Successful treatment of tacrolimusâ related pure red cell aplasia and autoimmune hemolytic anemia with rituximab in a pediatric cardiac transplant patient

Acquired pure red cell aplasia (PRCA) and autoimmune hemolytic anemia (AIHA) are rare complications of immunosuppression in pediatric solid organ transplant patients. We report a 14â monthâ old female child who developed Coombs positive hemolytic anemia and reticulocytopenia while on tacrolimus after cardiac transplantation. She was successfully treated with rituximab after failing treatment with corticosteroids and intravenous immunoglobulins. Clinicians should consider PRCA differential diagnosis in a patient presenting with reticulocytopenia and hemolysis. In addition, the coexistence of PRCA with AIHA, and the response to therapy with rituximab, supports a common immuneâ mediated pathogenesis for both disorders.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138854/1/pbc26674_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138854/2/pbc26674.pd

JMML evolving to AML in a 14-year-old male acquiring an additional i(X)(q10)

Review on JMML evolving to AML in a 14-year-old male acquiring an additional i(X)(q10

The genomic landscape of juvenile myelomonocytic leukemia

Juvenile myelomonocytic leukemia (JMML) is a myeloproliferative neoplasm (MPN) of childhood with a poor prognosis. Mutations in NF1, NRAS, KRAS, PTPN11 and CBL occur in 85% of patients, yet there are currently no risk stratification algorithms capable of predicting which patients will be refractory to conventional treatment and therefore be candidates for experimental therapies. In addition, there have been few other molecular pathways identified aside from the Ras/MAPK pathway to serve as the basis for such novel therapeutic strategies. We therefore sought to genomically characterize serial samples from patients at diagnosis through relapse and transformation to acute myeloid leukemia in order to expand our knowledge of the mutational spectrum in JMML. We identified recurrent mutations in genes involved in signal transduction, gene splicing, the polycomb repressive complex 2 (PRC2) and transcription. Importantly, the number of somatic alterations present at diagnosis appears to be the major determinant of outcome

Apheresis red blood cells associated with repeated hemolysis during blood priming of the Cellex Photopheresis System

Extracorporeal photopheresis (ECP) in young pediatric patients has a risk for procedural hypotension and anemia due to extracorporeal fluid shifts. A standard mitigation policy in these patients is to prime the device with packed red blood cells (RBC) or whole blood. We now report multiple episodes of hemolysis while attempting to prime the Therakos Cellex in a pediatric transplant patient undergoing a course of ECP for severe graft‐vs‐host‐disease. Over the course of 40 ECP treatments, hemolysis was observed on five occasions. An extensive investigation found an association between hemolysis and apheresis RBC (A‐RBC). Of 46 RBC units dispensed for blood priming, hemolysis occurred with 22% (4 of 18) of A‐RBC and accounted for 80% (4 of 5) of all hemolysis episodes. Hemolysis was significantly higher with A‐RBC when compared with RBC collected by whole blood donations (WB‐RBC: 3.5% [1 of 28]; P = .049). A comparison of RBC attributes, including unit age, showed that hemolyzed A‐RBC units tended to be younger than both nonhemolyzed RBC (6.5 vs 10.3 days, P = .018) and WB‐RBC (8.5 days, P = .10). We hypothesize that A‐RBC may exhibit “sublethal” RBC damage following prior exposure to centrifugal shear and negative forces at the time of collection, leading to a decrease in RBC deformability and increased susceptibility to hemolysis. This is the first report showing an increased susceptibility to hemolysis with A‐RBC during priming of the Cellex.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153230/1/jca21740.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153230/2/jca21740_am.pd

Apheresis red blood cells associated with repeated hemolysis during blood priming of the Cellex Photopheresis System

Extracorporeal photopheresis (ECP) in young pediatric patients has a risk for procedural hypotension and anemia due to extracorporeal fluid shifts. A standard mitigation policy in these patients is to prime the device with packed red blood cells (RBC) or whole blood. We now report multiple episodes of hemolysis while attempting to prime the Therakos Cellex in a pediatric transplant patient undergoing a course of ECP for severe graft‐vs‐host‐disease. Over the course of 40 ECP treatments, hemolysis was observed on five occasions. An extensive investigation found an association between hemolysis and apheresis RBC (A‐RBC). Of 46 RBC units dispensed for blood priming, hemolysis occurred with 22% (4 of 18) of A‐RBC and accounted for 80% (4 of 5) of all hemolysis episodes. Hemolysis was significantly higher with A‐RBC when compared with RBC collected by whole blood donations (WB‐RBC: 3.5% [1 of 28]; P = .049). A comparison of RBC attributes, including unit age, showed that hemolyzed A‐RBC units tended to be younger than both nonhemolyzed RBC (6.5 vs 10.3 days, P = .018) and WB‐RBC (8.5 days, P = .10). We hypothesize that A‐RBC may exhibit “sublethal” RBC damage following prior exposure to centrifugal shear and negative forces at the time of collection, leading to a decrease in RBC deformability and increased susceptibility to hemolysis. This is the first report showing an increased susceptibility to hemolysis with A‐RBC during priming of the Cellex.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153230/1/jca21740.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153230/2/jca21740_am.pd

Successful Management of Blue Rubber Bleb Nevus Syndrome (BRBNS) with Sirolimus

Blue rubber bleb nevus syndrome (BRBNS) is a rare disease with vascular malformations in several systems of the body, most commonly the skin and gastrointestinal tract. Bleeding from the gastrointestinal (GI) tract is a major complication, which may lead to chronic iron deficiency anemia and the need for frequent blood transfusions due to ongoing gastrointestinal blood loss. In this case report, we describe a now 19-year-old female with BRBNS who required six blood transfusions per year and after starting sirolimus is symptom- and transfusion-free

The role of continuous renal replacement therapy in the management of acute kidney injury associated with sinusoidal obstruction syndrome following hematopoietic cell transplantation

Maintaining fluid balance, preâ and postâ MAâ HCT is essential and usually requires frequent administration of diuretics. Hepatic sinusoidal obstructive syndrome is potentially lifeâ threatening, especially when associated with AKI and MOF. This study describes six patients who developed AKIâ associated SOS and diureticâ resistant FO who subsequently underwent CRRT using standardized management guidelines for fluid balance postâ HCT. Retrospective chart review was done for HCT patients between September 2011 and October 2013 at a tertiary care children’s hospital. Thirtyâ four patients underwent MAâ HCT in the study period. Six patients had SOS complicated by diureticâ resistant FO and underwent CRRT. Defibrotide was used in three patients. Median time on CRRT was 10.5 days. Sixtyâ six percent (N = 4 of 6) of patients had full resolution of SOS symptoms with a mortality rate of 34% (N = 2 of 6). Among patients who had full recovery of SOS symptoms, one patient developed AKI, endâ stage renal diseases and underwent kidney transplantation 34â months postâ HCT. Thus, of six included patients, two died and one developed ESRD with only 50% (N = 3 of 6) good outcome. Use of a standardized, evidenceâ based fluid balance protocol and early initiation of CRRT for HCTâ related AKI/SOS was associated with good outcomes.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142494/1/petr13139.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142494/2/petr13139_am.pd