unrelated umbilical cord blood transplantation augmented with aldhbr umbilical cord blood cells

Conditions: MDS; Anemia, Aplastic; Inborn Errors of Metabolism; Congenital Marrow Failure; Congenital Immunodeficiency Syndrome

Summary: the main purpose of this investigational (not approved by the fda) phase i research is to test whether transplantation of umbilical cord blood cells can be safely supplemented with a transfusion of a portion of these cells that have been sorted (collected from a special machine called a cell sorter) and then either infused a few hours after the standard transplant or for some patients grown in a special system in the laboratory prior to the transplant, designed to increase the number of stem cells transplanted. this system is currently in the early phases of testing.

the main purpose of this study is to test whether transplantation of umbilical cord blood cells can be safely supplemented with transfusion of a portion of these cells that have been grown in a special system (designed to increase the number of cells transplanted) in the laboratory prior to the transplant. this system is currently in the early phases of testing in a fda-ind-sponsored clinical trial. if the patient consents to participate in this study, approximately 1/5th (20%) of the cord blood unit selected for the transplant will be treated per protocol. the first 3 patients will receive aldhbr sorted cells but not primed in culture. this is to test the safety of the aldhbr cells. the treated cells will be given to the patient on the day of transplant approximately 4 hours after the standard or conventional transplant which will be given from the 80% fraction of the cord blood unit. a total of 26 evaluable patients are to be enrolled as outlined below (protocol has been amended to allow this enrollment): * 10 evaluable patients who received aldhbr freshly sorted cells (20% portion) * 10 evaluable patients who received aldhbr sorted and cytokine primed cells (20% portion) * 3 evaluable patients who received a conventional cord blood unit and a cord blood unit that has been aldhbr sorted (sort of the ucb unit will be done on day -1 due to the time it takes to actually perform the sort) * 3 evaluable patients who received a conventional cord blood unit and a cord blood unit that has been aldhbr sorted and cytokine primed (sort and priming will be done on day -5 as described later in the protocol)

Eligibility criteria:
inclusion criteria: -hematologic malignancy: high risk all in first complete remission all or anll in second or subsequent remission anll in relapse mds cml in any chronic phase or accelerated phase severe aplastic anemia refractory to medical therapy the subject is negative for cns disease at time of enrollment. * inborn errors of metabolism hurler syndrome (mps i) hurler-scheie syndrome hunter syndrome (mps ii) sanfilippo syndrome (mps iii) morquio syndrome (mps iv) maroteaux-lamy syndrome (mps vi) krabbe disease (globoid leukodystrophy) metachromatic leukodystrophy (mld) adrenoleukodystrophy(ald and amn) sandhoff disease tay sachs disease the subject does not have uncontrolled seizures, apnea, evidence of aspiration pneumonia or evidence of brain stem involvement on mri scans * congenital marrow failure amegakaryocytic thrombocytopenia tar kostmann's syndrome schwachman-diamond syndrome blackfan-diamond anemia * congenital immunodeficiency syndromes requiring myeloablative therapy wiscott aldrich syndrome lad cgd fel/hlh cvid/cid * subject's donor subject does not have a 6/6 or 5/6 antigen matched related bone marrow donor. suitably matched cord blood unit with adequate cell dose is available. unit must be in a dual compartment bag. performance status and organ function * \<55 years of age at time of enrollment. * lansky score between 60% and 100%, or a karnofsky score between 50% and 100% * adequate function of other organ systems * creatinine \ 50 cc/min/m2 * hepatic transaminases (alt/ast) \< 4 x normal, bilirubin \< 2.0 mg/dl * normal cardiac function by echocardiogram or radionuclide scan * pulmonary function tests demonstrating fvc, cvc, and fev1 of \>60% of predicted for age. for adult patients dlco \> 60% of predicted. if patient cannot perform pfts, clearance by the pediatric or adult pulmonologist will be required * no uncontrolled infections at the time of cytoreduction * not pregnant or lactating (must have a current negative pregnancy test) * hiv negative * subject is not concurrently involved in any other clinical trial that affects engraftment or immune reconstitution (e.g. other hematopoietic growth factors). * subject does not have any co-morbid condition, which in the view of the principal investigators, renders the patient at too high a risk from treatment complications and regimen related morbidity/mortality.

Keywords: aldhbr umbilical cord blood transplantation hematological malignancy mds severe aplastic anemia inborn error of metabolism congenital marrow failure or congenital immunodeficiency syndrome hurler's disease tay sach's pmd hunter's syndrome krabbe mld ald all aml