Linege switch:Acute lymphoblastic leukaemia relapsing as acute myeloid relapsing as acute mleukaemia:A case report

Abstract

Lineage switch in a leukaemia is very rare where the initial lymphoid or myeloid clone switches to the other at relapse. We report a case of acute lymphoblastic leukaemia relapsing as a myeloid leukaemia. A 9 year old girl was diagnosed to have B-cell acute lymphoblastic leukaemia in Sep 2015 when she presented with low grade fever and pain involving lower limbs for one month duration.Physicalexamination revealed generalized lymphadenopathy and a mild hepatosplenomegaly. At diagnosis she had a total WBC of 7500/cu.mm with few    atypical cells seen in the blood film. Bone marrow showed 95% blasts which were Sudan black B negative and block positive for Periodic acid Schiff. Immunophenotyping revealed a B cell phenotype where CD19, CD10 were positive along with HLA DR and CD34. Myeloid markers were negative.  Cytogenetics showed a complex karyotype however there were no ALL specific chromosomal abnormalities detected.           RT-PCR for BCR-ABL, TEL-AML, E2A-PBX and MLL-AF4 were all negative. CNS was not involved at diagnosis. She was treated with BFM intermediate risk protocol with induction, consolidation, reinduction and maintenance. Following induction she showed a good steroid response and achieved a morphologic remission however end-induction MRD was positive (0.04%). She was continued on the same protocol where she completed consolidation including 4 medium dose methotrexate infusions (each once in 2 weeks) and reinduction. She was started on final   maintenance since June 2016. In June 2017 she  relapsed as acute myeloid  leukaemia when she  presented with presented with headache and fever.  Total WBC was 282900/cu.mm with monoblasts and promonocytes seen in the blood film. Bone marrow showed 68% monoblasts and  24% promonocytes which were positive for non-specific esterase. Immunophenotyping revealed myeloid markers with a monocytoid  differentiation (CD13, CD33, HLA DR, CD38, CD56, CD64, CD11b, CD14, MPO). Lymphoid markers were negative. Cytogenetics revealed t(9;11) in all the 21 metaphases examined.  CNS was involved as few      atypical cells were seen infiltrating the CSF. CT brain was normal. Thus a diagnosis of MLL rearranged AML with CNS involvement was made. She was started on salvage chemotherapy with FLAG-Ida, however on the same day of initiation of chemotherapy she had a hypoxemia, haemoptysis associated with a high grade fever. She    required intubation and ventilation for the same. HRCT thorax revealed diffuse central ground glass opacities predominantly involving both the upper lobes and  perihilar regions. Differential diagnosis of   pulmonary leucostasis versus fungal /viral        pneumonia with  pulmonary haemorrhage was considered. In the ICU she deteriorated further requiring increasing ventilator  supports and inotropes to maintain optimal perfusion pressures. However  despite best supportive measures and critical care management she expired on the second day.