Timed Sequential Busulfan and Post Transplant Cyclophosphamide for Allogeneic Transplantation

Study Groups:

You will be assigned to 1 of 5 study groups, depending on what type of stem cells you will
receive, your age, diagnosis, and health status. You will be placed in the study group that
the the study doctor feels is in your best interest.

If you are in Group 1, 3, or 5, you will receive busulfan, cyclophosphamide, fludarabine,
tacrolimus, thiotepa, and mycophenolate mofetil (MMF) and a stem transplant with cells from a
haploidentical donor (a donor that is a half match to yours). If you are in Group 5, you will
receive a lower dose of thiotepa than Group 1 and Group 3.

If you are in Group 2 or 4, you will receive busulfan, cyclophosphamide, fludarabine, and
tacrolimus and a stem cell transplant with cells from a matched related or unrelated donor (a
donor that is a full match). If you are in Group 2 and have a matched unrelated donor or if
you are in Group 4, you will receive MMF.

Central Venous Catheter:

The chemotherapy you receive, some of the other drugs in this study, and the stem cell
transplant will be given by vein through a 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. Some 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:

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.

Group 1:

You will receive busulfan by vein over about 3 hours on 2 separate days as either an
outpatient in the clinic or as an inpatient in the hospital.

If you receive busulfan as an outpatient, you will receive busulfan by vein over about 3
hours on Days -13 and -12. You will be admitted to the hospital on Day -8 and will receive
fluids by vein as part of your standard care.

If you receive busulfan as an inpatient, you will be admitted to the hospital on Day -14 and
will receive fluids by vein as part of your standard care. You will receive busulfan by vein
over about 3 hours on Days -13 and -12.

You will rest on Days -11 through -8.

On Day -7, you will receive thiotepa by vein over 4 hours.

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

You will rest on Days -2 and -1.

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

You will rest on Days +1 and +2.

On Days +3 and +4, you will receive cyclophosphamide by vein over 3 hours to help lower the
risk of graft-versus-host disease (GVHD -- when transplanted immune tissue, such as stem
cells, attacks the tissues of the recipient's body). You will also receive mesna by vein over
30 minutes every 4 hours for a total of 10 mesna doses on Days +3 and +4. Mesna is given to
lower the risk of side effects to the bladder caused by cyclophosphamide.

Starting on Day +5, you will receive tacrolimus nonstop by vein 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. You will receive MMF as a tablet by mouth 3 times a
day for 90 days or longer, if the doctor thinks it is in your best interest.

Starting 1 week after your stem cell transplant, you will receive filgrastim as an injection
under the skin 1 time a day until your blood cell levels return to normal. Filgrastim is
designed to help with the growth of white blood cells and is part of your standard care.

Group 2:

You will receive busulfan by vein over about 3 hours on 2 separate days as either an
outpatient in the clinic or as an inpatient in the hospital.

If you receive busulfan as an outpatient, you will receive busulfan by vein over about 3
hours on Days -13 and -12. You will be admitted to the hospital on Day -7 and will receive
fluids by vein as part of your standard care.

If you receive busulfan as an inpatient, you will be admitted to the hospital on Day -14 and
will receive fluids by vein as part of your standard care. You will receive busulfan by vein
over about 3 hours on Days -13 and -12. You will rest on Days -11 through -7.

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

You will rest on Days -2 and -1.

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

You will rest on Days +1 and +2.

On Days +3 and +4, you will receive cyclophosphamide by vein over 3 hours to help lower the
risk of graft-versus-host disease (GVHD -- when transplanted immune tissue, such as stem
cells, attacks the tissues of the recipient's body). You will also receive mesna by vein over
30 minutes every 4 hours for a total of 10 mesna doses on Days +3 and +4. Mesna is given to
lower the risk of side effects to the bladder caused by cyclophosphamide.

Starting on Day +5, you will receive tacrolimus nonstop by vein 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. If you have a matched unrelated donor, you will
receive MMF as a tablet by mouth 3 times a day for 90 days or longer, if the doctor thinks it
is in your best interest.

Starting 1 week after your stem cell transplant, you will receive filgrastim as an injection
under the skin 1 time a day until your blood cell levels return to normal. Filgrastim is
designed to help with the growth of white blood cells and is part of your standard care.

Group 3 and Group 5:

You will receive busulfan by vein over about 3 hours on 2 separate days as either an
outpatient in the clinic or as an inpatient in the hospital.

If you receive busulfan as an inpatient, you will be admitted to the hospital on Day -21 and
will receive fluids by vein as part of your standard care. You will receive busulfan by vein
over about 3 hours on Days -20 and -13. You will rest on Days -12 through -8.

If you receive busulfan as an outpatient, you may receive busulfan on Days -20 and -13. You
will rest on Days -12 through -9. You will be admitted to the hospital on Day -8 and will
receive fluids by vein as part of your standard care.

On Day -7, you will receive thiotepa by vein over 4 hours. If you are in Group 5, you will
receive a lower dose of thiotepa than Group 3.

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

You will rest on Days -2 and -1.

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

You will rest on Days +1 and +2.

On Days +3 and +4, you will receive cyclophosphamide by vein over 3 hours to help lower the
risk of graft-versus-host disease (GVHD -- when transplanted immune tissue, such as stem
cells, attacks the tissues of the recipient's body). You will also receive mesna by vein over
30 minutes every 4 hours for a total of 10 mesna doses on Days +3 and +4. Mesna is given to
lower the risk of side effects to the bladder caused by cyclophosphamide.

Starting on Day +5, you will receive tacrolimus nonstop by vein 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. You will receive MMF as a tablet by mouth 3 times a
day for 90 days or longer, if the doctor thinks it is in your best interest.

Starting 1 week after your stem cell transplant, you will receive filgrastim as an injection
under the skin 1 time a day until your blood cell levels return to normal. Filgrastim is
designed to help with the growth of white blood cells and is part of your standard care.

Group 4:

You will receive busulfan by vein over about 3 hours on 2 separate days as either an
outpatient in the clinic or as an inpatient in the hospital.

If you receive busulfan as an inpatient, you will be admitted to the hospital on Day -21 and
will receive fluids by vein as part of your standard care. You will receive busulfan by vein
over about 3 hours on Days -20 and -13. You will rest on Days -12 through -7.

If you receive busulfan as an outpatient, you may receive busulfan on Days -20 and -13. You
will rest on Days -12 through -8. You will be admitted to the hospital on Day -7 and will
receive fluids by vein as part of your standard care.

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

You will rest on Days -2 and -1.

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

You will rest on Days +1 and +2.

On Days +3 and +4, you will receive cyclophosphamide by vein over 3 hours to help lower the
risk of graft-versus-host disease (GVHD -- when transplanted immune tissue, such as stem
cells, attacks the tissues of the recipient's body). You will also receive mesna by vein over
30 minutes every 4 hours for a total of 10 mesna doses on Days +3 and +4. Mesna is given to
lower the risk of side effects to the bladder caused by cyclophosphamide.

Starting on Day +5, you will receive tacrolimus nonstop by vein 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. If you have a matched unrelated donor, you will
receive MMF as a tablet by mouth 3 times a day for 90 days or longer, if the doctor thinks it
is in your best interest.

Starting 1 week after your stem cell transplant, you will receive filgrastim as an injection
under the skin 1 time a day until your blood cell levels return to normal. Filgrastim is
designed to help with the growth of white blood cells and is part of your standard care.

Pharmacokinetic (PK) Testing:

About 11 samples of blood (about 1-2 teaspoons each time) will be drawn for PK testing at
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 and will help the doctor decide your dose of busulfan for Days -6
through -3. If the doctor thinks it is needed, PK blood testing may also be done on Day -6
during your dose of busulfan.

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. The study doctor will discuss this with you.

Length of Study:

You will be on study for up to 3 years after the transplant. 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 doctor thinks 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.

Tests Before Study Drug Administration:

Before you receive study drugs, blood (about 2 teaspoons) will be drawn to check for
cytokines. Cytokine release syndrome (CRS) occurs when a large amount of proteins are
released into the blood. The risks of CRS, some of which are serious, are described in
greater detail below.

Study Tests:

On Day -2 and Day +3, blood (about 2 teaspoons each time) will be drawn to check for
cytokines. If you have CRS, you may receive steroids by mouth or by vein. Your doctor will
explain this to you.

As part of standard care, you will remain in the hospital for about 3-4 weeks after the
transplant. While you are in the hospital, blood (about 2 teaspoons) will be drawn every day
to check for side effects, for routine tests, to check your blood counts, to check your
kidney and liver function, and to check for infections.

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. At each visit,
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 and you will be checked for symptoms of GVHD.

- Blood (about 5 teaspoons) will be drawn to see how your body has reacted to the
transplant.

- If your doctor thinks it is needed, you will have a bone marrow aspiration to check the
status of the disease. 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.

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
lymphoproliferative disorder; e) Myelodysplastic syndrome; f) Myeloproliferative
syndromes; g) Non-Hodgkin's lymphoma; h) Hodgkin's Lymphoma; i) Multiple myeloma.

2. Patients must have a haploidentical related donor or a fully matched related or
unrelated donor.

3. Ages >/= 12 and
4. Performance score of >/= 70 by Karnofsky/Lansky or PS 0 to 1 (ECOG
5. Left ventricular ejection fraction >/= 50%.

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 by Cockcroft-Gault using
adjusted body weight if actual body weight is 20% greater than ideal is permitted)
should be >50 ml/min.

8. Bilirubin bilirubin due to Gilbert's Syndrome, hypersplenism, or hemolysis). SGPT (ALT) < 200.

9. Negative Beta HCG test in a woman with child bearing potential, defined as not
post-menopausal for 12 months or no previous surgical sterilization. Women of child
bearing potential must be willing to use an effective contraceptive measure while on
study.

10. Patient or patient's legal representative able to sign informed consent.

Exclusion Criteria:

1. HIV seropositivity.

2. Uncontrolled infections.

3. Patients with comorbidity score > 3. The principal investigator is the final arbiter
of eligibility for comorbidity score >3.

4. Prior allogeneic transplant

5. Patients with active Hepatitis B and C.