Vol 81, No 7 (2009)
- Year: 2009
- Articles: 18
- URL: https://journal-vniispk.ru/0040-3660/issue/view/1725
Editorial article
Acute leukemia and pregnancy - some postulates
Abstract
The aim of chemotherapy of acute leukemia in pregnant women is to save two lives. Abortion is not mandatory in acute leukemia as this disease is curable by chemotherapy. Effective treatment of pregnant women with acute leukemia diagnosis is now practiced not only by large clinics, it is also provided by regional centers. Overall 5-year actual survival for acute myeloid leukemia is 64%, for APL and ALL - 25%. All the children born by the patients during chemotherapy are healthy at maximal follow-up of 19 years, minimal - 11 months.
Terapevticheskii arkhiv. 2009;81(7):5-7
5-7
Results of the treatment of adult acute lymphoblastic leukemia according to ALL-2005 protocol as a basis for new trials
Abstract
Aim. To analyse the results of the treatment according to ALL-2005 protocol for adult patients with acute lymphoblastic leukemia (ALL); on the basis of the summarized evidence on ALL treatment to propose principles for development of a new program of ALL treatment in 15-55-year-old patients.
Material and methods. Five hematological centers (in Moscow, Saransk, Volgograd, Tambov, Kirov) participated in ALL-2005 protocol trial initiated in 2005. A total of 71 adult patients with ALL (age median 27 years) were treated. The results of the MB-2002 study with participation of 16 patients aged 16-23 years performed in the State Hematological Research Center (SHRC) were reviewed.
Results. The results of the induction therapy according to ALL-2005 protocol conducted in Moscow SHRC were good: a complete remission was achieved in 90% patients, early lethality was 6%, resistance was observed in 4%. In regional centers lethality in remission was higher, 5-year overall survival was 28% (in SHRC it was 56%), recurrence-free survival in regional center was 22% versus 51%, respectively. Long-term response by ALL-2005 and MB-2002 in patients aged 19-23 was the same, but toxicity of ALL-2005 treatment was higher (no lethality and 5, 4% in induction and remission, respectively).
Conclusion. The decision was made on design of a new protocol of treatment of Ph-negative ALL for patients aged from 15 to 55 years the main principles of which are the following: continuous treatment with modification of cytostatic drugs doses depending on myelosuppression severity; assessment of tumor cells sensitivity to prednisolone and its replacement for dexametasone throughout the treatment; prolongation of L-asparaginase treatment with elevation of its total dose; monitoring of minimal residual disease (MRD) for decision on late intensification in patients with MRD at late treatment stages (5 months).
Terapevticheskii arkhiv. 2009;81(7):8-15
8-15
Regulatory mechanisms of iron metabolism in patients with acute leukemia
Abstract
Aim. To estimate the levels of hepsidine, HIF-1alpha, erythropoietin, other proteins of iron metabolism; to characterize dysregulation of metabolic processes in leukogenesis.
Material and methods. Thirty eight patients with newly diagnosed acute leukemia (AL) were divided into three groups by anemia severity: group 1 (Hb > 90 g/l), group 2 (Hb 90-70 g/l), group 3 (Hb < 70 g/l). Erythropoietin concentration was measured with enzyme immunoassay, serum ferritin (SF) - by radioimmunoassay; HIF-1alpha, hepsidine - by sandvich enzyme immunoassay with use of monospecific antisera and monoclonal antibodies against relevant antigens.
Results. In AL patients SF before treatment was 10 times higher than in healthy subjects, administration of cytostatics elevated this concentration even more. Hepsidine and HIF-1alpha are also elevated. Treatment reduces hepsidine level twice in all the groups. This may be due to reduction of the tumor mass. Erythropoietin was 20-35 times higher in all the patients, especially in myelotoxic agranulocytosis (up to 1000 mU/ml) with reduction after recovery of hemopoiesis (in some patients to normal values 20-30 mU/ml). Hepsidine and HIF-1alpha concentrations were also maximal in myelotoxic agranulocytosis (20-28 pg/ml). After recovery of hemopoiesis these values fell to initial values 7-9 pg/ml). Transfusion of donor erythrocytic mass normalized HIF-1alpha concentration and decreased that of hepsidine. Its elevation and high HIF-1alpha were observed after the transfusion in 17% patients.
Conclusion. Disorders in regulatory mechanisms in AL patients throughout the observation confirm the role of the proteins studied in homeostasis. Changes in HIF-1alpha and hepsidine concentrations can be used as indicators of transfusion efficacy.
Terapevticheskii arkhiv. 2009;81(7):16-20
16-20
Leukemic dendritic cells in patients with acute myeloid leukemia
Abstract
Aim. To determine surface and intracellular expression of ACE antigen and Bip shaperon on leukemic dendritic cells (LDC); to study expression of ACE genes and Bip, Calnexin, calreticulin shaperons in LDC at diagnosis of acute myeloid leukemia (AML) under standard and stress cultivation.
Material and methods. Expression of ACE antigens and Bip was studied with immunophenotyping and flow cytometry using monoclonal antibodies to shaperon Bip and to CD143), expression of genes of ACE and shaperons Bip, Calnexin, Calreticulin - with polymerase chain reaction (RT-PCR). Dendritic cells (DC) were obtained by culturing of a monoclonal fraction of donor peripheral blood and AML patients in the presence of 180 ng/ml calcium ionophor A23187 (Sigma) for 4 days in parallel at 37°C and 33°C in the atmosphere of 5% CO2. The trial included 9 patients (5 males and 4 females) aged 39-53 years (median 43 years). The control group consisted of 8 healthy donors.
Results. Lowering of cultivation temperature did not increase ACE expression. Intracellular shaperon Bip rose insignificantly (1.3-fold) in DC of the controls. ACE and Bip shaperon expression on LDC membrane increased 15- and 11-fold, respectively, while the level of intracellular ACE and Bip decreased 11- and 2-fold, respectively. Expression of the genes was investigated in cultivation temperature lowering from 37 to 33°C and was presented as a logarithmic scale. Changes in expression of the genes Bip, Calnexin, Calreticulin in LDc and DC of the controls were insignificant. ACE expression in LDC significantly differed from ACE gene expression in DC (p = 0.05).
Conclusion. LCD and DC of healthy donors are cells which differ by genetic and functional characteristics. Therefore, LDC may response inadequately in development of antitumor immune response. The phenomenon of ACE antigen expression normalization on cell membrane in stress open new opportunities for regulating functional activity of LDC.
Terapevticheskii arkhiv. 2009;81(7):20-28
20-28
Trisomy of chromosome 8 in Ph-negative cells of the bone marrow in patients with chronic myeloid leukemia treated with inhibitors of BCR-ABL tyrosinkinases
Abstract
Aim. To analyse clinical implications of chromosome 8 trisomy in Ph-negative cells of the bone marrow in patients with chronic myeloid leukemia (CML) treated with inhibitors of tyrosinkinases (ITK).
Material and methods. A total of 386 patients with CML (chronic phase - 288, acceleration phase - 77) received imatinib (400-800 mg/day). Because of resistance and/or intolerance some patients were switched to ITK II (nilotinib, dasatinib, bozutinib). This study included 8 CML patients (7 in a chronic phase, 1 in acceleration phase) treated with BCR-ABL ITK inhibitors of the first (imatinib) and the second line (ITK-II). The standard cytogenetic examination, on demand - investigation of the interphase nuclei with FISH, in some cases morphological, cytochemical and histological examinations of the bone marrow were made.
Results. The existence of a Ph-negative clone with trisomy of chromosome 8 had no negative effect on the course of the disease. The patients showed a stable hematological and cytogenetic response and no need in changing treatment policy. In long-term follow-up Ph-negative clone with trisomy of the chromosome 8 persisted without a clear trend to rise in most patients.
Conclusion. Detection of a Ph-negative clone with chromosome 8 trisomy at early stages suggests parallel existence of Ph-positive and Ph-negative clones. None of the patients had myelodisplasia.
Terapevticheskii arkhiv. 2009;81(7):29-36
29-36
Pharmacodynamic characteristics of velkeid efficacy in resistant and recurrent multiple myeloma: determination of free light chains of blood serum immunoglobulins
Abstract
Aim. To ascertain individual sensitivity to veikeid in patients with resistant and recurrent multiple myeloma (MM) by determination of free light chains (FLC) of serum immunoglobulins.
Material and methods. Forteen patients with MM stage III (Gcappa-5, Glambda-2, Acappa-3, Alambda-1, BJcappa-3) aged 52-75 years with documented resistance to treatment or recurrence received second-line monotherapy with velkeid. The drug was injected intravenously (jet) in a dose 1.3 mg/m2 on the treatment day 1, 4, 8 and 11. Free light chains concentration was examined with antibodies to their latent determinants (Binding Site, UK) on nephelometer (Hitathi-911, Japan) on velkeid treatment day 1, 2, 3, 5, 9 and 12.
Results. Nine patients showed lowering of FLC concentration and responded to treatment by Durie criteria.
Conclusion. Dynamic follow-up of FLC concentration of the tumor clone in resistant and recurrent MM evaluates pharmacodynamics of the drug. The method provides prognosis of late clinical results.
Terapevticheskii arkhiv. 2009;81(7):37-41
37-41
Dasatinib treatment of imatinib-resistant and imatinib-intolerant patients with chronic myeloid leukemia in a chronic phase
Abstract
Aim. To analyse resistance to imatinib therapy, efficacy and safety of dasatinib.
Material and methods. A total of 18 patients with chronic myeloid leukemia (CML) in a chronic stage received dasatinib for 9-30 months (median 30 months) to September 2008.
Results. Lethal outcomes during dasatinib treatment were absent. To September 2008, 16(89%) patients were alive, 2(11%) patients died of the disease progression after dasatinib discontinuation. A complete clinicohematological response was observed in all the patients. Major cytogenetic, complete cytogenetic, major molecular, complete molecular responses were achieved in 12(67%), 10(55%), 7(39%) and 5(28%) patients, respectively. Hematological and non-hematological toxicity occurred in 9(50%) patients. Now 12(67%) patients continue dasatinib treatment, in 6(33%) patients the drug was discontinued.
Conclusion. The results from trials in Russian Hematological Research Center are the same as in the international study. Dasatinib is effective and well tolerated therapeutic option for imatinib-resistant patients with a chronic phase of CML.
Terapevticheskii arkhiv. 2009;81(7):41-46
41-46
Clinical and epidemiological features of Berkitt's lymphoma
Abstract
Aim. To characterize clinical and epidemiological features of adult Berkitt's lymphoma (BL).
Material and methods. The trial enrolled 72 patients (51 males and 21 females, age 14-69, mean age 27 years) treated in 1995-2008.
Results. Stage I BL (by S.B. Murphy) was diagnosed in 5 patients, stage II - in 9, stage III - in 25, IV - in 14 patients, B-cell acute lymphoblastic leukemia (ALL) (L3) - in 19 patients. Intoxication was seen in 56(78%) patients, 38% patients had severe cachexia. Elevated concentration of lactatedehydrogenase (LDG) was detected in 57(79%) patients. In all the cases clinical symptoms developed for 1-3 months, median 6 weeks. Bone marrow involvement was diagnosed in 22 (31%) patients, CNS was affected in 17(24%) patients, of them 14 were males. Fifty two (72%) patients had abdominal, retroperitoneal and/or small pelvis tumors. Intestinal, hepatic, renal and gastric tumors occurred most frequently. Specific ascitis was detected in 25(48%), tumor pleuritis - in 11(15%) patients. BL of the facial skeleton, Waldeyer's ring, oro- and nasopharynx was in 12(17%) patients. Seven patients had concomitant involvement of the CNS. Eight (38%) and 2(10%) women had tumors of the ovaries and uterus, respectively.
Conclusion. BL is characterized by the following clinical features: young age of the patients, most of them are males, B-symptoms, short history, generalized stages, extranodal lesions, frequent involvement of the bone marrow and CNS.
Terapevticheskii arkhiv. 2009;81(7):47-53
47-53
High-dose polychemotherapy of patients with poor-prognosis anaplastic T.0-large cell ALK+ lymphosarcoma
Abstract
Aim. To evaluate efficacy of the protocol NHL BFM-90 in the treatment of adult anaplastic large cell lymphosarcoma (ALCL) ALK+ and validity of addition of transplantation of autologous stem hemopoietic cells (ASHC) into first line treatment.
Material and methods. We treated 13 patients with stage III-IV ALCL ALK+. The age of the patients ranged from 17 to 44 years (median 26 years). The diagnosis was made using morphological, histological, immunohistochemical methods with application of monoclonal antibodies to CD30, ALK, CD3, CD4, CD8, CD7, CD34, CD15, CD68, CD20, CD45RO, CD45RA. The patients were treated according to the protocol NHL BFM-90. ASHC was made in two patients with the disease stage IV.
Results. We obtained a complete remission in 12 of 13 patients, one woman died of infectious complications in the beginning of the treatment, one man had early recurrence 45 days after the end of the treatment with lethal outcome and disease progression. Two patients at stage IV and poor prognosis had undergone ASHC transplantation. They are now in remission for 5 and 12 months.
Conclusion. ALCL ALK+ is characterized by an aggressive clinical course (11 of 13 patients had stage III-IV), high rate of extranodal lesions. Twelve patients achieved a complete remission, 11 (91.6%) of 12 patients are alive in observation median 27 months. We effectively used ASHC transplantation in the first-line treatment of 2 patients with stage IV of the disease and poor prognosis.
Terapevticheskii arkhiv. 2009;81(7):53-57
53-57
Diagnosis and treatment of skin T-cell lymphoma undergoing transformation in lymphosarcoma
Abstract
Aim. To define complex of parameters characterizing transformation of skin T-cell tumors in lymphosarcoma; to show specific treatment of patients with this transformation.
Material and methods. Of 57 patients with primary T-cell lymphomas of the skin (mycosis fungoides, Sezary's disease), we studied 12 patients with transformation of the process into lymphosarcoma by clinical, histological, moleculobiological and immunophenotypical parameters.
Results. We found that transformation of T-cell lymphoma into lymphosarcoma occurred in different time from the disease onset (2-12 years). In patients with mycosis fungoides (MF) the transformation was local while in those with Sezary's disease (SD) transformation of the tumor clone was determined by appearance of peripheral blood tumor cells rejuvenation. Morphological alterations were accompanied with immunomorphological parameters of progression. Most significant of them were high expression of the proliferative activity marker Ki-67 (10-70%), enhancement of activation (CD30, CD25), loss of some linear T-cell markers. Treatment of lymphosarcoma arising on the background of lingering MF or SD may combine two types of antitumor treatment - intensive and supporting because of coexistence of different clones of one tumor.
Conclusion. Verification of skin T-cell lymphoma diagnosis and its transformation into lymphosarcoma must be based on the evidence from a number of examinations: histological, immunophenotyping, moleculobiological and clinical. Among criteria of the transformation, markers of lymphoproliferative activation are of great importance.
Terapevticheskii arkhiv. 2009;81(7):57-61
57-61
Pilot experience in the treatment of poor-prognosis primary diffuse large-B-cell lymphosarcoma of the bones and soft tissues with a modified program NHL-BFM-90
Abstract
Aim. To evaluate efficacy of intensive modified program NHL-BFM-90 (mNHL-BFM-90) in adult poor-prognosis patients with diffuse large B-cell lymphosarcoma (DLBCL) of the bones and soft tissues.
Material and methods. The mNHL-BFM-90 program was used in the treatment of 3 male and 2 female patients aged 17-69 years (median 42 years). Four patients had DLBCL of the bones and one patient - DLBCL of the soft tissues. All the patients had tumors more than 10 cm in size. B-symptoms, a high concentration of lactate dehydrogenase (LDG) were registered in 3 patients. One patient had stage IE by Ann-Arbor, two - stage IIE (involvement of regional lymph nodes), two - stage ME (multiple bone lesions). A total of 4-6 blocks of polychemotherapy according to mNHL-BFM-90 program were performed.
Results. Complete remissions were achieved in all the patients. They had no recurrences after 6 to 20 month (median 13 months) follow-up.
Conclusion. Positive results of the program mNHL-BFM-90 in poor-prognosis patients with DLBCL of the bones and tissues necessitate further studies of this therapy.
Terapevticheskii arkhiv. 2009;81(7):61-65
61-65
The study of parameters of mesenchymal stromal cells differentiation in donors and patients with aplastic anemia
Abstract
Aim. To examine ability of mesenchymal stromal cells (MSC) of the bone marrow (BM) for differentiation in adipogenic and osteogenic differentiation in donors and patients with aplastic anemia (AA).
Material and methods. We obtained MSC cultures from BM cells of donors and AA patients and induced differentiation of mesenchymal cells with use of relevant reagents. Morphological changes in MSC were studied with light microscopy. A relative level of expression of differentiation marker genes in MSC cultures before and after induction of differentiation was analysed with reverse transcription-polymerase chain reaction.
Results. By morphological characteristics, MSC cultures in AA patients before and after differentiation induction do not differ from donor cultures, but relative expression of the genes of differentiation markers demonstrated that expression was different in male and female donors; MSC before and after induction of differentiation differ in donors and AA patients.
Conclusion. Further studies are needed for detection of functional changes in precursors of stromal microenvironment and understanding of the disease pathogenesis.
Terapevticheskii arkhiv. 2009;81(7):66-70
66-70
Pilot experience of using modified high-dose therapy NHL-BFM-90 in diffuse large B-cell lymphosarcoma with primary skin involvement. A case report
Abstract
Primary skin large B-cell lymphosarcomas (PLBCL) present with skin lesions, other organs and systems are not involved. As CHOP courses are not high effective in PLBCL, we were the first to treat a patient with modified block therapy NHL BFM-90. A complete remission was achieved after the first course of polychemotherapy and was consolidated by two courses of treatment. Further follow-up is needed.
Terapevticheskii arkhiv. 2009;81(7):71-75
71-75
Tumor development from follicular dendritic cells in a hyaline-vascular variant of Castleman's disease
Abstract
Literature gives only few reports of hyaline-vascular variant of Kastleman's disease associated with tumor from dendritic cells. A case of simultaneous detection of these diseases in the tumor located in the retroperitoneal space and successfully removed surgically is reported.
Terapevticheskii arkhiv. 2009;81(7):75-77
75-77
Renal monoclonal immunoglobuline deposition disease as a rare variant of renal damage in multiple myeloma
Abstract
A case of the immunoglobuline deposit disease diagnosis in MM patient having the symptoms of intensive proteinuria, macrohematuria and terminal renal failure is reported. The disease was diagnosed by the evidence from electron microscopy of the kidney and liver biopsies.
Terapevticheskii arkhiv. 2009;81(7):78-82
78-82
Syndrome of extrahepatic portal hypertension and chronic abdominal ischemia in subleukemic myelosis and congenital immunodeficiency
Abstract
The article demonstrates objective difficulties and subjective mistakes in assessment of a clinical picture in a patient with subleukemic myelosis and thrombosis of the portal system. A careful examination of such patients is necessary to reveal latent disorders (in this case - a complete selective IgA deficiency) influencing treatment policy.
Terapevticheskii arkhiv. 2009;81(7):82-84
82-84
Primary lymphoproliferative diseases of the central nervous system
Abstract
Primary CNS lymphomas have worse prognosis than other extranodal lymphomas: remissions are rare, recurrences are frequent. Literature is analysed on diagnosis, prognostic factors, perspectives and problems of treatment of primary CNS lymphomas.
Terapevticheskii arkhiv. 2009;81(7):85-91
85-91
Significance of matrix metalloproteinases and their ihhibitors in normal subjects, solid and blood cancer patients
Abstract
Matrix metalloproteinases and their inhibitors play an essential role in invasion and dissemination of malignant tumors. The study of expression of MMP and their inhibitors in solid and blood cancer may appear a key study giving assessment of antitumor response.
Terapevticheskii arkhiv. 2009;81(7):91-96
91-96