Recently, the Histiocyte Society revised the diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH) to include low or absent natural killer (NK) cell activity, according to local laboratory reference. The aim of this study was to establish reference interval for functional NK-cell activity in 63 healthy Korean individuals using a flow-cytometric assay. We used peripheral blood mononuclear cells (PBMCs) as effector cells and Fluorescein isothiocyanate-labeled K562 cells as target cells. NK-cell activity was calculated using the following equation: NK-cell activity (%) = (test lysis - spontaneous lysis) x 100/(maximum lysis - spontaneous lysis). NK-cell activity was analyzed in 13 known HLH patients and 16 suspected non-HLH patients using a flow-cytometric assay. The mean (+/-SD) cytotoxicity of PBMCs from healthy individuals was 20.9 +/- 5.3% and the reference interval was 11.8-31.9%. The mean NK-cell activity of HLH patients (8.3 +/- 8.9%) was significantly lower (P = 0.001) than that of non-HLH patients (20.1 +/- 7.8%). The sequential changes in NK-cell activity in the HLH group corresponded to clinical and laboratory findings following treatment. We successfully developed a functional NK-cell activity test for use in the clinical laboratory and obtained a reference interval of NK-cell activity from healthy donors. This assay, and associated reference interval, was used to analyze 30 clinically relevant specimens and the results were shown to be well correlated.

Summary:Donor leukocyte infusion (DLI) alone has very limited efficacy for patients with acute lymphoblastic leukemia (ALL) who have relapsed after allogeneic bone marrow transplantation (BMT). We, therefore, prospectively tested the efficacy of cytoreductive chemotherapy (intermediate-dose cytarabine þ idarubicin þ etoposide) followed immediately by G-CSF-primed DLI (Chemo-DLI) in 10 relapsed ALL patients after allogeneic BMT. Seven achieved complete remission (CR) at a median of 25 days (19-73 days) after DLI. Of these seven CR patients, only one remains alive in CR 907 days after DLI. Two CR patients died in CR of graft-versus-host disease. The remaining four CR patients relapsed at a median of 153 days (120-991 days) after DLI. One is alive with leukemia at post-DLI day 1217. The median survival duration after DLI was 175 days (15-1217 days). In summary, although Chemo-DLI for relapsed ALL after allogeneic BMT induced a relatively high CR rate, durable remissions were rare. Although our data should be interpreted cautiously considering the small number of patients, these results suggest that poor outcome of DLI in relapsed ALL may be primarily due to intrinsic resistance to graft-versus-leukemia effect rather than to the rapid pace of the disease. For patients with acute lymphoblastic leukemia (ALL) receiving allogeneic bone marrow transplantation (BMT), relapse remains the major cause of treatment failure and is associated with a very poor prognosis. The optimal salvage treatment for patients with ALL who relapse after allogeneic BMT has not yet been established, since most therapies are of limited benefit. While reinduction chemotherapy can induce remission in about 40-60% of patients, most of these patients eventually relapse and die of uncontrolled leukemia, with a 3-year disease-free survival (DFS) rate of less than 10%. 1-4 A second BMT results in long-term event-free survival in only 10-20% of patients with relapsed ALL. 5-7 However, even these poor results may be an overestimate because only a small proportion of relapsed patients is suitable for second BMT, and hence the results may reflect the positively biased outcome of a highly selected group of patients. Only 7-20% of patients has been reported to reach the stage of a second BMT after relapse according to the performance and remission status after salvage chemotherapy. 2,8 Moreover, second BMT is associated with extremely high treatment-related mortality, ranging from 40% to 50%. [6][7][8] Another approach to the treatment of ALL patients who relapse after allogeneic BMT is donor leukocyte infusion (DLI), which may induce a graft-versus-leukemia (GVL) effect. DLI has been shown to be highly effective in patients with chronic myelogenous leukemia (CML) who relapse into the chronic phase, achieving complete and durable remission in 70-80% of these patients. 9,10 In contrast, DLI for relapsed ALL has been much less effective. Although there have been many case reports showing that patients with ALL respond to DLI, [11][12][13][14][15][16][17][18][...

Summary:To evaluate the significance of clinical abnormalities occurring during the peri-engraftment period following allogeneic hematopoietic cell transplantation (HCT), we retrospectively analyzed the data of 216 allogeneic HCT recipients. The most frequently observed peri-engraftment clinical abnormality (PECA) was noninfectious fever in 58 patients, followed by hepatic dysfunction in 39, weight gain in 22, and renal insufficiency in 11. Frequently identified predictive factors for a higher incidence of each PECA were HCT from an unrelated or mismatched donor, GVHD prophylaxis with cyclosporine alone, and rapid engraftment. Considering that donor type and GVHD prophylaxis are closely related to GVHD, these observations suggest that the development of PECAs might be associated with a graft-versus-host reaction. This hypothesis was supported by the fact that the patient group with each PECA showed a higher incidence of grades 3-4 acute or chronic extensive GVHD, with varying degrees of statistical significance. Although our data should be interpreted cautiously in view of their retrospective nature, some of the PECAs occurring after allogeneic HCT may be atypical manifestations of GVHD and may be associated with severe forms of acute or chronic GVHD. Bone Marrow Transplantation (2003) 32, 809-813. doi:10.1038/sj.bmt.1704224 Keywords: peri-engraftment clinical abnormality; allogeneic hematopoietic cell transplantation; graft-versus-host disease; engraftment syndrome Following hematopoietic cell transplantation (HCT), various clinical abnormalities such as noninfectious fever, weight gain due to capillary leakage, hepatic dysfunction, and renal insufficiency have been reported to occur immediately before, or at the time of neutrophil engraftment. 1-6 These peri-engraftment clinical abnormalities (PECAs) have been described most often in the setting of autologous HCT, 1,2 usually as a part of the engraftment syndrome or capillary leakage syndrome, with widely variable incidences and heterogenous risk factors. While cellular and cytokine interactions associated with neutrophil and lymphocyte recovery are believed to be responsible for the occurrence of PECAs, the distinct pathophysiologic mechanisms have not been clearly defined. 3 PECAs have also been described in the allogeneic HCT setting. [4][5][6] However, only a few studies with a limited number of patients have been reported to date, and thus, little is known about the clinical significance of PECAs in the allogeneic HCT setting. To characterize PECAs and to evaluate their clinical significance following allogeneic HCT, we retrospectively analyzed the data of 216 consecutive allogeneic HCT recipients. Patients and methods Patients and transplant procedureWe retrospectively reviewed the data of all consecutive adult patients who underwent allogeneic HCT between December 1993 and December 2001 at the Asan Medical Center, University of Ulsan, Seoul, Korea. Data were retrieved from the allogeneic HCT database of Asan Medical Center that includes all the clinical...