Is screening for Factor V Leiden and Prothrombin G20210A Mutations in Renal Transplantation worthwhile? Results of a large single-center U.K. study

This single center study is the largest series of renal transplant recipients and donors screened for the commonest prothrombotic genotypes. A total of 562 transplant recipients and 457 kidney donors were genotyped for the factor V Leiden and prothrombin G20210A mutations. The prevalence of heterozygous factor V Leiden was 3.4% and 2.6% and prothrombin G20210A was 2.0% and 1.1% in recipients and donors, respectively, similar frequencies to that of the general U.K. population. The 30-day and 1-year graft survival rates in recipients with thrombophilic mutations were 93% and 93%, compared with 88% and 82% in patients without these mutations (log-rank P =0.34). Thrombophilia in recipients (odds ratio 0.55; confidence interval 0.06-2.29; P =0.56) or in donors (odds ratio 1.53; confidence interval 0.27-5.74; P =0.46) did not correlate with graft loss at 30 days after transplantation. In contrast to recent reports, this study did not demonstrate an association between thrombophilia and renal allograft loss, and routine screening is not recommended.

The endogenous granulocyte colony-stimulating factor response following autologous peripheral blood stem cell transplantation is inpaired in patients with myeloma

Granulocyte colony-stimulating factor (G-CSF) levels were studied in 23 patients (10 myeloma, 13 relapsed Hodgkin's disease, non-Hodgkin's lymphoma or germ cell tumours), post autologous peripheral blood stem cell transplantation (PBSCT). The two groups had similar previous chemotherapy and numbers of CD34+ cells transplanted. All patients received G-CSF by injection starting 8 d post transplantation. Twenty out of 23 patients showed raised endogenous levels of G-CSF before cytokine administration. Myeloma patients showed significantly lower levels of endogenous G-CSF than the other patients (0.767 versus 3.262 ng/ml, P <0.05). Further rises in G-CSF levels were seen following the administration of exogenous G-CSF which then fell, despite ongoing administration of G-CSF, as neutrophil recovery occurred.

Level of renal function and serum erythropoietin levels independently predict anaemia post-renal transplantation

Background. Post-renal transplant anaemia is a potentially reversible cardiovascular risk factor. Graft function, immunosuppressive agents and inhibition of the renin-angiotensin system have been implicated in its aetiology. The evaluation of erythropoietin (EPO) levels may contribute to understanding the relative contributions of these factors. Methods. Two-hundred and seven renal transplant recipients attending the Belfast City Hospital were studied. Clinical and laboratory data were extracted from the medical records and laboratory systems. Results. Of the 207 patients (126 male), 47 (22.7%) were found to be anaemic (males, haemoglobin (Hb) <12 g/dl, females Hb <11g/dl). The anaemic group had a significantly higher mean serum creatinine level (162.8 µmol/l vs 131.0 µmol/l, P <0.001) and lower mean estimated glomerular filtration rate (eGFR) (41.5 ml/min vs 54.9 ml/min, P <0.001) than the non-anaemic group. Individual immunosuppressive regimens were comparable between those with and those without anaemia. Angiotensin converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) administration was not more prevalent in those with anaemia compared with those without (36.2 vs 38.8, P = 0.88). There was a significant inverse correlation between Hb levels and serum EPO levels (R = -0.29, P <0.001), but not between EPO levels and eGFR (R = 0.02, P = 0.74). Higher EPO levels were predictive of anaemia, independent of eGFR in multivariate analysis. Conclusion. Anaemia is common in post-renal transplant patients. The levels of renal function and serum EPO and not immunosuppressive regimens or ACE-I/ARB use, are strong and independent predictors of anaemia. © The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Pim2 cooperates with PML-RAR alpha to induce acute myeloid leukemia in a bone marrow transplantation model

Although the potential role of Pim2 as a cooperative oncogene has been well described in lymphoma, its role in leukemia has remained largely unexplored. Here we show that high expression of Pim2 is observed in patients with acute promyelocytic leukemia (APL). To further characterize the cooperative role of Pim2 with promyelocytic leukemia/retinoic acid receptor alpha (PML/RAR alpha), we used a well-established PML-RAR alpha (PR alpha) mouse model. Pim2 coexpression in PR alpha-positive hematopoietic progenitor cells (HPCs) induces leukemia in recipient mice after a short latency. Pim2-PR alpha cells were able to repopulate mice in serial transplantations and to induce disease in all recipients. Neither Pim2 nor PR alpha alone was sufficient to induce leukemia upon transplantation in this model. The disease induced by Pim2 overexpression in PR alpha cells contained a slightly higher fraction of immature myeloid cells, compared with the previously described APL disease induced by PR alpha. However, it also clearly resembled an APL-like phenotype and showed signs of differentiation upon all-trans retinoic acid (ATRA) treatment in vitro. These results support the hypothesis that Pim2, which is also a known target of Flt3-ITD (another gene that cooperates with PML-RAR alpha), cooperates with PR alpha to induce APL-like disease. (Blood. 2010; 115(22): 4507-4516)