Subjects are being asked to participate in this study because treatment of their disease requires them to receive a stem cell transplant. Stem cells or "mother" cells are the source of normal blood cells and lead to recovery of blood counts after bone marrow transplantation (BMT). Unfortunately, there is not a perfectly matched stem cell donor (like a sister or brother) and the subject's disease is considered rapidly progressive and does not permit enough time to identify another donor (like someone from a registry list that is not their relative). We have, however, identified a close relative of the subject's whose stem cells are not a perfect match, but can be used. However, with this type of donor, there is typically an increased risk of developing graft-versus-host disease (GVHD), a high rate of transplant failure, and a longer delay in the recovery of the immune system.

GVHD is a serious and sometimes fatal side effect of stem cell transplant. GVHD occurs when the new donor cells (graft) recognizes that the body tissues of the patient (host) are different from those of the donor. When this happens, cells in the graft may attack the host organs, primarily the skin, liver, and intestines. The number of occurrences and harshness of severe GVHD depends on several factors, including the degree of genetic differences between the donor and recipient, the intensity of the pre-treatment conditioning regimen, the quantity of transplanted cells, and the recipient's age. In recipients of mismatched family member or matched unrelated donor stem cell transplants, there is a greater risk of GVHD so that 70-90% of recipients of unchanged marrow will develop severe GVHD which could include symptoms such as marked diarrhea, liver failure, or even death.

In an effort to lower the occurrences and severity of graft-versus-host disease in patients and to lower the rate of transplant failure, we would like to specially treat the donor's blood cells to remove cells that are most likely to attack the patient's tissues. This will occur in combination with intense conditioning treatment that the patient will receive before the transplant.

To participate in this study, the subject will need to have a central line (a thin plastic catheter or tube that is placed during surgery into one of the large veins in the neck or chest).

Also before treatment can begin, we will test the subject's blood for viruses which can cause problems after the transplant.

Before treatment can begin, stem cells will be collected from the donor that has been selected as the best match for the subject. White blood cells will be collected from the donor. The cells will then be mixed with a special protein called a CD34 antibody that binds to the stem cells which will then be separated out from the white blood cells by a special machine called a CLINIMACs CD34 Reagent System in the laboratory. This is an investigational and experimental device which is not approved by the FDA. Although this device is not approved for use in this country, it has been in use for years and is approved in other countries. The stem cells will be collected and frozen before we start to give chemotherapy.

TREATMENT PLAN

To prepare the subject's body for transplantation, the subject will be given high dose chemotherapy (also called a conditioning treatment) for 8 days prior to the transplant as follows:

The subject will be given a drug called Ara-C in high doses through the central line every 12 hours starting 8 days before transplant (called day - 8) until 5 days before transplant (called day - 5). Starting one day after receiving the first Ara-C dose (day - 7), we will add a drug called cyclophosphamide once a day to the treatment for the next two days. This will be given in high doses (also through the central line). Also on day - 7, we will add a drug called MESNA. MESNA is used to decrease the side effects caused by cyclophosphamide. After the medication treatment is finished (day - 4), radiation treatment will be given to the entire body twice a day for 4 days. The chemotherapy and radiation treatment will last 8 days. If the subject has abnormal cells in the spinal fluid, 6 extra daily doses of radiation treatment may be given to the head. This would be done before any of the drugs are given and before the subject is admitted for transplant.

NOTE: Depending on the subjects health status, the doctor may decide the subject should not receive Ara-C. If this is a possibility, the doctor will discuss this with the subject.

On the second day of radiation (day -3), the subject will receive CAMPATH-1H as a daily 4-hour IV (intravenous, by vein). The subject will receive this infusion once a day for a total of three days. CAMPATH 1H is a special type of protein called an antibody, that works against certain types of blood cells. CAMPATH 1H is important because it stays active in the body for a long time after infusion, which means it may work longer at preventing GVHD symptoms.

The day after the radiation treatment is completed (day 0), the subject will receive the specially selected donor stem cells. Once in the bloodstream, the cells will go to the bone marrow and should begin to grow. If the subject is at risk for developing GVHD or if the subject begins to develop GVHD, the doctor will prescribe medicines to help prevent or treat this side effect. The doctor will describe these medicines at that time.

To learn more about the way the new cells are growing blood will be taken for research purposes at approximately 3 months, 6 months, 9 months, and a year after the transplant. On day 100, the subject will have the same tests/evaluations the subject has been experiencing since the transplant, however, the subject will also have a bone marrow aspirate (we take a sample of bone marrow to evaluate the disease and GVHD status). For patients who do not develop GVHD, they may have an additional bone marrow aspirate on day 180 (about 2 months after the previous one).

After day 365, the subject will be asked to return to the clinic once a year for evaluations. These evaluations will be similar to the ones the subject had on day 100.

INCLUSION CRITERIA:

• Lack of suitable conventional donor (i.e. 5/6 or 6/6 related or 5/6 or 6/6 unrelated donor) or presence of a rapidly progressive disease not permitting time to identify an unrelated donor
• Age less than or equal to 55 years of age
• Patients with high risk ALL in CR1 or ALL or high grade (stage III or IV) NHL after first relapse or with primary refractory disease or minimal residual diseases.
• Myelodysplastic syndrome
• Patients with high risk AML in CR1 or after first relapse or with primary refractory disease or minimal residual disease.
• CML
• Hemophagocytic lymphohistiocytosis (HLH), familial hemophagocytic lymphohistiocytosis (FLH), viral-associated hemophagocytic syndrome (VAHS), X-linked lymphoproliferative disease (XLP), Severe chronic active Epstein Barr virus infection (SCAEBV) with predilection for T- or NK-cell malignancy
• Donor cells should be collected and frozen before conditioning starts

EXCLUSION CRITERIA:

• Patients with a life expectancy (< / = 6 weeks) limited by diseases other than leukemia
• Patients with symptomatic cardiac disease, or evidence of significant cardiac disease by echocardiogram (i.e., shortening fraction < 25%)
• Patients with severe renal disease (i.e., creatinine clearance less than 40 cc/1.73 m^2)
• Patients with pre-existing severe restrictive pulmonary disease (FVC less than 40% of predicted)
• Patients with severe hepatic disease (direct bilirubin greater than 3 ug/dl or SGPT (serum glutamic-pyruvic transaminase) greater than 500 ug/dl)
• Patients with severe personality disorder or mental illness
• Patients with a severe infection that on evaluation by the Principal Investigator precludes ablative chemotherapy or successful transplantation
• Patients with documented HIV positivity

'High risk' ALL or AML refers to those acute leukemias identified by the presence of specific biologic features, which predict high likelihood of failure to conventional chemotherapy. As biologic features of high risk disease evolve with improvement of conventional chemotherapy, it is not practical to define this indication with any further specificity. Therefore, high risk AML/ALL will be determined by the primary physician.