Clinical Drug Experience Knowledgebase

Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

Patient exclusion criteria

HIV positive.
Active uncontrolled infection at time of scheduled MSC infusion.
Relapsing or progressing malignancy.

MSC donor exclusion criteria

HIV positive
Known allergy to Lidocaine
If donor other than HSC donor : any risk factor for transmissible infectious diseases.