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Fetal and neonatal thrombopoietin levels in alloimmune thrombocytopenia
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and the recipient (R) on mortality posttransplant. CMV-seronegative patients received seronegative or leukoreduced blood products (residual white blood cells <5 X lo6 cells/product). All subjects were monitored weekly from engraftment to day 100 for CMV reactivation in CMV-seropositive recipients or primary infection in CMV-seronegative recipients by pp65 antigenemia assay and blood viral cultures. The data were analyzed with a multivariable Cox regression model. The majority of the patients had SCT for either acute leukemia (37.5%) or chronic myelogenous leukemia (34.7%), and more than half received a mismatched or unrelated donor product. Of the 1,750 patients, 628 (35.9%) were CMV serostatus D-/R-, 262 (15%) were D+/R-, 467 (26.7%), were D+/R+ and 393 (22.4%) were D-/R+. The D+/R+ and D+/Rpatients were found to have the highest risk of mortality. However, after controlling for neutropenia and clinical CMV disease, the D+/Ipatients were found to be at a significantly higher risk for mortality. Furthermore, bacteremia or invasive fungal infection was more common in the D+IRgroup (18.3%) than in the D-/Rgroup (9.7%, P < ,001). The authors concluded that despite prophylactic antiviral therapy, CMV serostatus is still associated with mortality. They state that ganciclovir administration and resultant neutropenia in CMV proven disease explains the association with mortality in seropositive recipients. Yet, in the D+/Rpatients with increased rates of bacterial and fungal infection associated mortality, the authors postulate an immunomodulatory effect of subclinical primary CMV infection that occurred despite rigorous monitoring throughout the transplant. They propose that future studies looking at impact of CMV serostatus on treatment-related mortality should integrate information from serogroup pairs rather than on separate CMV status of either the donor or recipient. Furthermore, the investigators encourage more aggressive prophylactic anti-CMV strategies for the group and improved strategies to specifically target D+IRprevention of bacterial and fungal infections in this population. (C.H.)
Fetal and neonatal thrombopoietin levels in alloimL. Porcelijn, C.Folman, M. mune thrombocytopenia. deHaas, et al. Ped Research 52:105-108, 2002. Patients with autoimmune thrombocytopenia have normal or slightly increased thrombopoeitin (Tpo) lev& that aIe attributed to megakaryocyte and platelet Tpo receptor uptake before antibody-mediated peripheral destruction. In this study, the investigators measured Tpo levels in fetuses and infants with neonatal alloimmune thrombocytopenia (NAIT) to understand the role of TPO in this disease. The authors measured Tpo levels in umbilical cord plasma samples from 50 fetuses before treatment for NAIT and 51 fetuses after treatment for NAIT, in addition to peripheral blood samples from 21 untreated newborns with NAIT. The results were compared with control samples from umbilical cords of 14 nonthrombocytopenic fetuses with hemolytic disease of the newborn, umbilical cords of 51 healthy newborns, and peripheral blood of 193 healthy adults. A solid-phase sandwich enzyme-linked immunosorbent assay was used to measure Tpo concentrations, the same technique used to obtain Tpo levels in autoimmune thrombocytopenia study. Tpo levels were found to be significantly higher in all fetuses
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and neonates including all control and NAIT plasmas as compared with levels in healthy adults. However, the Tpo levels in the NAIT plasma samples were not significantly different from their age-matched controls. Therefore, the authors concluded that NAIT patients have normal to slightly increased Tpo levels just as in patient with autoimmune thrombcytopenia. This information furthers our understanding of the pathophysiology of NAIT. (C.H.) Quantification and facilitated comparison of von Willebrand factor multimer patterns by densitometry. J. Studt, U. Budde, R. Schneppenheim, et al. J Clin Pathol 116:567-574, 2001. von Willebrand factor (vWF) multimer analysis is a vital laboratory test for differentiating between the various subtypes of von Willebrand disease (vWD). Currently, laboratories visualize the multimers after isolating them with electrophoresis. However, reproducibility and interlaboratory consistency with this current method is considered inadequate. The investigators in this study applied densitometry to quantify and visualize vWF multimer patterns in healthy donors, patient vWD variants, and several factor VIIVvWF concentrates. Luminagraphic separation and visualization of multimers produced on x-ray film were analyzed by densitometry to identify the variation observed within vWF multimer analysis and quantify the range of mulitmer patterns for normal donor plasma. Furthermore, in patients with known vWD varients, such as type I, 2A, 2B, 2M, and 2N vWD, and in factor concentrates containing FVIIVvWF with low or absent large multimers, this method showed strut-tural defects and quantified differences in the distribution of multimer proportions. The authors conclude that densitometry can provide an accurate, quantitative comparison of multimer structure and patterns. Therefore, this technique can be used for reproducible quantification and further visualization of normal and abnormal vWF multimer patterns. They suggest that densitometry may be a valuable tool to standardize vWF multimer analysis .and in the diagnosis of TTP. (C.H.) Severe cold hemagglutinin disease (CHD) successfully treated with rituximab. M. Engelhardt, A. Jakob, 13. Ruter, eta/. Blood 2002; 100: 1922-23. Rituximab (Rituxan, anti-CD20) is a mouse-human chimeric hybridoma with activity against cells expressing the CD20 antigen. Intravenous injection of rituximab results in clearance of CD20-expressing B-lymphocytes. Originally used for B-cell lymphomas, rituximab has been increasingly applied to autoimmune disorders characterized by B-cell over activity. This report describes the use of rituximab in two patients with cold hemagglutinin disease. The first patient was a 50-year-old woman who presented with cold autoimmune hemolytic anemia and a hemoglobin concentration of 7.3 g/dL. She was initially treated with highdose prednisone. However, 5 months later, her hemolysis recurred, and she was given cyclophosphamide and mycophenolate mofetil. Her hemolysis worsened, and she was treated with plamapheresis with little improvement. Finally, rituximab was given at 375 mg/m2 intravenously weekly for 4 courses. Her hemolysis went into remission. The second patient was a 60-year-old woman with a known
and the recipient (R) on mortality posttransplant. CMV-seronegative patients received seronegative or leukoreduced blood products (residual white blood cells <5 X lo6 cells/product). All subjects were monitored weekly from engraftment to day 100 for CMV reactivation in CMV-seropositive recipients or primary infection in CMV-seronegative recipients by pp65 antigenemia assay and blood viral cultures. The data were analyzed with a multivariable Cox regression model. The majority of the patients had SCT for either acute leukemia (37.5%) or chronic myelogenous leukemia (34.7%), and more than half received a mismatched or unrelated donor product. Of the 1,750 patients, 628 (35.9%) were CMV serostatus D-/R-, 262 (15%) were D+/R-, 467 (26.7%), were D+/R+ and 393 (22.4%) were D-/R+. The D+/R+ and D+/Rpatients were found to have the highest risk of mortality. However, after controlling for neutropenia and clinical CMV disease, the D+/Ipatients were found to be at a significantly higher risk for mortality. Furthermore, bacteremia or invasive fungal infection was more common in the D+IRgroup (18.3%) than in the D-/Rgroup (9.7%, P < ,001). The authors concluded that despite prophylactic antiviral therapy, CMV serostatus is still associated with mortality. They state that ganciclovir administration and resultant neutropenia in CMV proven disease explains the association with mortality in seropositive recipients. Yet, in the D+/Rpatients with increased rates of bacterial and fungal infection associated mortality, the authors postulate an immunomodulatory effect of subclinical primary CMV infection that occurred despite rigorous monitoring throughout the transplant. They propose that future studies looking at impact of CMV serostatus on treatment-related mortality should integrate information from serogroup pairs rather than on separate CMV status of either the donor or recipient. Furthermore, the investigators encourage more aggressive prophylactic anti-CMV strategies for the group and improved strategies to specifically target D+IRprevention of bacterial and fungal infections in this population. (C.H.)
Fetal and neonatal thrombopoietin levels in alloimL. Porcelijn, C.Folman, M. mune thrombocytopenia. deHaas, et al. Ped Research 52:105-108, 2002. Patients with autoimmune thrombocytopenia have normal or slightly increased thrombopoeitin (Tpo) lev& that aIe attributed to megakaryocyte and platelet Tpo receptor uptake before antibody-mediated peripheral destruction. In this study, the investigators measured Tpo levels in fetuses and infants with neonatal alloimmune thrombocytopenia (NAIT) to understand the role of TPO in this disease. The authors measured Tpo levels in umbilical cord plasma samples from 50 fetuses before treatment for NAIT and 51 fetuses after treatment for NAIT, in addition to peripheral blood samples from 21 untreated newborns with NAIT. The results were compared with control samples from umbilical cords of 14 nonthrombocytopenic fetuses with hemolytic disease of the newborn, umbilical cords of 51 healthy newborns, and peripheral blood of 193 healthy adults. A solid-phase sandwich enzyme-linked immunosorbent assay was used to measure Tpo concentrations, the same technique used to obtain Tpo levels in autoimmune thrombocytopenia study. Tpo levels were found to be significantly higher in all fetuses
JOURNAL
CLUB
and neonates including all control and NAIT plasmas as compared with levels in healthy adults. However, the Tpo levels in the NAIT plasma samples were not significantly different from their age-matched controls. Therefore, the authors concluded that NAIT patients have normal to slightly increased Tpo levels just as in patient with autoimmune thrombcytopenia. This information furthers our understanding of the pathophysiology of NAIT. (C.H.) Quantification and facilitated comparison of von Willebrand factor multimer patterns by densitometry. J. Studt, U. Budde, R. Schneppenheim, et al. J Clin Pathol 116:567-574, 2001. von Willebrand factor (vWF) multimer analysis is a vital laboratory test for differentiating between the various subtypes of von Willebrand disease (vWD). Currently, laboratories visualize the multimers after isolating them with electrophoresis. However, reproducibility and interlaboratory consistency with this current method is considered inadequate. The investigators in this study applied densitometry to quantify and visualize vWF multimer patterns in healthy donors, patient vWD variants, and several factor VIIVvWF concentrates. Luminagraphic separation and visualization of multimers produced on x-ray film were analyzed by densitometry to identify the variation observed within vWF multimer analysis and quantify the range of mulitmer patterns for normal donor plasma. Furthermore, in patients with known vWD varients, such as type I, 2A, 2B, 2M, and 2N vWD, and in factor concentrates containing FVIIVvWF with low or absent large multimers, this method showed strut-tural defects and quantified differences in the distribution of multimer proportions. The authors conclude that densitometry can provide an accurate, quantitative comparison of multimer structure and patterns. Therefore, this technique can be used for reproducible quantification and further visualization of normal and abnormal vWF multimer patterns. They suggest that densitometry may be a valuable tool to standardize vWF multimer analysis .and in the diagnosis of TTP. (C.H.) Severe cold hemagglutinin disease (CHD) successfully treated with rituximab. M. Engelhardt, A. Jakob, 13. Ruter, eta/. Blood 2002; 100: 1922-23. Rituximab (Rituxan, anti-CD20) is a mouse-human chimeric hybridoma with activity against cells expressing the CD20 antigen. Intravenous injection of rituximab results in clearance of CD20-expressing B-lymphocytes. Originally used for B-cell lymphomas, rituximab has been increasingly applied to autoimmune disorders characterized by B-cell over activity. This report describes the use of rituximab in two patients with cold hemagglutinin disease. The first patient was a 50-year-old woman who presented with cold autoimmune hemolytic anemia and a hemoglobin concentration of 7.3 g/dL. She was initially treated with highdose prednisone. However, 5 months later, her hemolysis recurred, and she was given cyclophosphamide and mycophenolate mofetil. Her hemolysis worsened, and she was treated with plamapheresis with little improvement. Finally, rituximab was given at 375 mg/m2 intravenously weekly for 4 courses. Her hemolysis went into remission. The second patient was a 60-year-old woman with a known