A 46-year-old male with past medical history of hypertension presented with two-month history of cervical adenopathy. His family members had no history of genetic diseases and similar diseases. Physical examination revealed bilateral multiple enlarged lymph nodes in his neck and axillae. The largest lymph node was located in the left side of the neck (3.0 cm * 3.0 cm), which was firm, fixed, and non-tender.
On admission, his complete blood count and metabolic panel were normal. Positron emission tomography (PET) showed the presence of fluorodeoxyglucose avid uptake in multiple parts, including the posterior peritoneum, pelvis, groin, bilateral submaxillary, cervical, and axillary lymph nodes, along with a similar uptake in the 6th anterior rib on the right and the left iliac bone, which was considered as likely lymphoma infiltration. In addition, there was no mediastinal mass or involvement of the central nervous system (CNS) in this patient at diagnosis. The biopsy of the left cervical lymph node (biopsy was completed in other hospital before admission) showed diffuse infiltration with TdT-positive lymphoblasts expressing CD3, BCL2, MYC, and Ki-67. Myeloperoxidase (MPO) and CD20 were negative. Bone marrow (BM) aspiration and flow cytometry analysis revealed a 15.5 and 22% infiltration of immature T-lineage lymphoblastic cells, respectively. Immunophenotype showed a T-lineage phenotype (CD7, CD34, cCD3, CD5), which was similar to that of the lymph node tissue (Figure 1). TCR beta (TRB), TRD, TCR gamma (TRG), immunoglobulin heavy (IgH), light chains kappa (IgK), and lambda (IgL) rearrangement were negative. Cytogenetic analysis was implemented with R-banding showed a noncomplex karyotype: 46XY, (9:22) (q34;q11) [1]/46, XY, [19] (Figure 2), and fluorescence in situ hybridization (FISH) confirmed the presence of a translocation of 9q34 (ABL1) to 22q11 (BCR) in 18% of the nuclei (300 nuclei were analyzed) (Figure 3). Multiplex polymerase chain reaction (PCR) showed the e1a2 BCR-ABL1 fusion transcript. Next-generation sequencing (NGS) revealed DNA methyltransferase 3 alpha (DNMT3A c.2645G>C p.Arg882Pro, mutation rate is 2.3%) and mediator complex subunit 12 (MED12 c.4278G>A p.Trp1426, mutation rate is 4.3%) gene mutation. Diagnosis of T-cell lymphoblastic lymphoma was made based on his clinical presentation, histological and immunological evaluation of lymph node specimens and bone marrow. He was in stage IV according to the Ann Arbor system.
The patient received initial induction with hyper CVAD regimen: hyper-fractionated cyclophosphamide (CTX) given 300 mg/m2 intravenously over 2 h every 12 h for 6 doses on days 1 to 3 with 600 mg/m2 Mesna per day intravenously via continuous infusion on days 1 to 3 beginning 1 h prior to CTX and completed by 12 h after the last dose of CTX; 2.5 mg/m2 vincristine intravenously on days 4 and 11; 50 mg/m2 doxorubicin intravenously over 24 h via central venous catheter on day 4; and 40 mg dexamethasone daily intravenously on days 1 to 4 and days 11 to 14. In addition, dasatinib 100 mg daily was started as soon as cytogenetic analysis and FISH examination verified the existence of Ph chromosome. Complete hematological and cytogenetic remission was achieved after the induction chemotherapy, but nested real time-polymerase chain reaction (RT-PCR) was still positive for the BCR-ABL1 (ela2) transcript. The enlarged lymph nodes located at groins and posterior peritoneal resolved, but adenopathy still existed in the cervical and axillary regions after the induction chemotherapy. Later, the patient achieved complete molecular remission (CMR) after the first consolidation therapy. Meanwhile, the patient underwent CNS prophylaxis with the triple intrathecal therapy (methotrexate, cytarabine, dexamethasone). He then underwent an allogeneic hematopoietic stem cell transplantation (allo-HSCT) from a HLA-haploidentical daughter with the improved TBI/CY conditioning regimen (total body irradiation 8 Gy on days -8 to -6, 2g/m2 cytarabine intravenously over 3 h on day -5, CTX was given 1.8 g/m2 intravenously over 3 h on days -4 to -3 with 600 mg/m2 Mesna per day intravenously via continuous infusion on days -4 to -3 beginning 1 h prior to CTX and completed by 12 h after the last dose of CTX). There were no major complications, and he is currently alive in continuous CMR 2 years after allo-HSCT.