PURPOSE: Recipients of allogeneic bone marrow transplants (BMTs) who have relapsed may attain complete remissions when treated with transfusions of leukocytes obtained from the original bone marrow donor. We performed a retrospective study to characterize better this new treatment modality. PATIENTS AND METHODS: We surveyed 25 North American BMT programs regarding their use of donor leukocyte infusions (DLI). Detailed forms were used to gather data regarding the original BMT, relapse, DLI, response to DLI, complications of DLI, and long-term follow-up evaluation. Reports of 140 patients were thus available for analysis. RESULTS: Complete responses were observed in 60% (95% confidence interval [CI], 51.9% to 68.1%) of chronic myelogenous leukemia (CML) patients who received DLI and did not receive pre-DLI chemotherapy; response rates were higher in patients with cytogenetic and chronic-phase relapse (75.7%; 95% CI, 68.2% to 83.2%) than in patients with accelerated-phase (33.3%; 95% CI, 19.7% to 46.9%) or blastic-phase (16.7%; 95% CI, 1.9% to 31.9%) relapse. The actuarial probability of remaining in complete remission at 2 years was 89.6%. Complete remission rates in acute myelogenous leukemia (AML) (n = 39) and acute lymphocytic leukemia (ALL) (n = 11) patients who had not received pre-DLI chemotherapy were 15.4% (95% CI, 9.6% to 21.2%) and 18.2% (95% CI, 6.6% to 29.8%), respectively. Complete remissions were also observed in two of four assessable myeloma patients and two of five assessable myelodysplasia patients. Complications of DLI included acute graft-versus-host disease (GVHD) (60%; 95% CI, 51.4% to 68.6%), chronic GVHD (60.7%; 95% CI, 50.3% to 71.1%), and pancytopenia (18.6%; 95% CI, 12.2% to 25.0%). Pre-DLI characteristics predictive of complete response in CML patients were post-BMT chronic GVHD, pre-DLI disease status of chronic phase, and time interval between BMT to DLI less than 2 years. Acute and chronic GVHD post-DLI were highly correlated with disease response (P < .00001). CONCLUSION: DLI results in complete remissions in a high percentage of patients with relapsed chronic-phase CML. Complete remissions are observed less frequently in patients with advanced CML and acute leukemia. GVHD and pancytopenia occur commonly; GVHD is highly correlated with response.

It is here reported that mesenchymal stem cells known to give rise to limb-bud mesoderm can, at the single-cell level, also differentiate into cells of visceral mesoderm and can be expanded extensively by means of clinically applicable methods. These cells were named mesodermal progenitor cells (MPCs). MPCs were selected by depleting bone marrow mononuclear cells from more than 30 healthy human donors of CD45+/glycophorin-A (GlyA)+ cells. Cells were cultured on fibronectin with epidermal growth factor and platelet-derived growth factor BB and 2% or less fetal calf serum. It was found that 1/5 × 103CD45−GlyA− cells, or 1/106 bone marrow mononuclear cells, gave rise to clusters of small adherent cells. Cell-doubling time was 48 to 72 hours, and cells have been expanded in culture for more than 60 cell doublings. MPCs are CD34−, CD44low, CD45−, CD117 (cKit)−, class I–HLA−, and HLA-DR−. MPCs differentiated into cells of limb-bud mesoderm (osteoblasts, chondrocytes, adipocytes, stroma cells, and skeletal myoblasts) as well as visceral mesoderm (endothelial cells). Retroviral marking was used to definitively prove that single MPCs can differentiate into cells of limb bud and visceral mesoderm. Thus, MPCs that proliferate without obvious senescence under clinically applicable conditions and differentiate at the single-cell level not only into mesenchymal cells but also cells of visceral mesoderm may be an ideal source of stem cells for treatment of genetic or degenerative disorders affecting cells of mesodermal origin.

Limited umbilical cord blood (UCB) cell dose compromises the outcome of adult UCB transplantation. Therefore, to augment graft cell dose, we evaluated the safety of the combined transplantation of 2 partially human leukocyte antigen (HLA)–matched UCB units. Twenty-three patients with high-risk hematologic malignancy (median age, 24 years; range, 13-53 years) received 2 UCB units (median infused dose, 3.5 × 107 nucleated cell [NC]/kg; range, 1.1-6.3 × 107 NC/kg) after myeloablative conditioning. All evaluable patients (n = 21) engrafted at a median of 23 days (range, 15-41 days). At day 21, engraftment was derived from both donors in 24% of patients and a single donor in 76% of patients, with 1 unit predominating in all patients by day 100. Although neither nucleated or CD34+ cell doses nor HLA-match predicted which unit would predominate, the predominating unit had a significantly higher CD3+ dose (P < .01). Incidences of grades II-IV and III-IV acute GVHD were 65% (95% confidence interval [CI], 42%-88%) and 13% (95% CI, 0%-26%), respectively. Disease-free survival was 57% (95% CI, 35%-79%) at 1 year, with 72% (95% CI, 49%-95%) of patients alive if they received transplants while in remission. Therefore, transplantation of 2 partially HLA-matched UCB units is safe, and may overcome the cell-dose barrier that limits the use of UCB in many adults and adolescents.