EXPERIMENTAL AND CLINICAL TRANSPLANTATION

A 57-year-old woman with relapsed Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia developed diffuse nonblanching erythematous skin lesions following allogeneic hematopoietic stem cell transplant. The lesions appeared concomitantly with hepatic sinusoidal obstruction syndrome and persisted despite engraftment and supportive therapy. Skin biopsy excluded graft-versus-host disease. Upon initiation of defibrotide for moderate hepatic sinusoidal obstruction syndrome, both hepatic and cutaneous findings resolved completely. This case underscores the systemic endothelial-protective potential of defibrotide, extending beyond the hepatic microvasculature, and highlights cutaneous endotheliopathy as a possible manifestation of transplant-associated endothelial injury.

Key words : Allogeneic hematopoietic stem cell transplantation, Leukemia, Sinusoidal obstruction syndrome

Endothelial injury has been increasingly recognized as a unifying mechanism linking multiple posttransplant complications, including sinusoidal obstruction syndrome, transplant-associated thrombotic microangiopathy, idiopathic pneumonia syndrome, and atypical inflammatory skin eruptions.^1-4
Defibrotide, a polydisperse mixture of single-stranded polydeoxyribonucleotides, exerts profibrinolytic, antithrombotic, and anti-inflammatory properties while stabilizing endothelial cells.^5-7 Although defibrotide has been approved for sinusoidal obstruction syndrome, accumulating data have indicated broader endothelial-protective effects in systemic and localized vascular injury syndromes.^8,9
We present a case of cutaneous vasculitis-like lesions following allogeneic hematopoietic stem cell transplant that responded exclusively to defibrotide, suggesting endothelial recovery as the central mechanism. Written informed consent was obtained from the patient for publication of this case and the accompanying images.

A 57-year-old woman with Philadelphia-negative B-cell acute lymphoblastic leukemia achieved morphological remission after multiple chemotherapy regimens, including rituximab-modified hyper-CVAD regimen (ie, cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine), blinatumomab, and inotuzumab ozogamicin. She underwent allogeneic peripheral blood hematopoietic stem cell transplant from a 10/10 human leukocyte antigen-matched related female donor in August 2025.
The conditioning regimen included fludarabine 30 mg/m²/d from day -7 to day -3, total body irradiation, with 12 Gy total delivered as 3 fractions (day -3 to day -1), and anti-T lymphocyte globulin 2.5 mg/kg/d from day -6 to day -4. Graft-versus-host disease prevention included posttransplant cyclophosphamide 25 mg/kg on day +3 and day +4, followed by cyclosporine A 1.5 mg/kg twice daily, started on day +5.
Neutrophils engrafted on day +13, and platelets engrafted on day +18. During the early period after engraftment, the patient developed engraftment syndrome, which resolved with supportive management. Moderate hepatic sinusoidal obstruction syndrome was diagnosed on day +31, characterized by hepatomegaly, ascites, and a bilirubin level of 2.4 mg/dL.
Simultaneously, diffuse erythematous, nonblanching, vasculitis-like lesions appeared symmetrically on both lower extremities (Figure 1). Platelet counts were above 30 × 10⁹ cells/L, and coagulation parameters were within reference limits.
A skin biopsy showed superficial and middermal perivascular inflammation, endothelial cell swelling, and erythrocyte extravasation. No fibrinoid necrosis or epidermal apoptosis was observed, thereby excluding cutaneous graft-versus-host disease.
A systematic differential diagnostic evaluation was performed. Initially, radiation dermatitis resulting from total body irradiation was excluded, because (1) the lesion distribution was not confined to radiation fields, (2) the timing was inconsistent with radiation-induced injury, and (3) the clinical morphology was atypical. Drug reaction was also considered unlikely due to the absence of recently initiated high-risk medications. Moreover, the lack of morbilliform rashes and systemic hypersensitivity reactions (such as eosinophilia) eliminated the possibility of drug reaction.
Polymerase chain reaction testing for cytomegalovirus, which was used to rule out viral infection, showed negative results. Engraftment syndrome was not consistent with the new onset of lesions because the rashes were not accompanied by fever, and there were no pulmonary infiltrates or capillary leaks. Taken together, the findings supported a transplant-associated endothelial dysfunction process. Defibrotide was initiated at a dose of 6.25 mg/kg, 4 times daily. Within 7 days, the cutaneous lesions markedly improved, and, by day +37, lesions had completely resolved (Figure 2). Both bilirubin levels and liver function tests concurrently returned to reference ranges. Defibrotide was administered for 21 days with no bleeding or renal problems.
At discharge on day +52, the patient experienced complete hematological and measurable disease-negative remission, with 99% donor chimerism. The patient was followed for 6 months after discharge, and no recurrence of cutaneous lesions was observed during this period. Hepatic sinusoidal obstruction syndrome did not recur, and no additional endothelial complications, including transplant-associated thrombotic microangiopathy, were detected. Furthermore, no clinical evidence of acute or chronic graft-versus-host disease was detected. At the most recent follow-up, the patient remained with complete hematological and measurable residual disease-negative remission.

This case highlights a rare presentation of cutaneous endothelial injury following allogeneic hematopoietic stem cell transplant that was responsive to defibrotide. The temporal association between hepatic sinusoidal obstruction syndrome and cutaneous vasculitic lesions suggested a systemic endothelial activation and microvascular dysfunction process rather than isolated organ pathology.
Defibrotide is known to protect endothelial cells by restoration of prostacyclin/thromboxane balance, enhancement of nitric oxide availability, reduction of leukocyte adhesion, and suppression of proinflammatory cytokines.^5,6 Richardson and colleagues have shown that defibrotide reduces the activation and death of endothelial cells caused by plasma from patients with sinusoidal obstruction syndrome.² In preclinical models of lung injury, defibrotide has been shown to reduce endothelial inflammation and the expression of adhesion molecules.⁶
Clinically, defibrotide has shown efficacy beyond sinusoidal obstruction syndrome, including transplant-associated thrombotic microangiopathy, idiopathic pneumonia syndrome, and chimeric antigen receptor T-cell-related endothelial syndromes, all of which support the role of defibrotide as a broad endothelial stabilizer.^7-9
In our patient, the cutaneous lesions did not improve despite adequate platelet recovery and antimicrobial therapy but resolved rapidly after defibrotide initiation. This temporal and mechanistic relationship supports endothelial injury as the unifying pathophysiology.
Recent reviews have proposed that the capacity of defibrotide to reverse complement-mediated and cytokine-driven endothelial stress may extend its use to nonhepatic microvascular injury syndromes.⁹
In conclusion, cutaneous vasculitis-like lesions following allogeneic hematopoietic stem cell transplant may reflect localized manifestations of systemic endothelial dysfunction rather than classic graft-versus-host disease. Defibrotide, through its multimodal endothelial-protective mechanisms, can induce complete recovery when standard therapies fail. Early recognition of endothelial injury patterns and timely defibrotide initiation may improve outcomes in this underrecognized spectrum of posttransplant complications.

Volume: 24 Issue: 4 April 2026

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