Successful Reversion of Chronic Myelogenous Leukemia with Myelofibrosis by Allogeneic Peripheral Blood Stem Cell Transplantation.

Objective: To observe the effect of allogeneic peripheral blood stem cell transplantation (allo-PBSCT) on hematopoietic reconstitution of chronic myelogenous leukemia (CML) and reversion of myelofibrosis (MF).

Methods: A 39 years old male patient diagnosed with CML complicated with MF and hepatitis B carrier condition (HBsAg+)underwent allo-PBSCT. The donor was the patient’s sibling, his 48 years old sister. Six loci on HLA-A, B, and DRB1 were completely matched with that of the recipient and HbsAb(+). Four days after the administration of G-CSF (250ug/day), PBSCs were collected from the donor for 3 consecutive days. A total volume of 168 ml was harvested. A median nucleated cell (MNC) count of 8.54 ×10⁸/kg with 5.1 ×10⁶ /kg of CD34+ cells were actually administered to the recipient. The 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 given from Days +1 to +28 for prophylaxis of acute graft-versus-host disease (GVHD). If the concentration of hemoglobin (Hb) decreased to less than 70 g/L and/or platelet count (BPC) less than 10×10⁹ /L, the recipient was transfused with ⁶⁰Co 25cGy irradiated and leuko-depleted red blood cells (RBCs) and/or single-donor platelets. Started from Day +3, the recipient was given G-CSF until white blood cells (WBC) increased to at least 3.0× 10⁹ /L. EPO and Interleukin-11 were also given to stimulate the proliferation of the progenitors of erythrocytes and megakaryocytes. The recipient also received anisodamine with a 24 hour-maintenance dose to improve the microenvironment of hematopoiesis in bone marrow.

Results: DNA-STR on Day +30 indicated a complete chimerism in the recipient. Bone marrow biopsy on Day +50 showed a dramatic decrease of myelofibrosis in the ground substance and active hematopoiesis. Reticulinfibers reduced to 1+. No significant change on splenomegaly was observed but the hepatitis B antigen had turned negative and HBsAb had appeared.

Conclusion: 1. In order to prevent aggravation of MF, Allo-PBSCT needs to be considered as early as possible once the diagnosis of CML complicated with MF is made. 2. Transfusion with a large quantity of donor hematopoietic stem cells is beneficial for engraftment. 3. Strict Immunoinhibition of the recipient will decrease the incidence and degree of GVHD and improve engraftment. 4. The addition of agents which improve the microenvironment of hematopoiesis will enhance engraftment. 5. Recovery of the platelet count is promising post-transplantation whereas significant changes on splenomegaly was not observed. 6. Allo-PBSCT may be a promising therapy for hepatitis B.