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\begin{document}

\title{Aprepitant for Severe Refractory Pruritus in a Patient with Relapsed
Hodgkin's Lymphoma}



\author[1]{Anwar Al Nassan}%
\author[1]{Faiha Bazzeh}%
\author[1]{Iyad Sultan}%
\affil[1]{King Hussein Cancer Center}%


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  \date{May 29, 2024}


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\textbf{Aprepitant for Severe Refractory Pruritus in a Patient with
Relapsed Hodgkin's Lymphoma}

\textbf{Authors' Full Names and Affiliations:}

Anwar Al Nassan \textsuperscript{1*}, Faiha Bazzeh\textsuperscript{1,2},
Iyad Sultan \textsuperscript{1,2,3}

\textsuperscript{1} Department of Pediatrics, King Hussein Cancer
Center, Amman, Jordan

\textsuperscript{2} Department of Pediatrics, Jordan University
Hospital, Amman, Jordan\textsuperscript{3} Artificial Intelligence and
Data Innovation Office, King Hussein Cancer Center, Amman, Jordan

\textsuperscript{*} Correspondence to:

Anwar Al Nassan, MD, Department of Pediatrics, King Hussein Cancer
Center, Amman, Jordan 11194; Tel 00962-6-5300460 Email: anassan@khcc.jo

Additional Information:

\begin{itemize}
\tightlist
\item
  Text word count: {[}505{]}
\item
  Short running title: Aprepitant in Refractory Pruritus
\item
  Keywords: Hodgkin's Disease, Lymphoma, Pediatric hematology/oncology,
  Quality of Life, Aprepitant, Refractory Pruritus
\item
  No figures or tables
\item
  No conflict of Interest
\end{itemize}

\textbf{Article Type Modification:}

Manuscript type: Letter to the Editor (Previously: Editorial)

\textbf{Aprepitant for Severe Refractory Pruritus in a Patient with
Relapsed Hodgkin's Lymphoma}

Anwar Al Nassan \textsuperscript{1*}, Faiha Bazzeh\textsuperscript{1,2},
Iyad Sultan \textsuperscript{1,2,3}

We present the case of a 27-year-old male pediatric patient with
relapsed Hodgkin's lymphoma (HL) who experienced severe, refractory
pruritus as a paraneoplastic effect. Despite multiple lines of therapy,
conventional treatments failed to alleviate his symptoms. A trial of
aprepitant, an NK1 receptor antagonist traditionally used for nausea and
vomiting control, initiated, resulting in a rapid and significant
improvement in pruritus, quality of life, and overall well-being.

According to our knowledge, this is the second case of Hodgkin Lymphoma
responded to aprepitant as treatment of refractory pruritus.

A 27-year old man diagnosed with multiple relapsed Hodgkin lymphoma,
which failed multiple lines of therapy. He presented with severe
generalized pruritus, which worsened over time and interfered with his
sleep and function. It improved slightly with cold showers but failed
all conventional therapies, including antihistamines, steroids, lotions,
and gabapentin.

Ten months after his last relapse, we initiated a trial of aprepitant at
a dose of 80 mg once daily for three days, resulting in an immediate
response with a significant improvement in his symptoms, sleep quality,
reduced itching, and an overall enhancement in his mood and quality of
life.

Of significance, the patient diagnosed earlier with HL at the age of 15
years, treated with chemotherapy, inducing a remission; followed by
multiple relapses, treated with high dose chemotherapy and Auto bone
marrow transplant, allogenic bone marrow transplantation, and courses of
chemotherapy and checkpoint inhibitors. He had complained of itching at
time of presentation and with subsequent relapses, successfully treated
with disease control.

Paraneoplastic pruritus has a reported prevalence of 30\% in patients
with HL.{[}1{]} There is a scarcity of studies evaluating the efficacy
of pharmacological interventions for HL associated pruritus, reflecting
a pressing need for innovative treatment approaches. Conventional
therapeutic modalities for chronic pruritus include corticosteroids,
antihistamines, and systemic therapies like gabapentin, UV light
therapy, and immunomodulatory treatments .{[}2--4{]} However, a subset
of patients remains unresponsive to these conventional therapies,
necessitating the exploration of alternative treatment avenues.
Aprepitant, conventionally known for its efficacy in preventing
chemotherapy-induced and postoperative nausea and vomiting, emerges as a
promising alternative. Remarkably, the patient had significant reduction
in pruritus following the initiation aprepitant therapy, with rapid
improvement of his quality of life.

Aprepitant operates by antagonizing the Neurokinin-1 (NK1) receptor, a
G-protein coupled receptor, thereby blocking the actions of its primary
ligand, Substance P, a nociceptive neurotransmitter. Substance P is
significantly involved in mediating various physiological processes such
as pain, depression, nausea, vomiting, and notably, pruritus
(itching). The NK1 receptors are distributed in both the central and
peripheral nervous systems, which is where Substance P generally exerts
its effects.{[}5{]}

Previous anecdotal data reveals the effectiveness of aprepitant in
providing relief to patients unresponsive to other treatments including
patients with S\selectlanguage{ngerman}ézary syndrome, mycosis fungoides, T-cell lymphoblastic
lymphoma and other malignancies.{[}4{]} In the presented case, the
employment of aprepitant, off-label, mirrored these findings, showcasing
a noteworthy improvement in the pruritus, which was solely attributable
to the aprepitant therapy. This is the second report of such a use in a
patient with HL. {[}1{]}

Our case highlights the potential of aprepitant as a novel and effective
treatment option for paraneoplastic pruritus in pediatric patients with
relapsed Hodgkin's lymphoma, particularly when conventional therapies
fail to provide relief. We believe that further investigation and
larger-scale studies warranted to explore the full scope of aprepitant's
utility in managing pruritus in this population.

References

1. Villafranca JJA, Siles MG, Casanova M, Goitia BT, Domínguez AR.
Paraneoplastic pruritus presenting with Hodgkin's lymphoma: a case
report. J Med Case Rep , 2014 8: 300.

2. Huh JW, Jeong Y-I, Choi K-H, Park H-J, Jue M-S. Treatment for
Refractory Pruritus Using Oral Aprepitant. Ann Dermatol , 2016 28:
124--125.

3. Williams KA, Kwatra SG. Emerging Research in Chronic Pruritus: From
Bedside to Bench and Back Again. Medicines (Basel) , 2020 7: 24.

4. Yosipovitch G. Chronic pruritus: a paraneoplastic sign. Dermatol Ther
, 2010 23: 590--596.

5. He A, Alhariri JM, Sweren RJ, Kwatra MM, Kwatra SG. Aprepitant for
the treatment of chronic refractory pruritus {[}Internet{]}. BioMed
research international , 2017 2017. {[}cited 2023 Oct 5{]} Available
from: https://www.hindawi.com/journals/bmri/2017/4790810/

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