Patient case: 13-year-old male with acute myeloid leukemia; genetic feature: FLT3

Clinical trial: Combined Cord Blood Transplant

Summary: 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.

Detailed 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 g 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

Relevance to patient case: not relevant