Disseminated form of the Kaposi sarcoma in HIV-negative patient associated with Hodgkin's lymphoma.

We report a case of a 35-year-old, non-HIV-infected male diagnosed simultaneously with a disseminated form of Kaposi's sarcoma (KS; skin, stomach and colon are involved) and Hodgkin's lymphoma. There is no sign of changes in the immune status, but three herpes viruses were detected in the patient's blood (EBV, HHV6 and HHV8). He received ABVD chemotherapy and achieved complete metabolic remission for Hodgkin's lymphoma. Moreover, the signs of the disseminated KS were resolved. Our observations indicate that a combination of distinct types of viruses may play an important role in triggering the development of angio- and lymphoproliferative disorders in the same person. In addition, treatment with chemotherapy cycles, which included doxorubicin and vinblastine, led to the stable remission of both diseases.

[Incidence of hepatitis B virus infection in patients with blood disease].

AIM: To define incidence of HBV infection in patients with blood diseases caused by blood components transfusion; correlation between infection rate and blood disease nosological entity, intensity of hemoreplacement therapy, time of hepatitis B incubation period in patients with hematological malignancies after the diagnosis and initiation of polychemotherapy (PCT). MATERIAL AND METHODS: In 2000-2007 a prospective clinicoepidemiological trial was made to detect markers of HBV infection among 303 patients 15 to 76 years of age treated in the department of acute leukemia chemotherapy of N.N. Burdenko Military Hospital for acute lymphoid and myeloblastic leukemia, chronic myeloid leukemia in a blastic crisis, myelodysplastic syndrome in blast transformation, lymphoproliferative diseases with bone marrow affection. Statistic processing was performed with standard methods. RESULTS: HBV infection markers were detected in 30 (9.9%) of 303 examinees. Among the infected patients there were 16 (53.4%) patients with different variants of acute myeloblastic leukemia, 12 (40.0%) with different immunophenotypes of acute lymphoblastic leukemia, 1 (3.3%) patient with acute biphenotypical leukemia and 1 (3.3%) with lymphoma/leukemia. HBV infection was registered in patients 2 to 32 months after the beginning of the treatment. Most of the patients - 23 (74%) of 30 - were infected with HBV within the first year after hematological diagnosis and PCT induction course. HBV was diagnosed within treatment year two in 5 (16%) patients and within year three after PCT in 3 (10%). CONCLUSION: High incidence of HBV infection in patients with hematological malignancies points to a high epidemiological risk of hemoreplacement therapy, unsatisfactory quality of donor blood testing and necessity of updating methods of donor infection detection. To lower the risk of HBV infection in patients with hematological malignancies it is necessary to perform vaccine prophylaxis of hepatitis B before PCT.

[A case of primary amyloidosis].

Diagnostics of primary (AL) amyloidosis is difficult enough; treatment of this disease in not less difficult or more adequate. Because of similarity of the pathogenesis of AL-amyloidosis and that of multiple myeloma, similar therapeutic regimens, directed towards depression of plasma cell dyscrasia, are used in both cases: administration of melphalan in various doses together with prednisolone, administration of vincristine, adriablastine and dexamethasone, as well as high-dose chemotherapy with melphalan and autologic stem cell transplantation. This therapeutic approach makes it possible to reach clinico-laboratory remission and prolong the life of patients with AL-amyloidosis. The article contains a case description of a patient with AL-amyloidosis, who underwent a successful high-dose melphalan therapy with subsequent autologic stem cell transplantation.

[Acute lymphoblastic leukemias with aberrations of BCR-ABL genes].

AIM: To develop an original therapeutic strategy in Ph-positive acute lymphoblastic leukemia (ALL). MATERIAL AND METHODS: In November 2001 Hematological Research Center (HRC) initiated the study of chimeric BCR-ABL gene. During the first stage of the study (November 2001-July 2004), 18 primary ALL patients were recruited in HRC, from July 2004 to January 2005--16 patients in HRC, N.N. Burdenko Central Military Hospital, regional Samara hospital. The diagnosis of Ph-positive ALL was established in detection of translocation t(9;22) by standard cytogenetic test or fluorescent hibridization in situ with double signal (D-FISH), or by polymerase chain reaction with reverse transcription (RT-PCR). In detection of aberration of BCR-ABL gene the patients received stem hemopoietic cells, from June 2004 imatinib was added to chemotherapy in the period of induction and consolidation. RESULTS: Incidence rate of BCR-ABL-positive ALL by standard cytogenetic test and D-FISH makes up 20%, by RT-PCR--25%. Differences in chimeric transcripts detectability by different methods may be explained by different sensitivity of the methods. Complete hematological remissions were achieved in the majority of the patients (6 of 8) irrespective of imatinib administration. Achievement of molecular remission in BCR-ABL-positive ALL occurs also in standard chemotherapy but molecular remissions begin 2-4 months later than clinicohematological ones. CONCLUSION: In using imatinib combination with chemotherapy, molecular remission can be achieved simultaneously with hematological one. Long-term results will be analysed later.

[The condition of intestinal microflora in patients with hematologic tumors receiving polychemotherapy].

The subjects of the study (105 patients with blood system tumors), were divided into 4 groups. The patients of the first group received only cytostatic therapy. The subjects of the second, third and fourth groups were administered a combination of cytostatic and antibacterial agents. In addition to this, the patients of the third and fourth groups received prebiotic preparations as means of corrective therapy. The results obtained by measurement of short-chain fatty acids (SCFA) in feces by means of liquid-gas chromatography were used as criteria for evaluation of the therapy influence on intestinal microflora. The study shows that the cytostatic and combined treatment worsen the disbalance between aerobe and anaerobe populations, which manifests in SCFA spectrum alteration. Use of prebiotic preparations results in improvement of intestinal microflora condition or prevents the aggravation of its disturbance caused by the treatment of the fundamental illness, which becomes apparent in stabilization or normalization of SCFA profile in feces. Study of SCFA makes it possible to monitor microbiocenosis, adjust corrective therapy individually and evaluate its effectiveness.

[Morphological and pathogenetic aspects of aplastic anemia]. / Morfologicheskie i patogeneticheskie aspekty aplasticheskoi anemii.

A complex study of colony-stimulating properties of cells-precursors of granulomonocytopoiesis, morphological parameters of the marrow histological structures and immunological parameters was carried out in 90 patients to specify pathogenic mechanisms of aplastic anemia (AA) development. 95% of patients appeared to have sharp decrease of the marrow colony-stimulating properties and only 5% had normal initial indexes. In most patients endostal cell number increased, while the content of reticulocytes grew higher in more than 30% of patients. Defect of the marrow stroma functioning was registered in 23% of patients. Increase of the osseous tissue volume and osteocyte number was found. Dysbalance in cellular link of immunity was demonstrated. Only temporal increase of the marrow colony-stimulating properties was marked in some patients on the background of treatment with antilymphocyte globulin, despite the clinic-hematological improvement. Multifactor pathophysiological mechanisms, the main of which is the stem cell defect lies in the base of AA pathogenesis. Hemopoietic microenvironment pathology is not the leading reason of the hemopoiesis depression but it contributes greatly in its development. Immunological alterations in patients with AA are secondary and can be partly corrected with treatment with ALG.

[Morphofunctional characteristics of stromal structures of bone marrow in aplastic anemia patients]. / Morfofunktsional'naia kharakteristika stromal'nykh struktur kostnogo mozga u bol'nykh aplasticheskoi anemiei.

Stromal structures of the bone marrow in 22 patients with aplastic anemia (AA) were studied histophotometrically. A significant increase of the fat tissue volume and a decrease of hematopoietic tissue volume were observed. Bone tissue volume was significantly increased in 81.8% of patients, the number of endosteal cells was increased in all the patients and that of reticular cells in one third of them. The conclusion is made that hematopoietic microenvironment of the bone is not a determining factor in the majority of AA patients. Excessive bone formation might be one of the mechanisms of aplasia development.

[The necessity for the combined use of the ultrasonic study of the abdominal cavity organs and of the histomorphometry of the bone marrow in chronic myeloleukemia]. / O neobkhodimosti sochetannogo ispol'zovaniia ul'trazvukovogo issledovaniia organov briushnoi polosti i gistomorfometrii kostnogo mozga pri khronicheskom mieloleikoze.

Forty-one patients with chronic myeloid leukemia (CML) were divided into 3 groups: 13 patients in a chronic phase prior to cytostatic treatment group 1; 17 patients in a chronic phase treated with myelosan group 2; 11 patients in a blast transformation phase group 3. All of them underwent abdominal sonography in line with marrow histomorphometry. Ultrasound investigation is thought indispensable in examination of CML patients as it registers negligible enlargement of the liver and spleen and provided their echo structure. It makes possible to trace stages of the tumor process development. CML involves in the pathological process the kidneys as shown by changes in the echo pattern, concrements are often formed in the pelvicalyceal system. Group 1 patients demonstrated reduced area of the bone tissue by morphometrical evaluation of the bone marrow. This means prevalence of osteolysis in CML onset. In group 3 patients this value is higher indicating osteosclerosis predominance. Comparison of the ultrasonic and histomorphometric data suggest that enlargement of the spleen and liver with diffuse vegetations of the connective tissue and their fibrotic lesion of the parenchyma correlated with the severity dissemination of hemopoietic tissue collagen fibrosis. It is evident that CML is characterized by fibrosis involving simultaneously bone marrow, splenic and hepatic parenchyma.

[Choice of therapy and overall survival in patients with chronic myeloproliferative diseases]. / Vybor terapii i obshchaia vyzhivaemost' bol'nykh khronicheskimi mieloproliferativnymi zabolevaniiami.

A retrospective analysis of 106 case histories of primary chronic myeloproliferative diseases (CMPD) was undertaken: idiopathic myelofibrosis--71 (67%), polycythemia vera--29 (27.3%), and essential thrombocythemia--6 (5.7%), median age--65 years (26-84 yrs). Hydroxyurea and myelosan were mostly used as cytostatic drugs while erythrocyte mass transfusions and hemoexfusions (phlebotomy)--for life-support. Median overall survival in patients untreated with cytostatics was 95.2 years as compared with 156 months in recipients of such drugs. Survival rates in all CMPD patients with hypocellular bone marrow who had received cytostatics were lower than in those with normal or hypercellular marrow (p=0.005). Cytostatic therapy had either no impact on survival in patients with hypocellular bone marrow or was followed by decrease. Among CMPD patients who had received erythrocyte mass transfusions survival rates were significantly lower than in intact ones (p=0.0009). Median overall survival in patients receiving hemoexfusions was 193.6 months, as compared with 110.3 months in intact ones (p=0.008). Our data may be useful in selecting therapy for CMPD.

[The effectiveness of reaferone in chronic myeloid leukemia assessed with ultrasonic and histomorphologic examination]. / Effektivnost' reaferona pri khronicheskom mieloleikoze s uchëtom rezul'tatov sonograficheskogo i gistomorfologicheskogo issledovanii.

The effectiveness of reapherone administration for treatment of chronic myeloid leukemia has been studied using sonography of the liver and spleen as well as morphometry of histological patterns of the bone marrow. The study group included 17 patients (chronic disease-16; progressing disease-1). Ten patients received reapherone and 7-myelosan. Dynamic evaluation of scanning evidence for liver and spleen proved instrumental in assessing the effect of reapherone therapy of chronic myeloid leukemia. Similar tendencies were identified by sonography and morphometry applications: reapherone-treated patients revealed decreased liver and spleen, foci of fibrosis dissolving while the morphometric findings pointed to the decreasing indices of collagenous fibrosis and megacariocytic source of the bone marrow. It is suggested that reapherone acts upon the hemopoietic tissue indirectly-via endosal cells of the bone marrow stroma.

[The efficacy of polychemotherapy programs in treating multiple myeloma patients]. / Effektivnost' nekotorykh programm polikhimioterapii pri lechenii bol'nykh mnozhestvennoi mielomoi.

AIM: To compare efficiency of the programs MCVP, VCAP and ARA-COP in the treatment of multiple myeloma (MM) as regards completeness of the response, duration of the remission and toxicity. MATERIALS AND METHODS: A total of 41 MM patients entered the study (27 females, 14 males, age from 41 to 72 years, MM duration from 1 month to 8 years). 16, 10 and 15 patients were treated according to MCVP, VCAP and ARA-COP programs. RESULTS: Both in the resistant and primary patients the response was the highest to ARA-COP treatment. The remission or stabilization was achieved in 93.4% of patients. VCAP program was less effective. However, clinicohematological remission was achieved in 50% of patients. This program is rather heart toxic. MCVP program was the least effective. Survival was followed up in 16 patients (10 MCVP, 3 VCAP and 3 ARA-COP patients). The survival was 20-62, 16-36, 23.6-64.8 months for ARA-COP, VCAP and MCVP, respectively. CONCLUSION: ARA-COP program proved most effective of the three programs both in primary and drug-resistant patients. VCAP and MCVP programs are less effective but can be used in primary management of MM patients.

[Low doses of alpha-interferon preparations in the treatment of patients with chronic myeloleukemia]. / Malye dozy preparatov al'fa-interferona v lechenii bol'nykh khronicheskim mieloleikozom.

AIM: To compare the effects of low-dose alpha-interferons with those of cytostatics (hydroxyurea or myelosan) on survival of patients and duration of chronic phase of chronic myeloid leukemia (CML). MATERIAL AND METHODS: 107 CML patients were divided into two groups. 28 patients (15 males and 13 females) aged 17-59 entered group treated with alpha-interferon drugs. 79 control patients (35 males and 44 females) aged 15-79 received standard chemotherapy (hydroxyurea or myelosan). RESULTS: 3-year survival in the study group and controls was 94 and 67.5%, respectively. 5-year survival--70.8 and 28.9%, respectively. The survival medians for the groups were 66 and 48 months, respectively. 36 months after CML diagnosis, chronic phase of the disease still continued in 90.2% of the study group patients and in 53.4% of patients on chemotherapy. 54 months after the diagnosis the chronic phase was registered in 56.5 and 24% of patients, respectively. The medians made up 54 and 39 months, respectively. CONCLUSION: Treatment of CML with low-dose alpha-interferons increases duration of the CML chronic phase and survival of CML patients.

[Alpha-interferons in the treatment of patients with chronic myeloid leukemia]. / Al'fa-interferony v lechenii bol'nykh khronicheskim mieloleikozom.

Chronic disease duration and survival have been investigated in three groups of patients suffering chronic myeloid leukemia (CML). The first group included 13 patients on alpha-interferons 6-9 mln MU/24 h (mean dose--48 mln MU/week). 31 patients received 2 mln MU/m2/24 h; mean weekly dose--15 x 10(6) MU. Standard chemotherapy was given to another 79 patients (group III). Actual survival and chronic disease duration were computed after Kaplan-Meyer: 4-year survival in group I--88%; group II--85.6% and group III--54%. Five-year survival in patients who had received standard or lower doses of alpha-interferon was 78.7%; chemotherapy alone--28.9%. Median survival in alpha-interferon-treated patients was 66 months; chemotherapy--48 months. After standard alpha-interferon, chronic disease three years after CML diagnosis was in 87% of those treated with standard alpha-interferon, 89% of those receiving lower doses of the drug and 53.4% of chemotherapy-treated patients. After 4 years, chronic disease was registered in 75.5% (alpha-interferon)--74.8% in group I and 72.9% in group II, and in 34.4% of patients treated with myelosan or hydroxyurea. Median chronic stage duration after interferon was 51 months and 39 months in group III, hence, both standard and lower doses of alpha-interferon prolong chronic disease and improve survival in CML patients.

[Low-dose cytosine-arabinoside (Ara-C) therapy for chronic myeloid leukemia]. / Primenenie malykh doz tsitozin-arabinozida (Ara-C) dlia lecheniia bol'nykh khronicheskim mieloleikozom.

The effects of low doses of cytosine-arabinoside (Ara-C) were studied in 17 patients with chronic myeloid leukemia: chronic, resistant to IFN and hydroxyurea therapy (including 4 cases of advanced chronic disease)--7, and tumor progression--10. Hematologic effect was recorded in 7 chronic patients tolerant to hydroxyurea and alpha-interferon therapy. Among 10 cases of tumor progression, chronic stage II was observed in 3, stabilization (tumor progression short of blastic crisis)--5, and without effect--1. Low-dose Ara-C treatment was considered effective in 15 (88%) out of 17 patients.

[Effect of various chemotherapy regimens on survival and cause of death in patients with multiple myeloma (retrospective study)]. / Vliianie razlichnykh rezhimov khimioterapii na dlitel'nost' zhizni i prichiny smerti bol'nykh mnozhestvennoi mielomoi (retrospektivnyi analiz)

A retrospective analysis of survival time and causes of death has been undertaken in 109 patients treated for multiple myeloma (MM) at the Hematologic Clinic of the Russian Research Institute of Hematology and Transfusiology in 1979-1995. Group I included cases of mono- and group II-polychemotherapy (PCT). Survival in patients with MM increased significantly (from 27 to 43 months) after PCT. The main causes of death in MM patients of group I were chronic renal failure and infectious complications, while in group II-intoxication syndrome including blood toxicity, toxic hepatitis, etc. In cases of this grave disease, the effectiveness of therapy appeared to depend on both main and supporting treatment. Of great importance was profuse hydration using diuretics, active rheologic preparations, plasmapheresis and other counter-complication means. Following the administration of immunity correction drugs (thymaline, tactivin, immunoglobulin), infectious complication incidence in group II dropped from 22 to 8.3%. It is suggested that the effectiveness of MM therapy is determined by stage-by-stage approach, course cycling of PCT and adequate evaluation of its criteria. PCT courses should be supplemented with infusion detoxication measures, particularly, in cases of highly aggressive PCT schemes, and procedures of immunity correction, hemo-component therapy and plasmapheresis.

[The importance of studies of the glycosaminoglycans in the peripheral blood leukocytes of patients in the diagnosis of the phases of chronic myeloleukemia]. / Znachenie issledovanii glikozaminoglikanov leikotsitov perifericheskoi krovi bol'nykh v diagnostike faz khronicheskogo mieloleikoza.

To elucidate new diagnostic markers of chronic myeloid leukemia (CML) phases, we investigated quantitative and qualitative composition of glycosaminoglycans (GAG) of leukocytes from peripheral blood of 72 patients. Chronic CML phase was characterized by elevated GAG levels (2 times compared to normal values), weakening of anionic properties of chondroitin sulfate (CS) and high amount of heparan sulfate (HS). In CML transformation in the progressive phase overall concentration of GAG grew still higher, GAG fraction composition changed. In the blast crisis there was a sharp fall in the overall GAG, new electrophoretic fractions emerged. In the myeloid variant of the crisis an additional GAG component appeared (GAG-m), whereas in the lymphoid variant another component was found (GAG-1). It is suggested that the number and composition of GAG in peripheral blood leukocytes may serve markers of CML phase.

[Experience with the use of reaferon (alfa 2-interferon) for treating patients with chronic myeloleukemia]. / Opyt primeneniia reaferona (al'fa 2-interferona) dlia lecheniia bol'nykh khronicheskim mieloleikozom.

The effectiveness of domestic alpha 2-interferon preparation reaferon was studied in vivo and in vitro for eradication of pathological hemopoietic clone in chronic myeloid leukemia. Reaferon administration for 1-30 months produced cytogenetic remission in 7%, hematological remission in 21%, partial hematological remission in 36% of the patients. Reaferon is indicated in chronic myeloid leukemia without splenomegaly. In the disease progression reaferon is uneffective. Mechanism of reaferon therapeutic action comprises three components: a direct antiproliferative effect on hemopoietic precursor cells, activation of cellular immunity, an effect on stem cell microenvironment.

[Is the cytogenetic verification of chronic myeloleukemia always obligatory?]. / Vsegda li obiazatel'na tsitogeneticheskaia verifikatsiia khronicheskogo mieloleikoza?

To elucidate feasibility of accurate diagnosis of chronic myeloid leukemia (CML) without cytogenetic and molecular-genetic investigations as well as to specify CML diagnostic criteria, clinicohematological parameters were compared in two groups of patients: with Ph'-chromosome and/or rearrangement of fragment bcr (group 1), with unknown karyotype in whom detection of bcr fragment rearrangement was not made. Clinicohematological parameters in both groups were close in absolute value and underwent parallel changes in the course of leukemia progression. In group 1, patients in progressive and blastic phase compared to patients in chronic phase had a 14-fold increase in the number of additional cytogenetic anomalies. In patients with tumor transformation fragment bcr underwent rearrangement according to type B2A2. Thus, the diagnosis of typical CML variants is feasible without detection of Ph'-chromosome and/or rearrangement of bcr fragment. It is especially true and essential for patients in the chronic phase. The data obtained provide more accurate diagnostic criteria of CML.

[Certain biochemical features of leukocytes in blast crisis of chronic myelogenous leukemia]. / Nekotorye biokhimicheskie osobennosti leikotsitov pri blastnom krize khronicheskogo mieloleikoza.

The content of nuclear high mobility group (HMG) proteins, activities of ornithine decarboxylase (ODC), adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) and also glycosaminoglycan (GAG) content and composition were studied in leukocytes of patients with chronic myelogenous leukemia in the phase of blast crisis (BC CML). Myeloid and lymphoid cytochemical variants of BC CML differ by biochemical parameters. It is suggested, that the content of HMG-proteins, activities of ODC and PNP, and electrophoretic patterns of GAGs could be used in diagnostics of two main variants of BC CML.

[The efficacy of treatment with native lymphoblast alpha-interferon (Wellferon) in patients with chronic myeloleukemia]. / Effektivnost' lecheniia nativnym limfoblastoidnym alfa-interferonom (vellferonom) bol'nykh khronicheskim mieloleikozom.

Data are submitted on treatment with vellferon of patients with chronic myeloid leukemia (CML) in the chronic phase of the illness. The data obtained suggest that vellferon has a pronounced therapeutic effect in CML patients. The drug has a positive effect on both the clinical- and hematological status and cytogenetic changes in bone marrow cells. After 3-month treatment of patients with vellferon the sizes of the liver and spleen returned to normal as did the peripheral blood leucocyte and platelet counts. Two patients revealed a minimum cytogenetic response to therapy, one patient achieved a complete cytogenetic remission, and only 1 patient failed to demonstrate a cytogenetic response. A six-month therapy was associated with a complete clinical-and-hematological remission in 4 (80%) patients, with its duration ranging between 4 to 5 months, all patients maintaining a minimum cytogenetic response to vellferon treatment. Thus, treatment with vellferon permits obtaining not only a clinical and hematological but also a cytogenetical response to therapy in a major proportion of CML patients.