scholarly journals Potential Impact of Sickle Hemoglobin Concentration on Survival Among Patients with Renal Medullary Carcinoma and Sickle Cell Trait

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4843-4843
Author(s):  
Marcus A. Carden ◽  
Jonathan Metts ◽  
John M. McCarty ◽  
Sarah Mitchell ◽  
Bradley Carthon ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Survival Data ◽  
Sickle Cell Trait ◽  
Case Reports ◽  
Globin Gene ◽  
Medullary Carcinoma ◽  
Exponential Relationship ◽  
Sickle Hemoglobin ◽  
Renal Medullary Carcinoma ◽  
Alpha Globin

Background: Renal medullary carcinoma (RMC) is a rare, aggressive form of renal cell carcinoma almost exclusively (>90%) diagnosed in individuals with sickle cell trait (SCT), and 2/3 of those affected are male. Based on population-surveillance data, only 246 patients were diagnosed with RMC between 2005-2014 (Carden etal. J Sickle Cell Disease and Hemoglobinopathies, 2018) and many patients have metastatic disease at diagnosis (Msaeoul et al., Clin Genitourin Cancer, 2019). Median overall survival (OS) in patients with metastatic RMC (mRMC) at diagnosis is less than 12 months and predictors of survival are largely unknown, although case reports suggest novel chemotherapeutic strategies are important (Carden et al., Ped Blood Cancer, 2017&2018). The role SCT plays in RMC pathobiology, however, is largely unknown, as many patients do not have a complete hemoglobin subtype profile completed at diagnosis. Studies evaluating sickle hemoglobin concentrations (%HbS) in relation to survival for patients with RMC are needed, as SCT is associated with renal dysfunction and researchers have hypothesized that HbS polymerization within red cells traversing the kidney disrupts blood perfusion, which leads to kidney injury and an increased possibility for cancer formation (Msaeoul et al, Clin Cancer Res, 2018). Patients with %HbS≤36%, such as patients with SCT and concomitant alpha-globin gene deletion(s) might be protected against HbS polymerization and renal concentrating defects (Gupta etal., J Clin Invest, 1991). We hypothesize that lower %HbS is associated with higher survival. In this preliminary multi-institutional study, we retrospectively reviewed available charts from patients diagnosed with mRMC and SCT to evaluate for an association between %HbS and OS. Methods: We found nine patients (3 adults, 6 children) who were diagnosed with mRMC and SCT at our various institutions between 2002-2017 who had survival data. Eight patients had %HbS levels by hemoglobin quantification at diagnosis. In a post-hoc analysis, patients were separated into two groups (%HbS>36% and %HbS≤36%), levels similar to that found in patients with alpha-globin gene deletions described by Gupta et al. Fit-curves were determined for OS vs. %HbS. Three-year OS was determined using Kaplan-Meier analysis and the log-rank method. P<0.05 was considered statistically significant. Results: Clinical characteristics of patients are shown in Table 1. Average age (standard deviation) at diagnosis was 15.2 years (4.9) and most patients were male (87.5%). Six patients had %HbS >36% and 2 patients had %HbS ≤36%. Median OS was 17.8 months. Using fit-function testing, analysis of survival vs. %HbS yielded an exponential relationship (R2=0.69), suggesting higher survival when %HbS≤36% (p=0.05). OS of the two patients with %HbS≤36% was greater than those with %HbS>36%, though results were not statistically significant (p = 0.09). Conclusion: While there are limitations to this small, retrospective analysis, these data suggest that lower intracellular red cell %HbS concentrations could be protective in patients with mRMC and SCT. Chemotherapy and other treatment regimens may also play a role in survival and need to be studied. Further investigation is needed to determine the role SCT plays in RMC pathobiology and to determine if %HbS concentrations, as well as alpha-thalassemia deletion(s), may be protective in patients with RMC. Disclosures Carden: GBT: Honoraria; NIH: Research Funding.

Renal Medullary Carcinoma in a White Adolescent With Sickle Cell Trait

2014 ◽  
Vol 36 (5) ◽  
pp. e285-e289 ◽  
Author(s):  
Paul Daher ◽  
Ali Bourgi ◽  
Edward Riachy ◽  
Antoine Khoury ◽  
Caline Rehayem ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Medullary Carcinoma ◽  
Renal Medullary Carcinoma

A Novel β Globin Gene Mutation, Reported As An α Chain Hemoglobin Variant By High Performance Liquid Chromatography (HPLC) & As Sickle Cell Trait On New Born Screening: A case Report

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 954-954
Author(s):  
Kranthi Nandan Seelaboyina ◽  
Jennifer Alison Busse ◽  
Sandeep Malik ◽  
Thomas Moulton
Keyword(s):  
Sickle Cell ◽  
Copy Number ◽  
Sickle Cell Trait ◽  
Globin Gene ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Thalassemia Intermedia ◽  
Exon 2 ◽  
Alpha Globin ◽  
Hemoglobin Variants

Abstract Introduction There are 827 variants of β thalassemia reported to the registry of human hemoglobin variants and thalassemias registry 1. Genetic mutations of β thalassemia are very diverse but can be broadly divided in to non deletion forms and deletion forms. The new mutation is a frame shift insertion in exon 2 of the β globin gene. To the best of our knowledge this mutation has never been described before and presents as a mild form β thalassemia intermedia. Objective To describe the phenotypic presentation of the new β globin variant, due to insertion of 9 nucleotides (AAAGTGCTC) between nucleotides c.207 and c.208. Case report A 22 months-old Hispanic boy who was referred for evaluation of persistent anemia. The new born screening for the child was positive for sickle cell trait. Initial hemoglobin (Hb) was 8.8, hematocrit was 27 and MCV was 65.5, which were decreased. RDW was 25.2, which was increased. Hemoglobin evaluation by acid and alkaline electrophoresis and HPLC revealed a HbS 0%, HbF 6.5% HbA 78.4%, HbA2 4.9% and a Hb variant 10.2%. The interpretation of the results was an α globin variant suggestive of Hb Montefiore and β thalassemia trait. Alpha thalassemia PCR for the 7 most common deletions in the α globin chain was negative. Subsequent α globin gene sequencing revealed no α globin gene mutations. On physical exam there were no bony changes or hepatosplenomegaly. Family History The mother is 29-year-old with HbAA. The father is 39-years-old with the same mutation on beta globin gene analysis. Hb electrophoresis also suggested an α and β globin mutation. Alpha thalassemia PCR was negative and he had a normal α globin gene copy number. At age 19 he had a splenectomy secondary to splenomegaly and hypersplenism. He is consistently anemic with Hb< 9 and MCV < 70. The child has a paternal half brother, who is 21 years old and has similar problems as father. He had a splenectomy at the age of 17 after admission for abdominal pain. The patient has a 5-year-old sibling, who is normal with HbAA and another paternal half sibling reported as no anemia. Discussion Though β thalassemia intermedia is most commonly homozygous or compound heterozygous, less frequently it can be due to single locus mutation. DNA sequencing of the α globin gene of the index case was completely normal and there was normal copy number of the α globin gene in the father. No Hb S was found on Hb electrophoresis. The new mutation adds 9 base pairs to exon 2 and 3 amino acids (Lys-Val-Leu) between amino acid 68 and 69 of the protein. This elongates the beta chain which can lead to instability and precipitation of Hb as well as hemolysis and anemia2. Further studies like short time incubation and pulse chase globin chain synthesis experiments are needed to know the stability of the β globin protein3. In addition, an increase of α globin gene copy number can also be a reason for increasing the severity of β thalassemia trait2. However the α gene copy was normal in the father. Conclusion We present a case of a child with a false positive abnormal newborn screen suggestive of sickle cell trait, as well as a Hb electrophoresis suggestive of an alpha globin mutation. As the father and paternal brother have had a splenectomy in their teen years with noted hepatosplenomegaly, suggestive of increased hemolysis, and the anemia is more severe than usual for β thalassemia trait, this suggests that phenotypically the c.199_207dup variant presents as a mild β thalassemia intermedia. In addition, there does not seem to be any bony abnormalities associated with marrow hyperplasia. As both our patients are heterozygous for this novel mutation with normal α globin gene copy number and alpha globin sequencing, we suspect that elongation of the β globin produces an unstable hemoglobin with a mild β thalassemia intermedia phenotype2. References 1. Databases of human hemoglobin variants and other resources at the globin gene server. Hemoglobin. 25(2):183-93, 2001 May. 2. Galanello R, Cao A. Relationship between genotype and phenotype. Thalassemia intermedia. Annals of the New York Academy of Sciences 1998; 850:325-33. 3. Is hemoglobin instability important in the interaction between hemoglobin E and beta thalassemia? Blood September 15, 1998 vol. 92 no. 6 2141-2146. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Renal Medullary Carcinoma in an Adolescent With Unknown Sickle Cell Trait

Cureus ◽  
2021 ◽  
Author(s):  
Brian D Noreña-Rengifo ◽  
Jorge Ochoa-Gaviria ◽  
Alejandro Vélez-Escobar ◽  
Juan P Muñoz ◽  
Marcela Riveros-Ángel
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Medullary Carcinoma ◽  
Renal Medullary Carcinoma

Renal Medullary Carcinoma and Sickle Cell Trait

1997 ◽  
pp. 1349 ◽  
Author(s):  
Paul Friedrichs ◽  
Patrick Lassen ◽  
Edith Canby ◽  
Christopher Graham
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Medullary Carcinoma ◽  
Renal Medullary Carcinoma

scholarly journals Renal Medullary Carcinoma with an Aggressive Clinical Course: A Case Report and Review of the Literature

2017 ◽  
Vol 10 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Madhumati R. Kalavar ◽  
Sami Ali ◽  
Damoun Safarpour ◽  
Saroj Davi Kunnakkat
Keyword(s):  
Case Report ◽  
Sickle Cell ◽  
Clinical Course ◽  
Sickle Cell Trait ◽  
African Descent ◽  
Young Patients ◽  
Medullary Carcinoma ◽  
Review Of The Literature ◽  
Renal Medullary Carcinoma ◽  
Aggressive Clinical Course

Renal medullary carcinoma (RMC) is a rare, yet aggressive malignancy of the kidney that is found predominantly in young patients with African descent and sickle cell hemoglobinopathies and most specifically sickle cell trait. Due to its aggressive nature, most cases have metastasis or local invasion at the time of diagnosis. Prognosis is extremely poor with survival less than 1 year after diagnosis. Here we present a case of metastatic RMC in a 29-year-old African female. Despite chemotherapy with cisplatin, gemcitabine, and paclitaxel, and initial shrinkage of the tumor, the patient died 5 months after diagnosis.

Sign in / Sign up

Export Citation Format

Share Document