Clinical characteristics and management of iron overload in 631 patients with chronic transfusion dependency: results from a multicentre, observational study.

BACKGROUND: Long-term red blood cell transfusion therapy results in iron overload. Consensus documents have been developed for several transfusion-dependent groups of patients to provide clinicians with guidance on the monitoring and treatment of this transfusion complication. The objective of this study was to describe the clinical characteristics and current standard of care for patients with transfusion dependency in Spain. MATERIAL AND METHODS: This observational, multicentre study was conducted from November 2008 to December 2009 in 41 Spanish hospitals and day-care centres. Patients who received their first transfusion after January 2007, and who had received at least 10 units of packed red blood cells at the time of inclusion were eligible for the study. RESULTS: We collected data from 631 patients with a mean age of 65±17 years. Haematological disease (84% of patients) was the most frequent underlying disorder. Patients had received a mean of 30±26 red blood cell units from diagnosis until inclusion in the study, and a mean of 18±18 red blood cell units in the previous year. Ferritin levels were available before and after starting the study for 116 (18%) and 412 (65%) patients, respectively. Mean ferritin level at study inclusion was 1,570 ng/mL, and 58% of patients had a ferritin level of at least 1,000 ng/mL. In spite of this, only 89 (14%) patients were receiving chelation therapy. DISCUSSION: The management of patients with transfusion dependency could be improved by using ferritin levels to diagnose iron overload and guide the timely start of chelation therapy.

Follow-up of healthy donors receiving granulocyte colony-stimulating factor for peripheral blood progenitor cell mobilization and collection. Results of the Spanish Donor Registry.

BACKGROUND: Information about the long-term follow-up and safety of granulocyte colony-stimulating factor administration to healthy donors is limited. The aims of this study were to analyze the side effects of granulocyte colony-stimulating factor administration in donors included in a Spanish Registry of hematopoietic stem cell donors and to determine the long-term outcome of these donors. DESIGN AND METHODS: The Spanish National Donor Registry was developed to record the short- and long-term results of granulocyte colony-stimulating factor administration to mobilize peripheral blood progenitor cells in normal donors. To date, 1436 donors (771 males, 665 females) with a median age of 37 years (range, 1 to 74 years) have been registered. Granulocyte colony-stimulating factor was the only cytokine administered. A baseline investigation was performed in every donor before granulocyte colony-stimulating factor administration and follow-up investigations (controls) were planned at 4 weeks and annually thereafter for up to 5 years after the mobilization. RESULTS: At least one of the scheduled controls was performed in 736 donors, while 320 donors have been followed for 2 years or more. The peripheral white blood cell count decreased significantly from 6.8 x 10(9)/L at baseline to 5.9 x 10(9)/L at 4 weeks after leukapheresis (p<0.0001) and remained at values lower than those observed premobilization until 2 years after mobilization. In contrast, hemoglobin concentration and platelet count returned to normal values within 1 year after mobilization. Bone pain (90%) and headache (33%) were the most frequently reported granulocyte colony-stimulating factor-related side effects. Five patients (0.68%) were diagnosed as having solid tumors (lung cancer in two patients and thyroid carcinoma, choroid melanoma, and colon carcinoma in one patient each) between 10 and 64 months after administration of granulocyte colony-stimulating factor. No hematologic malignancies have been reported. CONCLUSIONS: The clinical side effects of granulocyte colony-stimulating factor administration in healthy donors are generally mild. Changes in blood counts were minimal and mainly affected white blood cell counts, which returned to normal values within 2 years after granulocyte-colony stimulating factor administration. No patient developed a hematologic malignancy. A larger number of donors and longer follow-up are needed to determine the safety of granulocyte colony-stimulating factor administration definitively.

Factors predicting peripheral blood progenitor cell collection from pediatric donors for allogeneic transplantation.

BACKGROUND AND OBJECTIVES: Although several studies have reported on the use of children as donors for peripheral blood progenitor cells (PBPC), no specific characteristics have been identified as predictors of PBPC collection in this population. In this study we analyzed predictive factors for PBPC collection in pediatric donors. DESIGN AND METHODS: We retrospectively analyzed factors predicting the yield for a target CD34+ cell dose of > or =4x10(6)/Kg donor or recipient body weight, in 105 aphereses from 76 healthy pediatric donors (36 boys and 40 girls) included in the Spanish National Donor Registry. Mobilization consisted of granulocyte colony-stimulating factor (G-CSF) in single doses of 10 microg/kg per day subcutaneously for 4 or 5 days. Apheresis started after the fourth dose of G-CSF. RESULTS: Median age and body weight were 10 years (range 1-18) and 42 kg (range 9-89), respectively. The median number of CD34+ cells/kg recipient body weight was 4.22 (range 0.1-32). On multivariate analysis variables that had a significant negative impact on the CD34+ cell yield, considering the recipient's body weight were the total blood volume processed (regression coefficient (RC): 0.41, 95% CI: 0.21-0.81; p=0.01) and day of apheresis other than first (RC: 0.16, 95% CI: 0.07-0.34; p<0.0001). When considering donor's body weight the variables that positively influenced collection were younger age (RC: 6.79, 95% CI: 1.57-29.25; p<0.01) and large volume leukapheresis (RC: 3.33, 95% CI: 1.13-9.77; p<0.02). INTERPRETATION AND CONCLUSIONS: Our data suggest that pediatric donors mobilized by G-CSF may donate sufficient numbers of CD34+ cells for allogeneic transplantation. The variables that influenced the yield were the donor's age, blood volume processed and the first day of the apheresis.

Second mobilization and collection of peripheral blood progenitor cells in healthy donors is associated with lower CD34(+) cell yields.

We have retrospectively evaluated the results of two cycles of mobilization and collection of peripheral blood progenitor cells (PBPC) from 46 healthy donors included in the Spanish National Donor Registry. Mobilization involved the administration of granulocyte colony-stimulating factor (G-CSF) at a median dose of 10 microg/kg per day, and apheresis was begun after the fourth dose of G-CSF in both cycles. The median interval between both mobilizations was 187 days (range, 7-1428 days). The incidence and types of side-effects were similar after both donations, with 25 and 26 donors developing some toxicity after the first and second donations, respectively. The median number of CD34(+) cells collected was higher after the first mobilization than after the second (5.15 versus 3.16 x 10(6)/kg, respectively; p = 0.05), and 29 donors yielded fewer CD34(+) cells after the second mobilization (p = 0.018). A lower proportion of donors yielded CD34(+) cell counts >4 x 10(6)/kg after the second cycle than after the first (52% versus 76%, respectively; p = 0.057). Our study shows that second rounds of PBPC collection from normal donors are well tolerated but are associated with a significantly reduced number of CD34(+) cells collected when the same mobilization scheme is used.

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.