[Present status in hematopoietic stem cell transplantation: peripheral blood stem cell transplantation].
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Peripheral blood stem cell transplantation (PBSCT) is the process of removing circulating stem cells from the peripheral blood through apheresis and returning these cells to the patient after dose-intensive chemotherapy. Clinical trials using PBSCT and dose-intensive chemotherapy are underway at cancer centers across the country. Nurses caring for patients who are undergoing PBSCT need an understanding of all aspects of the process in order to competently manage the toxicities, as well as to educate patients, families, and other staff. Nurses need to consider issues for nursing research to improve the quality of life for these patients.
Peripheral blood stem cell (PBSC) transplantation is a promising new therapy in the treatment of malignancies. It is being used to supplement and in place of bone marrow transplantation to restore hematopoiesis after myeloablative therapy. PBSCs are collected through apheresis, generally after a course of myelosuppressive therapy to prime the progenitor cells. Problems that potentially could arise during PBSC collection include citrate toxicity, hypovolemia, and thrombocytopenia. PBSC infusion is similar to the infusion of bone marrow. Engraftment following PBSC transplantation progresses rapidly, resulting in shorter hospital stays. The future of PBSC therapy looks promising, but much still has to be learned about this innovative treatment.
Peripheral blood stem cells (PBSC) are increased dramatically during a recovery phase after myelosuppressive chemotherapy. PBSC can be used for hematological reconstitution after marrow-ablative therapy. Autologous blood stem cell transplantation (ABSCT) has increasingly been used for the treatment of malignant diseases. Cytokines, especially hematopoietic cytokines are utilized for mobilization of PBSC, enhancement of chemosensitivity of leukemic cells having cytokine receptors and enhancement of hematologic recovery after ABSCT. We studied effects of granulocyte colony-stimulating factor (G-CSF) in these settings. In cytotoxic drug plus G-CSF mobilization of PBSC, granulocyte/macrophage and erythroid progenitor cells were significantly increased in PBSC harvests compared to cytotoxic drug-induced mobilization. When G-CSF was administered prior to the marrow-ablative conditioning before ABSCT, clinical results suggest that chemosensitivity of leukemic cells may be increased. When G-CSF was given after ABSCT, hematologic recovery from marrow aplasia was enhanced substantially. These observations clearly indicate that G-CSF is useful to mobilize PBSC and to facilitate ABSCT.
Peripheral blood stem cells (PBSCs) are being used as an alternative to autologous marrow rescue for hematopoietic reconstitution after high-dose chemotherapy in patients with neuroblastoma and other solid malignancies. Use of PBSCs is preferred by some because of the belief that there is less risk of tumor contamination. Because tumor stem cell contamination is thought to be one contributing cause of relapse after myeloablative therapy and autologous reconstitution, we examined the potential risk of reinfusing circulating neuroblastoma cells by in vitro evaluation of their clonogenicity. Immunocytologic and tumor cell clonogenic analyses were performed on 74 blood samples obtained from 56 children with advanced-stage neuroblastoma. Concurrently drawn bone marrow specimens were evaluated in 30 instances. Circulating neoplastic cells were detected in 19 of 74 (26%) for all specimens and by immunologic techniques (26%). Using a clonogenic assay, 13 grew identifiable tumor colonies. Comparing results with the two techniques showed tumor colony growth in 10 of the 19 positive specimens by immunocytology. However, 3 of 53 samples (6%) that were negative by immunocytology were positive by the clonogenic assay. Of the 11 positive blood samples, 9 concurrent marrows contained neuroblastoma cells; of the 19 negative blood specimens, 3 concurrent marrows had metastatic disease. We conclude that circulating neuroblastoma cells are present in peripheral blood and have clonogenic properties in vitro. This supports the view that tumor cell contamination may well be one cause of relapse after autologous reconstitution. Consequently, PBSC collections should also undergo meticulous monitoring for tumor contamination before autologous reinfusion.
Peripheral blood stem cells were collected by granulocyte-colony stimulating factor (G-CSF) mobilization in normal volunteers and patients with hematological malignancy in complete remission without anti-cancer drug synchronization. The yields of PBSC and the possibility of G-CSF mobilization in steady state for PBSC transplantation (PBSCT) were studied. For collecting PBSC, G-CSF was subcutaneously injected at the dose of 100 micrograms/m2 on 5 consecutive days. PBSC collection was performed on day 4 and/or 5 by using cell separator, CS-3000. In normal volunteers, the yields of colony forming unit in granulocyte and macrophage (CFU-GM) was 1.9 x 10(4) kg by processing the plasma of 1.5L, and CD34 positive cell was 1.4% on the average. In patients with hematological malignancy in complete remission, the processing volume ranges from 10 to 18L/1-2 cycles, the average CFU-GM number was 2.2 x 10(5)/kg, and the average CD34 positive cell was 2.2%. In acute leukemia case, PBSCT was performed by using G-CSF mobilized PBSC, engraftment was achieved earlier. In conclusion, the yields of G-CSF mobilized PBSC from normal volunteers suggested the possibility of PBSCT and the yields of PBSC from patients in complete remission proved that G-CSF mobilization method in complete remission status could take the place of drug synchronized G-CSF mobilization for which the timing of collection and the drug choice for synchronization are intricate.
Peripheral blood stem cell transplantation after reduced-intensity conditioning (RIC-PBSCT) regimen is an alternative to conventional regimens with less immediate toxicity. Since immune recovery is of crucial importance for the control of infections, we retrospectively studied the recovery of T-, B- and NK cell subsets in 20 consecutive patients undergoing RIC-PBSCT. We also studied the thymic output using T-cell receptor excision circle assay. Engraftment was rapid and few infectious complications were seen: three early (before 2.5 months) cases of asymptomatic cytomegalovirus reactivation, two late Gram-negative bacterial infections and no fungal infection. While CD4+ T-cell reconstitution was slow, CD8+ T-cell counts were close to normal values at 4 months. Median CD19+ B-cell counts reached normal values at 11 months. Rapid CD56+ NK cell reconstitution was noticed as early as 1.5 months. Low T-cell receptor excision circle numbers and preponderance of memory-type subsets among T cells further suggested that CD8+ T-cell reconstitution resulted predominantly from peripheral expansion and that thymic-dependent reconstitution was severely impaired. In conclusion, large peripheral T-cell expansion may compensate for late thymic-dependent lymphopoiesis, and may, with other factors such as NK and B-cell reconstitution and careful antiinfectious prophylaxis, help limit the incidence of severe infections after RIC-PBSCT.
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Allogeneic peripheral blood stem cell transplantation (Allo-PBSCT) has been performed as an alternative to bone marrow transplantation (BMT). Here we report poor mobilization with granulocyte-colony stimulating factor (G-CSF) and engraftment kinetics in Allo-PBSCT. Sixteen patients (aged 6-61 yr, median 34 yr) received allogeneic peripheral blood stem cells from related donors (aged 15-68 yr, median 37 yr) after myeloablative therapy. Nine of the patients had standard-risk disease and 7 had high-risk disease. The donors received G-CSF at a dose of 10 micrograms/kg/day by subcutaneous injection for 4 to 6 days. Peripheral blood stem cells were subsequently collected in 1 to 3 aphereses and infused immediately. All patients received G-CSF after transplantation. Fifteen patients underwent Allo-PBSCT and one underwent Allo-PBSCT plus BMT. The mean number of CD34+ cells infused in the 15 Allo-PBSCT patients was 6.32 x 10(6)/kg (range 1.28-14.20). The outcomes were compared with 9 identically treated patients who underwent Allo-BMT. The median times until engraftment for neutrophils > 500/microliter and platelets > 20,000/microliter were 14 (range 10-17) and 15 (range 11-50) days in the Allo-PBSCT group and 17 (range 13-29) and 20 (range 16-160) days in the Allo-BMT group, respectively (p = 0.0177 and p = 0.003). Three donors were considered to have poor mobilization (< 2 x 10(6) CD34+ cells/kg of the recipient); two of them yielded 1.28 and 1.78 x 10(6) CD34+ cells/kg in 3 apheresis procedures. The patients who received cells from these donors showed prompt neutrophil engraftment, but one showed delayed platelet engraftment and another died of grade IV acute GVHD before reaching 20,000 platelets/microliter. An additional bone marrow harvest was necessary from one donor because of poor mobilization(0.17 x 10(6) CD34+ cells/kg). Thus, Allo-PBSCT results in more rapid engraftment. It will be necessary to clarify the minimum CD34+ cell dose for complete engraftment in a larger series of trials.
Autologous peripheral blood stem cell transplantation (APBSCT) as a rescue for myeloablative chemotherapy has become the standard of care for several malignancies. The majority of pre-transplant treatment is provided in outpatient oncology clinics and early discharge post-transplant is facilitated by the use of colony stimulating factors. The patient/family is then required to manage complex self-care in the home environment (Johns, 1998; Poloquin, 1997; Schulmeister et al., 2005). This needs assessment was undertaken to determine how to improve the quality of care delivery for patients/families undergoing APBSCT. This qualitative research utilized unstructured interviews, observation, and field notes for data collection. Data were analyzed using thematic content analysis. Four key concepts to enhance the quality of care delivery emerged: knowledge, communication, support, and skill.
Autologous peripheral blood stem cell transplantation (PBSCT) has been demonstrated to result in rapid. stable long-term engraftment. However, there has been considerable debate concerning the cells responsible for early and late hematopoietic reconstitution after PBSCT. Recently, CD34+ hematopoietic stem and progenitor cells have been clearly divided into two subpopulations by flow cytometry; namely undifferentiated pluripotent stem cells and differentiated committed progenitor cells. However, only a few studies have defined which subset contained in graft products might be the most predictive for late hematopoietic reconstitution after PBSCT. In this review, we present updated information regarding the relationships between the number of infused CD34+ cells or their immature subsets such as CD34+ CD90+ cells and the late hematopoietic reconstitution after PBSCT, and discuss the threshold dose of CD34 + CD90+ cells required for sustained long-term engraftment.
Allogeneic peripheral blood stem cell transplantation (alloPBSCT) is an emerging technology. As this technology develops, transplant centers are concerned with looking for technologic advances that will result in improvements in clinical outcomes and lower costs. We provide comparative estimates of costs and resource use for alloPBSCT in comparison to allogeneic bone marrow transplantation (alloBMT) for persons with hematologic malignancies from the time of harvest to 100 days post transplant. A retrospective, cost-identification analysis was conducted for patients in two consecutive phase II clinical trials at the University of Nebraska Medical Center. Identical preparative regimens, graft-versus-host disease prophylaxis, post-transplant hematopoietic colony-stimulating factor treatment regimens, and discharge criteria were used. Total median costs were $18,304 lower for alloPBSCT, with lower costs during recovery; specifically for hospitalization, platelet products, hematopoietic growth factors, intravenous hyperalimentation, supportive care agents, supplies, and antibacterial agents. This study provides preliminary evidence for short-term cost savings associated with alloPBSCT. However, concerns exist over the potential for higher costs due to preliminary reports of higher rates of chronic graft-versus-host disease, as well as more intensive induction regimens that may result in lower relapse rates. The premature adoption of new technologies based on short-term economic factors, in the absence of adequate clinical trial data, may prove to be ill-advised, particularly for complex medical treatments such as allogeneic transplantation.
Nonmyeloablative peripheral blood stem cell transplantation (PBSCT) is a novel therapeutic strategy for patients with malignant and non-malignant hematologic diseases. Infectious complications of this procedure have not been previously well described. Data on 12 patients transplanted at a tertiary care center were collected prospectively and verified retrospectively. Neutropenia developed in a third of patients, lasting for a median of 5 days. All patients developed some degree of graft-versus-host disease, as intended. Most patients achieved full chimerism by week 5. Bacterial infections occurred in two patients (17%). Cytomegalovirus (CMV) viremia occurred in five patients (42%) at a median of 80 days; none had received CMV prophylaxis. Viremia was associated with fever and fatigue in three patients, possible gastrointestinal involvement in one patient and was asymptomatic in one patient. All viremic patients responded to intravenous ganciclovir therapy. No fungal infections were documented. No patients died as a result of infection. The incidence of CMV viremia in our patients was high, but the incidence of invasive disease due to CMV was low. The best strategy to prevent CMV in patients undergoing nonmyeloablative PBSCT remains to be determined, but strategies employed in traditional allogeneic bone marrow transplantation should be considered in these patients.
Allogeneic peripheral blood stem cell transplantation (allo-PBSCT) has been increasingly used as an alternative to allogeneic bone marrow transplantation (allo-BMT). Medication of granulocyte colony stimulating factor (G-CSF) and apheresis are well tolerated by donors and supply adequate numbers of stem cells for the engraftment. Patients engraft sooner using PBSCT compared to allo-BMT. Allo-PBSCT is a safe alternative to allo-BMT and has distinct advantages for donors and patients. Faster engraftment results in fewer transfusion, shorter hospitalization, and decreased cost. However future research to determine if long-term side effects from G-CSF will negatively affect donors is essential. Data regarding durability of hematopoiesis and incidence for graft versus host disease warrant further analysis.
Allogeneic peripheral blood stem cell transplantation (allo-PBSCT) has been increasingly used as an alternative to allogeneic bone marrow transplantation (allo-BMT). In comparison with allo-BMT, preliminary results indicate that rapid hematopoietic engraftment can be obtained, and there is no increase in the incidence and severity of acute GVHD after allo-PBSCT. Furthermore, general anesthesia is not required to collect a sufficient number of PBSCT, which are usually mobilized by G-CSF administration. Therefore, allo-BMT will be replaced by allo-PBSCT in near future.
Six patients with multiple myeloma and chronic renal insufficiency (serum creatinine >3.0 mg/dl), including four on dialysis, received high-dose busulfan and cyclophosphamide (BUCY) followed by autologous peripheral stem cell transplantation. Peripheral blood stem cells were collected after priming with cyclophosphamide, etoposide and G-CSF. Patterns of engraftment and toxicities were not apparently different from those seen in myeloma patients with normal renal function. There was one toxicity-related death, resulting from a massive spontaneous subdural hematoma. One patient died of disease progression 6 months after transplant, while the remaining four patients are alive and free of myeloma progression 6 to 39 months after high-dose therapy. Two of these patients have remained in complete remission for 28 and 39 months. Our experience suggests that high-dose therapy with BUCY and autologous peripheral blood stem cell rescue is feasible in patients with multiple myeloma and renal failure.
Autologous peripheral blood stem cells, obtained by CD34+ stem cell selection, are being used with increasing frequency for transplantation in patients with neuroblastoma. Here, we examined the surface membrane antigens of neuroblastoma cells with a panel of hematopoietic monoclonal antibodies (mAbs), including anti-CD34 mAbs, by flow cytometric analysis. We found stronger binding of anti-CD34 mAbs to clonogenic, less differentiated, non-adherent neuroblastoma cells than to adherent neuroblastoma cells. Moreover, the majority of neuroblastoma cell lines shared hematopoietic-associated antigens with all blood cells. Because of these cross-reactions, especially found with the anti-CD34 mAbs 12.8 and ICH3, we have demonstrated that there is a potential risk of cell harvest contamination by circulating neuroblastoma cells during CD34+ stem cell selection.
PURPOSE: Peripheral blood stem cell (PBSC) apheresis provides an alternative to autologous marrow harvest as a source of hematologic stem cells for transplantation in children with solid tumors. PATIENTS AND METHODS: Eight children with metastatic or recurrent solid tumors underwent 27 apheresis procedures. Recovery from myelosuppressive chemotherapy occurred without continuous daily growth factor support prior to mobilization. Granulocyte colony stimulating factor (G-CSF) at 16 microgs/kg/day was used to increase stem cells in the peripheral circulation. CD 34 positive cells, mononuclear cells (MNC), and CFU-GM were measured in the apheresis products. Prior chemotherapy was examined as a clinical factor that affected PBSC yield. RESULTS: A significant correlation was found between CD 34+/kg and CFU-GM/kg of the products (r = 0.758, P < 0.001). Patients receiving cumulative doses of carboplatin over 1,600 mg/m2 produced adequate MNC (1 x 10(8)/kg) but yielded significantly less CD 34+ cells or CFU-GM than those patients receiving less carboplatin. Prior doses of etoposide and ifosfamide did not effect PBSC yield. CONCLUSIONS: The mobilization technique was well tolerated, and the products obtained produced trilineage engraftment in the patients that underwent peripheral blood stem cell transplantation. Peripheral blood stem cell apheresis in children can be optimized by selection of appropriate candidates and mobilization with G-CSF after an absence of hematopoietic growth factor support.