Title (Pediatric) Nonmyeloablative Hematopoietic Cell Transplantation for Patients with Fanconi Anemia Using Alternative Marrow Donors: A Phase I/II Dose-Finding Study


CC 12-090

Hospital Main Campus

Stage N/A

Phase Phase 1, Phase 2

Disease Blood & Marrow Transplant (BMT), Fanconi Anemia

Drug Cyclophosphamide , Cyclosporine , Fludarabine, Mesna, Mycophenolate Mofetil



A. Primary Objectives

  • Identify doses of total body irradiation (TBI) that lead to sufficient probability of donor engraftment (>5% donor CD3 chimerism) by day +200.
  • Evaluate the probability of severe acute graft-versus-host disease.

B. Secondary Objectives

  • Evaluate the probabilities of overall survival, regimen-related toxicity (RRT), and recurrent hematopoietic malignancy in those patients with a prior underlying history of such.
  • Examine the degree to which mixed chimerism provides for amelioration of symptoms (ie, infections due to neutropenia, hemorrhage due to thrombocytopenia) associated with bone marrow failure
  • Determine if the FA complementation group and % initial mosaicism predict engraftment and RRT outcomes
Inclusion Criteria

Inclusion Criteria

Patients must meet one of the following criteria (1-4) and 5 to be eligible for this study:

  • Any patient with FA and BM failure involving 2 of the following 3 lineages: granulocyte count <0.5 x 10^9/L, platelet count <20 x 10^9/L, or hemoglobin <8 g/dL.
  • Any patient with FA who requires red blood cell or platelet transfusions because of marrow failure
  • Any patient with FA who has a life-threatening BM failure involving a single hematopoietic lineage.
  • Any patient with FA and pre-existing cytogenetic abnormality including hematopoietic malignancy (AML or MDS) in morphological remission (defined as absence of circulating blasts and bone marrow blasts <5% as assessed by morphology). Note that hematopoietic recovery is not required for remission status.
  • Patients must have a negative cytotoxic crossmatch with donor.
Exclusion Criteria

Exclusion Criteria

  • Patients having available HLA-matched related donors.
  • Significant organ dysfunction that would prevent compliance with conditioning, GVHD prophylaxis, or would severely limit the probability of survival, such as liver disease/failure (active hepatitis, moderate to severe portal fibrosis/cirrhosis confirmed by biopsy or uncorrectable hepatic synthetic dysfunction), lung disease, or cardiac disease (ejection fraction <35%, or if unable to obtain ejection fraction, shortening fraction of <26%; if shortening is <26% a cardiology consult is required with PI having final approval of eligibility).
  • HIV seropositive patients
  • Fertile females who are unwilling to use contraceptive techniques during and for the twelve months following treatment, as well as females who are pregnant or actively breast feeding
  • Fertile males who are unwilling to use contraceptive techniques during and for the twelve months following treatment
  • AML/MDS in morphological relapse, defined as having circulating blasts or bone marrow blasts ≥5% as assessed by morphology
  • Active infectious disease concerns
  • Karnofsky performance score <50 or Lansky performance score <40