T-cell Depleted Hematopoietic Stem Cell Boosts Without Conditioning for Poor Marrow Graft Function Following Allogeneic Hematopoietic Stem Cell Transplantation
Condition: Hematopoietic Stem Cell Transplant; Poor Marrow Graft Function
Intervention: Donor peripheral blood progenitor cells: stimulation, harvesting, isolation and T-cell depletion; CliniMACS Cell Selection System
Intervention description: For related donors, beginning 5-6 days before the day of HPC(A) or HPC (M) TCD boost infusion, the normal donor will receive GCSF per institutional guidelines. On the fifth and sixth days of this course of G-CSF, the donor will undergo daily leukapheresis designed to provide a minimum of 5x10^6 CD34+ cells/kg of the transplant recipient's weight. For unrelated donors, the G-CSF will be administered and the leukapheresis obtained according to the National Marrow Donor Program protocol IND, and institutional guidelines. Mononuclear cell fractions (i.e., CD34+ cells) collected on the fourth and fifth days will be pooled.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Healthy volunteers: No
Keywords: T-cell Depleted Hematopoietic Stem Cell; Allogeneic Hematopoietic Stem Cell Transplantation; CliniMACS Cell Selection System; 14-228; HSCT

Summary:

      The purpose of this study is to see if giving the patient stem cells their original donor
      (boost) after removing the T cells (T cell depleted- TCD boost) without further chemotherapy.
      The investigators want to see if this can improve bone marrow function. This would also
      improve the patients white blood counts, red blood counts and platelets. This may make the
      patients chances of improving and surviving better. The investigators will also be looking at
      the short term side effects and risks of the TCD boost.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients who are diagnosed with PGF are candidates for this trial.

          -  Patients who underwent transplant at another facility and suffer from PGF will be
             eligible as well as long as a donor is available. PGF can be primary (no counts
             recovery after the preparative regimen) or secondary (cytopenia after engraftment has
             occurred).

          -  Patients with auto-immune cytopenia with auto antibodies to neutrophils or platelets
             or positive Coombs test that did not respond to immunosuppressive agents within 3
             months from initiation of therapy are eligible as well.

          -  Persistent cytopenia requiring growth factors and/or blood products AND evidence of
             hypocellular BM (<25%). Persistent cytopenia (at least 4 weeks period) is defined by
             presence of TWO of the following:

               1. ANC <1.0x10^9/L without filgrastim support or any ANC value that requires
                  recurrent support by filgrastim (administered at least once a week).

               2. Plt<50x10^9/L

               3. Hb<8 or PRBC transfusion dependent (once every 2 weeks or more) with reticulocyte
                  count of < 40x10^9/L.

        This criteria for persistent cytopenia and hypocellular bone marrow does not apply to
        patients with auto-immune cytopenia, ONLY PGF patients

          -  Full donor myeloid chimerism. Patients after T cell depletion transplant can have a
             significant mixed T cell chimerism and this can affect the testing of marrow
             chimerism. In this case, the neutrophil chimerism will be used to determine
             eligibility for this trial. Patients will be excluded if neutrophils are less than 90%
             donor cells; a higher percentage of host cells could be due to relapse or impending
             relapse.

          -  Age: pediatrics and adults patients. No age exclusion.

          -  Each patient must be willing to participate as a research subject and must sign an
             informed consent form.

          -  For infections and end organs related criteria (at time of TCD boost administration)
             see table in protocol.

        Exclusion Criteria:

        Patients will be excluded from the trial if at time of enrollment:

          -  Evidence of relapsed disease by morphologic, cytogenetic or molecular diagnostic
             tools.

          -  Hypersplenism documented by imaging study (US or CT)

          -  Pregnant women

          -  Patient who underwent TCD boost without counts recovery and are considered for another
             TCD boost will be treated off protocol.