NYMC-526 Familial Haploidentical T-Cell Depleted Transplantation in High-Risk Sickle Cell Disease (IND 14359)

Hypothesis/Aims

1.1 Hypothesis One

Host myeloimmunsuppressive conditioning (MIC) followed by familial haploidentical (FHI) T-cell depleted (TCD) allogeneic stem cell transplantation (AlloSCT) in patients with high risk Sickle Cell Disease (SCD) will be safe and well tolerated, and result in sustained donor chimerism, acceptable engraftment and immune reconstitution
1.1.1 Sub-objective 1A
To determine the safety (treatment related mortality [TRM], event-free survival [EFS]) and feasibility (acceptable rate of hematopoietic engraftment, acute and chronic graft-versus-host disease [GHVD]) of MIC followed by FHI TCD AlloSCT in patients with high-risk SCD.
1.1.2 Sub-objective 1B
To measure whole blood, red cell, T-cell and NK cell donor chimerism following MIC and FHI TCD AlloSCT in patients with high-risk SCD.
1.1.3 Sub-objective 1C
To determine if donor-specific HLA antibodies in serum from day -60, day 0, and day 60 are associated with graft failure.
1.1.4 Sub-objective 1D
To measure quantitative and qualitative immune reconstitution and estimate the incidence of invasive fungal and systemic viral infections (IFI and SVI) following MIC and FHI TCD AlloSCT in patients with high-risk SCD.

1.2 Hypothesis Two
Host myeloimmunsuppressive conditioning (MIC) followed by familial haploidentical (FHI) T-cell depleted (TCD) allogeneic stem cell transplantation (AlloSCT) in patients with high-risk SCD will limit SCD related organ damage resulting in improved and/or stable neurological and neurocognitive and pulmonary and pulmonary vascular function and health-related quality of life (HRQL).

Treatment Regimen

Patients will receive hydroxyurea and azathioprine starting day -59 to day -11, G-CSF on days -59 to day -19 PRN ANC <1000/mm3; fludarabine on Days -17, -16, -15, -14, -13; busulfan twice daily on Days -12, -11, -10, -9; thiotepa on day -8; cyclophosphamide on Days -7, -6, -5, -4; TLI on day -2 rabbit ATG on day -5,-4,-3, and -2. GVHD prophylaxis will consist of tacrolimus for 100 days post SCT and then tapered if ≤grade I AGVHD.

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