[Chronic lymphocytic leukemia]. / La leucémie lymphoïde chronique.

Chronic lymphocytic leukemia (CLL) is a low-grade B cell lymphoma with circulating cells, often revealed by hyperlymphocytosis. Its diagnosis and therapeutic indications (not systematic) have been defined in 2018. In fact, CLL can be separated in two entities differentiating themselves by their IGHV mutational status, but the search of other prognostic parameters like TP53 disruption is mandatory before treatment. Numerous genetic alterations and mutations exist in CLL. CLL cells are highly dependent from their b-cell receptor stimulation and from their microenvironment, which takes a central place in disease progression. Infections, dysimmune manifestations, cancers and Richter transformation are classic complications, and patients have poor vaccine response even without a treatment. Chemoimmunotherapy is being challenged by the new highly active drugs such as Bruton tyrosine-kinase inhibitors (ibrutinib, acalabrutinib) and by the association of venetoclax and anti-CD20. Future treatment strategies might integrate both new drugs and classical chemoimmunotherapy.

[Richter Syndrome: Diagnostic and Therapeutic Management]. / Syndrome de Richter : prise en charge diagnostique et thérapeutique.

Richter syndrome (RS) is defined as the occurrence of an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL) and rarely Hodgkin lymphoma (HL), in a patient with prior or concomitant chronic lymphocytic leukemia (CLL). RS is estimated to occur in 0.5-1 % per year and is associated with adverse outcome. In the vast majority of patients (80 %), RS is clonally related to the prior CLL. Those with unrelated RS appear to have better outcome. The therapeutic approach is based on those of de novo DLBCL or HL. However, even with modern immunochemotherapy regimens, response rate remains low. In eligible patients with related RS, a consolidation by autologous or allogeneic stem-cell transplantation must be proposed. Combinations including therapies targeting BCR or BCL2 and effective in CLL are currently being evaluated in RS. Novels immunotherapies could be promising approaches based on preliminary results.

[Secondary ITP in adults]. / Les purpuras thrombopéniques immunologiques secondaires de l'adulte.

Secondary forms of immune thrombocytopenia (ITP) represent approximately 20% of all ITP cases in adulthood and this rate increases with age. Since some causes may influence both the prognosis and outcome but also the management of ITP, a minimal workup must be performed at ITP diagnosis to look for an associated or underlying cause. Among adults, B-cell lymphomas and mainly chronic lymphocytic leukemia, systemic auto-immune diseases such as systemic lupus or primary immunodeficiencies mainly represented by common variable immunodeficiency are the most frequent causes of secondary ITP. Whereas first-line therapy used for secondary ITP is usually similar to the one commonly used in primary ITP and relies mostly on corticosteroids±intravenous immunoglobulin according to the severity of bleeding, second and third-line treatments must take into account the type and degree of activity of the underlying disease.

[Evaluation of management disparity in patients with chronic lymphocytic leukemia in France]. / Évaluation de la disparité de prise en charge des patients avec une leucémie lymphoïde chronique en France.

Environmental factors have an impact on the effectiveness of treatments for chronic lymphocytic leukemia: vulnerability, organization of the supply of care and proximity of the patient to health professionals. The disparity of care was assessed; vulnerability by the European index of deprivation, the provision of care by values of localized potential accessibility to general practitioners, nurses and pharmacists and hospital supply by the density of hematologists and time access to the center. The data, extracted from the public databases for each grouped island for statistical information, were cross-referenced to apply a principal component analysis and group them into 4 clusters. Cluster 1 has an average EDI, easy access to city professionals, remote access to the referral center, and a good density of hematologists. Cluster 2 has low EDI, satisfactory access to professionals, satisfactory proximity to the referral center and average density of hematologists. Cluster 3 has good EDI, access to professionals is difficult, access to the reference center is long, and the density of hematologists remains average. Cluster 4 has a good EDI, with access to professionals easier than in Cluster 3 but still difficult. The access time to the reference center is better than that of cluster 3 but remains elongated, the density of hematologists remaining average. Mapping is a tool for hospitals and institutions to evaluate care and compare it to other territories.

[Minimal residual disease in chronic lymphocytic leukemia: A still current issue in 2018]. / Maladie résiduelle minime dans la leucémie lymphoïde chronique : un enjeu restant d'actualité.

Minimal residual disease (MRD) is widely used in oncohematology. In chronic lymphocytic leukemia (CLL), it can be measured by flow cytometry or polymerase chain reaction and is getting a greater place, owing to the dramatic therapeutic advances in the management this disease. As MRD decrease after chemoimmunotherapy is associated with improved progression free and overall survivals, its measure is now recommended as a surrogate marker for cytotoxic drugs licensures. This association is independent from treatment received and raises a few questions, such as sequential MRD measures to stop treatment in case of an early deep response and on the opposite, treatment continuation until reaching undetectable MRD (with the possible use of maintenance therapy). Furthermore, following MRD after a cytotoxic treatment could lead clinical trials investigators to propose pre-emptive treatments in case of MRD re-growth, to avoid overt relaspe. MRD re-growth kinetics and CD4 count after treatment completion can improve MRD-based survival predictions. On the other hand, BCR inhibitors do not lead to undetectable MRD, but their association with chemoimmunotherapy increases the proportion of patients reaching that goal. Moreover, BCL2 inhibitors do lead to deep response including in the relapse/refractory setting, giving to MRD a central place in currently investigated treatments evaluation.

[Chronic lymphoid leukemia and renal complication: Report on 10 cases from Marseille over 16 years]. / Néphropathies au cours de la leucémie lymphoïde chronique : à propos d'une étude monocentrique de 10 cas.

INTRODUCTION: Chronic lymphoid leukemia (CLL) is a hematological malignant disease, associated with a clonal B cell proliferation. The incidence is 4400 new cases per year in France. The prevalence increases with age with a median age at diagnostic of 65 years. Renal involvement is rare and estimated at 1.2% of patients with CLL. Renal pathological diagnoses associated with CLL are variable and are not always related to the hematological disease. We report here on cases of patients with CLL who underwent a renal biopsy over the past 16 years in Marseille. METHODS: All cases of renal biopsies performed in patients with CLL between2000 and 2016 in Marseille were included. Pathological analysis was performed by the same experimented pathologist. Data were collected at the time of biopsy and after treatment. RESULTS: Ten patients were included in this study. The reason for renal biopsy was acute kidney injury or the onset of nephrotic syndrome. We report on 4 cases of membranous nephropathy, 1 minimal change disease, 1 cryglobulinemia-related membrano-proliferative glomerulonephritis, 1 light chain amyloidosis, 1 fibrillary glomerulonephritis, 1 interstitial monoclonal infiltration and one case of non-specific tubular lesions. Only one patient was treated before the biopsy, 7 patients received a specific hematological treatment of CLL because of its renal involvement. Renal and hematological responses were variable. CONCLUSION: Renal involvement of CLL is rare and is not mentioned in the Binet classification. Yet, it can be severe, with acute kidney injury or nephrotic syndrome, and can lead to the initiation of a specific treatment. The most frequent presentation this series was secondary MN, which differs from previous series.

[Acquired, non-amyloid related factor X deficiency: A first case associated with atypical chronic lymphocytic leukemia and literature review]. / Déficit non amyloïde acquis en facteur X : un premier cas satellite d'une leucémie lymphoïde chronique atypique et revue de la littérature.

INTRODUCTION: Acquired factor X deficiency is in most cases associated with AL amyloidosis. Acquired non-amyloid related factor X deficiency (DNAA-FX) has been exceptionally reported in the literature. CASE REPORT: We report the first case of acquired, non-amyloid related factor X deficiency associated with atypical chronic lymphoid leukemia in a 66-year-old patient with spontaneous hematomas. After therapeutic failure with polyclonal intravenous immunoglobulins, specific lymphoid malignancy treatment allowed symptoms and coagulation disorder resolution. CONCLUSION: DNAA-FX should be considered in case of bleeding events or coagulation disorders during low-grade hematological malignancies. Its occurrence can be considered as a treatment indication to prevent potentially fatal bleeding complications.

[Rituximab-induced acute thrombocytopenia in a patient with chronic lymphocytic leukemia]. / Un cas de thrombopénie aiguë au rituximab dans la leucémie lymphoïde chronique.

INTRODUCTION: Rituximab is a chimeric anti-CD20 monoclonal antibody generally well tolerated. However, a severe but rare rituximab-related immune-toxic syndrome, associating fever, chills and thrombocytopenia can occur shortly after the infusion. CASE REPORT: We report a case of severe acute rituximab-induced thrombocytopenia with favorable outcome in a patient with chronic lymphocytic leukemia and discuss the possible underlying mechanisms. CONCLUSION: Despite the potential initial severity of rituximab-induced thrombocytopenia in CLL, chemotherapy should not be discontinued; tolerance might increase as the hematologic disorder is controlled.

[Autoimmune and inflammatory disorders associated with lymphoid hematological malignancies]. / Manifestations auto-immunes et inflammatoires des hémopathies lymphoïdes.

In this literature review, we reported autoimmune and inflammatory disorders associated with lymphoid hematological malignancies, including non-Hodgkin's lymphoma, Hodgkin's lymphoma and chronic lymphocytic leukemia. The different types of systemic involvement are classified by affected organ. We listed in this review the joint diseases, skin, neurologic, hematologic, renal, and vasculitis. We tried to determine whether there is a correlation between each autoimmune manifestation and a specific type of lymphoma or a particular feature that may support a paraneoplastic origin, if there is an impact on the prognosis of the hematological malignancy, and finally, we identified the different therapeutic strategies used in the literature.

An uncommon cause of dysuria solved by "boom-boom" radiotherapy.

BACKGROUND: Chronic lymphocytic leukaemia is a common disease affecting the hematopoietic organs. The disease remains classically indolent for years preceding a blast crisis. However, the disease can affect all parts of the body. We report here an unusual localization. CASE PRESENTATION: A 72-year-old man was followed for 2 years for an indolent chronic lymphocytic leukaemia while he presented a rapidly progressive dysuria. Prostate biopsies were performed concluding to a prostate involvement by the chronic lymphocytic leukaemia. In the absence of progression according to RAI staging system and Binet's classification, he was treated with local low-dose radiotherapy, twice 2 Gy, allowing for a rapid resolution of the symptoms. No systemic treatment was introduced, and 1 year after the completion of his treatment, he is still under watchful waiting strategy for his chronic lymphocytic leukaemia. CONCLUSION: Low-dose radiotherapy is an underused effective strategy in indolent lymphoma. In this case, urinary symptoms from a prostate involvement were relieved non-invasively at low cost.

[Ibrutinib prescription in B-cell lymphoid neoplasms]. / Rationnel et modalités de prescription de l'ibrutinib dans les hémopathies lymphoïdes B.

Ibrutinib is a new-targeted therapy that irreversibly and specifically inhibits the Bruton's Tyrosine Kinase (BTK), a key component of the signaling pathways of B cells. The results are very encouraging as monotherapy in the treatment of chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenström's macroglobulinemia. Following the results of recent studies, ibrutinib is now available in France for these three diseases.

Des lymphocytes supérieurs à 5 000/mm3 plus de 3 mois.

Definition, classification and prognostic factors in chronic lymphocytic leukemia. Chronic lymphoid leukaemia is characterized by the monoclonal proliferation of mature lymphocytes with or without tumoral syndrome. It is the malignant blood disease most frequent in Occident characterized by a monoclonal lymphocytary proliferation > 5 000/mm3 over one duration higher than 3 months. The prognostic classification of this pathology is at the same time clinical resting on the stage of Binet but also biological. It is very heterogeneous character in term of clinical and biological presentation, but especially of evolution in fact an enthralling and complex pathology with a major current challenge: that to define prognostic factors allowing to establish an evolutionary risk.

Définition, classification et facteurs pronostiques de la leucémie lymphoïde chronique. La leucémie lymphoïde chronique est caractérisée par une hyperlymphocytose sanguine composée d'une population de lymphocytes matures monoclonaux avec ou sans syndrome tumoral. Il s'agit de l'hémopathie maligne la plus fréquente en Occident caractérisée par une prolifération lymphocytaire monoclonale supérieure à 5 000/mm3 sur une durée supérieure à 3 mois. La classification pronostique de cette pathologie est à la fois clinique reposant sur le stade de Binet mais également biologique. Son caractère très hétérogène en termes de présentation clinique et biologique, mais surtout d'évolution, en fait une pathologie complexe avec un enjeu actuel majeur : celui de définir des facteurs pronostiques permettant d'établir un risque évolutif.

Traiter les formes actives de la maladie.

Therapeutic indications in chronic lymphocytic leukemia. Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries, while it is rare in Asia. It is defined by the presence of more than 5 G/L of B cell clonal. If its evolution is very heterogeneous, the treatment required in the active forms of the disease, progressive stages A and B and stage C of the classification of Binet, benefited in recent years of considerable progress. We consider in this paper the treatment of CLL front line and in patients with relapsed or refractory (R/R), with or without inactivation of TP53: deletion or del(17p) and/or mutations of the TP53 gene. We will discuss the place of immunochemotherapy, including the choice of anti-CD20 monoclonal antibodies: rituximab, ofatumumab or obinutuzumab. For BCR inhibitors, we will limit to the most mature drugs that have obtained marketing authorization: inhibitors of Bruton tyrosine kinase (BTK) ibrutinib and phosphatidyinositol 3-kinase (PI3K) delta, idelalisib. Given its impact, research inactivation of TP53 should be performed before each line of therapy, his presence modifying therapeutic strategies. The treatments, if properly codified, must consider the often little known side effects, whose management is complex.

Indications thérapeutiques dans la leucémie lymphoïde chronique. La leucémie lymphoïde chronique (LLC) est la plus fréquente des leucémies dans les pays occidentaux, alors qu'elle est rare en Asie. Elle est définie par la présence de plus de 5 G/L de lymphocytes B clonaux. Si son évolution est très hétérogène, le traitement des formes actives de la maladie, stades A et B progressifs et stade C de la classification de Binet, a bénéficié ces dernières années de progrès considérables. Nous envisagerons dans cet article le traitement de la LLC en première ligne et celui des patients en rechute ou réfractaires, avec ou sans inactivation de TP53 : délétion 17p et/ou mutations du gène TP53. Nous discuterons la place de l'immuno-chimiothérapie, notamment le choix de l'anticorps monoclonal anti-CD20 : rituximab, ofatumumab ou obinutuzumab. Pour les inhibiteurs du BCR, nous nous limiterons aux molécules validées qui ont obtenu leur autorisation de mise sur le marché : inhibiteurs de la Bruton's tyrosine kinase (BTK), ibrutinib et de la phosphatidylinositol 3-kinase delta, idélalisib. Compte tenu de son impact, la recherche d'une inactivation de TP53 doit être réalisée avant chaque ligne thérapeutique, sa présence modifiant les stratégies thérapeutiques. Les traitements, s'ils sont bien codifiés, doivent tenir compte des effets secondaires, dont la prise en charge est parfois complexe.