Stem Cell Transplant for Hematologic Diseases (HIMSUM)

• Assess the treatment related mortality [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
• Assess the time to engraftment and incidence of graft failure [ Time Frame: 100 days ] [ Designated as safety issue: No ]
• Assess the safety, pharmacokinetics and immunologic activity of Campath 1H [ Time Frame: 2 yrs ] [ Designated as safety issue: No ]

Patients are being asked to participate in this study because they have a cancer in their blood, Fanconi's Anemia, or have been unsuccessfully treated for bone marrow failure such as Aplastic Anemia and Paroxysmal nocturnal hemoglobinuria. Any of these conditions could benefit from an allogeneic stem cell transplant using a donor that is related to the patient.

Stem cells are created in the bone marrow. They grow into different types of blood cells that the patient needs, including red blood cells, white blood cells, and platelets. In a transplant, the patient's own stem cells would be killed and then replaced by stem cells from the donor.

Usually, patients are given very strong doses of chemotherapy prior to receiving a stem cell transplant. However, because of the patient's condition, they have a high risk of getting life-threatening treatment-related side effects. Recently, some doctors have begun to use chemotherapy that does not cause as many side effects before patients receive a transplant.

This research study that the patient is being asked to participate in adds CAMPATH 1H to a low-dose chemotherapy regimen followed by an allogeneic stem cell transplantation. We want to see if adding CAMPATH 1H to the transplant medications helps in treating the disease. We also want to see if there are fewer life-threatening side effects from the treatment. CAMPATH 1H is a drug that is still being studied. CAMPATH 1H stays active in the body for a long time after patient's receive it, which means it may work longer at preventing GVHD symptoms.

Before treatment begins, stem cells will be collected from the donor's blood or bone marrow. The stem cells will be collected and frozen before we start to give the patient chemotherapy.

After admission to the hospital, patients will receive total body irradiation (very strong type of x-rays that kill cells in the bone marrow), Fludarabine and Campath 1H prior to the Stem cell transplant (infusion of the donors stem cells).

Starting 7 days after the transplant, the patient will be given G-CSF by subcutaneous injection until a blood test shows that granulocytes (a type of white blood cell) are more than 1000/ul. This is to help increase blood counts.

After transplantation, the patient will have several evaluations at different times. These are standard evaluations and tests done for any patient who has received a stem cell transplant as part of routine clinical monitoring:

We will also be looking at the patient's immune function (how the body protects itself to prevent and fight infections and diseases). To do this blood tests will be done at regular intervals (every 3 to 6 months) for 2 years.

Depending on how well the donors stem cells work in the body after the transplant, the patient may receive one or more Donor Leukocyte Infusions (DLI). This is when leukocytes (a type of white blood cell) collected from the same donor that provided the stem cells are given to the patient through a central line into a vein.

• Biological: Campath 1H
  Day -5 through day -2 Campath 1H dosed as per institutional standard
• Drug: Fludarabine
  Day -5 to Day-2: Fludarabine 30mg/m2
• Procedure: Stem Cell Transplant
  Day 0 stem cells infused
• Radiation: TBI
  Day-6: Total body irradiation of 600cGy as two doses

INCLUSION CRITERIA:

1. Diagnosis of myelodysplastic disorders, Fanconi's anemia, Acute Myelogenous Leukemia (including secondary), Acute Lymphoblastic Leukemia, Multiple Myeloma, Plasma Cell Dyscrasia, Lymphoproliferative disorders (Non-Hodgkin Lymphoma, Hairy Cell Leukemia, or Chronic Lymphocytic Leukemia and Hodgkin's Disease). Diagnosis of Myelodysplastic disorders which is not good risk by IPSS, Fanconi's anemia, Acute Myelogenous Leukemia (1st or subsequent relapse or 2nd or subsequent CR or refractory disease), Acute Lymphoblastic Leukemia in 2nd or subsequent remission or relapse or refractory disease, or Philadelphia chromosome positive, Chronic Myelogenous Leukemia (failed STI and interferon), Multiple Myeloma (stage II or III), Lymphoma, Chronic Lymphocytic Leukemia (primary refractory or recurrent disease), Hodgkin's Disease (after relapse), Hemophagocytic Lymphohistiocytosis (failed chemotherapy and/or anti-viral therapy), or bone marrow failure such as Aplastic Anemia and Paroxysmal nocturnal hemoglobinuria, PNH (failed prior therapies).
2. Conditions that increase treatment related mortality: (need one or more to be eligible): Age > / = 50 years; EF of less than 45%; DLCO less than 50% or FEVI 50-75% of predicted value; Diabetes Mellitus; Renal Insufficiency (but creatinine clearance not less than 25 ml/min); Prior recent history of systemic fungal infection; 3rd or greater remission of AML or ALL; Significant grade III or IV neurologic or hepatic toxicity from previous treatment; More than 1 year of diagnosis (CML or Myeloma patients ONLY); Multiple types of treatment regimens (equal to or more than 3); significant Grade III or IV neurologic or hepatic toxicity from previous treatment; Prior autologous or allogeneic stem cell transplantation.

3. Haploidentical family member donor. The protocol is open to patients who lack a 5/6 or 6/6 HLA antigen matched donor. Due to the increased risk of GVHD, patients with Fanconi anemia and a 5/6 HLA match will also be eligible.

   For this protocol, the "best" donor will be defined as a first-degree haploidentical family member who matches at the most MHC loci. Matching will be determined by class I and class II DNA typing. The donor should be sufficiently healthy not to be at increased risk from the mobilization procedure. Should more than one "equally" MHC incompatible donor be identified, other selection criteria will include: age and size of donor, CMV status and sex. The Principal Investigator will make final decisions.

4. Available healthy donor without any contraindications for donation.
5. Patient and/or responsible person able to understand and sign consent.
6. Age between birth and 70 years.
7. Women of child bearing potential must have a negative pregnancy test.

EXCLUSION CRITERIA:

1. Pregnant, lactating or unwilling to use contraception.
2. HIV positive patient.
3. Uncontrolled intercurrent infection.
4. Untreated Blast Crisis for CML.
5. Uncontrolled High-grade lymphoproliferative disease / lymphoma.
6. Unstable angina and uncompensated congestive heart failure (Zubrod of 3 or greater).
7. Severe chronic pulmonary disease requiring oxygen (Zubrod of 3 or greater).
8. Hemodialysis dependent.
9. Active hepatitis or cirrhosis with total bilirubin, SGOT, and SGPT greater than 3 x upper limit of normal.
10. Unstable Cerebral vascular disease and recent hemorrhagic stroke (less than 6 months).
11. Active CNS disease from hematological disorder.

• Texas Children's Hospital
• The Methodist Hospital System