Summary. To date, no randomized study has compared different doses of recombinant human granulocyte colonystimulating factor (rhG-CSF) following submyeloablative mobilization chemotherapy. Therefore, we evaluated the effect of different doses of rhG-CSF following mobilization chemotherapy on yields of CD34 + peripheral blood stem cells (PBSC). Fifty patients were randomized to receive 8 (n 25) versus 16 lg/kg/d (n 25) of rhG-CSF following mobilization chemotherapy. The median number of CD34 + cells collected after 8 lg/kg/d of rhG-CSF was 2á36´10 6 /kg (range, 0á21±7á80), compared with 7á99 (2á76±14á89) after 16 lg/kg/d (P < 0á001). Twenty out of 25 (80%) patients in the low-dose and 23 out of 25 (92%) in the high-dose rhG-CSF arm underwent high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). Median days to white blood cell engraftment in patients mobilized with 8 lg/kg and 16 lg/kg of rhG-CSF were 12 (10±20) and 9 (8±11) respectively (P < 0á001). There was no difference between the two groups regarding the other parameters of peritransplant morbidity: days to platelet engraftment (P 0á10), number of red blood cell (P 0á56) and platelet transfusions (P 0á22), days of total parenteral nutrition requirement (P 0á84), fever (P 0á93) and antibiotics (P 0á77), and number of different antibiotics used (P 0á58). These data showed that higher doses of rhG-CSF following submyeloablative mobilization chemotherapy were associated with a clear dose±response effect based on the collected cell yields. Based on the parameters of peritransplant morbidity, 8 lg/kg/d was as effective as 16 lg/kg/d except for a rapid neutrophil engraftment in the high-dose arm. Therefore, in routine clinical practice, despite some advantage in the use of higher doses of rhG-CSF, lower doses may be used for PBSC collections following chemotherapy-based mobilization regimens in this cost-conscious era.

Summary. This study evaluated of the effect of post-transplant recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration on the parameters of peritransplant morbidity. Three sequential and consecutive cohorts of 20 patients each received either post-transplant rhG-CSF at a dose of 5 lg/kg/d i.v. in the morning, starting on d 0, d 5, or no rhG-CSF. Patients who received rhG-CSF starting on d 0 and 5 recovered granulocytes more rapidly than those not receiving rhG-CSF (P < 0AE001 for ANC ‡ 0AE5 and 1 · 10 9 /l). RhG-CSF administration was not significantly associated with more rapid platelet engraftment. RhG-CSF administration starting on d 0 and 5 was significantly associated with a decreased duration of fever (P ¼ 0AE002 and 0AE001 respectively), antibiotic administration (P < 0AE001 and 0AE006 respectively) and shorter hospitalization (P < 0AE001 and 0AE001 respectively) compared with the reference group. There was no difference between the d 0 and d 5 arms regarding the parameters of peritransplant morbidity. In conclusion, rhG-CSF administration was associated with a faster granulocyte recovery, shorter hospitalization, and shorter period of fever and nonprophylactic antibiotic administration. This study also showed that starting rhG-CSF administration on d 5 may be as effective as d 0 on the clinical outcome and may be an economical approach in routine clinical practice in this costconscious era.

The purpose of this study was to evaluate the correlation of preleukapheresis circulating CD34+ cells/μL, white blood cells (WBC), and platelet counts on the first day of apheresis with the yield of collected CD34+ cell counts in 40 patients with hematological malignancies (n = 29) and solid tumors (n = 11). The median numbers of apheresis cycles, numbers of CD34+ cells, peripheral blood (PB) mononuclear cells, and total nucleated cells collected were 2 (range, 1–4), 5.5 × 106/kg (range, 0.05–33.78), 2.59 × 108/kg (range, 0.04–20.68), and 7.36 × 108/kg (range, 0.15–28.08), respectively. There was a strong correlation between the number of preleukapheresis circulating CD34+ cells/μL and the yield of collected CD34+ cells per kilogram (r = 0.962, p < 0.001). The threshold levels of PB CD34+ cell/μL to obtain ≥1 × 106/kg and ≥2.5 × 106/kg CD34+ cell in one collection were 12/μL and 34/μL, respectively. Fifteen of 17 (88%) patients who had ≥34 CD34+ cells/μL in the PB before collection reached the level of ≥2.5 × 106/kg in a single apheresis. Despite a low r value, WBC and platelet counts on the first day of apheresis also correlated with the yield of collected daily CD34+ cells per kilogram (r = 0.482, p < 0.01 and r = 0.496 p < 0.01, respectively). These data suggest that preleukapheresis circulating CD34+ cells/μL correlated significantly better with the yield of collected CD34+ cells than WBC and platelet counts on the first day of apheresis. Using a value of 34/μL preleukapheresis circulating CD34+ cells as a guide for the timing of peripheral blood stem cells collections can be time saving and cost‐effective.

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Summary:It is logical to expect that large-volume leukapheresis may be able to collect adequate numbers of PBSC with fewer procedures. To date, there is no agreement on the optimal volume of leukapheresis. Therefore, in this study we compared 8 l volume with 12 l and assessed whether a 50% increase in the blood volume processed would decrease the number of leukaphereses each patient needed to collect у2.5 ؋ 10 6 CD34 ؉ cells/kg in normal mobilizers. PBSC mobilization was done with cyclophosphamide etoposide followed by rhG-CSF in all patients. Forty patients were randomized to undergo 8 l leukaphereses (n ‫؍‬ 20 patients) or 12 l leukaphereses (n ‫؍‬ 20). The median numbers of leukaphereses required in order to collect у2.5 ؋ 10 6 CD34 ؉ cells/kg in patients processed with 8 l and 12 l were 1 (range 1-5) and 1 (1-4), respectively (P ‫؍‬ 0.50). The median number of total nucleated cells (TNC) collected per patient was greater for the 12 l group (7.47 ؋ 10 8 /kg vs 3.90 ؋ 10 8 /kg, P Ͻ 0.001), as was the median number of total mononuclear cells (TMNC) (4.26 ؋ 10 8 /kg vs 2.16 ؋ 10 8 /kg, P Ͻ 0.001), whereas there was no difference between the two groups for the median number of CD34 ؉ cells collected per patient (8.94 ؋ 10 6 /kg vs 8.60 ؋ 10 6 /kg, P ‫؍‬ 0.85). The TNCs and TMNCs collected per leukapheresis were again greater for the 12 l group (3.64 ؋ 10 8 /kg vs 1.91 ؋ 10 8 /kg, P ‫؍‬ 0.001 and 2.17 ؋ 10 8 /kg vs 0.88 ؋ 10 8 /kg, P Ͻ 0.001), whereas there was no difference between the two groups for the median number of CD34 ؉ cells collected per leukapheresis (3.98 ؋ 10 6 /kg vs 3.26 ؋ 10 6 /kg, P ‫؍‬ 0.90). This study showed that there is no difference between 8 l and 12 l volumes in regard to collected CD34 ؉ cells/kg and also the use of a 12 l leukapheresis volume did not decrease the number of leukaphereses performed compared with a

A decrease in bone mass is observed in hemophilic patients. The aim of this study was to evaluate bone mineral density (BMD), parathyroid hormone (PTH), 25-hydroxy vitamin D (vitamin D), and a bone formation and resorption marker, procollagen type I N-terminal propeptide (PINP) and urinary N-terminal telopeptide (uNTX) respectively, in hemophilic patients and healthy controls. Laboratory parameters related to the pathogenesis of bone loss such as neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were also evaluated. Thirty-five men over 18 years of age, with severe hemophilia (A and B) and receiving secondary prophylaxis, were included in the study. The same number of age-, sex-, and ethnicity-matched healthy controls were evaluated. Anthropometric, biochemical, and hormonal parameters were determined in both groups. No significant difference in anthropometric parameters was found between the two groups. The BMD was low in 34% of hemophilic patients. Vitamin D, calcium, and free testosterone levels were significantly lower (p < 0.001, p = 0.011, p < 0.001, respectively), while PTH, PINP, and activated partial thromboplastin time (aPTT) levels were significantly higher (p < 0.014, p = 0.043, p < 0.001, respectively), in hemophilic patients compared to controls. There was no significant difference between the two groups in NLR, PLR, phosphorus, thyroid-stimulating hormone, and uNTX level. The reduction of bone mass in hemophilic patients may be evaluated using the markers of bone formation and resorption, enabling early detection and timely treatment.

Colorectal cancers are one of the most common malignancies associated with coagulation abnormalities ranging from asymptomatic laboratory changes to massive thromboembolism or hemorrhage. It was previously shown that global fibrinolytic was increased in non-metastatic colorectal cancer. In this study global fibrinolytic capacity was measured in patients with colorectal cancer and metastatic liver disease, which always more commonly displays various coagulation disorders. Nineteen patients with biopsy-proven colorectal cancer, 30 patients with metastatic colorectal cancer, and 20 healthy control subjects were involved into the study. Using standart silicated fibrin pellets and tissue plasminogen activator, fibrinolytic capacity of the plasmas was detected with the amount of d-dimer produced before the reaction was stopped by adding aprotinin to the medium. Mean global fibrinolytic capacity (GFC) was increased to higher levels in patients with metastatic disease compared to levels in non-metastatic disease (p<0.05). Fibrinogen/GFC ratio correlated to the increase of d-dimer levels. Global fibrinolytic capacity was much higher in metastatic disease, reflecting a progression to overt disseminated intravascular coagulation.