Allogeneic Mixed Chimerism Stem Cell Transplant Using Campath for Hemoglobinopathies & Bone Marrow Failure Syndromes
Condition: Sickle Cell Anemia; Severe Aplastic Anemia; Paroxysmal Nocturnal Hemoglobinuria (PNH); Pure Red Cell Aplasia
MeSH terms: Hemoglobinuria; Anemia; Anemia, Aplastic; Anemia, Sickle Cell; Hemoglobinuria, Paroxysmal; Bone Marrow Failure Disorders; Pancytopenia; Hemoglobinopathies; Red-Cell Aplasia, Pure
Intervention: Campath, Chemo and/or TBI Allo SCT
Intervention description: Allogeneic PBSC/marrow will be collected/harvested from the donor after granulocyte colony-stimulating factor (G-CSF) priming. The allogeneic PBSCs will be infused as per current institutional practice.
Intervention MeSH terms: Alemtuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: sickle cell anemia; severe aplastic anemia

Summary:

      RATIONALE: Although used primarily to treat malignant disorders of the blood, allogeneic stem
      cell transplantation can also cure a variety of non-cancerous, inherited or acquired
      disorders of the blood. Unfortunately, the conventional approach to allogeneic stem cell
      transplantation is a risky procedure. For some non-cancerous conditions, the risks of this
      procedure outweigh the potential benefits. This protocol is designed to test a new approach
      to allogeneic stem cell transplantation. It is hoped that this approach will be better suited
      for patients with non-cancerous blood and bone marrow disorders.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have their clinical material reviewed at the transplanting institution
             and the diagnosis confirmed

          -  Performance status must be Cancer and Leukemia Group B (CALGB) Performance Status (PS)
             0, 1, or 2.

          -  Patients must have a 5/6 to 6/6 HLA matched family member donor who is evaluated and
             deemed able to provide PBSCs and/or marrow by the transplant team. Donor must have <
             50% Hemoglobin S (HgS) on hemoglobin electrophoresis. Cytomegalovirus (CMV) status of
             the donor will be assessed, but not used as an exclusion criterion.

          -  Patients must meet the following laboratory parameters unless due to disease status as
             determined by the treating physician:

               1. bilirubin and hepatic transaminases and creatinine must be reviewed by the
                  transplantation center and deemed acceptable.

               2. HIV antibody negative.

               3. hematocrit, white cell count, platelet counts and hematologic status will be
                  reviewed by the treating physician before patient is deemed acceptable.

          -  Patient must agree to use some form of adequate birth control during the periods that
             they receive chemotherapy and any post-chemotherapy medications related to the
             transplant.

          -  Patients must also have a resting multiple gated acquisition scan (MUGA) or
             echocardiogram and Pulmonary Function Tests (PFTs) with Diffusing Capacity of the Lung
             for Carbon Monoxide (DLCO) performed before transplant. Recommended minimum standards
             include an Ejection Fraction (EF) greater than 40% and DLCO greater than 40% for this
             less toxic regimen.

          -  Appropriate cardiology or pulmonary consultations should be considered if the patient
             has severe cardiac or lung disease at the initiation of therapy.

        I) Hemoglobinopathies:

        (a)Sickle Cell Anemia having history of one or more of the following despite treatment with
        standard therapies such as hydroxyurea: i) 2 or more episodes of acute chest syndrome since
        age 13 years ii) pulmonary hypertension as measured by tricuspid regurgitant jet velocity
        of greater than 2.5m/s iii) 2 or more painful crisis per year requiring medical care and
        analgesia in excess of what is needed at baseline.

        iv) history of cerebrovascular accident (b)Thalassemia major: Those eligible will have
        either cardiac or hepatic sequela of thalassemia as documented by biopsy or functional
        studies. For those with hepatic damage, this would be an increase in size by 50% of the
        liver or a doubling of the total bilirubin, aspartate transaminase (AST), alanine
        aminotransferase (ALT), or alkaline phosphatase. To be eligible for transplant due to
        cardiac damage, there must be evidence of left ventricular dysfunction as measured by MUGA
        scan or echocardiography.

        II) Bone marrow failure Disorders

          1. Severe Aplastic Anemia: Cytopenia consisting of at least 2 of the following 3:
             absolute neutrophil count less than 500/μL, platelet count less than 20,000/μL, and
             reticulocyte count less than 50,000/μL.

          2. Paroxysmal nocturnal hemoglobinuria (PNH): Patients must have a history of either
             life-threatening thrombosis, cytopenia, transfusion dependence or recurrent,
             debilitating hemolytic crisis

          3. Pure red cell aplasia: Patients must be transfusion dependent.

        Exclusion Criteria:

          -  pregnant or lactating women,

          -  patients with other major medical or psychiatric illnesses which the treating or
             transplant physician feels could seriously compromise compliance to this protocol

          -  patients with known history of allergies to murine protein