Randomized open comparison of montelukast and sublingual immunotherapy as add-on treatment in moderate persistent asthma due to birch pollen.

BACKGROUND: No studies have directly compared the effects of immunotherapy and antileukotrienes due to the long time required to appreciate the clinical effects of immunotherapy. We compared the effect of montelukast (MK) and SLIT added to standard therapy in moderate asthma over 5 years. METHODS: Open randomized controlled trial. Patients with moderate asthma (and rhinitis) solely due to birch pollen were randomized to receive either MK (10 mg/d) or birch sublingual immunotherapy (SLIT) in the pollen seasons, in addition to formoterol/fluticasone. All the patients also received salbutamol and cetirizine as rescue medications. Asthma and rhinitis symptoms were recorded on diary cards from February to May at baseline and after 3 and 5 years of study. In-season nasal eosinophils and bronchial hyperresponsiveness were also evaluated. RESULTS: Thirty-three adult patients were enrolled and 29 completed the study. The groups were homogeneous at baseline. Bronchial and nasal symptom scores were lower at 3 and 5 years compared to baseline in the SLIT group. Bronchial hyperresponsiveness and bronchodilator use decreased significantly in both groups at 5 years, but only in the SLIT group at 3 years. In the SLIT group there was a significant decrease in nasal eosinophils compared to baseline and to the MK group. CONCLUSION: In patients with birch pollen-induced moderate asthma and rhinitis, the addition of SLIT provides a greater clinical benefit than that of MK.

The type of sensitizing allergen can affect the evolution of respiratory allergy.

BACKGROUND: Numerous factors affect the evolution of respiratory allergy, in children, but little is known in adults. We assessed in a prospective study the influence of the type of allergen on the progression of disease. METHODS: Outpatients, with respiratory allergy underwent skin tests and pulmonary function/methacholine challenge at baseline and after 3 years. Patients were subdivided in pure rhinitis or rhinitis + bronchial hyperreactivity (BHR). In polysensitized subjects a single relevant allergen (mites, grasses, birch, Parietaria) was identified based on symptom distribution and when needed on nasal challenge. RESULTS: 6750 patients (age range 12-46) were studied. Of them, 17.8% were monosensitized but this percentage decreased to 10.4% after 3 years (P < 0.05). Subjects with pure rhinitis were 81% at the beginning and 48% at the end. After 3 years, the patients with bronchial responsiveness increased from 18% to 58% for mites, 22% to 49% for birch, 18% to 44% for grasses, 17% to 32% for Parietaria, with a significant difference among allergens (P < 0.05). Almost the same was seen in monosensitized subjects, being mites most likely to cause a worsening. All patients with BHR at baseline received immunotherapy. In these patients the onset of new sensitizations was significantly lower than in the group (pure rhinitis) receiving drugs only and lower airways symptoms disappeared more frequently. CONCLUSION: The different type of allergen influences the course of the disease, as well as the use of immunotherapy.

Two cases of foodborne botulism with home-preserved asparagus.

Botulism is a rare but potentially fatal disease caused by toxins produced by Clostridium botulinum. We report botulism in two adult females, one of them just tasting from "bad" asparagus and the other eating the full portion. Both patients survived after intermittent mechanical ventilation and trivalent antitoxin administration. The diagnosis was confirmed by detection of botulinum toxin. Acute onset of bilateral cranial neuropathies associated with symmetric descending weakness as well as some key features of the botulism syndrome including absence of fever, symmetric neurologic deficits, the patients remaining responsive and no sensory deficits, with the exception of blurred vision, led to the clinical diagnosis in the first presenting case which was then easily made in the second. Despite the fact that amount of toxin ingested, time-to-symptom development, and time-to-recovery markedly differed in the two patients, their maximal disease severity was similar.

Allergy to ragweed in northern Italy and prevention strategies.

Ragweed is spreading in Europe and in northern Italy, particularly in the Lombardia and Friuli areas. It constitutes a cause of significant morbidity for asthma and rhinoconjuntivitis involving as much as 12% of the general population in those countries most at risk. The public campaign to fight ragweed promoted in 1999 by the Lombardia Region failed to achieve significant results since the count of ragweed pollen in the subsequent years is similar to the previous and reached peaks of 700 pollens per m3.

Cold-induced rhinitis in skiers--clinical aspects and treatment with ipratropium bromide nasal spray: a randomized controlled trial.

Cold-induced rhinitis (CIR) is common among skiers and is perceived as a troublesome disease. We studied the clinical characteristics of CIR in a population of skiers and we evaluated the effectiveness of ipratropium bromide nasal spray (IBNS) in relieving symptoms in a double-blind placebo-controlled fashion. By means of specific questionnaires, we evaluated 144 subjects (69% men; mean age, 42.2 years). The prevalence of CIR was 48.6% and the distinctive symptom was rhinorrhea (96%), often severe. The prevalence of atopy was higher in the CIR patients (chi2; p = 0.004). Twenty-eight CIR subjects participated in a double-blind placebo-controlled cross-over trial for evaluating the effectiveness of IBNS (80 microg twice per day [b.i.d.]). The severity of symptoms was assessed by a visual analog scale, and the number of cleaning tissues used also was evaluated. The actively treated group showed a significant improvement of rhinorrhea (p = 0.0007) and a reduction in the number of cleaning tissues used (p = 0.0023). Only four mild local side effects were reported. We conclude that IBNS could be regarded as an optimal therapeutic option for treating CIR symptoms in skiers.

Short and long-term evaluation of two structured self management programmes on asthma.

In recent years education programmes for adults have been developed focusing on improving patient self-management. The aim of this study was to evaluate the efficacy of two different educational programmes on asthma at one year (short-term efficacy) and three years (long-term efficacy). Changes in pulmonary function (FEV1), knowledge of disease and skill concerning inhalation technique were evaluated to determine the efficacy of the educational programme. Forty patients were randomly assigned to the two different educational programmes. Twenty subjects (mean age 49 +/- 11 yrs; FEV1 79% +/- 15 of predicted) were assigned, to a basic educational programme, while the others (mean age 44 +/- 11 yrs; FEV1 79% +/- 14 of predicted) were assigned to an "asthma school" programme. In both "basic" and "asthma school" groups there was a significant increase from baseline to one year (p < 0.05) and three years (p < 0.05) in FEV1, number of correct answers to the knowledge questionnaire, and number of correct steps during the inhalation procedure. No significant differences were found between the two groups at baseline, one year and three years for all three variables studied. This study confirms that both educational programmes determine in asthmatics an improvement in lung function, knowledge of disease and skill for inhalation technique at one year and three years following commencement of the programme. A "basic" educational programme is as effective as an "asthma school" one.

Reliability of a questionnaire for evaluating the understanding of asthma.

The present study was designed to evaluate the repeatability of a questionnaire developed to assess the understanding that asthma patients have of their disease and, on the basis of its variability, estimate the sample size necessary for determining the efficacy of a future structured program on asthma knowledge. The repeatability of the Asthma Questionnaire (AQ) was evaluated by asking 89 patients to complete it twice within a period of 7-10 days without the subject being exposed to any programme on asthma knowledge between the two administrations. The AQ was demonstrated to have good content and face validity. Results showed that neither age nor sex had a significant influence on total scores, and that the degree of reliability was adequate (R = 0.769). The mean percentage of correct answers was observed to be approximately 70% in both sessions, suggesting a consistent area for possible improvement which could be targeted by means of an appropriately structured programme on asthma knowledge. For comparative purposes before and after the programme, or for measuring its efficacy, the AQ should be recommended. In conclusion the Asthma Questionnaire could provide a useful tool for the general practitioner, chest physician and other health professionals, to assess what the patient really does understand or does not, concerning asthma management, and hence be the starting point for a well-tailored educational intervention.

Antitumor vaccination: where we stand.

BACKGROUND AND OBJECTIVES: Vaccination is an effective medical procedure of preventive medicine based on the induction of a long-lasting immunologic memory characterized by mechanisms endowed with high destructive potential and specificity. In the last few years, identification of tumor-associated antigens (TAA) has prompted the development of different strategies for antitumor vaccination, aimed at inducing specific recognition of TAA in order to elicit a persistent immune memory that may eliminate residual tumor cells and protect recipients from relapses. In this review characterization of TAA, different potential means of vaccination in experimental models and preliminary data from clinical trials in humans have been examined by the Working Group on Hematopoietic Cells. EVIDENCE AND INFORMATION SOURCES: The method employed for preparing this review was that of informal consensus development. Members of the Working Group met four times and discussed the single points, previously assigned by the chairman, in order to achieve an agreement on different opinions and approve the final manuscript. Some of the authors of the present review have been working in the field of antitumor immunotherapy and have contributed original papers to peer-reviewed journals. In addition, the material examined in the present review includes articles and abstracts published in journals covered by the Science Citation Index and Medline. STATE OF THE ART: The cellular basis of antitumor immune memory consists in the generation and extended persistence of expanded populations of T- and B-lymphocytes that specifically recognize and react against TAA. The efficacy of the memory can be modulated by compounds, called "adjuvants", such as certain bacterial products and mineral oils, cytokines, chemokines, by monoclonal antibodies triggering co-stimulatory receptors. Strategies that have been shown in preclinical models to be efficient in protecting from tumor engraftment, or in preventing a tumor rechallenge, include vaccination by means of soluble proteins or peptides, recombinant viruses or bacteria as TAA genes vectors, DNA injection, tumor cells genetically modified to express co-stimulatory molecules and/or cytokines. The use of professional antigen-presenting cells, namely dendritic cells, either pulsed with TAA or transduced with tumor-specific genes, provides a useful alternative for inducing antitumor cytotoxic activity. Some of these approaches have been tested in phase I/II clinical trials in hematologic malignancies, such as lymphoproliferative diseases or chronic myeloid leukemia, and in solid tumors, such as melanoma, colon cancer, prostate cancer and renal cell carcinoma. Different types of vaccines, use of adjuvants, timing of vaccination as well as selection of patients eligible for this procedure are discussed in this review. PERSPECTIVES: Experimental models demonstrate the possibility of curing cancer through the active induction of a specific immune response to TAA. However, while pre-clinical research has identified several possible targets and strategies for tumor vaccination the clinical scenario is far more complex for a number of possible reasons. Since experimental data suggest that vaccination is more likely to be effective on small tumor burden, such as a minimal residual disease after conventional treatments, or tumors at an early stage of disease, better selection of patients will allow more reliable clinical results to be obtained. Moreover, a poor correlation is frequently observed between the ability of TAA to induce a T-cell response in vitro and clinical responses. Controversial findings may also be due to the techniques used for monitoring the immune status. Therefore, the development of reliable assays for efficient monitoring of the state of immunization of cancer patients against TAA is an important goal that will markedly improve the progress of antitumor vaccines. (ABSTRACT TRUNCATED)

Clinical study on Alternaria spores sensitization.

BACKGROUND: sensitization to fungi spores is often associated with sensitization to other allergens and so it is difficult to estabilish the exact cause of illness. OBJECTIVE: the aim of the study was to evaluate a group of patients monosensitized to Alternaria and to establish the prevalence, periodicity and clinical profile of this kind of sensitization. METHODS: 37 subjects who were monosensitized to Alternaria (prick-test positive), according to a previous epidemiological study were evaluated. Clinical symptoms and the period of their occurrence were taken into consideration as well as immunological parameters (RAST). RESULTS: 20 patients (over 50%) included in the study proved to be affected by asthma associated with other allergic symptoms and 22 patients (60%) presented perennial symptoms. The RAST carried out on 34 monosensitized subjects proved positive in 11 and negative in 23. CONCLUSIONS: Alternaria sensitization is characterized by a perennial periodicity with severe respiratory symptoms (asthma) which occur primarily in children. Prick test is preferable to and more reliable than RAST as a diagnostic test.

Clinical study on Alternaria spores sensitization

Background: sensitization to fungi spores is often associated with sensitization to other allergens and so it is difficult to estabilish the exact cause of illness. Objective: the aim of the study was to evaluate a group of patients monosensitized to Alternaria and to establish the prevalence, periodicity and clinical profile of this kind of sensitization. Methods: 37 subjects who were monosensitized to Alternaria (prick-test positive), according to a previous epidemiological study were evaluated. Clinical symptoms and the period of their occurrence were taken into consideration as well as immunological parameters (RAST). Results: 20 patients (over 50%) included in the study proved to be affected by asthma associated with other allergic symptoms and 22 patients (60%) presented perennial symptoms. The RAST carried out on 34 monosensitized subjects proved positive in 11 and negative in 23. Conclusions: Alternaria sensitization is characterized by a perennial periodicity with severe respiratory symptoms (asthma) which occur primarily in children. Prick test is preferable to and more reliable than RAST as a diagnostic test (AU)

Introducción: la sensibilización a esporas de hongos se asocia frecuentemente con la sensibilización a otros alergenos, con lo que es difícil establecer la causa exacta de la enfermedad. Objetivo: la finalidad del estudio fue evaluar a grupos de pacientes monosensibilizados a Alternaria y establecer la prevalencia, periodicidad y perfil clínico de esta clase de sensibilización. Métodos: se estudiaron 37 pacientes monosensibilizados a Alternaria (prick test positivo) seleccionados en un estudio epidemiológico previo. También se consideraron los síntomas clínicos y su frecuencia, así como algunos parámetros inmunológicos (RAST). Resultado: 20 pacientes (por encima del 50 por ciento) padecían asma asociada con otros síntomas alérgicos y 22 pacientes (60 por ciento) presentaban síntomas perennes. El RAST llevado a cabo en 34 pacientes monosensibilizados, fue positivo en 11 y negativo en 23. Conclusiones: la sensibilización a Alternaria se caracterizó por ser perenne, cursar con síntomas respiratorios graves (asma) y tener lugar principalmente en niños. Es preferible y más fiable como test diagnóstico el test cutáneo que el RAST. (AU)

Cell therapy: achievements and perspectives.

BACKGROUND AND OBJECTIVE: Cell therapy can be considered as a strategy aimed at replacing, repairing, or enhancing the biological function of a damaged tissue or system by means of autologous or allogeneic cells. There have been major advances in this field in the last few years. This has prompted the Working Group on Hematopoietic Cells to examine the current utilization of this therapy in clinical hematology. EVIDENCE AND INFORMATION SOURCES: The method employed for preparing this review was that of informal consensus development. Members of the Working Group met three times, and the participants at these meetings examined a list of problems previously prepared by the chairman. They discussed the single points in order to reach an agreement on different opinions and eventually approved the final manuscript. Some of the authors of the present review have been working in the field of cell therapy and have contributed original papers in peer-reviewed journals. In addition, the material examined in the present review includes articles and abstracts published in journals covered by the Science Citation Index and Medline. STATE OF THE ART: Lymphokine-activated killer (LAK) and tumor-infiltrating lymphocytes (TIL) have been used since the '70s mainly in end-stage patients with solid tumors, but the clinical benefits of these treatments has not been clearly documented. TIL are more specific and potent cytotoxic effectors than LAK, but only in few patients (mainly in those with solid tumors such as melanoma and glioblastoma) can their clinical use be considered potentially useful. Adoptive immunotherapy with donor lymphocyte infusions has proved to be effective, particularly in patients with chronic myeloid leukemia, in restoring a state of hematologic remission after leukemia relapse occurring following an allograft. The infusion of donor T-cells can also have a role in the treatment of patients with Epstein-Barr virus (EBV)-induced post-transplant lymphoproliferative disorders. However, in this regard, generation and infusion of donor-derived, virus specific T-cell lines or clones represents a more sophisticated and safer approach for treatment of viral complications occurring in immunocompromised patients. Whereas too few clinical trials have been performed so far to draw any firm conclusion, based on animal studies dendritic cell-based immunotherapy holds promises of exerting an effective anti-tumor activity. Despite leukemic cells not being immunogenic, induction on their surface of co-stimulatory molecules or generation of leukemic dendritic cells may induce antileukemic cytotoxic T-cell responses. Tumor cells express a variety of antigens and can be genetically manipulated to become immunogenic. The main in vitro and in vivo functional characteristics of marrow mesenchymal stem cells (MSCs) with particular emphasis on their hematopoietic regulatory role are reviewed. In addition, prerequisites for clinical applications using culture-expanded mesenchymal cells are discussed PERSPECTIVES: The opportuneness of using LAK cells or activated natural killer (NK) cells in hematologic patients with low tumor burden (e.g. after stem cell transplantation) should be further explored. Moreover the role of new cytokines in enhancing the antineoplastic activity of NK cells and the infusion of selected NK in alternative to CTL for graft versus leukemia (GVL) disease (avoiding graft versus host disease (GvHD) seems very promising. Separation of GVL from GvHD through generation and infusion of leukemia-specific T-cell clones or lines is one of the most intriguing and promising fields of investigations for the future. Likewise, strategies devised to improve immune-reconstitution and restore specific anti-infectious functions through either induction of unresponsiveness to recipient alloantigens or removal of alloreactive donor T-cells might increase the applicability and success of hematopoietic stem cell transplantation. (ABSTRACT TRUNCATED)

[Acute silicosis in jewelry casting]. / Silicosi acuta nella microfusione artistica.

An accelerated silicosis case made our Occupational Health Unit focus on a pathology thought dropping so far to die out. Furthermore this event occurred in a manufacturing (lost-wax process in jewelry casting) regarded as a low-risk exposure. Besides unsuitable procedures, the user had underestimated the specific risk of that raw material (talcum-like powder at 60-80% silica crystalline level), commonly called "gypsum", inappropriately labelled since not yet adequately classified by the hazardous substances list. The widespreading of this manufacture in our area (Vicenza district) and the recent inclusion of Silica Crystalline in the Class 1 made by IARC (Jan 1997) have urged this Unit to take action in industrial hygiene investigations, instructions to the workers, mandatory directions to dealers concerning the proper hazard labelling for products containing silica crystalline and circulation of information among other Occupational Health Units involved.

Ex vivo expansion of hematopoietic cells and their clinical use.

BACKGROUND AND OBJECTIVE: Hematopoietic stem cells are being increasingly used for treatment of malignant and nonmalignant disorders. Various attempts have been made in recent years to expand and manipulate these cells in order to increase their therapeutic potential. A Working Group on Hematopoietic Cells has analyzed the most recent advances in this field. EVIDENCE AND INFORMATION SOURCES: The method used for preparing this review was an informal consensus development. Members of the Working Group met three times, and the participants at these meetings examined a list of problems previously prepared by the chairman. They discussed the single points in order to achieve an agreement on different judgments, and eventually approved the final manuscript. Some authors of the present review have been working in the field of stem cell biology, processing and transplantation, and have contributed original papers in peer-reviewed Journals. In addition, the material examined in the present review includes articles and abstracts published in Journals covered by the Science Citation Index and Medline. STATE OF ART: Over the last decade, recombinant DNA technology has allowed the large scale production of cytokines controlling the proliferation and differentiation of hemo-lymphopoietic cells. Thus, in principle, ex vivo manipulation of hemopoiesis has become feasible. The present review covers three major area of interest in experimental and clinical hematology: manipulation of hematopoietic stem/progenitor cells, cytotoxic effector cells and antigen presenting dendritic cells. Preliminary data demonstrate the possibility of using, in a clinical setting, ex vivo expanded hematopoietic cells with the aim of reducting, and perhaps abrogating, the myelosuppression after high-dose chemotherapy. Concurrently, other important potential applications for ex vivo manipulation of hematopoietic cells have recently been investigated such as the generation and expansion of cytotoxic cells for cancer immunotherapy, and the large scale production of professional antigen presenting cells capable of initiating the process of immune response. CONCLUSIONS AND PERSPECTIVES: Present and future challenges in this field are represented by the expansion of true human stem cells without maturation, to extend this strategy to allogeneic stem cell transplantation as well as the manipulation of cycling of primitive progenitors for gene therapy programs. The selective outgrowth of normal progenitor cells over neoplastic cells to achieve tumor-free autografts may ameliorate the results of autologous transplantation. The selective production of cellular subsets to manipulate the graft versus-host and graft versus-tumor effects and anti-tumor vaccination strategies may be important to improve cellular adoptive immunotherapy.

Clinical use of allogeneic hematopoietic stem cells from sources other than bone marrow.

BACKGROUND AND OBJECTIVE: Peripheral blood stem cells (PBSC) are being increasingly used as an alternative to conventional allogeneic bone marrow (BM) transplantation. This has prompted the Working Group on CD34-Positive Hematopoietic Cells to evaluate the current utilization of allogeneic PBSC in clinical hematology. EVIDENCE AND INFORMATION SOURCES: The method employed for preparing this review was that of informal consensus development. Members of the Working Group met three times, and the participants at these meetings examined a list of problems previously prepared by the chairman. They discussed the single points in order to reach an agreement on different opinions and eventually approved the final manuscript. Some of the authors of the present review have been working in the field of stem cell transplantation and have contributed original papers in peer-reviewed journals. In addition, the material examined in the present review includes articles and abstracts published in journals covered by the Science Citation Index and Medline. STATE OF THE ART: Review of the current literature shows that unmanipulated allogeneic PBSC give prompt and stable engraftment in HLA-identical sibling recipients. Despite the much higher number of T-cells infused, the incidence and severity of acute GVHD after PBSC transplant seems comparable to that observed with bone marrow (BM) cells. In comparison to the latter, PBSC probably ensure faster immunologic reconstitution in the early post-transplant period. Controversial results on the incidence and severity of acute-GVHD have been reported when CD34+ selection methods are used. Prospective randomized trials are underway to compare the results of PBSC and BM allogeneic transplantation. In mismatched family donor transplants, T-cell depleted PBSC successfully engraft immune-myeloablated recipients through a megacell-dose effect able to overcome the HLA barrier. Experience with PBSC in the context of unrelated donor transplants is currently anecdotal and prospective trials should be completed before that practice becomes routine. Finally, there is also limited evidence that, following induction chemotherapy, the addition of PBSC to donor lymphocyte infusion (DLI) for treatment of leukemia relapse after BMT may improve the safety and effectiveness of DLI itself. Concerning cord blood (CB) transplants, the most interesting aspects are the ease of CB collection and storage, the low risk of viral contamination and the low immune reactivity of CB cells. This last property has its clinical counterpart in an apparently reduced incidence and severity of acute GVHD both in sibling and unrelated CB transplants, probably making the level of donor/recipient HLA disparity acceptable a greater degree with respect to what is required for transplants from other sources.

Prevalence of sensitization to Alternaria in allergic patients in Italy.

BACKGROUND: The actual prevalence of sensitization to Alternaria is not known, partly due to the unreliability of diagnostic extracts. OBJECTIVE: To assess skin positivity to extracts of Alternaria in a wide population of Italian patients suffering from respiratory symptoms using a biologically standardized extract. METHODS: A total of 2942 patients were skin prick tested with Alternaria, and a panel of common inhalant allergens. Blood samples for specific IgE quantitation were taken both from patients positive and from patients negative (control group) to Alternaria extract. RESULTS: Three hundred six patients (10.4%, ranging from 1.8% in Turin to 29.3% in Cagliari) were positive to Alternaria; 37 were sensitized to only this mold, while the remaining 269 were sensitized to at least one other allergen. Of the Alternaria-positive patients, 79.7% suffered from rhinitis and 53.3% from asthma, either alone or associated with other symptoms. CONCLUSIONS: We suggest that, at least in Italy and in countries with similar climatic and environmental situations, standardized Alternaria extract should be included in the panel commonly used in investigating the allergen responsible in patients suffering from respiratory allergy.

Cefepime versus ceftazidime in the treatment of lower respiratory tract infections.

The objective of the study was to compare the safety and efficacy of cefepime and ceftazidime in the treatment of community acquired lower respiratory tract infections of moderate intensity. Eighty-six patients were randomized at a 2:1 ratio to receive respectively cefepime 1 g b.i.d. or ceftazidime 1 g t.i.d. The drugs were well tolerated and the occurrence of adverse events in each group was comparable. The rates of satisfactory clinical response were 96% (49/51) for cefepime and 89% (24/27) for ceftazidime. A total of 73 pathogens were isolated and pathogen eradication rates were 98% and 96% respectively for the cefepime and ceftazidime treatment groups. In conclusion, the data confirmed that cefepime could be a good alternative to ceftazidime.

Allogeneic hematopoietic stem cells from sources other than bone marrow: biological and technical aspects.

BACKGROUND AND OBJECTIVE: Identification and characterization of hematopoietic stem cells in peripheral blood (PB) and cord blood (CB) have suggested feasible alternatives to conventional allogeneic bone marrow (BM) transplantation. The growing interest in this use of allogeneic stem cells has prompted the Working Group on CD34-positive Hematopoietic Cells to review this subject by analyzing its biological and technical aspects. EVIDENCE AND INFORMATION SOURCES: The method used for preparing this review was informal consensus development. Members of the Working Group met three times, and the participants at these meetings examined a list of problems previously prepared by the chairman. They discussed the individual points in order to reach an agreement on the various concepts, and eventually approved the final manuscript. Some of the authors of the present review have been working in the field of hematopoietic stem cell biology and processing, and have contributed original papers published in peer-reviewed journals. In addition, the material examined in the present review includes articles and abstracts published in journals covered by the Science Citation Index and Medline. STATE OF ART: Several studies have now shown that hematopoietic stem cells collected from peripheral blood after the administration of G-CSF, or from cord blood upon delivery, are capable of supporting rapid and complete reconstitution of BM function in allogeneic recipients. Perhaps more importantly, reinfusion of large numbers of HLA-matched T-cells from PB collections or T-cells with various degrees of HLA disparity from CB did not result in a higher incidence or greater severity of acute graft-versus-host disease than expected with BM. Based on the data reviewed, operative guidelines for mobilization, collection and graft processing are provided. PERSPECTIVES: It should be remembered that despite the growing interest, these procedures must be still considered as advanced clinical research and should be included in formal clinical trials aimed at demonstrating their definitive role in stem cell transplantation. In this regard, a large European randomized study is currently comparing PB and BM allografts. However, the possibility of collecting large quantities of hematopoietic progenitor-stem cells, perhaps with reduced allo-reactivity, offers an exciting perspective for widening the number of potential stem cell donors and greater leeway for graft manipulation than is possible with BM.