Effect of rapamycin on spleen size in longstanding renal transplant recipients.

BACKGROUND: Based on evidence available in the literature, rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, but not calcineurin inhibitors (CNIs), has been shown to decrease spleen size. Small spleen, in some instances, is associated with hyposplenism, a condition recently reported in patients with longstanding renal transplant. Accordingly, the effect of immunosuppressive drugs on spleen size was evaluated. METHODS: Renal transplant recipients (35 taking mTOR and 68 CNI) were included, in whom a standardized investigation of the kidney allograft and spleen with the use of color Doppler ultrasound was performed and a peripheral smear were reviewed for the presence of Howell-Jolly bodies (HJBs). RESULTS: We enrolled 103 patients (64 men; 66 from a deceased donor). The mean age was 47.7 years (range, 23.0-74.0 y). Mean transplant duration was 1,899 days (range, 181-6,883 d). According to the presence of HJBs, the prevalence of hyposplenism was 47.6% for the entire cohort. The differences between the mTOR and CNI groups regarding sex and the presence of HJBs were not statistically significant (P > .05). Age, creatinine, hemoglobin, leukocytes, platelets, and Doppler parameters in spleen and kidney were similar in both groups (P > .05). mTOR patients had a decreased spleen length size (90.09 ± 13.02 mm vs 111.95 ± 18.66 mm; P < .001), a longer transplant duration (3,576 ± 1,594 d vs 1,036 ± 1,369 d; P < .001) and higher serum cholesterol (227.50 ± 38.75 mg/dL vs 182.67 ± 37.74 mg/dL; P < .001) and triglycerides (194.23 ± 79.88 mg/dL vs 148.70 ± 55.54 mg/dL; P = .003) levels compared with the CNI group. A multivariate analysis showed mTOR inhibitor to be the most important predictor of spleen size. In both the mTOR and CNI groups, the comparison between the subgroups of present and absent HJBs did not show any difference. CONCLUSIONS: The findings of this study suggest that small spleens in transplant recipients may be linked to treatment with an mTOR inhibitor, although this apparently does not compromise splenic function.

Functional hyposplenism in long-standing renal transplant recipients.

BACKGROUND: A nephrologist with expertise in ultrasonography noticed that patients with longstanding renal grafts had smaller spleens than subjects undergoing initial post-transplantation imaging. This putative finding prompted us to pursue a further investigation into splenic function based on Doppler ultrasound and hematologic parameters. METHODS: We enrolled 47 patients with functioning long-standing kidney grafts, measuring longitudinal diameter of the spleen, hilar and intrasplenic peak systolic velocities (PSV), and hilar and intrasplenic resistivity indices of the splenic artery as well as mean arterial blood pressure (MAP). Giemsa-stained peripheral blood smears were examined for the presence of Howell-Jolly bodies (HJBs) using light microscopy. The patients were then divided into HJB present (HJ(+)) or absent (HJ(-)) groups for further comparison. RESULTS: The overall mean age of 21 females and 26 males was 47.8 ± 12.0 years, and the mean time after transplantation was 2750 ± 1818 days (range, 208-6446). HJBs were detected in 23/47 patients (48.9%). The intrasplenic artery PSV was significantly lower and MAP higher in the HJ(+) group (P < .05). There was no difference in spleen size between the groups. DISCUSSION: HJBs in peripheral blood red cells, an indicator of hyposplenism, was associated with reduced intrasplenic artery PSV, suggesting dysfunction, which may play a role in the known vulnerability of renal transplant recipients to infections.

Complex karyotype and N-RAS point mutation in a case of acute megakaryoblastic leukemia (M7) following a myelodysplastic syndrome.

The development of acute megakaryoblastic leukemia (ANLL-M7) following myelodysplastic syndrome (MDS) has been described only in a few reports, and the mutations necessary for this transformation are still unknown. In this study, we describe a case of ANLL-M7 with a previous history of MDS presenting a complex karyotype 46,XX, t(4;11)(q21;q23),del(5)(q13q33),t(12;13)(p13;q21) and N-RAS point mutation. During MDS, the patient showed a hypercellular myelogram with dysplasia of the three myeloid lineages and the clinical symptoms characteristic of the 5q- syndrome. During the follow-up, we observed the appearance of two additional subclones, one with an isochromosome 17q and another with polyploidy. The presence of an isochromosome 17q in one subclone and polyploidy in another is probably due to the genetic instability generated by the malignant transformation.