[Overview of the general management of acute leukemia for adults]. / Principes généraux de la prise en charge des leucémies aiguës de l'adulte.

Acute leukemias are a heterogeneous group of malignant hemopathies which are subdivided according to the cytological orientation of the pathological blast cell into lymphoblastic (ALL) and myeloblastic (AML) acute leukemias. Recent advances in the biological and genetic understanding of these diseases have led to improved treatments. Specific chemotherapy treatment or so-called «targeted¼ treatments, advances in bone marrow transplantation and better supportive care have gradually improved the prognosis. This review, focused on the adult patient, aims to describe recent progress in terms of diagnosis, prognostic markers and therapy.

Les leucémies aiguës sont un ensemble hétérogène d'hémopathies malignes qui se subdivisent, en fonction de l'orientation cytologique de la cellule blastique pathologique, en formes lymphoblastique (LLA) et myéloblastique (LMA). Les récents progrès dans la compréhension biologique et génétique de ces maladies ont permis d'améliorer les traitements. Le traitement spécifique de chimiothérapie ou traitements dits «ciblés¼, les progrès de la greffe de moelle et de meilleurs soins de support ont permis d'améliorer graduellement le pronostic. Cette revue, centrée sur le patient adulte, a pour objectif de décrire les progrès récents en termes de diagnostic, de marqueurs pronostiques ainsi que thérapeutiques.

[Diffuse large B-cell lymphoma: a revolutionary treatment based on genetically-modified immune cells called CAR T cells]. / Le lymphome diffus à grandes cellules B : nouveau traitement révolutionnaire par des cellules immunitaires génétiquement modifiées appelées «CART cells¼.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Firstline immunochemotherapy cures approximatively 60 % of patients. The prognosis of patients with refractory disease or with relapsed disease within the first two years after the end of treatment is highly unfavourable. Since June 2019, a new third-line treatment with CAR T cells (chimeric antigen receptor T cells) seems to completely modify the prognosis of these patients. A significant proportion of long-lasting complete responses is obtained with this revolutionary treatment. Quick specialized intervention is required for the unique side effects of this therapy.

Le lymphome B diffus à grandes cellules (LBDGC) est le type histologique de lymphome non Hodgkinien le plus fréquent. Le traitement de première ligne par immunochimiothérapie ne permet de guérir qu'environ 60 % des patients. Les patients présentant une maladie réfractaire à une première ligne de traitement ou en rechute dans les deux premières années suivant le traitement présentent un mauvais pronostic. Disponible depuis juin 2019, un nouveau traitement de 3ème ligne sous forme d'immunothérapie par CAR T cells (acronyme anglais de «chimeric antigen receptor T cells¼) semble modifier complètement le pronostic de ces patients, avec l'obtention d'une proportion importante de réponses complètes de longue durée. Les effets indésirables spécifiques liés à ce traitement demandent une prise en charge rapide et spécialisée.

[Clinical case of the month. Chemotherapy, immunodepression and secondary neoplasms: a case report]. / Chimiothérapie, immunodépression et cancers secondaires: rapport d'un cas clinique.

We report the case of a multi-metastatic mucinous adenocarcinoma of the colon discovered pre-mortem in a patient with a history of multiple myeloma. This case gives the opportunity to discuss the prognostic value of histological typing of colorectal cancer and secondary neoplasms to chemotherapy and/or immunodepression.

[Chronic myelomonocytic leukemia: from diagnosis to treatment]. / Leucémie myélomonocytaire chronique: diagnostic et thérapeutique.

Chronic myelomonocytic leukemia (CMML) is a disease typically of the elderly. It is suspected when monocytosis reaches 1000/microl. It may be associated with "B" symptoms (fever, sweating, and weight loss) but also visceral, skin and autoimmune complications. Current treatment strategies aim at reducing the symptoms and have no curative goals. In this context hypomethylating agents have shown a good efficacy. Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative option but remains difficult to perform in elderly patients population, even if transplantation with a reduced intensity conditioning has reduced the risks. A new prognostic scoring helps to recognize the patients with poor prognosis and to better selected candidates for the HSCT.

Spontaneous pneumomediastinum caused by bleomycin-induced pneumonitis.

We report the case of a 24-yr-old woman treated for lymphoma who developed bleomycin-induced interstitial pneumonia. This interstitial pneumonia was complicated by spontaneous pneumomediastinum. Pneumomediastinum is an unfrequent side effect of high dose bleomycin-induced pneumonitis (BIP) and we describe the first case occurring with low-dose of bleomycin.

[Diffuse large B cell lymphoma: management in 2012]. / Prise en charge du lymphome B diffus à grandes cellules en 2012.

Diffuse Large B Cells Lymphoma (DLBCL) is the most common non-Hodgkin lymphoma and comprises a large number of different entities with different clinico-pathological characteristics. The role of positron emission tomography is essential during the initial staging and post treatment assessment, and potentially at early- or mid-treatment evaluation of response. First line therapy comprises immuno-chemotherapy with rituximab and different cytotoxic agents that differ for components, dosages and frequency of administration taking worldwide-recognized pre-treatment prognostic variables into account. After relapse, peripheral blood stem cells transplantation remains the only chance of cure. This review attempts to summarize the current state of our knowledge by highlighting the leads pursued to further improve current therapeutic results.

[Mantle cell lymphoma: management in 2011]. / Lymphome du manteau: prise en charge 2011.

Mantle cell lymphoma is a rare form of non Hodgkin lymphomas. Diagnosis is made by demonstrating a typical immunophenotype as well as the presence of a translocation between chromosomes 11 and 14 with overexpression of cyclin D1. First line therapy for young patients consists in 3 cycles of "R-CHOP21" alternated with 3 "R-DHAP21" and followed by an autograft conditioned by total body irradiation, cyclophosphamide and aracytine. For patients over 65 years of age, the treatment of choice consists in 8 cycles of "R-CHOP21". Maintenance treatment is under evaluation. Allografting is the only chance of cure in relapsed patients with good performance status. Targeted therapies will improve the prognosis of this disease.

[Current management of myelodysplastic syndromes]. / Prise en charge actuelle des syndromes myélodysplasiques.

Treatment of myelodysplastic syndromes (MDS) has improved in recent years with better results of allogeneic stem cell therapy (SCT), the advent of new therapeutic options such as hypomethylating agents and lenalidomide, the introduction of iron chelation therapy and the implication of erythropoietic stimulating agents in the treatment of anemia. In this review, we summarize the different diagnostic and prognostic criteria and outline the different treatment options we have in 2011.

The Belgian 2010 consensus recommendations for the treatment of multiple myeloma.

Since the introduction of novel therapeutic agents including thalidomide, lenalidomide and bortezomib, the prognosis of multiple myeloma (MM) has significantly improved. These agents have been incorporated into numerous treatment schedules for newly diagnosed as well as more advanced MM patients. Hence, the therapeutic options for MM have become more complex and subject to rapid changes. The multiple myeloma study group (MMSG) of the Belgian Hematological Society has established recommendations for the treatment of MM as based on an extensive review of the literature which is also summarized in this paper. The recommendations are the result of a consensus opinion between haematologists with experience in the field and representing most haematology centres in Belgium. Where applicable, reimbursement criteria are also taken into account. The consensus recommendations should be a reference for use by clinical haematologists in daily practice.

[Mantle cell lymphoma]. / Le lymphome du manteau.

Mantle cell lymphoma comprises 3 to 10% of non-Hodgkin's lymphomas. Cyclin D1 expression due to t(11 ;14) (q13 ;32) is considered as a hallmark of this lymphoma and plays a pivotal role in the pathophysiology of lymphoma transformation. Median age at diagnosis ranges from 60 to 70 years, and diagnosis is often made at an advanced stage with widespread lymphadenopathy and extranodular (particularly bone marrow and gastrointestinal) infiltration. First line treatment consists of combination chemotherapy followed with autologous hematopoietic cell transplantation (HCT) in younger patients, while allogeneic HCT following non-myeloablative conditioning might have a role in patients relapsing after autologous HCT.

[Cerebral toxoplasmosis complicating an allograft with hematopoietic stem cells from peripheral blood]. / Toxoplasmose cérébrale compliquant une mini-allogreffe de cellules souches hématopoïétiques du sang périphérique.

We report the occurrence of a cerebral toxoplasmosis 52 days after a non-myeloablative allogeneic stem cell transplantation as treatment for acute myeloid leukemia.

[Monoclonal antibodies in hematology in 2009]. / Les anticorps monoclonaux en hématologie en 2009.

Directed against the CD20 antigen on B lymphocytes, rituximab (MabThera) is now incorporated in the first line therapy of symptomatic follicular as well as diffuse large B cell non-Hodgkin's lymphoma and offers superior response and survival rates. 90Y ibritumomab tiuxetan (Zevalin) combines the specificity of rituximab for the CD20 antigen and the therapeutic effect of beta irradiation. Given in monotherapy, it constitutes an interesting alternative therapy for follicular lymphomas in second relapse. Alemtuzumab (MabCampath) recognizes the CD52 antigen and offers encouraging results in chronic lymphocytic leukemia resistant to classical chemotherapy.

[How I treat... Acute myeloid leukemia in older patients with good performance status]. / Comment je traite...La leucémie myéloblastique aiguë (LMA) du sujet âgé en bon état général.

This article describes the treatment of acute myeloid leukemia in older patients with good performance status, and then discusses briefly some future therapeutic perspectives.

[Current therapies in hematology]. / Actualités thérapeutiques en hématologie.

This article focuses on recent advances in four important areas of hematology: aggressive lymphomas, allogeneic hematopoietic stem cell transplantation, multiple myeloma, and molecular therapy of cancer.

Cryptic t(4;11) encoding MLL-AF4 due to insertion of 5' MLL sequences in chromosome 4.

The t(4;11) translocation is the cytogenetic hallmark of a subset of acute lymphoblastic leukemias characterized by pro-B immunophenotype and a dismal prognosis. This translocation fuses the MLL gene on chromosome band 11q23 and the AF4 gene on 4q21, resulting in the expression of fusion transcripts from both translocated chromosomes. The MLL-AF4 chimeric transcript is thought to mediate the leukemic transformation. The MLL genomic disruption detected by Southern blot and the RT-PCR for the MLL-AF4 chimeric transcript expression are molecular evidence of this chromosomal translocation. However, similar molecular rearrangements have also been identified in cases without the cytogenetic t(4;11). We report a 30-year-old patient with high risk ALL, a normal karyotype, and molecular evidence of MLL-AF4 fusion. Using a double color FISH assay with MLL specific PAC probes, a cryptic t(4;11) due to insertion of 5' MLL sequences in chromosome 4q21 was demonstrated. Consequently the MLL-AF4 was encoded by der(4). This insertion mechanism precludes the genomic recombination of AF4-MLL and supports the crucial role played by MLL-AF4 in leukemogenesis. The findings of our case, along with others, show the importance of complementing the karyotype with molecular and FISH techniques.

A pilot study of busulfan and melphalan as preparatory regimen prior to allogeneic bone marrow transplantation in refractory or relapsed hematological malignancies.

In this pilot study; we assessed the immunosuppressive and the antileukemic potential of a combination of busulfan and melphalan prior to allogeneic BMT in 25 adult patients with refractory or relapsed hematological malignancies. Twelve patients were transplanted for acute myeloid leukemia (relapse: five patients; primary refractory: four patients; second remission: two patients), two patients for primary refractory acute lymphoblastic leukemia, nine patients for chronic myelogenous leukemia (accelerated phase: six patients; blastic phase: three patients) and two patients for primary refractory lymphoma. All received an unmanipulated marrow from HLA-identical siblings. All patients but one engrafted (median time to ANC > or = 0.5 x 10(9)/l = 17 days, to platelets > or = 50 x 10(9)/l = 29 days). Full chimerism was documented in the seven evaluable patients. The probability for developing acute GVHD was 58%. Complete remission was obtained in 17/18 measurable patients. With a 42 month median follow-up, eight patients are alive in unmaintained remission. The 4-year probabilities for relapse, survival, and DFS are respectively: 42%, 35%, and 31%. These results show that the combination of busulfan and melphalan ensures an effective immunosuppression allowing long-term engraftment. This regimen can provide long-term disease-free survival in patients with high-risk disease and thus represents an interesting alternative to the CY and/or TBI-containing regimens.