Four patients with chronic inflammatory demyelinating polyneuropathy (CIDP) who were refractory to conventional treatment were treated with high-dose cyclophosphamide (200 mg/kg over 4 days). All improved in functional status and muscle strength. Nerve conduction studies improved in three of four. Other immunomodulatory medications have been discontinued. High-dose cyclophosphamide can be given safely to patients with CIDP and patients with disease persistence after standard therapy may have a response that lasts for over 3 years and results in long-term disease remission.

We studied the feasibility, toxicity, and efficacy of a 2-step approach to autologous stem cell transplantation for patients with acute myeloid leukemia in first remission. Step 1 consisted of consolidation chemotherapy including cytarabine 2000 mg/m2 twice daily for 4 days concurrent with etoposide 40 mg/kg by continuous infusion over 4 days. During the recovery from this chemotherapy, peripheral blood stem cells were collected under granulocyte colony-stimulating factor stimulation. Step 2, autologous stem cell transplantation, involved the preparative regimen of busulfan 16 mg/kg followed by etoposide 60 mg/kg and reinfusion of unpurged peripheral blood stem cells. A total of 128 patients were treated. During step 1, there was 1 treatment-related death. A median CD34+ cell dose of 14 (x10(6)/kg) was collected in 3 aphereses. Ten patients suffered relapse before transplantation, and 117 patients (91%) proceeded to transplantation. During step 2, there were 2 treatment-related deaths, and 35 patients subsequently suffered relapse. With median follow-up of 30 months, 5-year disease-free survival for all patients entered in the study is projected to be 55%. By cytogenetic risk group, 5-year disease-free survival is 73% for favorable-risk patients, 51% for intermediate-risk patients, and 0% for poor-risk patients. We conclude that this 2-step approach to autologous transplantation produces excellent stem cell yields and allows a high percentage of patients to receive the intended therapy. Preliminary efficacy analysis is very encouraging, with outcomes that appear superior to those of conventional chemotherapy.

Thrombotic thrombocytopenic purpura (TTP) after bone marrow transplantation (BMT) is an uncommon complication presumably associated with extensive endothelial cell damage due to Cyclosporine, total body irradiation, or other drugs. While the majority of patients with primary TTP, which is considered to be an autoimmune process, respond to plasma exchange, TTP after BMT has a very poor prognosis. A total of 7 patients out of 307 patients who underwent BMT were diagnosed with TTP during 1989-1999. The diagnosis of TTP was made based on thrombocytopenia and microhemangiopathic hemolytic anemia characterized by an elevated LDH and the presence of schistocytes on the peripheral blood smear. Five patients were treated with plasma exchange (PE) using fresh frozen plasma and/or cryoprecipitate poor plasma as replacement fluid. One patient was treated using a protein A column. One patient did not receive plasma exchange because the 125 patient was clinically stable and was discharged. It was hard to assess the efficacy of PE due to the multiplicity of the patients' clinical condition and laboratory data. At least 4 patients did not respond to PE and 2 patients were not able to be evaluated due to multi organ failure. However, all patients died. It is not clear at this moment if PE for patients with TTP after BMT is truly beneficial.

Cytotoxic therapy is a cornerstone for patients with severe systemic lupus erythematosus (SLE). High-dose cyclophosphamide, 200 mg/kg, can induce a complete remission without the need for stem cell rescue in patients with autoimmune illnesses. Here we report on our first four patients treated for severe SLE with this treatment approach. Patients received cyclophosphamide, 200 mg/kg, divided over 4 days. Starting day 10, patients received filgrastim, 5 micrograms/kg/day, until their absolute neutrophil count (ANC) rose to 10.0 x 10(9)/l for two consecutive days. Disease activity as evaluated by scores from the Systemic Lupus Activity Measure-2, the SLE Disease Activity Index and the Responder Index for Lupus Erythematosus were completed before and after high-dose therapy. Before high-dose cyclophosphamide, SLE disease duration ranged from 8 to 21 (mean 12.5) years. Their average disease activity measured by SLAM-2 and SLEDAI was 15.5 (range 11-19) and 23.25 (range 20-26), respectively. At a median of 22 (range 12-39) months of follow-up, mean disease activity measured by SLAM-2 and SLEDAI decreased to 6.25 and 7.75, respectively. All patients experienced febrile neutropenia. No long-term morbidities or mortalities were observed. High dose cyclophosphamide is a therapy capable of decreasing disease severity in poor prognosis SLE patients. Future study is warranted for both refractory patients as well as primary therapy for patients with moderate to severe disease presentations.

While half of all patients receiving bone marrow transplantation (BMT) for malignancies and related diseases may achieve prolonged disease-free survival, 2-10% of patients undergoing allogeneic transplantation develop bronchiolitis obliterans (BrOb). We have hypothesized that total body irradiation (TBI) which has been used for pretreatment may influence the subsequent development of BrOb in patients undergoing allogeneic BMT. Since 1976, we have treated 104 patients undergoing allogeneic BMT with non-TBI preconditioning. Of 60 patients that survived and were evaluable for chronic graft versus host disease (GVHD) 26 developed chronic GVHD (43%). Four of 104 patients (3.9%) developed BrOb by clinical and/or pathologic findings. Four of 4 patients (100%) with BrOb had chronic GVHD. Two of these 4 patients (50%) were alive at the end of 2 years. These data demonstrate that chronic GVHD is a risk factor for BrOb in patients receiving non-TBI preconditioning regimens. The similar incidence of BrOb in this population compared to other studies using TBI suggest that the preconditioning regimen is not a factor in the development of BrOb. Further study is needed to confirm these findings. Allogeneic bone marrow transplantation (BMT) has revolutionized the therapeutic approach toward acute and chronic leukemias, aplastic anemia and rare immunodeficiency disorders. Half of all patients that undergo BMT achieve long-term disease-free survival but a similar number develop significant complications [1]. Prior to the realization of long-term survival in these patients there was an emphasis on the early pulmonary complications of BMT including infectious and noninfectious pneumonitis, acute graft-vs.-host disease (GVHD), chronic aspiration, obstructive airways disease, and pulmonary vascular thrombotic disease [1]. Now with prolonged survival after BMT there is increased attention focused on the relatively late finding of bronchiolitis obliterans (BrOb). BrOb is an obstructive pulmonary disorder affecting the small airways that is associated with connective tissue disease, drug administration, and recently heart-lung transplantation [2,3]. Since 1982, there have been several reports recognizing BrOb to be a late complication of allogeneic BMT [2,4-15]. The etiology of BrOb in these cases is unclear but may in part be due to preconditioning regimens given the results of earlier studies which demonstrated a decline in lung function following TBI [16,17]. We will describe the outcome at our institution of 104 patients that received allogeneic BMTs without TBI preconditioning and compare these results to the experience of other transplant centers where TBI is used in order to determine if preconditioning regimens increase the risk of developing BrOb [2,15].