The Experts below are selected from a list of 49801875 Experts worldwide ranked by ideXlab platform
Davi D J Kuter - One of the best experts on this subject based on the ideXlab platform.
-
evaluation of bone marrow reticulin formation in chronic immune thrombocytopenia patients treated with romiplostim
Blood, 2009Co-Authors: Davi D J Kuter, Wende Davis, Ghulam J Mufti, Barbara J Bain, Robert P. Hasserjian, Mark RutsteinAbstract:Romiplostim is a thrombopoietin receptor agonist that increases platelet counts in patients with chronic immune thrombocytopenia (ITP). Thrombopoietin receptor agonists are reported to increase the risk for reticulin fiber deposition within bone marrow. This report describes bone marrow findings from romiplostim-treated rats, a retrospective analysis of reticulin observed in romiplostim ITP clinical trials, and a prospective clinical study of the effects of romiplostim on bone marrow morphology. In rats, romiplostim produced a dose-dependent increase in bone marrow fibrosis that resolved after treatment withdrawal. Of 271 ITP patients in romiplostim clinical trials, 10 were reported to have reticulin deposition; reticulin grade was increased in 4 of 5 patients with both pretreatment and on-treatment bone marrow results. Reticulin grade often decreased soon after romiplostim discontinuation. In the prospective study, reticulin grade during romiplostim treatment remained within the normal range for all patients and was increased in only 1 of 6 patients with pretreatment and on-treatment bone marrow results. This report suggests that romiplostim produces reversible, dose-dependent bone marrow changes in rats and produces modest increases in bone marrow reticulin in some ITP patients that decrease when therapy is discontinued. These studies were registered at www.clinicaltrials.gov as #NCT00102323, #NCT00102336, #NCT00861224, and #NCT00116688.
-
evaluation of bone marrow reticulin formation in romiplostim treated adult patients with chronic immune thrombocytopenic purpura itp
Blood, 2008Co-Authors: Davi D J Kuter, Barbara Bain, Ghulam J Mufti, Robert P. Hasserjian, Mark RutsteinAbstract:Introduction: Romiplostim is an investigational Fc-peptide fusion protein (peptibody) that stimulates platelet production by a mechanism similar to endogenous thrombopoietin and is being investigated for its ability to treat patients with chronic ITP. Some degree of reticulin deposition is often a normal finding in bone marrow, and increased reticulin has been detected in patients treated with thrombopoietin mimetics (Kuter et al, Br J Haem 2007). We analyzed bone marrow biopsy samples from ITP patients at baseline and after romiplostim treatment for the presence and degree of reticulin. Methods: Baseline and post-treatment samples were analyzed from two sets of bone marrow data: (1) a prospective study in which both baseline (pre-treatment) and follow-up (post-treatment) samples were taken, and (2) a retrospective study of spontaneously reported observations of reticulin occurring across all romiplostim clinical trials. Assessments were made from aspirate smears, core biopsies, reticulin stains, trichrome stains, and written reports. Only patients with evaluable baseline and post-treatment samples are included in this report. Reticulin was graded according to the following scale: 0 (absent), 1 (fine fibers), 2 (diffuse fine fiber network), 3 (diffuse fiber network with scattered coarse fibers), and 4 (areas of collagen). Grade 0–2 reticulin can be found in bone marrow from healthy individuals, and reticulin grades 1 to 2 have been described in the bone marrow of 66% of ITP patients (Mufti et al, ASH 2006). Results: Six of 10 prospective study patients had both evaluable baseline and follow-up samples. Reticulin grades in all 6 samples at baseline were 0–1. Only 1 patient demonstrated an increase in reticulin (from 0–1 to 1–2 after 3 months of romiplostim). Higher degrees of reticulin deposition (grades >2) were not observed, and trichrome staining demonstrated absence of collagen in all 6 cases. Baseline and follow-up bone marrow samples were available in 5 of 9 retrospective study patients, including one patient from the prospective study in whom reticulin was also spontaneously reported following romiplostim administration. In these 5 patients, the baseline reticulin grade was 0 to 1 in all cases and increased after treatment in all but one case. Reticulin typically decreased soon after discontinuation of romiplostim. Two patients were exposed to drug doses exceeding those used in current clinical studies (≥ 10 μg/kg). One patient showed minimal collagen deposition (reticulin grade 4) that was absent in a further follow-up sample after treatment discontinuation. Conclusion: Increased reticulin was observed in the bone marrow of some romiplostim-treated patients and typically decreased soon after drug withdrawal. There was no evidence that romiplostim exposure led to development of chronic idiopathic myelofibrosis or other clonal disorders in this small sample of patients. Table 1. Reticulin scores in bone marrow samples from ITP patients before and following romiplostim therapy
-
bone marrow reticulin in patients with immune thrombocytopenic purpura
Blood, 2006Co-Authors: Ghulam J Mufti, Lyndah Dreiling, Davi D J Kuter, Adam Bagg, Barbara J Bain, Robert P. Hasserjian, Janet L NicholAbstract:Immune thrombocytopenic purpura (ITP) is an uncommon disorder, and research that characterizes the bone marrow stroma in ITP patients is lacking. It is known that megakaryocytes are often increased in number in ITP patients. Megakaryocytes are associated with reticulin formation in other conditions, including malignant and nonmalignant diseases, such as systemic lupus erythematosus and other immune disorders. Our objective was to determine if the reactive megakaryocyte proliferations in ITP are associated with increased reticulin deposition. We identified 40 ITP patients from clinical records in a retrospective survey of bone marrow biopsy material. Patients were required to have had a diagnosis of ITP, a bone marrow biopsy with available tissue blocks, and a complete blood count at the time of the biopsy. Paraffin-embedded sections from the bone marrow biopsy specimens were stained for reticulin using standard silver-impregnation methods. Reticulin was quantified using the Bauermeister scale (0 = no reticulin fibers demonstrable; 1 = occasional fine individual fibers and foci of a fine fiber network; 2 = fine fiber network throughout most of the section but no coarse fibers; 3 = diffuse fiber network with scattered thick coarse fibers but no mature collagen; and 4 = diffuse often coarse fiber network with areas of collagen). In addition, bone marrow cellularity and megakaryocyte numbers were evaluated. Of the 40 patients, 13 (33%) were considered to have absent (grade 0) bone marrow reticulin, 1 (2%) had grade 0–1, 20 (50%) had grade 1, 5 (13%) had grade 1–2, and 1 (2%) had grade 2. Thus, reticulin was present in the bone marrow of approximately two-thirds of the patients, with 15% having greater than grade 1. Previous research on bone marrow reticulin in 100 hematologically normal subjects found that 27% had Bauermeister reticulin grade 1 and 4% had grade 2 (Arch Pathol Lab Med1990;114:1241–3). Analysis is ongoing to further characterize the deposition of reticulin in the bone marrow of patients with ITP, the relationship of reticulin deposition to megakaryocyte numbers and location, and correlations with patient clinical findings.
Ghulam J Mufti - One of the best experts on this subject based on the ideXlab platform.
-
evaluation of bone marrow reticulin formation in chronic immune thrombocytopenia patients treated with romiplostim
Blood, 2009Co-Authors: Davi D J Kuter, Wende Davis, Ghulam J Mufti, Barbara J Bain, Robert P. Hasserjian, Mark RutsteinAbstract:Romiplostim is a thrombopoietin receptor agonist that increases platelet counts in patients with chronic immune thrombocytopenia (ITP). Thrombopoietin receptor agonists are reported to increase the risk for reticulin fiber deposition within bone marrow. This report describes bone marrow findings from romiplostim-treated rats, a retrospective analysis of reticulin observed in romiplostim ITP clinical trials, and a prospective clinical study of the effects of romiplostim on bone marrow morphology. In rats, romiplostim produced a dose-dependent increase in bone marrow fibrosis that resolved after treatment withdrawal. Of 271 ITP patients in romiplostim clinical trials, 10 were reported to have reticulin deposition; reticulin grade was increased in 4 of 5 patients with both pretreatment and on-treatment bone marrow results. Reticulin grade often decreased soon after romiplostim discontinuation. In the prospective study, reticulin grade during romiplostim treatment remained within the normal range for all patients and was increased in only 1 of 6 patients with pretreatment and on-treatment bone marrow results. This report suggests that romiplostim produces reversible, dose-dependent bone marrow changes in rats and produces modest increases in bone marrow reticulin in some ITP patients that decrease when therapy is discontinued. These studies were registered at www.clinicaltrials.gov as #NCT00102323, #NCT00102336, #NCT00861224, and #NCT00116688.
-
evaluation of bone marrow reticulin formation in romiplostim treated adult patients with chronic immune thrombocytopenic purpura itp
Blood, 2008Co-Authors: Davi D J Kuter, Barbara Bain, Ghulam J Mufti, Robert P. Hasserjian, Mark RutsteinAbstract:Introduction: Romiplostim is an investigational Fc-peptide fusion protein (peptibody) that stimulates platelet production by a mechanism similar to endogenous thrombopoietin and is being investigated for its ability to treat patients with chronic ITP. Some degree of reticulin deposition is often a normal finding in bone marrow, and increased reticulin has been detected in patients treated with thrombopoietin mimetics (Kuter et al, Br J Haem 2007). We analyzed bone marrow biopsy samples from ITP patients at baseline and after romiplostim treatment for the presence and degree of reticulin. Methods: Baseline and post-treatment samples were analyzed from two sets of bone marrow data: (1) a prospective study in which both baseline (pre-treatment) and follow-up (post-treatment) samples were taken, and (2) a retrospective study of spontaneously reported observations of reticulin occurring across all romiplostim clinical trials. Assessments were made from aspirate smears, core biopsies, reticulin stains, trichrome stains, and written reports. Only patients with evaluable baseline and post-treatment samples are included in this report. Reticulin was graded according to the following scale: 0 (absent), 1 (fine fibers), 2 (diffuse fine fiber network), 3 (diffuse fiber network with scattered coarse fibers), and 4 (areas of collagen). Grade 0–2 reticulin can be found in bone marrow from healthy individuals, and reticulin grades 1 to 2 have been described in the bone marrow of 66% of ITP patients (Mufti et al, ASH 2006). Results: Six of 10 prospective study patients had both evaluable baseline and follow-up samples. Reticulin grades in all 6 samples at baseline were 0–1. Only 1 patient demonstrated an increase in reticulin (from 0–1 to 1–2 after 3 months of romiplostim). Higher degrees of reticulin deposition (grades >2) were not observed, and trichrome staining demonstrated absence of collagen in all 6 cases. Baseline and follow-up bone marrow samples were available in 5 of 9 retrospective study patients, including one patient from the prospective study in whom reticulin was also spontaneously reported following romiplostim administration. In these 5 patients, the baseline reticulin grade was 0 to 1 in all cases and increased after treatment in all but one case. Reticulin typically decreased soon after discontinuation of romiplostim. Two patients were exposed to drug doses exceeding those used in current clinical studies (≥ 10 μg/kg). One patient showed minimal collagen deposition (reticulin grade 4) that was absent in a further follow-up sample after treatment discontinuation. Conclusion: Increased reticulin was observed in the bone marrow of some romiplostim-treated patients and typically decreased soon after drug withdrawal. There was no evidence that romiplostim exposure led to development of chronic idiopathic myelofibrosis or other clonal disorders in this small sample of patients. Table 1. Reticulin scores in bone marrow samples from ITP patients before and following romiplostim therapy
-
bone marrow reticulin in patients with immune thrombocytopenic purpura
Blood, 2006Co-Authors: Ghulam J Mufti, Lyndah Dreiling, Davi D J Kuter, Adam Bagg, Barbara J Bain, Robert P. Hasserjian, Janet L NicholAbstract:Immune thrombocytopenic purpura (ITP) is an uncommon disorder, and research that characterizes the bone marrow stroma in ITP patients is lacking. It is known that megakaryocytes are often increased in number in ITP patients. Megakaryocytes are associated with reticulin formation in other conditions, including malignant and nonmalignant diseases, such as systemic lupus erythematosus and other immune disorders. Our objective was to determine if the reactive megakaryocyte proliferations in ITP are associated with increased reticulin deposition. We identified 40 ITP patients from clinical records in a retrospective survey of bone marrow biopsy material. Patients were required to have had a diagnosis of ITP, a bone marrow biopsy with available tissue blocks, and a complete blood count at the time of the biopsy. Paraffin-embedded sections from the bone marrow biopsy specimens were stained for reticulin using standard silver-impregnation methods. Reticulin was quantified using the Bauermeister scale (0 = no reticulin fibers demonstrable; 1 = occasional fine individual fibers and foci of a fine fiber network; 2 = fine fiber network throughout most of the section but no coarse fibers; 3 = diffuse fiber network with scattered thick coarse fibers but no mature collagen; and 4 = diffuse often coarse fiber network with areas of collagen). In addition, bone marrow cellularity and megakaryocyte numbers were evaluated. Of the 40 patients, 13 (33%) were considered to have absent (grade 0) bone marrow reticulin, 1 (2%) had grade 0–1, 20 (50%) had grade 1, 5 (13%) had grade 1–2, and 1 (2%) had grade 2. Thus, reticulin was present in the bone marrow of approximately two-thirds of the patients, with 15% having greater than grade 1. Previous research on bone marrow reticulin in 100 hematologically normal subjects found that 27% had Bauermeister reticulin grade 1 and 4% had grade 2 (Arch Pathol Lab Med1990;114:1241–3). Analysis is ongoing to further characterize the deposition of reticulin in the bone marrow of patients with ITP, the relationship of reticulin deposition to megakaryocyte numbers and location, and correlations with patient clinical findings.
Mark Rutstein - One of the best experts on this subject based on the ideXlab platform.
-
evaluation of bone marrow reticulin formation in chronic immune thrombocytopenia patients treated with romiplostim
Blood, 2009Co-Authors: Davi D J Kuter, Wende Davis, Ghulam J Mufti, Barbara J Bain, Robert P. Hasserjian, Mark RutsteinAbstract:Romiplostim is a thrombopoietin receptor agonist that increases platelet counts in patients with chronic immune thrombocytopenia (ITP). Thrombopoietin receptor agonists are reported to increase the risk for reticulin fiber deposition within bone marrow. This report describes bone marrow findings from romiplostim-treated rats, a retrospective analysis of reticulin observed in romiplostim ITP clinical trials, and a prospective clinical study of the effects of romiplostim on bone marrow morphology. In rats, romiplostim produced a dose-dependent increase in bone marrow fibrosis that resolved after treatment withdrawal. Of 271 ITP patients in romiplostim clinical trials, 10 were reported to have reticulin deposition; reticulin grade was increased in 4 of 5 patients with both pretreatment and on-treatment bone marrow results. Reticulin grade often decreased soon after romiplostim discontinuation. In the prospective study, reticulin grade during romiplostim treatment remained within the normal range for all patients and was increased in only 1 of 6 patients with pretreatment and on-treatment bone marrow results. This report suggests that romiplostim produces reversible, dose-dependent bone marrow changes in rats and produces modest increases in bone marrow reticulin in some ITP patients that decrease when therapy is discontinued. These studies were registered at www.clinicaltrials.gov as #NCT00102323, #NCT00102336, #NCT00861224, and #NCT00116688.
-
evaluation of bone marrow reticulin formation in romiplostim treated adult patients with chronic immune thrombocytopenic purpura itp
Blood, 2008Co-Authors: Davi D J Kuter, Barbara Bain, Ghulam J Mufti, Robert P. Hasserjian, Mark RutsteinAbstract:Introduction: Romiplostim is an investigational Fc-peptide fusion protein (peptibody) that stimulates platelet production by a mechanism similar to endogenous thrombopoietin and is being investigated for its ability to treat patients with chronic ITP. Some degree of reticulin deposition is often a normal finding in bone marrow, and increased reticulin has been detected in patients treated with thrombopoietin mimetics (Kuter et al, Br J Haem 2007). We analyzed bone marrow biopsy samples from ITP patients at baseline and after romiplostim treatment for the presence and degree of reticulin. Methods: Baseline and post-treatment samples were analyzed from two sets of bone marrow data: (1) a prospective study in which both baseline (pre-treatment) and follow-up (post-treatment) samples were taken, and (2) a retrospective study of spontaneously reported observations of reticulin occurring across all romiplostim clinical trials. Assessments were made from aspirate smears, core biopsies, reticulin stains, trichrome stains, and written reports. Only patients with evaluable baseline and post-treatment samples are included in this report. Reticulin was graded according to the following scale: 0 (absent), 1 (fine fibers), 2 (diffuse fine fiber network), 3 (diffuse fiber network with scattered coarse fibers), and 4 (areas of collagen). Grade 0–2 reticulin can be found in bone marrow from healthy individuals, and reticulin grades 1 to 2 have been described in the bone marrow of 66% of ITP patients (Mufti et al, ASH 2006). Results: Six of 10 prospective study patients had both evaluable baseline and follow-up samples. Reticulin grades in all 6 samples at baseline were 0–1. Only 1 patient demonstrated an increase in reticulin (from 0–1 to 1–2 after 3 months of romiplostim). Higher degrees of reticulin deposition (grades >2) were not observed, and trichrome staining demonstrated absence of collagen in all 6 cases. Baseline and follow-up bone marrow samples were available in 5 of 9 retrospective study patients, including one patient from the prospective study in whom reticulin was also spontaneously reported following romiplostim administration. In these 5 patients, the baseline reticulin grade was 0 to 1 in all cases and increased after treatment in all but one case. Reticulin typically decreased soon after discontinuation of romiplostim. Two patients were exposed to drug doses exceeding those used in current clinical studies (≥ 10 μg/kg). One patient showed minimal collagen deposition (reticulin grade 4) that was absent in a further follow-up sample after treatment discontinuation. Conclusion: Increased reticulin was observed in the bone marrow of some romiplostim-treated patients and typically decreased soon after drug withdrawal. There was no evidence that romiplostim exposure led to development of chronic idiopathic myelofibrosis or other clonal disorders in this small sample of patients. Table 1. Reticulin scores in bone marrow samples from ITP patients before and following romiplostim therapy
David J Unsworth - One of the best experts on this subject based on the ideXlab platform.
-
anti tissue transglutaminase anti endomysium and anti r1 reticulin autoantibodies the antibody trinity of coeliac disease
Clinical and Experimental Immunology, 1999Co-Authors: Richard J. Lock, J E M Gilmour, David J UnsworthAbstract:Anti-tissue transglutaminase has been recently described as the predominant autoantigen in coeliac disease. We purified serum anti-tissue transglutaminase antibodies from three patients with coeliac disease by column chromatography and eluted tissue section-bound R1-anti-reticulin antibodies from sections of rat tissue for two of these. Lastly, we generated seven mouse MoAbs to guinea pig tissue transglutaminase. Each preparation was examined for anti-tissue transglutaminase, anti-endomysium, anti-R1 reticulin and anti-gliadin antibodies. Column-purified patient antibodies and 2/7 mouse MoAbs gave characteristic anti-endomysium/anti-R1 reticulin reactivity on rat, monkey and human tissue. All positive sera gave indistinguishable patterns of immunofluorescence on rat liver, kidney and stomach, monkey oesophagus, and human umbilical cord. Anti-R1-reticulin eluted from sections showed anti-tissue transglutaminase reactivity in 2/2 cases, but 0/2 showed anti-gliadin reactivity. In both, tissue section-eluted anti-R1 reticulin gave endomysial staining on monkey oesophagus. None of the mouse monoclonals, or any of the purified patient's anti-tissue transglutaminase or anti-R1-reticulin antibody showed any reactivity with gliadin. These data confirm tissue transglutaminase as the predominant autoantigen in coeliac disease and suggest that both anti-endomysium and anti-R1 reticulin reactivities seen in coeliac disease arise due to an immune response to tissue transglutaminase. Rigorous immunoabsorption was sufficient to abrogate reactivity in the tissue transglutaminase ELISA, but failed to completely absorb anti-endomysium and anti-reticulin activity. The possibility remains that some of the anti-endomysium and anti-reticulin activity was directed against antigens other than tissue transglutaminase.
-
anti tissue transglutaminase anti endomysium and anti r1 reticulin autoantibodies the antibody trinity of coeliac disease
Clinical and Experimental Immunology, 1999Co-Authors: Richard J. Lock, J E M Gilmour, David J UnsworthAbstract:Anti-tissue transglutaminase has been recently described as the predominant autoantigen in coeliac disease. We purified serum anti-tissue transglutaminase antibodies from three patients with coeliac disease by column chromatography and eluted tissue section-bound R1-anti-reticulin antibodies from sections of rat tissue for two of these. Lastly, we generated seven mouse MoAbs to guinea pig tissue transglutaminase. Each preparation was examined for anti-tissue transglutaminase, anti-endomysium, anti-R1 reticulin and anti-gliadin antibodies. Column-purified patient antibodies and 2/7 mouse MoAbs gave characteristic anti-endomysium/anti-R1 reticulin reactivity on rat, monkey and human tissue. All positive sera gave indistinguishable patterns of immunofluorescence on rat liver, kidney and stomach, monkey oesophagus, and human umbilical cord. Anti-R1-reticulin eluted from sections showed anti-tissue transglutaminase reactivity in 2/2 cases, but 0/2 showed anti-gliadin reactivity. In both, tissue section-eluted anti-R1 reticulin gave endomysial staining on monkey oesophagus. None of the mouse monoclonals, or any of the purified patient's anti-tissue transglutaminase or anti-R1-reticulin antibody showed any reactivity with gliadin. These data confirm tissue transglutaminase as the predominant autoantigen in coeliac disease and suggest that both anti-endomysium and anti-R1 reticulin reactivities seen in coeliac disease arise due to an immune response to tissue transglutaminase. Rigorous immunoabsorption was sufficient to abrogate reactivity in the tissue transglutaminase ELISA, but failed to completely absorb anti-endomysium and anti-reticulin activity. The possibility remains that some of the anti-endomysium and anti-reticulin activity was directed against antigens other than tissue transglutaminase.
Robert P. Hasserjian - One of the best experts on this subject based on the ideXlab platform.
-
evaluation of bone marrow reticulin formation in chronic immune thrombocytopenia patients treated with romiplostim
Blood, 2009Co-Authors: Davi D J Kuter, Wende Davis, Ghulam J Mufti, Barbara J Bain, Robert P. Hasserjian, Mark RutsteinAbstract:Romiplostim is a thrombopoietin receptor agonist that increases platelet counts in patients with chronic immune thrombocytopenia (ITP). Thrombopoietin receptor agonists are reported to increase the risk for reticulin fiber deposition within bone marrow. This report describes bone marrow findings from romiplostim-treated rats, a retrospective analysis of reticulin observed in romiplostim ITP clinical trials, and a prospective clinical study of the effects of romiplostim on bone marrow morphology. In rats, romiplostim produced a dose-dependent increase in bone marrow fibrosis that resolved after treatment withdrawal. Of 271 ITP patients in romiplostim clinical trials, 10 were reported to have reticulin deposition; reticulin grade was increased in 4 of 5 patients with both pretreatment and on-treatment bone marrow results. Reticulin grade often decreased soon after romiplostim discontinuation. In the prospective study, reticulin grade during romiplostim treatment remained within the normal range for all patients and was increased in only 1 of 6 patients with pretreatment and on-treatment bone marrow results. This report suggests that romiplostim produces reversible, dose-dependent bone marrow changes in rats and produces modest increases in bone marrow reticulin in some ITP patients that decrease when therapy is discontinued. These studies were registered at www.clinicaltrials.gov as #NCT00102323, #NCT00102336, #NCT00861224, and #NCT00116688.
-
evaluation of bone marrow reticulin formation in romiplostim treated adult patients with chronic immune thrombocytopenic purpura itp
Blood, 2008Co-Authors: Davi D J Kuter, Barbara Bain, Ghulam J Mufti, Robert P. Hasserjian, Mark RutsteinAbstract:Introduction: Romiplostim is an investigational Fc-peptide fusion protein (peptibody) that stimulates platelet production by a mechanism similar to endogenous thrombopoietin and is being investigated for its ability to treat patients with chronic ITP. Some degree of reticulin deposition is often a normal finding in bone marrow, and increased reticulin has been detected in patients treated with thrombopoietin mimetics (Kuter et al, Br J Haem 2007). We analyzed bone marrow biopsy samples from ITP patients at baseline and after romiplostim treatment for the presence and degree of reticulin. Methods: Baseline and post-treatment samples were analyzed from two sets of bone marrow data: (1) a prospective study in which both baseline (pre-treatment) and follow-up (post-treatment) samples were taken, and (2) a retrospective study of spontaneously reported observations of reticulin occurring across all romiplostim clinical trials. Assessments were made from aspirate smears, core biopsies, reticulin stains, trichrome stains, and written reports. Only patients with evaluable baseline and post-treatment samples are included in this report. Reticulin was graded according to the following scale: 0 (absent), 1 (fine fibers), 2 (diffuse fine fiber network), 3 (diffuse fiber network with scattered coarse fibers), and 4 (areas of collagen). Grade 0–2 reticulin can be found in bone marrow from healthy individuals, and reticulin grades 1 to 2 have been described in the bone marrow of 66% of ITP patients (Mufti et al, ASH 2006). Results: Six of 10 prospective study patients had both evaluable baseline and follow-up samples. Reticulin grades in all 6 samples at baseline were 0–1. Only 1 patient demonstrated an increase in reticulin (from 0–1 to 1–2 after 3 months of romiplostim). Higher degrees of reticulin deposition (grades >2) were not observed, and trichrome staining demonstrated absence of collagen in all 6 cases. Baseline and follow-up bone marrow samples were available in 5 of 9 retrospective study patients, including one patient from the prospective study in whom reticulin was also spontaneously reported following romiplostim administration. In these 5 patients, the baseline reticulin grade was 0 to 1 in all cases and increased after treatment in all but one case. Reticulin typically decreased soon after discontinuation of romiplostim. Two patients were exposed to drug doses exceeding those used in current clinical studies (≥ 10 μg/kg). One patient showed minimal collagen deposition (reticulin grade 4) that was absent in a further follow-up sample after treatment discontinuation. Conclusion: Increased reticulin was observed in the bone marrow of some romiplostim-treated patients and typically decreased soon after drug withdrawal. There was no evidence that romiplostim exposure led to development of chronic idiopathic myelofibrosis or other clonal disorders in this small sample of patients. Table 1. Reticulin scores in bone marrow samples from ITP patients before and following romiplostim therapy
-
bone marrow reticulin in patients with immune thrombocytopenic purpura
Blood, 2006Co-Authors: Ghulam J Mufti, Lyndah Dreiling, Davi D J Kuter, Adam Bagg, Barbara J Bain, Robert P. Hasserjian, Janet L NicholAbstract:Immune thrombocytopenic purpura (ITP) is an uncommon disorder, and research that characterizes the bone marrow stroma in ITP patients is lacking. It is known that megakaryocytes are often increased in number in ITP patients. Megakaryocytes are associated with reticulin formation in other conditions, including malignant and nonmalignant diseases, such as systemic lupus erythematosus and other immune disorders. Our objective was to determine if the reactive megakaryocyte proliferations in ITP are associated with increased reticulin deposition. We identified 40 ITP patients from clinical records in a retrospective survey of bone marrow biopsy material. Patients were required to have had a diagnosis of ITP, a bone marrow biopsy with available tissue blocks, and a complete blood count at the time of the biopsy. Paraffin-embedded sections from the bone marrow biopsy specimens were stained for reticulin using standard silver-impregnation methods. Reticulin was quantified using the Bauermeister scale (0 = no reticulin fibers demonstrable; 1 = occasional fine individual fibers and foci of a fine fiber network; 2 = fine fiber network throughout most of the section but no coarse fibers; 3 = diffuse fiber network with scattered thick coarse fibers but no mature collagen; and 4 = diffuse often coarse fiber network with areas of collagen). In addition, bone marrow cellularity and megakaryocyte numbers were evaluated. Of the 40 patients, 13 (33%) were considered to have absent (grade 0) bone marrow reticulin, 1 (2%) had grade 0–1, 20 (50%) had grade 1, 5 (13%) had grade 1–2, and 1 (2%) had grade 2. Thus, reticulin was present in the bone marrow of approximately two-thirds of the patients, with 15% having greater than grade 1. Previous research on bone marrow reticulin in 100 hematologically normal subjects found that 27% had Bauermeister reticulin grade 1 and 4% had grade 2 (Arch Pathol Lab Med1990;114:1241–3). Analysis is ongoing to further characterize the deposition of reticulin in the bone marrow of patients with ITP, the relationship of reticulin deposition to megakaryocyte numbers and location, and correlations with patient clinical findings.
