Long-term persistent donor–recipient mixed chimerism without disease recurrence after myeloablative single-unit cord blood transplantation in adult acute myeloid leukemia following myelodysplastic syndrome

Umbilical cord blood transplantation (UCBT) has increased access to potentially curative therapy for patients with life-threatening disorders of the bone marrow and immune system. The introduction of reduced intensity conditioning (RIC) regimens and double cord unit infusions (DUCBT) has broadened the applicability of UCBT to more frail or larger recipients. The kinetics of chimerism following RIC DUCBT and their clinical utility are poorly understood. The RIC CBT trial reported here sought to prospectively evaluate the role of lineage specific chimerism following DUCBT in adult patients with haematological malignancies in the UK. Fifty-eight patients with a median age of 52 years were recruited, with an overall and progression free survival of 59% (95%CI 45% to 71%) and 52% (95%CI 39% to 64%) respectively at 2 years. Nonrelapse mortality was 4% (95% CI 1% to 13%) at day 100 and the relapse rate was 31% (95%CI 21% to 45%) at 1 year. Peripheral blood lineage specific chimerism was feasible from day 7 post-transplant onwards. Five patterns of chimerism were observed including i) complete single unit dominance (39 patients), ii) sustained donor-donor mixed chimerism (3 patients), iii) sustained donor-recipient mixed chimerism (5 patients), iv) dominance reversion (1 patient) and v) primary graft failure (4 patients). The RIC CBT trial enabled adult patients with high-risk hematological malignancies to safely access UCBT in the UK and provided novel insights into the kinetics of donor and recipient chimerism following RIC DUCBT which are clinically relevant. (Clinical Trials.gov identifier: NCT00959231; EudraCT identifier: 2004-003845-41).

show abstract

“…Indeed, 1 patient is reported to be alive in remission with stable donor-recipient chimerism 15 years after single CBT. 33 …”

Section: Discussionmentioning

confidence: 99%

Primary graft failure, but not relapse, may be identified by early chimerism following double cord blood unit transplantation

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Chemotherapy, target therapy, radiotherapy and hematopoietic stem cell (HSC) transplantation are common therapies for leukemia (3,4). However, chemoresistance and severe side-effects caused by high-dose chemotherapy drugs are current hurdles to effective treatment (5,6). Therefore, the screening of target-specific small-molecule drugs for leukemia treatment is crucial.…”

Section: Introductionmentioning

confidence: 99%

2-Phenyl-4-quinolone (YT-1) induces G2/M phase arrest and an intrinsic apoptotic mechanism in human leukemia cells

Lin

Yang

et al. 2017

Oncol Rep

View full text Add to dashboard Cite

The present study aimed to investigate the biological effects of the new compound 2‑phenyl‑4‑quinolone (YT‑1) on human leukemia cells. Cell viability was determined by propidium iodide (PI) exclusion method followed by flow cytometry. Our results showed that YT‑1 inhibited the cell viability and resulted in morphologic changes to the U937, HL‑60 and K562 cells, respectively. Among them, U937 cells were the most sensitive cell line. On the contrary, YT‑1 had no cytotoxic effects on human fetal skin fibroblast WS1 cells. Flow cytometric analysis indicated that YT‑1 induced G2/M phase arrest and apoptosis (sub‑G1 population) in U937 cells. The presence of apoptotic bodies evidenced by DAPI staining and DNA fragmentation detected by agarose gel electrophoresis further supported the induction of apoptosis in the YT‑1‑treated U937 cells. Annexin V/PI staining of U937 cells confirmed that the early apoptotic event occurred after YT‑1 exposure. YT‑1 disrupted the mitochondrial membrane potential (ΔΨm) in a time‑dependent manner. YT‑1 increased the protein levels of Bax and Bak but decreased Bcl‑2 and Bid protein levels in U937 cells in a time‑dependent manner. In addition, YT‑1 stimulated the expression of cytochrome c and proteolytic activation of caspase‑3 and caspase‑9 after exposure to YT‑1 in U937 cells. In summary, YT‑1 suppressed the viability of U937 leukemia cells through the intrinsic apoptosis pathway. YT‑1 is a potential chemotherapeutic candidate for the treatment of leukemia.

show abstract

Long-term persistent donor–recipient mixed chimerism without disease recurrence after myeloablative single-unit cord blood transplantation in adult acute myeloid leukemia following myelodysplastic syndrome

Cited by 2 publications

References 15 publications

Primary graft failure, but not relapse, may be identified by early chimerism following double cord blood unit transplantation

Primary graft failure, but not relapse, may be identified by early chimerism following double cord blood unit transplantation

2-Phenyl-4-quinolone (YT-1) induces G2/M phase arrest and an intrinsic apoptotic mechanism in human leukemia cells

Contact Info

Product

Resources

About