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The goal of this clinical research study is to learn what dose of a kind of immune cell called T-lymphocytes (T-cells) given as a donor infusion about 8-9 weeks after a stem cell transplant has the best results. The safety of this treatment will also be studied. This will be tested in patients with leukemia, MDS, lymphoma, Hodgkin disease, and multiple myeloma. These results are measured as helping to control the disease without severe graft-versus-host disease (GvHD). GvHD is when transplanted donor tissue attacks the tissues of the recipient's body.

Fludarabine, melphalan, and alemtuzumab are commonly given before stem cell transplants:

• Fludarabine is designed to interfere with the DNA (genetic material) of cancer cells, which may cause the cancer cells to die.
• Melphalan is designed to bind to the DNA of cells, which may cause cancer cells to die.
• Alemtuzumab is designed to weaken the immune system and reduce the risk of rejection of the transplant and graft-vs-host disease (GvHD).

The donor infusion of T-cells is designed to help restore the immune system after the transplant, cause an immune reaction against the cancer, and reduce the risk of the cancer coming back.

Study Groups:

If you agree to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups involving the dose of T-cells in the donor lymphocyte infusion.

• Group 1 will receive a low dose of donor T-cells.
• Group 2 will receive a higher dose of donor T-cells than Group 1.

Both you and your study doctor will know which group you are in. Both groups will have a stem cell transplant. The stem cells will be given by vein. The cells will travel to your bone marrow where they are designed to make healthy, new blood cells after several weeks.

Study Drug Administration:

Patients receive fludarabine, melphalan and alemtuzumab to kill malignant cells and suppress immunity to prevent rejection of the stem cell transplant. The day you receive the stem cells is called Day 0. The days before you receive your stem cells are called minus days. The days after you receive the stem cells are called plus days.

On Day -7, you will be admitted to the hospital and given fluids by vein to hydrate you.

On Days -6 through -3, you will receive fludarabine by vein over 1 hour each day.

On Day -2, you will receive melphalan by vein over 30 minutes.

On Day -1, you will receive alemtuzumab by vein over 2 hours.

On Day 0, you will receive the stem cell transplant as a cell infusion by vein.

After the transplant, you will receive tacrolimus and methotrexate. At first, you will receive tacrolimus as a continuous (nonstop) infusion until you are able to take it by mouth. You will then take tacrolimus by mouth 2 times a day for about 5 weeks and then your doctor will tell you how to taper it off (gradually stop taking it). On Days 1, 3, and 6 after the transplant, you will receive methotrexate by vein over 30 minutes.

You will receive filgrastim as an injection under the skin 1 time a day, starting 1 week after the transplant, until your blood cell levels return to normal. Filgrastim is designed to help with the growth of white blood cells.

Between Day +56 and +64, if you are in stable medical condition and have not developed GvHD, you will receive a donor lymphocyte infusion containing T-cells by vein over 10-30 minutes. You will receive Benadryl (diphenhydramine) by vein over 15 minutes before the infusion to lower the risk of an allergic reaction.

Study Visits:

Before the T-cell infusion:

• You will have a physical exam, including measurement of your vital signs (blood pressure, heart rate, temperature, and breathing rate).
• You will be asked about how you are feeling and about any side effects you may be having.
• Blood (about 2 teaspoons) will be drawn to see how well the transplant has "taken".
• You will have a bone marrow aspiration and biopsy to check the status of the disease, if your doctor thinks it is needed. To collect a bone marrow aspiration/biopsy, an area of the hip or other site is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle.

After the T-cell infusion, you will have a physical exam every week for at least 6 weeks.

About 3, 6, and 12 months after the transplant:

• You will have a physical exam, including measurement of your vital signs.
• You will be asked about how you are feeling and about any side effects you may be having.
• Blood (about 4 tablespoons) will be drawn for routine tests and to check the level of the infused T-cells, for immune function tests, and to check the status of the disease.
• You will have a bone marrow aspiration, blood tests and CT scans as medically necessary to check the status of the disease, if your doctor thinks it is needed.

During the study, you will have blood draws (about 2 teaspoons) and urine will be collected for routine tests, to check your blood counts, kidney and liver function, and/or to check for infections as often as the doctor thinks is needed during this time.

Length of Treatment:

You will be off study after your 12-month follow-up visit. You will be taken off study early if you have graft failure (the donor cells did not "take") or if the cancer comes back and needs another treatment.

This is an investigational study. Melphalan, fludarabine, and alemtuzumab are FDA approved and commercially available for the treatment of blood cancers. Donor T-cell infusions are commonly used to treat blood cancers that come back after a stem cell transplant. The investigational part of this study is to find the best dose of T-cells that are given with the goal of helping to prevent the cancer from coming back.

Up to 56 patients will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Age >/= 18 years and </= 65 years with one of the following: a. Acute leukemia past first remission, in first or subsequent relapse, in second or greater remission. Patients in first remission should have intermediate or high cytogenetic risk factors or flt3 mutation. Patients with primary induction failure or relapse are eligible if they have <10% bone marrow blasts, and no circulating blasts. b. Myelodysplastic syndrome with intermediate or high risk IPSS score, or treatment related MDS. c. CML resistant to tyrosine kinase inhibitor treatment in a first or subsequent chronic phase, or in accelerated phase. d. CLL, Lymphoma or Hodgkin's disease which has failed to achieve remission or recurred following initial chemotherapy. Patients must have at least a PR to salvage therapy, or low bulk untreated relapse (<2 cm largest mass). e. Multiple myeloma which has relapsed or progressed and has achieved a partial response to salvage chemotherapy.
2. Patients must have one of the following donor types identified and willing to donate: a. Related donor, HLA-matched for HLA-A, -B, C and DR matched or, b. Matched Unrelated Donor (MUD), HLA-matched for HLA A, B, C and DRB1 using allele level typing.
3. Performance score of at least 80% by Karnofsky or performance score 0 to 2 (ECOG).
4. Estimated creatinine clearance >40 ml/min (based on serum creatinine)
5. Bilirubin <1.5 mg/dl except for Gilbert's disease.
6. ALT < 300 IU/ml d.
7. Left ventricular ejection fraction equal or greater than 40%.
8. Pulmonary function test (PFT) demonstrating a diffusion capacity (corrected for hemoglobin) of least 50% predicted.
9. Patient or patient's legal representative able to sign informed consent.

Exclusion Criteria:

1. Patients who have had prior autologous transplants or prior allogeneic transplants are not eligible.
2. Uncontrolled active infection.
3. Positive Beta HCG test in a woman with child bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization.
4. Women of child bearing potential not willing to use an effective contraceptive measure while on study.
5. Subject has known sensitivity to any of the products that will be administered during the study.
6. Patients who are HIV seropositive.