ABSTRACT
Prognostic value of N-terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP) was analyzed in patients with multiple myeloma complicated by dialysisdependent renal failure. The prospective study included 20 patients with newly diagnosed multiple myeloma. The concentrations of NT-proBNP were measured before antimyeloma chemotherapy. The median age of the patients was 67 (63-76) years. The median glomerular filtration rate was 4 (4, 5) ml/min/1.73 m2. For overall survival, the area under ROC curve was 0.75 and the cut-off point was 7000 pg/ml. At median follow-up of 17.3 months, the overall survival was 76.6±14.8 and 27.3±13.4% (p=0.02) for cases with NT-proBNP levels below and above the cut-off point, respectively. There were no cases of death due to cardiovascular causes. We concluded that the increase in serum concentration of NT-proBNP>7400 pg/ml is associated with the severity of kidney damage and the risk of non-cardiac mortality.
Subject(s)
Multiple Myeloma/blood , Multiple Myeloma/pathology , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Aged , Biomarkers/blood , Female , Glomerular Filtration Rate/physiology , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Renal Dialysis , Renal Insufficiency/blood , Renal Insufficiency/pathologyABSTRACT
Aim of the issue was to compare clinical characteristics and treatment results of patients with follicular lymphoma (FL) with translocations involving loci of c-MYC/8q24, BCL2/18q21 and/or BCL6/3q27 genes and patients with high - grade B-cell lymphoma [High - grade B-cell lymphoma (HGBL), double - hit (DH)]. Materials and methods. Since 2004 to 2017 years in National Research Center for Hematology 12 patients with high - grade B-cell lymphoma double - hit (HGBL DH) and 6 FL patients with translocations involving c-MYC and BCL2 and/or BCL6 had been treated. We performed a comparative analysis of clinical characterisctics in both groups. As primary endpoints was assessed frequency of complete remission (CR) or progressive disease (PD); as secondary endpoints - overall (OS) and event - free survival (EFS). Results. 5 patients with HGBL DH had c-MYC/BCL6, 7 - c-MYC/BCL2 rearrangements; 2 patients with FL had c-MYC/BCL2, 3 - c-MYC/BCL6, 1 - c-MYC/BCL2/BCL6 rearrangements. FL was represented by grade 3A in 2, grade 3B - in 4 cases, 3 of them had large - cell transformation. In HGBL DH and FL patients had no significant differences in clinical characteristics. The majority of patients had a widespread tumour, increased LDH activity, high frequency of extranodal and bone marrow involvement. Ki-67 expression level was lower in patients with FL (p.
Subject(s)
Biomarkers, Tumor/genetics , Lymphoma, Follicular/genetics , Lymphoma, Large B-Cell, Diffuse/genetics , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-6/genetics , Proto-Oncogene Proteins c-myc/genetics , Transcription Factors/genetics , Translocation, Genetic , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/analysis , Humans , Lymphoma, Follicular/pathology , Lymphoma, Follicular/therapy , Lymphoma, Large B-Cell, Diffuse/mortality , Proto-Oncogene Proteins/genetics , Retrospective Studies , Survival Rate , Treatment OutcomeABSTRACT
AIM: to evaluate the efficiency of high-dose chemotherapy (HDCT) with further autologous blood stem cell transplantation (auto-BSCT) in the first-line therapy of patients with follicular lymphoma (FL) and poor prognostic factors. SUBJECTS AND METHODS: In 2000 to 2015, the National Research Center for Hematology, Ministry of Health of the Russian Federation, performed therapy in 39 patients with FL and poor prognostic factors (a total of 215 patients with FL). The R-CHOP treatment was done as induction therapy. Sequential HCT and further auto-BSCT were performed in 29 (74%) of the 39 patients, who had shown a partial tumor response to the induction therapy or achieved partial remission after 4-6 cycles of CT, but had poor prognostic factors. 22 of the 29 patients underwent auto-BSCT in first-line therapy after induction R-CHOP regimens. Among them, there were 17 men with a median age of 46 years (31-68 years). 21 of the 22 patients were recorded to have Stage IV by the Ann Arbor staging classification. Bulky peritoneal and retroperitoneal tumors larger than 7 cm were detectable at disease onset in 14 of the 22 cases. Two patients were noted to have phenomena of leukemization. 16 patients had bone marrow (BM) involvement. According to the Follicular Lymphoma International Prognostic Index-1 (FLIPI-1), the patients were divided into 3 groups: 1) a low risk (n=5); 2) an intermediate risk (n=3); a high risk (n=14). B-symptoms were observed in 16 cases. 16 patients were diagnosed with cytological grade I-II FL and 6 had grade IIIA. According to the tumor proliferative pattern, the distribution turned out to be as follows: nodular (n=6), nodular-diffuse (n=13), and diffuse (n=3). The proliferative activity index averaged 30% (8-90%). Serum and urine proteins were immmunochemically assayed in 18 cases, out of them 8 patients were diagnosed as having serum ß2-microglobulin concentrations above normal as a poor prognostic factor. In 14 of the 22 patients, the activity of lactate dehydrogenase was greater than normal (266-7806 U/l). RESULTS: Out of the 22 patients, 20 who have undergone auto-BSCT in first-line therapy are survivors and have remission of the underlying disease: 18 and 2 patients achieved complete and partial remission, respectively. The follow-up period was 7 to 178 months (median, 32 months). After auto-BSCT in the first remission, 2 patients developed disease recurrences: an early recurrence after 9 months in one case and a late recurrence 6 years after completion of therapy in the other. CONCLUSION: The first prospective study of intensive therapy for FL in Russia has demonstrated that HDCT with further auto-BSCT in first-line therapy allows complete remission in patients with poor prognostic factors and higher overall and progression-free survival rates.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Hematopoietic Stem Cell Transplantation/methods , Lymphoma, Follicular/diagnosis , Lymphoma, Follicular/therapy , Outcome Assessment, Health Care , Adult , Aged , Female , Humans , Lymphoma, Follicular/drug therapy , Lymphoma, Follicular/surgery , Male , Middle Aged , Neoplasm Grading , Prospective Studies , Russia , Transplantation, AutologousABSTRACT
AIM: To evaluate the efficiency and toxicity of the intensive Burkitt's lymphoma (BL) therapy protocol BL-M-04. SUBJECTS AND METHODS: A total of 70 patients diagnosed with BL, including 45 men and 25 women whose age was 15 to 62 years (median age 31 years), were followed up in 2003 to 2014. Stage I (according to S. Murphy) was diagnosed in 4 (5.7%) patients; II in 9 (12.9%), III in 25 (35.7%), IV in 11 (15.7%), and Burkitt's leukemia in 21 (30%). There were tumor involvements of the bone marrow and central nervous system in 23 (32.9%) and 15 (21.4%) patients, respectively. B symptoms were detected in 56 (80%) patients; enhanced lactate dehydrogenase (LDH) activity was found in 50 (78.1%) out of 64 patients; moreover, in 34 (56.2%) out of 64 patients, LDH activity was more than twice as high as the reference values. The median LDH activity was 2398 (238-20,300) U/I. Acute renal failure at disease onset was identified in 17 (24.2%) patients; chemotherapy was initiated in 8 patients during renal replacement therapy. The treatment was performed using the BL-M-04±R protocol (4 successive blocks of A-C-A-C±R). Six blocks of A-C-A-C-A-C with rituximab has been carried out in patients with bone marrow involvement since 2011. RESULTS: Sixty-two (89%) patients achieved complete remission. At this time, 6 patients died from therapy complications during remission induction; 2 patients were observed to have disease progression; 3 developed disease recurrence (2 patients had early recurrence; 1 patient developed recurrence 2 years after treatment). Five-year overall survival (OS) was 85%; 5-year relapse-free survival (RFS) was 95%. The Cox multivariate regression analysis revealed that Burkitt's leukemia and bone marrow involvement were independent factors that influenced OS and RFS. The poor somatic status (3-4 ECOC scores versus 0-2 scores) proved to be statistically significant for OS rather than RFS. CONCLUSION: Despite the optimistic results obtained by our study group, there is a need to further improve BL treatment protocols and to elaborate novel approaches to therapy particularly for older patients and patients with Burkitt's leukemia.
Subject(s)
Antineoplastic Agents/therapeutic use , Burkitt Lymphoma/drug therapy , Forecasting , Adolescent , Adult , Disease-Free Survival , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young AdultABSTRACT
B-cell lymphoma that is unclassifiable and intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt's lymphoma (BL)--(UBL) is an aggressive lymphoma that has simultaneously morphological, immunophenotypical, and cytogenetic signs of both DLBCL and LB. At the same time due to its biological characteristics and clinical manifestations, UBL cannot be referred to as one of the above nosological entities. UBL has been first identified as an individual nosological entity in the 2008 World Health Organization classification. The review details the epidemiology, clinical manifestations, morphological pattern, immunophenotypic and karyotypic features, as well as therapeutic approaches and prognostic factors.
Subject(s)
Antineoplastic Agents/therapeutic use , B-Lymphocytes/immunology , Immunity, Cellular , Lymphoma, B-Cell , Burkitt Lymphoma/diagnosis , Burkitt Lymphoma/drug therapy , Burkitt Lymphoma/immunology , Diagnosis, Differential , Humans , Lymphoma, B-Cell/diagnosis , Lymphoma, B-Cell/drug therapy , Lymphoma, B-Cell/immunology , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/immunologyABSTRACT
AIM: To estimate the informative value of ultrasonography (USG) in the diagnosis of lung injuries in pregnant women with blood system tumors. SUBJECTS AND METHODS: Lung ultrasound was performed in 5 pregnant patients with blood cancers. The women's age was 29-38 years; gestational age was 14-33 weeks. Four women had different types of acute leukemia; one had primary mediastinal large B-cell lymphoma. All the women received chemotherapy for blood cancer. When there were signs of lung injury, USG was conducted, the results of which necessitated therapy or bronchoalveolar lavage (BAL). RESULTS: Three patients developed acute respiratory failure; 2 of them required noninvasive ventilation. Based on the detection of consolidation with a dynamic air bronchogram and pleural effusion, the authors diagnosed bilateral pneumonia and alveolar-interstitial syndrome in 1 patient, right-sided pneumonia in 1, left-sided one in 1, and transfusion-related pulmonary edema in 1. Lung ultrasound did not verify the diagnosis of pneumonia in 1 patient. According to USG data, BAL procedures were performed in 2 patients; one of them was diagnosed as having Pneumocystis pneumonia; the other was found to have no pathogens in lavage fluid. Treatment resulted in clinical improvements and normalization of the lung ultrasound pattern in all the pregnant women. Later on, 4 women delivered via cesarean section done at 32-34 weeks' gestation and gave birth to healthy babies. One patient died from infectious complications after chemotherapy. CONCLUSION: Lung sound may be used to diagnose lung injury in pregnant women with blood cancers.
Subject(s)
Hematologic Neoplasms/diagnostic imaging , Lung/diagnostic imaging , Pneumonia, Bacterial/diagnostic imaging , Pregnancy Complications, Hematologic/diagnostic imaging , Pregnancy Complications, Infectious/diagnostic imaging , Adult , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Gestational Age , Hematologic Neoplasms/complications , Hematologic Neoplasms/drug therapy , Humans , Pneumonia, Bacterial/complications , Pneumonia, Bacterial/microbiology , Pregnancy , Pregnancy Complications, Hematologic/drug therapy , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/microbiology , Treatment Outcome , UltrasonographyABSTRACT
AIM: To characterize a group of patients with B-cell lymphoma (BCLU) unclassified that is intermediate between diffuse large B-cell lymphoma and Burkitt's lymphoma, to identify poor prognostic factors, and to evaluate therapeutic efficiency in patients with BCLU. SUBJECTS AND METHODS: Twenty-five patients with BCLU were examined. Double-hit lymphoma (DHL) was diagnosed in 8 (32%) patients. According to the Ann-Arbor classification of lymphoma, its stages II, III, and IV were diagnosed in 3 (12%), 2 (8%), and 20 (80%) patients, respectively. MYC rearrangement was observed in 11 (48%) out of 23 patients: single-hit lymphoma in 3 patients and DHL in 8 (BCL2+/MYC+ in 6 cases and BCL6+/MYC+ in 2). The expression of Ñ-MYC (cut off ≥40%) was revealed in 17 (74%) out of 23 patients; that of BCL2 (cut off ≥50%) was detected in 14 (58%) out of 24 patients; coexpression of both proteins was seen in 12 (52%) out of 23 patients. The DHL group showed a correlation between the rearrangement of the BCL2+/MYC+ genes and the expression of MYC and BCL2 proteins in 5 out of 6 patients. Taking into account the heterogeneity of the entire patient group, DHL and non-DHL subgroups were considered separately. Both subgroups were comparable by clinical characteristics. BCLU patients younger than 60 years of age received treatment according to the LB-M-04 ± rituximab; those aged 60 or older had CHOP-like regimens ± rituximab. Autologous stem cell transplantation (auto-SCT) was performed in 5 patients belonging to a high-risk group. RESULTS: The 3-year overall survival (OS) was 62% and the 3-year event-free survival (EFS) was 51%. The 3-year OS was lower for the DHL group than that for the non-DHL group (43 and 75%, respectively). CONCLUSION: In the DHL group, both OS and EFS are significantly lower (the risk of poor outcome, including death, is higher) than those in the non-DHL group. It is conceivable that intensified chemotherapy with auto-SCT increases treatment results in patients with BCLU; however, a larger number of observations are needed to obtain valid data.
ABSTRACT
AIM: To study the clinical manifestations, diagnosis, and treatment of lymphoproliferative diseases (LPD) concurrent with tuberculosis. SUBJECTS AND METHODS: In 1990 to 2013, the Hematology Research Center, Ministry of Health of Russia, followed up 4422 patients with LPD. Lymphomas and leukemias were diagnosed using the universally protocols. Tuberculosis was verified by the results of a comprehensive examination involving the histological study of biopsy specimens. RESULTS: Tuberculosis was identified in 85 (2%) patients with LPD. According to the nosological entity, the tuberculosis detection rates were 3% (40/1350) in Hodgkin lymphoma (HL), 1.2% (20/1627) in aggressive lymphomas, 1.4% (16/1136) in mature cell lymphomas and chronic lymphocytic leukemia, and 2.9% (9/309) in hairy cell leukemia. In accordance with its site, pulmonary tuberculosis was 73%; extrapulmonary tuberculosis, 14%; generalized tuberculosis, 12%. In pulmonary tuberculosis, its disseminated and focal involvements were found in 71 and 18% of cases, respectively. Tuberculosis was detected in 43% of the patients with HL in remission; it occurred only in other hemoblastoses in its active phase. When tuberculosis and LPD were simultaneously found, both diseases were concurrently treated. If the chemotherapy of LPD was effective, tuberculosis was cured in all the patients. CONCLUSION: Patients with LPD are a group at increased risk for tuberculosis. The diagnosis of recurrent LPD must be histologically proven. When tuberculosis and LPD are simultaneously found, both diseases should be concurrently treated.
Subject(s)
Leukemia/epidemiology , Lymphoma/epidemiology , Tuberculosis/epidemiology , Adult , Antineoplastic Agents/therapeutic use , Biopsy , Humans , Leukemia/complications , Leukemia/pathology , Lymphoma/complications , Lymphoma/pathology , Risk Factors , Russia/epidemiology , Tuberculosis/etiology , Tuberculosis/therapy , Tuberculosis, Pulmonary/epidemiology , Tuberculosis, Pulmonary/etiology , Tuberculosis, Pulmonary/therapyABSTRACT
AIM: To assess the results of diagnosing and treating Pneumocystis pneumonia (PP) in patients with Hodgkin lymphoma (HL) over 15 years. SUBJECTS AND METHODS: In 1999 to 2013, PP occurred in 22 (3%) of 741 HL patients receiving programmed polychemotherapy (PCT). The male/female ratio was 1:1.1; median age was 32 (18-65) years. Advanced stages (IIB-IV) of the disease were seen in 82% of the patients. The diagnosis of PP was established when Pneumocystis (more than 5 cysts in the specimen) was detected in the lavage fluid by indirect immunofluorescence assay. RESULTS: PP developed after 4 or more cycles of PCT. Along with Pneumocystis, all the cases were found to have additional pathogens: herpes virus in 72% and bacteria and fungi in 33%. All the patients received combined antimicrobial therapy using high doses of intravenous trimethoprim-sulfamethoxazole. Ten (45%) patients required mechanical ventilation (MV). The total mortality in PP was 32% (7 patients died); moreover, none of the patients without MV died whereas the mortality among those who had MV was 70% (7 of the 10 patients died). High death rates (80%) were noted among the patients with recurrent and resistant HL. CONCLUSION: PP should be prevented with trimethoprim-sulfamethoxazole in patients with LH during PCT. If respiratory failure and X-ray signs of interstitial pneumonia appear, there is a need for fibrobronchoscopy with bronchoalveolar lavage and comprehensive microbiological testing of lavage fluid.