Haploidentical Bone Marrow Transplantation for Treatment of Patients with Aggressive and Refractory Lymphoma.

Abstract

Allogeneic bone marrow transplantation (Allo-BMT) is a potential curative treatment for patients with aggressive and refractory non-Hodgkin's lymphoma (NHL) who relapse after autologous stem cell transplantation (Auto-SCT) or have bone marrow involvement. However Allo-BMT limited by the availability of a suitably matched donor. With only 30–40% of patients having a matched-related donor available, haploidentical transplantation may increase the applicability of Allo-BMT. The high incidence of severe GVHD is a barrier of the application of haploidentical BMT. Based on our encouraging results of haploidentical BMT of using G-CSF primed marrow and sequential immunosuppressants for high-risk leukemia, we extended the study to treatment of patients with aggressive and refractory NHL. From May 2000 to November 2003, eight patients underwent BMT from HLA two or three loci mismatched related donor. The median patient age was 15 year (range 7–44 y). All patients were transplanted for aggressive and refractory NHL of bone marrow involvement. Two of them relapsed after Auto-SCT. The donors were given G- CSF 300ug/day for seven doses prior to marrow harvest. Conditioning comprised TBI, Ara-C and Cyclophosphamide. Patient 1 received CSA, MTX , ATG and Mycophenolate mofetil (MMF) for GVHD prophylaxis. The remainder seven patients added CD25 monoclonal antibody (Simulect, Novartis Pharma Switzerland) with CSA, MTX , ATG and Mycophenolate mofetil (MMF) for GVHD prophylaxis. A total 40mg Simulect was given in two doses of 20mg each by 30 min intravenous infusion on 2h before transplant and day 4 after transplant. All patients established sustained trilineage engraftment. The median days of granulocytes exceeding 0.5x109/L and platelets exceeding 20x109/L were 17 and 22 days. All patients had 100% donors hematopoietic cells after transplantation by cytogenetic evidence analysis. Two (patient 1 and patient 7) of eight patients experienced the gut II-IV acute GVHD. The incidence of aGVHD II-IV was 25%. Six patients evaluated for chronic GVHD experienced chronic GVHD. One of them developed clinical extensive cGVHD which responded to the administration of steroids and CSA. The median follow-up duration of patients was 23 months (range 7–46 months), two patients died from transplant related mortality.Causes of deaths were acute GVHD in 1 patient who did not added CD25 monoclonal antibody for GVHD prophylaxis, fungal infection in 1 patient.No patient relapsed during follow-up duration. Six patients were alive in disease free situation. The survival patients had Karnofsky clinical performance status of 100%. In conclusion,the transplants from haploidentical graft in which the donors received G-CSF prior to harvest and five kinds of immunosuppression added to recipient for treatment of patients with aggressive and refractory NHL is effective and feasibility. The addition of CD25 monoclonal antibody to immunosuppression as GVHD prophylaxis may reduced severe lethal acute GVHD.