Refractory Non-Hodgkin Lymphoma in Beta-thalassemia Trait Egyptian Female Patient: A Case Report

Introduction:
β-Thalassemia is an inherited genetic disorder characterized by an imbalance in the α/β globin chain ratio. Transfusion-dependent thalassemia and non-transfusion-dependent thalassemia (NTDT) patients appeared to have a 1.47-fold higher risk of developing a malignancy, especially hematological. This case study is to determine the clinical course of NHL in β-thalassemia.
Methods:
An observational prospective study (October 2012- December 2013) at Oncology Center Mansoura University (OCMU), Hematology unit. A 29-year-old β-thalassemia-trait, NTDT female, underwent splenectomy at the age of 20 years. Ferritin level 2000mg/L. Hemoglobin (Hb) levels always 8-9.6 g/dL. She was maintained on folic acid (5 mg/d). Hb electrophoresis: 6.7%, 89% and 3.9%. She presented with constitutional symptoms, generalized lymphadenopathy and abdominal pain. : microcytic hypochromic anemia, total leucocytic count ( : 17k/uL) with normoblastemia, absolute neutrophilic count ( : 10.8 k/uL). Target cells in peripheral blood smear. LDH level was 1250 mg/dL. CT scan revealed marked hepatomegaly, abdominal (porta hepatis lymph node; 5cm) and malignant looking peripheral lymphadenopathies.
Results:
Cervical lymph node biopsy revealed predominantly large atypical B cell (CD20 ); . Bone marrow biopsy for staging revealed grade IV myelofibrosis. She received 4 cycles and (40 mg/kg/d, 5d/week, IVI for iron chelation); she required PRBCs transfusion/21–35 days (Hb =7.8–10). No response was documented post chemotherapy, 2 courses of salvage were received, then CT scan revealed: right paraspinal soft tissue mass (3.8cm) at the level of Dorsal (D3-4) vertebrae with intraspinal extension and osteolytic/sclerotic lesions scattered in vertebrae and sacrum (largest 3x2.5cm); at this stage we were facing an extramedullary hematopoiesis (EMH) . lymphoma progression for differential diagnosis. BM examination and LN re-biopsy confirmed atypical CD20 lymphomatus infiltration. She received 3 line chemotherapy (3 courses) and 10 sessions of involved field radiotherapy ( ) on the STM, she developed severe anemia, acute kidney injury, convulsions and disturbed conscious level, she was admitted to the intensive care unit (ICU), and was planned for CSF analysis after neurological assessment and radiology of the brain, but unfortunately her condition progressed rapidly to multiorgan failure and died.
Discussion:
The occurrence of hematological malignancies as lymphoma in thalassemia patients could be a pure coincidence or a combination of genetic and environmental factors. Immunomodulation or transmission of oncogenic viruses such as EBV, CMV and HTLV-1 due to multiple transfusions could be considered as a probable predisposing factor in development of lymphoma in thalassemic patients. The effects of iron overload and treatment with iron chelators could be another hypothesis for development of malignancies in these patients.