Leukotriene B₄(LTB4) is lipid mediator derived from membrane phospholipids during the process of inflammation, having many roles(ie; inducer of chemotaxis, the production of nitric oxide, transepithelial migration of neutrophil). The major activities of LTB4 include the recruitment and activation of leukocytes, suggesting that it may involve the process for transendothelial migration of nuclear cells in bone marrow environment. Reactive Oxygen Species (ROS) have a cell signaling roles that are involved in signal transduction cascades of numerous growth factor-, cytokine-, and hormone-mediated pathways, and regulate many biological systems. In this present study, we focused on the role of LTB4 and ROS on transmigration of bone marrow nuclear cells across endothelial or stromal cell monolayer.

MS-5, murine stromal cell line cells, or bEnd.3, murine microvascular cell line cells, were grown to confluence on microporous transwell membrane. Murine marrow cells were placed on top of the prepared transwell membrane. The transwells were then seated in wells containing media and LTB4 with or without pretreatment of N-acetylcysteine(NAC), an oxygen free radical scavenger, or diphenylene iodonium(DPI), an inhibitor of NADPH oxidase-like flavoproteins. Cells that migrated through the stromal or endothelial layer into the wells were assayed for transendothelial migration.

The numbers of migrated bone marrow nuclear cells through the bEnd.3 were increased by treatment of LTB4(control, 12.5±0.2%; 50nM, 22.7±0.9%; 100nM, 44.3±1.4%; 200 nM, 36.3±0.9%; p<0.05). The numbers of migrated bone marrow nuclear cells through the MS-5 were also increased by treatment of LTB4(control, 11.0±0.9%; 50nM, 25.7±0.9%; 100nM, 35.8±1.8%; 200nM, 32.1±0.9%; p<0.05). However, increasing effect of LTB4 to the transmigration of bone marrow nuclear cells through the MS-5 or bEnd.3 were inhibited by pretreatment of NAC or DPI.

Through our data, it is suggested that LTB4 could induce the transmigration of bone marrow nuclear cells and ROS might be involved on the transendothelial migration of bone marrow nuclear cells by LTB4. It would be very interesting to test the effects of LTB4 and ROS on stem cell mobilization and homing in the future.

This study was performed to evaluate the impact of various peri-transplant factors on transfusion requirements in 45 patients with leukemia or severe aplastic anemia undergoing HLA-matched allogeneic bone marrow transplantation(BMT).

All patients were treated in an isolated room with HEPA filtration, and the combination of cyclosporin and short-course of methotrexate was used for GVHD prophylaxis. Patients received irradiated packed red cells to maintain the hematocrit ≥30% and irradiated platelet pheresis to keep the platelet count ≥20,000/µl.

In the first month, the mean(range) number of red cells and platelet pheresis were 4.9(0-21), 26.7(8-61), respectively. On univariate analyses, pre-BMT status(high-risk : 7.94±5.14 vs standard-risk: 3.78±2.99, p=0.0076) and concurrent infection(present : 8.41±4.70 vs absent : 3.33±2.72, p=0.0005) and sex incompatibility(match : 4.67±3.72 vs female → male : 3.78±3.07 vs male → female : 9.13±5.74, p=0.0161) were significantly associated with red cell requirements in the first month. Also, high-risk pre-BMT status(32.25±16.15 vs 20.25±14.64, p=0.0l56), the presence of concurrent infection(39.35±16.42 vs 15.33±5.67, p=0.0001) and veno-occlusive disease(45.00±14.47 vs 22.00±14.49, p=0.0055) increased platelet requirements significantly after allogeneic BMT. In particular, pre-BMT disease status was found to be independently associated with transfusion requirements.

This study demonstrates that pre-BMT status does influence transfusion requirements in the first month after HLA-matched allogeneic BMT. Further studies are necessary to confirm these results and to define optimal transfusion strategies.

Hepatic veno-occlusive disease(VOD) is a major life-threatening complication of bone marrow transplantation(BMT) caused by high-dose chemotherapy or radiotherapy. The aim of this study is to evaluate the incidence, risk factors, prophylactic effects of low-dose heparin and pentoxifylline(PTX) and therapeutic response to recombinant human tissue plasminogen activator(rt-PA) in VOD patients with leukemia after allogeneic BMT.

Thirty-two consecutive leukemia patients who underwent HLA-matched allogeneic BMT were included in this study. VOD was clinically defined as having two of the following features : hyperbilirubinemia(≥2mg/dL), tender hepatomegaly, unexplained weight gain(>2% from baseline) and/or ascites. Low-dose heparin(l00unit/kg/day, IV) and PTX(1,600mg/day, P0) were administered for the prevention of VOD.

The median age of recipients in this study was 27(17 - 44) years. Patients were treated for the following diseases : 17(53.1%) for acute myeloid leukemia(AML), 10(31.3%) for acute lymphoblastic leukemia(ALL) and 5(15.6%) for chronic myeloid leukemia(CML). Fourteen patients(43.7%) were classified as having high-risk pre-BMT status. Of the 32 consecutive patients undergoing allogeneic BMT, 5(15.6%) developed VOD. A higher risk of developing VOD was associated with pre-BMT disease status(p<0.01). All VOD patients received rt-PA-based thrombolytic therapy and complete resolution was achieved in-4(80.0%) of 5 patients without significant bleeding complications.

Further studies are needed to develop more effective prophylactic and thera-peutic approaches of VOD in patients with high-risk leukemia after allogeneic BMT.