The purpose of this study is to evaluate the feasibility and efficacy of reduced-intensity conditioning allogeneic HCT followed by prophylactic dose-escalating DLIs in patients with higher risk MDS.

Conditioning therapy

• Busulfan 3.2 mg/kg/d on d-7 to -6
• Fludarabine 30 mg/m2 on d-7 to -2
• ATG 1.5-3.0 mg/kg/d on d-3 to -1
• Methylpred 2 mg/kg/d on d-4 to -1

Mobilization and harvest

• Donor
• G-CSF 10 mcg/kg/d s.c. on d-3 to 0
• Harvest of PBMCs on d 0 to +1

Infuse G-PBMCs on d 0 to d+1.

• Donor G-PBMC infusion

GVHD prophylaxis

• Cyclosporine 1.5 mg/kg i.v. q 12 hrs beginning on d-1 and changed to oral dosing (with twice the i.v. dose) when oral intake is possible. Tapered beginning between d+30 and d+60.
• Methotrexate 15 mg/m2 i.v. on d+2, and 10 mg/m2 i.v. on d+4 and d+7

Prophylactic dose-escalating DLIs

• Begin at d+120 or at least 2 wks after IST discontinuation.
• No evidence of recurrence or GVHD CD3+ cell dose increment q 4 wks 4Three dose levels

Inclusion Criteria:

1. Patients with higher risk MDS including chronic myelomonocytic leukemia

   • RAEB-1 or RAEB-2
   • IPSS Intermediate-2 or High risk category
   • Chronic myelomonocytic leukemia

2. Patients with appropriate hematopoietic cell donor

   • HLA-matched sibling
   • HLA-matched unrelated donor
   • HLA-mismatched familial donor 3.16 years old or older

Exclusion Criteria:

• • Presence of significant active infection

  • Presence of uncontrolled bleeding
  • Any coexisting major illness or organ failure
  • Patients with psychiatric disorder or mental deficiency severe as to make compliance with the treatment unlike, and making informed consent impossible

Patients with higher risk MDS