Vol 84, No 7 (2012)
- Year: 2012
- Articles: 17
- URL: https://journals.rcsi.science/0040-3660/issue/view/1765
Editorial
Treatment for recurrent hairy cell leukemia.
Abstract
Aim. To give data on the frequency of recurrent hairy cell leukemia (HCL) and to characterize the immediate and late results of its treatment in this group of patients. Materials and methods. The data on the frequency of recurrences were analyzed in 165 patients with HCL after remission achieved by the purine analogue cladribin in the period 1995 to 2011. The treatment of recurrent HCL included splenectomy, interferon-α, cladribin, and rituximab. Results. After a course of cladribin therapy, the total frequency of recurrent HCL was 22%. The high (47%) frequency of recurrences was found in young patients (less than 45 years) as compared to that (9%) in older patients. A combination of cladribin and rituximab showed a high efficacy in treating the early recurrence of HCL. Conclusion. The differences found in the frequency of recurrences give grounds to incorporate rituximab into the standard therapy regimen for HCL in young patients and in patients with early disease recurrence.
Terapevticheskii arkhiv. 2012;84(7):4-9
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The first results of treatment for adult acute myeloid leukemia according to the AML-01.10 protocol of the Research Group of the Hematology Centers of Russia
Abstract
Aim. To give the preliminary results of the AML-01.10 Russian multicenter randomized trial to treat adult acute myeloid leukemia (AML), the basic principle of which is to use high-dose anthracycline antibiotics in induction/consolidation. Subjects and methods. By December 2011, 145 patients with AML had been randomized from 18 hematology centers of 15 cities and towns of the Russian Federation; the median age of all the patients was 44 years. Seventy-one patients were analyzed in August 2011 (a 1.5-year follow-up). Results. The efficiency of 2 courses 7+3 using high-dose daunorubicin (60 mg/m2 per administration) and continuous infusion of cytarabine during the second course was high and comparable with that in the use of a high-dose HAM protocol as a second induction course and can achieve a complete remission in 74.6%. The protocol toxicity evaluated from its early mortality (11.3%) and its death in complete remission (16.6%) was permissible, particularly by taking into consideration the multicenter pattern of the trial. At the completion of analysis, 53 (68.8%) out of the 77 patients on whom the data on their vital status were available were alive. In this follow-up period, the frequency of recurrences was 19.2% (10/52). Only 3 (4.2%) patients out of the 71 patients in whom the efficiency of the protocol had been completely evaluated underwent allogeneic bone marrow transplantation. Conclusion. The total high dose (720 mg/m2) of anthracycline antibiotics, which is used in the period of induction and consolidation, determines the long periods of myelosuppression and intercourse intervals. Protocol deviations (no course of consolidation therapy, lower-dose idarubicin during consolidation therapy, a course of low-dose cytarabine between the courses of induction and consolidation chemotherapy, and very long intercourse intervals) were recorded in a total of 20 (28%) patients.
Terapevticheskii arkhiv. 2012;84(7):10-15
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Complex karyotype is a marker of very poor prognosis in over 70-year-old patients with acute myeloid leukemia and extended types of myelodysplastic syndrome and high comorbidity index
Abstract
Aim. To identify a category of persons with very low overall survival (OS) rates, whose intensive chemotherapy is unreasonable, amongst the patients with acute myeloid leukemia (AML) with extended forms of myelodysplastic syndrome (MDS) and complex karyotype. Materials and methods. OS rates were retrospectively analyzed in 41 patients with AML and 26 with MDS; their median age was 61 years (range 15 to 77 years). Thirty-four (50.7%) patients received standard induction courses; 19 (28.4%) patients had low-intensity therapy. Restraining therapy was used to treat 14 (20.9%) patients. The length of follow-up was 1.5 to 171 months. Results. Irrespective of the type of disease, the median OS was 6 months. A difference in OS was found when the patients were divided into 4 age groups: those who were under 40 years of age (n=11), 41-60 years (n=21), 61-69 years (n=21), and ≥70 years (n=14). With age, the median OS decreased from 9.5 to 4 months (p=0.041). Multivariate analysis revealed that the intensity of induction courses was the cause that affected OS. High comorbidity index and, first of all, cardiovascular diseases were the main reason for discontinuing standard chemotherapy courses in patients aged 70 years or older. Conclusion. Standard induction courses of cytostatic therapy are not indicated for patients aged ≥70 years with AML and extended stages of MDS with complex karyotype and high comorbidity index.
Terapevticheskii arkhiv. 2012;84(7):16-21
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Dynamic Β-endorphin determination in hematologic patients
Abstract
Aim. To perform a dynamic study of Β-endorphin, hypoxia-inducible factor-1α (HIF-1α), and cytokines in hematologic patients. Subjects and methods. Fifty-nine patients with different types of acute leukemia (AL), 30 with anaplastic anemia (AA), 24 with thrombocytopenic purpura, and 20 healthy volunteers were examined during their 40-day stay at 3200 m above sea level. Β-Endorphin and HIF-1α were measured by a sandwich-type enzyme immunoassay using the Abcam antibodies. Cytokines (interleukin (IL)-2, IL-6, and tumor necrosis factor-α) were estimated by enzyme immunoassay applying the Pro Con kits (Saint Petersburg). Results. Serum Β-endorphin concentrations were 1.5-2-fold above the normal values in the majority of patients with AL. The patients with initial leukocytosis at onset of disease were noted to have elevated white blood cell Β-endorphin concentrations up to 85.9±22.4 pg/ml; moreover, during chemotherapy this index increased about two times (170.74±33.8 pg/ml). There was a direct correlation between the concentrations of Β-endorphin and HIF-1α (r = 0.9) and an inverse correlation between the levels of IL-6 and Β-endorphin (r = -0.7). On ascending to 3200 m, under the conditions of hypoxic hypoxia the patients with AA or idiopathic thrombocytopenic purpura showed a considerable increase in serum Β-endorphin concentrations, mainly in the acute period of being at high altitudes. Conclusion. Stress factors (tumor, use of cytostatics, pain, anemia, hypoxia, high environment temperature) stimulate the elaboration of Β-endorphin, particularly in the white blood cells of patients with AL during chemotherapy. The highest elevation in the index was seen during acute adaptation to hypoxic hypoxia.
Terapevticheskii arkhiv. 2012;84(7):22-25
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Treatment of acute host-versus-graft reaction in patients after allogeneic hematopoietic cell transplantation with multipotent mesenchymal stromal cells from a bone marrow donor
Abstract
Aim. To evaluate the efficiency of administration of multipotent mesenchymal stromal cells obtained from a bone marrow donor for the treatment of an acute host-versus-graft reaction (HVGR) resistant to therapy with glucocorticosteroids (GCS). Subjects and methods. The experience in treating 6 patients with GCS-resistant acute HVGR following allogeneic hematopoietic stem cell transplantation is given. The patients were intravenously injected cultured multipotent mesenchymal stromal cells (MMSC) in a dose of 106 per kg body weight. Results. Four weeks after MMSC administration, a complete or partial response was obtained in 3 cases; clinical improvement was noted in 2; one patient showed no response. MMSC therapy proved to be effective in 5 of the 6 cases with acute HVGR resistant to GCS therapy. Conclusion. MMSC therapy turned out to be effective in case of acute HVGR resistant to GCS therapy.
Terapevticheskii arkhiv. 2012;84(7):26-30
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The specific features of renal lesion in Burkitt's lymphoma
Abstract
Aim. To analyze the causes of renal lesion in patients with Burkitt's lymphoma (BL) and to develop optimal treatment policy. Materials and methods. The data of examination and treatment were analyzed in 20 patients with BL (14 men and 6 women aged 15 to 57 years (median age 24 years)) who had been followed up for renal lesion at the Hematology Research Center (HRC) in 2003 to 2011. When admitted to hospital, all the patients were found to have ureteric compression, renal parenchymal tumor infiltration, massive tumor cytolysis syndrome (MTCS). Polychemotherapy (PCT) was performed in accordance with the original intensive BL-M-04 protocol. The extent of the process was estimated according to the classification developed by S.B.Murphy: L3 variant B of acute lymphoblastic leukemia in 10 cases; Stage IV in 2; Stage III in 8. Acute renal failure (ARF) was identified in 13 patients. A control group comprised 36 patients with BL without ARF who had been followed up at the HRC in 2003 to 2011 and included into the BL-M-04 protocol. The ratio of patients with bone marrow lesion was 7:13 and 9:36 in the BL+ARF and BL-ARF groups, respectively. Results. Decreased urine specific gravity and proteinuria (0.4 to 1.3 g/l) were the first manifestations of renal lesion and were seen in approximately 50% of all cases both on admission to hospital and in the first stages of PCT (10 and 9, 8 and 7 of the 20 cases, respectively). Microhematuria more commonly developed after initiation of PCT (7 and 3 of the 20 cases, respectively). ARF was diagnosed in 13 patients (24% of the 55 BL patients followed up at HRC in 2003 to 2011). One female patient developed ARF after the start of PCT. Twelve patients developed this condition at the onset of disease; in 4 patients, ARF existing prior to PCT began progressing after drug administration. The etiology of ARF was generally mixed. At the onset of disease, MTCS (n=6) and specific renal parenchymal infiltration (n=6) were more common causes of ARF. Postrenal anuria was present in 2 cases. ARF after PCT initiation resulted from the toxic effects of methotrexate and MTCS (3 and 4 cases, respectively). ARF regressed in the early periods: in the prophase (n=4) and during or the first PCT block A (n=9). The BL patients with ARF, as compared to those without the latter, showed a statistically significant earlier onset of myelotoxic agranulocytosis (MTA): on day 3 of an intercourse interval (95 CI from 0 to 3 days) versus its day 5 (95% CI from 2 to 5 days) and a statistically significant longer duration of MTA - 12 days (95% CI from 7 to 16 days) versus 7 days (95% CI from 3 to 10 days); they were observed to have more severe mucositis. Despite the longer intercourse interval, 10 patients with ARF achieved remission; 4 patients died from therapy-refractory sepsis and 1 patient from thrombocytopenia. In the patients with ARF, mortality rates were significantly higher than in those without ARF (33% versus 10%; p=0.04). Conclusion. Although there is a high risk of worsening renal dysfunction, PCT is a necessary condition for ARF resolution in BL.
Terapevticheskii arkhiv. 2012;84(7):31-34
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Effect of bortezomib on the efficiency of hematopoietic stem cell mobilization in patients with multiple myeloma
Abstract
Aim. To study the results of mobilizing and collecting autologous hematopoietic stem cells (HSC) in patients with multiple myeloma (MM) receiving bortezomib as part of induction therapy regimens. Materials and methods. In June 2001 to April 2010, the Department of Bone Marrow Transplantation, Hematology Research Center, Ministry of Health and Social Development of Russia, mobilized autologous HSC in 93 patients with MM, by using cyclophosphan (CF) and granulocyte colony-stimulating factor. The analysis covered 73 patients who received VAD and/or bortezomib-containing courses as induction therapy. Group 1 comprised 30 patients whose induction therapy was performed as 3-4 courses of VAD. Group 2 included 19 patients who had 2-4 courses of PAD or 4-8 courses of bortezomib + dexamethasone in addition to 1-3 courses of VAD. Group 3 combined 24 patients who used 6-8 courses of bortezomib + dexamethasone or 3-4 courses of PAD + 4-6 courses of bortezomib + dexamethasone. Results. In Group 1 patients whose induction therapy was performed as 3-4 courses of VAD, baseline peripheral blood CD34+ cell counts were 3,575±631 in 1 ml, which was statistically significantly higher than those in Group 2 patients who had bortezomib-containing courses in addition to VAD courses. In Group 2 patients, premobilization CD34+ cell counts were 2,164±516 in 1 ml. The lowest blood CD34+ cell levels (1,586±405 in 1 ml) were observed in Group 3 patients in whom bortezomib was used as first-line therapy. In Group 1 patients, the maximum peripheral blood counts of CD34+ cells were 322,287±73,994 in 1 ml, which was significantly higher than their maximum level in Groups 2 (231,624±39,708 in 1 ml) and 3 (161,007±44,266 in 1 ml) patients. The efficiency of mobilization proved to be high; more than 4.0·106/kg of CD34+ cells were collected in all the patients with bortezomib-containing induction therapy, which allowed two autologous HSC transplantations to be carried out.Conclusion. Adding bortezomib at the stage of induction has no significant impact on the results of HSC mobilization and collection. By taking into account the possibility of achieving a complete or very good partial response in 40-60% of the patients using the bortezomib-containing regimens as first-line therapy, bortezomib should be considered as an essential drug as part of induction therapy.
Terapevticheskii arkhiv. 2012;84(7):35-41
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Primary lymphomas of bones and soft tissues: comparative assessment of treatment results
Abstract
Aim. To evaluate the efficiency of intensive polychemotherapy (PCT) in adult patients having diffuse large B-cell lymphoma (DLBL) of bones and soft tissues with and without poor prognostic factors (PPF). Subjects and methods. Out of 58 enrolled patients, 51 were diagnosed as having DLBL. Burkitt's lymphoma (BL) was diagnosed in 6 patients. One patient had marginal zone B-cell lymphoma. Thirty-five patients with DLBL (10 patients with PPF and 25 without PPF) and 3 patients with BL were treated with the CHOP/R-CHOP regimen. The NHL-BFM-90 program was used in 3 patients with BL and 16 with DLBL (15 patients with PPF and 1 patient without PPF).Results. After radiotherapy, the patient with marginal zone B-cell lymphoma achieved a 20-month remission; three BL patients receiving CHOP died. All the BL patients receiving NHL-BFM-90 achieved complete remissions of 48 to 72 months. In 9 patients having DLBL without PPF, who received CHOP, five-year overall and event-free survival rates were 100%; in 22 patients with PPF, these were 50 and 45%, respectively. In the patients with and without PPF, who received CHOP/R-CHOP, the survival rates differed statistically significantly (p=0.01; logrank test). In the group of 15 patients having DLBL with PPF, who were treated with the NHL-BFM-90 protocol, 14 achieved an average remission of 17 months. In the patients having DLBL with PPF who used NHF-BFM-90, therapeutic efficiency was significantly higher (p=0.05; Fisher's exact test).Conclusion. Differential therapy for primary lymphomas of bones and soft tissues indicated that the NHL-BFM-90 protocol used in the PPF group was significantly more effective than the CHOP regimens.
Terapevticheskii arkhiv. 2012;84(7):42-49
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Invasive mycoses during hematopoietic stem cell transplantation
Abstract
Aim. To define the frequency, etiology, and risk factors of invasive mycoses (IM) in patients with allogeneic (allo) and autologous (auto) hematopoietic stem cell transplantation (HSCT) and to evaluate the impact of IM on overall survival (OS). Materials and methods. Data on 356 patients after allo-HSCT (n=237) and auto-HSCT (n=119) from 2000 to 2010 were analyzed. The diagnosis of IM was established according to the EORTC/MSG 2008 criteria. Results. The incidence of myocardial infarction (MI) was 19.1%; that was 23.2 and 10.9% in allo-HSCT and auto-HSCT recipients, respectively. The incidence of MI following allo-HSCT was significantly higher than that after auto-HSCT. Aspergillus spp. (82.3%), Candida spp. (11.8%), zygomycetes (Mucor spp., Rhizopus spp.) (4.4%), and Cryptococcus neoformans (1.5%) are involved in the etiology of MI. Its risk factors are acute lymphoblastic leukemia; non-myeloablative conditioning regimen; use of fludarabine and antilymphocyte globulin; peripheral blood stem cells as a source for grafting; long-term lymphopenia, neutropenia; use of granulocyte colony-stimulating factor (G-CSF); acute graft-versus-host reaction; grade 3-4 mucositis; infections, such as cytomegalovirus, sepsis. The development of MI in HSCT recipients did not significantly reduce one-year OS after allo-HSCT and auto-HSCT - 53.6 and 55% and 86.7 and 90.3% (with and without MI, respectively). In patients with invasive aspergillosis, OS (12 weeks after IM being diagnosed) was significantly longer in those with other invasive mycoses (91.3 and 50%, respectively). Conclusion. The incidence of MI after allo-HSCT was higher than that after auto-HSCT. MI induced by the fungal genus Aspergillus spp. was most common. Along with known risk factors, there was a poor prognostic factor, such as G-CSF. The development of MI failed to affect one-year OS, which was indicative of the adequate quality of its early diagnosis and therapy. The prognosis was poor in patients with invasive candidiasis, zygomycosis, and cryptococcosis. Investigations need to be continued to specify the reasons for high morbidity rates and the factors provoking discussion by investigators worldwide.
Terapevticheskii arkhiv. 2012;84(7):50-57
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Microcirculatory investigations in hemophilia patients
Abstract
Aim: to evaluate microcirculation (MC) and its influencing factors in hemophilia patients. Subjects and methods. In 44 hemophilia patients with recurrent hemarthrosis, laser Doppler flowmetry was used to evaluate resting MC above the index fingers, knee and ankle joints during an occlusion test, with allowance made for muscle and adipose tissue mass. Results. The increased perfusion value above the afflicted joints was found to correspond to the phase of an exacerbation of posthemorrhagic inflammation and to be a risk factor of recurrent hemarrthrosis. Analysis of the occlusion test above the knee joints and index fingers revealed a diminished MC reserve and a tendency to precapillary spasm. MC changes were more pronounced in a shortage of muscle and adipose tissue mass. Conclusion. Hemophilia patients must regularly do physical exercises to make skeletal muscles develop well in order to prevent an exacerbation of the joint inflammatory process.
Terapevticheskii arkhiv. 2012;84(7):58-60
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Deposition of 51Cr-labeled donor platelets in health and myelosuppressive thrombocytopenias
Abstract
Aim. To study the deposition of donor platelets (DP) in myelosuppressive thrombocytopenia (TP) in patients with acute leukemia (AL) or lymphosarcoma (LSA), by using a radionuclide label (51Cr) for DP. Subjects and methods. Complex clinical, hematological and radionuclide studies were conducted in 63 patients divided into 3 groups: 1) 7 healthy volunteers (a control group); 2) 37 patients with AL; 3) 19 patients with LSA. Results. Changes were found in the deposition of labeled DPs used to prevent and treat hemorrhagic syndrome in myelosuppressive TP in patients with AL or LSA. In AL, this function was established to be virtually completely suppressed whereas in LSA, some functional activity of mononuclear phagocytes was preserved. Different degrees of suppression of this function were probably related to the nature of these diseases and particularly due to varying degrees of leukemic infiltration of depot organs. A mechanism for increased consumption of transfused DP in profound TP, one of the causes of which is the myelosuppression as a result of programmed polychemotherapy, cannot be ruled out. Conclusion. By and large, the radionuclide labeling technique for DP may be useful in specifying a number of uncertain mechanisms for derangements of the thrombocytic component of hemostasis in oncohematologic diseases.
Terapevticheskii arkhiv. 2012;84(7):61-65
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Acquired hemorrhagic coagulopathy due to contact with the rodenticide brodifacoum in the Nutcracker bait
Abstract
Rodenticide (RD) application is the most effective chemical procedure against rodents. RDs containing indirect-action anticoagulants have received currently wide acceptance. When the recommended standards for handling these agents and precautionary measures in their use are violated, there may be poisoning, the main manifestation of which is hemorrhagic coagulation. The paper provides a literature review on poisoning by RDs having anticoagulant properties. This communication gives a detailed description of a clinical case of poisoning with brodifacoum contained in the ready-to-use Nutcracker bait due to long-term exposure to the rat poison that has a cumulative effect. Careful history data collection and coagulogram analysis make it possible to establish a correct clinical diagnosis and to use appropriate therapy that leads to patient recovery.
Terapevticheskii arkhiv. 2012;84(7):66-71
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The silicone spleen (description of a clinical case)
Abstract
The paper describes a rare case of verified foreign body (silicone) migration into the spleen. The specific feature of this clinical case is a rare clinical finding through histological study and the use of inductively coupled plasma-mass spectrometry for the determination of silicone in splenic tissues.
Terapevticheskii arkhiv. 2012;84(7):72-74
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Crystalline histiocytosis
Abstract
The paper describes a case of diagnosis of the rare monoclonal secretion-associated disease crystalline histiocytosis with kidney and bone marrow involvement. The female patient with multiple myeloma (MM) was found to have intralysosomal crystals in the cells of the bone marrow (histiocytes, plasmocytes), kidneys proper (mesangiocytes, podocytes), and subsequently in those of a kidney graft. Lower secreted monoclonal IgG and ceased Bence-Jones protein secretion after MM chemotherapy were accompanied by improved and stabilized kidney graft function. However, a repeat morphological study of a renal biopsy specimen showed that the crystalline inclusions were preserved in the podocytes. By comparing the immunological and renal responses, it is reasonable to suggest that monoclonal IgG rather than Bence-Jones protein is of value in the pathogenesis of crystal formation.
Terapevticheskii arkhiv. 2012;84(7):75-78
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Differential diagnosis of Wegener's granulomatosis and extranodal NK/T-cell lymphoma, nasal type
Abstract
Men aged over 40 years more commonly develop NK/T-cell lymphomas (NK/T-CL). The paper describes a case of NK/T-CL in a 20-year-old man. Despite the fact that the disease (nasal septum perforation, hard palate bone destruction, recurrent nasopharyngeal bleeding, considerable weight loss, and high erythrocyte sedimentation rate,) progressed rapidly for 5 months, the patient was found to be diagnosed as having Wegener' granulomatosis (WG). Repeated incisional biopsies showed massive necrotic changes with no clear histological verification of the diagnosis. The absence of lung and kidney lesions typical of WG, the lack of antineutrophil antibodies, and the detection of Epstein-Barr virus DNA in blood could presume NK/T-CL and confirm it by extended biopsy to have materials sufficient for morphological and immunomorphological studies. This observation shows that the disease may occur at a young age and rapidly progress; only early diagnosis can improve prognosis in patients with this type of lymphomas.
Terapevticheskii arkhiv. 2012;84(7):79-83
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A case of spontaneous chylothorax complicating pregnancy
Abstract
The paper gives a clinical case of left-sided chylothorax developing in a young woman in the second half of pregnancy due to thrombosis of the left internal jugular vein, left subclavian vein, and brachiocephalic trunk. Cesarean section was made. Medical treatment thereafter proved to be effective. The possible mechanisms for spontaneous venous thrombosis and chylothorax during pregnancy and the methods of their diagnosis and treatment are discussed.
Terapevticheskii arkhiv. 2012;84(7):84-88
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The problem of hemorrhagic syndrome in its treatment with vitamin K antagonists (a review of literature)
Abstract
Vitamin K antagonists (warfarin, syncumar, phenylin, etc.) are commonly used to treat and prevent thrombotic diseases. The risk for varying degrees of hemorrhagic syndrome (intracranial hemorrhage in particular) is the most important problem in the use of drugs from this group. The rapid neutralization of the effects of used anticoagulants, which is verified by correcting the international normalized ratio (INR), is required in these cases and when emergency surgical interventions are needed. Transfusions of prothrombin complex concentrates (PCCs) in combination of vitamin K preparations are optimal for this purpose. The reason for the rational use of PCCs to promptly correct INR is the balanced composition of this transfusion medium (a combination of blood coagulation factors and biological anticoagulants). This regimen for emergency correction of INR minimizes the risk of thrombotic events.
Terapevticheskii arkhiv. 2012;84(7):89-94
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