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Phase 2
60 Years
Not Enrolling
Leukemia, Myelodysplastic Syndromes

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Trial Information


OBJECTIVES: I. Determine overall and leukemia-free survival of patients with acute
nonlymphocytic leukemia or myelodysplastic syndrome treated with busulfan and
cyclophosphamide (low-risk patients) or cytarabine, busulfan, and cyclophosphamide
(high-risk patients) followed by allogeneic or syngeneic bone marrow transplantation. II.
Compare the therapeutic effects of these cytoreduction regimens with those reported in the
literature for similar patients who undergo syngeneic or allogeneic marrow transplantation
following cytoreduction that includes total-body irradiation. III. Determine the early and
late toxic effects produced by these chemotherapy regimens in this patient population.

OUTLINE: Low-risk patients (those in first complete remission (CR) who achieved CR with 1
course of chemotherapy) are treated on Regimen A. High-risk patients (those in second or
subsequent CR who required more than 1 course of chemotherapy to achieve first CR or those
with myelodysplastic syndrome) are treated on Regimen B. All patients undergo diagnostic
lumbar puncture prior to beginning therapy and fluid is examined for CNS disease. Patients
receive methotrexate IT along with the tap. Prior to initiation of chemotherapy, patients
with CNS disease present on diagnostic lumbar puncture receive methotrexate IT every 2-3
days until lumbar puncture shows no leukemia cells and then 1 additional dose. Cytoreductive
chemotherapy begins 3 days after the last dose of methotrexate. Regimen A: Patients receive
oral busulfan every 6 hours on days -7 to -4 for a total of 16 doses and cyclophosphamide IV
over 2 hours on days -3 and -2. Allogeneic bone marrow is infused on day 0. Regimen B:
Patients receive oral busulfan every 6 hours on days -9 to -6 for a total of 16 doses.
Patients receive cytarabine IV over 1 hour every 12 hours on days -5 and -4 and
cyclophosphamide IV over 2 hours on days -3 and -2. Allogeneic bone marrow is infused on day
0. Graft versus host disease prophylaxis: Patients receive cyclosporine IV continuously on
days -1 to 28 followed by a taper of oral cyclosporine until day 180. Patients receive
methotrexate IV on days 1, 3, 6, and 11. CNS disease prophylaxis: Patients receive 5 more
doses of methotrexate IT weekly beginning between days 50 and 70. In addition, patients with
history of CNS disease receive 1 dose of methotrexate IT monthly for 1 year. Patients are
followed frequently during the first 100 days, at 6 months, 1 year, and then annually

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 2.7 years.

Inclusion Criteria

DISEASE CHARACTERISTICS: The following hematologic malignancies are eligible: Acute
nonlymphocytic leukemia in one of the following categories: In complete remission In early
relapse Newly diagnosed FAB types M6 and M7 Myelodysplastic syndromes including:
Refractory anemia with excessive blasts Refractory anemia with excessive blasts in
transformation Chronic myelomonocytic leukemia Secondary acute myeloid leukemia
Transplantation priority given in decreasing order of: First remission Second remission
Third remission Early relapse, with priority further reduced for: Refractory response to
platelet transfusion Severe infection within 6 weeks prior to referral History of major
organ pathology or insult (hepatitis, renal damage, pulmonary disease, cystitis, etc.) CNS
disease allowed but priority status for transplantation lowered Donor Criteria: Sibling or
matched related/unrelated donor required Donor priority as follows: Monozygotic twin
Genotypical or phenotypical HLA-A, -B, -C, and -D match Match at any 2 loci (A, B, Dr) on
the other haplotype ABO-compatible donor preferred Marrow processed to eliminate
mismatched erythrocytes if ABO incompatible In case of multiple donors, priority is: ABO
compatibility Age over 18 Same sex No physiologic, psychologic, or medical
contraindication to donation procedure No increased anesthetic risk due to pre-existing
illness HIV negative

PATIENT CHARACTERISTICS: Age: 6 months to 60 years Performance status: No preterminal or
moribund patients Life expectancy: No severe limits on life expectancy due to diseases
other than leukemia Hematopoietic: See Disease Characteristics Hepatic: Bilirubin no
greater than 2.0 mg/dL Transaminases no greater than 3 times normal No severe hepatic
disease Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance at least 60
mL/min No severe renal disease No history of severe cystitis with cyclophosphamide
Cardiovascular: LVEF at least 50% No symptomatic cardiac disease Pulmonary: FEV1 and FVC
at least 75% of normal No severe pulmonary disease Other: HIV negative No severe
personality disorder or severe mental illness No condition (such as substance abuse) that
would markedly increase the morbidity and mortality of transplantation Criteria of
hepatic, renal, cardiac, and pulmonary function and mental illness are used only for
initial screening of potential candidates; patients who do not meet these criteria may
still be eligible at the discretion of the transplant team

PRIOR CONCURRENT THERAPY: See Disease Characteristics

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Esteban Abella, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Barbara Ann Karmanos Cancer Institute


United States: Federal Government

Study ID:




Start Date:

August 1987

Completion Date:

October 2003

Related Keywords:

  • Leukemia
  • Myelodysplastic Syndromes
  • recurrent childhood acute myeloid leukemia
  • recurrent adult acute myeloid leukemia
  • untreated adult acute myeloid leukemia
  • untreated childhood acute myeloid leukemia and other myeloid malignancies
  • adult acute myeloid leukemia in remission
  • childhood acute myeloid leukemia in remission
  • adult acute erythroid leukemia (M6)
  • adult acute myeloblastic leukemia without maturation (M1)
  • adult acute myeloblastic leukemia with maturation (M2)
  • adult acute promyelocytic leukemia (M3)
  • adult acute myelomonocytic leukemia (M4)
  • adult acute monoblastic leukemia (M5a)
  • adult acute megakaryoblastic leukemia (M7)
  • childhood acute myeloblastic leukemia without maturation (M1)
  • childhood acute myeloblastic leukemia with maturation (M2)
  • childhood acute promyelocytic leukemia (M3)
  • childhood acute myelomonocytic leukemia (M4)
  • childhood acute monoblastic leukemia (M5a)
  • childhood acute monocytic leukemia (M5b)
  • childhood acute erythroleukemia (M6)
  • childhood acute megakaryocytic leukemia (M7)
  • refractory anemia with excess blasts
  • refractory anemia with excess blasts in transformation
  • chronic myelomonocytic leukemia
  • secondary acute myeloid leukemia
  • adult acute monocytic leukemia (M5b)
  • previously treated myelodysplastic syndromes
  • childhood myelodysplastic syndromes
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia



Barbara Ann Karmanos Cancer InstituteDetroit, Michigan  48201