Philadelphia chromosome (+) T-cell acute lymphoblastic leukaemia after renal transplantation

Ali Arican1, Namik Özbek2, Volkan Baltaci3 and Mehmet Haberal4

1 Departments of Medical Oncology 2 Paediatric Haematology 3 Medical Genetics 4 General Surgery and Transplantation Baskent University School of MedicineAnkara, Turkey

Sir,

Post-transplant lymphoproliferative disorders (PTLD) is a well- known complication of immunosupressive treatment after solid organ transplantation [1]. The majority of PTLD are of B-cell origin and associated with Epstein-Barr virus (EBV) infection [2]. T-cell variants of PTLD are much less common and not well characterized. They exhibit heterogeneous clinical, morphological and phenotypical characteristics and EBV does not appear to be involved in their pathogenesis [3]. Although cases with acute myeloblastic leukaemia, chronic myelocytic leukaemia, and adult T-cell leukaemia/lymphoma following renal transplantation have been reported frequently, there are a few cases with acute lymphoblastic leukaemia (ALL) in the literature [47]. In this report, we described a patient who developed Philadelphia (Ph) (+) T-cell ALL after renal transplantation.

The patient, a 50-year-old male, was weak, complained of pain in the right upper abdominal quadrant and was producing dark urine at the time of admission. He had a history of chronic renal failure requiring haemodialysis at the age 45. Five months after beginning dialysis, he underwent a living-related renal transplantation, receiving a kidney from his daughter and immunosuppressive agents including prednisolone, azathioprine and cyclosporine-A were started. Three months before the last admission he was operated because of acute cholecystitis. In that time, pancytopenia and eosinophilia were observed on peripheral smear, however, bone marrow aspirates and biopsy were normal. The haematological findings returned to normal and the patient was discharged a month after this surgery.

Upon admission, jaundice and hepatosplenomegaly were observed in physical examination and an abdominal ultrasonography demonstrated paraceliac lymphadenopathies. Laboratory studies revealed the following: blood urea-nitrogen 24 mg/dl, creatinine 0.7 mg/dl, haemoglobin 5.6 g/dl, white blood cell count 2.7x109/l, platelet count 50x109/l and 66% blasts on a peripheral blood smear. Bone marrow aspiration smear and biopsy revealed 90% L2-type lymphoblast infiltration. Immunophenotyping of bone marrow blasts disclosed positive PAS and negative myeloperoxidase reaction and flow cytometric analysis showed that the blasts were positive for CD10, CD3, CD5 and CD7 antigens. Ph chromosome was determined with cytogenetic analysis. Figure 1Go shows the metaphase plaque and its caryotype. The patient was diagnosed as Ph (+) T-cell ALL and induction therapy including vincristine, doxorubicine and L-asparaginase was started. In addition to thrombocytopenia that was resistant to replacement treatment, number of blasts increased up to 90% on the peripheral smear in the second week of treatment. The patient died on day 18 of hospitalization as a result of intracerebral haemorrhage.



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Fig. 1. Figure shows the metaphase plaque and its caryotype. The arrows show the Philadelphia chromosomes.

 
PTLD of T-cell lineage has most often been described in the form of a case report or as part of larger series involving primarily B-cell PTLD [3,8]. Most of these reports have included a wide clinical and morphologic spectrum of lesions. Hanson et al. [3] reported six cases of distinct, aggressive T-cell PTLD characterized by an acute leukaemia-like presentation. The median time from transplant to diagnosis of PTLD was 15 years (range 7–26 years) and all patients had been splenectomized as part of the transplant protocol of the time. Frei et al. [4] described a male patient who developed ALL 10 years after renal transplantation, and who exhibited resistance to treatment with cytotoxic agents. In our case, the time to diagnosis of T-cell ALL was 5 years and splenectomy had not been performed.

Ph(+) ALL is an aggressive form of acute leukaemia that represents about one third of all adult ALL [9]. The presence of Ph chromosome is an indicator of poor prognosis, reflected by short duration of complete response and survival period, even for patients treated with current intensive chemotherapy regimens [10]. Features associated with Ph(+) ALL include older age, male predominance, high white blood cell count, FAB L2 morphology and a B-lineage phenotype. To our knowledge, this is the first case of Ph (+) T-cell ALL to occur after solid organ transplantation. It is well-known that immunosuppressed patients who developed malignancy respond poorly to cytotoxic treatment. Our patient died very soon after diagnosis. Poor prognostic factors associated with this patient, including previous immunosuppressive treatment and the presence of Ph chromosome may have caused the resistance to chemotherapy and fatal outcome.

References

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