Nephrotic syndrome after allogeneic hematopoietic stem cell transplantation as a late complication of chronic graft-versus-host disease.

Background. This study aims to determine the incidence and outcome of nephrotic syndrome in patients who underwent allogeneic stem cell transplantation in a single center. Methods. Records of 279 adult patients with hematological diseases who underwent allogeneic hematopoietic stem cell transplantation were analyzed to evaluate the incidence and outcome of nephrotic syndrome. The diagnosis of chronic graft-versus-host disease was based on clinical evidence with histological confirmation whenever possible. Results. Of the 279 patients, 105 with a minimum follow-up of 100 days developed chronic graft-versus-host disease: six of these had nephrotic syndrome. The cumulative incidence of nephrotic syndrome was 8% at day1681. Patients grafted with peripheral blood stem cells had a higher probability of developing nephrotic syndrome than did those grafted with bone marrow: 24% and 3%, respectively. The pathological diagnosis was membranous glomerulonephritis in four patients, and minimal change disease in one; the diagnosis could not be histologically confirmed in the sixth patient. All patients had extensive chronic graft-versus-host disease and were receiving treatment with cyclosporine A and steroids (four patients). Response to immunosuppressive therapy with cyclosporine A and steroids was achieved in all patients at a median time of 12 weeks after transplantation. Conclusion. Patients with chronic graft-versus-host disease may be considered to be at risk of nephrotic syndrome: careful monitoring of renal function is advisable, particularly in patients receiving allogeneic peripheral stem cell grafts

Optimal timing of allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndrome

Allogeneic hematopoietic stem cell transplantation (HSCT) represents the only curative treatment for patients with myelodysplastic syndrome (MDS), but involves non-negligible morbidity and mortality. Registry studies have shown that advanced disease stage at transplantation is associated with inferior overall survival. To define the optimal timing of allogeneic HSCT, we carried out a decision analysis by studying 660 patients who received best supportive care and 449 subjects who underwent transplantation. Risk assessment was based on both the International Prognostic Scoring System (IPSS) and the World Health Organization classification-based Prognostic Scoring System (WPSS). We used a continuous-time multistate Markov model to describe the natural history of disease and evaluate the effect of allogeneic HSCT on survival. This model estimated life expectancy from diagnosis according to treatment policy at different risk stages. Relative to supportive care, estimated life expectancy increased when transplantation was delayed from the initial stages until progression to intermediate-1 IPSS-risk or to intermediate WPSS-risk stage, and then decreased for higher risks. Modeling decision analysis on WPSS versus IPSS allowed better estimation of the optimal timing of transplantation. These observations indicate that allogeneic HSCT offers optimal survival benefits when the procedure is performed before MDS patients progress to advanced disease stages

Transplant results in adults with Fanconi anaemia

The outcomes of adult patients transplanted for Fanconi anaemia (FA) have not been well described. We retrospectively analysed 199 adult patients with FA transplanted between 1991 and 2014. Patients were a median of 16 years of age when diagnosed with FA, and underwent transplantation at a median age of 23 years. Time between diagnosis and transplant was shortest (median 2 years) in those patients who had a human leucocyte antigen identical sibling donor. Fifty four percent of patients had bone marrow (BM) failure at transplantation and 46% had clonal disease (34% myelodysplasia, 12% acute leukaemia). BM was the main stem cell source, the conditioning regimen included cyclophosphamide in 96% of cases and fludarabine in 64%. Engraftment occurred in 82% (95% confidence interval [CI] 76-87%), acute graft-versus-host disease (GvHD) grade II-IV in 22% (95% CI 16-28%) and the incidence of chronic GvHD at 96 months was 26% (95% CI 20-33). Non-relapse mortality at 96 months was 56% with an overall survival of 34%, which improved with more recent transplants. Median follow-up was 58 months. Patients transplanted after 2000 had improved survival (84% at 36 months), using BM from an identical sibling and fludarabine in the conditioning regimen. Factors associated with improved outcome in multivariate analysis were use of fludarabine and an identical sibling or matched non-sibling donor. Main causes of death were infection (37%), GvHD (24%) and organ failure (12%). The presence of clonal disease at transplant did not significant impact on survival. Secondary malignancies were reported in 15 of 131 evaluable patients

Marrow versus peripheral blood for geno-identical allogeneic stem cell transplantation in acute myelocytic leukemia: Influence of dose and stem cell source shows better outcome with rich marrow

Several studies have compared bone marrow (BM) and peripheral blood (PB) as stem cell sources in patients receiving allografts, but the cell doses infused have not been considered, especially for BM. Using the ALWP/EBMT registry, we retrospectively studied 881 adult patients with acute myelocytic leukemia (AML), who received a non-T-depleted allogeneic BM (n = 515) or mobilized PB (n = 366) standard transplant, in first remission (CR1), from an HLA-identical sibling, over a 5-year period from January 1994. The BM cell dose ranged from 0.17 to 29 × 108/kg with a median of 2.7 × 108/kg. The PB cell dose ranged from 0.02 to 77 × 10 8/kg with a median of 9.3 × 108/kg. The median dose for patients receiving BM (2.7 × 108/kg) gave the greatest discrimination. In multivariate analyses, high-dose BM compared to PB was associated with lower transplant-related mortality (RR = 0.61; 95% CI, 0.39-0.98; P = .04), better leukemia-free survival (RR = 0.65; 95% CI, 0.46-0.91; P = .013), and better overall survival (RR = 0.64; 95% CI, 0.44-0. 92; P = .016). The present study in patients with AML receiving allografts in first remission indicates a better outcome with BM as compared to PB, when the dose of BM infused is rich. © 2003 by The American Society of Hematology

Marrow versus peripheral blood for geno-identical allogeneic stem cell transplantation in acute myelocytic leukemia: Influence of dose and stem cell source shows better outcome with rich marrow

PubMed ID: 12829583Several studies have compared bone marrow (BM) and peripheral blood (PB) as stem cell sources in patients receiving allografts, but the cell doses infused have not been considered, especially for BM. Using the ALWP/EBMT registry, we retrospectively studied 881 adult patients with acute myelocytic leukemia (AML), who received a non-T-depleted allogeneic BM (n = 515) or mobilized PB (n = 366) standard transplant, in first remission (CR1), from an HLA-identical sibling, over a 5-year period from January 1994. The BM cell dose ranged from 0.17 to 29 × 10 8 /kg with a median of 2.7 × 10 8 /kg. The PB cell dose ranged from 0.02 to 77 × 10 8 /kg with a median of 9.3 × 10 8 /kg. The median dose for patients receiving BM (2.7 × 10 8 /kg) gave the greatest discrimination. In multivariate analyses, high-dose BM compared to PB was associated with lower transplant-related mortality (RR = 0.61; 95% CI, 0.39-0.98; P = .04), better leukemia-free survival (RR = 0.65; 95% CI, 0.46-0.91; P = .013), and better overall survival (RR = 0.64; 95% CI, 0.44-0. 92; P = .016). The present study in patients with AML receiving allografts in first remission indicates a better outcome with BM as compared to PB, when the dose of BM infused is rich. © 2003 by The American Society of Hematology

Long-term survival of patients with CLL after allogeneic transplantation: A report from the European Society for Blood and Marrow Transplantation

Even with the availability of targeted drugs, allogeneic hematopoietic cell transplantation (allo-HCT) is the only therapy with curative potential for patients with CLL. Cure can be assessed by comparing long-term survival of patients to the matched general population. Using data from 2589 patients who received allo-HCT between 2000 and 2010, we used landmark analyses and methods from relative survival analysis to calculate excess mortality compared with an age-, sex- and calendar year-matched general population. Estimated event-free survival, overall survival and non-relapse mortality (NRM) 10 years after allo-HCT were 28% (95% confidence interval (CI), 25-31), 35% (95% CI, 32-38) and 40% (95% CI, 37-42), respectively. Patients who passed the 5-year landmark event-free survival (N=394) had a 79% probability (95% CI, 73-85) of surviving the subsequent 5 years without an event. Relapse and NRM contributed equally to treatment failure. Five-year mortality for 45- and 65-year-old reference patients who were event-free at the 5-year landmark was 8% and 47% compared with 3% and 14% in the matched general population, respectively. The prospect of long-term disease-free survival remains an argument to consider allo-HCT for young patients with high-risk CLL, and programs to understand and prevent late causes of failure for long-term survivors are warranted, especially for older patients