2. Case:2
leukemia
دينا نعمان جرادة
جيهان ايمن مقاط

3. 42-year-old woman with a long-standing history of Crohn's disease had been followed up in the haematology clinic for anaemia
She was diagnosed with iron deficiency anaemia due to chronic diarrhoea and was treated with intravenous iron therapy intermittently.
. In addition to iron therapy, she was treated with vitamin B12, folic acid and blood transfusions occasionally. 
 Her previous therapy for Crohn's disease 

4. She was started on standard intravenous
She was started on standard intravenous. She responded well to the treatment and was kept on maintenance infusions of infliximab for approximately 24 months. With intravenous iron supplement, her anaemia improved. Her white cell count (WCC) and platelets were normal. She remained in stable condition for more than 2 years.

5. However, gradually, over a period of few months, it became noticeable that she developed leucopenia and worsening anaemia. Her complete blood count showed WCC 1700/mm3 and haemoglobin 7.6 g/dL. Her platelet count remained normal. These abnormalities prompted a bone marrow biopsy

6.  Flow cytometry analysis of the bone marrow aspirate revealed 15% blasts/immature cells positive for CD117, CD13 and CD33 blasts, but negative for CD34 and HLA

7. The immunophenotypical findings were highly suspicious for APL (AML-M3) was performed on interphase nuclei using probes for the PML gene on chromosome 15 and the RARA gene on chromosome 17

8. M3 – hypergranular promyelocytic
This form of AML has a bone marrow with >15% blasts
Is more virulent than other forms
Occurs with a medium age of 39
The WBC count is decreased
Treatment causes a release of the granules and may send the patient into disseminated intravascular coagulation
It is characterized by a 15,17 chromosomal translocation

10. The bone marrow aspirate smear showed myeloid cells with irregular nuclear contours, indented and bilobed and granular cytoplasm; some with Auer rods were seen (figures 1 and ​and2).2). Bone marrow biopsy showed 80–90% cellularity with sheets of immature myeloid cells, morphologically compatible with atypical promyelocytes and represented more than 30% of total cellularity. 

11. The bone marrow biopsy section showing moderate cellularity with aggregates of promyelocytes

12. High power image showing promyelocytes identified by their relative uniformity with abundant cytoplasm and oval-to-round nuclei that are often eccentrically located

13. with careful monitoring of the coagulation fibrinogen due to the risk of developing disseminated intravascular coagulation.
Myeloid maturation was markedly decreased. megakaryocytes were present. Routine cytogenetic analysis revealed normal female karyotype.

14. She tolerated the induction treatment without major complications
She tolerated the induction treatment without major complications. Repeat bone marrow aspiration and biopsy after blood count recovery revealed less than 2% blasts. The bone marrow was normocellular .All three cell lines were present with good maturation. PCR studies for t(15,17) PML/RAR-α were negative confirming complete molecular remission. She received consolidation treatment with idarubicin and ATRA for two cycles.

15. Outcome
The patient remains in remission for more than 5 years. She still follows-up in the haematology clinic for her chronic anaemia and receives intravenous iron treatment and vitamin B12 injection monthly.

16. Infliximab has been effectively used in various inflammatory conditions such as Crohn's disease

17. Background
It is a very rare and possibly one of the few case reports of acute promyelocytic leukaemia (APL; acute myeloid leukaemia M3, AML-M3) to be reported in a patient with refractory Crohn's disease on maintenance infliximab therapy

18. Conclusion
The patient presented here developed APL (AML M3) after a long exposure to infliximab, raising the concern that infliximab may be involved in leukaemia development. The presence of an autoimmune disease such as Crohn's disease may also potentiate leukaemia. It is difficult to define a single aetiology for therapy-related AML because there are multiple host and environmental factors, which can influence the development of leukaemia..