tAPL is not exceptional, and develops usually less than 3 years after a primary neoplasm (especially breast carcinoma) treated in particular with topoisomerase II-targeted drugs (anthracyclines or mitoxantrone and less often etoposide). Characteristics and outcome of tAPL seem similar to those of de novo APL.
dard chemotherapy have a median survival ranging from Among the 248 patients evaluable for response 125 24 to 36 months with less than 5% of patients surviving at (51%) had a CR and 100 had a PR (40%). The median 10 years. 1-3 The response rates to most conventional duration of progression-free survival (PFS) and overall chemotherapy regimens are usually between 40 and 60%, survival (OS) after transplantation was 23 and 35and only 5 to 10% of these responses consist of complete months, respectively. Univariate analysis showed that remissions (CR).
Summary. Reduced-intensity conditioning (RIC) regimens for allogeneic haematopoietic stem cell transplantation (SCT) have been shown to lead to engraftment of donor stem cells without the severe extra-haematological toxicities of traditional myeloablative transplants. Between December 1998 and December 2000, 76 patients underwent a RIC peripheral blood SCT in a prospective multicentre study. The median age was 53 years, and 57 patients were beyond the early phase of their disease. The conditioning regimens consisted of fludarabine (150 mg/ m 2 ) plus melphalan (140 mg/m 2 ) or busulphan (10 mg/kg). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin A plus short-course methotrexate. The preparative regimens were well tolerated. All patients experienced severe pancytopenia, but haematological recovery was prompt in all but two cases (early deaths). The 100-d probability of developing grade II±IV acute GVHD was 32% (10% grade III±IV), and the 1-year probability of developing chronic extensive GVHD was 43%. Early complete donor chimaerism was observed in 52/68 patients, and 16 evaluable patients were in complete chimaerism 1 year post transplant. With a median follow-up of 283 d (355 in 48 survivors), the 1-year probability of transplant-related mortality was 20%, and the 1-year overall and progression-free survivals were 60% and 55% respectively. In conclusion, RIC regimens lead to low early toxicity after allografting, with stable donor haematopoietic engraftment, with an apparent low risk of acute GVHD. Chronic GVHD, however, develops in a significant proportion of patients.
A study on 315 patients undergoing transplantation with CD34 ؉ selected blood cells from HLA-identical siblings was performed to determine risk factors for acute GVHD (aGVHD). Recipients of a dose of CD34 ؉ cells (؋ 10 6 /kg) of 2 or less, more than 2 to 4, and more than 4 had a cumulative incidence of aGVHD grades I-IV of 21%, 35%, and 43%, respectively (log-rank P ؍ .01); similarly, recipients of a dose of CD3 ؉ cells (؋ 10 6 /kg) of 0.05 or less, more than 0.05 to 0.1, and more than 0.1 had a cumulative incidence of aGVHD grades I-IV of 18%, 35%, and 44%, respectively (log-rank P ؍ .007). Using a Cox regression model, 4 independent factors for aGVHD I-IV were identified: increased CD34 ؉ cell dose (P ؍ .02), increased CD3 ؉ cell dose (P ؍ .02), female patients (P ؍ .01), and higher patient age (> 42 years IntroductionAcute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after allogeneic stem cell transplantation. 1,2 Although widely accepted risk factors for aGVHD have been identified in patients receiving unmodified grafts, 3-6 these parameters may not have the same predictive value in patients receiving a graft in which donor T cells, the major determinant of GVHD, have been depleted. The isolation of risk factors for aGVHD in T-cell-depleted transplantations could be useful to identify individual patients at a high probability of developing this complication. The present study was directed at identifying factors predictive of aGVHD in 315 adult patients receiving an HLAidentical sibling transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells T-cell depleted by means of CD34 ϩ selection (allo-PBT/CD34 ϩ ). We observed a strong association between the incidence of aGVHD and 2 controllable variables: the number of CD34 ϩ and CD3 ϩ cells infused. Study designThis study included 315 consecutive adult patients with hematologic malignancies treated with an allo-PBT/CD34 ϩ from an HLA-identical sibling donor between March 1995 and December 2000. Granulocyte colony-stimulating factor administration and leukapheresis procedures have been previously described. 7 This study was approved by local ethic committees and by the Spanish Department of Health. Informed consent was provided according to the Declaration of Helsinki. Patient and donor characteristics are shown in Table 1. CD34 ϩ cells and CD3 ϩ cells were quantified as previously published. 7 There was no correlation between CD34 ϩ and CD3 ϩ cell dose (Pearson correlation coefficient Ϫ0.04; P ϭ .47). Phase of disease, time to engraftment, diagnosis of graft failure, and transplantation-related mortality (TRM) have been previously defined. 8 The diagnosis and grading of aGVHD was established according to the Seattle criteria. 9 Probabilities of aGVHD were calculated by the cumulative incidence method (marginal probability) and statistically compared by Gray method. 10,11 In this study, graft failure or relapse, without aGVHD, were considered competing risks. Characteristics consi...
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