Nonmyeloablative stem cell transplantation with CD8-depleted or CD34-selected peripheral blood stem cells.

in Journal of Hematotherapy & Stem Cell Research (2002), 11(2), 301-14

To decrease the incidence of graft-versus-host disease (GVHD) observed after nonmyeloablative stem cell transplantation (NMSCT), we studied the feasibility of CD8-depleted or CD34-selected NMSCT followed ... [more ▼]

To decrease the incidence of graft-versus-host disease (GVHD) observed after nonmyeloablative stem cell transplantation (NMSCT), we studied the feasibility of CD8-depleted or CD34-selected NMSCT followed by CD8-depleted preemptive donor lymphocyte infusion (DLI) given in incremental doses on days 40 and 80. Fourteen patients with high-risk malignancies and an HLA-identical sibling (n = 8) or alternative donor (n = 6) but ineligible for a conventional transplant were included. Nonmyeloablative conditioning regimen consisted in 2 Gy total body irradiation (TBI) alone, 2 Gy TBI and fludarabine (previously untreated patients) or cyclophosphamide and fludarabine (patients who had previously received > or =12 Gy TBI). Patients 1-4 (controls) received unmanipulated peripheral blood stem cells (PBSC) and DLI and patients 5-14 CD8-depleted or CD34-selected PBSC followed by CD8-depleted DLI. Post-transplant immunosuppression was carried out with cyclosporine A (CsA) and mycophenolate mofetil (MMF). Initial engraftment was seen in all patients, but 1 patient (7%) later rejected her graft. The actuarial 180-day incidence of grades II-IV acute GVHD was 75% for patients 1-4 versus 0% for patients 5-14 (p = 0.0019). Five of 14 patients were in complete remission (CR) 180 days after the transplant and 6/14 had partial responses. The 1-year survival rate was 69%, and nonrelapse and relapse mortality rates were 16 and 18%, respectively. We conclude that CD8-depleted or CD34-selected NMSCT followed by CD8-depleted DLI is feasible and considerably decreases the incidence of acute GVHD while preserving engraftment and apparently also the graft-versus-leukemia (GVL) effect. Further studies are needed to confirm this encouraging preliminary report. [less ▲]

Hyperammonemia after high-dose chemotherapy and stem cell transplantation.

in Bone Marrow Transplantation (2000), 26(3), 343-5

We report a patient with multiple myeloma who suffered from hyperammonemia after a second stem cell autograft. This syndrome is not well known but is associated with a high mortality rate. Considering the ... [more ▼]

We report a patient with multiple myeloma who suffered from hyperammonemia after a second stem cell autograft. This syndrome is not well known but is associated with a high mortality rate. Considering the possibility of this diagnosis in patients developing confusion and neurological degradation with respiratory alkalosis after intensive chemotherapy, could allow earlier treatment and perhaps improved survival. Possible mechanisms and potential therapies are discussed. With rapid recognition and treatment of the syndrome, the patient fully recovered. One and a half years later, she is still alive and well, on interferon for persisting myeloma. [less ▲]