Unrelated Umbilical Cord Blood Transplantation With Coinfusion of Mesenchymal Stem Cells

A pilot study to assess the feasibility of unrelated umbilical cord blood transplantation with coinfusion of third-party mesenchymal stem cells after myeloablative or nonmyeloablative conditioning in patients with hematological malignancies. This is a multicenter single arm, phase I-II pilot study. The primary objective of this study is to determine the feasibility of Umbilical Cord Blood (UCB) Hematopoietic Stem Cell Transplantation (HSCT) with co-infusion of third party mesenchymal stem cells as assessed by the treatment-related mortality at d100 after transplant. Patient inclusion criteria: Age 15-60 yrs, Patients for whom allogeneic stem cell transplantation is the preferred treatment option, with the following hematological malignancies: acute myeloid leukemia, acute lymphoblastic leukemia, high risk myelodysplastic syndrome, advanced lymphoproliferative disorders, chronic myeloid leukemia (refractory or intolerant to second-line tyrosine kinase inhibitors), multiple myeloma, Informed consent given, Patient exclusion criteria, Previous allogeneic transplant, Progressive malignant disease, Significant organ damage as a contraindication to allotransplantation, Significant psychiatric or neurological disorder, Uncontrolled viral, fungal or bacterial infection, Pregnancy, HIV positive, Patients will receive either myeloablative or reduced intensity conditioning. One or 2 cord blood transplants will be transplanted, followed by infusion of a third-party mesenchymal stem cell transplant, Adverse event reporting Belgian Hematology Society (BHS) transplant committee will establish a protocol review committee which will organize a central monitoring of the study. Within the context of allogeneic Hematopoietic Stem Cell Transplantation (HSCTx) many severe events are likely to occur. Statistics and stopping rules: The trial will be stopped at any time that there is reasonable evidence that the true rate of day +100 nonrelapse mortality exceeds 0.40. It is the intention to include an initial 20 patients.

Sex

All

Minimum age

15 Years

Maximum age

60 Years

Inclusion Criteria:

* Allogeneic stem cell transplantation is the preferred treatment option:
* High risk acute myeloid leukemia (AML) in first complete remission (CR)
* Preceding myelodysplastic syndrome
* High risk karyotypes (e.g. monosomy 5 or 7, complex)
* FLT3 alteration
* \> 2 cycles to obtain CR
* Erythroblastic or megakaryocytic leukemia
* High risk acute lymphoblastic leukemia (ALL) in first CR
* High risk karyotypes (e.g. t\[9;22\], t\[4;11\], t\[1;19\], complex)
* MLL rearrangements
* Acute leukemia in second or third remission
* High risk myelodysplastic syndrome: IPSS Intermediate-2 or high risk
* Advanced lymphoproliferative disorders
* Diffuse large B-cel non-Hodgkin lymphoma (NHL) or mantle cell NHL or
* B-prolymphocytic leukemia
* Sensitive relapse after autologous HSCTx
* T-prolymphocytic leukemia
* Chronic lymphocytic leukemia
* Refractory to fludarabine
* Adverse karyotypes (del p17)
* Chronic myeloid leukemia
* Refractory or intolerant to second-line tyrosine kinase inhibitors
* Multiple myeloma
* Advanced disease (selected cases)
* Informed consent given

Exclusion Criteria:

* Previous allogeneic transplant
* Progressive malignant disease
* Significant organ damage as a contraindication to allotransplantation
* Creatinine clearance \< 60 ml/min
* AST/ALT \> 3x normal value and/or serum bilirubin \> 3 mg/dL
* Cardiac failure (LVEF \< 50%)
* Clinical relevant pulmonary disease: DLCO \< 50% normal
* Significant psychiatric or neurological disorder
* Uncontrolled viral, fungal or bacterial infection
* Pregnancy
* HIV positive