The Experts below are selected from a list of 1131 Experts worldwide ranked by ideXlab platform
Harry L. Malech - One of the best experts on this subject based on the ideXlab platform.
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WHIM Syndrome: Congenital Immune Deficiency Disease
Current opinion in hematology, 2009Co-Authors: Toshinao Kawai, Harry L. MalechAbstract:Purpose of review Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is characterized by susceptibility to human papilloma virus infection-induced warts and carcinomas; neutropenia, B-cell lymphopenia and hypogammaglobulinema-related infections; and bone marrow myelokathexis (myeloid hyperplasia with apoptosis). The purpose of this report is to review new findings about WHIM. Recent findings Most WHIM patients have heterozygous C-terminus deletion mutations of the intracellular carboxy terminus of the chemokine receptor CXCR4. WHIM leukocytes have enhanced responses to CXCL12, the cognate ligand of CXCR4. Enhanced activity of CXCR4 delays release of mature neutrophils from bone marrow, resulting in neutropenia and apoptosis of mature neutrophils retained in the marrow. Finding two patients with WHIM who do not have detectable mutations of CXCR4 but whose cells are hyperresponsive to CXCL12 raises the possibility that there is more than one genetic basis for WHIM. One patient had low levels of G-protein receptor kinase 3, and the functional hyperactivity response to CXCL12 was corrected by forced gene transfer-mediated overexpression of G-protein receptor kinase 3, implicating defects in function of this protein as a potential alternate genetic cause of WHIM. Summary Subjects reviewed include clinical presentation, diagnosis, and treatment of WHIM and advances in understanding the genetic basis of WHIM.
Joanne Kurtzberg - One of the best experts on this subject based on the ideXlab platform.
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late effects after umbilical cord blood transplantation in very young children after busulfan based myeloablative conditioning
Biology of Blood and Marrow Transplantation, 2016Co-Authors: Heather Allewelt, Jill Elkhorazaty, Adam Mendizabal, Mahsa Taskindoust, Paul Martin, Vinod K Prasad, Kristin Page, J E Sanders, Joanne KurtzbergAbstract:Abstract Infants and young children who undergo allogeneic cord blood transplantation (CBT) are at increased risk for late effects because of exposure of developing organs to chemotherapy and radiation therapy typically used in transplant conditioning regimens. Busulfan (Bu)-based myeloablative regimens were developed to eliminate radiation exposure in these young children with the hope that late effects would be minimized. We now describe the late effects in 102 consecutive patients surviving a minimum of 5 years (median follow-up, 12.9 years) post-CBT. Patients were conditioned with high-dose chemotherapy using Bu-containing regimens. No patient received total body irradiation. The median age at transplant was 1 year (range, .1 to 2). Diagnoses included inherited metabolic diseases (59.8%), leukemia (17.6%), Congenital Immune Deficiency (20.2%), bone marrow failure/myelodysplastic syndrome (3.9%), and hemoglobinopathy (2%). Among patients surviving 5 years, the overall survival rate at 10 years post-CBT was 93% (95% CI, 84.9 to 96.8). Virtually all patients (98%) experienced at least 1 significant late effect. Most (83.3%) experienced 2 or more late effects, and more than half of the patients (64.7%) experienced 3 or more late effects. The most commonly observed late effects included dental problems (92.2%), short stature (55.9%), cognitive deficits (53.6%), pulmonary dysfunction (18.6%), and abnormal pubertal development (27.9%). This is the first report of late effects of Bu-based conditioning in a cohort of very young patients at the time of transplant. These results will inform clinical care guidelines for long-term follow-up and add to the growing information regarding outcomes of hematopoietic stem cell transplantation.
Toshinao Kawai - One of the best experts on this subject based on the ideXlab platform.
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WHIM Syndrome: Congenital Immune Deficiency Disease
Current opinion in hematology, 2009Co-Authors: Toshinao Kawai, Harry L. MalechAbstract:Purpose of review Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is characterized by susceptibility to human papilloma virus infection-induced warts and carcinomas; neutropenia, B-cell lymphopenia and hypogammaglobulinema-related infections; and bone marrow myelokathexis (myeloid hyperplasia with apoptosis). The purpose of this report is to review new findings about WHIM. Recent findings Most WHIM patients have heterozygous C-terminus deletion mutations of the intracellular carboxy terminus of the chemokine receptor CXCR4. WHIM leukocytes have enhanced responses to CXCL12, the cognate ligand of CXCR4. Enhanced activity of CXCR4 delays release of mature neutrophils from bone marrow, resulting in neutropenia and apoptosis of mature neutrophils retained in the marrow. Finding two patients with WHIM who do not have detectable mutations of CXCR4 but whose cells are hyperresponsive to CXCL12 raises the possibility that there is more than one genetic basis for WHIM. One patient had low levels of G-protein receptor kinase 3, and the functional hyperactivity response to CXCL12 was corrected by forced gene transfer-mediated overexpression of G-protein receptor kinase 3, implicating defects in function of this protein as a potential alternate genetic cause of WHIM. Summary Subjects reviewed include clinical presentation, diagnosis, and treatment of WHIM and advances in understanding the genetic basis of WHIM.
Heather Allewelt - One of the best experts on this subject based on the ideXlab platform.
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late effects after umbilical cord blood transplantation in very young children after busulfan based myeloablative conditioning
Biology of Blood and Marrow Transplantation, 2016Co-Authors: Heather Allewelt, Jill Elkhorazaty, Adam Mendizabal, Mahsa Taskindoust, Paul Martin, Vinod K Prasad, Kristin Page, J E Sanders, Joanne KurtzbergAbstract:Abstract Infants and young children who undergo allogeneic cord blood transplantation (CBT) are at increased risk for late effects because of exposure of developing organs to chemotherapy and radiation therapy typically used in transplant conditioning regimens. Busulfan (Bu)-based myeloablative regimens were developed to eliminate radiation exposure in these young children with the hope that late effects would be minimized. We now describe the late effects in 102 consecutive patients surviving a minimum of 5 years (median follow-up, 12.9 years) post-CBT. Patients were conditioned with high-dose chemotherapy using Bu-containing regimens. No patient received total body irradiation. The median age at transplant was 1 year (range, .1 to 2). Diagnoses included inherited metabolic diseases (59.8%), leukemia (17.6%), Congenital Immune Deficiency (20.2%), bone marrow failure/myelodysplastic syndrome (3.9%), and hemoglobinopathy (2%). Among patients surviving 5 years, the overall survival rate at 10 years post-CBT was 93% (95% CI, 84.9 to 96.8). Virtually all patients (98%) experienced at least 1 significant late effect. Most (83.3%) experienced 2 or more late effects, and more than half of the patients (64.7%) experienced 3 or more late effects. The most commonly observed late effects included dental problems (92.2%), short stature (55.9%), cognitive deficits (53.6%), pulmonary dysfunction (18.6%), and abnormal pubertal development (27.9%). This is the first report of late effects of Bu-based conditioning in a cohort of very young patients at the time of transplant. These results will inform clinical care guidelines for long-term follow-up and add to the growing information regarding outcomes of hematopoietic stem cell transplantation.
Mahsa Taskindoust - One of the best experts on this subject based on the ideXlab platform.
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late effects after umbilical cord blood transplantation in very young children after busulfan based myeloablative conditioning
Biology of Blood and Marrow Transplantation, 2016Co-Authors: Heather Allewelt, Jill Elkhorazaty, Adam Mendizabal, Mahsa Taskindoust, Paul Martin, Vinod K Prasad, Kristin Page, J E Sanders, Joanne KurtzbergAbstract:Abstract Infants and young children who undergo allogeneic cord blood transplantation (CBT) are at increased risk for late effects because of exposure of developing organs to chemotherapy and radiation therapy typically used in transplant conditioning regimens. Busulfan (Bu)-based myeloablative regimens were developed to eliminate radiation exposure in these young children with the hope that late effects would be minimized. We now describe the late effects in 102 consecutive patients surviving a minimum of 5 years (median follow-up, 12.9 years) post-CBT. Patients were conditioned with high-dose chemotherapy using Bu-containing regimens. No patient received total body irradiation. The median age at transplant was 1 year (range, .1 to 2). Diagnoses included inherited metabolic diseases (59.8%), leukemia (17.6%), Congenital Immune Deficiency (20.2%), bone marrow failure/myelodysplastic syndrome (3.9%), and hemoglobinopathy (2%). Among patients surviving 5 years, the overall survival rate at 10 years post-CBT was 93% (95% CI, 84.9 to 96.8). Virtually all patients (98%) experienced at least 1 significant late effect. Most (83.3%) experienced 2 or more late effects, and more than half of the patients (64.7%) experienced 3 or more late effects. The most commonly observed late effects included dental problems (92.2%), short stature (55.9%), cognitive deficits (53.6%), pulmonary dysfunction (18.6%), and abnormal pubertal development (27.9%). This is the first report of late effects of Bu-based conditioning in a cohort of very young patients at the time of transplant. These results will inform clinical care guidelines for long-term follow-up and add to the growing information regarding outcomes of hematopoietic stem cell transplantation.