HEMATOLOGIC MALIGNANCIES: DIAGNOSIS, TREATMENT, SUPPORTIVE CARE
Hodgkin lymphoma (HL) represents one of the great success stories in hematology going from a uniformly fatal disease; to one that is curable in the vast majority of cases. Despite this success; approximately 5–10 % HL patients are refractory to initial treatment and 10–30 % of patients will relapse after achieving an initial complete remission. The standard treatment is second-line therapy followed by autologous hematopoietic stem cell transplantation (autoHSCT); which cures an additional 50 % of patients. Brentuximab Vedotin; “antibody-drug conjugate”; dramatically changed the possibilities of therapy for relapses/refractory HL. The article presents a review of the literature on the treatment of relapses/refractory HL.
In 2004–2016 we prospectively observed 59 oncohematology patients with mucormycosis; 21 children and 38 adults. The most frequent underlying diseases were acute myeloid leukemia and acute lymphoblastic leukemia (64 %); and main risk factors were сytostatic chemotherapy and allogeneic HSCT with prolonged (median – 30 days) neutropenia and lymphocytopenia. The etiology agents were Rhizopus spp. (47 %); Rhizomucor spp. (28 %); Lichtheimia corуmbifera (17 %) and Mucor spp. (8 %). Lichtheimia corуmbifera was found more often in children; Rhizopus and Mucor spp. in adults. Pulmonary mucormycosis was main clinical form (73 %); and ≥2 organs involvement was noted in 44 % patients. Antifungal therapy was used in 78 % patients; surgery – in 47 %. In treated with antifungals patients 12 weeks overall survival was 59 %. The positive prognostic factors were remission of underlying disease and combination antifungal therapy.
Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) is a rare subgroup of lymphomas. This disease is predominantly found in older people and often has extranodal involvement including skin and soft tissues. To verify the diagnosis, it is necessary to perform histological and immunohistochemical tests, which show the expression of CD30 activation antigen in different proportions (less than 10 %, not more than 80 %) in addition to the expression of other T-cell antigens (CD2, CD4, CD5, CD7). When choosing the induction regimen in older people with relevant cardiac history, it is preferable to use non-anthracycline-containing chemotherapy courses. However, despite the low intensity of such regimens, treatment of elderly patients is associated with high risk of side effects. Using new drugs (monoclonal antibodies, epigenetic agents) in combination with polychemotherapy is a promising direction opening a possibility of successful management for all patients including those older than 65 years. In the described clinical case of PTCL-NOS, the patient had primary refractory disease. Significant clinical response (complete remission) was achieved as a result of targeted therapy with brentuximab vedotin containing anti-CD30 chimeric antibody conjugated to a microtubuledisrupting agent (monomethyl auristatin E) without toxicity and any infections. In case of ambiguous situation (an increase in the size of one of the tumor sites with regression of others, signs of infection – hyperemia, perifocal edema, the spread of the necrosis zone), histological verification is necessary to confirm the disease progression.
Background. Thrombosis and hemorrhage are the main category of complications, that affects the overall survival (OS), quality of life and therapy option choice in essential thrombocythemia (ET). Molecular marker presence (JAK2V617F (JAK2+), MPL (MPL+), CALR (CALR1+-type 1, CALR2+-type 2) or its absence (triple-negative status (TN)) in ET supposed to impact on the clinical course, thrombosis rate and ET prognosis.
The aim of this study was to investigate interactions between the presence of molecular marker, thrombosis/bleeding rates and the OS in ET.
Methods. Outpatient’s charts of 240 ET patients, who had been diagnosed with ET at our institution according to WHO 2008 criteria. The following data were assessed: complete blood count, bone marrow biopsy results, bone marrow cytogenetic, the restriction fragment length polymorphism (RFLP) results used for JAK2V617F detection, in case of JAK2V617F-negative status the PCR-RFLP results (MPL detection) and the direct sequencing results (CALR detection). Different thrombotic/bleeding complications rates were analyzed. The OS in ET patients was compared according to complications and IPSET-thrombosis groups.
Results. Among 240 pts 183 (76.3 %) hadn’t any thrombotic complication or bleeding event (no complications/NC), 57/240 (23.7 %) had complications: 49/57 (85.9 %) reported arterial or/and venous thrombosis, stroke or heart failure (thrombosis+) and 11/57 (19.3 %) had bleeding events (hemorrhage+). Thrombotic complications in JAK2+ had 27.4 % (50/182) pts, in TN – 30.7 % (8/26) pts, in CALR1+ – 18.2 % (2/11) pts and no cases of thrombosis were detected in CALR2+ and MPL+ subgroups (p < 0,001). There were significant statistical differences in median platelet count as follows: 742 . 10 9/L (thrombosis+) and 937 . 10 9/L (hemorrhage+) (p = 0.003). No significant statistical differences in median hemoglobin and leukocyte count (р = 0.75 and р = 0.47) were detected. There were more than a half pts older than 60 years in groups NC (51 %) and thrombosis+ (59 %) and in group hemorrhage+ only 36 % (p < 0,001). Cardiovascular risk factors were reported in 24 % pts (NC), 69 % pts (thrombosis+) and 36 % pts (hemorrhage+) (p < 0,001). There were no significant statistical differences in follows risk factors as platelets count > 1000 . 10 9/L and leukocytosis > 11 . 10 9/L (р = 0.85 and р = 0.72). No significant differences in OS among groups NC, thrombosis+ and hemorrhage+ (р = 0.21) and IPSET-thrombosis groups (р = 0,068) were found.
Conclusion. Along with common thrombotic risk factors (age > 60 and cardiovascular risk factors) mutational status may help to identify ET course. Leukocytosis > 10 . 10 9/L and thrombocytosis > 1000 . 10 9/L cannot be assessed as independent thrombosis risk factors in ET. The JAK2V617F mutation was associated with increased risk of thrombotic complications in ET. CALR mutations were associated with lower thrombosis risk, comparing to JAK2+ status despite the fact of CALR+ patients had higher platelets level.
HEMATOPOIETIC STEM CELL TRANSPLANTATION
Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective approach to cure numerous malignant and nonmalignant diseases. This method is more available now, respectively the number of survivors – recipients of HSCT increases every year. Among long-term complications of HSCT secondary solid cancers are one of the most life-threatening. We discuss different types of secondary solid tumours after HSCT and describe international recommendations of their screening and diagnostic. Several case reports from the single center could illustrate these serious late effects.
Secondary malignant diseases are dangerous long-term complications of allogeneic hematopoietic stem cell transplantation (HSCT). This article describes the group of secondary lymphoid neoplasms and presents a rare case of secondary Hodgkin disease in a 21-year patient 6 years after HSCT due to acute myeloid leukemia. This complication should be distinguished from the Hodgkin-like posttransplant lymphoproliferative disease, because of the different therapy approaches and outcomes. We describe their main features and differential diagnostic procedures.
The frequency of achieving complete remission, as well as overall and disease-free survival, in multiple myeloma (MM) had increased due to introduction in MM treatment regimens of high-dose chemotherapy with following autologous hematopoietic stem cell transplantation (ASCT). However the number of relapses remains high, caused by persistence of residual tumor cells, i.e., the presence of minimal residual disease (MRD). One of the methods for MRD study is multicolor flow cytometry (MFC) where abnormal expression of surface antigens on myeloma plasma cells (PC) is determined. The aim of our study was to investigate the MRD by MFC before and after ASCT, the frequency of MRD-negative status achievement in complete remission (CR) patients at +100 days after ASCT and the frequency of abnormal expressed antigens on myeloma plasma cells. The study included40 MMpatients in CR at +100 days after ASCT and showed that the most common aberrations of PC were: abnormal absence of CD19 and/or CD27, decreased expression of CD38 and abnormal presence of CD56. The proportion of myeloma PCs from all bone marrow cells decreased significantly after ASCT: 20 % of patients acquired MRD-negative status, 10 % had a decrease in the number of abnormal PCs by one fold. Analysis of probability of immunochemical relapse showed that the worst prognosis was in patients with MRD-positive status before and after ASCT. During the MRD monitoring within 3-18 months, MRD-relapses were detected with the subsequent development of immunochemical relapse. The detection MRD in the dynamics is more informative than the study at only one step of therapy. It may help to select more adequate treatment for patient with multiple myeloma in each specific case.
BASIC RESEARCH
Introduction. In patients after multiple blood transfusions, the serological determination of ABO and Rhesus blood groups becomes unreliable due to posttransfusion chimerism, i.e., circulation in the blood of two erythrocytes populations – own and donors. To solve this problem helps the genotyping of blood groups. The literature review includes 42 literature sources, including 9 Russian and 33 foreign articles.
Materials and methods. The authors typed blood samples of 24 patients with hematological disorders after numerous erythrocyte-containing transfusions. Antigens A and B, Rh D, Rh C/c, Rh E/e were determined by the serological method using monoclonal antibodies anti-A, antiB, anti-D, anti-C, anti-Cw , anti-c, E and anti-e (Moabs) (Hematologist, Russia). The presence of chimerism was established by hemagglutination typing in gel columns ID-Cards «DiaClon ABO / D + Reverse Grouping» and «DiaClon Rh-subgroups + K». The DNA extract was examined by PCR-SSP using commercial primers ABO-TYPE and RH-TYPE (BAG, Germany).
Results. In two patients with 50% chimerism with anti-A and anti-B monoclones, the ABO blood group was genotypically identified. Using molecular method presence of Rhesus system antigens was established in 24 patients with 20-95% chimerism for 1-5 antigens. Serological determination of blood groups at 4 months after the cessation of blood transfusions has confirmed all genotyping results.
Conclusion. Genotyping is advisable to use to determine the blood groups in patients after numerous erythrocyte-containing transfusions, which allows increasing immunological safety and preventing alloimmunization to clinically significant erythrocytes antigens.
Over the past 20 years, approaches to the therapy of multiple myeloma have undergone significant changes, and frequency of achieving remission of the disease increased. The new diagnostic methods allowed evaluating the more deep therapy response and predicting the relapse: allele-specific polymerase chain reaction, next generation sequencing, multicolor flow cytometry may detect a minimal residual disease (MRD) with a sensitivity of 10–5 to 10–6. Evaluation of MRD by flow cytometry is a dynamically developing direction of research. The aim of multicenter investigations using flow cytometry for MRD-searching in multiple myeloma is standardization, increasing the sensitivity and specificity of this method. The article presents data on the methods used in monitoring MRD, as well as advances in flow cytometry.
ISSN 2413-4023 (Online)