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Purpose To compare a reduced-intensity conditioning regimen (RIC) with a myeloablative conditioning regimen (MAC) before allogeneic transplantation in patients with myelodysplastic syndrome (MDS) within a randomized trial. Patients and Methods Within the European Society of Blood and Marrow Transplantation, we conducted a prospective, multicenter, open-label, randomized phase III trial that compared a busulfan-based RIC with MAC in patients with MDS or secondary acute myeloid leukemia. A total of 129 patients were enrolled from 18 centers. Patients were randomly assigned in a 1:1 ratio and were stratified according to donor, age, and blast count. Results Engraftment was comparable between both groups. The CI of acute graft-versus-host disease II to IV was 32.3% after RIC and 37.5% after MAC ( P = .35). The CI of chronic graft-versus-host disease was 61.6% after RIC and 64.7% after MAC ( P = .76). The CI of nonrelapse mortality after 1 year was 17% (95% CI, 8% to 26%) after RIC and 25% (95% CI, 15% to 36%) after MAC ( P = .29). The CI of relapse at 2 years was 17% (95% CI, 8% to 26%) after RIC and 15% (95% CI, 6% to 24%) after MAC ( P = .6), which resulted in a 2-year relapse-free survival and overall survival of 62% (95% CI, 50% to 74%) and 76% (95% CI, 66% to 87%), respectively, after RIC, and 58% (95% CI, 46% to 71%) and 63% (95% CI, 51% to 75%), respectively, after MAC ( P = .58 and P = .08, respectively). Conclusion This prospective, randomized trial of the European Society of Blood and Marrow Transplantation provides evidence that RIC resulted in at least a 2-year relapse-free survival and overall survival similar to MAC in patients with MDS or secondary acute myeloid leukemia.

Background: The prognosis of myelodysplastic syndromes (MDS) after allogeneic stem cell transplantation is critically determined by cytogenetic abnormalities, as previously defined by International Prognostic Scoring System (IPSS) cytogenetics. It has been shown that a new cytogenetic classification, included in the IPSS-R (cytogenetic-IPSS-R [C-IPSS-R]), can better predict the outcome of untreated MDS patients., Methods: In this study, we assessed the impact of the IPSS-R cytogenetic score (C-IPSS-R) on the outcome of 367 MDS patients transplanted from HLA-identical siblings or HLA allele-matched unrelated donors., Results: According to the C-IPSS-R, 178 patients (48%) fell in the good risk, 102 (28%) in the intermediate risk, 77 (21%) in the poor risk, and 10 (3%) in the very poor risk group. In multivariate analysis, after a median follow-up of 4 years, the poor and very poor-risk categories correlated with shorter overall survival (OS) (4-year OS, 32%; hazard ratio [HR], 1.59; P = 0.009 and OS, 10%; HR, 3.18; P = 0.002, respectively) and higher cumulative incidence of relapse (CIR) (CIR, 52%; HR, 1.82; P = 0.004 and CIR, 60%; HR, 2.44; P = 0.060, respectively)., Conclusions: Overall, the C-IPSS-R changed the IPSS cytogenetic risk only in 8% of cases but identified a new risk group, the very poor C-IPSS-R category, with dismal outcome after allogeneic stem cell transplantation (10% 4-year OS, 60% 4-year CIR). Posttransplantation maintenance therapy should be investigated in prospective trials for patients with high-risk C-IPSS-R karyotypes.

Allogeneic stem cell transplantation (ASCT) from related or unrelated donors may cure patients with myelodysplastic syndromes (MDS), a heterogeneous group of clonal stem cell disorders. We analysed 384 elderly patients (55-69 years) with advanced MDS who received either ASCT (n=247) and were reported to The European Group for Blood and Marrow Transplantation (EBMT) or a non -transplant approach (n=137) reported to the Düsseldorf registry. Besides an attempt to answer the question of "comparison", the purpose of this work is to explain the difficulties in comparing a non-transplant with a transplant cohort, when death before transplant is likely but unknown and the selection of patients for transplant is based on assumptions. It shows which methods are almost always biased and that even the most sophisticated approaches crucially rely on clinical assumptions. Using the most appropriate model for our data, we derive an overall univariate non-significant survival disadvantage for the transplant cohort (HR: 1.29, p = 0.11). We show that such an "average" hazard ratio is however misleading due to non-proportionality of the hazards reflecting early treatment related mortality, the occurring of which is logically correlated with the interval between diagnosis and transplant creating a disproportional drop in the (reconstructed) survival curve of the transplanted patients. Also in multivariate analysis (correcting for age > 60 (HR: 1.4, p = 0.02) and abnormal cytogenetics (HR: 1.46, p = 0.01)), transplantation seems to be worse (HR: 1.39, p = 0.05) but only in the (incorrect but commonly applied) model without time varying covariates. The long term (time depending) hazard ratio is shown to be virtually 1 and overall survival is virtually identical in both groups. Nonetheless no conclusion can be reached from a clinical point of view without assumptions which are by their very nature untestable unless all patients would be followed from diagnosis.

The combination of azacitidine and donor lymphocyte infusions (DLI) as first salvage therapy for relapse after allogeneic transplantation (allo-HSCT) was studied in 30 patients with acute myeloid leukemia (AML; n=28) or myelodysplastic syndromes (MDS; n=2) within a prospective single-arm multicenter phase-II trial. Treatment schedule contained up to eight cycles azacitidine (100 mg/m(2)/day, days 1-5, every 28 days) followed by DLI (from 1-5 × 10(6) to 1-5 × 10(8) CD3(+)cells/kg) after every second azacitidine cycle. A median of three courses azacitidine (range 1-8) were administered, and 22 patients (73%) received DLI. Overall response rate was 30%, including seven complete remissions (CRs, 23%) and two partial remissions (7%). Five patients remain in CR for a median of 777 days (range 461-888). Patients with MDS or AML with myelodysplasia-related changes were more likely to respond (P=0.011), and a lower blast count (P=0.039) as well as high-risk cytogenetics (P=0.035) correlated with the likelihood to achieve CR. Incidence of acute and chronic graft-versus-host disease was 37% and 17%, respectively. Neutropenia and thrombocytopenia grade III/IV occurred during 65% and 63% of treatment cycles, while infections were the most common grade III/IV non-hematological toxicity. Azacitidine and DLI as salvage therapy is safe, induces long-term remissions and may become an alternative for patients with AML or MDS relapsing after allo-HSCT.

A growing body of evidence suggests that iron overload is associated with inferior outcomes after myeloablative allogeneic hematopoietic stem cell transplantation (HSCT). However, all of those studies used surrogate markers of iron overload, especially serum ferritin, and most had a retrospective design. We conducted a prospective observational study in patients with myelodysplastic syndrome or acute leukemia undergoing myeloablative HSCT. Forty-five patients who were followed for over 1 year, with serial measurements of serum iron parameters, as well as liver and cardiac magnetic resonance imaging. There was no significant increase in ferritin, liver or cardiac iron content in the 12 months following HSCT. Although serum ferritin still appeared to have prognostic significance, as previously reported, pre-HSCT iron overload (as reflected in liver iron content) was not associated with increased mortality, relapse, or graft-versus-host disease. These results raise the possibility that the adverse prognostic impact of pre-HSCT hyperferritinemia may be related to factors independent of iron overload., (Copyright © 2012 Wiley Periodicals, Inc.)

A multicenter retrospective analysis of the influence of pretransplant serum ferritin (SF) was performed in 261 adult recipients of allogeneic hematopoietic stem cell transplant (allo-HSCT), including 159 patients with acute myeloid leukemia (AML), 66 with acute lymphoid leukemia (ALL) and 36 with myelodysplastic syndrome (MDS). Patients were divided into subgroups according to the pretransplant SF level [< 1000 ng/mL (low) vs. ≥ 1000 ng/mL (high)] and disease status at transplant. A high SF level was significantly associated with high disease risk (p = 0.041), but pretransplant SF and disease risk were independent significant prognostic factors for overall survival (OS), disease-free survival (DFS) and non-relapse mortality rate (NRM) on multivariate analysis. The high-SF group showed a worse outcome than the low-SF group among both standard-risk patients (OS: 54% vs. 64%, p = 0.043; DFS: 46% vs. 57%, p = 0.031) and high-risk patients (OS: 16% vs. 35%, p = 0.001; DFS: 15% vs. 34%, p = 0.001). In conclusion, a high SF at transplant adversely influences the outcome of allo-HSCT regardless of disease risk in patients with acute leukemia and MDS.

Objective: The aim of this study was to determine the optimum conditioning intensity for allogeneic stem cell transplantation (SCT) in young (age ≤50), lower-risk (INT-1 by IPSS) Myelodysplastic syndrome (MDS) patients without significant comorbidities (hematopoietic cell transplantation-comorbidity index score ≤3)., Methods: Transplant outcomes from 46 consecutive patients were retrospectively analyzed according to the conditioning intensity: reduced-intensity conditioning (RIC; n = 14), intensified RIC by adding low-dose total body irradiation (iRIC; n = 15), and myeloablative conditioning (MAC; n = 17)., Results: After a median follow-up of 73.7 months, RIC had a better 4-yr overall survival (OS) (92.9%) compared with the iRIC (64.2%) or MAC (70.6%). Multivariate analysis showed that RIC was associated with improved OS compared with the MAC [relative risk (RR) of 0.08, P = 0.022] because of a lower transplant-related mortality (TRM) (RR, 0.08, P = 0.035). iRIC failed to show survival benefits over the MAC (RR of 0.77, P = 0.689) because of similarly high TRM (RR of 0.41, P = 0.480). Cumulative incidence of acute and chronic graft-versus-host disease (GVHD) after RIC was higher, but GVHD-specific survival was significantly better (RIC 100% vs. iRIC 45.7% vs. MAC, P = 0.018). Relapse rate was not different among the three groups, but in the RIC group, azacitidine was available and useful for inducing remission in two patients., Conclusion: This study shows that RIC improved OS by directly lowering TRM and indirectly giving an additional chance for relapsed MDS in the era of hypomethylating treatment. RIC-SCT should be considered for relative healthy lower-risk MDS patients., (© 2011 John Wiley & Sons A/S.)

Purpose of Review: Use of a reduced intensity conditioning (RIC) regimen has now become standard practice among older or more infirmed stem cell transplantation candidates. Encouraging outcome in this population has led to the question of whether RIC should replace standard myeloablative conditioning (MAC) regimens. This review will summarize the available outcomes data comparing RIC and MAC approaches to stem cell transplantation in adult patients with acute myeloid leukemia, myelodysplastic syndrome (MDS) and acute lymphoid leukemia., Recent Findings: There are currently no completed prospective randomized controlled studies comparing outcomes of RIC to MAC. The best insight into differences in outcome comes from large registry-based retrospective studies. These studies demonstrate that the use of RIC is associated with a reduction in transplant-related mortality but an increased risk of disease relapse. As a result, for patients undergoing stem cell transplantation in remission, disease free and overall survival are similar., Summary: The current retrospective data provide justification for the use of RIC regimens in all adult stem cell transplant candidates with acute leukemia in remission and MDS. More definitive conclusions regarding differences between the MAC and RIC approach to stem cell transplantation await results of ongoing prospective randomized trials.

This retrospective report assessed the impact of rabbit antithymocyte globulins (ATG), incorporated within a standard myeloablative conditioning regimen prior to allogeneic stem cell transplantation (allo-SCT) using human leukocyte antigen-matched unrelated donors (HLA-MUD), on the incidence of acute and chronic graft-vs-host disease (GVHD). In this series of leukemia patients, 120 patients (70%) did not receive ATG ('no-ATG' group), whereas 51 patients received ATG ('ATG' group). With a median follow-up of 30.3 months, the cumulative incidence of grade 3-4 acute GVHD was 36% in the no-ATG group and 20% in the ATG group (P = 0.11). The cumulative incidence of extensive chronic GVHD was significantly lower in the ATG group as compared to the no-ATG group (4 vs 32%, respectively; P = 0.0017). In multivariate analysis, the absence of use of ATG was the strongest parameter associated with an increased risk of extensive chronic GVHD (relative risk) = 7.14, 95% CI: 1.7-33.3, P = 0.008). At 2 years, the probability of nonrelapse mortality, relapse, overall and leukemia-free survivals was not significantly different between the no-ATG and ATG groups. We conclude that the addition of ATG to GVHD prophylaxis resulted in decreased incidence of extensive chronic GVHD without an increase in relapse or nonrelapse mortality, and without compromising survival after myeloablative allo-SCT from HLA-MUD.

We report here the 10-year follow-up of 86 patients who underwent allogeneic stem cell transplantation (ASCT) for myelodysplastic syndrome (MDS). All patients received the busulfan, cytosine arabinoside, and cyclophosphamide (BAC) preparative regimen which consisted of busulfan 16 mg/kg, cytosine arabinoside 8 g/m(2) IV, and cyclophosphamide 120 mg/kg IV. Fifty-nine patients (69%) had de novo MDS; 26 (30%) had secondary MDS (treatment related), and one had a preceding aplastic anemia which progressed to MDS before transplant. Cytogenetics (80 patients) was classified as good (34%), intermediate (17%), or poor (42%). With a median follow-up for survivors of 124 months, the 10-year Kaplan-Meier estimates for overall survival (OS) was 43% (95% confidence interval [CI]: 31-53%). Cumulative nonrelapse mortality (NRM) and relapse was 43% (95% CI: 32-54%) and 19% (95% CI: 11-27%), respectively. No patient relapsed after 2 years. In patients with RAEB-T/AML, 10-year relapse-free survival (RFS), relapse, and NRM was 36%, 36%, and 27%, respectively. Younger age (P = 0.05), human leukocyte antigen (HLA) match (P = 0.002), good risk cytogenetics (P = 0.008), and having a related donor (P = 0.03) significantly improved overall and RFS in the multivariable analysis. The long-term follow-up of patients receiving the BAC regimen with ASCT in this study indicated durable relapse-free and OS with acceptable toxicity in this group of patients with high-risk features., ((c) 2010 Wiley-Liss, Inc.)

Background: The occurrence of autoantibodies has been reported in allogeneic stem-cell recipients, but the association of this occurrence with chronic graft-versus-host disease (cGVHD) or survival remains uncertain., Methods: A total of 121 consecutive patients who underwent allogeneic stem-cell transplantation from November 2001 to March 2008 and survived at least 3 months after transplantation were included in this study., Results: Forty-seven patients (38.8%) expressed at least one of various autoantibodies after transplantation. Antinuclear antibody was positive in 22 patients (18.2%), antidouble stranded DNA in seven (5.8%), antismooth muscle antibody in six (5%), rheumatoid factor in 17 (14.0%), and a positive Coombs test recorded for 12 patients (9.9%). cGVHD was more commonly diagnosed in the patients with autoantibody expression (61.7% vs. 43.2%, P=0.048). The patients expressing autoantibodies had a better 5-year overall survival than those without any autoantibody expression: 70.2% and 47.9% for the autoantibody-positive and autoantibody-negative patients, respectively (P=0.002). The cumulative incidence of relapse was 21.5% and 39.3% for the autoantibody-positive and autoantibody-negative patients, respectively (P=0.023). In particular, the patients expressing autoantibodies without cGVHD had a better overall survival (100%) than the patients in the other groups: 63.1% for the autoantibody- and cGVHD-positive patients, 59.6% for the autoantibody-negative and cGVHD-positive patients, and 36.6% for the autoantibody- and cGVHD-negative patients. The multivariate analysis identified autoantibody expression as a good prognostic factor regarding survival (hazard ratio=0.378, 95% confidence interval=0.185-0.775, P=0.008)., Conclusion: The occurrence of autoantibodies after allogeneic stem-cell transplantation was found to be related to cGVHD, and patients expressing autoantibodies had a better survival.

Decitabine is a hypomethylating agent with activity in myelodysplastic syndrome (MDS). It is largely unknown whether treatment with this drug before allo-SCT will increase the toxicity of the preparative regimen or otherwise affect the results of the transplant. We report the outcome of 17 patients with MDS with a median age of 55.5 years (range, 36-66 years) who underwent an allo-SCT (12 siblings, 5 unrelated) after prior therapy with decitabine. Preparative regimens consisted of fludarabine in combination with BU (n=8) or melphalan (n=9). The source of stem cells was marrow in four patients and peripheral blood (PB) in 13 patients. Thirteen patients were in CR within 100 days of transplant. With a median follow-up of 12 months (range, 3-35 months), 11 patients are alive; eight in CR and three with progressive disease. Prior therapy with hypomethylating agents did not increase toxicity and may improve the outcome of allogeneic transplant in MDS and should be evaluated in a prospective trial.

Aim: Tumour necrosis factor-alpha (TNF-alpha) serum levels may increase due to intensive conditioning regimes with high-dose-chemotherapy and total body irradiation (TBI) before stem cell transplantation. This increases the risk for developing acute graft versus host disease (aGvHD) after stem cell transplantation. In this prospective study we investigated the influence of radioimmunotherapy with 188Re-CD-66-mAb on changes on TNF-alpha serum levels., Patients, Methods: In 18 patients we measured TNF-alpha before and up to 96 hours after radioimmunotherapy, in 2 patients in addition following TBI, in 9 patients also following chemotherapy. For measuring TNF-alpha we used an automated immunochemiluminescence assay (Immulite 1000 DPC Biermann, Bad Nauheim). The mean follow up period to record incidence of aGVHD was 100 days after stem cell transplantation., Results: Compared to the basal levels before, the levels of TNF-alpha after conditioning with 188Re-CD-66-mAb did not increase significantly and remained in the physiological range. In contrast, these initial physiological cytokine levels increased and became pathological following 48 h after total body irradiation (13.2+/-6.6 pg/ml) and chemotherapy (10.8+/-15.7 pg/ml). In our study we found a low incidence of aGvHD (22.2%, n=4/18)., Conclusion: These results demonstrate that additional conditioning therapy with 188Re-CD-66-mAb does not increase proinflammatory cytokine levels of TNF-alpha. This finding may indicate that additive radioimmunotherapy may not be a significant factor for increasing the rate of conditioning-associated aGvHD.

Cytomegalovirus (CMV) infection causes high morbidity and mortality among allogeneic stem cell transplant recipients. Preemptive therapy with oral valganciclovir or intravenous ganciclovir has replaced universal prophylaxis. We prospectively studied 19 consecutive adult recipients of allogeneic peripheral blood stem cell transplants from May 2005 through February 2007 to analyze the safety and efficacy of preemptive therapy for the treatment of CMV infection. The antigenemia test was persistently negative in 8 patients (42%) and positive at least once in 11 (58%). Eight patients were treated with oral valganciclovir on an outpatient basis and they all became CMV negative after the first week of treatment. The other 3 patients received intravenous ganciclovir and were also CMV negative after the first week of treatment. No patient abandoned treatment, no severe secondary toxicity was noted, and there was no CMV-associated mortality.

Allogeneic stem cell transplantation can cure patients with myelodysplastic syndromes. However, more than 50% of the patients who underwent allogeneic stem cell transplantation have failed to benefit from this treatment approach either due to treatment-related mortality or to relapse. The introduction of toxicity or dose-reduced conditioning has significantly reduced the treatment-related mortality but did not affect the risk of relapse. New effective drugs, such as hypomethylating agents, histone-deacetylase inhibitors or lenalidomide, can be used alone or in combination to improve the pretransplant remission status before allogeneic stem cell transplantation or after transplantation to prevent relapse as maintenance or consolidation therapy. This review will focus on these new possibilities and give some perspectives as to how the results of allogeneic stem cell transplantation can be further improved.

Allogeneic stem cell transplantation is the only known curative therapy for myelodysplastic syndromes. However, the morbidity and mortality from this approach is high, especially in a population that tends to be elderly with comorbid conditions. In order to achieve a good outcome, the key is wise choice of the patient to undergo transplantation and appropriate timing of the therapy. Furthermore, consideration should be given to choosing whether the regimen should be fully myeloablative or reduced-intensity and whether marrow, peripheral-blood stem cells, or cord blood should be chosen for stem cell replacement. This article reviews the history of transplantation for this indication and the newer data driving decisions regarding the type of transplant and the optimal timing for best results.

We determined the outcome of patients with myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (sAML) after allogeneic stem cell transplantation according to their international prognostic scoring system (IPSS) risk categories at diagnosis. A total of 11 females and 7 males, with a median age of 45 years, were transplanted. With a median follow-up of 60 months, the 6-year actuarial event-free survival (EFS) for Less Advanced (Low and Intermediate-1 risk IPSS) and Advanced (Intermediate-2 and High risk IPSS) MDS was 71.4% and 43.6%, respectively (p=0.002). We did not observe a difference in EFS depending on cytogenetics at diagnosis (good risk 53.8% Vs intermediate and high risk 53.3%, p=ns), neither on the type of conditioning regimen used (myeloablative 50% Vs reduced intensity 52.2%, p=ns). Our results support that IPSS score at diagnosis may be used to predict EFS in patients with MDS undergoing allogeneic SCT.

We report on the outcomes of 53 patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia secondary to MDS, autografted in first complete remission. Five (9.4%) died from the procedure whereas hematological reconstitution occurred in all the remaining patients. Forty patients (75%) relapsed, with 87.5% of the relapses occurring within 2 years of the autologous transplant. With a median follow-up of 6.2 years, the median actuarial disease-free survival and overall survival were 8 and 17 months after autograft, respectively. Karyotype was the only prognostic factor for disease-free and overall survival. The eight survivors (15%), including two patients with unfavorable or intermediate karyotype, remained in first complete remission 50+ to 119+ months after transplantation and are probably cured.

Background and Objectives: Chromosome 5 and/or 7 abnormalities are cytogenetic findings indicative of a poor prognosis in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The only potential cure for such patients is allogeneic stem cell transplantation (SCT). As data on allogeneic SCT in this context are limited we did a retrospective study of allogeneic SCT in patients with AML or MDS who had chromosome 5 and/or 7 abnormalities., Design and Methods: This was a retrospective study of 65 patients (16 children, 49 adults) with AML (n=33) or MDS (n=32) who had chromosome 5 and/or 7 abnormalities and who underwent allogeneic SCT in six Dutch Centers between 1983 and 2001. Data on all these patients are recorded in the Netherlands Stem Cell Transplant Registry (Typhon)., Results: The 3-year overall survival rate among all patients was 25%. Patients below the age of 40 years had significantly fewer relapses (40%) and better survival (38%) than those above the age of 40 (86% and 8%, respectively). Relapses were less frequent in recipients of unrelated grafts than in those whose grafts were from HLA-identical siblings (30% versus 69%). The development of acute graft-versus-host disease (GVHD) grades II-IV was independently associated with significantly higher transplant-related mortality (TRM). Patients with either chromosome 5 or chromosome 7 abnormalities had a significantly better survival than patients with both chromosome 5 and 7 abnormalities. These patients with poor-risk chromosome 5 and/or 7 abnormalities were compared with a group of patients with a secondary AML/MDS and normal cytogenetics and were found to have significantly more relapses and significantly worse survival but a similar TRM., Interpretation and Conclusions: We conclude that patients with AML or MDS with chromosome 5 and/or 7 abnormalities do rather poorly after allogeneic SCT, mainly because of the very high relapse rate. Nevertheless, this is the only approach that can cure some of these patients.

Diffuse alvedar haemorrhage (DAH): a severe complication post haematopoietic stemcell transplantation (HSCT) with high mortality. Early diagnose and distinction from other pulmonary complications is essential. Radiologic imaging provides first cues to diagnose. Confirmation of diagnose by BAL. Therapeutic approach with high dose steroids

We recently reported that virtually all children with acute leukaemia and myelodysplastic syndrome (MDS) who develop the phenotype of increasing mixed chimaerism (MC) after allogeneic stem cell transplantation (allo-SCT) will relapse. We therefore performed a prospective, multi-centre study focused on children with MDS (n = 65; advanced MDS = 44, refractory cytopenia = 21) after allo-SCT in order to determine to what extent relapse can be prevented by pre-emptive immunotherapy on the basis of increasing MC. Analyses of chimaerism in 44 patients with advanced MDS revealed 31 cases with complete chimaerism (CC)/low-level MC/transient MC, 11 cases with increasing MC and two cases with decreasing MC. The same analyses in 21 MDS patients with refractory cytopenia revealed 17 cases with CC/low-level MC, one case with increasing MC and three cases with decreasing MC. Pre-emptive immunotherapy performed on each patient that showed increasing MC improved event-free survival from 0%, as seen in prior studies, to 50%. We therefore conclude that pre-emptive immunotherapy is an effective treatment option to prevent impending relapse in children with MDS after allo-SCT.

The present study applied the International Prognostic Scoring System (IPSS) to 306 consecutive myelodysplastic syndrome (MDS) patients diagnosed between August 1977 and September 2000 at the University Medical Centre Nijmegen. The aim was to investigate whether the IPSS could be used as a prognostic tool in MDS patients aged less than 61 years who were treated with acute myeloid leukaemia (AML)-like chemotherapy with or without transplantation, and whether the scoring system discriminated between the subgroups of patients who benefit from intensive treatment strategies. The patients were retrospectively assigned to the IPSS risk categories and compared with the IPSS workshop patients. Eighty-three of 159 patients aged < 61 years, classified as intermediate 1, intermediate 2 and high risk according to the IPSS, received intensive treatment consisting of chemotherapy only (n = 30), chemotherapy followed by either autologous stem cell transplantation (n = 7) or allogeneic stem cell transplantation (n = 46). After intensive treatment, the median survival was 2.6 years for the intermediate 1 risk group (n = 33), 3.4 years for the intermediate 2 risk group (n = 27) and 0.9 years for the high-risk group (n = 23). We conclude that the IPSS is an improved scoring system for patients receiving supportive care. Nevertheless, the scoring system does not seem to be the best method for predicting outcome after intensive antileukaemic treatment. In particular, intermediate 2 risk patients may benefit from intensive treatment.

Allogeneic transplantation is the only curative treatment for Fanconi anaemia (FA) patients who develop myeloid malignancies. Dose-intensive preparative regimens, to decrease disease recurrence, lead to unacceptable transplant-related toxicity in FA. We report the outcome of three FA patients with such malignancies who underwent transplantation with reduced-intensity preparative regimens. This approach was well tolerated, even as second transplantations, and resulted in complete leukaemic remissions. However, the graft-versus-leukaemia effect was associated with fatal graft-versus-host disease. Even after transplantation, myeloid malignancies remain associated with a poor outcome in FA, and this argues in favour of early intervention when suitable donors are available.

Thymidine ((3)H-TdR) incorporation remains the most commonly used method to quantifying T-cell proliferation. This method, however, does not provide information about specific lymphocyte subpopulations responding to different stimuli. In our study, we modified previously described nonradioactive flow-cytometric T-cell activation assay measuring the expression of a CD69+ antigen on T-cell subsets and applied it to analysis of lymphocyte subsets activation/proliferation in children after allogeneic hematopoietic cell transplantation (HCT). We compared the percentage of spontaneously activated lymphocyte subpopulations (background) and the percentage of PHA-P, PWM, and SEB-stimulated cell subsets from two groups of patients: group 1, children with Graft versus Host Disease (GvHD) and group 2, children without any signs of GvHD at the time of analysis. High rate of spontaneous T-cell subset activation was found in group 1 with CD3+CD8+Ts cells being the most affected cell population. High background activation of Th and B cells correlated with the occurrence of autoimmune phenomena posttransplant. Rapid quantification of CD69+ expression on unstimulated and stimulated T-cell subsets proved to be a valuable method for monitoring children after allogeneic HCT. High proportion of activated, unstimulated Ts cells observed in the GvHD group may underline the critical role of CD3+CD8+ cells in the pathogenesis of GvHD. Thus in future immunosuppressive therapy may be adjusted according to the proportion of activated Ts cells.