Neutropenia in Sirolimus Treated Patients of Lymphatic Malformation: A Case Series

Abstract

Background: Lymphatic malformations (LMs) are rare benign tumors that are at risk of various complications due to their progressive nature and critical locations. Considering the morbidity and mortality of such lesions, different therapeutic methods proposed are surgical excision, sclerotherapy, laser, aspiration, radiotherapy, and most recently sirolimus. Case Reports: We reviewed 3 cases with lymphatic malformation at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. Initially placed on various treatment sessions of surgical intervention, sclerotherapy or even both prior to sirolimus, minimal improvement was noted. Sirolimus initiation was associated with significant clinical improvement. However, sirolimus was associated with neutropenia, which was successfully managed by G-CSF. Conclusion: Sirolimus can cause bone marrow suppression due to cumulative effect.

Treatment of Lymphatic Malformations with the mTOR Inhibitor Sirolimus: A Systematic Review

“…15,18,19,22,25,28 The target blood level of sirolimus was similar (£15 ng/mL), but slightly differed between the studies. The target blood level was 10-15 ng/mL in seven studies, 8,12,18,22,23,26,27 5-15 ng/mL in four studies, 21,24,29,30 10-13 ng/mL in one study, 16 and 4-8 ng/mL in one study. 20 In seven studies, the authors did not mention the target blood level of sirolimus.…”

“…Through these methods, 20 articles were identified, containing a total of 71 cases in which sirolimus was used to treat lymphatic malformations, venolymphatic malformations, and capillary-lymphatico-venous malformations. 8,[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] After identifying these articles, all text and figures were carefully assessed for relevant data. The following information on study characteristics and clinical treatments was extracted from all included studies: publication metrics (name of first author and year of publication), subject information (age, gender, and localization of malformation), and treatment information (sirolimus dose, planned target trough level, treatment duration, treatment outcomes, additional therapies, and adverse events).…”

“…8,[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] Most studies were retrospective case series or case reports, and there was only one phase II trial. In all, 16 publications about 45 patients with lymphatic malformations were identified (Table 1), 8,[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] five publications about eight patients with venolymphatic malformations (Table 2), 12,21,[27][28][29] and four publications about 18 patients with capillary-lymphatico-venous malformations (Table 3). 8,12,29,30 All patients had extensive malformations, which were distributed about the w...…”

“…In most studies, sirolimus was administered orally at an initial dosage of 0.8 mg/m 2 per dose, twice daily at 12-hour intervals. 8,[12][13][14]16,20,23,24,26,29 The dose was then subsequently adjusted to reach the planned target blood level. In three studies a different dose was used; sirolimus was initially administered orally at a dosage of 0.1 mg/kg per 24 hours twice daily, 30 0.05 mg/kg twice daily, 21 or 0.07 mg/kg twice daily.…”

“…In 15 studies, data on the duration of treatment were presented. [14][15][16][17][19][20][21][22][23][24]26,27,29,30 In 16 patients sirolimus was not withdrawn at last follow-up, which ranged from six weeks to 53 months.…”