MSC and HSC Coinfusion in Mismatched Minitransplants

• Mesenchymal stem cells (Biological): Mesenchymal stem cell injection
• Isotonic solution (Other): Isotonic solution injection

Primary outcomes

• One-year overall survival in the 2 arms. [One year]

Secondary outcomes

• Incidence of grade II-IV and grade III-IV acute GVDH [100 days]
• Number of absolute donor T cells after HCT in each arm [28]
• Cumulative incidence of non-relapse mortality [100, 365 and 730 days]
• Incidence of extensive chronic GVHD in each arm [365 days]
• Incidence of graft rejection in each arm. [365 days]
• Quality and timing of immunologic reconstitution in each arm. [100, 365 and 730 days]
• Detection of MSC from donor origin in recipient marrow after HCT in patients given MSC [40 days]
• Proportion of patients with measurable disease at HCT who achieve a complete response in each arm. [100, 365 and 730 days]
• Cumulative incidence of relapse [365 and 730 days]
• Incidence of progression-free survival [365 and 730 days]
• Incidence of infections [100 days]

Sex: All, ages: any to 75 Years

Inclusion Criteria:

* 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.
* Male or female; fertile female patients must use a reliable contraception method
* Age ≤ 75 year old
* Informed consent given by patient or his/her guardian if of minor age.
* One or two HLA mismatches with PBSC:

  * One antigenic 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
  * Patients with one single allelic mismatch at HLA-A or -B or -C or -DRB1 or -DQB1 can also be included in the protocol.
* Hematological malignancies confirmed histologically and not rapidly progressing:

  * AML in complete remission
  * ALL in complete remission
  * 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 not rapidly progressing
  * CLL
  * Non-Hodgkin's lymphoma (aggressive NHL should be chemosensitive)
  * Hodgkin's disease

Exclusion Criteria:

* Any condition not fulfilling inclusion criteria
* HIV positive
* Terminal organ failure, except for renal failure (dialysis acceptable)

  * Cardiac: Symptomatic coronary artery disease or other cardiac failure requiring therapy; ejection fraction <35%; uncontrolled arrhythmia; uncontrolled hypertension
  * Pulmonary: DLCO < 35% and/or receiving supplementary continuous oxygen
  * Hepatic: Fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease
* Uncontrolled infection, arrhythmia or hypertension
* Previous radiation therapy precluding the use of 2 Gy TBI
* 10/10 HLA-A, -B, -C, DRB1 and DQBI allele-matched donor fit to/willing to donate PBSC.

• Yves Beguin, MD, PhD, Principal investigator, CHU-ULg
• Frédéric Baron, MD, PhD, Study chair, CHU-ULg
• Evelyne Willems, MD, Principal investigator, CHU-ULg
• Dominik Selleslag, MD, PhD, Principal investigator, AZ Brugge
• Pierre Zachée, MD, PhD, Principal investigator, ZNA Antwerpen
• Philippe Lewalle, MD, PhD, Principal investigator, Bordet Institute, Brussels
• Dominique Bron, MD, PhD, Principal investigator, Bordet Institute, Brussels
• Wilfried Schroyens, MD, PhD, Principal investigator, UZA Antwerpen
• Chantal Lechanteur, PhD, Principal investigator, CHU-ULg
• Etienne Baudoux, MD, Principal investigator, CHU-ULg
• Johan Maertens, MD, Principal investigator, KUL, Leuven
• Rik Schots, MD, PhD, Principal investigator, AZ VUB, Brussels
• Augustin Ferrant, MD, PhD, Principal investigator, UCL St. LUC, Brussels
• Lucien Noens, MD, PhD, Principal investigator, UZG Gent
• Chantal Doyen, MD, PhD, Principal investigator, Cliiques Universitaire Mont-Godinne, Yvoir
• Tessa Kerre, MD, PhD, Principal investigator, UZA, Antwerpen
• Carlos Graux, MD, PhD, Principal investigator, Cliniques Universitaires, Mont-Godinne