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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.

Serum free light chains (sFLC) assay is an important marker in plasma cell dyscrasia. It is thus recommended for the diagnosis of monoclonal gammopathy, together with serum protein electrophoresis and immunofixation. sFLC assay has also a prognostic value and is a criterion for treatment response and relapse of some monoclonal gammopathies. Three assays are currently available in France, the gold standard being the Freelite

PMCID: PMC4112539.-- International Myeloma Working Group: et al., Plasma cell leukemia (PCL) is a rare and aggressive variant of myeloma characterized by the presence of circulating plasma cells. It is classified as either primary PCL occurring at diagnosis or as secondary PCL in patients with relapsed/refractory myeloma. Primary PCL is a distinct clinic-pathological entity with different cytogenetic and molecular findings. The clinical course is aggressive with short remissions and survival duration. The diagnosis is based upon the percentage (≥20%) and absolute number (≥2 × 10 9/l) of plasma cells in the peripheral blood. It is proposed that the thresholds for diagnosis be re-examined and consensus recommendations are made for diagnosis, as well as, response and progression criteria. Induction therapy needs to begin promptly and have high clinical activity leading to rapid disease control in an effort to minimize the risk of early death. Intensive chemotherapy regimens and bortezomib-based regimens are recommended followed by high-dose therapy with autologous stem cell transplantation if feasible. Allogeneic transplantation can be considered in younger patients. Prospective multicenter studies are required to provide revised definitions and better understanding of the pathogenesis of PCL., This work has been supported in part by “Josep Font” Grant from Hospital Clínic de Barcelona and RD06/0020/0005 from Instituto de Salud Carlos III, Spain.

Results of radiotherapy in patients presenting with SP [62, 63]. (DOCX 36Â kb)

Grading of recommendations. (DOCX 12Â kb)

During the last few years, several new drugs have been introduced for treatment of patients with multiple myeloma, which have significantly improved treatment outcome. All of these novel substances differ at least in part in their mode of action from similar drugs of the same drug class, or are representatives of new drugs classes, and as such present with very specific side effect profiles. In this review, we summarize these adverse events, provide information on their prevention, and give practical guidance for monitoring of patients and for management of adverse events.Leukemia accepted article preview online, 18 December 2017. doi:10.1038/leu.2017.353.

Treatment with melphalan-prednisone-thalidomide improves the outcome of patients with multiple myeloma and is now considered a standard of care for patients not eligible for transplantation. However, this treatment is a major source of morbidity. A meta-analysis of data from individual patients (n=1680) in six randomized trials was performed, comparing the effects of melphalan-prednisone-thalidomide versus melphalan-prednisone. The main objective was to estimate the risk of serious adverse events and their impact on outcome. The primary endpoints were the 2-year cumulative incidence of grade 3-4 hematologic and non-hematologic toxicities. At least 75% of the grade 3-4 toxicities occurred during the first 6 months of treatment in both treatment groups. The cumulative incidence of grade 3-4 hematologic toxicities was higher in the melphalan-prednisone-thalidomide group than in the melphalan-prednisone group (28% versus 22%; HR 1.32, 95% CI 1.05-1.66) as was the cumulative incidence of non-hematologic toxicities (39% versus 17%, HR 2.78, 95% CI 2.21-3.50). Grade 3-4 non-hematologic toxicities were significantly increased in patients with poor Performance Status. Occurrence of grade 3-4 non-hematologic toxicities had a negative impact on both progression-free survival (HR 1.24, 95% CI 1.07-1.45) and overall survival, (HR 1.23, 95% CI 1.03-1.47). Besides toxicities, progression-free and overall survival were also negatively affected by advanced International Staging System stage, high creatinine levels and poor Performance Status. Age had a negative impact on survival as well. Although melphalan-prednisone-thalidomide improved outcome, it increased toxicities, especially non-hematologic ones. Serious non-hematologic toxicities, older age, poor Performance Status, and high creatinine levels negatively affected survival. (C) 2013 Ferrata Storti Foundation. This is an open-access paper. doi: 10.3324/haematol.2012.067058

Depuis les annees 1980, les traitements d’entretien dans le myelome multiple (MM) n’avaient pas fait la preuve d’un benefice. Avec l’arrivee ces dix dernieres annees des nouveaux agents et notamment des immunomodulateurs (IMiDs), la question du traitement d’entretien dans le MM a pu etre recemment reconsideree. De nombreux essais de phase 3 ontmontre un benefice de l’utilisation du thalidomide dans cette indication en termes de reponse, de survie sans progression et pour certains de survie globale. Cependant, la survenue d’effets secondaires necessite frequemment son arret premature. Le lenalidomide, un autre IMiD pourvu d’une meilleure tolerance clinique, est alors apparu comme le candidat ideal en traitement d’entretien dans le MM. Les resultats intermediaires des essais de phase 3 sont encourageants. Dans cette revue de la litterature, nous discuterons les resultats des essais de phase 3 portant sur le traitement d’entretien dans le MM par thalidomide et par lenalidomide.

Summary Multiple myeloma is a blood cancer characterized by plasma cells proliferation within the bone marrow and an excess of secreted monoclonal immunoglobulins. Myeloma is invariably preceded by a premalignant phase, monoclonal gammopathy of undetermined significance (MGUS). Multiple myeloma usually is a disease of the elderly, and bones lesions (pain, pathological fractures) frequently dominate the clinical picture. Diagnosis is easy, using a combination of excessive medullary plasma cells and a serum and/or urine monoclonal immunoglobulins. Serum β2-microglobulin and some cytogenetic abnormalities in malignant plasma cells (translocation t(4;14)(p16;q32) and deletion (17p)) are the main prognostic factors. In the near future, transcriptome analysis of tumor cells will likely define different prognosis. Major complications are skeletal destruction manifesting as osteolytic lesions, renal insufficiency, hypercalcemia, myelosuppression with anemia, bleeding and neurological disorders. Symptomatic treatment is essential. The advent of new agents such as proteasome inhibitors and immunomodulatory (IMiDs) and their association have improved the prognosis of patients with myeloma. The youngest patients (≤ 65 years) are treated with induction followed by intensification therapy with autologous stem cell and consolidation treatment. For ederly patients, several combinations of chemotherapy have demonstrated a good efficacy with an acceptable tolerance. Bisphosphonates are associated with chemotherapy.

Resume Objectif Evaluer l’apport de la TEP au 18F-FDG dans le bilan diagnostique, l’evaluation post-therapeutique et le suivi evolutif des plasmocytomes solitaires. Patients et methodes Vingt patients consecutifs ont ete inclus dans cette etude selon les criteres suivants : plasmocytome solitaire prouve histologiquement (osseux ; n = 16 et extraosseux ; n = 4) et ayant beneficie d’une TEP au 18F-FDG entre juillet 2004 et avril 2009. Le suivi clinique etait superieur a un an pour 13 patients et dix patients ont beneficie d’un examen de controle TEP post-therapeutique. L’analyse des images TEP a ete faite sur des criteres purement qualitatifs. Resultats La TEP a permis de confirmer la presence de la lesion principale dans tous les cas (sensibilite : 100 %) ; en plus, elle a permis la detection de lesions infracliniques chez huit patients. Le suivi des patients avec un recul de plus de deux ans a permis de constater une evolution vers un myelome multiple chez cinq patients parmi les six patients (83 %) ayant des lesions infracliniques a la TEP initiale. Des dix patients ayant eu une TEP post-therapeutique, quatre ont presente une reponse partielle et six une reponse complete au niveau de la lesion principale. Conclusion La TEP au 18F-FDG semble etre un outil diagnostique performant dans le classement des plasmocytomes solitaires et permet aussi de detecter des lesions infracliniques ignorees par les autres techniques d’imagerie.

Le sarcome granulocytique est une complication orbitaire rare des leucemies aigues et concerne essentiellement les enfants de moins de 10 ans presentant une leucemie aigue myeloide de novo . Ce type d’atteinte se rencontre exceptionnellement chez le sujet âge lors de l’acutisation d’un syndrome myelodysplasique, cela pose un probleme de diagnostic et par voie de consequence de prise en charge therapeutique. Nous rapportons le cas d’une patiente de 77 ans ayant presente une exophtalmie brutale au decours d’une ethmoidite droite en voie de resolution. Le diagnostic evoque par l’imagerie qui montre une tumeur intra-orbitaire extraconique a point de depart sinusien est confirme lors du bilan hematologique. Une exophtalmie brutale evoluant dans un contexte de leucemie aigue myeloblastique oriente fortement vers le diagnostic de sarcome granulocytique. Une chimiotherapie par cytarabine et hydroxycarbamide associee a une corticotherapie intraveineuse permet d’observer une disparition complete de l’exophtalmie en une dizaine de jours. Le but de ce cas clinique est de rappeler ce mode d’expression du syndrome tumoral au cours des leucemies aigues myeloides. Nous abordons aussi les differentes methodes de diagnostic, les differents abords therapeutiques, l’evolution et la surveillance des patients.

We construct a differential representation and covariant derivatives of the minimal vector clover extension of the Poincare algebra. In analogous way as in the supersymmetric case, there arises an enhanced superspace which allows to define superfields. The action of group transformations on such superfields determines a representation out of which the covariant derivatives are obtained.

Once characterized by a very poor outcome, multiple myeloma (MM) now has a significantly prolonged survival, with major improvements allowed by the use of "novel agents": proteasome inhibitors (first-in-class bortezomib) and immunomodulatory compounds (IMiDs; first-in-class thalidomide and lenalidomide). However, the vast majority - if not all - of patients with MM ultimately end up being refractory to all existing drugs, including these efficient novel agents. There is a clear unmet medical need in this situation, which warrants the development of the next generation of proteasome inhibitors and IMiDs, as well as new drug classes. This review focuses on pomalidomide, the next generation IMiD, recently approved by the US FDA and the EMA for patients with relapsed or refractory MM who have received at least two prior therapies, including lenalidomide and bortezomib, and have demonstrated disease progression on their last therapy.

Monoclonal gammopathy of undetermined significance (MGUS) is a frequent entity in the general population. The incidence rate of fortuitous discovery of a monoclonal component in asymptomatic patients is increasing nowadays. The majority of MGUS is being addressed to a hematologist for diagnosis or follow-up by their generalist practitioners. The management of MGUS consists of a clinical and biological surveillance as per published and validated international guidelines available for MGUS diagnosis and follow-up. MGUS thus may not necessarily need a specialized consultation and follow-up in a hematology ward, as we believe it could be performed by generalist practitioners.We studied 190 patients addressed to our hematology department of Lille for diagnosis or follow-up of MGUS.Among the patients, 9.5% developed a malignant hemopathy (multiple myeloma or Waldenström macroglobulinemia). Among patients diagnosed with MGUS of IgG isotype and a monoclonal component15 g/L, 96.2% showed no pejorative outcome: these represent simple and routine prognostic factors that can be assessed at diagnosis in order to predict the risk of progression. Those patients could have easily been followed by their generalist practitioner from the diagnosis of MGUS.A specialist's consultation would still be recommended for patients with pejorative factors at diagnosis, or if a clinical or biological event that could suggest progression occurs during follow-up, or in case of MGUS with complication, in which cases patients would need a specialized management in a hematology department.

Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell neoplasia, characterized by monoclonal plasma cell proliferation in the absence of end-organ damage, but with a high risk of progression to multiple myeloma. It has therefore to be distinguished from monoclonal gammapathy of undetermined significance (MGUS), which has a much lower risk of progression, but also from multiple myeloma, which remains an incurable disease and requires a specific treatment. The critical question in the management of SMM is whether an early therapeutic strategy could help delaying the progression to multiple myeloma, in order to lower the risk of serious complications related to this progression, or even to cure the disease. This early treatment could not be proposed to all SMM patients, who are indeed asymptomatic, and in whom the risk of toxicity could make it difficult to justify the potential benefit obtained. The challenge is to target early at diagnosis SMM patients with a high risk of progression, using available routine tests sufficiently reliable to warrant the therapeutic sanction which relies on it. Today however, apart from randomized studies, recommendations are to maintain therapeutic abstention in SMM patients.

Waldenström's macroglobulinemia (WM) is a B-cell disorder characterized primarily by bone marrow infiltration with lymphoplasmacytic cells, along with the presence of an IgM monoclonal gammopathy in the blood. WM remains incurable with a median of 8-year of overall survival for patients with symptomatic WM. Treatment is postponed for asymptomatic patients and progressive anemia is the most common indication for initiation of treatment. The main therapeutic options include alkylating agents, nucleoside analogues, and rituximab, either alone or in combination. Studies involving new combination chemotherapy are ongoing and preliminary results are encouraging. However, there are several limitations to these approaches. The complete response rate is low and the treatment free survival is short in many patients, no specific agent or regimen has been shown to be superior to another, and no treatment has been specifically approved for WM. As such, new therapeutic agents are needed for the treatment of WM. In ongoing efforts, we and others have sought to exploit advances made in the understanding of the biology of WM so as to better target therapeutics for this malignancy. These efforts have led to the development of proteasome inhibitors as bortezomib, several Akt/mTor inhibitors, such as perifosine and Rad001. Many other agents and monoclonal antibodies are currently being tested in clinical trials and seem promising. This article provides an update of the current preclinical studies and clinical efforts for the development of novel agents in the treatment of WM.

Introduction La tubulopathie myelomateuse (TM) est la complication renale la plus frequente du myelome. La coloration par le Rouge Congo de certains des cylindres myelomateux ou « amylose intratubulaire » (AMIT) est une constatation rare dont la signification est inconnue. En particulier, le lien entre l’AMIT et l’amylose AL systemique avec depots parenchymateux renaux ou extrarenaux n’a jamais ete etudie. Materiels et methodes Le critere d’inclusion etait un diagnostic de TM sur PBR entre 2002 et 2012. Une relecture histologique des PBR a ete effectuee avec coloration du Rouge Congo pour recherche d’AMIT et/ou de depots d’amylose au sein du parenchyme renal. La recherche d’amylose extra-renale a ete realisee retrospectivement par coloration du Rouge Congo sur tout prelevement histologique (biopsie, piece operatoire) disponible chez les patients inclus. Les donnees cliniques ont ete recueillies en parallele. Resultats Soixante-huit patients avec TM diagnostiquee sur PBR entre 2002 et 2012 ont ete inclus. La relecture histologique a mis en evidence une AMIT chez 18/68 (26,5 %) patients. Dans un cas, l’AMIT etait associee a la presence de depot d’amylose au sein du parenchyme renal ; dans 3 autres cas, une amylose renale etait mise en evidence sans AMIT. Une amylose extra-renale a ete mise en evidence chez 5/18 patients avec AMIT et chez 1/50 patients sans AMIT. Au total, des depots d’amylose parenchymateux renaux ou extrarenaux etaient detectes chez 6/18 patients avec AMIT et chez 4/50 patients sans AMIT (OR : 5,56 ; p = 0,017). Discussion La recherche d’une amylose AL est importante chez les patients atteints de TM. En effet, sa decouverte peut modifier le pronostic et le traitement. Conclusion Notre etude, qui semble indiquer pour la premiere fois que l’AMIT est associee a la presence d’une amylose AL systemique, souligne l’importance de la recherche systematique de l’AMIT au cours de la TM et, en cas de detection d’une AMIT, de la realisation d’un bilan approfondi a la recherche d’une amylose AL.