T Cell Depletion for Recipients of HLA Haploidentical Related Donor Stem Cell Grafts
Condition: Acute Lymphoblastic Leukemia; Non Hodgkins Lymphoma; Myelodysplastic Syndrome; Acute Myeloid Leukemia; Chronic Myelogenous Leukemia; Hemophagocytic Lymphohistiocytosis (HLH); Familial Hemophagocytic Lymphohistiocytosis (FLH); Viral-associated Hemophagocytic Syndrome (VAHS); X-linked Lymphoproliferative Disease (XLP)
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Preleukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myelodysplastic Syndromes; Lymphohistiocytosis, Hemophagocytic; Lymphoproliferative Disorders; Syndrome
Intervention: Ara-C; Cyclophosphamide; Campath-1H; Total Body Irradiation; Stem Cell Infusion
Intervention description: day-8 through day-5
3 g/m2 q 12 hours; day-7 and day-6
45 mg/kg; day-3 through day-1
Dosing for children:
5 - 15kg : 3mg IV in 30ml NS
15.1 - 30kg : 5mg IV in 50ml NS
>30 kg : 10mg IV in 100ml NS
Adults will receive 10mg IV in 100ml NS; day-4 through day-1
175 cGy x 2 at 24 cGy/min; Stem cells are infused on day 0
Intervention MeSH terms: Cytarabine; Cyclophosphamide; Alemtuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: All
Maximum age: 55 Years
Healthy volunteers: No
Keywords: haploidenticalstem cell transplant; acute lymphoblastic leukemia; Non Hodgkins Lymphoma; Myelodysplastic Syndrome; Acute myeloid leukemia; Chronic myelogenous leukemia; Hemophagocytic lymphohistiocytosis (HLH); Familial hemophagocytic lymphohistiocytosis (FLH); Viral-associated hemophagocytic syndrome (VAHS); X-linked lymphoproliferative disease (XLP)

Summary:

      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.
    

Eligibility criteria:

        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.