Paul Höcker

Regeneration of erythropoiesis after related- and unrelated-donor BMT or peripheral blood HPC transplantation: a major ABO mismatch means problems.

BACKGROUND: Blood group incompatibility in allogeneic BMT is common but does not appear to affect the outcome in terms of incidence of graft rejection or delayed engraftment. However, major ABO incompatibility may be associated with prolonged erythroid aplasia.

Long-term outcome and quality of life of patients who are alive and in complete remission more than two years after allogeneic and syngeneic stem cell transplantation.

We assessed long-term outcome in 155 patients who had undergone an allogeneic/syngeneic stem cell transplant (SCT) and were in complete remission for more than 2 years after transplant. Probability of late transplant-related mortality was 6%, and affected only patients with chronic graft-versus-host disease (cGVHD). Thirteen percent of patients experienced relapse. Overall survival projected at 10 and 15 years was 83% and 76%, respectively. Secondary malignancies occurred in two patients, 7.5 and 11 years after SCT. Three female and four male patients parented children 19 to 84 months after SCT. Quality of life (QoL) was assessed in a cross-sectional study by the means of a 30-item questionnaire (QLQ-C30) of the EORTC. The questionnaire was sent to 127 patients remaining alive and answered by 106 patients. Seventy-three percent reported a good to very good QoL within 5 years after SCT and 78% after this time point. However, patients with cGVHD had significant impairment of physical, role and social functioning and only 60% of them were fit for work. These results from long-term survivors show that high cure rates with good to very good QoL can be achieved by allogeneic or syngeneic SCT.

Severe immune hemolysis after minor ABO‐mismatched allogeneic peripheral blood progenitor cell transplantation occurs more frequently after nonmyeloablative than myeloablative conditioning

BACKGROUND : Hemolysis as a result of donor‐recipient minor ABO mismatching is a complication of allogeneic peripheral blood progenitor cell (PBPC) transplantation (PBPCT). The increased B‐lymphocyte content of PBPC grafts and immunosuppressive regimens without methotrexate (MTX) may increase incidence and severity of this event.

Antigenic analysis of human haemopoietic progenitor cells expressing the growth factor receptor c-kit.

Summary. The cell surface molecule encoded by the proto‐oncogene c‐kit has recently been identified as the receptor for a growth factor variously termed stem cell factor (SCF), mast cell growth factor or steel factor. Using the c‐kit antibody 17F11 we analysed, in triple staining experiments, the surface molecule profile and scatter characteristics of c‐kit+CD34+ human haemopoietic progenitor cells. In 10 normal bone marrow samples we found 19–51% of CD34+ bone marrow progenitor cells to coexpress c‐kit. These c‐kit+CD34+ bone marrow cells turned out to represent a phenotypically heterogeneous population. A considerable proportion coexpressed CD33 (52±23%), and/or CD71 (62 ±26) antigens, marker molecules previously shown to be expressed by committed in vitro colony forming cells but not by their precursors. In line with a relatively differentiated phenotype c‐kit+CD34+ cells also gave rise to on average higher forward and right‐angle light scattering signals. The proportions of CD38 and/or HLA‐D expressing cells were similar in the c‐kit+ and in the c‐kit− subsets of CD34+ progenitor cells. Coexpression of CD19 was found to be less frequent in the c‐kit+ (4 ± 5%) as compared to the c‐kit− (17 ± 14%) fraction of CD34+ cells. CD7+CD34+ bone marrow cells were hardly detectable and their numbers too low to allow further subdivision in c‐kit+ and c‐kit− subsets.

Differential induction of P-selectin expression on platelets by two cell separators during plateletpheresis and the effect of gender on the release of soluble P-selectin

BACKGROUND: Though a number of studies have elegantly characterized platelet activation during storage, less attention has been paid to the initial activation caused by different collection procedures. STUDY DESIGN AND METHODS: The effects of two blood cell separators on the initial activation of platelets were measured by flow cytometric analysis of P‐selectin expression in 13 male donors on one cell separator (CS 3000 Plus) and 11 men and 9 women on the other (MCS 3P). In addition, the storage and release of soluble P‐selectin (circulating P‐selectin [cP‐selectin]) by platelets were quantified, to determine whether the change in cP‐selectin is a more sensitive marker for initial platelet activation, and the influence of gender on measured endpoints was evaluated. RESULTS: The CS 3000 Plus increased the percentage of P‐selectin‐positive platelets from a median of 3.4 percent before apheresis to 7.6 percent (p = 0.006) in platelet concentrates (PCs), whereas the MCS 3P did not (p = 0.002 between the two cell separators). When preapheresis cP‐selectin levels were compared to those in apheresis PCs, cP‐selectin increased from 51 to 101 ng per mL in plasma of CS 3000 Plus PCs, whereas cP‐selectin levels increased from 53 to 78 ng per mL in MCS 3P PCs (men) and from 48 to 99 ng per mL in MSC 3P PCs (women) (p<0.005 for all). The relative increase in cP‐selectin was higher in women than in men in MCS 3P PCs (p = 0.013). Concomitantly, the amount of P‐selectin stored in platelets before apheresis decreased (p<0.025 for all). When donors undergoing apheresis on the MCS 3P were compared, the amount of P‐ selectin stored in the platelets of PCs was higher in men than women (p = 0.026). CONCLUSION: This trial shows 1) that initial activation of platelets obtained with the MCS 3P is less than that of platelets obtained with the CS 3000 Plus; 2) that the increase in cP‐selectin is a more sensitive marker for initial platelet activation than the expression of P‐selectin on the surface; and 3) that the relative amount of cP‐selectin is higher in women than in men given the same stimulus. Differences in platelet activation by various cell separators and the sex of the donor may contribute to variability of PC quality.

Platelet-reactive HLA antibodies associated with low posttransfusion platelet increments:a comparison between the monoclonal antibody-specific immobilization of platelet antigens assay and the lymphocytotoxicity test

BACKGROUND: Platelet‐reactive HLA antibodies are a major reason for low posttransfusion platelet increments. The clinical importance and value of the test systems for their in vitro determination is still controversial.

Red cell antibodies in frequently transfused patients with myelodysplastic syndrome

Abstract. Therapy for myelodysplastic syndrome (MDS) is often restricted to lifelong support with red blood cell units (RBCU). A variety of immune phenomena associated with antibody production have been reported in MDS patients. Therefore, we hypothesized that red cell antibodies are more frequent in patients with MDS compared to other regularly transfused patients. Red cell antibodies were determined in 42 MDS patients, in 28 patients with other hematological disorders, and in a historical group of 129 patients with end-stage renal failure. All of these patients received frequent red cell substitution therapy, at least two RBCU in biweekly intervals. Red cell antibodies were detected in 9 of 42 patients with MDS, in 3 of 28 patients with other hematological disorders, and in 4 of 129 patients with end-stage renal failure. Evidence of red cell antibodies was displayed by 6 of 27 MDS patients treated with prestorage leukocyte-depleted RBCU and 3 of 15 MDS patients transfused with bedside leukocyte-filtered RBCU. Red cell antibodies are frequent in patients with hematological disorders who require repetitive red cell transfusions. The formation of alloantibodies to red cell antigens is as frequent in MDS patients as in other patients with hematological disorders.

Increase in endogenous thrombopoietin in healthy donors after automated plateletpheresis

BACKGROUND: Thrombopoietin (TPO) is a key cytokine involved in the regulation of megakaryocytopoiesis and platelet production. The aim of the present study was to test whether platelet donation is associated with changes in the serum TPO levels in healthy donors undergoing plateletpheresis.

Deletion of chromosome 13q14 detected by fluorescence in situ hybridization has prognostic impact on survival after high-dose therapy in patients with multiple myeloma

Abstract. Interphase cytogenetic analysis of chromosome 13q14 was performed in 28 patients with multiple myeloma (MM) receiving high-dose therapy followed by autologous (n=24) or allogeneic (n=4) stem cell support. Eleven (39%) patients were found to have a deletion of chromosome 13q14. Response rates to high-dose therapy were independent of the chromosome 13 status, but patients with a deletion of 13q14 had a significantly shorter progression-free (p=0.001) and overall survival (p=0.012) than patients with normal chromosome 13q14. Our results indicate that high-dose therapy appears promising in patients with normal chromosome 13, whereas in patients with a deletion of 13q14 innovative therapeutic concepts are warranted.

Safety issues of plateletpheresis: comparison of the effects of two cell separators on the activation of coagulation, fibrinolysis, and neutrophils and on the formation of neutrophil-platelet aggregates.

BACKGROUND: Although many donors undergo repeated plateletpheresis, data on the consequences of plateletpheresis for the donors health remain scarce. Thus, the effect of plateletpheresis on the activation of coagulation, fibrinolysis, and neutrophils was investigated.