Acquisition of Isochromosome 7 Is a Late Change in the Pathogenesis of Hepatosplenic Lymphoma, Documented On a Case of Adolescent Girl 5 Years After Renal Transplant with Preceding TCR Gamma-Delta Positive LGL Leukemia.

Post-transplant lymphoproliferative disorders (PTLD) occur in 1-20% of recipients receiving solid organ transplantation. We describe a patient who suffered from hepatosplenic T-cell lymphoma occurring after previous PTLD in a renal transplant recipient.

An 11-yr-old girl underwent kidney transplantation for end-stage Fanconi's nephronophthisis in 2002. In October 2006 significant neutropenia (<200/uL) was firstly detected, without any abnormality in bone marrow (BM) aspirate and without hepato- or splenomegaly. Episodes of neutropenia resolved spontaneously or after enhanced immunosuppression and G-CSF. In January 2007 new episodes of neutropenia and newly significant “monocytosis” were detected in peripheral blood (PB) and BM. Percentage of “monocytes” corresponded with immunophenotypically atypical TCR gamma/delta positive T cells (CD7weak^posCD5^negCD3^bright) in PB and BM. Clonal TCR gamma and delta rearrangements were identified which enabled qPCR minimal residual disease (MRD) assessment. No lymphadenopathy was present, slight hepatosplenomegaly was identified by sonography. Conventional and molecular cytogenetic analyses didn't reveal any chromosomal aberration in PB and BM including changes on chromosome 7. No increased levels of EBV and CMV load by PCR were found. Partial increase of granulocytes and slight decrease of atypical TCR gamma/delta T cells were detected after administration of corticosteroid bolus and mercaptopurin. Three months later she presented with fever, rapidly progressive hepatosplenomegaly and pancytopenia, clinically corresponding with hepatosplenic lymphoma. At this time, newly acquired isochromosome 7q was detected by FISH.

Initial therapy with campath and fludarabine was ineffective. She didn't respond to the 2^nd line treatment (prednisone, vincristine, daunorubicine,asparaginase) and died 2 weeks later from lymphoma progression. Autopsy identified severe hemophagocytosis in the liver. Retrospectively, we identified identical clonal TCR rearrangements in the PB samples from March 2006 (∼0.03% of lymphoma PB MRD level), when neither changes in PB count nor clinical symptoms were found.

We detected a “pre-lymphoma” phase with clonal expansion of atypical TCR gamma/delta T cells more than 1 year before lymphoma manifestation. The presence of isochromosome 7q was a late change during this lymphoma genesis.

IGA NS/9997-4; IGA NR/9531-3, IGA NS 10480-3, Research Projects MZCR 000064203, MSM0021620813

No relevant conflicts of interest to declare.