Case Presentation: A 59 year old man with no past history presented with continuous gingival bleeding for 3 days. He underwent dental cleaning and tooth extraction 3 days prior and since then had been having bleeding from the extraction site associated with headache and dizziness. On presentation blood pressure 110/70mmHg, pulse 105/min, temperature 98F, respiratory rate 16/min. Physical examination showed left submandibular lymph node measuring 4x4cm and splenomegaly that was palpated 5cm below the costal margin. Blood work showed hemoglobin 5.7g/dl, leukocyte count 284.1x109cells/l (neutrophils, 184.66x109cells/l; lymphocytes, 11.36 x109cells/l; monocytes, 2.84 x109cells/l; absent basophils; and 2% blasts), platelet count of 113,000/mm3. He was also found to have acute kidney injury (CrCl 31ml/min). He underwent urgent bone marrow biopsy and was started on hydroxyurea and underwent 4 cycles of leukopheresis. Fluorescent in-situ hybridization (FISH) detected the presence of bcr-abl. Bone marrow biopsy results showed Ph+ CML mixed with 5% T cell population showing T-ALL. Hydroxyurea was stopped and he was started on Imatinib and induction chemotherapy with high-dose cytarabine 3g/m2 and Mitoxantrone 80mg/m2. His counts recovered and he achieved complete remission. Quantative bcr-abl with RT-PCR detected breakpoint in p210.
Discussion: Philadelphia chromosome is commonly associated with CML and is seen in 20-30% cases of adult B-cell leukemia and has therapeutic and prognostic significance. Ph+ B-ALL carries a poor prognosis and require stem cell transplant during the remission phase. Rarely, Philadelphia chromosome is seen in patients with T-ALL. It is a diagnostic dilemma to differentiate between Ph+ T-ALL and T cell lymphoblastic (T-LB) crises of CML. The majority of T-ALL cases reported in the literature and analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) had a BCR breakpoint which was the major one, typical of chronic myelogenous leukemia (CML) and minor breakpoint was detected in only 2 cases.
The factors that favor the diagnosis of T-LB crisis of CML includes previous diagnosis of CML, old age, massive splenomegaly, increased number of peripheral granulocytic precursors, eosinophils, and basophils. Regardless, therapeutic and prognostic value of Philadelphia chromosome is yet to be determined and most patients are treated with combination of Imatinib and T-ALL induction chemotherapy.
Our patient was a rare case of Philadelphia chromosome positive (Ph+) T-cell acute lymphoblastic leukemia (T-ALL) treated with Imatinib and induction chemotherapy with cytarabine and mitoxantrone. To the best of our knowledge, only 25 such cases have been reported.
Conclusions: With the modern advent of targeted therapies, recognizing new cell receptors and markers of tumor carry a prognostic and therapeutic significance. Recently, Ph+ T-ALL is being diagnosed as a separate clinical entity and further research is needed to assess the clinical, therapeutic and prognostic significance.