CT Scan Enumeration of Altered Spleen Status and Pulmonary Artery Size in Patients with Autoimmune Lymphoproliferative Syndrome (ALPS).

ALPS is a disorder of apoptosis resulting in elevated DNT (CD3⁺, TCRab⁺, CD4^-, CD8^-, B220⁺ double negative T lymphocyte) cells associated with childhood onset nonmalignant lymphadenopathy, splenomegaly and multilineage cytopenias due to splenic sequestration and autoimmune destruction. Patients with ALPS frequently have altered spleen status: splenomegaly or splenectomy, the latter often-related to refractory chronic AIHA and ITP. This altered spleen status has been associated with pulmonary arterial hypertension (PAH) in two patients with ALPS. Though traditionally diagnosed as elevated tricuspid regurgitant jet velocity > 2.6 m/sec, PAH can also be predicted using PA diameter, most commonly measured as the Main PA (MPA) diameter. Similar to Sickle Cell Disease patients who are evaluated for presence of PAH due to functional asplenia here we attempted to further elucidate the relationship between dilated pulmonary arteries (PA) and spleen status in ALPS patients.

CT scans of 162 patients with ALPS were studied; their age range at the time of the study was 1-63yrs, median age 16yrs. The CT scans were obtained as part of the routine monitoring of their LPD. Patients' most recent complete chest, abdomen and pelvis CT scans were evaluated. In 97 patients spleen sizes in two scans done 1-12 years apart were also measured. Each scan was evaluated using Kodak Carestream PACS Version 10.1.sp1 software. Point of maximal distension was visually identified in the Main, Left, and Right PA. Artery diameters were measured perpendicular to the vessel wall. Measurement of spleen length consisted of summing the distance between the axial slice in which the spleen first appears to the slice where it appears last. Digital Image Processing (IP) measurements are also underway to compute spleen and liver volumes in these patients.

Splenomegaly was defined as a CT estimated spleen length of > 9.76 cm. PA diameter was considered above the upper limits of normal if adults if MPA measured > 28.6 mm LPA > 22.1 mm; RPA> 19.8 mm. For children age specific sizes were adapted from published reports.

In our cohort of 162 ALPS patients, 51% had splenomegaly, 42% had undergone splenectomy due to hypersplenism prior to CT scan evaluations and 7% had normal size spleens. 26% of them demonstrated dilated MPA. However, contingency table analysis yielded a P value = 0.436 (P < 0.05) evaluating an association between splenic abnormalities and dilated MPA. ANOVA analysis of an association between MPA diameter and broad patient classifications of normal spleen, splenectomy, and splenomegaly yielded P = .02 (α < 0.05) and non-significant Tukey HSD statistical tests, the odds ratio = 0.93 for an association between spleen length and MPA diameter. Correlation R² = 0 between age, spleen length and MPA diameter, though this was only evaluated in 42 patients 17 years and older. Serial measurements of enlarged spleens in the 97 children and adults with at least 2 CT scans done at a median time of 4 yrs apart (range 1-12yrs) showed no further significant increase in spleen size with age. For most patients, their ALPS associated lymphoproliferative burden appears to be worse during early childhood and as they grow older it may become self-limited and stable. Further work is in progress to correlate changes in PA diameter with changes in spleen length, spleen volumes and age. There was no statistical correlation between MPA diameter and altered spleen status, though a quarter of these patients demonstrated dilated pulmonary arteries. Active surveillance for PAH by periodic echocardiograms is underway in these patients.

No relevant conflicts of interest to declare.