Summary. Recently, a consensus International Prognostic Scoring System (IPSS) for predicting outcome and planning therapy in the myelodysplastic syndromes (MDS) has been developed. However, the intermediate-risk cytogenetic subgroup de®ned by the IPSS includes a miscellaneous number of different single abnormalities for which real prognosis at present is uncertain. The main aims of this study were to evaluate in an independent series the prognostic value of the IPSS and to identify chromosomal abnormalities with a previously unrecognized good or poor prognosis in 640 patients. In univariate analyses, cases with single 1q abnormalities experienced poor survival, whereas those with trisomy 8 had a higher risk of acute leukaemic transformation than the remaining patients (P 0?004 and P 0?009 respectively).Patients with single del(12p) had a similar survival to patients with a normal karyotype and showed some trend for a better survival than other cases belonging to the IPSS intermediaterisk cytogenetic subgroup (P 0?045). Multivariate analyses demonstrated that IPSS cytogenetic prognostic subgroup, proportion of bone marrow blasts and haemoglobin level were the main prognostic factors for survival, and the ®rst two characteristics and platelet count were the best predictors of acute leukaemic transformation risk. A large international co-operative study should be carried out to clarify these ®ndings.
Attempts to optimize outcomes in cord blood transplantation (CBT) by using new conditioning regimens and standardization of cord blood unit selection are warranted. In all, 88 patients (18 children and 70 adults) with hematological malignancy from nine Spanish institutions underwent a single-unit CBT after an i.v. BU-based myeloablative conditioning regimen. All evaluable patients except one engrafted. The overall cumulative incidence (CI) of myeloid engraftment was 94% at a median time of 19 days. In multivariate analysis, nonadvanced disease stage was the only factor with a favorable impact on myeloid engraftment. The CI of acute GVHD grades II-IV and chronic extensive GVHD were 24% each. The CI of nonrelapse mortality at 100 days, 180 days and 5 years was 14, 23 and 44%, respectively. The 5-year CI of relapse was 18%, whereas disease-free survival (DFS) was 46%, 39% and 11% for patients transplanted in early, intermediate and advanced stages of the disease, respectively. Our study shows high rates of engraftment with fast neutrophil recovery in patients undergoing single-unit CBT using a BU-based conditioning regimen. Long-term DFS can be achieved in a substantial number of patients with high-risk hematological malignancies, particularly when transplanted in an early stage of the disease.
This cooperative study assessed prognostic factors for overall survival (OS) and risk of transformation to acute myeloid leukemia (AML) in 541 patients with de novo myelodysplastic syndrome (MDS) and deletion 5q. Additional chromosomal abnormalities were strongly related to different patients' characteristics. In multivariate analysis, the most important predictors of both OS and AML transformation risk were number of chromosomal abnormalities (Po0.001 for both outcomes), platelet count (Po0.001 and P ¼ 0.001, respectively) and proportion of bone marrow blasts (Po0.001 and P ¼ 0.016, respectively). The number of chromosomal abnormalities defined three risk categories for AML transformation (del(5q), del(5q) þ 1 and del(5q) þ X2 abnormalities) and two for OS (one group: del(5q) and del(5q) þ 1; and del(5q) þ X2 abnormalities, as the other one); with a median survival time of 58.0 and 6.8 months, respectively. Platelet count (P ¼ 0.001) and age (P ¼ 0.034) predicted OS in patients with '5qÀsyndrome'. This study demonstrates the importance of additional chromosomal abnormalities in MDS patients with deletion 5q, challenges the current '5qÀsyndrome' definition and constitutes a useful reference series to properly analyze the results of clinical trials in these patients.
Therapy planning in patients with myelodysplastic syndromes (MDSs) is complicated by its high prognostic heterogeneity. Forty-one patient and disease characteristics at onset of 370 patients with MDS were analyzed to identify significant prognostic factors for survival and transformation to acute myeloblastic leukemia (AML), and to develop and validate a regression model for predicting survival. Multivariate regression analysis showed that the total bone marrow percentage of blast cells, age, platelet count, WBC count, and hemoglobin level were the characteristics more significantly associated with survival in the overall series. The bone marrow percentage of type I blast cells was the most important factor predicting transformation into AML. Proportional hazards regression analysis in a randomly selected training sample of 240 patients demonstrated that the combination of total bone marrow percentage of blast cells, platelet count, and age had the strongest predictive relation to survival length. The resulting regression models, continuous and categorized, were validated in the remaining test sample of 130 patients by demonstrating its capability of segregating patients into low-, intermediate-, and high-risk groups, with distinctively different survival curves (P less than .0001). A scoring system derived from the categorized model also had a great prognostic value (P less than .0001). These regression models and the simpler scoring system may be accurately used for decision-making regarding therapy in MDS patients.
Summary:Early transplant-related mortality after cord blood transplantation from unrelated donors (UD-CBT) is close to 50%, mainly due to infectious complications. We have studied the incidence and characteristics of early infections (before day 100) in a series of 27 adult patients (median age 30 years, range 16-46) undergoing UD-CBT at a single institution. All 27 patients experienced at least one infectious episode and 18 (66%) suffered a severe infection. Bacteremia occurred in 55% of patients (13 with Gram-positive and 11 with Gramnegative microorganisms). Eleven of 19 CMV-seropositive patients (58%) developed CMV antigenemia and one patient had CMV disease. Fungal infections were documented in three patients (11%), comprising invasive fungal infections in two cases and a localized esophagitis in one. Ten patients (37%) died before day 100 after transplantation. Infection was considered the primary cause of death in four patients (sepsis by Acinetobacter spp. bacteremia in three cases) and contributed to death in another four. The most striking findings in this series were the high incidence of, and mortality due to multiresistant Acinetobacter spp. and the low incidence of and lack of mortality due to CMV disease. This report confirms that infection is a major complication in adults undergoing UD-CBT. Bone Marrow Transplantation (2002) 30, 937-943.
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