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.
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.
X-linked agammaglobulinemia (XLA) is a primary immunodeficiency characterized by marked reduction in all classes of serum immunoglobulins and the near absence of mature CD19+ B-cells. Although malignancy has been observed in patients with XLA, we present the first reported case of acute myeloid leukemia (AML) in a patient with XLA. We also demonstrate the complete correction of the XLA phenotype following allogeneic hematopoietic cell transplantation for treatment of the patient’s leukemia.
Certain patients who receive granulocyte colony-stimulating factor (GCSF) for autologous hematopoietic stem cell (AHSC) collection fail to mobilize well enough to proceed with transplant. When plerixafor is used with GCSF, the likelihood of achieving the CD34⁺ stem cell target in fewer collections is higher; plerixafor use in all patients is unlikely to be cost-effective. This study retrospectively evaluated the effectiveness of utilizing a peripheral blood CD34⁺ stem cell count (PBCD34) ≤8/µL on day 4 of GCSF-based AHSC mobilization as a threshold for plerixafor administration, and compared the efficacy of collection and cost analysis using historical controls. All patients in the study cohort reached their CD34⁺ targets in ≤3 collections. Significantly more patients who received plerixafor + GCSF versus GCSF alone reached their CD34⁺ target in one collection (P = 0.045); however, there were no significant differences in the number of collections or in cumulative product yields. The historical cohort had 10.3% mobilization failures; the number of collections per patient needed to reach the target was significantly higher in the historical cohort versus study cohort (P = 0.001) as was the number of patients requiring more than one collection to reach their target (P = 0.023). However, the average cost per patient was also significantly higher in the study cohort (P = 0.025). Further refinement of the algorithm may reduce the difference in cost between the two mobilization strategies.
Maintaining fluid balance, pre- and post-MA-HCT is essential and usually requires frequent administration of diuretics. Hepatic sinusoidal obstructive syndrome is potentially life-threatening, especially when associated with AKI and MOF. This study describes six patients who developed AKI-associated SOS and diuretic-resistant FO who subsequently underwent CRRT using standardized management guidelines for fluid balance post-HCT. Retrospective chart review was done for HCT patients between September 2011 and October 2013 at a tertiary care children's hospital. Thirty-four patients underwent MA-HCT in the study period. Six patients had SOS complicated by diuretic-resistant FO and underwent CRRT. Defibrotide was used in three patients. Median time on CRRT was 10.5 days. Sixty-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, end-stage renal diseases and underwent kidney transplantation 34-months post-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, evidence-based fluid balance protocol and early initiation of CRRT for HCT-related AKI/SOS was associated with good outcomes.
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