∙ Patient eligibility criteria

• Male or female of any age.

• Previous allogeneic transplantation (related or unrelated donor, any degree of HLA matching) or autologous transplantation (for part 2 only) of HSC at any time before.

• Any source of HSC (marrow, PBSC, cord blood) and any conditioning regimen.

• Informed consent given by donor or his/her guardian if of minor age.

• Additional criteria for each part of the protocol:

∙ Part 1: MSC for steroid-refractory grade II-IV acute GVHD

• Allogeneic transplantation.

• Grade II-IV acute GVHD (see appendix A for acute GVHD grading) de novo or following DLI.

• Acute GVHD refractory to mPDN 2 mg/kg/day or equivalent, defined as

‣ progression of GVHD on day 3 after initiation of steroids

⁃ no improvement of GVHD on day 7 after initiation of steroids

⁃ absence of complete resolution of acute GVHD on day 14 after initiation of steroids

⁃ relapse of acute GVHD during or after steroid taper.

• Ongoing therapy with Ciclosporine or Tacrolimus at therapeutic doses.

• Patient may have received previously any other form of treatment for acute GVHD, but no new treatment started within 1 month of study entry.

∙ Part 2: MSC for poor graft function (PGF)

• Allogeneic or autologous transplantation.

• Cytopenia in 2 or 3 lineages:

‣ Hb \< 8.0 g/dL and reticulocytes \< 1%, with or without transfusion

⁃ Plt \< 20,000/µL without transfusion

⁃ Neutrophils \< 500/µL, without G-CSF administration

• OR severe cytopenia in 1 lineage:

⁃ RBC transfusion dependent (if autologous transplantation; despite EPO administration if allogeneic transplantation)

⁃ Plt transfusion dependent

⁃ Neutrophils \< 500/µL despite G-CSF administration

• Cytopenia duration ≥ 2 weeks beyond day 28 after autologous HCT, or day 42 (day 60 for cord blood transplantation) after allogeneic HCT.

• Cytopenia is not related to CMV or other infection, myelosuppressive/toxic drugs, renal failure, peripheral cell destruction or other identifiable cause.

• In case of HLA-identical related donor and full donor chimerism, patient can only be included if a boost of donor CD34+ cells has been unsuccessful or is not feasible.

∙ Part 3: MSC + DLI for poor donor T-cell chimerism

• Nonmyeloablative allogeneic transplantation.

• Donor T-cell chimerism \< 50% for at least 2 consecutive weeks beyond day 21 after HCT OR

‣ 20% decrease in donor T-cell chimerism with the second value \< 50%.

∙ MSC donor inclusion criteria

• Related to the recipient (sibling, parent or child) or unrelated.

• Male or female.

• Age \> 16 yrs (no age limit if same as HSC donor).

• No HLA matching required.

• Fulfills generally accepted criteria for allogeneic HSC donation.

• Informed consent given by donor or his/her guardian if of minor age.