An ‘Uncommon early lineage switch’ in an MLL rearranged adult B-lineage Acute Lymphoblastic Leukemia to Mixed-phenotypic acute leukemia (B/Myeloid) by Narendra Agrawal in International Journal of Clinical Images and Medical Reviews
Case Report
Lineage switch is an infrequent phenomenon with an incidence of ~ 0.6% of all de novo leukemias and seen in almost 6% of relapsed cases. This phenomenon is observed following therapy or at the time of relapse. Switch in lineage tends to occur in younger patients and is associated with particularly poor outcomes.[1]
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Discussion
Our clinical report illustrates an adult refractory B -ALL with t (4;11) (q21;23), AF4:MLL fusion who transformed to Mixed-phenotypic acute leukemia;KMT2A-rearranged during his second month of therapy. Lineage switch in MLL rearranged paediatric ALL is common, but in adults it is not well reported. During the literature review, we found 2 cases of adult ALL harbouring t (4;11) transformed to AML [1,4]. First case illustrated chemotherapy responsive MLL rearranged B-ALL who underwent allogeneic stem cell transplantation (Allo SCT) in remission after induction therapy, who transformed to AML post 100 days of Allo SCT[4]. Second case illustrated refractory MLL rearranged B-ALL adult that rapidly transformed to AML following initiation of blinatumomab therapy [1]. However there was no case found to have switched from B acute lymphoblastic leukemia to Mixed-phenotypic acute leukemia;KMT2A-rearranged .Mechanism for lineage switch in MLL rearranged acute leukemia is not clear yet. Reports showing a strong trend of lineage switch involving B and myeloid lineages suggest that B myeloid progenitor might be involved in the mechanism of lineage switch. Studies reporting lineage switch post anti CD19 therapy; blinatumomab and CD19 chimeric antigen receptor (CAR-T), further advocates this theory [3].In our case it is not possible to state that transformation occurred post Venetoclax therapy, as flow cytometric evaluation was not done prior to start of venetoclax therapy. Development of secondary AML as a result of therapy related process can be ruled out in view of early lineage switch (< 6 months of therapy) and consistent finding of the t (4;11) (q21;23) at diagnosis of B-ALL and transformation. The (4;11) rearrangement detected at diagnosis, and phenotypic switch suggests that the original clone harboured a bi-lineage potential. If further genetic studies including NGS or gene expression studies done at baseline could have predicted the bi lineage potential is also unclear as the case reported by Haddox C et al did not show any change in the baseline NGS and the NGS performed during relapse.In conclusion, haematologists should be cognizant while treating MLL rearranged B -ALL adults for a lineage switch. It also underlies the importance of repeat evaluation of the disease if there is no response to standard therapy.
Declarations
Funding Funding information is not applicable to this study.Conflict of Interest All authors declare no conflict of interest to declare.Compliance with Ethical Standards Ethical Approval Statement: All authors stated that the study has been approved by the appropriate institutional review board and have been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.Acknowledgement We are thankful to our RGCI & RC staff of department of Hematology for their constant supportFor more details: https://ijcimr.org/editorial-board/