Peri-engraftment clinical abnormalities following allogeneic hematopoietic cell transplantation: a retrospective review of 216 patients

Abstract

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...

Cyclosporine alone vs cyclosporine plus methotrexate for post-transplant immunosuppression after HLA-identical sibling bone marrow transplantation: a randomized prospective study

“…However, the rate of grade I acute GVHD was higher in the CS arm (nine cases) than in the CS þ MTX arm (two cases), and many of these cases were characterized by skin rashes and febrile episodes that occurred early after bone marrow transplantation during the periengraftment period, but which responded well to treatment with systemic glucocorticosteroids. 26 Similar frequencies of grade II-IV acute GVHD have been observed in patients with severe aplastic anemia treated with CS alone (38%) or CS þ MTX (30%, P ¼ 0.37), and the onset of acute GVHD was shorter for the CS alone group. 22 Low frequency of grade II-IV acute GVHD in our study is in contrast to other studies from the United States and Europe, which reported the frequency of up to 54%.…”

Engraftment Syndrome after Allogeneic Hematopoietic Cell Transplantation Predicts Poor Outcomes

“…6-22 This is likely affected by the heterogeneity of center-specific definitions of ES. Furthermore, whether ES and GVHD are distinct syndromes in the allogeneic context remains unclear.…”

“…Furthermore, whether ES and GVHD are distinct syndromes in the allogeneic context remains unclear. 6,7,10,15,17,22 The prognostic impact of ES on outcomes, such as graft-versus-host disease (GVHD), relapse, NRM, and survival has not been well-characterized. Although the underlying pathogenesis of ES remains poorly understood, inflammatory mediators likely contribute to its development.…”

“…6-22 Spitzer's criteria is the most widely described 3 with variations related to the duration of the neutrophil peri-engraftment period for associated symptoms. 7,8,11-15 Risk factors noted to be associated with ES include: myeloablative conditioning, 10,17,18,20 unrelated donor, 6,7,10 female recipient, 9 use of G-CSF, 12 number of prior chemotherapy regimens received, 10 higher cell concentration infused at transplant, 12,15,22 donor-recipient HLA disparity, 13 and age 9,13,17 …”

Clinical impact of hyperacute graft-versus-host disease on results of allogeneic stem cell transplantation

“…6 Even though the term engraftment syndrome is widely used in autologous or allogeneic transplant settings, haGVHD would seem to be a more appropriate description of the immunological phenomena in an allogeneic setting. The use of this term to describe the clinical manifestations that occur before engraftment in an allogeneic transplant setting is necessary, because some symptoms or signs seen in the post-engraftment period can be described as acute GVHD (aGVHD) and a term describing the manifestations before engraftment is lacking.…”