Fludarabine Based RIC for Bone Marrow Failure Syndromes

  • End date
    Dec 26, 2023
  • participants needed
  • sponsor
    Children's Hospital of Philadelphia
Updated on 26 May 2022


This is a pilot study to determine whether fludarabine-based reduced intensity conditioning (RIC) regimens facilitate successful donor engraftment of patients with acquired aplastic anemia (AA) and Inherited bone marrow failure (iBMF) syndromes undergoing Matched related donor bone marrow transplant (MRD-BMT).


Acquired AA patients will receive the experimental regimen of fludarabine with dose-reduced cyclophosphamide, with results in this prospective single arm experimental group evaluated in the context of our institutional historical experience using HD Cy regimens as well as published outcomes using both fludarabine and high-dose cyclophosphamide-based regimens for MRD-BMT in aplastic anemia. iBMF syndrome patients will receive one of two fludarabine-containing regimens based on disease characteristics, and our outcomes will be compared to previously published data using a variety of regimens. Graft versus host disease (GvHD) prophylaxis will consist of cyclosporine/tacrolimus alone for patients with acquired AA or cyclosporine/tacrolimus plus mycophenolate for patients with iBMF syndromes. For both acquired AA and iBMF syndrome patients, donor chimerism will be assessed at scheduled intervals following BMT and will be used to define patients with full donor or mixed chimerism for comparisons of survival, graft failure, cytogenetic, GvHD, and immune reconstitution outcomes.

Condition Bone Marrow Failure Syndromes
Treatment MRD-BMT with Fludarabine-based RIC for Acquired AA, MRD-BMT with Fludarabine-based RIC for iBMF with trilineage aplasia, MRD-BMT with Fludarabine-based RIC for iBMF without trilineage aplasia
Clinical Study IdentifierNCT02928991
SponsorChildren's Hospital of Philadelphia
Last Modified on26 May 2022


Yes No Not Sure

Inclusion Criteria

Ages 0-22 years at time of enrollment
Patients with severe or very severe acquired AA, defined by
Bone marrow biopsy demonstrating cellularity of <25% (at least 2 weeks from last dose of G-CSF), in addition to 2 of the following: absolute neutrophil count (ANC) <500/µL, platelets < 20,000/µL and absolute reticulocytes <40,000/µL
Negative evaluation for inherited bone marrow failure conditions and negative evaluation for dysplasia or cytogenetic abnormalities associated with myelodysplastic syndromes
Patients with concurrent paroxysmal nocturnal hemoglobinuria (PNH) clones are eligible, as long as they meet criteria for severe or very severe aplastic anemia as defined above
Patients with clinically diagnosed and/or genetically proven iBMF syndromes
resulting in chronic red blood cell or platelet-transfusion dependence and/or
Fanconi Anemia
an absolute neutrophil count <500/µL. These disorders include, but are not
Dyskeratosis Congenita
Severe Congenital Neutropenia
Diamond-Blackfan Anemia
Congenital Dyserythropoietic/Sideroblastic Anemias
Congenital Amegakaryocytic Thrombocytopenia
Organ Function
Serum creatinine <1.5xupper limit of normal for age Hepatic: Transaminases <5x normal
Shwachman-Diamond Syndrome
Cardiac shortening fraction >27%
Lansky or Karnofsky performance >60
Bilirubin <2.5x normal (unless elevation due to Gilberts disease)
Donor Selection Criteria
HLA matched related donor available
Donor selection will comply with U.S. Food and Drug Administration's Code of Federal Regulations
No active untreated infection
Females of childbearing potential must have negative pregnancy test
Fully HLA-matched related donor
Donor must be at least 6 months of age
Donor suitable for bone marrow collection and meets eligibility for donation, including fulfilling infectious disease criteria as per SOP, including HIV, Hepatitis B, Hepatitis C Polymerase chain reaction (PCR) negative
If subject has confirmed iBMF syndrome, donor must be evaluated for this disorder and testing must be negative
Children's Hospital of Philadelphia (CHOP) bone marrow transplant (BMT) procedures apply for determining donor eligibility, including donor screening and testing for relevant communicable disease agents and diseases
Donor evaluation and collection procedure as per CHOP Standard Operating Procedures (SOP)

Exclusion Criteria

Uncontrolled bacterial, viral or fungal infections
HLA matched related donor unable to donate bone marrow
No eligible fully HLA-matched related donor
Pregnant females
Patients with a clinical diagnosis of Myelodysplastic syndrome (MDS) defined by combination of bone marrow dysplasia and classic cytogenetic lesion (Monosomy 7, Trisomy 8 eg.), with or without excess blasts
Patients with PNH without underlying bone marrow aplasia
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