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Single or Double Donor Umbilical Cord Blood Transplant in Treating Patients With High-Risk Hematologic Malignancies

ABSTRACT: This study will determine the safety and applicability of experimental forms of umbilical cord blood (UCB) transplantation for patients with high risk hematologic malignancies who might benefit from a hematopoietic stem cell transplant (HSCT) but who do not have a standard donor option (no available HLA-matched related donor (MRD), HLA-matched unrelated donor (MUD)), or single UCB unit with adequate cell number and HLA-match).

DISEASE(S): Extranodal Marginal Zone B-cell Lymphoma Of Mucosa-associated Lymphoid Tissue,Lymphoma, Large B-cell, Diffuse,Blastic Phase Chronic Myelogenous Leukemia,Myeloproliferative Disorders,Lymphoma, Large-cell, Immunoblastic,Myelodysplastic-myeloproliferative Diseases,Lymphoproliferative Disorders,Small Intestine Lymphoma,Recurrent Grade 1 Follicular Lymphoma,Refractory Hairy Cell Leukemia,Myelodysplastic/myeloproliferative Neoplasm, Unclassifiable,Sezary Syndrome,T-cell Large Granular Lymphocyte Leukemia,Neoplasm Metastasis,Adult Nasal Type Extranodal Nk/t-cell Lymphoma,Secondary Acute Myeloid Leukemia,Splenic Marginal Zone Lymphoma,Leukemia, Hairy Cell,Refractory Chronic Lymphocytic Leukemia,Mycosis Fungoides,Lymphoma, Mantle-cell,Leukemia-lymphoma, Adult T-cell,Previously Treated Myelodysplastic Syndromes,Adult Acute Myeloid Leukemia In Remission,Recurrent Adult Immunoblastic Large Cell Lymphoma,Recurrent Adult Burkitt Lymphoma,Multiple Myeloma,Leukemia, T-cell,Lymphomatoid Granulomatosis,Lymphoma, T-cell, Peripheral,De Novo Myelodysplastic Syndromes,Lymphoma, Extranodal Nk-t-cell,Plasmablastic Lymphoma,Preleukemia,Lymphoma, B-cell, Marginal Zone,Burkitt Lymphoma,Leukemia, Myelogenous, Chronic, Bcr-abl Positive,Recurrent Adult Diffuse Small Cleaved Cell Lymphoma,Post-transplant Lymphoproliferative Disorder,Adult Acute Myeloid Leukemia With T(8;21)(q22;q22),Nodal Marginal Zone B-cell Lymphoma,Recurrent Small Lymphocytic Lymphoma,Adult Acute Myeloid Leukemia With Inv(16)(p13;q22),Adult Acute Myeloid Leukemia With 11q23 (mll) Abnormalities,Lymphoma, T-cell, Cutaneous,Recurrent Marginal Zone Lymphoma,Recurrent Adult Grade Iii Lymphomatoid Granulomatosis,Lymphoma, Follicular,Waldenstrom Macroglobulinemia,Leukemia, Myeloid, Accelerated Phase,Leukemia, Lymphocytic, Chronic, B-cell,Intraocular Lymphoma,Recurrent Mantle Cell Lymphoma,Relapsing Chronic Myelogenous Leukemia,Recurrent Adult Acute Lymphoblastic Leukemia,Recurrent Grade 3 Follicular Lymphoma,Hodgkin Disease,Leukemia,Accelerated Phase Chronic Myelogenous Leukemia,Recurrent Adult Hodgkin Lymphoma,Adult Acute Lymphoblastic Leukemia In Remission,Mycoses,Waldenström Macroglobulinemia,Noncutaneous Extranodal Lymphoma,Recurrent Adult Lymphoblastic Lymphoma,Angioimmunoblastic T-cell Lymphoma,Leukemia, Myeloid, Acute,Leukemia, Large Granular Lymphocytic,Testicular Lymphoma,Lymphoma, Large-cell, Anaplastic,Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome,Lymphoma, T-cell,Blast Crisis,Myelodysplastic Syndromes,Adult Acute Myeloid Leukemia With T(16;16)(p13;q22),Hepatosplenic T-cell Lymphoma,Secondary Myelodysplastic Syndromes,Leukemia, Lymphoid,Recurrent Adult Acute Myeloid Leukemia,Leukemia, Myeloid,Immunoblastic Lymphadenopathy,Precursor Cell Lymphoblastic Leukemia-lymphoma,Recurrent Cutaneous T-cell Non-hodgkin Lymphoma,Refractory Multiple Myeloma,Lymphoma,Recurrent Mycosis Fungoides/sezary Syndrome,Anaplastic Large Cell Lymphoma,Recurrent Adult Diffuse Mixed Cell Lymphoma,Recurrent Grade 2 Follicular Lymphoma,Adult Acute Myeloid Leukemia With T(15;17)(q22;q12),Peripheral T-cell Lymphoma,Recurrent Adult T-cell Leukemia/lymphoma,Lymphoma, Non-hodgkin,Recurrent Adult Diffuse Large Cell Lymphoma,Lymphoma, B-cell,Cutaneous B-cell Non-hodgkin Lymphoma

PROVIDER: 2129398 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:Mesenchymal stem cells (MSC) are multipotent cells which can be obtained from several adult and fetal tissues including human umbilical cord units. We have recently shown that umbilical cord tissue (UC) is richer in MSC than umbilical cord blood (UCB) but their origin and characteristics in blood as compared to the cord remains unknown. Here we compared, for the first time, the exonic protein-coding and intronic noncoding RNA (ncRNA) expression profiles of MSC from match-paired UC and UCB samples, harvested from the same donors, processed simultaneously and under the same culture conditions. The patterns of intronic ncRNA expression in MSC from UC and UCB paired units were highly similar, indicative of their common donor origin. The respective exonic protein-coding transcript expression profiles, however, were significantly different. Hierarchical clustering based on protein-coding expression similarities grouped MSC according to their tissue location rather than original donor. Genes related to systems development, osteogenesis and immune system were expressed at higher levels in UCB, whereas genes related to cell adhesion, morphogenesis, secretion, angiogenesis and neurogenesis were more expressed in UC cells. These molecular differences verified in tissue-specific MSC gene expression may reflect functional activities influenced by distinct niches and should be considered when developing clinical protocols involving MSC from different sources. In addition, these findings reinforce our previous suggestion on the importance of banking the whole umbilical cord unit for research or future therapeutic use. Cy5- and Cy3-labeled cRNAs were obtained using 300 ng total RNA as template for amplification of poly(A) RNA by T7-RNA polymerase with the Agilent Low RNA Input Fluorescent Linear Amplification kit. The T7-polymerase amplified cRNA labeling approach advantageously replaces the reverse-transcriptase cDNA labeling used in early microarray experiments, because T7-RNA polymerase labeling of cRNA preserves the strand orientation of the original mRNA template. Reverse-transcriptase labeling can eventually generate a complementary cDNA second strand and cause artifactual labeling of a target with the opposite sense to that of the original message. Hybridization of 825 ng of Cy3- or Cy5-labeled RNA (dye swap technical replicate) from each UC sample with its paired UCB sample was performed with Agilent in situ Hybridization kit-plus, as recommended by the manufacturer, using a total of 4 intron-exon 44K expression oligoarrays. This array comprises a total of 13,699 exonic probes representing different protein-coding genes, along with custom-designed intronic probes for the antisense or sense strand. Slides were washed and processed according to the Agilent Two-Color Microarray-Based Gene Expression Analysis protocol (Version 5.5) and scanned on a GenePix 4000B scanner (Molecular Devices, Sunnyvale, CA, USA). Fluorescence intensities were extracted using Feature Extraction (FE) software (version 9.0; Agilent). A gene was considered expressed if its probe intensity was significantly higher than the local background intensity, as calculated by the FE software. Then, the software applies local background subtraction and corrects for unequal dye incorporation using the default LOWESS (locally weighted linear regression) method.

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Single or Double Donor Umbilical Cord Blood Transplant in Treating Patients With High-Risk Hematologic Malignancies

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