LETTER TO THE EDITOR ITK Deficiency: How Can EBV Be Treated Before Lymphoma? To the Editor: IL-2 inducible T-cell kinase (ITK) deficiency has been identified as an autosomal recessive form of lymphoprolifer- ative disease.[1] Until now, four different mutations have been identified in the ITK gene including missense (c.C1085T);[1] nonsense (c.C1764G;[2] c.C49T (as in our patients);[3]) and frameshift (c.468delT[4,5]) mutations. Here, we present two affected siblings with a homozygous nonsense mutation in the ITK gene. Patient 1, a 6-year-old female from non-consanguineous family, was admitted with pneumonia. Her clinical history revealed frequent upper respiratory infections. She had two sisters of whom one died from lymphoma. Her physical examination revealed multiple, hard, painless lymph nodes in the cervical and occipital regions, and extensive rales in both lungs. Low serum immunoglobulin levels (IgG: 446 mg/dl, IgA: 21 mg/dl, IgM: 24 mg/dl, IgE: 5 KU/L) and anti-A/anti-B antibody titers were found. The result of biopsy of a cervical lymph node was interpreted as EBV-induced non-Hodgkin lymphoma and she had a high EBV- DNA level in blood (14,800 copies/ml). She was treated with CHOP plus rituximab. While she was still in remission, at 18 months follow-up, she had positive peripheral blood EBV DNA again (12,500 copies/ml). She was hospitalized because of brain metastasis and died with disseminated CMV infection. Patient 2, who was the younger brother of the first patient, was admitted to the hospital at 2.5 years of age due to an acute EBV infection while his sister was in hospital. He received intra- venous acyclovir treatment for 14 days, and EBV viremia (42,000 copies/ml) responded initially. His lymphadenopathy and hep- atosplenomegaly improved but EBV persisted in blood for months. In addition to intravenous acyclovir treatment, oral acyclovir and oral valacyclovir treatments were also tried for clearing the infection. His laboratory results were all normal (Table I). While searching matched unrelated donor from banks, EBV (þ) Hodgkin lymphoma developed and chemotherapy was started. He was one of the three reported ITK deficiency patients[3,4] who have been diagnosed before lymphoma development. Nevertheless, we could not prevent the development of lymphoma. A recent review reported nine patients with ITK deficiency. While five of them had Hodgkin lymphoma, our first patient had non-Hodgkin lymphoma which has only rarely been reported in ITK deficiency.[6] The second patient received acyclovir and TABLE I. Summary of Laboratory Findings of Patients Laboratory parameters Patient 1 Patient 2 IgG 446 mg/dl (745–1,804) 793 mg/dl (604–2,010) IgA 21 mg/dl (57–282) 101 mg/dl (26–296) IgM 24 mg/dl (78–261) 68 mg/dl (71–235) IgE 5 KU/L 3.2 KU/L EBV VCA IgM Negative Negative EBV VCA IgG Positive Positive EBV EA Negative Negative EBV EBNA IgG Negative Negative EBV EBNA IgM Negative Negative CD3þ 16 56 (%) 63 (51–79) 58 (55–79) CD3 16þ 56þ (%) 15 (5–23) 22 (5–28) CD4þ (%) 29 (31–54) 19 (28–51) CD8þ (%) 47 (10–31) 27 (16–42) CD19þ (%) 23 (17–41) 18 (11–29) CD20þ (%) 21 (17–40) 16 (11–31) HLADRþ CD20þ (%) 23 (15–48) 24 (18–38) CD19þ IgM CD27þ IgD (%) (Switched memory B cells) 0.5 (6.5–29.2) 6 (6.5–29.2) CD19þ IgMþ CD27þ IgDþ (%) (Marginal zone B cells) 0.9 (7.2–30.8) 3.7 (7.2–30.8) CD19þ IgMþ CD27 IgDþ (%) (Naive B cells) 95 70 CD19þ CD38 low CD21 low (%) (Activated B cells) 3.2 (1.1–6.9) 6.2 (1.1–6.9) CD19þ CD38 hi IgM hi (%) (Transitional B cells) 11.1 (0.6–3.5) 8.0 (0.6–3.5) Conflict of interest: Nothing to declare.  Correspondence to: Funda Erol Cipe, Department of Pediatric Allergy-Immunology, Kanuni Sultan Suleyman Research and Training Hospital, Istanbul, Turkey. E-mail: ferol76tr@hotmail.com Received 1 June 2015; Accepted 4 June 2015  C 2015 Wiley Periodicals, Inc. DOI 10.1002/pbc.25648 (wileyonlinelibrary.com). Published online 14 July 2015 in Wiley Online Library Pediatr Blood Cancer 2015;62:2247–2248