G-CSF after PBSC transplantation.
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Adjuvants, Immunologic↗
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Spontaneous and cytokine-induced thrombocytopenia in myelodysplastic syndromes: serum thrombopoietin levels and bone marrow morphology. Scandinavian MDS Group, Sweden and Norway.
Thrombocytopenia is a substantial clinical problem for patients with myelodysplastic syndromes (MDS). Cytokine treatment for granulocytopenia and anaemia may further reduce the platelet counts. We studied serum thrombopoietin levels (S-TPO) in 52 patients with MDS and 96 healthy controls and related the results to clinical and morphological variables. S-TPO was also assessed after treatment with granulocyte-CSF (G-CSF) and erythropoietin (EPO) in 30 of these patients. S-TPO in MDS was not a normally distributed variable; mean value was 394 pg/ml, SD +/-831 and median value 123 (12-5000 pg/ml). The controls showed lower S-TPO levels than the patients (median 78 pg/ml, P = 0.003) whereas no differences between the MDS subgroups were observed (P = 0.86). Patients with ringed sideroblastic anaemia (RARS) showed the highest platelet counts and higher S-TPO levels than the controls (P = 0.005). No association between platelet counts and S-TPO levels was found in the patients (P = 0.67). TPO levels were generally low in patients with refractory anaemia with an excess of blasts (RAEB), but very high levels were found in five patients. Patients with a high transfusion need had higher S-TPO levels, whereas bone marrow blast counts, cellularity or megakaryocytes showed no correlation with S-TPO. Patients with 5q- showed lower TPO levels than the other patients, indicating that thrombopoietin is not a mediator of thrombocytosis in these cases. Treatment with G-CSF + EPO significantly reduced the platelet counts (P = 0.0002), but this change was not related to significant changes in S-TPO levels or morphology. Patients with RARS and thrombocytosis who normalized their platelet counts showed a concomitant reduction in S-TPO. This may suggest that the increased platelet counts observed in RARS may be caused by increased S-TPO levels. In conclusion, our study shows that platelet, megakaryocyte and thrombopoietin regulation is rather complex in myelodysplastic syndromes and that spontaneous or induced thrombocytopenia are not usually mirrored by increased S-TPO levels.
Aged↗
The phenotypic profile of CD34-positive peripheral blood stem cells in different mobilization regimens.
The type of regimen used might result in mobilization of phenotypically and functionally different CD34(+) cells. We compared the phenotype of CD34(+) cells in leukapheresis products of three homogeneous groups: I, healthy individuals treated with granulocyte colony-stimulating factor (G-CSF) alone (n = 13); II, patients mobilized with G-CSF following chemotherapy (n = 16); and III, patients mobilized with G-CSF after high-dose chemotherapeutic pretreatment (n = 24). Multiparameter flow cytometry was performed for CD34(+) subpopulation analysis and focused on adhesion molecules, differentiation markers and megakaryocytic markers relevant for stem cell homing, with special reference to the importance of L-selectin expression. Regimens I and II led to higher numbers of mobilized CD34(+) cells (mean 468 x 10(6) and 491 x 10(6) CD34(+) cells per leukapheresis procedure respectively) than regimen III (mean 41 x 10(6) CD34(+) cells per leukapheresis procedure). Both the expression of L-selectin and CD54 on CD34(+) cells was significantly lower in group III, as was the percentage of megakaryocytic (CD41(+)) progenitors. A higher percentage of primitive (CD38(-) and/or HLA(-)DR(-)) CD34(+) cells was found in group III, correlating with a higher clonogenicity of the CD34(+) cells. However, when comparing the CD34(+)_ subpopulations that were also positive for L-selectin, there was no significant difference between the three regimens. A similar approach for the megakaryocytic CD34+ population resulted in an even worse quality of regimen III: 5.1% of CD34(+) being CD41(+)/L-selectin(+) compared with 9.2% and 8.9% in regimens I and II respectively. We concluded that the phenotypes of the CD34(+) cells in the G-CSF (group I) and G-CSF-chemotherapy (group II) regimens are similar, whereas the phenotype of the CD34(+) cells mobilized in the high-dose regimen (group III) displayed features that might negatively influence homing of the cells. Future studies will be directed towards regimens that will lead to the mobilization of a higher amount of CD34(+) cells with a phenotypically favourable phenotype.
Antigens, CD34↗
Treatment of relapse after allogeneic bone marrow transplantation with reduced intensity conditioning (FLAG +/- Ida) and second allogeneic stem cell transplant.
Acute leukaemias in relapse after allogeneic stem cell transplantation (SCT) respond poorly to donor leucocyte infusions (DLI) compared with chronic myeloid leukaemia (CML), at least in part because of faster disease kinetics. Fludarabine-containing 'non-myeloablative' chemotherapy followed by further allo SCT may offer more rapid and effective disease control. We report 14 patients with relapse after allo SCT for acute leukaemia [seven acute myeloid leukaemia (AML), five acute lymphoblastic leukaemia (ALL)] or refractory anaemia with excess blasts in transformation (RAEB-t, n = 2) treated with fludarabine, high-dose cytosine arabinoside (ara-C) and granulocyte colony-simulating factor (G-CSF) with (n = 10) or without (n = 2) idarubicin (FLAG +/- Ida) or DaunoXome (FLAG-X) (n = 2) and second allo SCT from the original donor. Donors were fully human leucocyte antigen (HLA) -matched in 13 cases with a single class A mismatch in one. Actuarial overall survival was 60% and disease-free survival was 26% at 58 months. Remissions after the second SCT were longer than those after the first bone marrow transplantation (BMT) in eight of the 13 assessable patients to date. Haematopoietic recovery was rapid. Transplants were well tolerated with no treatment-related deaths. The major complication was graft-versus-host disease (GvHD, acute >/= grade II-2 cases, chronic - eight cases, two limited, six extensive) although there have been no deaths attributable to this. FLAG +/- Ida and second allo SCT is a safe and useful approach and may be more effective than DLI in the treatment of acute leukaemias relapsing after conventional allo SCT.
Acute Disease↗
Fludarabine, cytosine arabinoside, granulocyte-colony stimulating factor with or without idarubicin in the treatment of high risk acute leukaemia or myelodysplastic syndromes.
The combination of fludarabine (FDR), high dose cytarabine and granulocyte colony stimulating factor (FLAG) with or without idarubicin (Ida) was used in the treatment of poor risk acute leukaemia or myelodysplastic syndrome (MDS) in a single centre experience. A total of 105 patients were treated over a 4-year period with 59% achieving a complete remission (CR); no statistical difference observed between FLAG and FLAG-Ida. For patients responding to FLAG +/- Ida, the median event-free survival (EFS) was 11 months and 23% at 5 years. Such patients proceeded either to further chemotherapy or a haematopoietic stem cell transplant (HSCT). The median EFS (13 months vs. 8 months) and projected 5-year survival (37% vs. 13%) of patients undergoing HSCT was significantly better than those who did not (P = 0.021). In all, 14 of 72 patients remain alive in continuing CR (median duration 43 months) with 10 of 31 having had a HSCT vs. four of 41 that did not (P = 0.033). Both regimens were well tolerated, with the majority of patients experiencing grade 1 or less non-haematological toxicity (mainly nausea and vomiting). The median time to neutrophil and platelet recovery was 28 and 31 d, respectively. No significant differences were seen with the addition of ida. There was a 17% incidence of treatment-related deaths, of which 39% was caused by invasive aspergillus infection. The results show that FLAG +/- Ida is an effective and well-tolerated remission induction regimen for poor risk leukaemia and MDS.
Acute Disease↗
Severe bactrim-induced neutropenia with reversal of CD4+/CD8+ lymphocyte ratio: response to recombinant human granulocyte-colony stimulating factor (R-metHUG-CSF).
A patient presented with severe bactrim-induced neutropenia with a reversed CD4+/CD8+ lymphocyte ratio. R-metHUG-CSF at 300 micrograms daily produced a dramatic neutrophil response and the therapy was discontinued after 2 weeks.
Bone Marrow↗
Successful salvage of RAEB/AML relapsing early post allograft with FLAG-Ida conditioned mini-allograft: a report of two cases.
Management options are often limited for patients with AML or high grade myelodysplasia (MDS) relapsing within a year of allogeneic transplantation. We report, in two such patients, the use of re-induction with FLAG-Ida chemotherapy, followed by the infusion of GCSF-mobilized blood stem cells from the same HLA-matched donor. Both patients achieved durable complete remissions with good quality of life and longer disease-free survival than after the first myeloablative allografts. This mini-allograft approach offers a practical, well-tolerated salvage and a potentially curative treatment for relapsed AML/high grade MDS patients failing a first conventional myeloablative allogeneic transplants.
Anemia, Refractory, with Excess of Blasts↗
Clinical experience with the use of rhG-CSF in secondary autoimmune neutropenia.
This paper outlines the impact of granulocyte-colony stimulating factor (G-CSF) used as a single modality therapy in 17 patients with secondary autoimmune neutropenia (S-AIN) who had been treated a multiple number of times previously. Fifteen of these patients had demonstrable antineutrophil antibodies and two had cellular S-AIN with haemopoietic inhibitory T-cells present in the marrow. Prior to treatment, all had had problems with infection. All patients responded within 7 days of commencement of treatment. Provided G-CSF neutrophil counts were maintained above 1 x 109/l, no further infections occurred. This was achievable by using G-CSF administered as infrequently as once every 8 days. Eight of the 17 patients remained on G-CSF, although five switched to the glycosylated form because of side-effects. None have developed osteoporosis despite 47.29 patient years of total experience with G-CSF. In conclusion both glycosylated and nonglycosylated G-CSF can be used effectively in treating AIN on a long-term basis.
Adolescent↗
Treatment with recombinant granulocyte colony-stimulating factor (Filgrastin) stimulates neutrophils and tissue macrophages and induces an effective non-specific response against Mycobacterium avium in mice.
A role of neutrophils in the host response against Mycobacterium avium (MAC) has recently been suggested. To investigate this matter further, we determined the effect of granulocyte colony-stimulating factor (G-CSF) on the outcome of MAC infection in mice. C57BL/6bg+/bg- black mice were intravenously infected with 1 x 10(7) MAC and then divided into four experimental groups to receive G-CSF as follows: (i) 10 micrograms/kg/day; (ii) 50 micrograms/kg/day; (iii) 100 micrograms/kg/day; (iv) placebo control. Mice were killed at 2 and 4 weeks of treatment to determine the bacterial load of liver and spleen. Treatment with G-CSF at both 10 and 50 micrograms/kg/day doses significantly decreased the number of viable bacteria in liver and spleen after 2 weeks (approximately 70.5% and 69.0%, respectively), and after 4 weeks (approximately 53% and 52%, respectively, P < 0.05 compared with placebo control). Treatment with 100 micrograms/kg/day did not result in decrease of bacterial colony-forming units in the liver and spleen after 4 weeks. Administration of G-CSF induced interleukin-10 (IL-10) and IL-12 production by splenocytes. To examine if the protective effect of G-CSF was accompanied by the activation of phagocytic cells, blood neutrophils and splenic macrophages were purified from mice receiving G-CSF and their ability to kill MAC was examined ex vivo. Neutrophils and macrophages from G-CSF-treated mice were able to inhibit the growth of or to kill MAC ex vivo, while phagocytic cells from untreated control mice had no anti-MAC effect. These results suggest that activation of neutrophils appears to induce an effective non-specific host defence against MAC, and further studies should aim for better understanding of the mechanisms of protection.
Animals↗
Severe chronic neutropenia in Chinese children in Hong Kong.
OBJECTIVE: Severe chronic neutropenia (SCN) is a rare and heterogeneous disorder in children. The epidemiology, clinical features and outcomes of SCN in Chinese children were reviewed. METHODOLOGY: A retrospective analysis of case records was undertaken for 18 children with SCN managed during a 12-year period in a university teaching hospital in Hong Kong. RESULTS: The median (range) age of the patients at initial presentation was 6.5 months (4 days-19 months). The initial and lowest median absolute neutrophil counts (ANC) were 0.29 x 109 /L and 0.06 x 109 /L, respectively. Patients with congenital SCN had significantly fewer neutrophils in peripheral blood at diagnosis. Only five subjects received granulocyte colony-stimulating factor (G-CSF) treatment. All children were free from serious infection on follow up for 51 months. Only one child suffered from long-term infection-related morbidity. One patient with chronic neutropenia was subsequently shown to have common variable immunodeficiency. CONCLUSIONS: Most children with SCN in our series had favourable clinical outcomes. Our results support the recommendation that G-CSF should be used only in those with recurrent or severe infections.
China↗
Squamous cell vulvar carcinoma associated with Fanconi's anemia: a case report.
Fanconi's anemia (FA) is a rare autosomal recessive syndrome associated with a strong predisposition to cancer, particularly squamous cell carcinoma (SCC) of various organs. A few cases of lower genital tract neoplasia have been described. We present a 14-year-old black girl with an advanced squamous cell vulvar carcinoma treated with cisplatin chemotherapy plus radiation therapy. The patient died because of fungal sepsis. Polymerase chain reaction (PCR) was positive to human papillomavirus (HPV)-16. Vulvar carcinoma is a very rare condition in teenagers, but the association of Fanconi's anemia and SCC of many sites is common. Vulvar carcinoma when associated with Fanconi's anemia is a great treatment challenge.
Adolescent↗
Mobilization factors of peripheral blood stem cells in healthy donors.
As a source of hematopoietic stem cells for transplantation, the use of peripheral blood stem cells (PBSCs) has become routine and comparable to that of the use of bone marrow. Recently, elderly patients with hematological malignancies also have been allowed to receive minitransplantations with nonmyeloablative conditioning regimens under sufficient PBSC infusion. As a result of these minitransplantations, elderly donors have been chosen increasingly from the siblings of elderly patients. We analyzed factors influencing the condition of CD34+ cells in the first days of collection in 49 healthy donors from July 1995 to January 2001. The median dose of recombinant human granulocyte colony-stimulating factor was 8 microg/kg/day (range 8 - 10) over 3 days. The target number of CD34+ cells used in this study was > or = 3 x 10(6) cells/kg of recipient body weight. The median apheresis volume was 12 L. Except for one 60 year old man, we obtained an adequate number of stem cells. In the regression analysis, a negative correlation was seen between donor age and the number of CD34+ cells/kg of recipient body weight per 12 L volume (Y = aX + b; a = -0.07507; b = 6.629996; r = -0.50985; p = 0.000252). Significantly higher apheresis results were obtained in donors younger than 45 years compared with donors 45 years old and older (p < 0.0227). There were no correlations among the number of CD34+ cells, donor body weight, and the number of leukocytes in peripheral blood on the first day of apheresis.
Adolescent↗
Changes in blood counts after the administration of granulocyte-colony-stimulating factor and the collection of peripheral blood stem cells from healthy donors.
BACKGROUND: After the collection of granulocyte-colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells from healthy donors, the donor platelet counts fall. However, the magnitude and duration of this decrease are not known. STUDY DESIGN AND METHODS: Sixty healthy people were given G-CSF (5, 7.5, or 10 micrograms/kg/day) for 5 days (Days 1-5), and 1 peripheral blood stem cell component was collected on Day 6. The platelet count, white cell count, absolute neutrophil count, hematocrit, and red cell count were measured before administration of G-CSF (Day 0), before collection of peripheral blood stem cells on Day 6, and on Days 8, 10, 13, 16, and 20. RESULTS: The platelet count fell from 261 +/- 47 x 10(9) cells per L on Day 0 to 159 +/- 30 x 10(9) cells per L on Day 8 (p < 0.0001) and reached its lowest level on Day 10 (146 +/- 30 x 10(9)/L; p < 0.001). Compared to Day 0 levels, the platelet count was lower on Day 13 (185 +/- 49 x 10(9)/L, p < 0.001), was the same on Day 16 (270 +/- 53 x 10(9)/L), and was greater on Day 20 (333 +/- 60 x 10(9)/L, p < 0.0001). The white cell count returned to pretreatment values on Day 13, and the absolute neutrophil count returned to pretreatment values on Day 10 (Day 0 white cell count = 6.05 +/- 1.59 x 10(9)/L and Day 0 absolute neutrophil count = 3.97 +/- 1.52 x 10(9)/L). On Day 20, both were less than pretreatment values (white cell count = 5.14 +/- 1.24 x 10(9)/L, p = 0.0007 and absolute neutrophil count = 3.20 +/- 1.24 x 10(9)/L, p = 0.0036). The red cell counts on Day 16 (4.52 +/- 0.41 x 10(12)/L) and Day 20 (4.42 +/- 0.39 x 10(12)/L) were less than Day 0 values (4.73 +/- 0.43 x 10(12)/L, p = 0.008 and p < 0.0001, respectively). The hematocrit on Day 20 (39.2 +/- 3.2%) was also less than that on Day 0 (41.2 +/- 4.8%; p = 0.01). The changes in these blood counts were not affected by the dose of the G-CSF. CONCLUSION: After stimulation with granulocyte-colony-stimulating factor and the collection or peripheral blood stem cells, the platelet counts in normal donors were decreased for at least 7 days (Days 6-13). Two weeks after collection of peripheral blood stem cells (Day 20), platelet production was increased, but the production of neutrophils and red cells was decreased. If two or more peripheral blood stem cell components are collected, then the platelet count should be measured after the second and subsequent collections. Further studies on the long-term effect of G-CSF on blood counts are needed.
Adult↗
Treatment of normal individuals with granulocyte-colony-stimulating factor: donor experiences and the effects on peripheral blood CD34+ cell counts and on the collection of peripheral blood stem cells.
BACKGROUND: Granulocyte-colony-stimulating factor (G-CSF) has been used in patients to increase the level of circulating hematopoietic progenitors. Although G-CSF has been administered to some healthy individuals, the kinetics of mobilization of peripheral blood stem cells (PBSCs), the optimum dose schedule and the incidence and nature of adverse reactions in normal individuals are not completely defined. STUDY DESIGN AND METHODS: Normal individuals (n = 102) who received G-CSF for 5 or 10 days at doses of 2, 5, 7.5, or 10 micrograms per kg per day were studied. The subjects were observed for symptoms and physical changes, and blood samples were obtained for a variety of laboratory tests. After 5 or 10 days of G-CSF treatment, PBSCs were collected by apheresis and analyzed. RESULTS: Overall, 89 percent of the individuals completed the 5-day treatment protocol and 88 percent completed the 10-day protocol without modification of the dose of G-CSF administered. Ninety percent of donors experienced some side effect of G-CSF. The most frequent effects noted were bone pain (83%), headache (39%), body aches (23%), fatigue (14%), and nausea and/or vomiting (12%). The dose of G-CSF administered directly affected the proportion of people with bone pain (p = 0.025) or body aches (p = 0.045) or who were feeling hot or having night sweats (p = 0.02) or taking analgesics (p = 0.01). With the 5-day dose schedule, several changes in serum chemistries occurred, including increases in alkaline phosphatase (p = 0.001), alanine aminotransferase (p = 0.0013), lactate dehydrogenase (p = 0.0001), and sodium (p = 0.0001). Decreases occurred in glucose (p = 0.045), potassium (p = 0.0004), bilirubin (p = 0.001), and blood urea nitrogen (p = 0.0017). In donors who received G-CSF for 5 days, the absolute neutrophil count was increased after one G-CSF dose, and it reached a maximum on Day 6, as did the number of CD34+ cells (64.6 +/- 55.9 x 10(6) cells/L). In those same donors, the platelet count after apheresis on Day 6 was 32 +/- 13 percent lower than pretreatment values (250 +/- 42 x 10(9) cells/L). In donors receiving G-CSF for 10 days, the neutrophil count reached a maximum on Day 8, but the number of CD34+ cells peaked on Day 6 (58.3 +/- 52.1 x 10(5) cells/L) and then declined. The platelet count decreased from pretreatment values by 28 +/- 12 percent prior to apheresis on Day 11. When individuals were treated for 5 days with G-CSF, the quantity of CD34+ cells collected was directly related to the G-CSF dose. When 5 micrograms per kg per day was given, 2.80 +/- 1.81 x 10(8) cells were collected, compared with collection of 4.67 +/- 3.11 x 10(8) cells when 10 micrograms per kg per day was given (p = 0.04). More important, PBSCs collected after 10 days of G-CSF administration (5 micrograms/kg/day) had significantly fewer CD34+ cells (0.82 +/- 0.37 x 10(8) cells, p = 0.01) than did PBSCs collected after 5 days of G-CSF (5 micrograms/kg/day). CONCLUSION: Most normal donors receiving G-CSF experience side effects, but these are mild to moderate in degree. Some alterations in blood chemistries occur, but none were clinically serious. Because of the symptoms associated with G-CSF, these individuals must be monitored closely. The treatment of normal donors with G-CSF for more than 5 days significantly decreased the number of circulating CD34+ cells and the quantity collected by apheresis.
Adult↗
Analysis of factors associated with low peripheral blood progenitor cell collection in normal donors.
BACKGROUND: Predictive factors of the response to rHuG-CSF in normal donors have not been extensively studied. STUDY DESIGN AND METHODS: We analyzed factors influencing CD34+ cell yield in the 1st day of collection in 261 healthy donors from the Spanish National Donor Registry. The median age was 38 years (range, 2-72). The median dose of rHuG-CSF was 10 microg per kg per day (range, 5-20) over 4 days. In 103 donors (40%), <4 x 10(6) per kg CD34+ cells were collected. The variables that were analyzed included age, sex, weight, basal complete blood cell count, dose, type of rHuGCSF and schedule of administration, and maximum WBC count before apheresis. RESULTS: By univariate analysis, the maximum WBC count (<50 vs. >or=50 x 10(9)/L, p = 0.004), advanced age (p = 0.008), and number of daily rHuG-CSF doses (one vs. two; p = 0.01) correlated with the number of CD34+ cells collected. By multivariate analysis, donors age (<38 vs. >or=38 years; p = 0.014) and a single daily dose of rHuG-CSF (p = 0.005) were the two variables that significantly predicted a low CD34+ cell yield. CONCLUSION: Donors' age, with a threshold of 38 years or more, and the rHuG-CSF schedule are the factors that significantly affected CD34+ cell mobilization and collection in healthy donors.
Adolescent↗
Severe pancytopenia after leflunomide in rheumatoid arthritis.
Leflunomide is a novel drug recently introduced for treatment of rheumatoid arthritis as a DMARD (disease-modifying antirheumatic drug). So far, leflunomide has not been associated with severe bone marrow toxicity and pancytopenia. We report of a 62-year-old woman with a 14-year history of rheumatoid arthritis with bone marrow toxicity and reversible pancytopenia developing after treatment with leflunomide.
Anti-Inflammatory Agents, Non-Steroidal↗
Potentiation of the anti-tumour effects of Photofrin-based photodynamic therapy by localized treatment with G-CSF.
Photofrin-based photodynamic therapy (PDT) has recently been approved for palliative and curative purposes in cancer patients. It has been demonstrated that neutrophils are indispensable for its anti-tumour effectiveness. We decided to evaluate the extent of the anti-tumour effectiveness of PDT combined with administration of granulocyte colony-stimulating factor (G-CSF) as well as the influence of Photofrin and G-CSF on the myelopoiesis and functional activity of neutrophils in mice. An intensive treatment with G-CSF significantly potentiated anti-tumour effectiveness of Photofrin-based PDT resulting in a reduction of tumour growth and prolongation of the survival time of mice bearing two different tumours: colon-26 and Lewis lung carcinoma. Moreover, 33% of C-26-bearing mice were completely cured of their tumours after combined therapy and developed a specific and long-lasting immunity. The tumours treated with both agents contained more infiltrating neutrophils and apoptotic cells then tumours treated with either G-CSF or PDT only. Importantly, simultaneous administration of Photofrin and G-CSF stimulated bone marrow and spleen myelopoiesis that resulted in an increased number of neutrophils demonstrating functional characteristics of activation. Potentiated anti-tumour effects of Photofrin-based PDT combined with G-CSF observed in two murine tumour models suggest that clinical trials using this tumour therapy protocol would be worth pursuing.
Adenocarcinoma↗
[Expression of AC133 vs. CD34 in acute childhood leukemias].
AC133, a newly discovered antigen on human progenitor cells, demonstrating 5-transmembranous domains is expressed by 30-60% out of all CD34+ cells. Our aim therefore was to investigate the extent of human stem-/progenitor cells expressing AC133 antigen in umbilical cord blood, peripheral blood without or following an application of granulocyte-colony stimulating factor (rhG-CSF). The main task was the investigation of bone marrow aspirates derived from children suffering from newly diagnosed acute leukemias, as well as from patients with a relapse or during a complete remission. The determination of antigen expression was done by application of flow cytometry (FACScan analysis) and the usage of newly developed monoclonal antibodies (AC133/1 and AC133/2; Miltenyi Biotec GmbH) in combination with monoclonal antibody directed against CD34-antigens (HPCA-2; BD). Our studies till now show average percentages in umbilical cord blood derived from 43 newborns about 0.294 +/- 0.165% AC133+ vs. 0.327 +/- 0.156% CD34+ hematopoietic stem-/progenitor cells (HSPC). In peripheral blood from 11 healthy donors we verified up to 0.15% CD34+ as well as AC133+ HSPC's. The concentration of progenitor cells was found to be obviously higher in peripheral blood from children with various diseases (neuroblastoma, rhabdomyosarcoma, ALL/AML) and undergoing application with rhG-CSF in order to be prepared for PBSC-transplantation. In those cases we found up to 3.51% AC133+ cells as well as slightly higher values (3.94%) for CD34 antigens. Additionally we quantified 128 bone marrow (BM) samples for AC133+ and CD34+ cells. In 10 BM samples, derived from patients without any neoplasia, the CD34+ cells were about 0.03% and 1.49%, whereas AC133 values were up to 0.64%. Bone marrow aspirates from 53 children with acute leukemias at time of diagnosis (ALL: n = 41/AML: n = 12) have been immunophenotyped and leukemic blast cells have been proved for AC133- and CD34 antigen expression. 32/41 (78%) of lymphoblastic leukemic cells showed to be positive for CD34 antigen and 24/41 (58%) demonstrated AC133 antigens. Interestingly there were 2 ALL-patients with pathological blast cells positive for AC133 but lacking of any CD34 antigens. 42% (5/12) of investigated AML patients showed CD34+ phenotype, on the other hand there were only 25% (3/12) with AC133+ phenotype. Similar values were found in relapsed patients (n = 18). In BM samples from patients during complete remission (n = 47) we could detect percentages up to 5.55% for CD34 and up to 1.25% for AC133 positive stem-/progenitor cells. Such quite high data may be explained by occasionally application of rhG-CSF therapy. Our results till now lead to the conclusion, that it seems to be useful, to recruit quantification of CD34+ HPSC by additionally detecting AC133 antigens. This new stem cell marker (AC133) may be of great value in case of autologous peripheral blood stem cell transplantation (PBSCT) because it could be an alternative to the usual CD34+ MACS selection system.
AC133 Antigen↗