Umbilical Cord Blood Stem Cell Transplant in Treating Patients With Hematologic Cancer or Other Disease

OBJECTIVES:

Primary

- Determine the efficacy of double umbilical cord blood stem cell transplantation using a
conditioning regimen comprising lower doses of busulfan and fludarabine phosphate and
low-dose total body irradiation, in terms of stem cell engraftment at 60 days post
transplantation, in patients with hematologic cancer or other diseases.

- Determine the merits of conducting a larger, comparative study of this regimen.

Secondary

- Determine mortality within 100 days of transplantation in these patients.

OUTLINE: This is a pilot study.

- Reduced-intensity conditioning regimen: Patients receive busulfan IV over 3 hours on
days -9 to -8 and fludarabine phosphate IV on days -7 to -3. Patients then undergo
low-dose total body irradiation on day 0.

- Graft-versus-host disease prophylaxis: Patients receive tacrolimus IV twice daily and
mycophenolate orally or IV three times daily beginning on day -3.

- CNS prophylaxis and/or treatment: Patients with a history of CNS involvement receive
prophylactic cytarabine (Ara-C) intrathecally (IT) prior to transplant. Patients also
undergo lumbar puncture (LP) to test for active CNS disease. Patients with
cerebrospinal fluid positive for leukemia receive Ara-C IT every 2-3 days until a
repeat LP shows no remaining leukemic cells. Three days after the last LP and after one
final dose of Ara-C, patients begin the conditioning regimen.

- Double umbilical cord blood (UCB) donor stem cell transplantation (SCT): Patients
undergo double UCB donor SCT on day 0.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

- Histologically confirmed diagnosis of 1 of the following:

- Acute myeloid leukemia meeting the following criteria:

- M0-M7 histologic subtypes by French-American-British classification

- Previously treated disease

- Meets 1 of the following criteria:

- Persistent disease as evidenced by 5-30% persistent blasts in bone
marrow after induction or salvage therapy

- In second or subsequent complete remission (CR)

- In first CR with 1 of the following high-risk features:

- Philadelphia chromosome present

- Noncore-binding factor type of chromosomal abnormalities

- Myelodysplastic syndromes with 1 of the following International Prognostic
Scoring System (IPSS) scores:

- Intermediate-1

- Intermediate-2

- High-risk score with transfusion dependence

- Chronic myelogenous leukemia meeting 1 of the following criteria:

- In accelerated or blastic phase

- Failed prior imatinib mesylate therapy

- Acute lymphoblastic leukemia meeting 1 of the following criteria:

- In first CR with any of the following high-risk features:

- Philadelphia chromosome present

- Translocation t(4;11) present

- WBC > 30,000/mm³ (adult patients)

- More than 4 weeks from initiation of treatment was required to achieve
CR (adult patients)

- DNA index of near haploid (N=23 chromosomes) (pediatric patients)

- In second or subsequent CR

- Persistent disease as evidenced by 5-20% persistent blasts in bone marrow
after induction or salvage therapy

- Hodgkin's or non-Hodgkin's lymphoma meeting the following criteria:

- Recurrent or refractory disease

- Tumor ≤ 5 cm in diameter

- Myeloma or plasma cell neoplasm meeting 1 of the following staging criteria:

- Stage III at presentation

- Stage I-II at presentation

- Not responding OR progressed after first-line therapy

- Chronic lymphocytic leukemia or Waldenstrom's macroglobulinemia with refractory
or progressive disease after first-line therapy

- No 5-6/6 HLA-matched related or 7-8/8 HLA-matched unrelated marrow or peripheral
blood stem cell donor available

- No single 4-6/6 HLA-A, -B, or -DRB1-matched umbilical cord blood unit ≥ 3.5 x 10^7
nucleated cells/kg available

PATIENT CHARACTERISTICS:

- ECOG performance status (PS) 0-2 OR Karnofsky or Lansky PS 70-100%

- Not pregnant

- Fertile patients must use effective contraception prior to and during study
participation

- HIV negative

- Bilirubin < 3.0 mg/dL

- AST and ALT ≤ 3 times upper limit of normal

- Creatinine < 2.0 mg/dL OR creatinine clearance > 50 mL/min

- Cardiac ejection fraction > 50% by echocardiogram OR shortening fraction > 27%

- No uncontrolled symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

- FEV_1 > 50% of normal

- Forced vital capacity > 50% of normal

- DLCO normal

- Oxygen saturation > 92% on room air (for patients < 5 years of age)

- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to busulfan and fludarabine phosphate

- No ongoing or active infection

- No psychiatric illness or social situation that would preclude study compliance

- No other uncontrolled illness

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- At least 4 weeks since prior and no concurrent surgery

- At least 4 weeks since prior and no other concurrent investigational or commercial
agents or therapies for the malignancy, including chemotherapy, biologic therapy, or
radiotherapy