Induction of Effector and Memory Cellular Immunity in a Patient with Long-Term Complete Molecular Response to Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

Jo, Tatsuro; Shioya, Haruna; Tominaga, Hiroo; Sakai, Takahiro; Hayashi, Shizuka; Matsuzaka, Kaori; Kaneko, Yohei; Matsuo, Masaru; Taguchi, Jun

doi:10.1159/000508997

Cited by 1 publication

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“…Allogeneic donor lymphocyte infusion in patients with relapsed CML after allogeneic hematopoietic stem cell transplantation often shows effectiveness through cellular immunity [9]. In a previous study, we reported that long-lasting effector and memory CTLs with TCR clonality were detected in a patient with CP-CML who could achieve long-term survival with TKI-treatment-free remission and in a patient with Ph1-positive acute lymphoblastic leukemia with long-term complete molecular response [10, 11]. These effector and memory CTLs might play important roles in attacking leukemic stem cells and inhibiting regrowth.…”

Section: Discussion/conclusionmentioning

confidence: 99%

Clonal Upregulation of Effector Cytotoxic T Lymphocytes in a Patient with Multiple Tyrosine Kinase Inhibitor-Refractory Chronic Myeloid Leukemia with Long-Term Survival

Sakai

Matsuzaka

et al. 2021

Case Rep Oncol

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We present the case of a patient with multiple tyrosine kinase inhibitor (TKI)-refractory chronic phase chronic myeloid leukemia (CP-CML) with a T315I mutation of abl1. Dasatinib, a second-generation TKI, was administered as the initial treatment but achieved neither a cytogenetic nor molecular response. A mutational analysis of abl1 revealed that the patient had a T315I mutation. The patient was then administered ponatinib, a third-generation TKI, which is thought to be effective against T315I; however, the complete blood counts became within normal limits, and neither a cytogenetic nor molecular response was achieved. However, the patient has maintained a healthy chronic phase (with no blast crises) for more than 5½ years since the diagnosis of CP-CML. T-cell receptor (TCR) repertoire analyses using peripheral blood revealed a remarkable clonal expansion of effector cytotoxic T lymphocytes (CTLs) that contained TCR V beta 13.6. We observed the clonal expansion of naïve CTLs with TCR V beta 13.6; however, no clonality was observed in the memory CTLs. The naïve and effector CTLs persisted at very high percentages since the seventh month after starting dasatinib. The CTLs could not have led to the molecular response; therefore, there might be plenty of CML stem cells remaining in the bone marrow. Therefore, although the CTLs might have prevented the disease from developing blast crises over more than 5 years, the CTLs might not have been able to become memory CTLs.

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Section: Discussion/conclusionmentioning

confidence: 99%