Prospective evaluation of the diagnostic value of sensitive KIT D816V mutation analysis of blood in adults with suspected systemic mastocytosis

Abstract

This prospective study demonstrates that a D816V-positive result in a screening blood sample identifies SM among patients with hymenoptera venom-induced anaphylaxis in whom the diagnosis would most probably have been missed, with potential severe implications. The observed false-negative screening results also underline that BM investigation is mandatory in all adult patients with clear signs of, or highly suspected SM, regardless of the KIT mutation status.

Detection of KIT D816V in peripheral blood of children with manifestations of cutaneous mastocytosis suggests systemic disease

“…These patients also had relatively low serum tryptase levels (all <20 ng/ml) at the time when the PB ASqPCR assay was negative. We have reported a similar observation in adult patients with idiopathic anaphylaxis with isolated bone marrow mastocytosis (Carter et al, 2015(Carter et al, , 2018, which is supported by other reports (Erben et al, 2014;Kristensen et al, 2014Kristensen et al, , 2017Carter et al, 2018). This is consistent with the low frequency of cells bearing the mutated allele in patients with minimal disease or improving clinical status.…”

“…A recent prospective study in adult patients reports the PB ASqPCR assay as a reliable predictor of systemic mastocytosis without false positive results. This study also reports a negative PB KIT D816V mutational analysis in patients with positive bone marrow results in patients with a low mast cell burden (Kristensen et al, 2017). We found comparable results in our paediatric population, as shown in four patients with documented systemic mastocytosis and a low bone marrow mast cell burden and who only met minor WHO criteria for the diagnosis.…”

“…The PB ASqPCR for KIT D816V is available commercially for use as a screening test for the consideration of systemic disease (Erben et al , ; Kristensen et al , ). Therapeutic management is symptom‐based and only in unusual cases would children require cytoreductive therapy that would be guided by the KIT mutational status.…”

Clinical validation of a new commercial highly sensitive KIT D816V mutation analysis in mastocytosis

“…This includes analysis of blood with highly sensitive techniques when clinical symptoms may indicate underlying mastocytosis. This approach is supported by a reported high sensitivity and specificity and is now included in diagnostic algorithms for suspected mastocytosis . Presently, mutation analysis of blood is primarily based on laboratory developed tests (LDTs) due to the lack of sufficiently sensitive commercially available in vitro diagnostic tests.…”

“…The MastOUH‐assay is a KIT D816V mutation‐specific qPCR assay previously described in detail, including refined criteria for positivity . These and additional studies describe the validation of the MastOUH‐assay, including analysis of multiple KIT D816V mutation‐negative control samples, and the MastOUH‐assay is therefore validated from a technical perspective. This includes a specificity of 100% and a high clinical sensitivity …”