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Purine Analog-Based Conditioning for Allogeneic Stem Cell Transplantation in Patients With Severe Aplastic Anemia

70 Years
Not Enrolling
Aplastic Anemia

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Trial Information

Purine Analog-Based Conditioning for Allogeneic Stem Cell Transplantation in Patients With Severe Aplastic Anemia

Before treatment starts, patients will have their bone marrow checked and will have lung,
heart, and kidney tests.

Patients in this study will receive the drugs fludarabine, cyclophosphamide, and
antithymocyte globulin by vein through a previously inserted plastic catheter that extends
into the large chest vein. Fludarabine will be given daily for four days, cyclophosphamide
will given daily for four days, and antithymocyte globulin will be given daily for four days
(three days for related donor transplants).

Two days after the last dose of cyclophosphamide, donor marrow or stem cells will be infused
through a catheter (thin plastic tube). Drugs will be given to lower the chance of an
allergic reaction to the stem cells. Patients will also get shots of filgrastim (a drug
that helps white blood cell growth) and antibiotics by mouth. The blood cell counts will
fall to low levels during the first 2 weeks when patients may need transfusions of red blood
cells and platelets. The chemotherapy will be given in the hospital. After the infusion of
stem cells, patients will be monitored in the hospital. They will later be closely followed
as outpatients and will be required to remain in the Houston area for about three months
after the transplant.

Drugs (cyclosporine and methotrexate) to lower the chance of graft-versus-host disease will
be given. Cyclosporine will be given as a continuous infusion starting 2 days before
transplantation. Methotrexate will be given through the catheter on Days 1, 3, 6 and 11
after transplantation. Cyclosporine will be given as pills when the patient is able to
swallow. Cyclosporine will be continued for no less than 6 months after transplantation
after which it will be gradually stopped. The drug tacrolimus may be used instead of

Blood, urine, bone marrow, and x-ray exams will be done as needed to monitor the results of
bone marrow transplantation. Patients may require blood and platelet transfusions. Blood
tests will be done daily while hospitalized and several times a week until the blood counts
recover. Bone marrow aspiration and biopsies will be performed before the transplant, when
the donated cells show signs of engraftment, and at other times during the next 1 to 3
years. They will be done to evaluate the growth of the transplant marrow, possible
recurrence of malignancy, and recovery of immunity. If this treatment proves unsuccessful
in more than three of the first ten patients, the study will be stopped.

This is an investigational study. The FDA has approved all of the drugs in this study for
other indications. Up to 30 patients will be treated on this study. All will be enrolled at
M.D. Anderson.

Inclusion Criteria:

- Patients up to 70 years of age with a diagnosis of severe AA (Camitta et al., 1979)
and a matched unrelated donor who are unresponsive to IS or who have relapsed after
an initial response to IS. Patients with a diagnosis of SAA and an human leukocyte
antigen (HLA) - compatible sibling donor are eligible only if they are 40 years of
age or older (up to age 70) and regardless whether they have received IS or not.
Patients with primary or secondary graft failure following autologous or allogeneic
stem cell transplant are eligible.

- Patients must have a serum bilirubin of 2 mg/dl or less, serum creatinine < 2.0
mg/dl, no symptomatic cardiac or pulmonary disease and a PS of no more than 2. Life
expectancy not severely limited by concomitant illness (> 12 weeks). Left ventricular
ejection fraction > 40%, no uncontrolled arrhythmia or symptomatic cardiac disease.
Forced Expiratory Volume in 1 Second (FEV1), Forced Vital Capacity (FVC) and Carbon
Monoxide Diffusing Capacity (DLCO) > 40%. No symptomatic pulmonary disease. Negative
pregnancy test.

- Patients must have an HLA-compatible related or unrelated donor willing to donate
marrow or rhG-CSF-mobilized peripheral blood stem cells. In the event of transplants
from matched unrelated donors, a high-resolution allele match for HLA-A, -B, -C,
-DRB1 and DQB1 ("10 of 10 match") is preferred. However, a one-antigen mismatch
("micromismatch") is also considered acceptable matching ("9 of 10 match").

- Patients must sign informed consent. In the event of a pediatric patient (i.e., a
minor), consent will be provided by their guardian/parent.

- Lack of clonal cytogenetic abnormalities associated with acute myeloid leukemia
(AML), myelodysplastic syndrome (MDS) or other hematologic malignancies.

Exclusion Criteria:

- Life expectancy of less than 8 weeks. Inability to provide informed consent.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Patients With Engraftment Response

Outcome Description:

Engraftment defined as (1) the first of three consecutive days of an Absolute neutrophil count (ANC) >500/mL (b) the first of seven consecutive days of an unsupported platelet count 20,000. Patient needs to survive at least 28 days to be evaluable for engraftment. Chimerism studies need to demonstrate donor-derived hematopoiesis (>90%)

Outcome Time Frame:

First 100 days post transplant.

Safety Issue:


Principal Investigator

Paolo Anderlini, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

December 2000

Completion Date:

August 2009

Related Keywords:

  • Aplastic Anemia
  • Severe Aplastic Anemia
  • Bone Marrow Failure
  • Stem Cell Transplantation
  • Fludarabine
  • Cyclophosphamide
  • Antithymocyte Globulin
  • SAA
  • ATG
  • Cytoxan
  • Neosar
  • Fludarabine Phosphate
  • Thymoglobulin
  • Anemia
  • Anemia, Aplastic



U.T.M.D. Anderson Cancer Center Houston, Texas  77030