PROTOCOL SYNOPSIS~Title of the study 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.~Design of the study This is a multicenter single arm, phase I-II pilot study.~Primary objective The primary objective of this study is to determine the feasibility of UCB HSCT with co-infusion of third party mesenchymal stem cells as assessed by the treatment-related mortality at d100 after transplant.~Secondary objectives~Chimerism at multiple time points~Hematopoietic recovery (neutrophil and platelet engraftment)~Immune recovery~Incidence of acute and chronic graft-versus-host disease (GVHD)~Infectious complications~Disease free survival~Relapse incidence~Overall survival~Graft criteria~No peripheral blood or marrow donor available at the 9/10 compatibility level using high resolution typing techniques~Adequate cord blood transplant available:~a)Single cord blood~Minimal 4/6 match (DR1-high, A-low, B-low)~Minimal 2 (6/6), 2.5 (5/6) or 3 (4/6) x 10exp7 nucleated cells per kg in the graft b)Double cord blood~At least 4/6 common antigens shared by recipient and the 2 cord blood transplants~Minimal 3x 10exp7 nucleated cells per kg in the combined graft~Patient inclusion criteria~Age 15-60 yrs~Allogeneic stem cell transplantation is the preferred treatment option:~a)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 b)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 c)Acute leukemia in second or third remission d)High risk myelodysplastic syndrome: IPSS Intermediate-2 or high risk e)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) f)Chronic myeloid leukemia~Refractory or intolerant to second-line tyrosine kinase inhibitors g)Multiple myeloma~Advanced disease (selected cases)~Informed consent given~Patient 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~Study procedure 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 BHS transplant committee will establish a protocol review committee which will organize a central monitoring of the study. Within the context of allogeneic 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.
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 UCB 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 BHS transplant committee will establish a protocol review committee which will organize a central monitoring of the study. Within the context of allogeneic 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.