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In the two consecutive German studies III and IIIA on chronic myeloid leukemia, between 1995 and 2004, 781 patients were randomized to receive either allogeneic hematopoietic stem cell transplantation with a related donor or continued drug treatment. Despite comparable transplantation protocols and most centers participating in both studies, the post-transplant survival probabilities for patients transplanted in first chronic phase were significantly higher in study IIIA (144 patients) than in study III (113 patients). Prior to the decision on a combined analysis of both studies, reasons for this discrepancy had to be investigated.The Cox proportional hazard cure model was used to identify prognostic factors for post-transplant survival.Donor-recipient matching for human leukocyte antigen, patient age, time between diagnosis and transplantation, and calendar time showed a significant influence on survival and/or the incidence of cure. Added as a further factor, affiliation to study IIIA had no significant impact any longer.Discrepancies in influential prognostic factors explained the different post-transplant survival probabilities between the studies. The significance of calendar time suggests a lack of consistency of transplantation practice over time. Accordingly, the prerequisite for a common assessment of overall survival in the two randomized transplantation arms was not met. Moreover, our analyses provide an independent validation of established prognostic factors and their cutoffs. The statistical approach in investigating and modeling potential prognostic factors for survival sets an example for the examination of studies with unexpected outcome differences in concurrent treatment arms.

SummaryWe report 5 children from 3 families with homozygous antithrombin deficiency type II affecting the heparin binding site (99 Leu to Phe mutation). Four children had severe spontaneous thromboembolic events (deep leg or caval vein thrombosis, ischaemic stroke) at one week, 3 months, 13 and 14 years of age. The fifth patient, a 17 year-old boy was asymptomatic. Early manifestation of homozygous deficiency calls for prompt and accurate diagnosis. In doubtful cases genetic analysis is required. Long-term oral anticoagulation should be considered in affected individuals.

The chromosomal translocation t(8;21) (q22;q22) is often associated with acute myeloid leukemia with maturation (AML-M2) and can be detected by a reverse transcription-polymerase chain reaction (RT-PCR) for the AML1/ETO fusion mRNA. We investigated the prevalence of t(8;21) and AML1/ETO in 204 unselected patients with AML and compared the results of cytogenetic analysis with these of RT-PCR. Fifteen of 204 AML patients (7.4%) showed a t(8;21) in karyotype analysis. In 17 of 204 patients (8.3%) AML1/ETO was detected by RT-PCR. All patients who had a t(8;21) in conventional karyotyping also showed the gene rearrangement in molecular analysis, including one patient with a three-way translocation t(5;8;21). AML1/ETO was also detected in two AML patients lacking the t(8;21) cytogenetically. One had a normal diploid karyotype bone marrow (BM) at diagnosis; she has now been in CCR for 12 months. The second patient showed a complex chromosomal anomaly involving chromosome 21, but without a typical 8;21 translocation (BM in relapse). He died in relapse after an overall survival of 60 months. These data indicate that the results of karyotyping and RT-PCR are not completely identical, and molecular biology identifies approximately an additional 5-10% of AML1/ETO positive cases. The clinical relevance of our findings will have to be evaluated with larger patient numbers.

Mast cells (MC) are important cellular components of the immune network in diverse organs. The skin MC has likewise been implicated in IgE- and complement-mediated cutaneous reactions. Such reactions supposedly involve specific cell surface membrane receptors. In this study, the cell surface marker profile of human skin MC was established using monoclonal antibodies (MoAb) against defined CD antigens. MC were isolated from juvenile foreskin (n = 55) and adult mammary skin (n = 5). The reactivity of MC with MoAb was assessed by a combined toluidine blue/immunofluorescence staining technique. Confirming our previous analyses on lung MC, foreskin MC reacted with MoAb against CD9, CD29, CD33, CD43, CD44, CD45, CD46, CD51, CD54, CD55, CD58, CD59, CD61, and CD117 (c-kit). Foreskin MC were also recognized by MoAb to CD47, CD48, CD49d, CD53, CD60, CD63, CD81, CD82, CD84, CD87, CD92, CD97, CD98, and CD99. Recently clustered CD antigens detectable on foreskin MC were CD147 (neurothelin), CD149 (MEM133), CD151 (PETA-3), and CD157 (BST-1). In contrast to lung MC and MC from adult skin, foreskin MC were found to express CD88 (C5aR). Also, cutaneous MC (from both juvenile foreskin and adult mammary skin), but not lung MC, were found to bind the CD32 MoAb IV.3, 2E1, and FLI8.26 (Fc gammaRII). The CD50 antigen (ICAM-3) was detectable on lung MC, but not on foreskin MC or MC of adult mammary skin. In summary, our data show that cutaneous MC and lung MC express an almost identical phenotype; however, in contrast to lung MC, cutaneous MC appear to express substantial amounts of CD32 and to lack CD50. In addition, foreskin MC, unlike MC from adult skin or lung, express CD88.

Although imatinib has become standard first-line therapy in chronic myelogenous leukemia (CML), allogeneic hematopoietic stem cell transplantation (HSCT) is still considered to be an important treatment alternative for patients with drug resistance or advanced disease. We retrospectively analyzed 175 adult CML patients who underwent HSCT at our institution between 1983 and 2007, with the aim to compare outcomes in patient subgroups and to identify prognostic variables. The median follow-up was 65 months. The probability of overall survival (OS) for all patients was 62%, with a significant improvement seen in the imatinib-era (2001-2007) compared to previous time periods (P

Pure populations of human basophilic granulocytes were obtained from chronic myeloid leukemia (CML) blood by negative selection using a mixture of monoclonal antibodies and complement. 125I-radiolabeled recombinant human interleukin 3 (rhIL-3) bound to purified basophils in a specific manner. Quantitative binding studies and Scatchard plot analyses performed on samples from two donors revealed the presence of a single class of high-affinity IL-3 binding sites (500 and 2100 sites per cell; dissociation constant at equilibrium, 230 and 160 pmol/liter, respectively). Purified CML basophils maintained in suspension in the presence of rhIL-3 (100 units/ml) incorporated up to 12 times more [3H]thymidine than basophils in control cultures. Furthermore, after preincubation in vitro with rhIL-3 (100 units/ml) for 30 min, normal blood basophils released 2- to 3-fold more histamine than basophils pretreated with control medium when exposed to various concentrations of an anti-IgE antibody. Together, these results show that rhIL-3 binds to a specific receptor on blood basophils and is a regulator of basophil function.