Successful Reversion of Refractory Paroxysmal Nocturnal Hemoglobinuria (PNH) by Allogeneic Peripheral Blood Stem Cell Transplantation.

Objective: To observe the safety and effect of allogeneic peripheral blood stem cell transplantation (allo-PBSCT) on hematopoietic reconstitution of refractory paroxysmal nocturnal hemoglobinuria(PNH)and reversion of hemolysis.

Methods: A 20 years old female patient diagnosed with PNH complicated with cerebral infarction underwent allo-PBSCT. The donor was the patient’s 18 years old biological brother. Six loci on HLA-A, B, and DRB1 were completely matched with those of the recipient. Four days after the administration of G-CSF (250 μg/day) to the recipient, peripheral blood stem cells (PBSCs) were collected from the donor for 2 consecutive days. A total volume of 112 ml was harvested. A median nucleated cell (MNC) count of 6.2×10⁸/kg with 2.4×10⁶ /kg of CD34+ cells were actually administered to the recipient. The standard conditioning regimen was busulfan/cyclophosphamide (BU/CY). The recipient was started on intravenous infusion (IV) of cyclosporine A (CSA) on Day -1 and a plasma concentration of 150–250 ng/L was maintained. IV methotrexate (MTX) 10mg/m² was given on Days +1, +3, +6, and +11. Oral mycophenolate mofetil(MMF)was administrated from Days +1 to +28 for prophylaxis of acute graft-versus-host disease (GVHD). If the concentration of hemoglobin (Hb) decreased below 70 g/L and/or platelet count (BPC) below 15×10⁹ /L, the recipient was transfused with ⁶⁰Co 25cGy irradiated and leuko-depleted red blood cells (RBCs) and/or single-donor platelets. Starting from Day +3, G-CSF was given to the recipient until white blood cells (WBC) increased to above 3.0× 10⁹ /L. EPO and Interleukin-11 were also administrated to stimulate the proliferation of the progenitors of erythrocytes and megakaryocytes.

Results: DNA-STR on Day +33 indicated a complete chimerism in the recipient. Chromatin bodies were observed as 46XY on Day +45. CD55/CD59 expression on the membranes of leucocytes and erythrocytes, hemolysis index, and coagulation parameters returned to normal. The patient has been relapse-free for one year since the time of discharge.

Conclusion: 1. When conventional therapy with hormone and immunosuppressant becomes unsuccessful to control PNH, allo-PBSCT may be an alternative measure with promising effect. 2. In comparison to the reduced dose regimen, the standard dose regimen of BU/CY shown lower rate of relapse. 3. To decrease the mortality rate related to transplantation, allo-PBSCT needs to be considered as early as possible for refractory paroxysmal nocturnal hemoglobinuria.