High doses of corticosteroids in combination with rituximab remain an alternative in the treatment in relapsed or refractory chronic lymphocytic leukaemia (CLL) in the current era of targeted therapies. This study retrospectively evaluates the efficacy of an RCD (rituximab, cyclophosphamide and dexamethasone) regimen in the treatment of 51 patients with relapsed CLL (median age, 72 years). Unfavourable prognostic features, such as Rai stage III/IV, unmutated IGHV, del11q, TP53 mutation/deletion, complex karyotype and bulky lymphadenopathy, were frequent. The overall response or complete remission was of 57% and 7%, respectively, and the median progression-free survival (PFS) was of 12.3 months, median time to next treatment 23.1 months and median overall survival 39.2 months. Significant independent predictors of shorter PFS were TP53 deletion/mutation, advanced Rai stage and ≥2 previous lines of treatment. The incidence of neutropenia grade ≥ 3 was of 13%. Serious (CTCAE grade 3-5) infections were found in 20% of patients. Steroid-induced diabetes or diabetes decompensation occurred in 20% patients. Treatment-related adverse events resulted in RCD dose reduction in 35% of patients. In comparison with a historical R-Dex patient group, the treatment response and/or toxicity in our group was largely similar. However, the substantial differences in the baseline clinical characteristics of the groups may affect this comparison. In conclusion, the RCD regimen is an active, time-limited therapeutic strategy for elderly patients with relapsed CLL. Further, the results of our analysis indicate that the addition of cyclophosphamide to the R-Dex regimen maintains a similar efficacy, even after 50% reduction in the dexamethasone dose.
- MeSH
- Leukemia, Lymphocytic, Chronic, B-Cell drug therapy genetics pathology MeSH
- Cyclophosphamide administration & dosage MeSH
- Dexamethasone administration & dosage MeSH
- Diabetes Mellitus chemically induced epidemiology MeSH
- Progression-Free Survival MeSH
- Remission Induction MeSH
- Infections epidemiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Recurrence, Local drug therapy genetics pathology MeSH
- Survival Rate MeSH
- Tumor Suppressor Protein p53 genetics MeSH
- Neutropenia chemically induced epidemiology MeSH
- Antineoplastic Combined Chemotherapy Protocols therapeutic use MeSH
- Retrospective Studies MeSH
- Rituximab administration & dosage MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Neoplasm Staging MeSH
- Drug Tapering MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Most patients with chronic lymphocytic leukaemia (CLL) are nowadays diagnosed without any symptoms and do not require therapy. A prognostic score identifying patients within this large group who are at high risk of disease progression would be highly beneficial. The recently published International Prognostic Score for Early asymptomatic patients (IPS-E) uses combination of absolute lymphocyte count (ALC) >15 × 109 /l, palpable lymphadenopathy, and unmutated immunoglobulin heavy-chain variable-region (IGHV) gene to predict the time to first-line therapy (TTFT). Patients at low, intermediate, and high risk had estimated 5-year TTFT of 8%, 28%, and 61%. We performed an external validation of the IPS-E score using an unselected, consecutive group of 130 Binet A patients. The 5-year TTFT was 11%, 36%, and 78% (C-statistic 0·74). Furthermore, we propose an alternative system (AIPS-E) using cytogenetic aberrations instead of palpable lymphadenopathy. This system yielded 5-year TTFT of 14%, 40%, and 72%. These results were externally validated in 388 Binet A patients from five Czech centres; the 5-year TTFT was 16%, 37%, and 80% (C-statistic 0·74). In conclusion, we have successfully validated the IPS-E score for patients with early stage CLL. In addition, we propose a modified scoring system, the AIPS-E, combining IGHV, fluorescence in situ hybridisation, and ALC.
- MeSH
- Time-to-Treatment statistics & numerical data MeSH
- Chromosome Aberrations statistics & numerical data MeSH
- Leukemia, Lymphocytic, Chronic, B-Cell blood diagnosis mortality pathology MeSH
- Genes, Immunoglobulin Heavy Chain genetics MeSH
- In Situ Hybridization, Fluorescence methods MeSH
- Cohort Studies MeSH
- Humans MeSH
- Lymphadenopathy diagnosis MeSH
- Palpation methods MeSH
- Lymphocyte Count methods MeSH
- Prognosis MeSH
- Disease Progression MeSH
- Risk Factors MeSH
- Aged MeSH
- Neoplasm Staging methods MeSH
- Research Design trends MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
The paradigm of first-line treatment of chronic lymphocytic leukaemia (CLL) is currently undergoing a radical change. On the basis of several randomised phase III trials showing prolongation of progression-free survival, chemoimmunotherapy is being replaced by treatment based on novel, orally available targeted inhibitors such as Bruton tyrosine kinase inhibitors ibrutinib and acalabrutinib or bcl-2 inhibitor venetoclax. However, the use of these agents may be associated with other disadvantages. First, with the exception of one trial in younger/fit patients, no studies have so far demonstrated benefit regarding the ultimate endpoint of overall survival. Second, oral inhibitors are extremely expensive and thus currently unavailable due to the absence of reimbursement in some countries. Third, treatment with ibrutinib and acalabrutinib necessitates long-term administration until progression; this may be associated with accumulation of late side effects, problems with patient compliance, and selection of resistant clones. Therefore, the identification of a subset of patients who could benefit from chemoimmunotherapy would be ideal. Current data suggest that patients with the mutated variable region of the immunoglobulin heavy chain (IGHV) achieve fairly durable remissions, especially when treated with fludarabine, cyclophosphamide, and rituximab (FCR) regimen. This review discusses current options for treatment-naïve patients with CLL.
- Publication type
- Journal Article MeSH
- Review MeSH
INTRODUCTION: Oral manifestations of deficiency of iron, vitamin B12 and folic acid are thought to be common. Prevalence of these deficiencies among patients with compatible symptoms is not well known. The goal of this study was to summarize evidence from a dental practice of iron, vitamin B12 and folic acid deficiency in patients presenting with compatible oral manifestations. METHODS: 250 patients who presented with burning mouth syndrome, angular cheilitis, recurrent aphthous stomatitis, papillar atrophy of the tongue dorsum or mucosal erythema were identified. Patients underwent clinical examination, and the blood samples were taken. RESULTS: 250 patients (208 females; 42 males, mean age 44.1 years) with at least one corresponding symptom or sign were identified. The nutritional deficiency of one or more nutrients was found in 119 patients (47.6%). Seven times more females than males were noted to have one type of deficiency (104 females, 15 males). Iron deficiency as defined was diagnosed in 62 patients (24.8%), vitamin B12 or folic acid deficiency in 44 patients (17.6%) and both deficiencies (iron + vitamin B12/folic acid) in 13 patients (5.2%). The only predictive factor was gender and only for iron deficiency. The presence of more than one deficiency was noted in 10 patients (4.9%). CONCLUSION: The most commonly observed deficiency in dental practice over the course of 11 years was an iron deficiency in the female population. Age, diet and reported co-morbidities did not show statistically significant predictable value in recognizing these deficiencies.
- MeSH
- Adult MeSH
- Folic Acid blood MeSH
- Humans MeSH
- Folic Acid Deficiency * MeSH
- Vitamin B 12 Deficiency * MeSH
- Mouth Diseases * MeSH
- Malnutrition MeSH
- Sex Factors MeSH
- Vitamin B 12 blood MeSH
- Practice Patterns, Dentists' statistics & numerical data MeSH
- Iron * MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
The present study aims to evaluate the diagnostic yield of bronchoalveolar lavage (BAL) fluid in patients with hematological malignancies and describe the most common pathogens detected in BAL fluid (BALF.) An analysis of 480 BALF samples was performed in patients with hematological malignancies over a period of 7 years. The results of culture methods, PCR, and immunoenzymatic sandwich microplate assays for Aspergillus galactomannan (GM) in BALF were analyzed. Further, the diagnostic thresholds for Aspergillus GM and Pneumocystis jiroveci were also calculated. Microbiological findings were present in 87% of BALF samples. Possible infectious pathogens were detected in 55% of cases; 32% were classified as colonizing. No significant difference in diagnostic yield or pathogen spectrum was found between non-neutropenic and neutropenic patients. There was one significant difference in BALF findings among intensive care units (ICU) versus non-ICU patients for Aspergillus spp. (22% versus 9%, p = 0.03). The most common pathogens were Aspergillus spp. (n = 86, 33% of BAL with causative pathogens) and Streptococcus pneumoniae (n = 46, 18%); polymicrobial etiology was documented in 20% of cases. A quantitative PCR value of > 1860 cp/mL for Pneumocystis jirovecii was set as a diagnostic threshold for pneumocystis pneumonia. The absorbance index of GM in BALF of 0.5 was set as a diagnostic threshold for aspergillosis. The examination of BAL fluid revealed the presence of pathogen in more than 50% of cases and is, therefore, highly useful in this regard when concerning pulmonary infiltrates.
- MeSH
- Aspergillus genetics isolation & purification pathogenicity MeSH
- Bronchoalveolar Lavage Fluid microbiology MeSH
- DNA, Fungal genetics MeSH
- Adult MeSH
- Hematologic Neoplasms complications microbiology MeSH
- Intensive Care Units MeSH
- Middle Aged MeSH
- Humans MeSH
- Mannans analysis MeSH
- Adolescent MeSH
- Young Adult MeSH
- Neutropenia microbiology MeSH
- Pneumocystis carinii genetics isolation & purification pathogenicity MeSH
- Pneumonia, Pneumocystis diagnosis microbiology MeSH
- Retrospective Studies MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Streptococcus pneumoniae genetics isolation & purification pathogenicity MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Chylothorax is a rare condition which can be associated with malignant lymphoproliferative disorders (LPDs). We retrospectively analyzed the results of the conservative treatment of 10 patients with persistent non-traumatic malignant chylothorax. RESULTS: Conservative treatment lead to a decline of chylothorax after mean of 66 days and consisted of the treatment of the underlying disease and of simultaneous long-term supportive care (drainage of the thoracic cavity, dietary measures and nutrition management). In most cases (80%), chylothorax disappeared only after a successful therapeutic response of the underlying disease. Low-dose radiotherapy had very good effects in two patients. CONCLUSION: Conservative treatment of malignant chylothorax can be considered a suitable method. Based on our results, successful treatment of the lymphoproliferative disorder seems to be a very important factor for the disappearance of chylothorax.
- MeSH
- Chylothorax drug therapy radiotherapy therapy MeSH
- Thoracic Duct drug effects radiation effects MeSH
- Middle Aged MeSH
- Humans MeSH
- Leukemia, Lymphoid drug therapy radiotherapy therapy MeSH
- Lymphoproliferative Disorders drug therapy radiotherapy therapy MeSH
- Lymphoma, Non-Hodgkin drug therapy radiotherapy therapy MeSH
- Retrospective Studies MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH