BACKGROUND AND OBJECTIVES: Chronic myeloid leukaemia (CML) is a clonal haemopoietic stem cell disorder characterized by a Philadelphia (Ph) chromosome carrying a BCR/ABL1 fusion protein [1]. Tyrosine kinase inhibitors (TKIs) are well established first-line targeted therapy with improved outcomes in patients in chronic phase (CP) CML [2,3,10]. Blast crisis (BC) treatment requires allogeneic stem cell transplantation (allo-SCT) in eligible patients as well as more potent TKIs based on the mutational profile and [2, 3]. Unfortunately, in our centre, Dr George Mukhari Academic Hospital, Ga-Rankuwa (South Africa), allo-SCT is not readily available due to lack of facilities and paucity of donors. In addition, there is limited access to more potent TKIs. This case report of a 22-year old black male patient who presented with CML in B-lymphoblastic crisis adds to South African data of CML in which there is a paucity of data regarding the incidence, prevalence and outcome [8,12]
CASES PRESENTATION: A 22-year-old African male, HIV negative presenting with bone marrow failure symptoms and B symptoms. Physical examination revealed significant generalised lymphadenopathy and hepatosplenomegaly.
METHODS: The investigations included: Full Blood Count and Differential Count (FBCD), bone marrow aspirate (BMA), trephine biopsy and immuno-histochemical stains (IHS) of the trephine biopsy, immunophenotyping, FISH, PCR, Sanger sequencing and HIV testing.
RESULTS: FBCD: Hyperleucocytosis with a bimodal peak in the neutrophils and myelocytes, 26% blasts as well as severe anaemia and moderate thrombocytopenia. BMA: Similar to peripheral blood findings. Trephine biopsy: Diffuse infiltration by variable sized blast. IHS and imunophenotyping: Positive CD19 and CD34 with negative CD3 and MPO. FISH: 100% positive BCR/ABL1. PCR: p210 BCR/ABL1 transcript. HIV: Non-reactive. A diagnosis of CML in B-lymphoblastic transformation was made.
TREATMENT: Whilst awaiting sequencing mutation results, the index patient received imatinib 400mg orally daily followed by a modified low dose hyper-CVAD chemotherapy. Sequencing revealed two mutations with partial imatinib and nilotinib resistance. The imatinib dose was increased to 800mg daily owing to lack of resources for more potent TKIs as well as access to SCT in our setting.
CONCLUSION: CML in BC is still a major challenge to manage. The challenges faced in resource limited settings include high drug costs, comorbid diseases reducing drug tolerance, as well as limited access to SCT with paucity of African BM donors in BM registry. The index patient was treated with imatinib and hyper-CVAD despite partial resistant mutations to imatinib and nilotinib due to lack of more potent TKIs (e.g. Dasatinib) and allo-SCT. He has not reached complete haematological response, cytogenetic or molecular response at six months of therapy. This case illustrates disparities between diagnostic and management options in our centre.