Cytogenetic and Molecular Characterization of Sweet's Syndrome in Patients with Acute Myeloid Leukemia.

Abstract

AbstractAbstract 2587▪▪This icon denotes a clinically relevant abstract Background:Sweet's syndrome (SS), also known as acute febrile dermatosis, has been associated with hematologic malignancies including acute myeloid leukemia (AML). We sought to identify the disease characteristics of AML patients (pts) who develop SS, and to report the cytogenetic (CG) and molecular genetic (MG) abnormalities observed. Methods:We conducted a retrospective review of charts of newly diagnosed AML pts that underwent induction chemotherapy and had follow up at our institution. Pts with SS were identified if both the clinical signs and symptoms and a biopsy of the skin lesion were consistent with SS. CG and MG abnormalities are reported here as part of our descriptive analysis. Results:Between years 2000 to 2011, we identified a total of 2178 newly diagnosed AML pts that underwent induction chemotherapy and had follow-up at our institution. During this time, 697 pts (32%) underwent skin biopsies in the course of their AML treatment and follow-up. 21 pts (1% of all pts and 3% of all who underwent skin biopsy) demonstrated signs and symptoms and had skin biopsy consistent with SS. Table 1 summarizes the baseline characteristics of pts with AML at the time of dx of SS, including the CG and MG abnormalities observed. Myelodysplastic syndrome (MDS) prior to diagnosis of AML and SS was present in 9 pts (43%). CG analysis revealed diploid karyotype in 7 pts (33%), deletion 5p in 8 pts (38%; 4 pts had del5p as sole abnormality, and 4 pts with del5p as part of other accompanying/complex CG) and 4 patients had complex CG (19%). Most common MG abnormality was seen in the FLT3 gene, found in 7 out of 18 pts (39%) tested (FLT3 –ITD present in 4 pts while mutation of FLT3 codon 835 occurred in 3 pts). In addition, two out of 7 (28%) pts tested, had NPM1 gene mutation (one pt had concomitant FLT3 gene mutation). Other CG and MG abnormalities are summarized in Table 1. Eight pts (38%) with SS received systemic steroids for treatment, 1 pt (5%) received topical steroids while 19 (90%) received antibiotics and supportive care. The treatment for SS was effective in 16 out of 16 pts (100%) for whom follow-up information was available. Three pts required multiple courses of steroids while 5 pts required one course of steroids. The median time to improvement reported in the signs and symptoms of SS was 14 days (range 4–153). The median overall survival of AML pts who developed SS during course of their management was 14 months (95% confidence interval 12.6 – 15.4 months). Conclusions:SS is a frequent occurrence among AML pts as compared to its incidence in the general population. It can occur in AML pts during all phases of the disease. In this retrospective review, we found that SS frequently occurs in AML that has developed in the setting of prior MDS and where leukemic cells carry CG and MG abnormalities of del5p and FLT3 gene respectively.Table 1:SS in AML ptsNPercentage/RangeTotal AML pts2178Total pts undergoing skin biopsies during treatment of AML69732Pts diagnosed with SS211% of all pts 3% of all pts biopsiedAgeAt dx of AML5527-87At dx of SS5627-83GenderFemale1466Laboratory values at dx of AMLMedian AML Blast %4314-92Median absolute neutrophil count (ANC; 109/L)1.60.1-45Median hemoglobin (Hb; g/dl)97.3-11Median platelets (109/L)528-156SS dx before allogeneic HSCT5/683Status of AML at time of SS dxSS dx before AML dx15SS dx at the time of AML dx733SS dx during primary induction therapy629SS dx during treatment for relapsed AML733Symptoms at presentation of SSFever with skin rash1466Tenderness in the skin rash10/2148History of filgrastim (G-CSF) use210Location of skin rashHead and Neck943Upper extremity1048Trunk and back838Lower extremity1048Laboratory values at dx of SSMedian AML Blast%250-92Neutrophilia (ANC ≥6 × 109/L)15Neutropenia (ANC ≤1.5× 109/L)1466Anemia (Hb <10g/dl)1990Thrombocytopenia (≤100 × 109/L)21100Kidney Dysfunction (GFR<60 ml/min)210CG analysisDel5p (as sole abnormality, n=4, as part of complex CG, n=4)838––Diploid733Complex CG (≥ 3 chromosomal abnormalities)419Del7p210t(6;9)210Trisomy 815t(11;17)15t(15;17)15t(3;3)15MG analysisFLT3 (total tested =18)––Internal Tandem Duplication422D835317NPM1 (total tested=7)228RAS (total tested=13)00C-Kit (total tested=5)00CEBPA (total tested=3)00 Disclosures:No relevant conflicts of interest to declare.