A Study of the Effect of Blood Stem Cell Transplant After Chemotherapy Alone in Patients With Fanconi Anemia
Fanconi Anemia, Myelodysplastic Syndrome (MDS), Acute Myelogenous Leukemia (AML)
About this trial
This is an interventional treatment trial for Fanconi Anemia focused on measuring Blood Stem Cell Transplant, busulfan, cyclophosphamide, fludarabine, 17-498
Eligibility Criteria
Inclusion Criteria:
- Patients must have a diagnosis of Fanconi anemia (confirmed by mitomycin C or diepoxybutane [DEB] chromosomal breakage testing at a CLIA approved laboratory).
Patients must have one of the following hematologic diagnoses:
1. Severe Aplastic Anemia (SAA), with bone marrow cellularity of <25% OR Severe Isolated Single lineage Cytopenia
AND at least one of the following features:
- Platelet count <20 x 10^9/L or platelet transfusion dependence*
- ANC <1000 x 10^9/L
- Hgb <8 gm/dl or red cell transfusion dependence*
2. Myelodysplastic Syndrome (MDS) (Appendix 1: MDS Classification)
MDS at any stage, based on either one of the following classifications:
- WHO Classification
- Refractory anemia and transfusion dependence*
- Any of other stages
- IPSS Classification
- Low risk (score 0) and transfusion dependence*
Any other risk groups Score > 0.5 Note that patients with chromosome 1q cytogenetic abnormalities in the absence of morphologic dysplasia will not be considered to have MDS.
3. Acute Myelogenous Leukemia Patients with acute leukemia are included in this trial untreated, in remission or with refractory or relapsed disease.
* Transfusion dependence will be defined as greater than ONE transfusion of platelets or red blood cells in the last year prior to evaluation on protocol.
Donor
Donor choices will be determined by the investigators according to institutional criteria. Patients who will be enrolled on this protocol must have one of the following donor choices:
HLA-compatible unrelated volunteer donors Patients who do not have a related HLA-matched donor but have an unrelated donor who is either matched at all A, B, C and DRB1 (8/8) loci or who is mismatched at no more than 2/8 loci (A, B, C or DRB1) (6/8) as tested by DNA analysis (high resolution), will be eligible for entry on this protocol.
HLA-mismatched Related donors Patients who do not have a related or unrelated HLA-compatible donor must have a healthy family member who is at least HLA-haplotype identical to the recipient. First degree related donors must have a normal DEB test.
The donor must be healthy and willing and able to receive a 4-6 day course of G-CSF and undergo 1-3 daily leukaphereses, as per institutional guidelines.
Related and unrelated donors must be medically evaluated and fulfill the criteria for collection of PBSCs as per institutional guidelines.
Patients and donors may be of either gender or any ethnic background. Patients must have a Karnofsky adult, or Lansky pediatric performance scale status ≥ 70%.
Patients must have adequate physical function measured by :
- Cardiac: asymptomatic or if symptomatic then 1) LVEF at rest must be ≥ 50% and must improve with exercise or 2) Shortening Fraction ≥ 29%
- Hepatic: < 5 x ULN alanine transaminase (ALT) and < 2.0 mg/dl total serum bilirubin.
- Renal: serum creatinine ≤1.5 mg/dl or if serum creatinine is outside the normal range, then CrCl > 50 ml/min/1.73 m^2
- Pulmonary: asymptomatic or if symptomatic, DLCO > 50% of predicted (corrected for hemoglobin) Each patient must be willing to participate as a research subject and must sign an informed consent form. Parent or legal guardians of patients who are minors will sign the informed consent form. Assents will be obtained as per institutional guidelines.
Female patients and donors must not be pregnant or breastfeeding at the time of signing consent. Women must be willing to undergo a pregnancy test prior to transplant and avoid becoming pregnant while on study. Positive pregnancy test results will be reported to the parent(s) or guardian of minor participants, as required per institutional guidelines.
Exclusion Criteria:
Active CNS leukemia Female patients who are pregnant (positive serum or urine HCG) or breast-feeding. Women of childbearing age must avoid becoming pregnant while on study.
Active uncontrolled viral, bacterial or fungal infection Patient seropositive for HIV-I/II; HTLV -I/II
Sites / Locations
- Memorial Sloan Kettering Cancer Center
- Cincinnati Children's Hospital Medical Center
- Fred Hutchinson Cancer Research Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Good Risk Patients
Intermediate risk patients
High risk patients
Patients 18 years old or younger with marrow aplasia or single lineage cytopenias (Arm A) will be conditioned for transplantation with intravenous busulfan (busulfex®) (0.6-0.8 mg/Kg/dose q 12 hours x 4 doses), cyclophosphamide (10 mg/Kg/dose x 4 doses) and fludarabine (35mg/m2/day x 4 doses).
Patients 18 years old or younger with MDS or AML will be will be conditioned for transplantation with intravenous busulfan (busulfex®) (0.8-1.0mg/Kg/dose q 12 hours x 4 doses), cyclophosphamide (10 mg/Kg/dose x 4 doses) and fludarabine (35mg/m2/day x 4 doses).
Patients 19 years old or older with marrow aplasia or MDS or AML will be will be conditioned for transplantation with intravenous busulfan (busulfex®) (0.4mg/Kg/dose q 12 hours x 4 doses), cyclophosphamide (10 mg/Kg/dose x 4 doses) and fludarabine (35mg/m2/day x 4 doses).