Laboratory Assessment of Patients with Systemic Mastocytosis

系统性肥大细胞增多症患者的实验室评估

• 批准号: 10019275
• 负责人: Irina Maric
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10019275
• 关键词: Adult; Algorithms; Benign; Biological Assay; Biopsy; Bone Marrow; Bone marrow biopsy; Cells; Child; Clinical; Collaborations; Cutaneous; Cutaneous Mastocytosis; Data; Detection; Development; Diagnosis; Diffuse Cutaneous Mastocytosis; Disease; Disease Management; Dose; Evaluation; Freezing; Histopathology; Laboratories; Marrow; Morphology; Mutation; Mutation Analysis; Myeloproliferative disease; National Institute of Allergy and Infectious Disease; Patients; Pharmaceutical Preparations; Polymerase Chain Reaction; Procedures; Prospective Studies; Proto-Oncogene Protein c-kit; Proto-Oncogenes; Receptor Protein-Tyrosine Kinases; Recording of previous events; Reporting; Resolution; Restriction fragment length polymorphism; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; Sampling; Serum; Skin; Skin Mastocytoma; Somatic Mutation; Specificity; Systemic Mastocytosis; Systemic disease; Testing; Time; Tissues; Tryptase; Variant; Visceromegaly; body system; burden of illness; follow-up; infancy; mast cell; mastocytosis; mutational status; pediatric patients; peripheral blood; prospective; skin disorder; skin lesion

Mastocytosis may present with varied clinical manifestations depending on the mast cell burden and the extent of tissue involvement. Children are primarily represented on the benign end of the disease spectrum, with disease limited to skin and diagnosed with one of three cutaneous variants; maculopapular cutaneous mastocytosis (MPCM), diffuse cutaneous mastocytosis (DCM) or mastocytoma (MTOMA). Systemic mastocytosis is typically seen in adults with somatic mutations in KIT. However, children may also have systemic disease, with similar mutations in KIT and as early as infancy.The use of allelespecific quantitative polymerase chain reaction to identify KIT D816V in the peripheral blood of adults with mastocytosis has been reported to have value in the diagnosis, assessment of disease burden and management of this disease. To examine the value of this assay in children with cutaneous manifestations of mastocytosis, we assessed data on 65 patients with all variants of paediatriconset mastocytosis, including those known to have systemic disease, to correlate KIT mutation status with clinical findings, serum tryptase levels and bone marrow histopathology. The PB ASqPCR for the KIT D816V mutation was consistently negative in patients with cutaneous disease only (MCPM, DCM and MTOMA, n = 37) and without a history of organomegaly documented to be associated with systemic disease in paediatric patients. Of the 23 patients diagnosed with systemic disease (ISM), the PB ASqPCR was positive in 16/23 samples (0047384%). PB ASqPCR was negative in two ISM patients with organomegaly that had KIT D816Yassociated systemic disease (serum tryptase values 184 and 244 ng/ml), one patient with a bone marrow diagnosis of ISM and no KIT mutations detected in the marrow samples, as well as four patients diagnosed with ISM by bone marrow biopsy. These latter four patients had a low mast cell disease burden in bone marrow biopsies (mast cells 5% of total marrow cells); but positive KIT D816V mutation by RTPCR/RFLP in their marrow samples. As PB ASqPCR for the KIT D816V mutation was not performed at the time of the original bone marrow biopsy procedure in these four patients, we obtained their frozen PB samples collected at the time of the bone marrow biopsy procedure and analyzed them using ASqPCR for the KIT D816V mutation. The results were negative in all four samples. In addition, there has been a significant improvement in their clinical status, as evidenced by a major or complete resolution of skin lesions, a significant decrease in serum tryptase (average 339 to 110 ng/ml) and a decrease in medication usage to as needed medications from daily dosing over a period of 713 years. The specificity of PB ASqPCR KIT D816V assay was 100% for all variants of cutaneous disease. The sensitivity for the detection of the systemic disease when documented with a marrow biopsy, was 696%. We performed followup PB ASqPCR testing in most patients (615%). Data was found to yield consistent results when followed up to 36 months. Patients with a positive value remained positive and these results continued to correlate with serum tryptase values. In addition, the patients with negative values remained negative. These findings were the basis of the development of an algorithm to assist in the decision for when to perform a bone marrow biopsy in children presenting with cutaneous manifestations of mastocytosis.

肥大细胞增多症的临床表现随肥大细胞负荷和组织受累程度的不同而不同。儿童主要处于疾病谱系的良性一端，疾病仅限于皮肤，并被诊断为三种皮肤变异之一；斑疹样皮肤肥大细胞增多症（MPCM），弥漫性皮肤肥大细胞增多症（DCM）或肥大细胞瘤（MTOMA）。全身性肥大细胞增多症通常见于KIT体细胞突变的成人。然而，儿童也可能有全身性疾病，在KIT中有类似的突变，并且早在婴儿期就有。据报道，使用等位基因特异性定量聚合酶链反应鉴定肥大细胞增多症成人外周血中的KIT D816V在该病的诊断、疾病负担评估和管理中具有价值。为了检验该检测在有皮肤肥大细胞增多症表现的儿童中的价值，我们评估了65名患有所有儿童发病肥大细胞增多症变体的患者的数据，包括那些已知患有全身性疾病的患者，将KIT突变状态与临床表现、血清胰蛋白酶水平和骨髓组织病理学相关联。