Mesenchymal Stem Cell Infusion as Treatment for Steroid-Resistant Acute Graft Versus Host Disease (GVHD) or Poor Graft Function

Inclusion Criteria39

• 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
• % decrease in donor T-cell chimerism with the second value < 50%.
• 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.