This is a prospective, single-arm clinical study. It aims to evaluate the effectiveness and safety of a conditioning regimen containing thiotepa (in combination with busulfan and fludarabine, with or without ATG) of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with chronic myelomonocytic leukemia (CMML) who have an intermediate-2 or high-risk prognosis.

The main goal is to evaluate 1 year RFS and OS. Other goals include assessing engraftment, overall survival, transplant-related complications, and side effects. A total of 31 participants will be enrolled.

Inclusion Criteria:

• Age ≥ 18 years, any sex/gender.
• Confirmed diagnosis of chronic myelomonocytic leukemia (CMML) according to the 2022 WHO classification.
• Intermediate-2 or high-risk CMML based on CPSS or CPSS-mol score, and planned to receive allo-HSCT.
• Has a suitable hematopoietic stem cell donor:
• For haploidentical donor: at least 5/10 HLA match at HLA-A, -B, -C, -DQB1, and -DRB1.
• For unrelated donor: at least 9/10 HLA match at the same five loci.
• For matched sibling donor: 10/10 HLA match at the same five loci.
• Hematopoietic cell transplantation comorbidity index (HCT-CI) ≤ 2, with generally good health and no significant organ abnormalities or major comorbidities.
• Adequate organ function as defined below:
• Left ventricular ejection fraction (LVEF) ≥ 50%, and no uncontrolled tachycardia or bradycardia-tachycardia syndrome.
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN); ALT ≤ 2 × ULN; AST ≤ 2 × ULN.
• Serum creatinine ≤ 1.5 × ULN.
• Baseline oxygen saturation > 92%.
• Pulmonary function: DLCO (corrected for hemoglobin) ≥ 40%, FEV1 ≥ 50%.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Agrees not to participate in any other interventional study during the treatment period.
• Willing and able to provide written informed consent, understand the nature, purpose, and procedures of the study, and voluntarily comply with study requirements.

Exclusion Criteria:

• Previous allogeneic HSCT for CMML that later relapsed.
• Unwilling or unable to receive the study treatment regimen.
• Active hepatitis B or C, or chronic active hepatitis; known human immunodeficiency virus (HIV) infection.
• Active uncontrolled infection, including: hemodynamic instability related to infection, new or worsening signs/symptoms of infection, new infection lesions on imaging, or persistent fever without explanation despite no symptoms/signs.
• History of stroke or intracranial hemorrhage within 6 months before enrollment.
• Known pregnancy (positive urine pregnancy test), or currently breastfeeding.
• Diagnosis of another malignancy within the past 2 years, except for localized skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, breast cancer, or localized prostate cancer (Gleason score ≤ 6) that has been treated with curative intent.
• Any other condition that, in the investigator's judgment, makes the patient unsuitable for study participation.

Individual participant data will not be shared with other researchers.