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Summary:We studied the effect of the CD34 ؉ cell dose on transplant-related mortality (TRM) and survival in 39 patients randomized to receive lenograstim-mobilized PBSCT (n = 20) or BMT (n = 19) from HLA-identical siblings. Both marrow and blood were harvested, and one infused in a double-blind fashion. The median nucleated

Summary.A cross-over study of glycosylated and nonglycosylated G-CSF was performed in 20 healthy male volunteers to compare the effects of the different forms of G-CSF, the extent of inter-individual progenitor cell mobilization and to determine whether any differences observed were related to the serum concentrations of G-CSF attained. The peak WBC achieved during 6 d of G-CSF administration at a dose of 5 mg/kg/d was significantly higher with the glycosylated than the non-glycosylated product (P ¼ 0 . 02) as was the peak level of granulocyte-monocyte colony forming cells (GM-CFC) (P ¼ 0 . 03). The average GM-CFC count on days 5, 6 and 7 was 28% higher with the glycosylated product (P ¼ 0 . 003). Serum concentrations of G-CSF achieved were significantly higher with the nonglycosylated G-CSF, however, suggesting that the difference in bio-efficacy was not due to a difference in G-CSF stability. Marked inter-individual variation in progenitor mobilization was observed, but this was not related to serum G-CSF levels. The G-CSF concentrations on day 6 were approximately one third of those on day 1, with both forms of G-CSF.

Summary:Forty healthy adult donors underwent marrow (BM) as well as peripheral blood (PBSC) stem cell collections for their HLA-identical adult siblings with hematologic malignancies. BM was harvested on day 1 (target 3 ؋ 10 8 nucleated cells/kg, 10 g/kg lenograstim (glycosylated G-CSF) administered on days 2-6, and a single leukapheresis performed on day 6. The blood volume processed was the higher of 200% donor blood volume or 10 liters. The total nucleated cell (TNC) yields from PBSC were 1.1-to 4.3-fold higher than BM (median 7.0 vs 3.1 ؋ 10 8 /kg, P Ͻ 0.0001). Although BM contained a higher proportion of CD34 + cells (1.3% vs 0.7%, P Ͻ 0.0001) and a comparable proportion of CD3 + cells (median 29% vs 26%, P = 0.4), the absolute numbers of CD34 + and CD3 + cells and their subsets were several times higher in PBSC. There was a poor correlation between BM and PBSC CD34 and TNC numbers, but a significant correlation between BM and PBSC CD3 numbers. Only five of 40 BM harvests contained у2 ؋ 10 6 CD34 + cells/kg compared with 35 of 40 PBSC harvests (P Ͻ 0.0001). We conclude that the numbers of progenitor and immunocompetent cells in PBSC are several times higher than in BM. It is possible to collect adequate numbers of progenitor cells from blood after lenograstim stimulation more frequently than from marrow, and donors yielding low quantities of progenitor cells from BM usually deliver better quantities from PBSC. Bone Marrow Transplantation (2000) 25, 501-505.

Since December 1987, we have examined the use of high-dose chemotherapy and unpurged bone marrow rescue in 31 patients with advanced or refractory lymphoma. Twenty-one patients had Hodgkin's disease (HD) and 10 had Non-Hodgkin's lymphoma (NHL). At ABMT, 22 patients had relapsed or resistant disease. All patients, excluding 3 early deaths, engrafted. There was no relationship between cell numbers harvested, CFU-GM and bone marrow recovery. The mean times to 0.5 x 10(9)/l neutrophils and 50 x 10(9)/l platelets were 20 d and 43 d respectively. However, 5 patients with HD had a significantly slower platelet recovery time of up to 203 days (p = 0.05). Disease-free survival was 72% for HD and 40% for NHL at 40 months. Relapsed or refractory disease at ABMT, bulky disease, extensive salvage therapy and Karnofsky scores below 80% were all associated with a poorer outcome. The most striking observation has been the dramatic radiological response of some patients with advanced/refractory disease.

Background: In Japan, more than 20 rheumatoid arthritis (RA) patients died of interstitial pneumonia (IP) caused by leflunomide (LEF) were reported, but many of them were considered as the victims of opportunistic infection currently. In this paper, efficacy and safety of low-dose LEF classified by body weight (BW) were studied. Methods: Fifty-nine RA patients were started to administrate LEF from July 2007 to July 2009. Among them, 25 patients were excluded because of the combination with tacrolimus, and medication modification within 3 months before LEF. Remaining 34 RA patients administered 20 to 50 mg/week of LEF were followed up for 1 year and enrolled in this study. Dose of LEF was classified by BW (50 mg/week for over 50 kg, 40 mg/week for 40 to 50 kg and 20 to 30 mg/week for under 40 kg). The average age and RA duration of enrolled patients were 55.5 years old and 10.2 years. Prednisolone (PSL), methotrexate (MTX) and etanercept were used in 23, 28 and 2 patients, respectively. In case of insufficient response or adverse effect, dosage change or discontinuance of LEF were considered. Failure was defined as dosages up of PSL and MTX, or dosages down or discontinuance of LEF. Last observation carried forward method was used for the evaluation of failed patients at 1 year. Results: At 1 year after LEF start, good/ moderate/ no response assessed by the European League Against Rheumatism (EULAR) response criteria using Disease Activity Score, including a 28-joint count (DAS28)-C reactive protein (CRP) were showed in 14/ 10/ 10 patients, respectively. The dosage changes of LEF at 1 year were dosage up: 10, same dosage: 5, dosage down: 8 and discontinuance: 11 patients. The survival rate of patients in this study was 23.5% (24 patients failed) but actual LEF continuous rate was 67.6% (11 patients discontinued) at 1 year. The major reason of failure was liver dysfunction, and pneumocystis pneumonia was occurred in 1 patient resulted in full recovery. One patient died of sepsis caused by decubitus ulcer infection. DAS28-CRP score was decreased from 3.9 to 2.7 significantly. Although CRP was decreased from 1.50 to 0.93 mg/dl, it wasn't significant. Matrix metalloproteinase (MMP)-3 was decreased from 220.0 to 174.2 ng/ml significantly. Glutamate pyruvate transaminase (GPT) was increased from 19 to 35 U/l and number of leukocyte was decreased from 7832 to 6271 significantly. DAS28-CRP, CRP, and MMP-3 were improved significantly with MTX, although they weren't without MTX. Increase of GPT and leukopenia were seen significantly with MTX, although they weren't without MTX. Conclusions: It was reported that the risks of IP caused by LEF in Japanese RA patients were past IP history, loading dose administration and low BW. Addition of low-dose LEF is a potent safe alternative for the patients showing unsatisfactory response to current medicines, but need to pay attention for liver function and infection caused by leukopenia, especially with MTX. Disclosure statement: The authors have declared no conflicts of interest. Bac...

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