Vol 87, No 7 (2015)
- Year: 2015
- Articles: 15
- URL: https://journal-vniispk.ru/0040-3660/issue/view/1802
Editorial
Therapy for Burkitt’s lymphoma according to the BL-M-04 protocol: 12-year experience
Abstract
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/l. 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.
Terapevticheskii arkhiv. 2015;87(7):4-14
4-14
Autologous hematopoietic stem cell transplantation as late high-dose consolidation in adult patients with T-cell lymphoblastic leukemias: Results of a Russian multicenter study
Abstract
Aim. To analyze the efficiency of the ALL-2009 protocol (ClinicalTrials.gov NCT01193933) in patients with T-cell leukemias, particularly the role of autologous hematopoietic stem cell transplantation (auto-HSCT) after non-myeloablative BEAM conditioning, followed by maintenance therapy. Subjects and methods. Since 2009, the ALL-2009 study has enrolled 90 patients with T-cell acute lymphoblastic leukemia (T-ALL), the treatment results were assessed in 86 patients: 6 and 28 patients underwent allogeneic HSCT and auto-HSCT, respectively. A landmark analysis was used to compare survival rates in patients who had undergone auto-HSCT and in those who had not. For this, the median time from complete remission to the date of auto-HSCT was determined (the median was 6 months). Then to compare with the auto-HSCT group, only 27 patients who had been in complete remission for 6 months or more were included in a chemotherapy group. Results. The achievement of complete remission in patients with thymic T-ALL (100%) was significantly higher than in those with early (85.7%) or mature (70%) variants. The patients with early and mature T-ALL as compared to those with thymic T-ALL showed high death rates in the remission induction (7.4 and 10% versus 0) and the patients with mature T-ALL had a higher proportion of refractory forms (20% versus 0). The 5-year overall and relapse-free survival rates in all the T-ALL patients were 66 and 76%, respectively. After auto-HSCT, the risk of recurrence was 0% versus 21% after chemotherapy (p=0.03). The relapse-free survival rates significantly differed in the auto-HSCT and non-auto-HSCT groups: 100 and 66%, respectively (p=0.047). Conclusion. The long-term survival rates obtained during this multicenter study in the T-ALL patients treated according to the ALL-2009 protocol, the basis for which is the principle of continuity of cytostatic effects, are exclusively optimistic. Late consolidation with auto-HSCT following non-myeloablative BEAM conditioning, followed by maintenance therapy, considerably reduces the risk of recurrence.
Terapevticheskii arkhiv. 2015;87(7):15-25
15-25
Clinical and epidemiological characteristics of acute myeloid leukemias in adults according to the data of municipal hematology departments in Moscow
Abstract
Aim. To estimate the incidence of acute myeloid leukemias (AML) in Moscow adults and to evaluate the efficiency of their treatment. Subjects and methods. Data on Moscow residents who were first diagnosed with AML in 2010 were retrospectively collected. The efficiency of their treatment was evaluated from the rates of complete remissions (CR), recurrences, deaths, and 4-year overall (OS) and relapse-free survival (RFS). The data as of September 1, 2013, were analyzed. Results. According to the 2010 pooled materials of the city’s municipal hematology departments, AML (non-M3 types) was diagnosed in 286 patients whose median age at diagnosis was 64.9 years (range, 18.2-92.0 years). The notified incidence rate was 2.9 (3.3 for men and 2.6 for women) cases per 100,000 population. 118 (41%) patients received intensive chemotherapy (ICT); 119 (42%) had chemotherapy with low-dose cytarabine (LDC); 7 (2%) had that with hypomethylating agents (HA); and 42 (15%) had palliative therapy (PT). During first-line therapy, none of the patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the entire group, the early (within the first 60 days) mortality rates were 42% (119 deaths); that of patients with primary refractory disease was 32% (90 deaths). CR was achieved in 77 (27%) patients: 57 (48%) on ICT, 17 (14%) on LDC, and 3 (43%) on HA. Recurrences occurred in 37 (48%) of the 77 patients who had achieved CR at a median follow-up of 43.9 months. Four-year OS in all the patients receiving PT was 9.8±1.9% (18.2±3.9% in the patients on ICT versus 4.5±2% in those of LDC; p=0.028); 4-year RFS was 36.1±5.7% (39.6±6.7% in the patients on ICT versus 31.3±11.6% in those on LDC; p=0.8). Conclusion. High mortality rates in the induction, which are caused by the limited resources of accompanying therapy, poor sanitary conditions, and no own opportunities to perform allo-HSCT, remain a key problem of AML therapy in adults.
Terapevticheskii arkhiv. 2015;87(7):26-32
26-32
Treatment in adult patients with acute myeloid leukemias with hyperleukocytosis at disease onset
Abstract
Aim. To evaluate the efficiency of the treatment policy for patients with acute myeloid leukemia (AML) and hyperleukocytosis (HL), which is aimed at preventing rapid hypercytolysis and massive tumor lysis (cytolysis) syndrome and/or at reducing the degree of the latter at the start of induction polychemotherapy. Subjects and methods. In 2010 to 2014, the Hematology Research Center, Ministry of Health of Russia, treated 92 patients with AML, out of them 18 patients were found to have white blood cell counts of 100 to 408∙109/l (median, 130∙109/l) at the onset of the disease. All the examinees received cytoreductive therapy with hydroxyurea and, in presence of leukostasis and/or leukocytosis (≥150∙109/l), with leukocytapheresis. In case of reduced leukocytosis, plasmapheresis was carried out to prevent (treat) cytolysis. Daunorubicin was injected on days 3—5 of the 7+3 induction cycle. Results. The signs of leukostases were detected in more than half of the 18 patients with higher white blood cell counts: 13 (72%) with lung injury, including 5 of them with signs of respiratory distress syndrome, 6 (27.8%) with neurological symptomatology, 7 (38.9%) with disseminated intravascular coagulation syndrome, including 1 with intracranial hemorrhage. Cytoreduction therapy with hydroxyurea (10 mg/kg/day) was performed 1—5 (median 2) days before initiating induction chemotherapy in 17 patients; 9 patients underwent 1—2 (median 2) leukocytapheresis sessions. Sixteen patients received 1—4 (median 2) plasmapheresis sessions prior to and within the first days of the 7+3 treatment regimen. Daunorubicin (60 mg/m2) was administered to 16 patients on days 5—7 of the 7+3 cycle and to 2 patients on days 3—5 of the cycle. There were no signs of severe cytolysis with the development of multiple organ dysfunction in any patient. 50% (9/18) achieved remission after the first 7+3 cycle and 7 more examinees did after the second cycle. Thus, the remission rate was 89%; early mortality was 5.5% (1/18), three-year overall and relapse-free survival rates were 50%. Conclusion. Adequate cytoreductive and accompanying therapies for AML with HL can virtually completely prevent massive tumor cytolysis syndrome and early mortality during the first days of induction chemotherapy.
Terapevticheskii arkhiv. 2015;87(7):33-40
33-40
Age-related characteristics of the efficacy of different glucocorticosteroids in the therapy of acute lymphoblastic leukemia
Abstract
Aim. To determine predictors for decision-making on a differential approach to choosing glucocorticosteroids (GCS) for children and adolescents with acute lymphoblastic leukemia (ALL). Subjects and methods. The analysis covered 1064 primary patients aged to 1 to 18 years with ALL who had been registered at the clinics of Russia and Belorussia in April 2002 to November 2006. Before induction therapy, the patients were randomized into a dexamethasone (DEXA) 6 mg/m2 group (n=539) and a methylprednisolone (MePRED) 60 mg/m2 one (n=525). Results. The entire group showed no statistically significant differences in survival rates between the patients receiving DEXA or MePRED. However, an analysis of age groups revealed the benefits of DEXA in children younger than 14 years (the event-free survival (EFS) was 76±2 and 71±2%, respectively (p=0.048); the overall survival (OS) was 81±2 and 77±2%, respectively (р=0.046); therapy-induced mortality was 6.4% (DEXA) and11.1% (MePRED) (р=0.014); the rate of isolated extramedullary relapses was 1.5% (DEXA) and 4.4% (MePRED) ( р=0.009). At the same time, EFS and OS in 14-to-18-year-old adolescents were statistically significantly higher than in those who used MePRED (EFS, 65±6 and 52±6%, respectively (р=0.087); OS, 72±6 and 61±6%, respectively; (р=0.17). Conclusion. The findings suggest that it is possible that the choice of a GCS for ALL therapy must be also based on a patient’s age. There is a need for further studies of this matter in prospective randomized multicenter trials in children and adolescents.
Terapevticheskii arkhiv. 2015;87(7):41-50
41-50
Late cardiotoxicity of high-dose chemotherapy according to the modified NHL-BFM-90 program in adult patients with diffuse large B-cell lymphoma
Abstract
Aim. To evaluate the late cardiotoxicity (CT) of high-dose chemotherapy (CT) according to the modified NHL-BFM-90 (mNHL-BFM-90) protocol in adult patients with diffuse large B-cell lymphoma (DLBCL). Subjects and methods. The results of electrocardiography (ECG) and echocardiography (echoCG) were analyzed in 40 DLBCL patients treated according to the mNHL-BFM-90 program in the Hematology Research Center (HRC), Russian Academy of Medical Sciences (RAMS), in 2002 to 2009. A study group consisted of 20 men and 20 women whose age was 31 to 76 years; median age was 56.5 years at the time of their examination and the median follow-up time after therapy was 6 years. The individual cumulative dose of doxorubicin was 150-300 mg/m2. A comparison group included 19 patients receiving СНОР/R-СНОР CT in HRC, RAMS, in 2002 to 2009. Out of them, there were 8 men and 11 women whose age was 39 to 78 years median age was 70 years at the time of their examination. The individual cumulative dose of doxorubicin was 200—400 mg/m2. ECG and echoCG were carried out before and 5 years or more after CT. Results. Out of the 40 patients with DLBCL, the signs of subclinical cardiomyopathy (CMP) were detected in 24 (60%) patients; no clinical manifestations of congestive heart failure (CHF) were found in any patient. In the comparison group of 19 patients receiving СНОР/R-СНОР CT, 14 (74%) patients were found to have signs of subclinical CMP and no clinical signs of CHF. The summary toxicity index significantly depended on age (p=0.03) and a history of heart disease (p=0.3); it was significantly higher after CHOP/R-CHOP CT (p=0.05). There was a statistically significant relationship of the risk of subclinical CMP to the history of heart diseases (p=0.05). Conclusion. Late cardiotoxicity of the mNHL-BFM-90 program does not exceed the toxicity of standard CHOP/R-CHOP therapy. Post-CT Echo-CG and ECG findings showed that the patients with the most marked subclinical signs of CMP in both groups had cardiotoxicity risk factors, such as coronary heart disease, hypertensive disease, or diabetes in their history. No clinically significant CHF was identified in any patient.
Terapevticheskii arkhiv. 2015;87(7):51-57
51-57
Molecular analysis of immunoglobulin genes in the tumor B cells in splenic marginal zone lymphoma
Abstract
Aim. To determine the immunoglobulin variable heavy chain (IgVH) genes and their somatic mutations and to compare these data with the clinical and laboratory parameters of patients and the outcomes of the disease. Subjects and methods. The investigation enrolled 24 patients (9 men and 15 women whose age was 32 to 77 years (median age, 60 years) with splenic marginal zone B-cell lymphoma (SMZBCL). The latter was diagnosed on the basis of histological and immunohistochemical examinations of a bone marrow trephine biopsy specimen, immunophenotyping of peripheral lymphoid cells or bone marrow aspirates. Results. The mutational status of the IgVH genes was analyzed in all the 24 patients. It was found that the tumor cells contained mutated IgVH genes (the VH1-family genes participated in most cases) in 15 (62.5%) patients with SMZBCL and unmutated ones in 9 (37.5%). There was a tendency towards more common tumor progression in patients with unmutated IgVH genes than in those with mutated ones. Conclusion. The presence of SMZBCL cases with both mutated and unmutated IgVH genes and the higher frequency of the VH1-2 gene are likely to indicate the molecular heterogeneity of the origin of this lymphoma.
Terapevticheskii arkhiv. 2015;87(7):58-63
58-63
Clinical and morphological features of different types of Castleman’s disease
Abstract
Aim. To study the clinical features of Castleman’s disease (CD) and to elaborate therapeutic approaches in its different morphological types. Subjects and methods. The clinical and laboratory data were studied in 59 prospectively examined patients and 17 retrospectively examined ones with CD who had been treated at the Outpatient Department, Hematology Research Centre, in 1996 to 2014. There were a total of 37 men (median age, 36 years) and 39 women (median age, 34 years). The diagnosis was established from the results of histological and immunohistochemical examinations of removed lymph nodes (LN) or tumors in all the cases. Results. A hyaline vascular variant (HVV) with local LN involvement was diagnosed in 38 (50%) patients; a plasma cell variant (PCV) was in 38 (50%); among the latter, 17 (22%) patients were found to have local involvement and 21 (28%) had generalized (multicentric) involvement (multicentric Castleman’s diseases (MCD)). Five (24%) patients with MCD were established to be infected with human herpesvirus type 8 (HHV-8). HVV was more frequently diagnosed in women (4%) than in men (29%); PCV was equally common in both men (47%) and women (53%); MCD was statistically significantly more frequently encountered in men (86%) than in women (14%) (p=0.05). The basic involvement areas in local HVV and PCV were peripheral (38%), mediastinal (29), retroperitoneal (18%), abdominal (9%), and small pelvic (6%) LNs. HVV and local PCV were benign and these were cured by surgical removal of LNs involved in the pathological process. MCD took its aggressive course with obvious constitutional symptoms, generalized lymphadenopathy, hepatosplenomegaly, hypergammaglobulinemia, autoimmune hemolysis, thrombocytopenia, and involvement of extranodal foci in the pathological process. MCD transformation to plasmablastic lymphoma was observed in 4 of the 5 HHV8-positive patients and followed by a poor outcome. The prognosis of untreated MCD was unfavorable. In a number of cases prednisolone monotherapy worsened prognosis and the MCD patients receiving timely multiple-drug R-CHOP or R-VD chemotherapy could achieve sustained remission (the 5-year overall survival was 55%). Conclusion. CD must be included into the differential diagnosis of lymphadenopathies. When specific treatment is performed, the prognosis of HVV and local PCV is favorable: the disease is surgically cured in 95% of cases. Multidrug chemotherapy according to the B-cell lymphoproliferative disease program is indicated for the treatment of MCD: sustained remission can be achieved by the use of R-CHOP or R-VD programs. The HHV-8-positive variants of MCD increase the probability of transforming the disease to incurable plasmablastic lymphoma. Overall, prognosis and therapy choice in HIV-negative patients with CD depend on the histological variant of the disease, the extent of a tumor, and HHV-8 infection.
Terapevticheskii arkhiv. 2015;87(7):64-71
64-71
Dialysis-dependent renal failure in patients with multiple myeloma: Reversibility factors
Abstract
Aim. To establish the reversibility factors of dialysis-dependent renal failure (RF) in patients with multiple myeloma (MM) treated according to bortezomib-containing programs. Subjects and methods. The efficiency of treatment according to bortezomib-containing programs was evaluated in 40 patients with first diagnosed MM and dialysis-dependent RF. Prior to treatment, 34 patients underwent needle renal biopsy. The early mortality rate was 5%. Results. After treatment according to bortezomib-containing programs, 83% of the patients could achieve a hematologic response, including 66% who had complete and very good partial remission (CR and vgPR). A renal response (RenR) was observed in only 26% of the patients. RenR to antitumor therapy was found to be determined by the morphological variant of nephropathy. Improved kidney function was observed only in cast nephropathy (CN) and absent in other types of kidney injury. In CN, the rate of RenR depends on the degree of renal tubulointerstitial fibrosis at the initiation of treatment. Kidney function improved in 20% of the patients with disseminated tubulointerstitial fibrosis and in 57% of those with minimal fibrotic changes (p=0.04). To achieve RenR, it is important to have an early antitumor response in addition to baseline morphological changes in the nephrobiopsy specimen. When the number of monoclonal light chains (LC) in urine was reduced to 100 mg/day after 2 cycles of induction therapy, RenR was 55%; with a lower antitumor response it was as high as 28% (p=0.04). A LC decrease to the values of vgPR after 2 cycles of induction therapy was noted in only 32% of the patients; 44% of the patients achieved vgPR or CR after an average of 6 (3—13) therapy cycles. Conclusion. In MM patients with dialysis-dependent RF, RenR was caused by the morphological variant of kidney injury and by the degree of tubulointerstitial fibrosis at the therapy initiation, as well as by the rate at which monoclonal LCs reduced.
Terapevticheskii arkhiv. 2015;87(7):72-76
72-76
Factors influencing recovery in patients with hemoblastoses and candidemia
Abstract
Aim. To study the factors influencing the results of treatment for candidemia (CE) in patients with blood system tumors. Subjects and methods. The investigation enrolled patients with hemoblastoses and CE. 30-day all-cause mortality was analyzed. Results. In an 8-year period (2006—2013), CE was diagnosed in 55 patients (median age, 50 years); there was a preponderance of patients with lymphomas (47%) and acute leukemias (27%). The causative agents of CE were C. albicans (38%), С. parapsilosis (17%), С. krusei (11%), C. guilliermondii (11%), C. lusitaniae (6%), C. tropicalis (6%), С. glabrata (3%), С. famata (3%), C. pelliculosa (3%), and C. kefyr (2%). 30-day all-cause mortality was 43.6%. Recovery was statistically significantly more frequently seen following removal of a central venous catheter (67% versus 13%; p=0.004; odds ratio (OR), 14); after use of an antifungal drug on day 1 of isolation of Candida spp. from blood cultures (62% versus 13%; p=0.01; OR, 12); and that of echocandin as a first-line agent (86% versus 42%; p=0.005; OR, 8.4). The poor predictors were septic shock (5% recovery rate versus 86% in the patients without this factor; p<0.0001; OR, 0.01), granulocytopenia (42% versus 88%; p=0.001; OR, 0.1); use of amphotericin B as a first-line drug (26% versus 71%; p=0.002; OR, 0.15); hemoblastosis recurrence or resistance (39% versus 73%; p=0.01; OR, 0.24). Multivariate analysis showed the positive impact of antifungal administration on day 1 of isolation of Candida spp. from blood cultures on treatment results (p=0.03; OR, 27). Conclusion. High mortality rates were noted in the patients with hemoblastoses and CE. The recovery rates were statistically significantly higher after use of echinocandin as a first-line agent, after that of an antifungal agent on day 1 of positive blood cultures, after removal of a central venous catheter, and hemoblastosis remission.
Terapevticheskii arkhiv. 2015;87(7):77-87
77-87
Bacterial infections in the early period after allogeneic bone marrow transplantation
Abstract
Aim. To study the incidence and risk factors of bacterial infections and the efficiency of empirical antibacterial therapy in patients in the early period after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Subjects and methods. The study included 155 patients who had undergone allo-HSCT. Myeloablative conditioning was used in 39% of the patients. All the patients with neutropenia (NP) received antibiotic prophylaxis with fluoroquinolones until recovery of white blood cell counts or before systemic antibiotic therapy. Antibiotic therapy and a change of antibiotics were considered effective in achieving persistent apyrexia and positive clinical changes. Results. The incidence of febrile neutropenia (FNP) in the patients after allo-HSCT was 63%. The duration of grade 4 leukopenia did not depend on the conditioning regimen. Neutropenic fever was noted in 68% of the patients with NP lasting longer 10 days. In shorter-duration NP, the rate of fever was 52%. Among the patients with mucositis, the frequency of FNP episodes was significantly higher (69% versus 52%; p=0.02). The diverse spectrum of isolated bacteria was represented as gram-positive cocci in 45% of cases; Klebsiella pneumoniae and Enterobacter cloacae were more common among gram-negative ones (24%). The efficiency of empirical antibiotic therapy was 57% (25% for monotherapy, 53% for combined treatment regimens); the early mortality was 2%. Conclusion. Infection-related FNP is noted in 68% of the patients in the early posttransplantation period and the risk factors of its development are NP duration, oral colonization with pathogens, and the absence of invasive mycosis after allo-HSCT. Antibacterial prophylaxis significantly decreases the incidence of bacterial complications. Empirical monotherapy with third- or fourth-generation cephalosporins and carbapenems against infections in a transplantation patient is as effective as their combination with aminoglycosides.
Terapevticheskii arkhiv. 2015;87(7):88-93
88-93
Isolated sacral injury in hairy cell leukemia: A case report and analysis of literature data
Abstract
Hairy cell leukemia (HCL), a chronic B-cell lymphoproliferative disease with special villous morphology and immunophenotypic markers of lymphoid cells, is characterized by the involvement of bone marrow and spleen. The paper describes a case of a 29-year-old female patient without abnormal clinical blood tests and myelograms, with normal spleen sizes, in whom the only manifestation of HCL was massive scrotal injury with a soft tissue component in the small pelvic cavity.
Terapevticheskii arkhiv. 2015;87(7):94-96
94-96
The specific features of diagnosis of mixed-phenotype acute leukemia: A combination of B-cell antigen expressions according to the results of flow cytometry and morphological markers of myeloid differentiation in blast cells: A clinical case
Abstract
This rare type of acute leukemia, blast cells of which express myeloid and/or lymphoid markers, is mainly diagnosed using flow cytometric findings. The paper describes a clinical case of mixed-phenotype acute leukemia, in which B-cell lymphoid antigen expressions were revealed by a flow cytometric technique, while bone marrow morphological specimens showed the signs of myeloid differentiation specific to blast cells. It is concluded that there is a need for a comprehensive examination of patients with new-onset acute leukemia and for an aggregate analysis of flow cytometric results with morphological and cytochemical findings.
Terapevticheskii arkhiv. 2015;87(7):97-100
97-100
Composite lymphoma: Simultaneous development of three different lymphomas in a single patient: A clinical case
Abstract
In the past decades, there has been an increase in the incidence of malignancies, including polyneoplasms. Composite synchronous lymphoma characterized by the simultaneous development of several lymphoproliferative diseases occurs very rarely. This paper describes a case of development of 3 different lymphomas in the same patient. Aggressive T-cell lymphoma and indolent B-cell lymphoma are diagnosed during lifetime; primary central nervous system lymphoma is verified only by examination of autopsy material. Three different lymphomas could be identified by an integrated assessment of their clinical picture and by current diagnostic techniques, such as histology, immunohistochemistry, and molecular genetics.
Terapevticheskii arkhiv. 2015;87(7):101-104
101-104
SOCS1 gene mutations in patients with diffuse large B-cell lymphoma
Abstract
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of diseases, which accounts for 30% of all non-Hodgkin lymphomas. Current molecular studies have confirmed that there are several DLBCL subtypes characterized by different cellular origin, cytogenetic profile, molecular genetic disorders, and different pathogenesis. Impaired JAK-STAT signaling is a part of the pathogenesis of various cancers, including DLBCL. The review deals with the molecular genetic aspects of the occurrence of DLBCL and the function of the SOCS1 gene that has been proven to be responsible for the development of several cancers. Mutations of this gene result from spontaneously impaired B-cell somatic hypermutation and they are frequently inactivating. The presence of point mutations in the functionally significant region of this gene in DLBCL could identify a group of patients with poor prognosis during standard chemotherapy.
Terapevticheskii arkhiv. 2015;87(7):105-111
105-111