Clinical trial NCT06171906: Mesenchymal Stem Cells for Treatment of Poor Graft Function After Allogeneic Hematopoietic Stem Cell Transplantation
Official title: Clinical Study of MSCs for Treatment of Poor Graft Function After Allogeneic Hematopoietic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: MSC
Keywords: allo-HSCT
PGF
Lead sponsor: Southwest Hospital, China
Sponsor class: OTHER
Collaborators: name: Xinqiao Hospital of Chongqing
First posted: 2023-12-15
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective approach for treating both benign and malignant blood disorders. It primarily involves high-dose chemotherapy to eliminate tumor cells within the patient's body, as well as to suppress the recipient's hematopoiesis and immune function. The transplantation replaces the recipient's original hematopoietic stem cells (HSCs) with donor-derived HSCs, thereby reconstructing the donor's hematopoietic and immune functions to achieve disease cure.

Poor graft function (PGF) following transplantation, which refers to inadequate engraftment of the transplanted hematopoietic stem cells, is one of the major factors limiting the effectiveness of allo-HSCT. Mesenchymal stromal cells (MSCs), identified within the bone marrow stroma, are a type of non-hematopoietic multipotent stem cells. Several studies, including previous research by our research team, suggest that MSCs can improve the bone marrow hematopoietic microenvironment by secreting various cytokines. This leads to the promotion of hematopoietic stem cell proliferation and differentiation, enhancement of hematopoietic function, and support for hematopoiesis as well as direct or indirect promotion of vascular regeneration in damaged tissues and organs.

Therefore, exploring the efficacy of umbilical cord-derived MSCs in treating poor graft function after allo-HSCT, observing the recovery of blood parameters in patients with poor engraftment, monitoring transplantation-related complications and immune reconstitution, and conducting preliminary investigations into the underlying mechanisms can contribute to the exploration of new clinical techniques for the treatment of PGF following allo-HSCT.


Eligibility criteria: Inclusion Criteria:

1. Screening patients for allogeneic hematopoietic stem cell transplantation;
2. No gender limit, age ≥18 years old and ≤60 years old;
3. KPS score \>60 points, expected survival period \>3 months;
4. Those without serious functional damage to important organs throughout the body;
5. The patient has no other contraindications to hematopoietic stem cell transplantation
6. Voluntary test and informed consent.

Exclusion Criteria:

1. Have severe heart, kidney or liver dysfunction;
2. Those combined with other malignant tumors need treatment;
3. There are clinical symptoms of brain dysfunction or severe mental illness and the inability to understand or follow the research protocol;
4. Patients who cannot be guaranteed to complete the necessary treatment plan and follow-up observation;
5. Patients with severe acute allergic reactions;
6. Clinically uncontrolled active infection;
7. Patients who are participating in other clinical trials;
8. Researchers believe that the subject is not suitable for clinical trials for other reasons.

Primary outcomes:
measure: The Hemogram recovery of patients with poor graft function after treatment
timeFrame: 20~40 days after transplantation
Secondary outcomes:
measure: Infection rate
timeFrame: 20~40 days after transplantation
measure: graft-versus-host disease
timeFrame: within the initial 30 to 60 days or further
measure: survival rate
timeFrame: 1 year after transplantation
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Xinqiao Hospital
state: Shapingba District
city: Chongqing
country: China
facility: Second Affiliated Hospital, Army Medical University, PLA
Study officials:
affiliation: Xinqiao Hospital
name: Lei Gao
role: STUDY_CHAIR
References:
citation: Kong Y, Song Y, Tang FF, Zhao HY, Chen YH, Han W, Yan CH, Wang Y, Zhang XH, Xu LP, Huang XJ. N-acetyl-L-cysteine improves mesenchymal stem cell function in prolonged isolated thrombocytopenia post-allotransplant. Br J Haematol. 2018 Mar;180(6):863-878. doi: 10.1111/bjh.15119. Epub 2018 Feb 2.
citation: Michalicka M, Boisjoli G, Jahan S, Hovey O, Doxtator E, Abu-Khader A, Pasha R, Pineault N. Human Bone Marrow Mesenchymal Stromal Cell-Derived Osteoblasts Promote the Expansion of Hematopoietic Progenitors Through Beta-Catenin and Notch Signaling Pathways. Stem Cells Dev. 2017 Dec 15;26(24):1735-1748. doi: 10.1089/scd.2017.0133. Epub 2017 Nov 27.