Colony stimulating factors (CSFs), also called haematopoietic growth factors, regulate bone marrow production of circulating red and white cells, and platelets. They have been shown to be neuroprotective in experimental stroke. Some CSFs also mobilise the release of bone marrow stem cells into the circulation.

To support a review of the guidance issued by the National Institute for Health and Clinical Excellence (NICE) in December 2000 by examining the current clinical and cost-effectiveness evidence on autologous cartilage transplantation.

The research process is a balance between the inherent risks of new discoveries and the risks of research participant safety. Conflicts of interest, inherent to the research process, as well as those introduced by emerging cellular therapies, have the potential to compromise safety. The relationship of trust between the researcher and the clinical trial participant facilitates objective decision making, in the best interest of both parties. In the setup of each clinical trial, investigators incorporate ethical, political, legal, financial, and regulatory considerations as protocols are established. Responsibility to abide by these decisions ensures a systematic process and safeguards participants in this process. The integrity of the research process is strengthened by identifying potential conflicting issues with the guiding principles established in the protocols, which may threaten the objectivity of involved parties and jeopardize safety of the participants. The rapid pace and changing paradigms of new discoveries in cellular therapies exaggerate existing conflicts and introduce new ones. Ethical issues raised by emerging cellular therapies include the division of opinions regarding the use of embryonic and fetal tissue to develop stem cell lines for research, the individual versus professional conscience of a researcher, overselling of outcomes as a result of the researcher's desire to be the first to discover a cellular therapy, and therapeutic misconception resulting from a participant's desire for a miracle cure. The basic ethical issue of whether stem cells should be utilized as a cellular therapy raises heated debates because some believe that it is not acceptable to use fetal material as a source of research material for future cures and others feel equally as strong that inaction is unethical because it results in needless suffering and death owing to the absence of this research. Political issues include the divergent position statements of presidential administrations on cellular therapy, variations in individual state laws, and states becoming involved in research funding, such as California's Proposition 71. Legal concerns include expanding private litigation with diversity of lawsuits, expanding lists of defendants, and the use of class-action lawsuits in research cases. Ownership issues also arise in terms of intellectual property, patents, and ownership of stem cells collected from minors, as in umbilical cord blood donations. Situations that challenge the regulatory processes established to ensure participant safety include differences in reporting requirements for private- and public-funded research and the lack of adequate funding and resources to implement and support the institutional review board (IRB) process. Financial considerations influence the development of clinical protocols, because funding is often limited. Financial incentives, personal investment in companies funding research activities, and fundraising pressures may present potential conflicts. In addition, the increasing role of emerging biotechnology start-up companies and pharmaceutical companies in clinical research introduces additional financial considerations. Administrative policies are needed to address these possible conflicts and ensure research participant safety as cellular therapies progress from the research laboratories to the patient's bedside. Administrative policies to ensure minimum standards of quality for emerging products before human clinical trials, policies to enforce consistent reporting requirements for private and public cellular research, policies to minimize financial conflicts of interest, policies to strengthen implementation of the existing IRB process and to structure into the process a consistent, systematic review of these identified conflicts, and policies to limit private litigation will help to preserve the objectivity of the review process and ultimately increase participant safety.

Overall survival rates are disappointing for women with early poor prognosis breast cancer. Autologous transplantation of bone marrow or peripheral stem cells (in which the patient is both donor and recipient) has been considered a promising technique because it allows much higher doses of chemotherapy to be used.

Lymphoma patients who require high dose chemotherapy are 'rescued' by reinfusion of stem cells to repopulate their bone marrow and minimise the risk of fatal infections or haemorrhage. This review evaluated the evidence for the use of stem cells derived from the peripheral blood to speed the engraftment of neutrophil and platelets when compared to standard bone marrow transplant. A systematic search of the Cochrane Library, Medline and Embase was carried out to identify randomised controlled trials comparing haematological recovery following these two interventions which met predetermined inclusion and exclusion criteria. Four studies were critically appraised and found to follow heterogenous protocols but were otherwise of satisfactory quality. All four studies demonstrated an advantage of peripheral blood stem cell transplantation over bone marrow transplantation in terms of neutrophil recovery and three out of four demonstrated the same trend for platelet engraftment. In sum, there is evidence to support the use of peripheral blood stem cell transplantation for this population of lymphoma patients. Nurses can share this information confidently with patients and other staff. However, a more extensive review of studies which have investigated the association between extended neutrophil and platelet recovery and length of hospitalisation, number of septic neutropenic episodes and cost reduction is needed to give a fuller picture of the effects for treatment.

A group of experts appointed by the Norwegian Centre for Health Technology Assessment (SMM) has undertaken a systematic review of available literature on the clinical effectiveness of transplanting haematopoietic stem cells from cord blood. A total of 17 studies form the documentary basis of the review. Autologous transplants of stem cells from cord blood have not been published. Retrospective studies suggest that the clinical effect of allogeneic cord blood transplants, at least in children, is comparable to transplants with allogeneic stem cells from bone marrow or peripheral blood cells. This review demonstrates the need for prospective studies comparing transplantations of cord blood with bone marrow or peripheral blood stem cells.

Increasingly, clinicians advocate the use of nonmyeloablative allogeneic stem-cell transplants (NM-allo-SCTs, "mini-transplants") to manage hematologic malignancies. They hypothesize that NM-allo-SCT is equally efficacious to standard allo-SCT but produces less regimen-related toxicity.

To support evidence-based clinical guidelines on erythropoietin use for anemia in oncology, we conducted systematic reviews of controlled trials on four patient groups. These were patients with treatment-related anemia; patients with disease-related anemia; patients transplanted with allogeneic hematopoietic stem cells; and those transplanted with autologous hematopoietic stem cells. Two reviewers followed a prospective protocol to select studies, abstract relevant outcomes, evaluate study quality, and conduct meta-analysis where data sufficed. For treatment-related anemia, meta-analysis of available evidence (22 trials; N = 1,927) demonstrated reduced odds of transfusion after erythropoietin, but higher-quality trials reported smaller odds reductions. In several trials, erythropoietin improved quality of life for groups with mean baseline hemoglobin < or = 10 g/dL. However, evidence was insufficient to determine whether initiating erythropoietin treatment earlier for newly anemic patients reduced the odds of transfusion or improved quality of life more than waiting until hemoglobin approached l0 g/dL. Limited evidence (6 trials; N= 693) suggested that erythropoietin decreased the risk of transfusion for patients with disease-related anemia. For those undergoing allotransplants, evidence (7 trials; N = 493) showed erythropoietin modestly decreased time to red cell engraftment and transfusions. Studies on erythropoietin after autologous transplants (6 trials; N = 321) did not support a beneficial effect of erythropoietin.

A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for the evaluation of the scientific literature are described separately (Acta Oncol 2001; 40: 155-65). This synthesis of the literature on chemotherapy for B-cell chronic lymphocytic leukaemia (B-CLL) is based on data from 20 randomised controlled trials and one meta-analysis. Moreover, data from 19 prospective studies, one retrospective study and four other articles were used. Totally 44 scientific articles are included, involving 11,289 patients. The conclusions reached can be summarized into the following points: Primary treatment of patients with symptomatic B-CLL is recommended to be an oral alkylating agent such as chlorambucil. This drug induces tumour remission and symptomatic relief in a majority of patients with progressive disease. Response may be long-lasting, but cure is not obtained. Optimum dose and schedule of administration of chlorambucil or other alkylating agents have not been defined. It is recommended to defer initial therapy until required by disease progression. Large randomised trials have demonstrated that early treatment with chlorambucil in a continuous or an intermittent schedule does not prolong survival in B-CLL patients with low tumour burden (Binet stage A). The addition of corticosteroids to alkylator regimens has not been proven to give any benefit. Combination chemotherapy as primary treatment has not shown any advantage compared with single drugs. Early inclusion of anthracyclines to the therapy does not convincingly add to the activity of alkylating agents. The purine analogues fludarabine and 2-chlorodeoxyadenosine are active in B-CLL. However, like other drugs, they do not appear to be curative. In randomised multicentre trials a benefit from fludarabine as primary therapy compared with polychemotherapy (CHOP or CAP) has been observed in terms of tolerance and treatment response but not yet in survival. No randomised studies have been performed to show whether one of the purine analogues should be preferred. At relapse after single drug treatment, retreatment with the same drug often induces new remissions. However, the proportion of patients responding declines each time chlorambucil or any other single agent is readministered. At progression on single alkylating agents, the purine analogues or various combinations, mostly CHOP, frequently induce tumour remissions. For patients with advanced B-CLL failing to respond to fludarabine or CHOP, the prognosis is poor. None of the salvage regimens reported has produced durable remissions. High-dose chemo-radiotherapy with stem cell transplantation has been evaluated for young patients with B-CLL. A long survival has been shown in some patients following allogeneic and autologous transplantation. However, the risk of transplantation-related mortality is still high with allo-transplants and relapse is common after auto-transplantation. A benefit of purging autologous stem cells has been proposed but evidence is lacking. Thus, transplantation remains experimental; more patients and a longer follow-up are needed to assess if cure can be achieved. In the future an individual risk-adapted therapy will be required. The clinical heterogeneity of the disease has pointed to the necessity of new predictors for prognosis evaluated in prospective trials.