumors. We investigated the diagnostic role of perfusion and spectroscopic MR imaging using individual and combined classifiers of these modalities and assessed the added performance value that spectroscopy can provide to perfusion using optimal combined classifiers that have the highest differential diagnostic performance to discriminate lymphomas, glioblastomas, and metastases. MATERIALS AND METHODS: From January 2013 to January 2016, fifty-five consecutive patients with histopathologically proved lymphomas, glioblastomas, and metastases were included after undergoing MR imaging. The perfusion parameters (maximum relative CBV, maximum percentage of signal intensity recovery) and spectroscopic concentration ratios (lactate/Cr, Cho/NAA, Cho/Cr, and lipids/Cr) were analyzed individually and in optimal combinations. Differences among tumor groups, differential diagnostic performance, and differences in discriminatory performance of models with quantification of the added performance value of spectroscopy to perfusion were tested using 1-way ANOVA models, receiver operating characteristic analysis, and comparisons between receiver operating characteristic analysis curves using a bivariate χ2, respectively. RESULTS: The highest differential diagnostic performance was obtained with the following combined classifiers: maximum percentage of signal intensity recovery-Cho/NAA to discriminate lymphomas from glioblastomas and metastases, significantly increasing the sensitivity from 82.1% to 95.7%; relative CBV-Cho/NAA to discriminate glioblastomas from lymphomas and metastases, significantly increasing the specificity from 92.7% to 100%; and maximum percentage of signal intensity recovery-lactate/Cr and maximum percentage of signal intensity recovery-Cho/Cr to discriminate metastases from lymphomas and glioblastomas, significantly increasing the specificity from 83.3% to 97.0% and 100%, respectively. CONCLUSIONS: Spectroscopy yielded an added performance value to perfusion using optimal combined classifiers of these modalities, significantly increasing the differential diagnostic performances for these common brain tumors.

High-dose thiotepa-based chemotherapy with autologous stem cell support in elderly patients with primary central nervous system lymphoma: a European retrospective study.

In this retrospective multicentre study, we investigated the outcomes of elderly primary central nervous system lymphoma (PCNSL) patients (⩾65 years) who underwent high-dose chemotherapy followed by autologous stem cell transplantation (HDT-ASCT) at 11 centres between 2003 and 2016. End points included remission, progression-free survival (PFS), overall survival (OS) and treatment-related mortality. We identified 52 patients (median age 68.5 years, median Karnofsky Performance Status before HDT-ASCT 80%) who all underwent thiotepa-based HDT-ASCT. Fifteen patients (28.8%) received HDT-ASCT as first-line treatment and 37 (71.2%) received it as second or subsequent line. Remission status before HDT-ASCT was: CR 34.6%, PR 51.9%, stable disease 3.8% and progressive disease 9.6%. Following completion of HDT-ASCT, 36 patients (69.2%) achieved CR (21.2% first-line setting and 48.1% second or subsequent line setting) and 9 (17.3%) PR (5.8% first-line setting and 11.5% second or subsequent line setting). With a median follow-up of 22 months after HDT-ASCT, median PFS and OS were reached after 51.1 and 122.3 months, respectively. The 2-year PFS and OS rates were 62.0% and 70.8%, respectively. We observed two HDT-ASCT-associated deaths (3.8%). In selected elderly PCNSL patients, HDT-ASCT, using thiotepa-based conditioning regimes, is feasible and effective. Further prospective and comparative studies are warranted to further evaluate the role of HDT-ASCT in elderly PCNSL patients.

Comparison of whole-body diffusion MRI and conventional radiological assessment in the staging of myeloma.

PURPOSE: In multiple myeloma, skeletal radiographs are still regarded as the reference imaging examination because they help to establish the stage of the disease according to the Durie-Salmon Staging System. Whole-body MRI using T1 and STIR sequences increases the detection of myeloma lesions. MRI-measured diffusion has demonstrated high sensitivity in terms of detection in oncology. The main objective of this study is to compare conventional radiographic staging with an MRI whole-body diffusion technique (called DWIBS) in detecting bone lesion monoclonal plasma cell pathologies (multiple myeloma, plasma cell leukaemia, plasmacytoma and MGUS). MATERIALS AND METHODS: Twenty-seven patients were included (multiple myeloma: 24; plasma cell leukaemia, MGUS and plasmacytoma: 1 each). All of them had a whole-body MRI diffusion examination (using a DWIBS sequence). Diffusion MRI and conventional radiographs were compared according to the Durie-Salmon Staging System. In case of doubtful lesions, 12 months of monitoring was used as the reference method for the definitive diagnosis. RESULTS: The overall concordance rate between the two techniques was 63%. The DWIBS sequence detected a higher number of lesions leading to a higher Durie-Salmon stage in 37% of the patients: one stage I to II, seven stage I to III, and two stage II to III. In 18.5% of the patients, the MRI was positive while the radiographs were normal and these discrepancies were most often located in sites poorly explored by X-ray (spine, pelvis and ribs). In one patient (4%), the MRI provided a stage lower than that of the X-rays (stage II vs. III). In this case, the X-rays were positive at the humerus and femur, unlike the DWIBS sequence. Our per site analysis confirmed the clear superiority of the DWIBS sequence when compared with X-rays in the exploration of the cervical spine (56 vs. 0%, P<0.001), dorsal spine (81vs. 31%,P<0.0002), lumbar spine (70 vs. 35%, P<0.0124), pelvis (81 vs. 33%, P<0.0005) and ribs (74 vs. 36%, P<0.0009). CONCLUSION: The DWIBS MRI leads to an increase in the final Durie-Salmon stage. Although its place in the preoperative treatment of multiple myeloma still has to be assessed, this study suggests its potential interest.

Rituximab induction immunotherapy for first-line low-tumor-burden follicular lymphoma: survival analyses with 7-year follow-up.

BACKGROUND: The purpose of this study was to report long-term results of rituximab induction monotherapy in patients with low-tumor-burden follicular lymphoma (LTBFL). PATIENTS AND METHODS: Of 49 first-line LTBFL patients who received weekly doses of rituximab (375 mg/m(2)), 46 have been followed with a long-term analysis of clinical and molecular responses. RESULTS: Best clinical response (at any staging within a year following treatment) was 80%, 24 (52%) patients had complete or unconfirmed complete response, 13 (28%) had partial response and 9 (20%) had stable or progressive disease. Of 31 patients having a positive bcl2-JH rearrangement, 15 (48%) became negative following treatment. After 83.9 months of follow-up (95% confidence interval 6.4-92.8 months), the median progression-free survival is 23.5 months and overall survival (OS) is 91.7%. Five patients died (one progression, one myelodysplasia, one diffuse large B-cell lymphoma and two solid tumors). Seven patients (15%) are progression-free including five who are bcl2 informative. No unexpected long-term adverse event has been observed. CONCLUSION: A significant proportion of patients remain progression-free 7 years after a single 4-dose rituximab treatment in first-line LTBFL. The 7-year overall survivalOS is very high in this selected population of patients.

High-dose chemotherapy with autologous stem cell transplantation as first-line therapy for primary CNS lymphoma in patients younger than 60 years: a multicenter phase II study of the GOELAMS group.

The optimum treatment of primary CNS lymphoma (PCNSL) is not yet determined. The objective of this study was to assess the safety and efficacy of initial methotrexate-based chemotherapy followed by high-dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) in patients with newly diagnosed PCNSL. Twenty-five patients received two courses of initial chemotherapy combining methotrexate, etoposide, carmustine and methylprednisolone, and one course of ifosfamide-cytarabine followed by peripheral stem cell collection. Seventeen responsive patients then received HDT using carmustine, etoposide, cytarabine and melphalan with autologous stem cell rescue. After ASCT for responding patients or after salvage therapy for non-responders, whole brain radiation therapy at a dose of 30 Gy was delivered. The objective response rate to the induction chemotherapy was 84%. Four of the 21 responding patients did not have ASCT because of toxicity or refusal. With a median follow-up time of 34 months, the projected event free survival rate is 46% at 4 years. Projected overall survival is 64% at 4 years. Sixteen patients are actually in continuous complete response. No evidence of late treatment-related toxicity was observed. This treatment approach appears feasible in newly diagnosed PCNSL with encouraging results.

Prospective randomized study comparing MEMID with a chop-like regimen in elderly patients with aggressive non-Hodgkin's lymphoma.

OBJECTIVE: This multicenter phase III study compared the MEMID regimen (mitoxantrone, VP16, methylglyoxal, ifosfamide and dexamethasone) with CEOP, a CHOP-like regimen (cyclophosphamide, epirubicin, vincristine and prednisone), in elderly patients (> or =65 years) with aggressive non-Hodgkin's lymphoma (NHL). METHODS: One hundred and forty-nine patients were eligible, 72 in the MEMID arm and 77 in the CEOP arm. The primary endpoint was to compare overall survival (OS) between groups, and secondary endpoints were event-free survival (EFS), response rate and toxicity. RESULTS: Neutropenia (p < 10(-5)), anemia (p < 10(-5)) and thrombocytopenia (p = 0.0006) were significantly more frequent in patients who received MEMID. We observed an objective response rate of 55.5% in the MEMID arm and 64.9% in the CEOP arm (p = 0.24). The median OS and EFS were 15.4 and 8.5 months in the MEMID arm, and 20.3 and 10.5 months in the CEOP arm (p = 0.59 and 0.47), respectively. The median EFS was 15.4 months in the MEMID arm and 20.3 months in the CEOP arm (p = 0.59). CONCLUSION: The increased toxicity without survival benefit confirms the superiority of CHOP and CHOP-like regimens for elderly patient with aggressive NHL.

Long-term follow-up of a randomized trial of fludarabine-mitoxantrone, compared with cyclophosphamide, doxorubicin, vindesine, prednisone (CHVP), as first-line treatment of elderly patients with advanced, low-grade non-Hodgkin's lymphoma before the era of monoclonal antibodies.

BACKGROUND: This randomized study compared the efficacy and safety of fludarabine-mitoxantrone (FM) with mini-CHVP (cyclophosphamide, doxorubicin, vindesine, prednisone) in elderly patients with advanced, low-grade non-Hodgkin's lymphoma. PATIENTS AND METHODS: End points were remission rates [overall response (OR) and complete response (CR)], failure-free survival (FFS), survival and toxicity. One hundred and fifty-five patients were randomized, 144 were evaluable for safety and 142 for response. Each treatment arm was given as six monthly cycles, followed by three bimonthly cycles. FM comprised fludarabine (20 mg/m(2) i.v.), days 1-5, plus mitoxantrone (10 mg/m(2) i.v.), day 1. CHVP cycles comprised cyclophosphamide (750 mg/m(2) i.v. infusion), doxorubicin (25 mg/m(2) i.v.) and vindesine (3 mg/m(2) i.v.) on day 1, and prednisone (50 mg/m(2)) on days 1-5. RESULTS: FM therapy resulted in superior remission rates (OR 81% versus 64%, CR 49% versus 17%; P = 0.0004). Median FFS for FM patients was 36 months, compared with 19 months for CHVP patients, and has not yet been reached for early CR patients at 53 months. Treatment arm was the major risk factor influencing survival. Both treatments were well tolerated, with only few infectious complications. CONCLUSION: FM was more effective than CHVP in achieving OR and CR, and favorably affected the outcome.

[Treatment of high-grade, disseminated non-Hodgkin's lymphoma in elderly patients]. / Traitement du lymphome malin non hodgkinien de haut grade et de stade disséminé du sujet âgé.

PURPOSE: Treatment of non-Hodgkin's lymphoma (NHL) in the elderly is difficult because of an increased risk of toxicity and frequent chronic or debilitating diseases. The aim of this paper is to describe the main studies in this field. CURRENT KNOWLEDGE AND KEY POINTS: Most recent clinical trials deal with anthracyclin or assimilated drugs regimens. Potential interest of chemotherapy and associated immunotherapy is on study. Without any influence on survival duration, haematopoietic growth factors seem to improve the tolerance of the treatment. FUTURE PROSPECTS AND PROJECTS: For elderly patients with good performance status and without severe co morbidity, curative strategy with anthracyclin-containing regimen like CHOP is still the standard chemotherapy. Association with rituximab improves the prognosis. For patients with poor performance status and/or associated disease, optimal strategy remains to be defined with quality of life evaluation.

[Primary thyroid lymphoma: report of 8 cases]. / Lymphome malin primitif de la thyroïde: à propos de huit cas.

PURPOSE: Primary thyroid lymphoma (PTL) is a rare disease. Few patients are reported in the literature. We report eight new cases of PTL with long-term follow-up. RESULTS: The clinical presentation was usually an enlarging neck mass squeezing surrounding structures. The diagnosis was established after thyroidectomy with histopathologic and immunohistochemical studies. Histology showed infiltrates of chronic lymphocytic thyroiditis in all cases. Three patients had thyroid lymphoma arising from mucosa-associated lymphoid tissue. One patient died postoperatively. The other seven were treated with combined chemotherapy and radiotherapy. They were still in remission after a 6-year follow-up. CONCLUSION: Diagnosis of PTL should be suspected when there is a recent thyroid enlargement. Surgery associated with chemotherapy and radiation gave good results in our study with long-term follow-up, though surgery was not always recommended in previous reports.

Treatment of B-lymphoproliferative disorder with a monoclonal anti-interleukin-6 antibody in 12 patients: a multicenter phase 1-2 clinical trial.

Severe T-cell immunodeficiency after solid organ or bone marrow transplantation may result in the uncontrolled outgrowth of latently Epstein-Barr virus-infected B cells, leading to B-lymphoproliferative disorder (BLPD). Given the potentially important pathogenic role of IL-6 in BLPD, it was tested whether the in vivo neutralization of IL-6 by a monoclonal anti-IL-6 antibody could contribute to the control of BLPD. Safety and efficacy were assessed in 12 recipients of transplanted organs who had BLPD refractory to the reduction of immunosuppression over 8 days. Five patients received 0.4 mg/kg per day. The next 7 patients received 0.8 mg/kg per day. Treatment was scheduled to last 15 days. It was completed in 10 patients, and in the other 2 patients was discontinued early (days 10 and 13, respectively) because of disease progression. Treatment tolerance was good, and no major side effects were observed. High C-reactive protein levels were found in 9 patients before treatment but were normalized under treatment in all patients, demonstrating efficient IL-6 neutralization. Complete remission (CR) was observed in 5 patients and partial remission (PR) in 3 patients. Relapse was observed in 1 of these 8 patients in whom remission was observed. This relapse was unresponsive to treatment. Disease was stable in 1 patient, but it progressed in 3 patients. Seven patients are alive and well. Two patients died because of disease progression, and 3 patients died while in CR (chronic rejection in 2 patients and BLPD sequelae in 1 patient). These data suggest that the anti-IL-6 antibody is safe and should be further explored in the treatment of BLPD.

Rituximab (anti-CD20 monoclonal antibody) as single first-line therapy for patients with follicular lymphoma with a low tumor burden: clinical and molecular evaluation.

The clinical activity of rituximab, a chimeric monoclonal antibody which binds to the CD20 antigen, was evaluated as a single first-line therapy for patients with follicular non-Hodgkin lymphoma (NHL). Fifty patients with follicular CD20(+) NHL and a low tumor burden were analyzed for clinical and molecular responses. They received 4 weekly infusions of rituximab at a dose of 375 mg/m(2). The response rate a month after treatment (day 50) was 36 of 49 (73%), with 10 patients in complete remission, 3 patients in complete remission/unconfirmed, and 23 patients in partial remission. Ten patients had stable disease, and the disease progressed in 3 patients. One of 13 (8%) patients in complete remission, 9 of 23 (39%) patients in partial remission, and 5 of 10 (50%) patients with stable disease exhibited disease progression during the first year. Within the study population, 32 patients were initially informative for polymerase chain reaction (PCR) data on bcl-2-J(H) rearrangement. On day 50, 17 of 30 patients (57%) were negative for bcl-2-J(H) rearrangement in peripheral blood, and 9 of 29 (31%) were negative in bone marrow; a significant association was observed between molecular and clinical responses (P <.0001). At month 12, 16 of 26 patients (62%) were PCR negative in peripheral blood. These results indicate that early molecular responses can be sustained for up to 12 months and that this response is highly correlated with progression-free survival. Rituximab has a high clinical activity and a low toxicity and induces a high complete molecular response rate in patients with follicular lymphoma and a low tumor burden.

Autologous stem cell transplantation for anaplastic large-cell lymphomas: results of a prospective trial.

Autologous stem cell transplantation (ASCT) in the front line treatment of non-Hodgkin's lymphoma (NHL) remains controversial. Anaplastic large-cell lymphoma (ALCL) is known to have its own clinical and biological features. The outcome of ALCL patients treated with high-dose chemotherapy and ASCT as part of their first-line therapy was analysed in 202 intermediate or high-grade NHL patients in a prospective randomized trial. First-line chemotherapy comprised two alternating anthracycline-containing regimens. Responding patients were autografted after a BEAM (BCNU, cytarabine, etoposide and melphalan) regimen. Patients with bulky or residual masses were irradiated. Fifteen patients with ALCL were identified by morphological and immunological features (CD30 was expressed in 14 out of 15 patients, three patients expressed B-cell markers, five patients expressed T-cell markers and seven patients did not express cell markers). Anaplastic lymphoma kinase (ALK) expression was confirmed in seven cases. The median age was 39 years with a predominant male sex ratio (2.75). Thirteen patients were stage >/= III and six presented with two or more adverse prognostic factors. According to the international age-adjusted prognostic index, the expected complete remission (CR), event-free survival (EFS) and overall survival (OS) rates were 69%, 71% and 69%. Two deaths were observed (one due to interstitial pneumonitis, one due to pulmonary carcinoma). All patients entered CR, no relapse occurred and EFS and survival reached 87% with a follow-up of more than 5 years. These results differ significantly from those observed in the other 176 lymphoma patients: event-free survival was only 53 +/- 5% and OS reached 60 +/- 4% with a median follow-up of 56 months (P = 0.006). Intensified chemotherapy with autologous stem cell support appeared effective in the treatment of ALCL, offering patients the real chance of a cure.

Thrombotic thrombocytopenic purpura during interferon alpha treatment for chronic myelogenous leukemia.

Thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome have recently been observed in patients undergoing interferon alpha (IFN-alpha) therapy. However, the relationship between disease and therapy has not been established, essentially because of concomitant treatment or previous bone marrow transplantation. We present a case of TTP developing during IFN-alpha therapy for chronic myelogenous leukemia. In this case, IFN-alpha seems to be the only etiological agent.

Primary intracerebral malignant lymphoma: report of 248 cases.

OBJECT: The authors present a retrospective analysis of 248 immunocompetent patients with primary intracerebral lymphoma treated at 19 French and Belgian medical centers between January 1980 and December 1995. METHODS: This study involved 127 female and 121 male patients with a median age of 61 years (range 2-88 years). All tumors available for review were classic diffuse non-Hodgkin's lymphoma, for which the phenotype was determined in 220 patients: 212 (96.4%) were B-cell and eight (3.6%) were T-cell type tumors. According to the Revised European-American classification of lymphoid neoplasms, most lesions were diffuse large cell tumors (62%). A total of 196 tumors were reviewed in 127 patients for whom preoperative computerized tomography and magnetic resonance studies were available. There was a single lesion in 66% of the cases, with a supratentorial location in 87%. Tumor location in the basal ganglia, corpus callosum, or fornix, infiltration of the periventricular ependyma, or a mirror pattern, were strongly suggestive of a lesion of lymphomatous origin. The histological diagnosis was obtained after surgical resection in 116 patients, with the remainder undergoing biopsy sampling only. Of the 248 patients studied, 129 (52%) received chemotherapy plus radiation therapy, 60 (24%) received radiation therapy alone, 35 (14%) received chemotherapy alone, and 24 (10%) received no postsurgical treatment. CONCLUSIONS: Using univariate analysis, the authors determined prognostic factors that were significantly associated with a favorable impact on survival including age younger than 60 years, radiation therapy (without evidence of a dose-response relationship), radiation therapy combined with chemotherapy, and chemotherapy consisting of anthracycline. Partial surgical resection was an unfavorable prognostic factor. Multivariate analysis was used to confirm the independent prognostic value of radiation therapy, age, chemotherapy consisting of anthracyclines or methotrexate, and partial surgical resection. This European survey provides a reasonable basis for the treatment of primary intracerebral lymphoma with the following sequence: stereotactic biopsy sampling, chemotherapy with a methotrexate- and anthracycline-based regimen, followed by cranial irradiation.

Allogeneic bone marrow transplantation for hypereosinophilic syndrome with advanced myelofibrosis.

A 33-year-old man with an atypical course of hypereosinophilic syndrome including malignant hypercalcemia, osteolytic lesions and evolution into severe myelofibrosis was treated by allogeneic bone marrow transplantation after conditioning with cytoxan and total body irradiation. As the transplant was sex-mismatched, chimerism was studied by means of cytogenetic analysis and Y chromosomal DNA amplification by PCR assay. Long-term complete remission has been assessed by normalization of blood cell counts, magnetic resonance imaging and karyotypic analysis. A relapse was observed 40 months after transplantation. The patient remains alive 44 months post-BMT. This case report is compared with those reported in the literature.

Is the International Prognostic Index for aggressive lymphomas useful for low-grade lymphoma patients? Applicability to stage III-IV patients. The GOELAMS Group, France.

BACKGROUND: The International Prognostic Index (IPI) is widely used to predict outcome of patients with aggressive lymphomas. Our goal was to assess the prognostic value of this index for low-grade lymphoma. PATIENTS AND METHODS: One hundred eighty-two patients with disseminated (stage III or IV) low-grade lymphoma were enrolled in a prospective multicenter trial. According to the initial features, treatment either was started immediately or was deferred until indicated by disease progression. Patients received the same polychemotherapy regimen, given monthly for six cycles. They were assigned to one of four risk groups according to the number of presenting risk factors: low-risk (0 or 1), low-intermediate-risk (2), high-intermediate-risk (3), high-risk groups (4). RESULTS: Survival curves (Kaplan-Meier method) demonstrated a high significant difference for the four groups (log-rank: P < 0.0001). Median survival for the low-risk group has yet to be reached, while that for the three other groups are, respectively, 65, 34, and 12 months. CONCLUSIONS: In this study, the IPI has been found to be an important prognostic tool in low-grade lymphoma and may be used in the selection of appropriate therapeutic approaches for individual patients.