Combination Chemotherapy, Bone Marrow Transplant, and Post Transplant Cyclophosphamide for Hematologic Cancer

RATIONALE: Giving chemotherapy before a donor bone marrow transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclophosphamide, mycophenolate mofetil, or tacrolimus after transplant may stop this from happening.

PURPOSE: This clinical trial is studying how well giving combination chemotherapy together with tacrolimus and mycophenolate mofetil works in treating patients who are undergoing a donor bone marrow transplant for hematologic cancer.

OBJECTIVES:

Primary

* Determine the optimal dose of post-transplant immunosuppression comprising high-dose cyclophosphamide, tacrolimus, and mycophenolate mofetil administered after myeloablative conditioning chemotherapy comprising busulfan and cyclophosphamide followed by allogeneic bone marrow transplantation in patients with high-risk hematologic malignancies.
* Determine the incidence and severity of acute graft-versus-host disease in patients treated with this regimen.
* Determine other toxic effects of this regimen in these patients.

Secondary

* Determine immune reconstitution in patients treated with this regimen.
* Determine disease control in patients treated with this regimen.

OUTLINE: This is a pilot study. Patients are stratified according to age (≤ 19 years old vs \> 19 years old).

* Myeloablative conditioning chemotherapy: Patients receive busulfan IV or orally 4 times daily on days -7 to -4 OR days -6 to -3 and cyclophosphamide IV over 1 hour once daily on days -3 to -1 OR days -2 and -1.
* Allogeneic bone marrow transplantation: Patients undergo allogeneic bone marrow transplantation on day 0.
* Immunosuppression therapy: Patients receive high-dose cyclophosphamide IV over 1 hour on days 3 and 4.

After completion of study transplantation, patients are followed at 30 and 60 days, 6 months, 1 year, and then annually thereafter.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Diagnosis of 1 of the following hematologic malignancies:

  * Acute myeloid leukemia (AML), meeting 1 of the following criteria:

    * AML beyond first complete remission (CR1)
    * Refractory AML
    * AML arising from myelodysplastic syndromes (MDS)
    * Secondary AML
  * MDS

    * Refractory anemia with excess blasts with \> 10% blasts in bone marrow
  * Acute lymphoblastic leukemia (ALL), meeting 1 of the following criteria:

    * ALL in CR1 with 1 of the following high-risk features:

      * Philadelphia chromosome (Ph)-positive disease
      * Less than 1 year of age at diagnosis
      * Cytogenetic abnormalities involving chromosome 11q23
    * ALL beyond CR1
    * Refractory ALL
  * Chronic myeloid leukemia beyond first chronic phase
  * Chronic myelomonocytic leukemia
  * Chronic lymphocytic leukemia

    * Stage III-IV disease
    * Does not meet criteria for other bone marrow transplantation (BMT) studies
  * Myeloproliferative disorders

    * Ph-negative disease
  * Hodgkin's or non-Hodgkin's lymphoma

    * Chemotherapy-resistant disease
  * Paroxysmal nocturnal hemoglobinuria with life-threatening thrombosis
  * Multiple myeloma

    * Stage II or III disease
* Very high-risk disease

  * Having an unrelated donor is considered a high-risk condition
* Meets medical criteria for myeloablative BMT for the Sidney Kimmel Comprehensive Cancer Center
* Bone marrow donor available, meeting 1 of the following criteria:

  * Genotypically HLA-identical sibling
  * Phenotypically matched first-degree relative
  * Unrelated donor molecularly matched at HLA-A, -B, -C, -DRB1, and -DQB1

PATIENT CHARACTERISTICS:

Age

* 6 months to 65 years

Performance status

* Not specified

Life expectancy

* Not specified

Hematopoietic

* See Disease Characteristics

Hepatic

* Not specified

Renal

* Not specified

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* See Disease Characteristics

Endocrine therapy

* No concurrent dexamethasone as an antiemetic during immunosuppression therapy

Radiotherapy

* Not specified

Surgery

* Not specified

Other

* No concurrent immunosuppressants until ≥ 24 hours after the completion of cyclophosphamide (post-transplantation)