An unusual hematopoietic stem cell transplantation for donor acute lymphoblastic leukemia: a case report

Zhou, Di; Xie, Ting; Chen, Suning; Ling, Yipeng; Xu, Yueyi; Chen, Bing; Ouyang, Jian; Yang, Yonggong

doi:10.1186/s12885-020-6681-2

Cited by 3 publications

(3 citation statements)

References 26 publications

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“…The most effective leukemia treatments still rely on conventional, low-specificity chemotherapy followed by HCT (Cornelissen et al, 2016;Zhou et al, 2020). Importantly, HCT treatment requires immunosuppressive drugs increased risk of life-threatening microbial infections (Poutsiaka et al, 2007).…”

Section: Current Knowledgementioning

confidence: 99%

Dual-Activity Fluoroquinolone-Transportan 10 Conjugates Offer Alternative Leukemia Therapy during Hematopoietic Cell Transplantation

Lica,

Heldt,

Wieczór

et al. 2023

Mol Pharmacol

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Hematopoietic cell transplantation (HCT) is often considered a last resort leukemia treatment, fraught with limited success due to microbial infections, a leading cause of mortality in leukemia patients. To address this critical issue, we explored a novel approach by synthesizing antileukemic agents containing antibacterial substances. This innovative strategy involves conjugating fluoroquinolone antibiotics, such as ciprofloxacin (CIP) or levofloxacin (LVX), with the cell-penetrating peptide (CPP) transportan 10 (TP10). Here, we demonstrate that the resultant compounds display promising biological activities in preclinical studies. These novel conjugates not only exhibit potent antimicrobial effects but are also selective against leukemia cells. The cytotoxic mechanism involves rapid disruption of cell membrane asymmetry leading to membrane damage. Importantly, these conjugates penetrated mammalian cells, accumulating within the nuclear membrane without significant effect on cellular architecture or mitochondrial function. Molecular simulations elucidated the aggregation tendencies of TP10 conjugates within lipid bilayers, resulting in membrane disruption and permeabilization. Moreover, mass spectrometry analysis confirmed efficient reduction of disulfide bonds within TP10 conjugates, facilitating release and activation of the fluoroquinolone derivatives. Intriguingly, these compounds inhibited human topoisomerases, setting them apart from traditional fluoroquinolones. Remarkably, TP10 conjugates generated lower intracellular levels of reactive oxygen species (ROS) compared to CIP and LVX. The combination of antibacterial and antileukemic properties, coupled with selective cytostatic effects and minimal toxicity towards healthy cells, positions TP10 derivatives as promising candidates for innovative therapeutic approaches in the context of antileukemic HCT. This study highlights their potential in search of more effective leukemia treatments. SIGNIFICANCE STATEMENT Fluoroquinolones are commonly used antibiotics, while TP10 is a CPP with anticancer properties. In HCT, microbial infections are the primary cause of illness and death. Combining TP10 with fluoroquinolones enhanced their effects on different cell types. The dual pharmacological action of these conjugates offers a promising proof-of-concept solution for leukemic patients undergoing HCT. Strategically designed therapeutics, incorporating CPPs with antibacterial properties, have the potential to reduce microbial infections in the treatment of malignancies.

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Section: Current Knowledgementioning

confidence: 99%

Dual-Activity Fluoroquinolone-Transportan 10 Conjugates Offer Alternative Leukemia Therapy during Hematopoietic Cell Transplantation

Lica,

Heldt,

Wieczór

et al. 2023

Mol Pharmacol

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“…Even short‐term prophylactic G‐CSF in chemotherapy patients is now reported to synergistically enhance chemotherapy‐related risks for a secondary myeloid leukemia 4,5 . Among related HPC donors, there are rare reports of cancer occurring years after G‐CSF mobilization possibly reflecting familial genetic risk factors 6,7 . Studies by National Marrow Donor Program (NMDP), however, have shown no increased risk of cancer in healthy donors 2 .…”

Section: Introductionmentioning

confidence: 99%

“…4,5 Among related HPC donors, there are rare reports of cancer occurring years after G-CSF mobilization possibly reflecting familial genetic risk factors. 6,7 Studies by National Marrow Donor Program (NMDP), however, have shown no increased risk of cancer in healthy donors. 2 We now report an unusual case of G-CSF unmasking and mobilizing a new therapy-related acute lymphocytic leukemia (t-ALL) in a young male with a testicular embryonic germ cell tumor undergoing autologous HPC collection (HPCC).…”

Section: Introductionmentioning

confidence: 99%

A secondary CD34+ acute lymphoblastic leukemia unmasked and mobilized by G‐CSF in an autologous stem cell donor with testicular cancer

et al. 2023

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Background: Late complications of chemotherapy include treatment-related secondary leukemias. We describe an unusual case of a new treatment-related acute lymphoblastic leukemia (t-ALL) that was unmasked and mobilized by G-CSF during autologous hematopoietic progenitor cell collection (HPCC) in a young man with testicular cancer.Methods: Electronic chart review of the patient medical history and pertinent laboratory findings. Patient CD34 and blast results were compared to 4249 autologous and 437 allogeneic HPCC performed between 2004 and 2022. In autologous donors, the %blast and %CD34 were compared by linear regression and paired t-test using commercial software. Results:The patient was a 21-year-old male with relapsed testicular cancer referred for G-CSF cytokine-only mobilization and autologous HPCC. His premobilization WBC count and differential were normal. On the day of HPCC, his WBC = 37.9 K/mcL with 12% blasts and 9.75% circulating CD34+ cells. The patient was admitted 9 days after HPCC with a normal WBC count and 15% blasts. He was diagnosed with a pro-B t-ALL bearing an t(4:11)(q21:q23) translocation and KMT2A-AF4 rearrangement. Upon review, this patient had the highest %CD34 among 4686 HPCC and was the only donor with %CD34 > 1% after a cytokine-only mobilization. Conclusion:We report a case of t-ALL that mimicked CD34+ HPC and was mobilized by high-dose G-CSF. Up to 70% of secondary leukemias bear 11q23/ KMT2A rearrangements, which occur at the multipotent stem cell stage and can result in myeloid and lymphoid leukemias. Donors who have received past chemotherapy, especially with topoisomerase II inhibitors, are at increased risk for 11q23/KMT2A leukemias.

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A case of donor cell leukemia driven by a de novo NRAS mutation with complex karyotype

Jeong

Seo

et al. 2023

Ann Hematol

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An unusual hematopoietic stem cell transplantation for donor acute lymphoblastic leukemia: a case report

Cited by 3 publications

References 26 publications

Dual-Activity Fluoroquinolone-Transportan 10 Conjugates Offer Alternative Leukemia Therapy during Hematopoietic Cell Transplantation

Dual-Activity Fluoroquinolone-Transportan 10 Conjugates Offer Alternative Leukemia Therapy during Hematopoietic Cell Transplantation

A secondary CD34+ acute lymphoblastic leukemia unmasked and mobilized by G‐CSF in an autologous stem cell donor with testicular cancer

A case of donor cell leukemia driven by a de novo NRAS mutation with complex karyotype

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