Peripheral blood stem cells (PBSCs) have been used rarely for allogeneic transplantation because of concerns regarding graft failure and graft-versus-host disease (GVHD). We evaluated the results of allogeneic PBSC transplantation (allo-PBSCT) in 9 patients with refractory leukemia or lymphoma receiving myeloablative therapy followed by allo-PBSCT from an HLA-identical sibling donor. Three patients had relapsed 11 to 21 months after allogeneic bone marrow transplantation (allo-BMT) and underwent allo-PBSCT using the same donor. Six patients received PBSCs as their initial allogeneic transplant. Filgrastim-mobilized PBSCs were collected from the donors in 3 to 4 aphereses and cryopreserved. The apheresis collections contained a median nucleated cell count of 16.5 x 10(8)/kg (range, 10.8 to 28.7 x 10(8), 10.7 x 10(6) CD34+ cells/kg (range, 7.5 to 22.5 x 10(6)), and 300.0 x 10(6) CD3+ cells/kg (range, 127.8 to 1,523.2 x 10(6)). The median recovery of CD34+ progenitor cells after freezing, thawing, and washing was 106.4% (range, 36.7% to 132.0%). All patients received filgrastim posttransplant through engraftment, and cyclosporine and methylprednisolone were used for GVHD prophylaxis. Neutrophil recovery to greater than 0.5 x 10(9)/L and greater than 1.0 x 10(9)/L occurred at a median of 9 (range, 8 to 10) and 9 days (range, 8 to 11) posttransplant, respectively, which was similar to historical controls after allo-BMT and granulocyte colony-stimulating factor therapy. Platelets recovered to greater than 20 x 10(9)/L and greater than 50 x 10(9)/L at a median of 12 (range, 8 to 25) and 15 days (range, 11 to 59), respectively, which was significantly more rapid than for the controls (P < .01). Donor cell engraftment was documented by cytogenetics, fluorescence in situ hybridization, and/or restriction fragment length polymorphisms with longest follow-up of 283 + days. Three patients developed grade 2 acute GVHD involving only the skin. Three of five evaluable patients show limited chronic GVHD. Cryopreserved, filgrastim-stimulated allogeneic PBSCs may be a suitable alternative to allogeneic marrow for transplantation with the advantage of more rapid platelet recovery. Acute GVHD was minimal despite the infusion of 1 log more CD3 cells than with marrow allografts. Further studies are required to assess long-term risks of chronic GVHD.
Plasma exchange has been proposed as a treatment for multiple disorders. Three patients with amyotropic lateral sclerosis, who were hemostatically normal, were studied through a total of 11 4-liter exchanges. Plasma was replaced by an equal volume of 5% albumin or 5% plasma protein fraction. Serial studies revealed that immediately after the exchange transfusion, there was significant prolongation of the prothrombin, partial thromboplastin, and thrombin times with reduction of the fibrinogen and antithrombin III levels. Factors V, VII-X, IX, and X were all significantly decreased, as were the factor VIII antigen, procoagulant, and the ristocetin cofactor activities. Platelet counts were obtained before and after exchanges and revealed significant decreases. Four hours after exchange, all parameters remained abnormal except the factor IX, ristocetin cofactor, and factor VIII procoagulant activities. By 24 hr, all hemostatic parameters had returned to normal. These studies indicate that plasma-exchange transfusion with material devoid of coagulation factors results in a coagulation defect that may be of clinical significance in a hemostatically compromised patient.
Immunophenotypes for 272 patients with acute myelogenous leukemia (AML) were analyzed using a panel of 22 antibodies. Numerical evidence for unusual coexpressions (present in normal marrow at < or = 0.1%) of surface markers on = or = 10% of the blast cells was found in 85% of all cases. Asynchronous expression of myeloid differentiation antigens occurred in 70% of the cases. Unusual coexpression of T-lymphoid, B- lymphoid, or natural killer (NK) markers with myeloid markers occurred in 38%, 13%, and 21%, respectively, of all AML cases. Two- and three- color analyses confirmed coexpression in 15 of 15 cases, and indicated that these percentages are an underestimate, because coexpression can be demonstrated in cases without numerical overlap. These data indicate that the unusual coexpression of normal differentiation antigens is a common occurrence in AML. Markers in 12 of 13 patients were similar between presentation and relapse, and in two patients, unusual phenotypes detected at first relapse were shown at second relapse, indicating these immunophenotypes are stable in the majority of AML patients. Significant correlations were found between t(8;21) cytogenetics and coexpression of CD19 with CD15 or CD34, t(9;22) and coexpression of CD19 and CD34, and t(15;17) and coexpression of CD2 and myeloid antigens. Multiparameter fluorescence analysis allows detection of unusual phenotypes when the blast counts are < 5% (classical remission). Analysis of 16 patients in remission indicated the presence of presentation phenotypes in 0.2% to 7.9% of the lymphocyte + blast light scatter region, representing 0.03% to 1.4% of the total nucleated marrow cells. Of the 16 patients with = or = 4 months follow-up after detection of these cells, 6 of 6 patients with = or = 0.2% unusual presentation phenotypic marrow cells have relapsed, while 9 of 10 patients with < 0.2% remain in remission. The detection of cells with the unusual presentation phenotype may reflect residual AML cells, and their increase may predict relapse.
Hematopoietic cells from the malignant clone in chronic myelogenous leukemia (CML) maintain and expand a proliferative advantage over normal hematopoietic cells within the bone marrow. This advantage is often ameliorated or reversed in vivo by IFNa. Based upon earlier studies suggesting decreased
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