For patients with acute myeloid leukemia (AML) relapsed after allogeneic bone marrow transplantation (BMT), donor leukocyte infusion (DLI) as sole therapy has very limited efficacy. We tested the effects of cytoreductive chemotherapy, followed immediately by G-CSF-primed DLI (chemotherapy followed by DLI, Chemo-DLI), in 16 AML patients who relapsed after allogeneic BMT. In all, 10 of these patients achieved complete remission (CR), four of whom remain alive in CR at a median follow-up of 1488 days after DLI. The 2-year overall survival (OS) for the entire cohort was 31%. The 1-year OS for patients with post-BMT remission of 6 months or longer was 55%, compared with 0% for patients with post-BMT remission of less than 6 months, making post-BMT remission duration the only significant prognostic factor for OS (P ¼ 0.015). These findings suggest that Chemo-DLI could induce durable remissions in a proportion of relapsed AML patients with relatively long post-BMT remission duration. All five patients who relapsed after achieving CR with Chemo-DLI relapsed at extramedullary sites in the presence of continuous bone marrow remission, suggesting uneven graft-versus-leukemia effects in different parts of the body. Although our data should be interpreted cautiously considering the limited number of patients, isolated extramedullary relapse seems to be common after Chemo-DLI.

Summary:Delayed erythropoiesis and pure red cell aplasia (PRCA) have been reported after major ABO-incompatible BMT. We attempted to find risk factors for the development of PRCA in 27 patients who underwent major ABO-incompatible BMT. In all patients, the donor marrow was depleted of RBCs before infusion. In 22 patients, isoagglutinins were determined until they disappeared. In eight (29.6%) out of 27 patients, bone marrow examination following BMT showed the findings of PRCA. We analyzed various clinico-pathologic risk factors and isoagglutinin type was the only significant risk factor. Patients with anti-A isoagglutinins against donor RBC developed PRCA more frequently than patients with anti-B (8/17 vs 0/9). Median days to the disappearance of isoagglutinins tended to be longer in patients with PRCA (PRCA vs non-PRCA, 200 vs 66 days) and in cases with anti-A isoagglutinins (anti-A vs anti-B, 160 vs 51 days). Times to disappearance of isoagglutinins correlated with times to reticulocytes over 1% and initial appearance of donor type RBC (R 2 = 0.708 and 0.711). In conclusion, RBC engraftment following major ABO-incompatible BMT was dependent on the disappearance of isoagglutinins against donor RBC, and anti-A isoagglutinin was a risk factor for the development of PRCA after major ABO-incompatible allogeneic BMT. Bone Marrow Transplantation (2000) 25, 179-184. Keywords: anti-A isoagglutinin; PRCA; ABO-incompatible BMT Major donor-recipient ABO incompatibility is not considered to be a contraindication to successful bone marrow transplantation (BMT). Acute hemolysis by anti-A or anti-B isoagglutinins of recipient origin at the time of donor marrow infusion can effectively be prevented by the removal of anti-A or anti-B isoagglutinins from the recipients or by the depletion of red blood cells from marrow grafts. [1][2][3][4] Previous studies showed no significant effect of major ABO mismatch on the incidence of graft rejection, the incidence of graft-

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...

Summary:The role of methotrexate (MTX), given with cyclosporine (CS), after HLA-identical sibling bone marrow transplantation needs to be defined. In all, 80 patients with hematologic malignancies were enrolled in a prospective randomized trial. All were given BuCy conditioning. The 40 patients in the CS arm received CS 3 mg/kg/day intravenously, with subsequent oral dosing. Patients in the CS þ MTX arm received, in addition to CS, MTX intravenously, 15 mg/m 2 on day 1, and 10 mg/m 2 on days 3, 6, and 11. Transplantation-related mortality was low in both groups of patients (13 vs 11% for CS vs CS þ MTX groups, P ¼ 0.94). The CS group had a significantly higher frequency of chronic graft-versus-host disease (56 vs 32%, P ¼ 0.05). After a median follow-up of 22.1 months (5.1-47.8 months), three of 30 vs 10 of 28 patients with acute leukemia/myelodysplastic syndrome (MDS) in CS group vs CS þ MTX group relapsed (P ¼ 0.01) yielding better overall survival for patients with acute leukemia/MDS treated with CS (P ¼ 0.02). After HLAidentical sibling bone marrow transplantation, immunosuppression with CS, with or without MTX, resulted in similarly low transplantation-related mortality. In acute leukemia/MDS, decreased relapse with patient survival prolongation was observed in the CS group. The main method of post-transplant immunosuppression after HLA-identical sibling bone marrow transplantation has been the administration of immunosuppressive agents, including methotrexate (MTX), cyclosporine (CS), and glucocorticosteroids. [1][2][3] Early clinical trials were characterized by high transplantation-related mortality, of up to 42% of patients, especially those given CS or MTX alone. 1,2,4-11 Over half of the cases of transplantationrelated mortality were due to interstitial pneumonitis, with or without documented cytomegalovirus (CMV) disease. Post-transplant immunosuppression utilizing combinations of immunosuppressive agents showed a lower incidence of acute graft-versus-host disease (GVHD) and transplantation-related deaths. 3,6-11 Although combination therapy is widely accepted for post-transplant immunosuppression in various settings of allogeneic hematopoietic cell transplantation, including HLA-identical sibling bone marrow transplantation, 12 the optimum regimen for post-transplant immunosuppression in the latter requires further investigation, primarily because recent improvements in the management of patients with GVHD and resulting infectious complications, such as CMV, have been shown to significantly decrease the incidence of transplantationrelated mortality after allogeneic hematopoietic cell transplantation. 13 In addition, several studies have reported increased relapse rates of underlying leukemia resulting from combined immunosuppression after HLA-identical sibling bone marrow transplantation. 7,14 These findings indicate that, in HLA-identical sibling bone marrow transplantation, where the genetic disparity between the donor and the patient is relatively small, optimum posttransplant immunosuppression s...