Mesenchymal Stem Cell Infusion as Prevention for Graft Rejection and Graft-Versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation With Nonmyeloablative Conditioning from HLA-mismatched PBSC or cord blood: a Pilot Study

V.1. Patients

V.1.1. Diseases

Hematological malignancies confirmed histologically and not rapidly progressing:

• AML in CR;
• ALL in CR;
• CML unresponsive/intolerant to Imatinib but not in blast crisis;
• Other myeloproliferative disorders not in blast crisis and not with extensive myelofibrosis;
• MDS with < 5% blasts;
• Multiple myeloma;
• CLL;
• Non-Hodgkin's lymphoma (aggressive NHL should have chemosensitive disease);
• Hodgkin's disease.

V.1.2. Clinical situations

• Theoretical indication for a standard allo-transplant, but not feasible because:

  • Age > 55 yrs;
  • Unacceptable end organ performance;
  • Patient's refusal.

• Indication for a standard auto-transplant: perform mini-allotransplantation 2-6 months after standard autotransplant.

V.1.3. Other inclusion criteria

• Male or female; fertile female patients must use a reliable contraception method;
• Age < 75 yrs.
• Informed consent given by patient or his/her guardian if of minor age.

V.1.4. Exclusion criteria

• Any condition not fulfilling inclusion criteria;
• HIV positive;
• Terminal organ failure, except for renal failure (dialysis acceptable);
• Uncontrolled infection, arrhythmia or hypertension;
• Previous radiation therapy precluding the use of 2 Gy TBI;
• HLA-identical donor.

V.2. PBSC donors

V.2.1. Inclusion criteria

• Related to the recipient (sibling, parent or child) or unrelated;
• Male or female;
• Weight > 15 Kg (because of leukapheresis);
• Fulfills generally accepted criteria for allogeneic PBSC donation;
• Informed consent given by donor or his/her guardian if of minor age, as per donor center standard procedures.

V.2.2. Exclusion criteria

• Any condition not fulfilling inclusion criteria;
• HIV positive;
• Unable to undergo leukapheresis because of poor vein access or other reasons.

V.2.3. HLA matching

Related or unrelated donors who have 1-2 HLA mismatches, as either :

• One antigenic mismatch at HLA-A or -B or -C or -DRB1 or -DQB1
• One allelic mismatch at HLA-A or -B or -C or -DRB1 or -DQB1
• Two allelic mismatches at HLA-A or -B or -C or -DRB1 or -DQB1
• One antigenic mismatch + 1 allelic mismatch at HLA-A or -B or -C or -DRB1 or -DQB1.
• One antigenic mismatch at -DQB1 and one other antigenic mismatch at HLA-A or -B or -C or -DRB1

V.3. Cord blood unit

Banked cord blood units will be used if they fulfill the following criteria:

• No more than 2/6 HLA mismatches (antigenic mismatch at HLA-A or HLA-B or allelic mismatch at HLA-DRB1)
• > 2.5 x 107 TNC/kg
• Standard validation by FACT/Netcord criteria.