Ruxolitinib in myelofibrosis: to be or not to be an immune disruptor

Figures & data

Figure 1 Ruxolitinib and immune system.

Table 1 Bacterial infections associated with ruxolitinib in myelofibrosis

Clinical features	Laboratory features	Diagnosis and management	Outcomes	Reference
Male of 73 years Diagnosis of MF: 2009 6 weeks of RU treatment	Microbiological analysis of the debrided tissue positive Blood cultures Escherichia coli positive	Fever and necrotizing fascitis of the scrotum Drug discontinuation and ABT plus surgical approach	Improvement	^Citation35
Male of 78 years Diagnosis of MF: May 2015 8 months of RU treatment	Microbiological analysis of Klebsiella pneumoniae of liver abscess drainage	Fever and abdominal pain Drug discontinuation and ABT plus surgical approach	Improvement	^Citation36
Male of 82 years Diagnosis of PMF: 2005 Treatments reported: hydroxyurea, danazol, prednisolone 2 months of RU treatment	Culture of sputum positive	Pulmonary TBC reactivation Drug discontinuation and ABT	Improvement	^Citation37
Male of 69 years Diagnosis of PMF: May 2015 3 weeks of RU treatment	Histological analysis of cervical lump Quantiferon gold positive	Pulmonary TBC reactivation Drug discontinuation and ABT Ruxolitinib retreatment after ABT	Improvement of infection and MF	^Citation38
Male of 78 years Diagnosis of MF in RU treatment	Histological and microbiological analysis of lump	Disseminated TBC (lungs and lump) Drug discontinuation and ABT	Improvement	^Citation39
Male of 62 years Diagnosis of PMF: 1996 7–9 weeks of RU treatment	Microbiological analysis, PCR and culture of BAL Blood culture positive	Disseminated TBC (lungs and lump) Drug discontinuation and ABT Ruxolitinib retreatment after ABT	Improvement of infection and MF	^Citation40
Male Diagnosis of PMF: 1990	Histological and microbiological analysis of lump Culture of sputum positive Quantiferon gold positive	Disseminated TBC Drug discontinuation and ABT	Improvement	^Citation41
Female of 65 years Diagnosis of post-PV MF 4 months of RU treatment	Histological and culture analysis of lump	Extrapulmonary TBC Drug discontinuation and ABT Drug retreatment associated with secondary TBC prophylaxis	Improvement of infection and MF	^Citation42
Female of 78 years Diagnosis of PMF: 2011 Treatment reported: splenic irradiation 21 months of RU treatment	Histological analysis, PCR and culture of lump Quantiferon positive	Disseminated tuberculosis, spondylodiscitis Drug was continued and ABT	Improvement	^Citation43

Abbreviations: ABT, antibiotic therapy; BAL, bronchoalveolar lavage; MF, myelofibrosis; PCR, polymerase chain reaction; RU, ruxolitinib; PMF, primary myelofibrosis; TBC, tuberculosis.

Table 2 Viral infections associated with ruxolitinib in myelofibrosis

Clinical features	Laboratory features	Diagnosis and management	Outcomes	Reference
Male of 67 years Diagnosis of PMF: 2009 1 months of RU treatment	PCR of aqueuos humor positive	Bilateral CMV retinitis Drug discontinuation and AVT intravenously and intravitreally	Improvement	^Citation44
Female of 57 years Diagnosis of PV: 1990, MF: 2015 Treatments: splenectomy, hydroxyurea, anagrelide, prednisone, tacrolimus due to focal segmental glomeruloscerosis, interferon alfa 9 weeks of RU treatment	PCR of CSF positive No biopsy	EBV lymphoproliferative disorder of central nervous system plausible Drug discontinuation, Rituximab and temozolomide	Death 5 weeks after diagnosis	^Citation45
Male of 77 years Diagnosis of MF 6 months of RU treatment	PCR from gastric ulcer	EBV-related gastric ulcer Drug discontinuation AVT	Improvement	^Citation46
Male of 67 years Diagnosis of PMF 2014 4 days of RU treatment	Punch biopsy of cheek Cultures of lip positive for HSV-1	Dissemination HSV infection Drug discontinuation and AVT	Permanent vision loss	^Citation47
Male of 75 years Diagnosis of MF: 2013 10 weeks of RU treatment	Brain biopsy	PML Drug discontinuation	Worsening of neurologic signs	^Citation48
Female of 49 years Diagnosis of ET and MF: 2008 Treatments: hydroxyurea 4 weeks of RU treatment, carrier of HBV	Increased HBV-DNA titers	Reactivation of HBV Drug discontinuation and AVT	Improvement	^Citation49
Female of 72 years Diagnosis of ET and MF: 2014 8 months of RU treatment, carrier of HBV	Increased transaminases and HBV-DNA titers	Reactivation of HBV Drug discontinuation AVT	Transaminases and HBV-DNA titers improved	^Citation50

Abbreviations: ABT, antibiotic therapy; AVT, antiviral therapy; EBV, Epstein-Barr; CSF, cerebrospinal fluid; CMV, cytomegalovirus; ET, essential thombocythemia; HBV, hepatitis B Virus; HSV, herpes simplex virus; MF, myelofibrosis; PCR, polimerase chain reaction; PMF, primary myelofibrosis; PML, progressive multifocal leukoencephalopathy; PV, polycythemia vera; RU, ruxolitinib.

Table 3 Fungal and protozoan infections associated with ruxolitinib in myelofibrosis

Clinical features	Laboratory features	Diagnosis and management	Outcomes	Reference
Male of 65 years Diagnosis: PV and MF	PCR of acqueous fluid	Bilateral toxoplasmosis retinitis Drug discontinuation and ABT	Stable vision and retinal scar	^Citation56
Male of 66 years Diagnosis of PV and MF: 2001 Previous treatments: prednisone 18 months of RU treatment	Culture of BAL positive	Pneumonary criptoccosis Drug discontinuation AF and subsequently drug reintroduction	Improvement of infection and MF	^Citation57
Female of 69 years Diagnosis MF: 2011 More than 3 years of RU treatment	CSF with India link positive Culture of CSF positive	Criptococcal meningoencephalitis AF	Improvement	^Citation58
Male of 69 years Diagnosis MF: 2009 More than 3 years of RU treatment	Transbronchial biopsy PCR of BAL positive	Pneumocistis jiroveci pneumonitis Drug discontinuation and ABT	Improvement	^Citation59

Abbreviations: ABT, antibacterial therapy; AF, antifungal; BAL, bronchoalveolar lavage; CSF, cerebrospinal fluid; MF, myelofibrosis; PCR, polymerase chain reaction; PV, polycythemia vera; RU, ruxolitinb.

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