Immunotherapy with high-dose interleukin-2 (HD-IL2) results in long-term survival in some metastatic renal cell carcinoma (mRCC) patients but has significant acute toxicities. Biomarkers predicting response to therapy are needed to better select patients most likely to benefit. NLR (absolute neutrophil count (ANC)/absolute lymphocyte count (ALC)) is a prognostic and predicative biomarker in various malignancies. The goal was to determine whether NLR can predict response to HD-IL2 in this setting. Patients with clear cell mRCC treated with HD-IL2 were identified from an institutional database from 2003–2012. Baseline variables for the assessment of IMDC risk criteria, and neutrophil and lymphocyte count, were collected. Best response criteria were based on RECIST 1.0. Wilcoxon rank-sum test was used to evaluate the association of continuous baseline variables with disease control. NLR was stratified by ≤4 or >4. Progression free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method and Cox proportional hazard models assessed associations of NLR with survival. In 71 eligible patients, median NLR in those with an objective response (n = 14, 20%) was 2.3 vs 3.4 in those without (n = 57, 80%, p = 0.02). NLR ≤4 was associated with improved progression free and overall survival. After adjustment for IMDC risk criteria, NLR remained a significant predictor of OS (ANC/ALC ≤4 vs >4, HR 0.41, 95% CI 1.09-5.46, p = 0.03; ANC/ALC continuous variable per unit change in NLR, HR 1.08, 95% CI 1.01-1.14, p = 0.03). In this discovery set, NLR predicts overall survival in patients treated with HD-IL2 in mRCC, and may allow better patient selection in this setting. Data needs validation in an independent cohort.

Sickle cell disease (SCD) is a classic example of a disorder with recessive Mendelian inheritance, in which each parent contributes one mutant allele to an affected offspring. However, there are exceptions to that rule. We describe here the first reported case of conversion of inherited sickle cell trait to SCD by uniparental disomy (UPD) resulting in mosaicism for SS and AS erythrocytes. A 14-year-old boy presented with splenomegaly and hemolysis. Although his father has sickle cell trait, his mother has no abnormal hemoglobin (Hb). DNA sequencing, performed to rule out Hb S/β-thalassemia, detected homozygous Hb SS. Further studies revealed mosaic UPD of the β-globin locus, more SS erythroid progenitors than AS, but a reverse ratio of erythrocytes resulting from the survival advantage of AS erythrocytes. This report exemplifies non-Mendelian genetics wherein a patient who inherited sickle cell trait has mild SCD resulting from postzygotic mitotic recombination leading to UPD.

Hereditary spherocytosis (HS) is the most common cause of inherited red cell membrane disorders and affects approximately 1 out of every 2,000–5,000 people. Although seen in all ethnicities, it is more common in people from northern European ancestry. Clinical presentation is variable, ranging from asymptomatic to severe form of anemia, and can be exacerbated by pregnancy, sudden blood loss, or superimposed infection, i.e., parvovirus that targets the erythroid precursors. Some patients, who later on develop only mild or moderate anemia, can present with severe transfusion-dependent anemia in the neonatal period due to ineffective erythropoiesis as well as increased splenic function immediately after birth [1]. Due to marked hemolysis leading to increased bilirubin levels, these infants are prone to acute bilirubin encephalopathy, also known as kernicterus. Moreover, the diagnosis can be challenging in the neonatal period due to unreliability of biochemical tests like osmotic fragility and eosin-5′ maleimide if age-appropriate controls are not used. Furthermore, spherocytosis due to other causes, i.e., ABO incompatibility, can also confound some of these tests that rely mainly on the presence of spherocytes for diagnosis.