Hepatic sinusoidal obstruction syndrome during maintenance therapy of childhood acute lymphoblastic leukemia is associated with continuous asparaginase therapy and mercaptopurine metabolites

Toksvang, Linea Natalie; Pietri, Silvia; Nielsen, Stine Nygaard; Nersting, Jacob; Albertsen, Birgitte Klug; Wehner, Peder Skov; Rosthøj, Steen; Lähteenmäki, Päivi; Nilsson, Daniel; Nystad, Tove A.; Grell, Kathrine; Frandsen, Thomas Leth; Schmiegelow, Kjeld

doi:10.1002/pbc.26519

Cited by 24 publications

(21 citation statements)

References 39 publications

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“…In particular, specific warning is recommended when allo-HCT is planned shortly after inotuzumab ozogamicin salvage treatment for relapsed ALL. Similar risks are reported in clinical practice after pegylated asparaginase recent treatment with documented severe liver toxicity [17]. We also raise the question of the impact of immune checkpoint inhibitors (anti-CTLA4, anti-PD1, and anti-PDL1 monoclonal antibodies) on the risk of SOS/VOD.…”

Section: Risk Factorssupporting

confidence: 75%

Prophylactic, preemptive, and curative treatment for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a position statement from an international expert group

Mohty

Malard

Abecasis

et al. 2019

Bone Marrow Transplant

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Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life-threatening complication that can develop after hematopoietic cell transplantation (HCT). While SOS/VOD may resolve within a few weeks in the majority of patients with mild-to-moderate disease, the most severe forms result in multiorgan dysfunction and are associated with a high mortality rate (>80%). Therefore, careful surveillance may allow early detection of SOS/VOD, particularly as the licensed available drug is proven to be effective and reduce mortality. The aim of this work is to propose an international consensus guideline for the treatment and prevention of SOS/VOD in adult patients, on behalf of an international expert group.

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Section: Risk Factorssupporting

confidence: 75%

Prophylactic, preemptive, and curative treatment for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a position statement from an international expert group

Mohty

Malard

Abecasis

et al. 2019

Bone Marrow Transplant

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“…Only one patient who developed SOS after reinduction treatment was exposed to 6‐TG chemotherapy, whereas all three patients were treated with VCR, high‐dose prednisone, PEG‐ l ‐ASP and doxorubicin. This is in line with the recently reported acute toxicity profile of PEG‐ l ‐ASP when combined with VCR and steroids…”

Section: Discussionsupporting

confidence: 91%

“…SOS is an emerging complication in patients with ALL, described initially in patients undergoing maintenance treatment with long‐term oral 6‐TG and more recently in patients receiving an intensified maintenance treatment, based on 6‐MP, biweekly PEG‐ l ‐ASP, alternating pulses with VCR/dexametasone, and high‐dose MTX …”

Section: Discussionmentioning

confidence: 99%

“…SOS has been reported after chemotherapy in different pediatric tumors such as Wilms tumor, rhabdomyosarcoma, and medulloblastoma . In acute lymphoblastic leukemia (ALL), SOS has been associated with maintenance treatment using 6‐thioguanine (6‐TG) or with pegylated‐ l ‐asparaginase (PEG‐ l ‐ASP) and 6‐mercaptopurine (6‐MP), whereas it has rarely been seen during induction–reinduction treatment …”

Section: Introductionmentioning

confidence: 99%

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Venoocclusive disease due to chemotherapy for pediatric acute lymphoblastic leukemia is associated with increased levels of plasminogen‐activator inhibitor‐1

Mauro

Saggiorato

Sartori

et al. 2018

Pediatric Blood & Cancer

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We describe three cases of sinusoidal obstruction syndrome/venoocclusive disease (SOS) in pediatric patients with acute lymphoblastic leukemia (ALL). All three episodes occurred during or just after the induction or reinduction phase of treatment based on prednisone/dexamethasone, vincristine, daunorubicin, and pegylated-l-asparaginase. SOS episodes were categorized as mild/moderate and resolved in 7, 10, and 16 days using supportive measures or defibrotide therapy. In all three episodes, the clinical diagnosis of SOS was associated with a significant increase in plasminogen-activator inhibitor-1 (PAI-1) that reduced with patient clinical improvement. PAI-1 warrants study as a diagnostic marker for SOS in ALL.

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“…VOD is a well‐established liver complication of hematopoietic stem cell transplantation (HSCT) characterized by hepatomegaly, weight increase, and hyperbilirubinemia, and has an average incidence of 20% in pediatric patients . VOD has been also described after conventional chemotherapy in patients with acute lymphoblastic leukemia, rhabdomyosarcoma, medulloblastoma and, more frequently, WT . The incidence of VOD in children treated for WT ranges from 1.2% to 8% .…”

Section: Introductionmentioning

confidence: 99%

PAI‐1 and protein C as early markers of veno‐occlusive disease in patients treated for Wilms tumor

Cesaro

Mauro

Sattin

et al. 2019

Pediatric Blood & Cancer

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Background Hepatic veno‐occlusive (VOD) disease has been described in hematopoietic stem cell transplantation (HSCT), solid tumors, and acute lymphoblastic leukemia. The incidence of VOD in Wilms tumor (WT) ranges from 1.2% to 8%. The diagnosis of VOD is clinical, and there are no validated laboratory biomarkers. Procedure We prospectively evaluated the specificity and sensitivity of plasminogen‐activator inhibitor‐1 (PAI‐1) and protein C as diagnostic markers of VOD in WT patients. Fifty patients treated from 2008 to 2016 for WT were eligible. VOD was diagnosed according to modified Seattle criteria and retrospectively reclassified according to the recently published criteria for VOD in pediatric HSCT patients. Results VOD occurred in 6 of 50 patients (12%) after 20 to 97 days from starting chemotherapy. The average duration of VOD was 10 days (range, 4–13 days). PAI‐1 levels were elevated in all VOD patients, while a decrease in protein C levels was observed in 33% of patients with VOD. PAI‐1 antigen (Ag) values ≥ 26.4 ng/mL demonstrated high sensitivity and specificity for the clinical diagnosis of VOD with sensitivity 100%, specificity 93%; whereas protein C levels below 34.5% had sensitivity 67%, specificity 100%. Both PAI‐1 and protein C had an high negative predictive value: PAI‐1 Ag 100%; protein C 95%. Conclusions PAI‐1 Ag and protein C have good sensitivity and specificity for the diagnosis of VOD in WT patients. Their high negative predictive value can be used in the differential diagnosis of liver toxicity, especially in VOD episodes with absent or delayed hyperbilirubinemia.

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Hepatic sinusoidal obstruction syndrome during maintenance therapy of childhood acute lymphoblastic leukemia is associated with continuous asparaginase therapy and mercaptopurine metabolites

Abstract: PEG-asparaginase increases cytotoxic 6MP metabolite levels and risk of SOS, potentially interacting with other chemotherapy pulses.

Cited by 24 publications

References 39 publications

Prophylactic, preemptive, and curative treatment for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a position statement from an international expert group

Prophylactic, preemptive, and curative treatment for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a position statement from an international expert group

Venoocclusive disease due to chemotherapy for pediatric acute lymphoblastic leukemia is associated with increased levels of plasminogen‐activator inhibitor‐1

PAI‐1 and protein C as early markers of veno‐occlusive disease in patients treated for Wilms tumor

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