Meta-Analysis of Clinicopathological and Biological Characteristics of Myeloid Sarcoma

Introduction

Myeloid sarcoma (MS), is a rare neoplastic condition which can occur without bone marrow involvement as isolated MS, concurrently with bone marrow involvement as acute myeloid leukemia (AML) or other myeloid malignancies, or as a secondary type which occurs as a result of therapy or relapse after achieving AML remission. Apart from the unique presentation, different reviews have reported both favorable and unfavorable outcomes in patients with MS when compared with AML. Literature involving systematic studies of MS patients are limited, with sample sizes of studies over the last two decades rarely exceeding 100 patients. The aim of this study was to perform a meta-analysis of the largest cohort of MS and describe clinical and pathological parameters in order to comprehensively characterize MS.

Methods

A PubMed literature search involving all available research articles pertaining to MS across all age groups from 1999-2023 was conducted using keywords and MeSH search terms. Results from the literature search were independently reviewed by two authors, and references of each study were also reviewed for any relevant additions. The primary meta-analytic approach for descriptive data was a random effects model to calculate the effect size in terms of proportion with 95% confidence interval (CI) (Neyeloff et al., 2012). Median age and survival data were analyzed using a meta-analysis of medians approach with a random effects model to calculate pooled estimates using R software (McGrath et al., 2023). I² statistic and Q-statistic were used to assess for heterogeneity. PROSPERO systematic review registration pending under ID# 450876.

Results

A total of 5178 patients with MS from 57 studies were included. After dividing studies by age group, the median age of adult patients was 52 ys. (95% CI: 49-56) and 5 ys. (95% CI: 3-6) for the pediatric population. The proportion of males was 56.7% (95% CI: 54.5-59), with an I² statistic of 0% suggesting homogeneity in reported gender data. Diagnosis of myeloid sarcoma with concurrent AML had a higher proportion of cases than isolated disease (64 vs. 38.6%). Presence of leukemia cutis was 28.8% (95% CI: 24.2-33.3). There was a higher proportion of patients with abnormal karyotype, including those with complex and intermediate/poor risk, compared to normal karyotype (43.6 vs. 29%). Pooled weighted median white blood cell count was 16.7 x10³/mL (95% CI: 10.9-22.5), with hemoglobin of 11.6 g/dL (95% CI: 10.0-13.1) and platelet count of 140 x10⁹/L (95% CI: 68.9-212). Pooled immunohistochemistry (IHC) data revealed highest proportions with markers MPO, CD117, and CD68 (61.5, 44.7, and 38.1%, respectively), and least with CD56 (18.6%). Proportions of gene mutations of FLT3, TP53, and NPM1, including both bone marrow and extramedullary samples, were 14.8% (95%CI: 9.6-19.9), 6% (95%CI: 2.6-9.4), and 15% (95%CI: 10-20), respectively.

Median survival data was screened for complete data parameters including median survival of entire cohort and reported 95% CI. Outcomes data was pooled from 4 studies representing 301 patients, wherein 3 examined adult populations and 1 was mixed. Weighted median overall survival was 14 months (95% CI: 10.6-18.4). A large proportion of patients received intensive chemotherapy (82%), whereas 38.2% of patients received hematopoietic stem cell transplant. The proportion of those who received radiotherapy was 21.8%, and 10.4% of patients received only supportive measures.

Conclusions

Our large cohort meta-analysis of myeloid sarcoma patients further highlights the clinical and biologic characteristics of this rare presentation. The results of our study suggests a predilection for males, and further studies are needed to validate this finding. Further analysis including the effect on bone marrow transplant on MS outcomes will be presented at the ASH 2023 meeting.