There is substantial need to improve the outcome of patients with high-risk acute myeloid leukemia (AML). The clinical trial reported here investigated a new approach of up-front allogeneic hematopoietic stem cell transplantation (HSCT), provided a median of 40 days (range 22–74) after diagnosis, in twenty-six consecutive patients with newly-diagnosed high-risk AML characterized by poor-risk cytogenetics (n=19) or inadequate blast clearance by induction chemotherapy (IC, n=7). The median age was 49 years (range 17–68). During IC-induced aplasia after the 1st (n=11) or 2nd (n=15) cycle, patients received allogeneic peripheral blood stem cells (PBSC) from related (n=11) or unrelated (n=15) donors following a fludarabine-based reduced-intensity regimen. Seventeen patients were not in remission before HSCT with a median marrow blast count of 34% (range 6–70). All patients achieved rapid engraftment and went into remission with complete myeloid and lymphatic chimerism. Grades II to IV acute GvHD occurred in 14 (56%) and extensive chronic GvHD was documented in 8 (35%) patients. The probability of disease-free survival was 61% with only three patients relapsing 5, 6 and 7 months after transplantation, respectively. Up-front allogeneic HSCT as part of primary induction therapy seems to be an effective strategy in high-risk AML patients and warrants further investigation.

Introduction: Hematopoietic progenitor cells from unrelated donors are increasingly used for allogeneic stem cell transplantation (SCT). A second donation of peripheral blood stem cells (PBSC) or bone marrow is widely accepted in case of graft failure of relapse.

Prognosis of patients (pts.) with refractory or relapsed acute myeloid leukaemia (AML) or advanced myelodysplasia (MDS) is poor. Preliminary reports suggest that induction of aplasia by a standard AML regimen followed by reduced intensity conditioned stem cell transplantation (RIC-SCT) in aplasia may be an effective strategy in this situation. A survey was conducted by the German Cooperative Transplant Study Group (GCTSG) to investigate the outcome after such an approach. In April 2006, GCTSG centers were asked if they had performed RIC-SCT in aplasia. Centers with positive response received a questionnaire including details on patient and donor characteristics, disease status, induction chemotherapy, transplant procedure and outcome.

Abstract:  Objective: To analyse the results of allogeneic haematopoietic cell transplantation (HCT) in patients with advanced stages of Philadelphia chromosome‐positive chronic myelogenous leukaemia (CML) who had previously been treated with imatinib mesylate (IM). Methods: We analysed the outcome of 61 patients with CML who had received allogeneic HCT from sibling (n = 18) or unrelated (n = 43) donors after having been treated with IM. Forty‐one patients had received IM because of accelerated or blast phase CML. Conditioning therapy contained standard doses of busulfan (n = 25) or total‐body irradiation (n = 20) in conjunction with cyclophosphamide in the majority of cases. Sixteen patients received dose‐reduced conditioning with fludarabine‐based regimens. Results: The incidence of grades II–IV and III–IV graft‐versus‐host disease was 66% and 38% respectively. The probability of overall survival (OS), disease‐free survival (DFS) and relapse at 18 months for the whole patient cohort were 37%, 33% and 24% respectively. The probability of non‐relapse mortality (NRM) at 100 d and 12 months was 30% and 46% respectively. Univariate analysis showed that fludarabine‐based conditioning therapy, age ≥40 yr and >12 months interval between diagnosis and transplantation were associated with a significantly lower OS and DFS and a higher NRM. Conclusion: These data suggest that although pretreatment with IM is not an independent negative prognostic factor, it cannot improve the dismal prognosis of CML patients at high risk for transplant‐related mortality.

The use of anti-B cell antibodies before allogeneic hematopoietic stem cell transplantation (HSCT) induces a depletion of recipient B cells. This leads to a reduction of the number of potential antigen presenting cells and thereby might hamper the induction phase of graft-versus-host disease (GvHD). The humanized anti-CD20 antibody Rituximab has been used with increasing frequency to treat patients with B cell Non-Hodgkin's Lymphoma. Only recently, several investigators have reported on the efficacy of Rituximab for the treatment of chronic GvHD. We therefore hypothesized, that patients who received Rituximab before being scheduled for allogeneic HSCT may have a decreased risk of GvHD.

Respiratory failure is a serious early complication confounding the clinical effect of allogeneic stem cell transplantation and early detection may be crucial for efficient treatment. We introduced a system of intensive oxigenation monitoring in patients transplanted in our center between November 2001 and December 2003. All allogeneic transplanted patients were followed by a twice daily measurement of oxi-index (paO2/FiO2) during the transplantation period (untill day + 25). Patients that fulfilled criteria of acute lung injury (oxi-index <300) were treated by O2 application vs. non-invasive ventilation (NIV). Failure to increase oxi-index above the threshold of 300 led to referral of the patient to ICU were intensified NIV was applied and/or mechanical ventilation (MV) was initiated based on a defined scoring system. 165 patients were followed for the development of ALI. 48 (29.1%) developed oxiindices <300 (ALI). Development of ALI predicted for a significantly higher rate of ICU admissions (37.5% vs. 6.8% in non-ALI patients; p<0.001) and MV (20.8 % vs. 1.7 in non-ALI patients; p<0.001). ALI was most commonly diagnosed during the engraftment period but was at diagnosis not associated with other criteria like respiration rate, CRP and tachycardia. Since members of the pulmonary innate immune system may be associated with the development of ALI and ARDS we screened the 165 patients for the presence of alternative alleles in the Surfactant Protein B (SP-B) gene. A polymorphism at position +1580 (T/C variation) of SP-B has been previously found to be associated with the development of ARDS. Polymorphism of SP-B were not associated with the development of ALI and did not predict for the need of intensified ICU treatment. However, the rate of MV varied considerably. Nine patients with the T/T genotype (9 out of 42, 21.4%) required intubation and mechanical ventilation whereas none of the patients with C/C had to receive MV (0 out of 30; p=0.01).The data indicate that measurement of the oxiindex is an early sensitive parameter of respiratory failure in allogeneic transplantation and that severity of respiratory damage may be predicted by the T allele at the SP-B +1580 site

We read with interest the recent report by Giebel et al,[1][1] who showed a dramatic effect of KIR ligand incompatibility on survival and transplant-related mortality in a heterogeneous patient population after allogeneic hematopoietic stem cell transplantation using unrelated donors. The authors