Polypoid colon mucosa in a leukemia patient.

A woman, followed for chronic myeloid leukaemia, presented for a routine examination. Her medical history was marked by recurrent Helicobacter pylori gastritis and polymyalgica rheumatica. She was under dasatinib and hormone replacement therapy. At clinical examination, she complained about digestive disorders with altered bowel habits. Biology, including leucocyte count, remained normal. A colonoscopy was performed. Endoscopic examination revealed a colonic mucosa covered by multiple tiny nodular lesions (<5mm) from the hepatic angle to the sigmoid and with an abnormal pattern of vascularisation (Fig. 1). Staged biopsies were taken. Microscopic examination revealed discrete achi-tectural distortions. The stroma contained a mixed inflammatory infiltrate composed of neutrophils, eosinophils and lymphocytes. Immunohistochemistry for CD3, CD5, CD20 and CD79 did not bring arguments for a lymphoma. There were no malignant or dysplastic cells. (Fig. 2). What is your diagnosis?

Determining clinically important differences in health-related quality of life in older patients with cancer undergoing chemotherapy or surgery.

PURPOSE: Using the EORTC Global Health Status (GHS) scale, we aimed to determine minimal clinically important differences (MCID) in health-related quality of life (HRQOL) changes for older cancer patients with a geriatric risk profile, as defined by the geriatric 8 (G8) health screening tool, undergoing treatment. Simultaneously, we assessed baseline patient characteristics prognostic for HRQOL changes. METHODS: Our analysis included 1424 (G8 ≤ 14) older patients with cancer scheduled to receive chemotherapy (n = 683) or surgery (n = 741). Anchor-based methods, linking the GHS score to clinical indicators, were used to determine MCID between baseline and follow-up at 3 months. A threshold of 0.2 standard deviation (SD) was used to exclude MCID estimates too small for interpretation. Logistic regressions analysed baseline patient characteristics prognostic for HRQOL changes. RESULTS: The 15-item Geriatric Depression Scale (GDS15), Visual Analogue Scale (VAS) for Fatigue and ECOG Performance Status (PS) were selected as clinical anchors. In the surgery group, MCID estimates for improvement and deterioration were ECOG PS (5*, 11*), GDS15 (5*, 2) and VAS Fatigue (3, 9*). In the chemotherapy group, MCID estimates for improvement and deterioration were ECOG PS (8*, 7*), GDS15 (5, 4) and VAS Fatigue (5, 5*). Estimates with * were > 0.2 SD threshold. Patients experiencing pain or malnutrition (surgery group) or fatigue (chemotherapy group) at baseline showed a significantly stable or improved HRQOL (p < 0.05) after their treatment. CONCLUSION: The reported MCID for improvement and deterioration depended on the anchor used and treatment received. The estimates can be used to evaluate significant changes in HRQOL and to determine sample sizes in clinical trials.

[Malignant or benign hyperleukocytosis ?] / Hyperleucocytose maligne ou bénigne ?

Leukocytosis or an increase of white blood cells in the peripheral blood is a frequent anomaly. It is important to immediately distinguish if it is a benign or malignant leukocytosis and the analysis of the blood formula is the first step. The presence of abnormal cells such as blast cells is an alarm which must immediately consider the diagnosis of leukemia, and medullogram has to be performed. The presence of lymphoma cells will lead to the conclusion of lymphoproliferative disorder and the presence of myeloid precursors to a myeloproliferative disorder. However, a benign leukemoid reaction should be excluded. If there are no abnormal cells in the differential count, it will be necessary to distinguish hyperleucocytosis from myeloid origin (neutrophilies, eosinophilies, basophilies) from lymphoid origin. In the latter case, it is the lymphocytic phenotype that will confirm the malignancy by the presence of a clone of T or B lymphocytes but also by the monomorphic appearance of lymphocytes. In cytologically pleomorphic lymphocytosis, lymphoid reactions related to viral infections, autoimmune diseases or drug-related lymphoid reactions will be sought. The different causes are discussed in detail.

L'hyperleucocytose ou l'augmentation des globules blancs dans le sang périphérique est une anomalie fréquemment rencontrée. Il est important de distinguer immédiatement une hyperleucocytose bénigne d'une hyperleucocytose maligne par l'analyse de la formule sanguine. La présence de blastes est une alarme qui doit immédiatement faire envisager le diagnostic de leucémie aiguë. La présence de cellules lymphomateuses orientera vers un désordre lymphoprolifératif et la présence de précurseurs myéloïdes vers un syndrome myéloprolifératif. Toutefois, une réaction leucémoïde bénigne peut mimer un syndrome myéloprolifératif. S'il n'y a pas de cellules anormales dans l'examen de la formule sanguine, il faudra distinguer les hyperleucocytoses d'origine myéloïde (neutrophilies, éosinophilies, basophilies) des pathologies lymphoïdes. Dans ce dernier cas, c'est le phénotype lymphocytaire qui permettra de confirmer la malignité par la présence d'un clone de lymphocytes T ou B, mais également par l'aspect monomorphe des lymphocytes. Dans les lymphocytoses cytologiquement pléomorphe, on recherchera plutôt les réactions lymphoïdes liées à des infections virales, des maladies autoimmunes ou des réactions lymphoïdes liées à des drogues. Les différentes causes sont discutées en détail.

Adherence to geriatric assessment-based recommendations in older patients with cancer: a multicenter prospective cohort study in Belgium.

Background: In the general older population, geriatric assessment (GA)-guided treatment plans can improve overall survival, quality of life and functional status (FS). In GA-related research in geriatric oncology, studies mainly focused on geriatric screening and GA but not on geriatric recommendations, interventions and follow-up. The aim of this study was to investigate the adherence to geriatric recommendations and subsequent actions undertaken in older patients with cancer. Patient and methods: A prospective Belgian multicenter (N = 22) cohort study included patients ≥70 years with a malignant tumor upon oncologic treatment decision. Patients with an abnormal result on the geriatric screening (G8 ≤14/17) underwent GA. Geriatric recommendations were formulated based on GA results. At follow-up the adherence to geriatric recommendations was documented including a description of actions undertaken. Results: From November 2012 till February 2015, G8 screening was carried out in 8451 patients, of which 5838 patients had an abnormal result. Geriatric recommendations data were available for 5631 patients. Geriatric recommendations were made for 4459 patients. Geriatric interventions data were available for 4167 patients. A total of 12 384 geriatric recommendations were made. At least one different geriatric recommendation was implemented in 2874 patients. A dietician, social worker and geriatrician intervened most frequently for problems detected on the nutritional, social and functional domain. A total of 7569 actions were undertaken for a total of 5725 geriatric interventions, most frequently nutritional support and supplements, extended home care and psychological support. Conclusions: This large-scale Belgian study focuses on the adherence to geriatric recommendations and subsequent actions undertaken and contributes to the optimal management of older patients with cancer. We identified the domains for which geriatric recommendations are most frequently made and adhered to, and which referrals to other health care workers and facilities are frequently applied in the multidisciplinary approach of older patients with cancer.

[Diagnostic approach of an IgM monoclonal gammopathy and clinical importance of gene MYD88 L265P mutation]. / Approche diagnostique d'une gammapathie monoclonale à IgM et intérêt clinique de la recherche de la mutation L265P du gène MYD88.

INTRODUCTION: An IgM monoclonal gammopathy points to a diagnosis of Waldenstrom's Macroglobulinemia. Other B lymphoproliferatives disorders should be ruled out but the limits are sometimes difficult to define. The discovery of the L265P mutation of the MYD88 gene simplified potentially the situation. POPULATION AND METHODS: 383 patients of the Jules Bordet Institute with an IgM level above 2 g/L were reviewed. For the 49 who had a monoclonal peak, we analysed the underlying pathology in termes of general, clinical and biological characteristics. We checked if the MYD88 mutation had been detected. The overall survival rate was studied. RESULTS: 5 histological groups were identified: Waldenstrom's Macroglobulinemia (MW, N = 27), lymphoplasmacytic lymphoma (LLP, N = 10), marginal zone lymphoma (LMZ, N = 7), monoclonal gammopathy of unknown significance and multiple myeloma (MGUS/MM, N = 5). The MW group was compared to the other groups. Regarding biological characteristics, the IgM level upon diagnosis was statistically higher in the MW group with a median level at 19.5 g/L (2.3-101 g/L) (p-value = 0,0001). Concerning the clinical characteristics, a splenomegaly was more frequent in the LMZ group (p-value = 0,04). The L265P mutation of the MYD88 gene was found in 77 % of patients in the MW group, 60 % of patients in the LLP group and 67 % in the LMZ group (p-value = 0,38). For the 49 patients, the 10-yearoverall survival was 85 % (CI 95 %, 67 % to 94 %) and the 15-year-overall survival was 65 % (CI 95 %, 41 % to 81 %). CONCLUSION: A monoclonal IgM peak suggests a MW but other B lymphoproliferatives disorders should be excluded. Even if the L265P mutation is frequent in the LLP/MW, it is not specific. A precise diagnosis requires collating clinical, histological, immunophenotypical and genetical data.

INTRODUCTION: Une gammapathie monoclonale à IgM évoque généralement le diagnostic de maladie de Waldenström. D'autres syndromes lymphoprolifératifs B doivent être exclus mais les " frontières " entre les différentes entités sont parfois mal définies. La découverte de la mutation L265P du gène MYD88 a potentiellement simplifié cette situation. Population et méthodes : 383 patients de l'Institut Jules Bordet présentant un taux d'IgM supérieur à 2 g/L ont été étudiés. 49 d'entre eux présentaient un pic monoclonal pour lesquels nous avons réalisé l'analyse de la pathologie sous-jacente en terme de caractéristiques générales, cliniques et biologiques et avons identifié si une recherche de mutation MYD88 avait été réalisée. La survie globale a également été étudiée. Résultats : 5 groupes histologiques ont été identifiés : maladie de Waldenström (MW, N = 27), lymphome lymphoplasmocytaire (LLP, N = 10), lymphomes de la zone marginale (LMZ ; tous types confondus, N = 7), gammapathie monoclonale de signification indéterminée et myélome multiple (MGUS/MM, N = 5). Le groupe MW a été comparé aux autres groupes. En terme de caractéristiques biologiques, c'est le taux d'IgM au diagnostic qui est statistiquement plus élevé dans le groupe MW avec un taux médian de 19,5 g/L (2,3-101 g/L) (p-valeur = 0,001). Concernant les caractéristiques cliniques, une splénomégalie est plus souvent présente dans le groupe LMZ (p-valeur = 0,04). La mutation L265P du gène MYD88 est retrouvée chez 77 % des patients du groupe MW, 60 % des patients du groupe LLP et 67 % des patients du groupe LMZ (p-valeur = 0,38). La survie globale des 49 patients est de 85 % à 10 ans (IC 95 %, 67 % à 94 %) et de 65 % à 15 ans (IC 95 %, 41 % à 81 %). CONCLUSION: Un pic d'IgM monoclonal évoque généralement une MW, mais il faut toujours exclure d'autres syndromes lymphoprolifératifs B. Alors que la mutation L265P du gène MYD88 est fortement exprimée chez les patients porteurs d'un LLP/MW, elle n'en est pas pour autant spécifique. Un diagnostic précis nécessite aujourd'hui d'intégrer les données cliniques, histologiques, immunophénotypiques et génétiques.

Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma.

BACKGROUND: Copanlisib is a pan-class I phosphatidylinositol 3-kinase inhibitor with predominant activity against the α- and δ-isoforms. PATIENTS AND METHODS: This phase II study evaluated the response rate of copanlisib administered intravenously on days 1, 8, and 15 of a 28-day cycle, in patients with indolent or aggressive malignant lymphoma. Archival tumor tissues were used for immunohistochemistry, gene-expression profiling, and mutation analysis. RESULTS: Thirty-three patients with indolent lymphoma and 51 with aggressive lymphoma received copanlisib. Follicular lymphoma (48.5%) and peripheral T-cell lymphoma (33.3%) were the most common histologic subtypes. Most patients (78.6%) had received prior rituximab and 54.8% were rituximab-refractory. Median duration of treatment was 23 and 8 weeks in the indolent and aggressive cohorts, respectively (overall range 2-138). Eighty patients were evaluated for efficacy. The objective response rate was 43.7% (14/32) in the indolent cohort and 27.1% (13/48) in the aggressive cohort; median progression-free survival was 294 days (range 0-874) and 70 days (range 0-897), respectively; median duration of response was 390 days (range 0-825) and 166 days (range 0-786), respectively. Common adverse events included hyperglycemia (57.1%; grade ≥3, 23.8%), hypertension (54.8%; grade ≥3, 40.5%), and diarrhea (40.5%; grade ≥3, 4.8%), all generally manageable. Neutropenia occurred in 28.6% of patients (grade 4, 11.9%). Molecular analyses showed enhanced antitumor activity in tumors with upregulated phosphatidylinositol 3-kinase pathway gene expression. CONCLUSION: Intravenous copanlisib demonstrated promising efficacy and manageable toxicity in heavily pretreated patients with various subtypes of indolent and aggressive malignant lymphoma. Subtype-specific studies of copanlisib in patients with follicular, peripheral T-cell, and mantle cell lymphomas are ongoing. This trial is registered with ClinicalTrials.gov number NCT01660451 (Part A).

[Practical approach of lymphomas: major role of general practitioner who has to face all these emerging drugs]. / Approche pratique des lymphomes : rôle majeur du médecin généraliste face à l'explosion des nouvelles thérapeutiques.

Malignant lymphoma and other lymphoproliferative disorders represent a group of malignant hemopathies where immunotherapy has allowed spectacular progresses over the last ten years. The recent W.H.O. classification, based upon tumor immunology, and cytogenetical anomalies, allows a better identification of each lymphoma and the comparison of homogeneous populations within various clinical studies. The increase in the incidence of non-Hodgkin lymphoma is related to the aging of the population as well as to other factors that are still to be analysed - a real challenge for the future. We have tried to offer an overview of the latest therapeutical advances while focusing on the major role of general practitioner. The most frequency askeed questions will be discussed.

[Current management of marginal zone lymphomas]. / Prise en charge actueLe du lymphome de la zone marginale.

Marginal zone lymphomas (MZL) encompass three sub-types: MALT (Mucosae Associated Lymphoid Tissue) MZL, nodal MZL and splenic MZL. Immunophenotyping is essential for accurate diagnosis. Helicobacter Pylori is frequently associated with gastric localizations and its eradication can be sufficient for cure. Treatment of nodal MZL is similar to that of follicular lymphoma. Eradication of hepatitis C virus, frequently associated with splenic MZL development, can be sufficient. Without HCV infection, splenectomy constitutes first line therapy. As other indolent lymphomas, disseminated MZL are incurable and treatment should be started only in symptomatic patients.

Myelofibrosis patients in Belgium: disease characteristics.

OBJECTIVE: To date, only a small number of epidemiological studies on myelofibrosis have been performed. The current study aimed to characterize the myelofibrosis patient population in Belgium according to pre-defined disease parameters (diagnosis, risk categories, hemoglobin <10 g/dl, spleen size, constitutional symptoms, platelet count, myeloblast count), with a view to obtaining a deeper understanding of the proportion of patients that may benefit from the novel myelofibrosis therapeutic strategies. METHODS: A survey was used to collect data on prevalence and disease parameters on all myelofibrosis patients seen at each of 18 participating hematologic centers in 2011. Aggregated data from all centers were used for analysis. Analyses were descriptive and quantitative. RESULTS: A total of 250 patients with myelofibrosis were captured; of these, 136 (54%) were male and 153 (61%) were over 65 years old. One hundred sixty-five (66%) of myelofibrosis patients had primary myelofibrosis and 85 (34%) had secondary myelofibrosis. One hundred ninety-three myelofibrosis patients (77%) had a palpable spleen. About a third of patients (34%) suffered from constitutional symptoms. Two hundred twenty-two (89%) myelofibrosis patients had platelet count ≧50 000/µl and 201 (80%) had platelet count ≧100 000/µl. Of 250 patients, 85 (34%) had a myeloblast count ≧1%. Six (2%) patients had undergone a splenectomy. Thirteen (5·2%) patients had undergone radiotherapy for splenomegaly. CONCLUSIONS: The results of this survey provide insight into the characteristics of the Belgian myelofibrosis population. They also suggest that a large proportion of these patients could stand to benefit from the therapies currently under development.

[Cardiac arrhythmias and superior vena cava syndrome revealing a Richter's syndrome]. / Troubles du rythme cardiaque et syndrome cave supérieur révélateurs d'un syndrome de Richter.

Richter's syndrome is the aggressive transformation of chronic lymphocytic leukemia in a diffuse large cell lymphoma. The locations and the clinical manifestations are varied. We report the case of a Richter's syndrome revealed by cardiac arrhythmias and superior vena cava syndrome in a patient of 78 years followed during 2 years for chronic lymphocytic leukemia.

[Anemia in the elderly]. / L'anémie de la personne âgée.

Anaemia is a problem that affects almost 10% over 65 years and 20% over 85 years. There is no physiological anaemia in the elderly. Any anaemia expresses the existence of a pathological process, regardless of its severity. Anaemia in the elderly is always associated with a poor prognosis that is in terms of mortality, morbidity and risk of fragility. The diagnostic approach to anemia in the elderly is the same as in younger individual. There are many causes of anaemia; anaemia balance is a complex diagnostic process. Most anaemias are due to a deficiency, chronic inflammation or comorbidity. However, in the elderly, the etiology of anaemia is often multifactorial. In a number of cases remain unexplained anaemia. In a number of cases, anemia remain unexplained. Treatment of anaemia is the treatment of the cause, but specific therapeutic aspects to the elderly should be considered, as among other martial substitution or use of erythropoietin (EPO).

[Rational approach of leucocytosis in adults]. / Approche rationnelle d'une hyperleucocytose.

Several factors may influence the increased level of white blood cells (physical and/or emotional stimuli, infections, inflammations, drugs, toxins, etc.). The best approach to identify these disorders gets through a physical examination and a precise history. A particular attention should be focused on the onset of lymph nodes and/or splenomegaly. Among severe haematological disorders to take into consideration, we should exclude acute leukemias, chronic leukemias and myeloproliferative disorders.

Relevance of a systematic geriatric screening and assessment in older patients with cancer: results of a prospective multicentric study.

BACKGROUND: To evaluate the large-scale feasibility and usefulness of geriatric screening and assessment in clinical oncology practice by assessing the impact on the detection of unknown geriatric problems, geriatric interventions and treatment decisions. PATIENTS AND METHODS: Eligible patients who had a malignant tumour were ≥70 years old and treatment decision had to be made. Patients were screened using G8; if abnormal (score ≤14/17) followed by Comprehensive Geriatric Assessment (CGA). The assessment results were communicated to the treating physician using a predefined questionnaire to assess the topics mentioned above. RESULTS: One thousand nine hundred and sixty-seven patients were included in 10 hospitals. Of these patients, 70.7% had an abnormal G8 score warranting a CGA. Physicians were aware of the assessment results at the time of treatment decision in two-thirds of the patients (n = 1115; 61.3%). The assessment detected unknown geriatric problems in 51.2% of patients. When the physician was aware of the assessment results at the time of decision making, geriatric interventions were planned in 286 patients (25.7%) and the treatment decision was influenced in 282 patients (25.3%). CONCLUSION: Geriatric screening and assessment in older patients with cancer is feasible at large scale and has a significant impact on the detection of unknown geriatric problems, leading to geriatric interventions and adapted treatment.

Therapeutic drug monitoring of posaconazole in patients with acute myeloid leukemia or myelodysplastic syndrome.

Posaconazole is a broad-spectrum triazole antifungal available as an oral suspension. Pharmacokinetic data showed a high variability of plasma posaconazole concentrations (PPCs) in patients, suggesting a potential interest in drug monitoring. The aim of our prospective study was to measure the PPCs in prophylactically treated patients to evaluate the impact of different factors on these concentrations. In 40 patients treated prophylactically with posaconazole for acute myeloid leukemia or myelodysplastic syndrome between February 2009 and August 2010, PPCs were measured at day 7 of treatment and then twice weekly. Demographic data, clinical data (including gastrointestinal disorders, comedications, and treatment compliance), caloric and fat intake, and biological data were collected and evaluated. We obtained 275 measurements of PPCs, with a median of 430 ng/ml. PPCs were significantly lower in patients with mucositis (P < 0.001), nausea (P = 0.03), diarrhea (P = 0.03), or vomiting (P = 0.05). PPCs were higher in patients with a higher caloric intake (P = 0.02), while the proportion of fat intake had no influence on PPCs (P = 0.84). The concomitant use of proton pump inhibitors decreased the PPCs (P = 0.02), while the use of tacrolimus increased the PPC (P = 0.03). In the multivariate analysis, the factors influencing the PPCs independently were the concomitant use of tacrolimus (P < 0.001), the presence of mucositis (P = 0.01), and food intake (P = 0.02). Our study confirmed the high variability of posaconazole bioavailability and showed the significant influence of gastrointestinal disorders, food intake, and concomitant medication on the PPCs. However, the optimal PPCs still remain to be defined and correlated with clinical efficacy.

[Mastocytosis: revisited with new cytogenetic data]. / La mastocytose: une maladie revisitée a la lumière des nouvelles données génétiques.

Mastocytosis is a heterogenous disorder due to abnormal proliferation and infiltration of mast cells in different tissues, primarily the skin and the bone marrow. Cutaneous mastocytosis is often benign and regresses spontaneously. Systemic mastocytosis is a chronic disease in which some types are indolent but other types such as mast cell leukemia are very aggressive. Pathogenesis of systemic mastocytosis involves a somatic mutation of the gene coding for the c-kit receptor, the most frequent mutation being D816V. Diagnostic criteria have been established by the WHO using histopathological, molecular and biochemical parameters. Treatment of systemic mastocytosis remains a challenge for the clinician due to variability and complexity of the disease. There is, in addition, a lack of a standard and efficient treatment. New targeted therapies with tyrosine kinase inhibitors directed against the c-kit receptor are currently being studied, with the purpose to act specifically on the " primum movens "of the disease. The current review provides an overview of pathogenesis, clinical presentation, diagnosis and classification of cutaneous and systemic mastocytosis. We also discuss the prognosis and the different treatments currently available according to the sub-type of mastocytosis.

[Non Hodgkin's lymphomas: a major breakthrough with immunotherapy]. / Les lymphomes non hodgkiniens: apports considérables de i'immunothérapie.

Non hodgkin's lymphomas are a group of haematological malignancies in which spectacular progress has been made over the last ten years thanks to immunotherapy. Furthermore, the new WHO classification, based upon tumour immunology, the degree of tumour differentiation and cytogenetic abnormalities, has finally improved identification of each lymphoma and has enabled comparison of homogeneous populations between different clinical studies. The increase in the incidence of non hodgkin's lymphoma is related to the aging of the population and to other factors that are yet to be elucidated--a real challenge for the future. We have tried to offer an overview of the latest therapeutic advances, with a focus on (radio-) immunotherapy and haemopoietic stem cell transplantation.

Antileukemic activity of valproic acid in chronic lymphocytic leukemia B cells defined by microarray analysis.

Epigenetic code modifications by histone deacetylase inhibitors have recently been proposed as potential new therapies for hematological malignancies. Chronic lymphocytic leukemia (CLL) remains incurable despite the introduction of new treatments. CLL B cells are characterized by an apoptosis defect rather than excessive proliferation, but proliferation centers have been found in organs such as the bone marrow and lymph nodes. In this study, we analyzed gene expression modifications in CLL B cells after treatment with valproic acid (VPA), a well-tolerated anti-epileptic drug with HDAC inhibitory activity. CLL B cells obtained from 14 patients were treated in vitro with a concentration of 1 mM VPA for 4 h. VPA effects on gene expression were thereafter studied using Affymetrix technology, and some identified genes were validated by real-time PCR and western blot. We observed that VPA induced apoptosis by downregulating several anti-apoptotic genes and by upregulating pro-apoptotic genes. Furthermore, VPA significantly increased chemosensitivity to fludarabine, flavopiridol, bortezomib, thalidomide and lenalidomide. VPA inhibited the proliferation of CpG/IL2-stimulated CLL B cells and modulated many cell cycle messenger RNAs. In conclusion, exposure of CLL B cells to VPA induced apoptosis, potentiated chemotherapeutic agent effects and inhibited proliferation. These data strongly suggest the use of VPA in CLL treatment, particularly in combination with antileukemia agents.

A general chemotherapy myelotoxicity score to predict febrile neutropenia in hematological malignancies.

BACKGROUND: Chemotherapy-induced neutropenia is the most common adverse effect of chemotherapy and is often complicated by febrile neutropenia (FN). The objective of this study is to validate a classification of aggressiveness of a chemotherapy regimen and to evaluate its usefulness in a risk prediction model of FN in patients with hematological cancer at the beginning of a chemotherapy cycle. PATIENTS AND METHODS: Two hundred and sixty-six patients were prospectively enrolled and followed during 1053 cycles. Relevant patient informations were collected at the beginning of the first cycle and the number of days of FN were counted in the follow-up [dichotomized (no FN versus >or= 1 day of FN)]. RESULTS: Aggressive chemotherapy regimen is the major predictor of FN [odds ratio 5.2 (3.2-8.4)]. The other independent predictors are the underlying disease, an involvement of bone marrow, body surface