Diffuse large B-cell lymphoma of Waldeyer's ring has distinct clinicopathologic features: a GELA study.

BACKGROUND: Diffuse large B-cell lymphomas (DLBCLs) arising in specific extranodal sites have peculiar clinicopathologic features. PATIENTS AND METHODS: We analyzed a cohort of 187 primary Waldeyer's ring (WR) DLBCLs retrieved from GELA protocols using anthracyclin-based polychemotherapy. RESULTS: Most patients (92%) had stage I-II disease. A germinal center B-cell-like (GCB) immunophenotype was observed in 61%, and BCL2 expression in 55%, of WR DLBCLs. BCL2, BCL6, IRF4 and MYC breakpoints were observed in, respectively, 3 of 42 (7%), 9 of 36 (25%), 2 of 26 (8%) and 4 of 40 (10%) contributive cases. A variable follicular pattern was evidenced in 30 of 68 (44%) large biopsy specimens. The 5-year progression-free survival (PFS) and the overall survival (OS) of 153 WR DLBCL patients with survival information were 69.5% and 77.8%, respectively. The GCB immunophenotype correlated with a better OS (P = 0.0015), while BCL2 expression predicted a worse OS (P = 0.037), an effect overcome by the GCB/non-GCB classification. Compared with matched nodal DLBCLs, WR DLBCLs with no age-adjusted international prognostic index factor disclosed a better 5-year PFS rate (77.5% versus 70.7%; P = 0.03). CONCLUSIONS: WR DLBCLs display distinct clinicopathologic features compared with conventional DLBCLs, with usual localized-stage disease, common follicular features and a high frequency of GCB immunophenotype contrasting with a low rate of BCL2 rearrangements. In addition, they seem to be associated with a better outcome than their nodal counterpart.

Comparison of thrombotic microangiopathy after allogeneic hematopoietic cell transplantation with high-dose or nonmyeloablative conditioning.

The role of conditioning intensity on occurrence of thrombotic microangiopathy (TMA) after allogeneic hematopoietic cell transplantation (HCT) has remained unclear thus far. Here, we retrospectively compared the incidence of TMA in patients given allogeneic hematopoietic stem cells after either nonmyeloablative (n=176) or high-dose (n=111) conditioning. The 1-year cumulative incidence of TMA was 13% in nonmyeloablative recipients versus 15% in high-dose conditioning recipients (P=0.5). In multivariate Cox analysis, occurrence of grade 3-4 acute graft-versus-host disease (GVHD) (hazard ratio (HR)=2.3, P<0.001), older age (HR=1.01, P=0.045), and unrelated donors (HR=1.6, P=0.01) were each associated with a higher risk of TMA, whereas nonmyeloablative conditioning was associated with a lower risk of TMA (HR=0.6, P=0.01). We conclude that acute GVHD, age, donor type, and conditioning intensity might have a role in the physiopathology of TMA after allogeneic HCT.

[Current treatment of follicular lymphoma]. / Traitements actuels du lymphome folliculaire.

After diffuse large B-cell lymphoma, follicular lymphoma is the most frequent non-Hodgkin's lymphoma. It remains incurable, except for localized diseases. Advanced disease has to be treated only in the presence of clinical and/or biology aggressiveness. These patients should be treated by rituximab (Mab-Thera) associated to polychemotherapy comprising cyclophosphamide, vincristine and prednisone. After this therapy, the benefit of rituximab in maintenance has to be confirmed. Autologous stem cell transplantation is now reserved for young patients in first relapse. Allogenic stem cell transplantation is also an interesting option. The other therapeutic options comprise radio-immunotherapy with 90Y ibritumomab tiuxetan (Zevalin) and bortezomib (Velcade).

[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.

[Monoclonal antibodies and breast cancer. Current therapeutic progress]. / Anticorps monoclonaux et cancer du sein. Actualités thérapeutiques.

About 9,500 new breast cancers are diagnosed in Belgium every year. Improvement of our knowledge of altered molecular events leading to the proliferation of tumor cells has resulted in the development of targeted therapies in subgroups of cancers. One of the first validation of targeted therapy is the anti-HER-2 monoclonal antibody trastuzumab (Herceptin) in patients with overexpression of human epidermal growth factor receptor type 2 (HER2) occurring in 20 to 25% of invasive breast carcinoma. Trastuzumab binds the extracellular juxtamembrane domain and is only active in tumor with HER2 gene amplification detected by fluorescence in situ hybridization (FISH). The results from randomized trials have rapidly lead to the approvement of the drug in the metastatic and then in the adjuvant setting. Another targeted therapy, also approved in the treatment of breast cancer, is the monoclonal antibody bevacizumab with an anti-VEGF (Vascular Endothelial Growth Factor) activity. We will review the benefit of these targeted therapies in breast cancer and their role in the treatment of breast cancer.

[Radiation recall dermatitis after oral cyclophosphamide]. / Le cas clinique du mois. Réaction de rappel d'irradiation induite par l'administration de cyclophosphamide.

Radiation recall dermatitis is an inflammatory skin reaction occurring in a previously irradiated field following the delivery of a promoting agent. It has been described after a number of antineoplastic agents such as gemcitabine, taxanes, anthracyclines. We report the case of a 50-year-old man with metastatic prostate cancer who developed two consecutive radiation recall dermatitis episodes triggered by oral cyclophosphamide. They occurred 4 to 5 weeks after palliative radiotherapy on bone metastasis. Spontaneous resolution was observed within 6 weeks after discontinuation of cyclophosphamide and with local supportive care. To our knowledge this is the first reported case of radiation recall dermatitis after oral cyclophosphamide.

[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.

[Chemotherapy of ovarian cancer: state of the art]. / Traitement chimiotérapique actuel du cancer de l'ovaire.

Epithelial ovarian cancer is frequently diagnosed at advanced-stage disease and chemotherapy is nearly always required. Optimally debulked patients may need adjuvant chemotherapy while, most of the time this chemotherapy will be given to those with advanced-stage disease. Also relapses will be treated differently whether they occur early or late in the course of the disease. This paper reviews medical treatment modalities according to stage based on published data. Maintenance and consolidation treatments are also discussed. Finally a brief insight into new therapeutic tools is also given.

[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.

[Current therapeutic progress in oncology: the development of targeted therapies]. / Actualités thérapeutiques en oncologie: l'essor des thérapeutiques ciblées.

Over the last decades, significant advances were make in basic research as concerns the malignant transformation of normal cells. As a result, new targets for treatment were identified. "Targeted therapies" indicates that treatments are directed against specific molecular targets that play a major role in the activation of cell division and in the growth and dissemination of tumors. In particular, targeted therapies were developed against epithelial growth factor receptors and angiogenesis. We can expect specifise therapies against many other targets in the near future. Several drugs have obtained a marketing license. Predictive factors for tumor response and long term outcome should be developed for a better selection of the patient population who will benefit from these treatments. New imaging techniques are under development in order to assess the molecular response to these new approaches.

[Targeted therapies in breast cancer: current status and perspectives]. / Actualités thérapeutiques en oncologie sénologique: place actuelle et perspectives des traitements ciblés.

The introduction of targeted therapies has largely modified the treatment strategies in oncology. Two targets are currently used for defining the systemic treatment of breast cancer: hormone receptors and HER2 overexpression. Trastuzumab, a monoclonal antibody, is the only registered antiHER2 treatment in Belgium. The association of trastuzumab with chemotherapy is now the recommended adjuvant treatment for early breast cancer overexpressing HER2. Other antiHER2 medications are available and some will probably be registered soon. Angiogenesis is another potential target for improving the treatment results. The CHU Liège, as a reference center for the systemic treatment of solid tumors, participates in many international trials in order to validate these new approaches. The highest quality of care is required to be in compliance with the conduct of these clinical trials. Another benefit for the patient is the easy access to last generation medical treatments, generally not accessible in our health care system in Belgium outside of clinical trials.

Non-infusional vs intravenous consolidation chemotherapy in elderly patients with acute myeloid leukemia: final results of the EORTC-GIMEMA AML-13 randomized phase III trial.

In this trial, acute myeloid leukemia patients (pts) aged 61-80 years received MICE (mitoxantrone, etoposide and cytarabine) induction chemotherapy in combination with different schedules of granulocyte colony-stimulating factor administration. Pts in complete remission were subsequently randomized for two cycles of consolidation therapy: mini-ICE regimen (idarubicin, etoposide and cytarabine) given according to either an intravenous (i.v.) or a 'non-infusional' schedule. Among the 346 pts randomized for the second step, 331 pts received consolidation-1 and 182 consolidation-2. A total of 290 events (255 relapses, 35 deaths in first CR) have been reported. The median follow-up was 4.4 years. No significant differences were detected in terms of disease-free survival (median 9 vs 10.4 months, P=0.15, hazard ratio (HR) =1.18, 95% confidence interval (CI) 0.94-1.49) - primary end point - and survival (median 15.7 vs 17.8 months, P=0.19, HR=1.17, 95% CI 0.92-1.50). In the 'non-infusional' arm grade 3-4 vomiting (10 vs 2%; P=0.001) and diarrhea (10 vs 4%; P=0.03) were higher than in the 'i.v.' arm, whereas time to platelet recovery >20 x 10(9)/l (median: 19 vs 23 days; P=0.02) and duration of hospitalization (mean: 15 vs 27 days; P<0.0001) was shorter. The 'non-infusional' consolidation regimen resulted in an antileukemic effect similar to the intravenous regimen, which was less myelosuppressive and associated with less hospitalization days.

[Hic et Nunc. Naevus or melanoma?]. / Hic et Nunc. Naevus ou mélanome?

In Wallonia, the incidence of cutaneous melanoma has steadily increased over the past decades. Hopefully, the early diagnosis made at the premetastatic stage has benefited from great advances both in the clinical and laboratory fields. Thanks to the "Groupement Oncologique Universitaire Wallonie-Liège" (GOUWL) organization, some efforts are currently made in order to better frame and normalize the management of cancer patients. Some medical staffs involved in prospective clinical research bring by their own experience further practical insights for the benefit to the patients. In this field, Belgium is not destituted. We report a brief review of the contribution of the Mosan Study Group of Pigmentary Tumors (GMETP) at the University Hospital of Liège.

Infections after allogeneic hematopoietic stem cell transplantation with a nonmyeloablative conditioning regimen.

Hematopoietic cell transplantation (HCT) following nonmyeloablative conditioning (NMSCT) may be associated with a reduced risk of infection compared to standard allogeneic HCT. We retrospectively analyzed incidence and risk factors of infection in 62 patients undergoing NMSCT with low-dose TBI +/- fludarabine and postgrafting CsA and MMF. The proportion of patients with any infection was 77%, but the majority of infectious events occurred beyond day 30. Donor other than sibling, older age, early disease and male gender were significant risk factors. The incidence of bacteremia was 55% at 1 year and the number of bacteremic episodes was 0.9 per patient (0.08 before day 30). The risk of bacteremia increased with older age and the use of a donor other than an HLA-identical sibling, but not with neutropenia. The incidence of infections other than bacteremia correlated with the use of corticosteroids. The risk of CMV infection increased with high-risk CMV serology, and risk of CMV disease with high-risk CMV serology, older age, first transplantation and a diagnosis of lymphoma. In conclusion, after NMSCT, infections are not frequent in the first 30 days post transplant but careful long-term monitoring is necessary thereafter.

[Anemia by self-injury: the Lasthenie de Ferjol syndrome]. / L'anémie par spoliation sanguine volontaire: le syndrome de Lasthénie de Ferjol.

Patients with factitious disorders need to be ill and to defy physicians. These syndromes are difficult to diagnose because of the permanent disorder appearing inside the therapeutic relation. The case of a young woman who presents with a factitious anemia, also called Lasthenie de Ferjol syndrome, shows the complexity of such psychosomatic symptoms.

[Nonmyeloablative stem cell transplantation as cancer immunotherapy]. / Immunothérapie du cancer par minigreffe de cellules souches hématopoïétiques.

Allogeneic hematopoietic stem cell transplantation (HSCT) is used for the treatment of selected haematological malignancies. Its curative potential is based on two different mechanisms, i.e. the conditioning regimen and the graft-versus-host immunologic reactions. However, because of its toxicity, it is restricted to younger and fitter patients. These observations led several groups to set up new (less toxic) transplant protocols. These transplants are called nonmyeloablative HSCT or minitransplants. These are feasible with a relatively low transplant-related mortality even in patients up to 70 years. In addition, strong anti-tumor responses are observed in several haematological malignancies.