MAIN TEXT
To the editor: Hepatosplenic T Cell Lymphoma (HSTCL) is a rare
malignancy that occurs most often in young adult males, and is
associated with immunosuppressive medications1–3.
Less than 10% of patients with HSTCL survive five years after
diagnosis4, and there is no consensus for treatment,
particularly for pediatric patients2.
A 14 year old female with Turner Syndrome and Crohn’s disease previously
treated with mercaptopurine for seven years presented following two
weeks of facial and truncal rash (Figure 1), fatigue, night sweats, and
hepatosplenomegaly. Mercaptopurine was discontinued 19 months prior to
presentation. Laboratory evaluation revealed blast-like cells, white
blood cell count 17500/mm3, hemoglobin 10.7 g/dL,
platelet count 119000/ mm3, and lactate dehydrogenase
5,885 u/L. Bone marrow aspirate contained 31% malignant
cells—positive for CD3, CD7, and CD56, and negative for alpha/beta T
cell receptor—with isochromosome 7q and 8q gain. Computed tomography
(CT) and positron emission tomography/computed tomography (PET/CT)
confirmed hepatosplenomegaly and hypermetabolic splenic lesions (Figure
2). The diagnostic workup was consistent with HSTCL.
She received induction therapy with ifosfamide, carboplatin, and
etoposide (ICE)5. After one cycle, rash resolved and
splenomegaly markedly improved. She achieved a complete response with
negative PET/CT scan and 0.009% minimal residual disease (MRD) after
four cycles. She underwent allogeneic hematopoietic stem cell transplant
(HSCT) from a matched unrelated donor following conditioning with total
body irradiation, thiotepa, and cyclophosphamide. Bone marrow aspirate
obtained 30 days after HSCT had rare suspicious cells, but MRD was
<0.001%. One year after HSCT, bone marrow evaluation was MRD
negative and PET/CT was negative for disease.
Patients with exposure to thiopurines and other immunomodulators have
increased risk of HSTCL1–3,6,7. However, this is the
first reported case of HSTCL in a patient with Turner Syndrome. While
patients with Turner Syndrome have increased risk of solid tumors,
increased hematologic malignancy is not reported in this
group8,9. A systematic review of patients with HSTCL
following immunosuppressive therapy for inflammatory bowel disease found
that this cohort of patients were >90%
male6, an interesting finding considering this female
patient had only one X chromosome. Also notable is the development of
malignancy after more than a year from discontinuation of
immunomodulators, indicating that risk may be sustained over months to
years after exposure.
Outcomes among HSTCL case series are dismal7,10,11,
and treatment regimens vary widely. National Comprehensive Cancer
Network (NCCN) guidelines revised January 2020 suggest ICE followed by
allogeneic HSCT1. Ifosfamide, cytarabine, etoposide
(IVAC) has been used with some success4; while
cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and
prednisone (CHOP) has been largely accepted as
inadequate1,10. While NCCN guidelines recommend
allogeneic HSCT, American Society of Blood and Marrow Transplantation
recommends autologous HSCT for older adults and those who have achieved
complete response prior to transplant12.
In summary, we successfully treated a 14 year old with Turner syndrome
and HSTCL with ICE and allogeneic HSCT. She remains in remission 16
months from diagnosis and 12 months following HSCT. Some patients with
this challenging disease can achieve sustained remission with aggressive
induction chemotherapy followed by consolidation with allogeneic HSCT.
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