Fludarabine and Cyclophosphamide in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Chronic Lymphocytic Leukemia or Waldenstrom's Macroglobulinemia

RATIONALE: Giving chemotherapy before a donor bone marrow transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. Also, monoclonal antibodies, such as alemtuzumab, can find cancer cells and either kill them or deliver cancer-killing substances to them without harming normal 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 methotrexate, cyclosporine and mycophenolate mofetil after the transplant may stop this from happening. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them (called graft-versus-tumor effect). Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) may boost this effect. PURPOSE: This phase I/II trial is studying the side effects of giving fludarabine together with cyclophosphamide and to see how well they work in treating patients who are undergoing donor stem cell transplant for B-cell chronic lymphocytic leukemia or Waldenström's macroglobulinemia.

Sex

All

Minimum age

18 Years

Maximum age

65 Years

DISEASE CHARACTERISTICS:

* Diagnosis of B-cell chronic lymphocytic leukemia or lymphoplasmocytic lymphoma (Waldenstrom's macroglobulinemia)

  * Must have poor prognostic features and low probability of successful autografting, defined by one of the following criteria:

    * Progressive disease with unfavorable cytogenetics (deletion or mutation of critical regions on chromosomes 11q and/or 17p \[p53\]; and/or unmutated status of the immunoglobulin V\_H gene region; and/or usage of the V\_H 3-21 gene), defined as 1 of the following:

      * Doubling of lymphocyte count or nodal involvement within 3 months or less
      * Progressive decline of platelet count and/or hemoglobin values defining Binet stage C disease (or to 50% or less of baseline values within 3 months) not due to immune mechanisms
      * Symptomatic splenomegaly
      * Discomfort or imminent complications due to large tumor masses
      * B symptoms
    * Refractory disease or early relapse (within 12 months) after treatment with a fludarabine-containing regimen
    * Relapsed after autologous stem cell transplant (SCT)
    * Insufficient stem cell harvest for intended autologous SCT
* Presence of a clonal CDR III rearrangement detected by polymerase chain reaction
* No Richter's syndrome
* HLA-identical sibling or unrelated donor available

PATIENT CHARACTERISTICS:

* ECOG performance status ≤ 1
* Creatinine clearance \> 60 mL/min
* SGOT, SGPT, and bilirubin \< 2 times normal
* Normal cardiac function determined by ECG and echocardiographic examination
* Inspiratory vital capacity, FEV\_1, and DLCO \> 50% of predicted
* No serious localized or systemic infections
* No other concurrent malignant disease
* No impaired organ function
* No uncontrolled diabetes
* No uncontrolled hypertension
* Not pregnant or nursing
* Fertile patients must use effective contraception
* No HIV infection
* No hepatitis B or C infection
* No concurrent alcohol or drug abuse
* No dementia or altered mental status that would preclude giving informed consent

PRIOR CONCURRENT THERAPY:

* Not specified

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• RESULTKramer I, Stilgenbauer S, Dietrich S, Bottcher S, Zeis M, Stadler M, Bittenbring J, Uharek L, Scheid C, Hegenbart U, Ho A, Hallek M, Kneba M, Schmitz N, Dohner H, Dreger P. Allogeneic hematopoietic cell transplantation for high-risk CLL: 10-year follow-up of the GCLLSG CLL3X trial. Blood. 2017 Sep 21;130(12):1477-1480. doi: 10.1182/blood-2017-04-775841. Epub 2017 Jul 17. No abstract available.