# First case of classical Hodgkin-like EBV-positive lymphoproliferative disorder under ruxolitinib therapy

Pierre-luc Mouchel, Charlotte Syrykh, Camille Laurent, Suzanne Tavitian, Martin Gauthier

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Pierre-luc Mouchel, Charlotte Syrykh, Camille Laurent, Suzanne Tavitian, Martin Gauthier. First case of classical Hodgkin-like EBV-positive lymphoproliferative disorder under ruxolitinib therapy. American Journal of Hematology, 2020, 96 (6), pp.755 - 756. 10.1002/ajh.26026 . inserm-04791622

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Submitted on 19 Nov 2024

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# First case of classical Hodgkin-like EBV-positive lymphoproliferative disorder under ruxolitinib therapy

Pierre-Luc Mouchel MD, MSc<fnref n="1" />,<fnref n="2" /> ID

Charlotte Syrykh MD, MSc<fnref n="3" /> |

Camille Laurent MD, PhD<fnref n="2" />,<fnref n="3" />

Suzanne Tavitian MD, MSc<fnref n="1" /> |

Martin Gauthier MD, MSc<fnref n="1" />,<fnref n="2" /> ID

### Correspondence

Martin Gauthier, MD, MSc, Department of Hematology, centre hospitalier universitaire de Toulouse, IUCT-O, 1 avenue Irène Joliot-Curie, 31059 Toulouse Cedex, France.

Email: martin.gauthier@hotmail.fr

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**IMAGE 1** Histological and immunohistochemical findings of the patient's bone marrow (top left) and lymph node (top right, below left, below center left, below center right and below right). Hypercellular marrow containing loose clusters of large staghorn megakaryocytes (top left, H&E stain x50 and x400). Lymph node biopsy shows an effaced architecture with polymorphous inflammatory infiltrate containing large atypical cells morphologically consistent with Hodgkin and Reed-Sternberg (HRS) cells. Immunohistochemical studies show that the HRS cells are positive for CD30 (strong) (below left, x200), PAX 5 (weak) (below center left, x200), CD20 (focal and weak) (below center right, x200) and highlighted by EBV-encoded small RNA (EBER) in situ hybridization (below right, x200)

<footnote n="1">¹Department of Hematology, centre hospitalier universitaire de Toulouse, Toulouse, France</footnote>

<footnote n="2">²Université Paul Sabatier Toulouse III, Toulouse, France</footnote>

<footnote n="3">³Department of pathology, Cancer University Institute of Toulouse, Toulouse, France</footnote>
A 56-year-old man under ruxolitinib therapy (Janus kinase (JAK) inhibitor) over a 14-month period for a myelofibrosis secondary to essential thrombocythemia (ET) with CALR mutation, was investigated for persistent night fever, sweat and progressive splenomegaly.

Blood tests showed pancytopenia, increased inflammatory markers, high serum LDH level and elevated Epstein-Barr virus (EBV) DNA load (6.7 log IU/mL). Positron emission tomography (PET) imaging revealed multiple hypermetabolic lymphadenopathies and a high metabolic activity of the spleen, the liver, bones and bone marrow. Bone marrow biopsy and marrow smear examination were in accordance with the previously diagnosed ET with secondary myelofibrosis (top left Image) with no other finding, in particular there was no hemophagocytic lymphohistiocytosis. A lymph node excision revealed scattered large atypical cells with Hodgkin/Reed-Sternberg appearance in a mixed inflammatory background (top right Image). The large atypical cells were diffusely positive for CD30 (below left Image), weakly positive for PAX5 (below center left Image), focally and weakly positive for CD20 (below center right Image), CD79a positive, CD15 negative and highlighted by EBV-encoded small RNA (EBER) in situ hybridization (below right Image). Given the context of drug-induced immune suppression, a diagnosis of classical Hodgkin lymphoma (CHL)-like EBV-associated lymphoproliferative disorder was made.

The patient was subsequently treated by a combination of rituximab (for EBV replication) and polychemotherapy active against Hodgkin lymphoma (PVAG, prednisone, vinblastine, doxorubicin, gemcitabine)¹ associated with a tapering of ruxolitinib,² leading to a good clinical response and a rapid viral load drop (undetectable EBV after two infusions of rituximab). After four courses of PVAG, PET-scanner revealed a partial metabolic response, with only one remaining bone hypermetabolism (Deauville score: four, decrease in uptake value in the remaining bone spot: 53%), allowing the continuation of PVAG protocol, still ongoing.

Susceptibility to opportunistic infections in patients under ruxolitinib therapy has already been documented, with many reports of mycobacterial and viral infections.³⁻⁵ Recent data also warn of a possible increased risk of developing aggressive lymphomas with JAK inhibitors, with a delay of several months between the initiation of JAK inhibitor and the diagnosis of lymphoma,⁶ which is consistent with our case and assumes a role of ruxolitinib-induced immune suppression in the pathogenesis of these lymphomas. Reactive lymphocytosis secondary to EBV reactivation in a patient under ruxolitinib has been described elsewhere,⁷ and one of the aggressive lymphomas described in patients under ruxolitinib was positive for EBV⁶, but no CHL-like EBV-associated lymphoproliferative disorder has been described in patients under ruxolitinib. As our patient carried vascular comorbidities and was initially altered, he was considered ineligible for a treatment with ABVD,⁸ and was subsequently treated with the PVAG protocol, which has been designed for elderly patients.

Herein we report the first case of CHL-like EBV-associated lymphoproliferative disorder in a patient under ruxolitinib, which

corroborates the apparent susceptibility to lymphoproliferative disorders under JAK inhibitors.

## CONFLICT OF INTEREST

The authors declare no conflict of interest.

## AUTHOR CONTRIBUTIONS

P.L.M., S.T. and M.G. managed the patient and designed treatment schedule; C.S. and C.L. performed the pathology and immunochemistry analyses; P.L.M., C.S. and M.G. wrote the manuscript. All authors approved the manuscript.

## DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.

## ORCID

Pierre-Luc Mouchel https://orcid.org/0000-0001-7832-9146

Martin Gauthier https://orcid.org/0000-0001-5338-2071

## REFERENCES

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2. Tefferi A, Barbui T. Polycythemia vera and essential thrombocythemia: 2021 update on diagnosis, risk-stratification and management. *Am J Hematol*. 2020;95(12):1599-1613.

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6. Porpaczy E, Tripolt S, Hoelbl-Kovacic A, et al. Aggressive B-cell lymphomas in patients with myelofibrosis receiving JAK1/2 inhibitor therapy. *Blood*. 2018;132(7):694-706.

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**How to cite this article:** Mouchel P-L, Syrykh C, Laurent C, Tavitian S, Gauthier M. First case of classical Hodgkin-like EBV-positive lymphoproliferative disorder under ruxolitinib therapy. *Am J Hematol*. 2021;96:755-756. https://doi.org/10.1002/ajh.26026