CUTANEOUS MANIFESTATIONS OF ANGIOIMMUNOBLASTIC T-CELL LYMPHOMA

Background: Angioimmunoblast T-cell lymphoma (AITL) is a rare T-cell lymphoproliferative disease that is accompanied by generalized lymphadenopathy, hepatosplenomegaly, intoxication symptoms and extranodal lesions. The extranodal manifestations of the disease frequently involve various skin changes. One of the first such manifestations is maculopapular rashes observed in about half of AITL patients and usually preceding the appearance of lymphadenopathy. Other forms of skin lesions accompany the disease considerably less frequently.Aim: To characterize the range of skin changes in patients suffering from AITL, to establish a correspondence between the nature of skin changes and their histological picture.Materials and methods: 54 AITL patients were being treated at the National Research Centre for Hematology from 2000 to 2017, with the male/female ratio being 30/24. The median age was 61 (29–81) years.Results: Changes in the skin were observed in 24 (44.4 %) of 54 AITL patients, out of whom 18 (75 %) and 6 (25 %) were male and female patients, respectively. Maculopapular rash was observed in 22 (91.7 %) out of 24 patients. The morphological and molecular investigations of skin biopsy specimens exhibiting maculopapular rash demonstrated nonspecific reactive changes. Patients with maculopapular rash demonstrated an increase in the level of total (polyclonal) IgE. Specific skin lesions detected in 8 (14.8 %) cases were represented by a ‘livedo reticularis’, focal skin hyperpigmentation, erythroderma, left eyelid tumour and tumour in 3, 2, 1, 1 and 1 cases, respectively.Conclusion: Maculopapular rash frequently observed in AITL patients is a reactive process not associated with a specific skin lesion. Specific skin lesions in AITL are much less common and can be represented by various forms. In some AITL cases, skin changes of the reactive and tumour nature can be simultaneously observed

First experience of using Brentuximab vedotin and modified program NHL-BFM-90 in the front-line treatment of patient with anaplastic large-cell lymphoma: a case report and a review of literature

Nodal anaplastic ALK-negative large cell lymphoma (nALCL, ALK-) is a Т-cell lymphoma that is characterized by aggressive clinical course and low sensitivity to СНОР (cyclophosphamide, doxorubicin, vincristine, prednisolone) and other chemotherapy regimen. In the article we present a literature review and describe our clinical case of nALCL, ALK-. For the first time a combination of Brentuximab vedotin with modified program NHL-BFM-90 was used as a first-line therapy. As a result of immunochemotherapy a complete antineoplastic effect was obtained. For consolidation of this effect high-dose chemotherapy with following autologous blood stem cell transplantation was performed. The chosen treatment tactics allowed to achieve a complete remission in a medium risk group patient

Diagnostics and treatment challenges of Ph-like acute lymphoblastic leukemia: a description of 3 clinical cases

B-cell acute lymphoblastic leukemia (B-ALL) is a diverse group of malignant blood disorders both with regard to the biological properties of the tumor and to therapeutic approaches. Immunophenotyping, molecular genetic techniques, whole-genome sequencing characterize B-ALL as a very diverse group for sensitivity to chemotherapy and prognosis. We present three clinical cases of patients with B-ALL and expected good response to standard therapy, in whom standard protocol treatment failured: refractoriness, persistence of minimal residual disease (MRD), and progression (MRD increase). The remission in these patients was achieved after chemotherapy change to immunological targeted therapy. Nowadays a unified therapeutic approach to all primary patients of the B-ALL is considered generally outdated. Great efforts are carrying out to develop molecular genetic classifications. The molecular dissection of subtypes of B-ALL goes on, and new protocols for selective treatment with targeting are clearly outlined for each subtype of B-ALL

Coinheritance of HbD-Punjab/β+-thalassemia (IVSI+5 G-C) in patient with Gilbert's syndrome

Thalassemia and qualitative hemoglobinopathy are hereditary disorders of Hb synthesis that lead to change in the Hb conformation or a decrease in the synthesis of structurally normal Hb, and consequently, to erythron pathology. Many variants of Hb are unstable or have altered affinity for oxygen, and, in heterozygous form can be associated with clinical and hematological manifestations (hemolytic anemia, hypochromic microcytic anemia, erythrocytosis). HbD-Punjab [β121 (GH4) Glu → Gln; HBB: C.364G> C] is variant of Hb carrying the amino acid substitution in the 121 position of β-globin chain. In all cases reported so far, patients with HbD-Punjab/β+-thalassemia (IVSI+5 G-C) combination experienced typical thalassemia with hypochromic microcytosis. HbD-Punjab was detected by electrophoresis from 37 to 94% of total Hb. The article describes rare clinical case of the cohabitation of HbD-Punjab/β+-thalassemia (IVSI+5 G-C) in a patient with homozygous variant of Gilbert's syndrome observed in AS Loginov Moscow Clinical Scientific Center

Assessment of bone marrow biopsy in patients with masked polycythemia vera

Masked polycythemia vera (PV) is characterized by presence ot Jak2 mutation, specific morphological pattern in the bone marrow biopsy, and the lack demanding levels of Hb in accordance with criteria WHO, 2008 for PV. The purpose of this study was assessment of the pathomorphologic peculiarities of bone marrow biopsies in patients with masked PV. The group of 24 patients with masked PV was formed on the basis of morphological picture, clinical, laboratory and molecular data. Histological examination of bone marrow trephine biopsy in most cases showed hypercellular marrow 18/24 (75%) (age adujsted). Enlargement and rejuvenation of erythroid lineage was observed in 23/24 and 22/24 cases (95.9% and 91.7%). The histotopography of megakaryocytes in the majority of cases, 20/24 (83.3%) was characterized by discrete arrangement of megakaryocytes and forming intertrabecular loose clusters (3-16 cells). Typical for PV morphology of megakaryocytes was detected in the majority of cases, 19/24 (79.2%). There were 5/24 (20,8%) cases with characteristic features of essential thrombocythemia (ЕТ-like features). The grade of stroma fibrosis in all cases was MF-0. Morphological picture in bone marrow biopsy of patients with masked PV was characteristic for PV in most cases. However, in some cases of masked PV the morphology part of megakaryocytes was similar to essential thrombocythemia or pre-fibrotic/early stage of primary myelofibrosis.Маскированная истинная полицитемия (ИП) является клинической формой истинной полицитемии, для которой характерно наличие мутации JAK2, соответствующей морфологической картины в костном мозге, и недостаточный для установления диагноза по критериям ВОЗ 2008 уровень НЬ. Целью данного исследования была оценка морфологии костного мозга на материале трепанобиоптатов костного мозга у пациентов с маскированной формой ИП. Методы. На основании клинических данных при динамическом наблюдении, патоморфологического диагноза, данных молекулярного исследования была сформирована группа из 24 пациентов с маскированной ИП. С помощью разработанного гистологического кодификатора проводилось детальное гистологическое исследование первичных трепанобиоптатов костного мозга. При оценке степени ретикулинового фиброза срезы окрашивали по Гомори. Результаты: При гистологическом исследовании трепанобиоптатов костного мозга в большинстве случаев определялся гиперклеточный (относительно возрастной нормы) костный мозг 18/24 (75%). Во всех случаях выявлена пролиферация мегакариоцитов, полиморфных по размеру и морфологии, с наличием атипичных форм с гиперсегментированными ядрами, со зрелой морфологией. Расширение и омоложение эритроидного ростка наблюдалось соответственно в 23/24 и 22/24 случаях (95,9% и 91,7%). При оценке гистотопографии мегакариоцитов в большинстве случаев 20/24 (83,3%) определялось сочетание разрозненного расположения мегакариоцитов и формирование рыхлых кластеров (3-16 клеток). Характерная для истинной полицитемии морфология элементов мегакариоцитарного ростка наблюдалась в большинстве случаев 19/24 (79,2%). В 5/24 (20,8) случаев были выявлены признаки, характерные для эссенциальной тромбоцитемии («ЕТ-like» признаки). Степень фиброза стромы во всех случаях составляла MF-0. Выводы: Морфологическая картина костного мозга пациентов с маскированной формой ИП в большинстве проанализированных нами случаев была характерной для истинной полицитемии. Вместе с тем, в части наблюдений при маскированной ИП в морфологии и гистотопографии мегакариоцитарного ростка определялись признаки, характерные для эссенциальной тромбоцитемии или пре-фиброзной/ранней стадии первичного миелофиброза

Results of program acute myeloid leukemia therapy use in National Medical Research Center for Hematology of the Ministry of Health of Russian Federation

Objective. To analyze treatment results of 172 patients with acute myeloid leukemia (AML) aged 18-60 years in National Medical Research Center for Hematology of MHRF. Materials and methods. Inductive and consolidation program for 139 (80%) patients was based on a standardized protocol: 4 courses “7+3” with different anthracycline use (2 courses of daunorubicin, idarubicin, mitoxantrone) and continuous use of cytarabine on the second inductive course. In 20% of patients cytarabine courses at the dose of 1 g/m2 2 times a day for 1-3 days combined with idarubicin and mitoxantrone were used as two consolidation courses. Allogenic bone marrow transplantation was performed in the first complete remission (CR) period in 40% of patients. Results. The frequency of CR achievement in all patients was 78.6%, refractory forms were observed in 13.9% of patients, early mortality - in 7.5% of patients. Seven-year overall survival (OS) rate was 40.7%, relapse free survival (RFS) - 43.2%. When estimating effectiveness depending on cytogenetic risk group it was demonstrated that 5-year OS and RFS in patients with translocation (8; 21) cannot be considered as satisfying, it accounted for 50 and 34%, respectively. At the same time in patients with 16th chromosome inversion (inv16) these characteristics accounted for 68.6 and 63.5%. Acquired results forced reconsidering of the consolidation program in AML patients of this subgroup. The median time to allogenic blood stem cells transplantation (allo-BSCT) in patients with first CR was 6.5 months that was taken as a reference point in landmark analysis of patients in whom allo-BSCT was not performed. Landmark analysis showed that in AML patients of favorable prognosis group allo-BSCT does not significantly reduce the probability of relapse (0 and 36%) and does not influence RFS (33 and 64%). In patients of border-line and poor prognosis allo-BSCT significantly reduces relapse probability (26 and 66%; 20 and 100%) and significantly increases a 7-year RFS (68.7 and 30%; 45.6 and 0%). Allo-BSCT also results in significant RFS increase and reduces the probability of relapse (25 and 78%) in patients in whom CR was achieved only after the second induction course. At the same time allo-BSCT does not influence patients who achieved CR after the first treatment course: 55 and 50%. Conclusion. Multivariate analysis showed that cytogenetic risk group (HR=2.3), time of CR achievement (HR=2.9), and allo-BSCT transplantation (HR=0.16) are independent factors for disease relapse prognosis after achieving CR

Genetic Lesions in Russian CLL Patients with the Most Common Stereotyped Antigen Receptors

Chronic lymphocytic leukemia (CLL) is one of the most common B-cell malignancies in Western countries. IGHV mutational status is the most important prognostic factor for this disease. CLL is characterized by an extreme narrowing of the IGHV genes repertoire and the existence of subgroups of quasi-identical stereotyped antigenic receptors (SAR). Some of these subgroups have already been identified as independent prognostic factors for CLL. Here, we report the frequencies of TP53, NOTCH1, and SF3B1 gene mutations and chromosomal aberrations assessed by NGS and FISH in 152 CLL patients with the most common SAR in Russia. We noted these lesions to be much more common in patients with certain SAR than average in CLL. The profile of these aberrations differs between the subgroups of SAR, despite the similarity of their structure. For most of these subgroups mutations prevailed in a single gene, except for CLL#5 with all three genes affected by mutations. It should be noted that our data concerning the mutation frequency in some SAR groups differ from that obtained previously, which could be due to the population differences between patient cohorts. The research in this area should be important for better understanding the pathogenesis of CLL and therapy optimization