PMC7314974_01
(A) Leukemic phenotype at baseline. The histograms report both the leukemic clone (in red) and the normal B cell compartment (in green) to underscore the expression of aberrant markers. (B) minimal residual disease (MRD) evaluation performed at 4 different timepoints (the number on the top of each panel represents the number of months from diagnosis) and compared with baseline phenotype. Dotplots are represented with a dimensionality reduction approach (principal component analysis or automatic population separator (APS) in infinicyt software, Cytognos) which allow the identification of the different immune population within the bone marrow (L, lymphocytes; ER, erythroblasts; N, granulocytes; M, monocytes; E, eosinophils; ALL, leukemic clone).
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F1
The subsequent bone marrow (BM) aspiration confirmed the diagnosis, showing the presence of aberrant cells with a B precursor immunophenotype (CD19+CD20-CD10brightCD45dimCD34+CD58+CD5-CD38low) (Figure 1A) and expression of the BCR-ABL1 p210 fusion gene. On May 5, 2016, the patient started an induction treatment with Vincristine 2 mg weekly (4 administrations), methylprednisolone (60 mg/m2/day for 28 days) and dasatinib 140 mg daily (early switch from imatinib due to intolerance after the first 7 days of treatment), associated with the intrathecal administration of cytarabine and methylprednisolone as a prophylaxis, which resulted in a rapid hematological complete response and BM negative minimal residual disease (MRD) (10-4.2 in PCR, 10-4.5 in FCM) after 5 months (Figure 1B).
(A) Trends in BCR-ABL transcript levels in peripheral blood coupled with different normal immune populations distribution within the bone marrow along disease evolution and in response to different treatments. BCR-ABL/ABL ratio values are reported on the left vertical axis while cell population abundance refers to the right axis. (B) T, NK, and B cell representation within the whole lymphocyte group at baseline and after ponatinib + donor lymphocytes infusion (DLI). Notably, within the T cell compartment we observed an inversion in the CD8/CD4 ratio, favoring the CD8 compartment after DLI treatment.
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F2
Interestingly, this clinical picture was accompanied by a substantial increase in normal B cell progenitors, an inversion between CD58+ and CD58- T/NK lymphocytes distribution (Figure 2A) and by an inversion of the CD8/CD4 ratio (Figure 2B) within the BM.