Use of infusion ports in patients with sickle cell disease: Indications and complications.

BACKGROUND: Peripheral venous access in patients with sickle cell disease (SCD) can become difficult over time due to frequent access and scarring. Infusion ports provide reliable central venous access. Deep venous thrombosis (DVT) and infections are complications associated with SCD and infusion ports. METHODS: We performed a 17.5-year single-institution retrospective chart review (January 2000 to July 2018) with literature review regarding use of infusion ports in patients with SCD. RESULTS: We identified 32 patients with infusion ports placed for a total of 63 devices (48 for chronic transfusion [CT] and 15 for poor venous access [PVA], not on CT) for a total of 99,272 catheter days. The mean age at first insertion was 8 years (range 1-20 years). Complications included malfunction, infection, thrombosis, difficult access, and pain over infusion port site. The rate of infection was 0.2 per 1000 catheter days. Thrombosis was identified in three devices (5%) in three patients (9%), with a rate of 0.03 per 1000 catheter days. There was no difference in complications by site in either the left or right subclavian vein (p = 1). The rate of premature removal was 0.36 per 1000 catheter days, which was higher among patients with infusion ports solely for PVA (0.87 per 1000 catheter days) compared with those placed for CT (0.29 per 1000 catheter days). CONCLUSION: Infusion ports in patients with SCD was associated with low rates of thrombosis, infection, and malfunction, and may be considered as an alternative to frequent intravenous access, especially in patients requiring CT.

IDH1 mutated acute myeloid leukemia in a child with metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria.

D-2-hydroxyglutaric aciduria (D-2-HGA) is a rare metabolic disorder characterized by developmental delay, hypotonia, and bi-allelic mutations in D-2-hydroxyglutarate dehydrogenase (D2HGDH) or a single gain-of-function mutation in isocitrate dehydrogenase 2 (IDH2). Metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria (MC-HGA) is a type of D-2-HGA that has been previously reported in ten patients (OMIM 614875), three of whom had somatic mosaicism for R132 variants in isocitrate dehydrogenase 1 (IDH1). We describe a 3-year-old boy with MC-HGA who subsequently developed acute myeloid leukemia (AML) and was found to have an IDH1 R132C mutation in a leukemic bone marrow sample. Further testing revealed presence of somatic mosaicism for IDH1 R132C variant, suggesting an association of IDH1 in inducing myeloid leukemogenesis.

Splenectomy is not associated with a higher tricuspid regurgitant jet velocity in people with sickle cell anemia.

BACKGROUND: Vascular complications such as pulmonary hypertension (PH) occur at an increased rate following splenectomy in patients with various hemolytic blood disorders including thalassemia. The goal of this retrospective cross-sectional analysis was to assess the independent association of splenectomy with an elevated tricuspid regurgitation velocity (TRV) in people with homozygous sickle cell disease (HbSS). TRV is a noninvasive screening test for PH and a surrogate marker of prognosis in sickle cell disease (SCD). PROCEDURE: Data were obtained from the multicenter Walk-PHaSST (treatment of pulmonary hypertension and sickle cell disease with sildenafil therapy) study of PH (NCT00492531). We compared TRV in the cohort of patients with HbSS who were surgically splenectomized with patients who were not surgically splenectomized. RESULTS: We found no significant differences in TRV between the two groups. CONCLUSIONS: The lack of difference in TRV between the two groups is most likely because members of the comparator nonsurgical group in many cases experienced autoinfarction of the spleen in childhood. Splenectomy does not seem to confer additional risk for the development of a higher TRV in HbSS, unlike in patients with thalassemia or other hemolytic anemias. This could be an important consideration when weighing the risks and benefits of splenectomy in patients with HbSS.

Tackling Acute Lymphoblastic Leukemia-One Fish at a Time.

Despite advancements in the diagnosis and treatment of acute lymphoblastic leukemia (ALL), a need for improved strategies to decrease morbidity and improve cure rates in relapsed/refractory ALL still exists. Such approaches include the identification and implementation of novel targeted combination regimens, and more precise upfront patient risk stratification to guide therapy. New curative strategies rely on an understanding of the pathobiology that derives from systematically dissecting each cancer's genetic and molecular landscape. Zebrafish models provide a powerful system to simulate human diseases, including leukemias and ALL specifically. They are also an invaluable tool for genetic manipulation, in vivo studies, and drug discovery. Here, we highlight and summarize contributions made by several zebrafish T-ALL models and newer zebrafish B-ALL models in translating the underlying genetic and molecular mechanisms operative in ALL, and also highlight their potential utility for drug discovery. These models have laid the groundwork for increasing our understanding of the molecular basis of ALL to further translational and clinical research endeavors that seek to improve outcomes in this important cancer.