Overview
This study is a single-center, treatment protocol with 4 possible preparative regimens, designed to validate the process of umbilical cord blood stem cell transplantation at our institution.
Description
This study is a single-center treatment protocol with four possible preparative regimens, designed to validate the process of umbilical cord blood stem cell transplantation at our institution. Enrolled patients will receive chemotherapy +/-total body radiation as a pre-transplant conditioning regimen. Patients will then receive cord blood stem cells followed by GvHD prophylaxis that will include Tacrolimus and Mycophenolate Mofetil, or Cyclosporin A and Methylprednisolone. Multiple data points will be collected prior to, during, and following transplantation to ensure safety of the process and to evaluate the stated objectives.
Eligibility
Inclusion Criteria:
- Appropriate diagnosis: Patients must have a disease or syndrome amenable to therapy
with hematopoietic stem cell transplantation. Diagnoses include, but are not limited
- to
- Congenital and Other Non-malignant Disorders:
- Immunodeficiency disorders (e.g. Severe Combined Immunodeficiency, Wiskott-Aldrich Syndrome)
- Congenital hematopoietic stem cell defects (e.g. Chediak-Higashi Syndrome, Congenital Osteopetrosis, Osteogenesis Imperfecta)
- Metabolic disorders (e.g. Hurler's Syndrome)
- Severe aplastic anemia
- High-Risk Leukemia:
- Acute Myelogenous Leukemia
- Refractory to standard induction therapy (more than 1 cycle required to achieve
remission)
- Recurrent (in CR ≥ 2)
- Treatment-related AML or MDS
- Evolved from myelodysplastic syndrome
- Presence of FLT3 abnormalities
- FAB M6 or M7
- Adverse cytogenetics
- Myelodysplastic Syndrome
- Acute Lymphoblastic Leukemia including T lymphoblastic leukemia:
- Refractory to standard induction therapy (time to CR >4 weeks)
- Recurrent (in CR ≥ 2)
- WBC count >30,000/mcL at diagnosis
- Age >30 at diagnosis
- Adverse cytogenetics, such as t(9:22), t(1:19), t(4:11), and other MLL
rearrangements.
- Chronic Myelogenous Leukemia in accelerated phase or blast crisis
- Biphenotypic or undifferentiated leukemia
- Burkitt's leukemia or lymphoma
- Lymphoma:
- Large cell, Mantle cell, Hodgkin lymphoma refractory or recurrent, chemo-sensitive, and ineligible for an autologous stem cell transplant or previously treated with autologous SCT
- Marginal zone or follicular lymphoma that is progressive after at least two prior therapies
- Multiple Myeloma, recurrent following high-dose therapy and autologous SCT or ineligible for an autologous HSCT
- Solid tumors, with efficacy of allogeneic HSCT demonstrated for the specific disease and disease status
- Adequate organ function:
- Cardiac - LVEF >45%, or shortening fraction >25%, Absence of congestive heart failure or conduction disturbances with high risk for sudden death
- Pulmonary - DLCO (corrected for hemoglobin), FEV1 and FVC ≥ 50% predicted;
- Renal - serum Cr < 1.5 times the upper limit of normal for age or GFR ≥ 50 ml/min/1.73m2
- Hepatic - total bilirubin level < 2 times the upper limit of normal (except for patients with Gilbert's syndrome or hemolysis); if the primary disease process is causal, this criterion will be reconsidered. ALT, AST, and Alkaline phosphatase ≤ 5 times upper limit of normal.
- Performance Status Karnofsky or Lansky score ≥ 70%.
- Informed Consent must be obtained prior to initiating conditioning therapy.
- Receipt of viable cord blood product(s), single or dual, must be confirmed with the stem cell processing laboratory prior to initiating conditioning therapy.
Exclusion Criteria:
- Availability of 10/10 or 9/10 HLA-matched related or unrelated donor within a reasonable timeframe dictated by the clinical urgency of the transplant
- Autologous HSCT < 6 months prior to proposed UCB transplant
- Pregnant or breast feeding
- Current uncontrolled infection
- Evidence of HIV infection or positive HIV serology