HEMATOLOGIC MALIGNANCIES: DIAGNOSIS, TREATMENT, SUPPORTIVE CARE
Treatment results in children with acute lymphoblastic leukemia (ALL) treating in St.-Petersburg hospitals according to two modified version of German protocol CO ALL-92 from 01.01.1993 to 01.01.2007 are presented. 438 primary A LL patients aged from 4 months to 17 year s have been included in the study . ALL diagnosed according to international criteria. Based on prognostic factors patients were a llocated to one of two risk groups, which determined therapy intensity . The total treatment duration in both groups w as 2 years and consist ed of 5.5–8 months intensive phase with subsequent maintenance therapy . A comparative treatment results analysis in children with A LL according to two modified versions of COALL-92 is presented.
This study aimed to evaluate treatment results in patients with diffuse large cell lymphoma (DBL CL) received R-CHOP program (as 1 st and
2 nd line therapy), including cases with complications. We observed 77 DBLCL patients (50 primary and 27 received other chemotherapy programs, in relapse, progression or treatment resistance phase). The median age is 54.1 years (21–79 years). 33 patients (43 %) had a high risk for unfavorable disease course according to IPI. Complications associated with development of severe compression syndromes, which required the appropriate surgical intervention, w as diagnosed in 45 (58.4 %) patients. From 50 primary patients received R-C HOP as the f irst line therapy objective treatment response was registered in 47 (94.0 %). Complete response was registered in 43 (86.0 %). The proportion of patients in whom response was maintained for 6 months w as 72.0 % in group with maintenance therapy and 28.0 % in group without it. These results were achieved when induction period density was 0.9. The last parameter is the ratio of the courses number to their time in mon ths. The density of standard induction R-C HOP-21 is 1.4. From 27 relapse or refractory patients received R-C HOP as the second line therapy objective
treatment response was registered in 85.1 % of patients. Induction period density w as 1.03. The proportion of patients in whom response was maintained for 6 months was 74.0 %. Three classes serum Ig concentrations analysis before and after induction period in 16 pati ents showed normal values. With the median (Me) follow-up time in all patients over 24 months 3-years survival w as 93 % and Me w as not achieved. 3-years survival was 100 % in primary patients and 80 % in patients with previously treatment, and Me is also not achieved.
Candidemia is one of the most serious infectious complications in children with hematological malignancies and has a high morta lity rate.
Seven-year experience of candidemia diagnosis and therapy in patients with various hematologic malignancies w as analyzed. Candidemia registered in 37 patients (AML and MDS — 14, ALL — 10, solid tumors — 5, histocytic syndromes — 4, AA — 3, other non-malignancy diseases— 2). C. non-albicans (36 isolates from 32 patients) was common cause of, while C. albicans isolated in 5 patients (8 strains). Antifungal prophylactic therapy was applied to 31 patients. 22 patients at the time of candidemia have neutropenia (< 0.5 × 10 9/l). Main clinical manifestations were febrile fever (100 % cases) and pneumonia (21.6 % cases). Less frequent multiorgan failure (8.1 %), septic shoc k (5.4 %), chronic disseminated candidiasis (5.4 %) and meningitis (2.7 %) were registered. All patients received antifungal therapy (monotherapy — 17, combination therapy — 20). Central venous catheter removed in 21 patients. In 14 patients hematopoietic recovery w as registered, none of these patients died, while from group of patients without hematopoietic recovery 6 patients died (p = 0.0001). Recurrent candidemia episodes were seen in 4 patients. Overall survival was 0.37 ± 0.09.
Recent advances in multiple myeloma (MM) treatment associated with new drug use including bortezomib. Experiences in wide ambul atory drug use confirm therapy success for this serious disease, but at the same time reveals the most common side effects. One of th e most significant is the reactivation of Herpes zoster , which leads to decrease MM therapy results because of inability to perform standard therapy in these patients. Literature data and own experiences about reactivation of Herpes zoster during bortezomib therapy as monothe rapy and in combination, which varies from 7 to 34% according to different authors and 25% of own experiences, is presented. Treatment and preventive schedule of this complication are shown.
Literature review of anemia pathogenesis in patients with lymphatic system malignancies is presented. Advantages and disadvanta ges of eritropoiesis-stimulating preparations (ESP) used for anemia correction are shown. Efficacy of anemia treatment with ESP in various types of lymphoproliferative disorders (LPD) is presented. Prognostic factors that predict positive response on ESP in LPD pati ents and reduce treatment cost are identified.
Central nervous system (CNS) involvement in advanced non-Hodgkin’s lymphoma (NHL) occurs in 5–29 % of cases. Primary CNS lymphoma (PLCNS) significantly less revealed: 1–2 % of lymphoma cases and 5 % of all malignant CNS diseases. Historically, PLCNS treated with radiotherapy, but the majority of patients had no long-term remission. Combined treatment (chemotherapy + radiation therap y) has been developed to improve radiotherapy efficacy. The research results, according to several authors, allowed to develop the bas is of modern medical approaches, which includes a combination of high-doses methotrexate and cytarabine with radiation therapy for remission consolidation. New drugs — temozolomide, topotecan and rituximab — in combination with conventional preparates have been studied. Treatment results of 11 patients with primary (8) or secondary (3) CNS lymphomas treated in Botkin Municipal Clinical Hospital was analyzed. In 9 from 11 (all with primary lesion) diffuse B-large cell lymphoma w as diagnosed (by immunohistochemistry). All primary patients received 3.5–5 g/m2 methotrexate and 2–4 doses 2 g/m2 cytarabine (except 2 patients); 3 patients in addition received ifosfamide, vincristine and etoposide under a pediatric protocol BFM-90. Subsequently , all patients received 46 Gy cranial irradiation. 75 % of pa tients achieved complete or partial remission. One patient died from infectious complication after 2nd chemotherapy course. 2 patients have early progression. Five patients are alive with follow-up from 6 months to 3.5 years and 4 of them remains in remission. Therapy with methotrexate + cytarabine was accompanied by III–IV grade neutropenia in the majority of patients, but its duration w as not great. The data obtained are consistent with results of modern treatment protocols PLCNS.
BASIC RESEARCH
117 cases of infant acute lymphoblastic leukemia without Down syndrome (aged from 1 to 365 days) were included in the current study.
Rearrangements of 11q23 (MLL) were revealed in 74 (63.2 %) patients. Among this group the most common rearrangement was t(4;11) q21;q23)/MLL-AF4 detected in 63.5 % cases, less frequently was found t(11;19)(q23;p13)/MLL-MLLT1 (in 18.9 % cases), t(10;11) p12;q23)/MLL-MLLT10 and t(1;11)(p32;q23)/ML L-EPS15 (each one in 6.8 %), t(9;11)(p22;q23)/MLL-MLLT3 in 2.7 %. Children under 6 months of age had significantly higher incidence of 11q23 (ML L) rearrangements in comparison with infants olde r than 6 months (84.0 % vs. 47.8 %, p < 0.001). P atients with translocations 11q23 (ML L) more frequently had BI-A LL and less frequently BII-ALL than children without these rearrangements (p < 0.001 f or both). Fusion gene transcript w as sequenced in 26 ML Lrearranged cases. Depending on breakpoint position within ML L and partner genes we detected 7 differ ent types of ML L-AF4 fusion gene transcript, 3 types of MLL-MLLT1, 2 types of MLL-EPS15. The most common fusion site within MLL gene was exon 11, detected in 14 (53.8 %) patients.
The role of p53 family proteins, both in the pathogenesis of chronic lymphoproliferative disorders, and in aspects of the growi ng interest in the
therapeutic potential of so-called small molecules capable of influencing the regulatory "relationship" of p53, MDM2, p21 and P UMA is currently actively debated. The article is an attempt to summarize the data on experimental tumor and mouse models and availablen ithe l iterature results of studies using human lymphoid tumors. Prognostic significance of p53 family proteins expression in lymphoproliferativ e diseases and possible therapeutic approaches using the features of the p53 relationship with regulators and effectors genes are considered.
Phase of incubation microarray with cell suspension is prolonged when cells are investigated. It takes from 20 to 60 min if cell sedimentation on the surface of microarray is the result of gravity . Decrease of this stage duration is possible due to centrifugation. In th is article influence of centrifugation on results of analysis is considered. Changes of morphological description of cells are estimated when they a re precipitated
with different acceleration. Also availability of centrifugation using when it is necessary to obtain the high density of cell binding in test regions of microarray if cells concentration in sample is small is demonstrated.
LECTURES
ISSN 2413-4023 (Online)