By collecting interventional clinical data to assess the survival and relapse conditionsof patients post-transplantation and comparing them with historical data, the primarystudy endpoint is the 1-year and 2-year relapse-free survival (RFS) post-transplantation.This includes the time from the start of treatment until the documentation of diseaseprogression (bone marrow smear blast cells > 5% or extramedullary relapse) or deathdue to any cause, whichever occurs first. This experiment aims to improve thepost-transplant survival rates of MDS patients classified as very high risk under theIPSS-M stratification and to explore pathways to prevent relapse.
Not Provided
Drug: Prophylactic Intervention for Relapse Prevention Post-Allogeneic Transplantation
1.1 AZA + BCL2 Inhibitor (Preferred Regimen) Subcutaneous injection of azacitidine at 32
mg/m² per day for 5 consecutive days, with a 28-day cycle; BCL2 inhibitor (VEN): 400 mg
per day orally for one week (if combined with a CYP450 inhibitor, reduce to 100 mg per
day).
1.2 AZA (DEC) + DLI For patients with TP53 mutations or those who do not respond to VEN,
subcutaneous injection of azacitidine at 32 mg/m² per day for 5 consecutive days, with a
28-day cycle; decitabine at 5 mg/m² per day for 5 consecutive days, with a 28-day cycle
(preferred for those with TP53 mutations). For patients without the option for DLI,
regimen 1.1 is recommended.
DLI: Begins 3 months post-transplantation, starting with a dose of 1×10^5 CD3+ T
lymphocytes for haploidentical transplants, with doses increasing every 4-6 weeks to
5×10^5 CD3+ T lymphocytes, 1×10^6 CD3+, and 5×10^6 CD3+ T lymphocytes; for full-matched
transplants, the starting dose is 5×10^5 CD3+ T lymphocytes with dose escalations as
above to 1×1
Inclusion Criteria:
1. Age between 18 and 70 years, inclusive, both male and female. Diagnosed with MDS
according to WHO criteria and classified as very high-risk by IPSS-M scoring. The
patient must have a suitable hematopoietic stem cell donor for allogeneic
transplantation: Related donors must be at least 5/10 matched for HLA-A, -B, -C,
-DQB1, and -DRB1
2. Unrelated donors must be at least 8/10 matched for HLA-A, -B, -C, -DQB1, and -DRB1.
Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) score of ≤ 2. ECOG
performance status of 0-2. Adequate liver, kidney, cardiac, and pulmonary functions
as follows: Serum creatinine ≤ 1.5× upper limit of normal (ULN)
3. Cardiac function: Ejection fraction ≥ 50%
4. Baseline oxygen saturation > 92%
5. Total bilirubin ≤ 1.5× ULN
6. ALT and AST ≤ 2.0× ULN
7. Pulmonary function: DLCO (corrected for hemoglobin) ≥ 40% and FEV1 ≥ 50%. Patients
must be capable of understanding and willing to participate in the study, and must
sign an informed consent form.
Exclusion Criteria:
1. Failure to proceed with stem cell reinfusion after unsuccessful pre-transplant
conditioning. History of previous hematopoietic stem cell transplantation (HSCT).
ECOG performance status > 2. Hematopoietic Cell Transplantation-Comorbidity Index
(HCT-CI) score ≥ 3. Any unstable systemic disease including, but not limited to:
unstable angina, cerebrovascular accident or transient ischemic attack within the
past 3 months, myocardial infarction within the past 3 months, congestive heart
failure (New York Heart Association [NYHA] class ≥ III), post-pacemaker implantation
requiring medication for severe arrhythmias, severe liver, kidney, or metabolic
diseases
2. patients with pulmonary arterial hypertension. Active, uncontrolled infection:
hemodynamic instability related to infection, new symptoms or signs of worsening
infection, radiological evidence of new infectious foci, persistent fever without
signs or symptoms that cannot exclude infection. Need for treatment for Grade ≥2
epilepsy, paralysis, aphasia, new cerebral infarction, severe brain trauma,
dementia, Parkinson's disease, schizophrenia. HIV infection. Active hepatitis B
(HBV) or hepatitis C (HCV) requiring antiviral treatment
3. patients at risk of HBV reactivation, indicated by positive hepatitis B surface
antigen or core antibody without antiviral therapy for hepatitis B. Pregnant or
breastfeeding women. Men and women of childbearing potential unwilling to use
contraception during the treatment and for 12 months post-treatment. Allergic to
intervention drugs such as azacitidine, decitabine, or venetoclax.
Shanghai General Hospital
Shanghai, China
Investigator: Wu Huixian
Contact: +86 18621127020
1011825696@qq.com
Xianmin Song, MD
+8613501672508
shongxm@139.com
Not Provided