Variant-specific BCR::ABL1 quantification discrepancy in chronic myeloid leukemia.

INTRODUCTION: Accurate quantification of the BCR::ABL1 fusion gene in whole blood is pivotal for the clinical management of chronic myeloid leukemia (CML) patients. The fusion protein encoded by BCR::ABL1 can vary in size, depending on the BCR and/or ABL1 gene breakpoint. The vast majority of CML patients have a p210 BCR::ABL1 fusion gene (M-BCR), which can be attributed to the presence of either e14a2 (b3a2) or e13a2 (b2a2) mRNA transcript junctions. METHODS: Twenty-five CML samples were analyzed in two different ISO15189-accredited centers that both use an Europe Against Cancer-based quantitative polymerase chain reaction (qPCR) protocol. Reanalysis of the sample set with transcript-specific standard curves and digital droplet PCR (ddPCR) were performed. RESULTS: qPCR quantification revealed a significant (up to 1 log) difference specifically for the e13a2 transcript variant in contrast to e14a2 transcripts (Hodges-Lehman 4.29; p < 0.001). Reanalysis of the sample set with transcript-specific standard curves abolishes the initial transcript-specific difference (Hodges-Lehman 0.003; p = 0.8192). Comparison of transcript-specific qPCR results of both centers with ddPCR, an absolute quantification method, showed a statically significant association, especially in the lower range, indicating the clinical utility of transcript-specific or absolute quantification methods. CONCLUSION: Our data show that differences between transcript-specific quantification might exist between centers, leading to potential clinical impact on the follow-up of CML patients. The use of transcript-specific standard curves for qPCR quantification, or absolute quantification, can significantly reduce these differences. Specific attention should be applied to the interpretation of quantification differences of CML patients that switch between diagnostic centers.

Meningitis in a patient with neutropenia due to Rothia mucilaginosa: a case report.

BACKGROUND: Rothia mucilaginosa is a Gram-positive bacterium occurring as a commensal in the oral cavity and upper respiratory tract. Although rarely pathogenic in an immunocompetent host, it can cause severe opportunistic infections in immunocompromised individuals. CASE PRESENTATION: A 67-year-old white woman had a routine blood analysis before undergoing knee surgery. The results showed leukopenia for which bone marrow examination was performed, showing an underlying acute myeloid leukemia. During the neutropenic phase after a second induction with cytarabine/idarubicin, she developed fever, headaches, and photophobia. Cultures of cerebrospinal fluid were positive for Rothia mucilaginosa. Despite full therapy with antibiotics, neurosurgical interventions, and intensive care support, our patient died due to refractory intracranial hypertension and transtentorial herniation. CONCLUSIONS: Meningitis due to Rothia mucilaginosa is a rare but potentially lethal infection in patients with neutropenia, and evidence-based guidelines for the treatment of this disease are lacking. We suggest an empirical therapy with amoxicillin/rifampicin until adjustments can be made based on an antibiogram. Intrathecal or intraventricular administration of antibiotics can be considered if neurosurgical access is already obtained because of disease-associated complications.