Clinical Utility of Quantitative PCR for Chimerism and Engraftment Monitoring after Allogeneic Stem Cell Transplantation for Hematologic Malignancies.

Although quantitative PCR (qPCR) has been explored for chimerism monitoring after allogeneic stem cell transplantation (SCT), evidence regarding its clinical utility compared with standard short tandem repeat (STR) is still limited. We retrospectively studied commercial qPCR and STR chimerism with respective positivity thresholds of .1% and 1% in 359 peripheral blood (PB) and 95 bone marrow (BM) samples from 30 adult patients after first HLA-matched SCT for myeloid malignancies or acute lymphatic leukemia. Concordance between the 2 methods was 79.5%, with all discordant samples positive in qPCR but negative in STR. Of the latter, sporadic qPCR positivity without clinical correlates was seen mostly in BM samples early post-transplant. In 7 of 21 patients with available follow-up samples in the first months after transplantation, qPCR but not STR revealed low levels (<1%) of sustained host chimerism in PB, reflecting delayed engraftment or persistent mixed chimerism (PMC). These conditions were associated with donor-recipient cytomegalovirus (CMV) serostatus and early CMV reactivation but not with immunosuppressive regimens or clinical outcome. qPCR predicted all 8/8 relapses with samples in the 6 months before onset by sustained positivity in both PB and BM compared with 1/8 relapses predicted by STR mainly in BM. The response kinetics to donor lymphocyte infusions for the treatment of PMC or relapse was shown by qPCR but not STR to be protracted over several months in 3 patients. Our results demonstrate the superior clinical utility of qPCR compared with STR for monitoring subtle changes of host chimerism associated with different clinical conditions, making a case for its use in the clinical follow-up of transplant patients.

[Biological responses of tin mine particles and their association with adverse effects on health in tin mine].

OBJECTIVE: To evaluate the biological and toxicity of tin mine particles mixed with crystalline silica using an in vitro test, and to compare to the pathogenesis of pneumoconiosis and lung cancer. METHODS: Respirable particle samples were sampled from four tin mines, in which elevated mortality of pneumoconiosis and lung cancer were reported in miners exposed to particles. Alveolar macrophages (AM) are considered as the target cells of primary dust effects. The samples were then measured in 15, 30, 60 and 120 microg particle per 106 AM for cytoxicity with the release of glucuronidase, lactate dehydrogenase, for reactive oxygen damage with H2O2 release, and for ability to induce fibrosis using the secretion of tumor necrosis factor-alpha (TNF-(alpha) in guinea pig and/or rat am. pure quartz (dq12) and corundum were used as controls. RESULTS: The results showed the samples from tin mines caused a higher cytoxicity when compared to corundum, yet lower when compared to quartz. However, reactive oxygen species release induced by the samples were significantly higher than that induced by quartz and corundum. Beside particle samples induced higher TNF-alpha secretion than corundum, samples from Limu tin mine also induced greatly higher TNF-alpha levels than that induced by pure quartz, even in the lowest concentration. The results from epidemiological research show that high incidence of silicosis among tin miners. And standardize mortality from all cancer (SMR = 1.58, 95% CI: 1.39-1.76) and lung cancer (SMR = 3.17, 95% CI: 2.59-3.76) are higher than national average level. CONCLUSION: The results from in vitro test may reasonable interpret high risk of pneumoconiosis and lung cancer in tin miners. The in vitro multidimensional reaction patterns of AM can be used to screen workplace particles for adverse effects to health.

Biological responses of workplace particles and their association with adverse health effects on miners.

Epidemiological research has demonstrated the relationship between exposure to quartz dust and an elevated risk of pneumoconiosis and possible elevated risk of cancer. The current study was designed to evaluate the biological responses of workplace particles containing crystalline silica using an in vitro cell test. Respirable particle samples were sampled from four tin mines, where the standardized mortality ratio (SMR) for pneumoconiosis was 51.6 and SMR for lung cancer was 2.2 in dust-exposed miners. Alveolar macrophages (AM) are considered as the target cells for primary dust effects. The samples were then measured at 15, 30, 60 and 120 microg particle per 10(6) AM for cytoxicity with the release of glucuronidase, lactate dehydrogenase, for reactive oxygen damage with H(2)O(2) release, and for ability to induce fibrosis using the secretion of tumor necrosis factor-alpha (TNF-alpha). Pure quartz (DQ12) and corundum were used as controls. The results showed the samples from tin mines caused a higher cytoxicity when compared to corundum, yet lower when compared to quartz. However, reactive oxygen species release (148-177 nmol/3 x 10(5) AM in high concentration of 120 microg/10(6) AM) induced by the samples were significantly higher than that induced by quartz (57 nmol/3 x 10(5) AM) and corundum (62 nmol/3 x 10(5) AM). Furthermore, particle samples induced higher TNF-alpha secretion than corundum, the samples from Limu tin mine induced much higher TNF-alpha levels than that induced by DQ12 quartz. The results from the in vitro tests help elucidate the degree of hazard of dust particles in tin mines. The in vitro reaction patterns of AM also constitute a powerful tool to monitor biological and pathogenic responses of humans following dust particle exposure.