Ruxolitinib Withdrawal Syndrome Leading to Tumor Lysis

Dai, Tong; Friedman, Ellen; Barta, Stefan K.

doi:10.1200/jco.2012.47.6473

Cited by 27 publications

(21 citation statements)

References 11 publications

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“…17 The events observed in that study included acute circulatory compromise, respiratory failure, and severe tumor lysis syndrome; and were similar to isolated events reported in non-HCT setting. 31,33–35 It is postulated that these symptoms are probably due to deranged cytokine milieu secondary to withdrawal of JAK-STAT inhibition. 31 Some investigators have referred these symptoms as return of MF-related symptoms in their description.…”

Section: Discussionmentioning

confidence: 99%

“…As the definition of “rebound symptoms”, “withdrawal symptom” or return of MF-related symptoms remain highly observer dependent, 17,31–33 we reported all the potential new symptoms that occurred during pre-transplant discontinuation of JAK1/2 inhibitors, and their relationship with timing of drug discontinuation was explored. Symptoms were graded as following using clinical judgment:…”

Section: Methodsmentioning

confidence: 99%

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Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients with Myelofibrosis with Prior Exposure to Janus Kinase 1/2 Inhibitors

Shanavas

Popat

Michaelis

et al. 2016

Biology of Blood and Marrow Transplantation

133

117

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The impact of JAK1/2 inhibitor therapy prior to allogeneic hematopoietic cell transplantation (HCT) has not been studied in a large cohort in myelofibrosis (MF). In this retrospective multicenter study, we analyzed outcomes of patients who underwent HCT for MF with prior exposure to JAK1/2 inhibitors. One hundred consecutive patients from participating centers were analyzed, and based on clinical status and response to JAK1/2 inhibitors at the time of HCT, patients were stratified into five groups: (a) clinical improvement (n=23), (b) stable disease (n=31), (c) new cytopenia/increasing blasts/intolerance (n=15), (d) progressive disease: splenomegaly (n=18), and (e) progressive disease: leukemic transformation (LT) (n=13). Overall survival (OS) at two years was 61% (95%CI, 49–71). This was 91% (95% CI, 69–98) for those who experienced clinical improvement, and 32% (95% CI, 8–59) for those who developed LT on JAK1/2 inhibitors. In multivariable analysis, response to JAK1/2 inhibitors (p=0.03), DIPSS score (p=0.003), and donor type (p=0.006) were independent predictors of survival. Among the 66 patients who remained on JAK1/2 inhibitors until stopped for HCT, two patients developed serious adverse events necessitating delaying of HCT, and another 8 patients had symptoms with lesser severity. Adverse events were more common in patients who started tapering or abruptly stopped their regular dose ≥6 days prior to conditioning therapy. We conclude that prior exposure to JAK1/2 inhibitors did not adversely affect post-transplant outcomes. Our data suggest that JAK1/2 inhibitors should be continued near to the start of conditioning therapy. The favorable outcomes of patients who experienced clinical improvement with JAK1/2 inhibitor therapy prior to HCT were particularly encouraging, and need further prospective validation.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients with Myelofibrosis with Prior Exposure to Janus Kinase 1/2 Inhibitors

Shanavas

Popat

Michaelis

et al. 2016

Biology of Blood and Marrow Transplantation

133

117

View full text Add to dashboard Cite

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“…In the COMFORT-I trial one patient experienced fever, acute respiratory failure, and splenic haemorrhage with infarction [7]. Other literature reports describe tumour lysis-like syndrome [50], ARDS [51], and recurring respiratory failure that resolved each time ruxolitinib was re-initiated [52]. RDS can be diagnosed only after exclusion of other possible causes and no clinical, laboratory or pathology finding can be called pathognomonic.…”

Section: How To Withdraw Ruxolitinib? Principles Of Ending Therapymentioning

confidence: 99%

Ruxolitinib in the treatment of patients with myelofibrosis — questions and answers

et al. 2019

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“…Disease symptoms and splenomegaly typically start to reappear within a week of stopping ruxolitinib, and most patients' symptom burden rapidly returns to baseline if ruxolitinib is stopped . This is not to be confused with an acute withdrawal syndrome (systemic inflammatory response syndrome) that has been reported in a small number of patients . Several of these cases involved stopping ruxolitinib because of an intercurrent illness, such as sepsis, that may have been a contributing factor.…”

Section: Safetymentioning

confidence: 99%

“…8 This is not to be confused with an acute withdrawal syndrome (systemic inflammatory response syndrome) that has been reported in a small number of patients. 29,30 Several of these cases involved stopping ruxolitinib because of an intercurrent illness, such as sepsis, that may have been a contributing factor. In such cases a tapered reduction of the ruxolitinib dose over 7 to 10 days, and/or concomitant steroid treatment (e.g.…”

Section: How Long To Treat For and How To Stop Treatmentmentioning

confidence: 99%

Practical management of myelofibrosis with ruxolitinib

Marlton

Tam

et al. 2015

Internal Medicine Journal

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Treatment for the majority of patients with myelofibrosis is primarily based on symptom control as curative allogeneic stem cell transplantation is typically offered only to younger patients, especially those with poor prognosis disease. Around 50% of patients with myelofibrosis have the JAK2 V617F mutation, but almost all patients have aberrant activation of the JAK-STAT signalling pathway. Recent efforts have focussed on the clinical use of JAK2 inhibitors to treat myelofibrosis. In this article, we present our recommendations for the practical management of myelofibrosis with ruxolitinib, a selective inhibitor of both JAK1 and JAK2. Ruxolitinib can significantly improve the quality of life of patients with myelofibrosis.There is also increasing evidence of a positive impact on survival. Consistent with the physiological role of JAK signalling the major toxicity of ruxolitinib is cytopenia. Managing cytopenia is key to maximising the therapeutic benefit of ruxolitinib. Further research into the safety of ruxolitinib in patients with thrombocytopenia is warranted, as is its role in special subgroups of patients, such as those undergoing stem cell transplantation and those experiencing thrombosis as a major manifestation of myelofibrosis.

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Ruxolitinib Withdrawal Syndrome Leading to Tumor Lysis

Cited by 27 publications

References 11 publications

Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients with Myelofibrosis with Prior Exposure to Janus Kinase 1/2 Inhibitors

Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients with Myelofibrosis with Prior Exposure to Janus Kinase 1/2 Inhibitors

Ruxolitinib in the treatment of patients with myelofibrosis — questions and answers

Practical management of myelofibrosis with ruxolitinib

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