The goal of this clinical research study is to learn if giving busulfan and fludarabine before a stem cell transplant can help control the disease better than the standard method in patients with leukemia, lymphoma, multiple myeloma, MDS, or MPD. In this study, 2 doses of busulfan will be given 2 weeks before a stem cell transplant followed by 4 doses of busulfan and fludarabine during the week before the stem cell transplant, rather than the standard method of giving 4 doses of busulfan and fludarabine only during the week before the stem cell transplant.

The safety of this combination therapy will also be studied.

Busulfan is designed to kill cancer cells by binding to DNA (the genetic material of cells), which may cause cancer cells to die. Busulfan is commonly used in stem cell transplants.

Fludarabine is designed to interfere with the DNA of cancer cells, which may cause the cancer cells to die.

Central Venous Catheter:

If you choose to take part in this study, the chemotherapy, some of the other drugs in this study, and the stem cell transplant will be given by vein through your central venous catheter (CVC). A CVC is a sterile flexible tube and needle that will be placed into a large vein while you are under local anesthesia. Blood samples will also be drawn through your CVC. The CVC will remain in your body during treatment. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form.

Study Drug Administration and Procedures:

For a stem cell transplant, the days before you receive your stem cells are called minus days. The day you receive the stem cells is called Day 0. The days after you receive the stem cells are called plus days.

You will receive a dose of busulfan by vein over about 3 hours on Day -13 and Day -12. With the Day -13 busulfan infusion, about 11 samples of blood (about 1-2 teaspoons each time) will be drawn for pharmacokinetic (PK) testing at various time points before and after you receive your first dose of busulfan. The study staff will tell you the blood testing schedule. PK testing measures the amount of study drug in the body at different time points. The PK testing will help the doctor decide your dose of busulfan for Days -6 through -3. If needed, PK blood testing may also be done on Day -6 during your dose of Busulfan. You may receive the Day -13 and Day -12 busulfan dose either as an outpatient in the clinic or as an inpatient in the hospital.

A heparin lock line will be placed in your vein to lower the number of needle sticks needed for these draws. If it is not possible for the PK tests to be performed for technical reasons, you will be taken off study and receive the standard fixed dose of busulfan.

On Days -13 and -12, you will receive busulfan by vein over 3 hours.

On Days -11 through -7, you will rest.

On Days -6 through -3, you will receive fludarabine by vein over 1 hour, then busulfan by vein over 3 hours.

On Days -2 and -1, you will rest.

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

After the transplant, you will receive tacrolimus, methotrexate, or other drugs to weaken the immune system in the standard manner to lower the risk of graft-vs-host disease (GVHD), a reaction of the donor's immune cells against the recipient's body.

You will receive tacrolimus by vein as a nonstop infusion until you are able to take it by mouth to help lower the risk of GVHD. You will then take tacrolimus by mouth 2 times a day for about 3 months. After that, your tacrolimus dose may be lowered if you do not have GVHD. Your doctor will discuss this with you. On Days 1, 3, and 6, if your stem cells are from a related or matched unrelated donor, you will receive methotrexate over 30 minutes each day by vein to help lower the risk of GVHD. Participants receiving a matched unrelated donor will also receive methotrexate on Day 11 after the transplant.

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.

Study Testing:

While you are in the hospital, you will be checked for any side effects as part of your standard of care. Blood (about 2 teaspoons) will be drawn every day to check for side effects, for routine tests, to check your blood counts, kidney and liver function, and to check for infections.

As part of standard care, you will remain in the hospital for about 3-4 weeks after the transplant. After you are sent home from the hospital, you must remain in the Houston area to be checked for infections and other transplant side effects until about 3 months after transplant. During this time, you will return to the clinic at least 1 time each week. The following tests and procedures will be performed:

• 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 for routine tests.

About 1, 3, 6, and 12 months after the transplant:

• 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 5 teaspoons) will be drawn to see how well the transplant has "taken."
• You will have a bone marrow aspiration to check the status of the disease, if your doctor thinks it is needed. To collect a bone marrow aspiration, an area of the hip or other site is numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large needle.

Length of Study:

You will be taken off study 3 years after the end of treatment. You may be taken off study early if the disease gets worse, if you have any intolerable side effects, of if you are unable to follow study directions.

You should talk to the study doctor if you want to leave the study early. If you are taken off study early, you still may need to return for routine follow-up visits after the transplant, if your transplant doctor decides it is needed.

It may be life-threatening to leave the study after you have begun to receive the study drugs but before you receive the stem cells.

This is an investigational study. Busulfan and fludarabine are both FDA approved and commercially available. The investigational part of this study is the addition of 2 more doses of busulfan.

Up to 200 patients will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Patients with high-risk hematologic malignancies with anticipated poor prognosis with non transplant therapy, including those in remission or with induction failure and after treated or untreated relapse. Diagnoses to be included a) Acute myeloid leukemia; b) Acute lymphocytic leukemia; c) Chronic myeloid leukemia; d) Chronic lymphocytic leukemia; e) Myelodysplastic syndrome; f) Myeloproliferative syndromes; g) Non-Hodgkins lymphoma; h) Hodgkins Lymphoma; i) Multiple myeloma.
2. Patients must have a histocompatible stem cell donor. An HLA-identical related donor or a 8/8 matched unrelated donor.
3. Age 5 to 75 years old.
4. Performance score of >/= 70 by Karnofsky/Lansky or PS 0 to 1 (ECOG </=1).
5. Left ventricular ejection fraction at least 40%.
6. Adequate pulmonary function with FEV1, FVC and DLCO >/=50% of expected corrected for hemoglobin and/or volume. Children unable to perform pulmonary function tests (e.g., less than 7 years old) pulse oximetry of >/= 92% on room air
7. Creatinine clearance (calculated creatinine clearance is permitted) should be >40 ml/min.
8. Bilirubin \