Identification of prognostic factors predicting outcome in Hodgkin's lymphoma patients relapsing after autologous stem cell transplantation.

BACKGROUND: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care for patients with relapsed Hodgkin's lymphoma (HL). However, there is currently little information on the predictors of outcome for patients whose disease recurs after ASCT. METHODS: Five hundred and eleven adult patients with relapsed HL after ASCT from EBMT-GITMO databases were reviewed. RESULTS: Treatments administered following ASCT failure included conventional chemotherapy and/or radiotherapy in 294 (64%) patients, second ASCT in 35 (8%), and alloSCT in 133 (29%). After a median follow-up of 49 months, overall survival (OS) was 32% at 5 years. Independent risk factors for OS were early relapse (<6 months) after ASCT, stage IV, bulky disease, poor performance status (PS), and age ≥50 years at relapse. For patients with no risk factors OS at 5 years was 62% compared with 37% and 12% for those having 1 and ≥2 factors, respectively. This score was also predictive for outcome in each group of rescue treatment after ASCT failure. CONCLUSION(S): Early relapse, stage IV, bulky disease, poor PS, and age ≥50 years at ASCT failure are relevant factors for outcome that may help to understand the results of different therapeutic approaches.

The first determination of Trichuris sp. from roe deer by amplification and sequenation of the ITS1-5.8S-ITS2 segment of ribosomal DNA.

Trichuris nematodes were isolated from roe deer (Capreolus capreolus). At first, nematodes were determined using morphological and biometrical methods. Subsequently genomic DNA was isolated and the ITS1-5.8S-ITS2 segment from ribosomal DNA (RNA) was amplified and sequenced using PCR techniques. With u sing morphological and biometrical methods, female nematodes were identified as Trichuris globulosa, and the only male was identified as Trichuris ovis. The females were classified into four morphotypes. However, analysis of the internal transcribed spacers (ITS1-5.8S-ITS2) of specimens did not confirm this classification. Moreover, the female individuals morphologically determined as T. globulosa were molecularly identified as Trichuris discolor. In the case of the only male molecular analysis match the result of the molecular identification. Furthermore, a comparative phylogenetic study was carried out with the ITS1 and ITS2 sequences of the Trichuris species from various hosts. A comparison of biometric information from T. discolor individuals from this study was also conducted.

Glycogen phosphorylase BB as a potential marker of cardiac toxicity in patients treated with anthracyclines for acute leukemia.

OBJECTIVES: The aim of the presented study was to assess plasma glycogen phosphorylase BB (GPBB) concentrations in acute leukemia patients treated with anthracycline containing chemotherapy. BACKGROUND: Anthracyclines represent the highest risk for development of cardiotoxicity. GPBB belongs to proposed biomarkers of cardiac injury with a very limited experience in this context. METHODS: Totally, 24 adult patients with acute leukemia were enrolled. Plasma GPBB concentrations were measured by ELISA at diagnosis (before chemotherapy), after first chemotherapy with anthracyclines and 6 months after the completion of treatment. The cut-off value for GPBB positivity was 10.00 µg/L as recommended by the manufacturer. RESULTS: Before chemotherapy, the mean plasma GPBB concentration was 5.25±3.81 µg/L, increased above the cut-off in 1 patient (4.2 %). After the first chemotherapy, the mean GPBB was 6.61±5.54 µg/L, positive in 7 (29.2 %) patients. Six months after treatment, the mean GPBB was 10.06±11.41 µg/L, positive in 8 (33.3 %) patients. Six months after treatment, we found a significant correlation between elevation in GPBB and diastolic left ventricular dysfunction on echocardiography (r=0.621; p<0.0001). The differences in plasma GPBB between healthy blood donors and patients treated for acute leukemia were statistically significant (p<0.01 in all cases). CONCLUSION: Our results suggested that GPBB could become a potential biomarker for detection of acute and chronic cardiotoxicity associated with anthracycline containing chemotherapy. The predictive value for development of treatment-related cardiomyopathy in future is not clear and will be evaluated during the follow-up. Further studies are needed to define the potential role of GPBB and other biomarkers in the assessment of chemotherapy-induced cardiotoxicity (Ref. 21). Text in PDF www.elis.sk.

Evaluation of serum levels of selected cytokine receptors in adult B-cell precursor acute lymphoblastic leukemia and their association with prognostic factors and survival.

AIM: To evaluate serum levels of selected cytokine receptors in B-cell precursor acute lymphoblastic leukemia (B-ALL) and their association with acknowledged prognostic factors, relapse-free survival (RFS) and overall survival (OS). MATERIALS AND METHODS: A total of 42 de novo adult B-ALL patients, 19 BCR/ABL positive, were included in this study. Soluble receptor α for IL-2 (sIL-2Rα), soluble receptor for IL-6 (sIL-6R), soluble receptor for TNF-α type I and II (sTNFR-1, sTNFR-2) and matrix metalloproteinase-9 (MMP-9) were measured by biochip array technology at diagnosis and in complete remission (CR). RESULTS: At diagnosis of B-ALL, we found significantly higher levels of sIL-2Rα, sIL-6R, sTNFR-1, sTNFR-2 and significantly lower levels MMP-9 in comparison with CR (p < 0.001 in all cases). BCR/ABL positive patients had higher levels of sIL-2Rα at diagnosis (r = 0.484; p = 0.014). Serum levels of evaluated cytokines were not associated with achievement of CR after one cycle of induction therapy, RFS or OS. CONCLUSION: Serum levels of all evaluated cytokines are significantly altered in newly diagnosed B-ALL reflecting activity of the disease. No significant correlations with response to first induction therapy, RFS or OS were found. Further studies with a longer follow-up will be needed.

Sexual dysfunction in females treated with peripheral blood progenitor cell transplantation: review of literature.

BACKGROUND: Peripheral blood progenitor cell transplantation (PBPCT) is a therapeutic modality used in the anti-tumorous treatment of hemato-oncological diseases and solid tumors. Apart of that, it is also used in therapy of non-malignant and hereditary diseases. AIM: As is the case with other treatments, PBPCT also affects not only the disease process but also the quality of life (QoL). MATERIALS AND METHODS: In the last decade of 20th century, several QoL studies among patients treated with PBPCT were undertaken and an influence on particular dimensions of QoL was observed. One of closely watched aspects was sexuality in patients treated with PBPCT. RESULTS: Sexuality and its expression belong to very important aspects of human behavior. It is also a very sensitive and sensible aspect, so with no doubts it is affected by the diagnosis of neoplasm and cancer treatment. CONCLUSION: Physical and psychosocial factors of PBPCT do affect patient's sexuality and sexual functioning as part of QoL. They remain in focus because of the complex care of patients treated with PBPCT (Fig. 2, Ref. 21).

Screening for depression in survivors of metastatic ovarian cancer in a programme of palliative cancer care.

BACKGROUND: Depression is seen in many cancer patients. It occurs in approximately 25% of palliative care patients. MATERIALS AND METHODS: This study was local, prospective and cross-sectional. It was carried at Department of Clinical Oncology and Radiation Therapy of Charles University Hospital and Faculty of Medicine in Hradec Králové, Czech Republic. RESULTS: The incidence of depression was 83.3% (25 of all 30 survivors). The relevance of depression is characterized: severely depressed was proved in 9 of all 30 survivors, the moderately depressed in 5 of all 30 survivors, the mildly depressed in 11 of all 30 survivors and normal range in 5 of all 30 survivors. The statistical evaluation not presents statistically significant dependence of ZSRDS on smoking abuse, marital status, age, number of associated diseases and type of palliative cancer care. CONCLUSION: The results of the pilot depression study showed that subsist clear association between metastatic ovarian cancer and depression (Fig. 2, Ref. 30). Full Text (Free, PDF) www.bmj.sk.

Capillary immunotyping electrophoresis and high resolution two-dimensional electrophoresis for the detection of mu-heavy chain disease.

Heavy chain disease with monoclonal incomplete mu-heavy chains (mu-HCD) is a rare disorder usually associated with an underlying lymphoproliferative malignancy. Laboratory diagnosis of patients with mu-HCD is usually challenging and the monoclonal protein is not detected by electrophoresis in up to 75% of mu-HCD cases. We describe a patient with multiple malignancies in whom we detected and characterized monoclonal mu-heavy chains using immunofixation electrophoresis, capillary zone electrophoresis with immunotyping, and high resolution two-dimensional electrophoresis. The high resolution 2D electrophoresis enabled us to determine the molecular weight of the mu-heavy chains. The abnormal protein concentration in the serum was unusually high, 38 g/l measured in our patient is the highest reported value in the literature so far.

Health-related quality of life in multiple myeloma survivors treated with high dose chemotherapy followed by autologous peripheral blood progenitor cell transplantation: a retrospective analysis.

A pilot study analyses an effect of selected demographic, psychosocial and health aspects on quality of life (QoL) in multiple myeloma survivors treated with high-dose chemotherapy followed by autologous peripheral blood progenitor cell transplantation (PBPCT). The total number of respondents with multiple myeloma treated with high-dose chemotherapy followed by autologous PBPCT between years 2001-2003 at the Department of Clinical Haematology of the 2nd Department of Internal Medicine of Charles University Hospital and Faculty of Medicine in Hradec Králové, Czech Republic was 32 (18 male, 14 female). The average age of respondents was 60 years old. The Czech version of an international generic European Quality of Life Questionnaire - Version EQ-5D was used. The effect of selected demographics, psychosocial and health aspects on QoL was determined by means of analysis of variance (ANOVA). The QoL questionnaires were evaluated by means of descriptive analysis. The above-mentioned aspects proved statistically significant dependence of QoL on respondents age and on smoking abuse. EQ-5D score (dimensions of QoL) and EQ-5D VAS (a subjective health condition) significantly decrease with increasing age and with smoking abuse. The effect of other aspects on QoL was not proven as statistically significant. Prevailing complaints in respondents with multiple myeloma were: 1. regular activity with complaints 81,2 % (26/32 respondents), 2. medium serious pain / discomfort 68,8 % (22/32 respondents), 3. movement with complaints 59 % (19/32 respondents), 4. medium serious anxiety / depression 59 % (19/32 respondents). The QoL in patients with multiple myeloma treated with high-dose chemotherapy followed by autologous PBPCT was on low level (mean EQ-5D score was 68,9 %, mean EQ-5D VAS was 66,6 %). The results had shown that with an increasing age, the QoL of patients with multiple myeloma treated with high-dose chemotherapy followed by autologous PBPCT, declines. The smokers and former smokers have lower QoL than non smokers. The global QoL in all studied patients with multiple myeloma treated with high-dose chemotherapy followed by autologous PBPCT was on low level.

Multimarker approach to evaluation of cardiac toxicity during preparative regimen and hematopoietic cell transplantation.

Cardiac toxicity of preparative regimen (PR) containing high-dose Cyclophosphamide (120 mg/kg) followed by hematopoietic cell transplantation (HCT) was evaluated with 6 biomarkers of cardiac injury: N-terminal pro brain natriuretic peptide (NT-proBNP), creatine kinase MB (CK-MB mass), cardiac troponins (cTnT, cTnI), heart-type fatty acid binding protein (H-FABP), glycogen phosphorylase BB (GPBB). Twenty-three patients (mean age 44.5+/-10.6 years, 15 males) with acute leukemia were studied. All biomarkers were measured the day before PR, the day after PR, the day after HCT and 14 days after HCT. We found NT-proBNP elevations above 500 ng/L in 6 (26.1 %) patients after PR, in 9 (39.1 %) after HCT and in 7 (30.4 %) 14 days after HCT. GPBB became elevated (above 7.30 microg/L) in 5 (21.7 %) patients after PR, remained elevated in 5 (21.7 %) after HCT and in 2 (8.7 %) 14 days after HCT. A significant correlation between elevation in NT-proBNP and GPBB was found. Other markers remained within the reference range early after PR and HCT. Our findings show that administration of PR and HCT for acute leukemia is associated with acute neurohumoral activation of cardiac dysfunction (significant rise in NT-proBNP) and may lead to GPBB elevation. These changes could indicate acute cardiac toxicity due to treatment and require further follow-up. The predictive value for development of cardiomyopathy in the future is unclear. Further studies will be needed to define the potential role of new biomarkers in this context.

Quality of life and arterial endovascular intervention by means of balloon angioplasty.

AIM: The aim of this study was to evaluate the quality of life (QoL) and the effect of arterial balloon angioplasty (ABA) on QoL of patients with peripheral arterial occlusive disease (PAOD). METHODS: The study is a prospective and longitudinal one and was carried out at the 2nd Internal Clinic of Charles University Hospital in Hradec Kralove, Czech Republic. Forty-two patients with PAOD, hospitalized for the endovascular intervention by means of percutaneous transluminal angiography, were evaluated for QoL. Thirty patients with PAOD (20 male, 10 female) were treated by endovascular intervention by means of ABA. The evaluation of QoL was performed by means of the Czech version of the international generic European Quality of Life Questionnaire EQ-5D. Statistical analysis was determined by means of analysis of variance and paired t-test. The QoL questionnaires were evaluated by means of descriptive analysis. RESULTS: The study has shown the following results: patients with PAOD had low global QoL; a statistically significant relation between QoL of patient with PAOD and the their age (P<0.01); a statistically significant relation between global QoL and stage of PAOD by Fontaine classification (P<0.01); and a statistically significant relation between global QoL and ABA (P<0.0001). CONCLUSION: The QoL of patients with PAOD is low. The QoL is lower with increasing age and with severity of PAOD. The results show the existence of a positive effect of ABA on QoL in patients with PAOD.

The spectrum and types of adverse side effects to biological immune modulators: a proposal for new classification.

In recent years, a growing number of biological agents such as cytokines, monoclonal antibodies and fusion proteins have become available for the treatment of various autoimmune, neoplastic, cardiovascular, infectious, allergic, and other conditions. Their introduction has resulted in marked clinical improvements for many patients. Nevertheless, a variety of adverse side effects have been observed with these agents. Based on the special features of biological agents a new classification of these side effects of biological agents is proposed--related but clearly distinct from the classification of side effects observed with chemicals and drugs. This classification differentiates five distinct types, namely clinical reactions due to high cytokine levels (type alpha), hypersensitivity due to an immune reaction against the biological agents (type beta), immune or cytokine imbalance syndromes (type gamma), symptoms due to cross-reactivity (type delta), and symptoms not directly affecting the immune system (type epsilon). This classification could help to better deal with the clinical features of these side effects, to identify possible individual and general risk factors and to direct research in this novel area of medicine.

Deep vein thromboembolism in malignant diseases.

Tumourous diseases are associated with haemorrhagic as well as thrombotic complications. Trousseau described in 1865 a mutual association between tumourous diseases and venous thromboembolism. As many as 15-20% patients with venous thromboembolism have an undetected malignity, which equals a prevalence of 2-3% in the population. From this ensues the relative risk of a newly diagnosed malignity which is higher during the first year after venous thromboembolism. Migrating thrombophlebitis is a relatively specific sign in tumours, in particular in pancreatic tumours. In the pathogenesis of venous thromboembolisms in tumourous diseases, the following factors play a significant part: elevated coagulation parameters, reduced fibrinolysis, frequent immobilization, surgical operations in the case history, chemotherapy, hormonal therapy and central venous catheters. Conventional long term management of VTE involves the use of vitamin K antagonists, such as warfarin, to reduce the risk of recurrence. Recent evidence-based approach in long term management of VTE in patients with tumorous disease shows that the use of LMWH offers an effective alternative to VKAs with higher efficacy, without a significantly increased risk of bleeding, and without the need for regular laboratory monitoring.

Prevention of infection transmission during stem cell transplantation.

Group of 152 patients (investigated before autologous transplantation) and 35 healthy donors for allogeneic transplantation was examined for the risk of infection transmission that can be associated with the infusion of cryopreserved peripheral blood progenitor cells to the patient and/or cross-contamination of stored grafts. No laboratory signs of active infection were found in 22 donors (63 %) and in 91 patients (60%). The most common was active infection by herpes viruses--50 cases in patients, 21 cases in donors; hepatitis B was found in only two cases. The rate of clinically unsuspected (but dangerous) infections in donors and patients thus remains relatively high in spite of the fact that the system of donor search and the whole transplantation procedure have improved in the last years. The system of safety assurance is extremely important and the whole palette of preventive tests according to EBMT (European Blood and Marrow Transplantation Group) and ISHAGE (International Society for Hemotherapy and Graft Engineering) is fully justified.

[Health and psychosocial aspects of quality of life in patients undergoing autologous progenitor stem cell transplantation]. / Zdravotní a psychosociální aspekty kvality zivota nemocných s akutní myeloidní leukémií po autologní transplantaci periferních kmenových bunek.

BACKGROUND: The haematopoietic stem cell transplantation is a specific therapy used not only for the treatment of haematooncological diseases, but also for the treatment of the solid tumours and some of the non-malignant diseases. The haematopoietic stem cell transplantation has an influence on the course of the disease and the quality of life as any other curative method. The authors explore the quality of life in 12 adult patients with acute myeloid leukaemia undergoing autologous progenitor stem cell transplantation at the Department of Clinical Haematology of the 2nd Department of Internal Medicine of Charles University Hospital in Hradec Králové. METHODS AND RESULTS: The European Quality of Life Questionnaire EQ-5D was used in evaluating effects of the selected healthy and psychosocial aspects on the quality of life (age, sex, level of education, religion, smoking abuse, polymorbidity, marital status and lapse time from transplantation). The results show that quality of life significantly depends on the age, level of education, smoking abuse, religion and polymorbidity. Effects of other aspects on the quality of life were not revealed. CONCLUSIONS: The global quality of life in our adult patients with acute myeloid leukaemia undergoing autologous progenitor stem cell transplantation at the Department of Clinical Haematology of 2nd Department of Internal Medicine of Charles University Hospital in Hradec Králové is on greatly good level (mean EQ-5D score was 75.1% and mean EQ-5D VAS was 67.5%).

Olfactory sensitivity in mammalian species.

Olfaction enables most mammalian species to detect and discriminate vast numbers of chemical structures called odorants and pheromones. The perception of such chemical compounds is mediated via two major olfactory systems, the main olfactory system and the vomeronasal system, as well as minor systems, such as the septal organ and the Grueneberg ganglion. Distinct differences exist not only among species but also among individuals in terms of their olfactory sensitivity; however, little is known about the mechanisms that determine these differences. In research on the olfactory sensitivity of mammals, scientists thus depend in most cases on behavioral testing. In this article, we reviewed scientific studies performed on various mammalian species using different methodologies and target chemical substances. Human and non-human primates as well as rodents and dogs are the most frequently studied species. Olfactory threshold studies on other species do not exist with the exception of domestic pigs. Olfactory testing performed on seals, elephants, and bats focused more on discriminative abilities than on sensitivity. An overview of olfactory sensitivity studies as well as olfactory detection ability in most studied mammalian species is presented here, focusing on comparable olfactory detection thresholds. The basics of olfactory perception and olfactory sensitivity factors are also described.

The use of biochemical markers in cardiotoxicity monitoring in patients treated for leukemia.

Cardiotoxicity is a serious and relatively frequent complication of anti-tumorous treatment. Anthracyclines represent the greatest risk. Biochemical markers of structural and functional myocardial damage have been gaining ground in cardiotoxicity monitoring. The aim of the study was to monitor cardiotoxicity of induction chemotherapy in acute myeloid leukemia (AML) patients and to assess the potential for use of biochemical markers in early diagnostics of cardiotoxicity. Fifteen consecutive adult patients with a newly diagnosed AML were studied. All patients received induction chemotherapy containing Idarubicin (IDA) 3 x 12 mg/m2 and intermediate doses of Cytarabine (8 x 1.5 g/m2). Serial measurements of plasma N-terminal pro brain natriuretic peptide (NT-proBNP) values were performed at the baseline, the day following each IDA infusion, after 14 days and after circa 1 month, i.e. before the next chemotherapy. Cardio-specific markers (cTnT, CK-MB mass) were measured at the baseline and after the last IDA infusion. The mean baseline value of NT-proBNP in newly diagnosed AML patients was 129.7+/-59.6 pg/ml. The mean NT-proBNP value increased after the first IDA infusion to 307.3+/-171.4 pg/ml (p=0.02). In most of the patients, the second and the third IDA infusions were not associated with a further increase in the NT-proBNP value and levels after 2 and 4 weeks were not significantly different from the baseline. However, in one of the patients the NT-proBNP values were increasing after each IDA infusion (after the last one 786.2 pg/ml) and within 14 days he developed congestive heart failure due to left ventricular diastolic dysfunction as assessed by echocardiography. At that time, the NT-proBNP value was 1,184.0 pg/ml; after diuretics it decreased significantly. In all patients, plasma cTnT and CK-MB mass concentrations were within the reference interval at the baseline and after the induction chemotherapy. Our results suggest that induction chemotherapy in AML (IDA 36 mg/m2 and intermediate doses of Cytarabine): 1. does not cause detectable damage of the myocyte structure, 2. is in all patients associated with acute neurohumoral activation (transient elevation of NT-proBNP) indicating acute subclinical cardiotoxicity, 3. may lead to congestive heart failure and NT-proBNP seems to be a promising early marker and predictor of this complication.

Selective decontamination of the digestive tract in hematological patients (Czechoslovakia-German Democratic Republic cooperative study.

A group of 55 hematological patients treated for the last 2.5 years by the method of selective decontamination was evaluated. Though both institutes (Bad Saarow, Hradec Králové) worked on the problem in the same conditions (indications for the treatment, characteristics of patients, basic drugs), many differences in details were found. However, the important clinical results were the same: A statistically significant decrease in infections and duration of fever in treated patients. A survey of therapy complications, surveillance of infections and incidence of microbes are presented. The evaluation showed that future research including microbiological and immunological investigation based on a standard protocol will be useful.

Antiapoptotic cytokine IL-3 + SCF + FLT3L influence on proliferation of gamma-irradiated AC133+/CD34+ progenitor cells.

Recovery from radiation-induced bone marrow aplasia depends on appropriate cytokine support. The aim of our work was to find a cytokine combination allowing in vitro gamma-irradiated (2.5 Gy) CD34+/AC133+ haematopoietic stem cells to evade radiation-induced apoptosis and to enhance damage reparation, which should enable proliferation and ex vivo expansion of cells. Cells were isolated using separation in a Cobe separator followed by immunomagnetic selection by antibody against the AC133 antigen. Thus isolated cells were 80% AC133+/CD34+ and 10% of them expressed the CD33+ antigen. Ten thousand of AC133+ cells formed 1146 CFU-GM and 304 BFU-E. We proved a high expansion efficiency of cytokine combination SCF + IL-3 + FLT3L in comparison with the combination SCF + IL-3 + IL-11 in both, non-irradiated cells and cells irradiated with a dose of 2.5 Gy. The D0 value for AC133+ cells was determined by the clonogeneity test. The D0 value for CFU-GM was estimated to be 1.08 Gy and for BFU-E 0.95 Gy. The results of DNA analysis showed that the majority of isolated AC133+ cells were in G0/G1 phase of the cell cycle. We proved that the dose of 2.5 Gy induced massive apoptosis (80%) of these cells without progression through the cell cycle, which indicates interphase cell death. Under the influence of cytokine combination (SCF + IL-3 + FLT3L), the surviving 20% of cells entered the cell cycle and, similarly to non-irradiated control cells, on 7th day 35% of cells were in S phase.

Biological skin covers in treatment of two cases of the Lyell's syndrome.

The treatment of two cases of toxic epidermal necrolysis (Lyell's syndrome) is described. Although some features were common for both ones (young men practically of the same age, reaction after using the same drug) the clinical course of illness was very different. Spontaneous epithelisation of partial-thickness lesions and definitive healing under the xenografts in one patient and full-thickness skin-loss on 12% of body surface with severe septic complications requiring application of cultured keratinocytes and/or skin autografting in the other patient were the main differences. The interdisciplinary approach using a burns treatment protocol in non-burned patient including the close co-operation with the tissue bank in preparing different types of biological covers has been applied.

Potential risk of infection transmission during storage and transplantation of hematological progenitor cells. Safety assurance.

In a group of 71 patients and 22 donors the danger of infection transmission by infusion of cryopreserved peripheral blood progenitor cells to the patient and/or cross contamination of stored grafts was evaluated. No laboratory signs of active infection were found in 15 donors (13 related, 2 unrelated; 68%) and in 55 patients (77%). Active infection by herpesviruses was the most common (in 13 patients and 7 donors), hepatitis B being found in only one case. The cytomegalovirus IgG test was the most common marker of previous infection; it was found in 14 donors and 55 patients. The rate of clinically unsuspected infections in donors and patients including cases requiring immediate treatment among the patients group is relatively high and fully justifies the practice of prophylactic serological testing in the whole range of tests according to the European Blood and Marrow Transplantation Group and International Society for Hematotherapy and Graft Engineering in both autologous and allogeneic transplantations of hematopoietic stem cells.