Reduced-intensity, Related-donor Bone Marrow Transplantation Followed by High-dose Cyclophosphamide for Hematologic Cancers

This research is being done to learn more about reduced-intensity bone marrow transplantation (BMT), also known as a "mini" transplant for patients with blood cancers, using bone marrow from a relative.

The main goal of the study is to determine how quickly the donor's bone marrow "takes" in your body. Other goals include describing how many people accept the bone marrow and how quickly the blood counts come up; describing Graft-versus-host disease (GVHD) and other complications; and describing how many people survive without progressive cancer and survive overall

At the present time there are few or no cures for people with cancer of the blood or lymph glands outside of a bone marrow transplant (BMT). BMT has developed over several decades of research as an effective treatment of various malignant and nonmalignant hematologic diseases.

This research is being done to learn more about reduced-intensity bone marrow transplantation (BMT), also known as a "mini" transplant for patients with blood cancers, using bone marrow from a relative. The bone marrow for this transplant comes from a relative who is a half-match or "haplo" match to you. Possible donors include parents, siblings, and children.

"Mini" transplants have been given to many people with various cancers but are considered experimental. Over 200 people at Johns Hopkins have received mini transplants with high doses of cyclophosphamide after the transplant. However, the chemotherapy combination and other treatment given before those transplants were different from what is in this study. Although all of the chemotherapy and immune-lowering drugs used in this study are approved by the Food and Drug Administration (FDA), the combination of medications used in this study are not FDA approved and are experimental.

Eligibility Criteria:
Inclusion Criteria:

* First-degree related donor who is at minimum HLA haploidentical
* Eligible diagnoses:

  1. Low-grade non-Hodgkin's lymphoma or plasma cell neoplasm that has progressed during multiagent therapy, failed at least two prior therapies (excluding single agent rituximab and single agent steroids), or in the case of lymphoma undergone histological conversion:

     * Follicular grade 1 or 2 lymphoma
     * Follicular lymphoma not otherwise specified
     * Marginal zone (or MALT) lymphoma
     * Lymphoplasmacytic lymphoma / Waldenstrom's macroglobulinemia
     * Hairy cell leukemia
     * Small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL)
     * Prolymphocytic leukemia
     * Low grade B-cell lymphoma, unspecified
     * Multiple myeloma
     * Plasma cell leukemia
  2. Poor-risk SLL or CLL, defined by an 11q or 17p deletion, histological conversion, or disease progression \< 6 months after a purine analog-containing regimen
  3. Aggressive lymphoma that has failed at least one prior regimen of multiagent chemotherapy, and patient is either ineligible for autologous BMT or autologous BMT is not recommended:

     * Hodgkin lymphoma
     * Follicular grade 3 lymphoma
     * Mantle cell lymphoma or leukemia
     * Diffuse large B-cell lymphoma (excluding primary CNS lymphoma). Eligible subtypes include primary mediastinal large B-cell lymphoma, T-cell rich large B-cell lymphoma, and large B-cell lymphoma not otherwise specified.
     * Burkitt's lymphoma/leukemia
     * Atypical Burkitt's lymphoma/leukemia (high grade B-cell lymphoma, unclassified, including that with features intermediate between Burkitt's and diffuse large B-cell lymphoma)
     * Anaplastic large cell lymphoma
     * Plasmablastic lymphoma
     * Peripheral T-cell lymphoma
  4. Relapsed or refractory acute leukemia in second or subsequent remission
  5. Poor-risk acute leukemia in first remission
  6. AML with at least one of the following:

     * AML arising from MDS or a myeloproliferative disorder, or secondary AML
     * Presence of Flt3 internal tandem duplications
     * Poor-risk cytogenetics
     * Primary refractory disease

       * ALL (leukemia and/or lymphoma) with at least one of the following:
     * Adverse cytogenetics
     * Clear evidence of hypodiploidy
     * Primary refractory disease

       * Biphenotypic leukemia
       * MDS with at least one of the following features:
       * Poor-risk cytogenetics
       * IPSS score of INT-2 or greater
       * Treatment-related MDS
       * MDS diagnosed before age 21 years
       * Progression on or lack of response to standard DNA-methyltransferase inhibitor therapy
       * Life-threatening cytopenias, including those generally requiring greater than weekly transfusions
  7. Interferon- or imatinib-refractory CML in first chronic phase, or non-blast crisis CML beyond first chronic phase
  8. Philadelphia chromosome negative myeloproliferative disease (including myelofibrosis)
  9. Chronic myelomonocytic leukemia
  10. Juvenile myelomonocytic leukemia

      * For patients with SLL, CLL, or prolymphocytic leukemia, \< 20% of bone marrow cellularity involved by this process
      * Adequate end-organ function:
* Left ventricular ejection fraction greater than or equal to 35%
* Bilirubin ≤ 3.0 mg/dL (unless due to Gilbert's syndrome or hemolysis), and ALT and AST \< 5 x ULN
* FEV1 and FVC \> 40% of predicted; or in pediatric patients, if unable to perform pulmonary function tests due to young age, oxygen saturation \>92% on room air

  * ECOG performance status \< 2 or Karnofsky or Lansky score \> 60

Exclusion Criteria:

* Pregnant or breast-feeding
* Uncontrolled infection Note: Infection is permitted if there is evidence of response to medication. Eligibility of HIV infected patients will be determined on a case-by-case basis.
* Any previous BMT within 3 months prior to start of conditioning
* Active extra-medullary leukemia or known active Central Nervous System (CNS) involvement by malignancy. Such disease treated into remission is permitted.