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Allogeneic stem cell transplantation

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https://www.readbyqxmd.com/read/27913520/myeloma-management-of-the-newly-diagnosed-high-risk-patient
#1
Angela Dispenzieri
Although there have been many definitions for high-risk (HR) myeloma, most recent consensus for classifying risk in patients with newly diagnosed multiple myeloma (NMM) comes from the International Myeloma Working Group. This recently published revised International Staging System includes del(17p) or t(4;14) by fluorescence in situ hybridization, β-2 microglobulin, albumin, and lactate dehydrogenase. These elements should be captured in all NMM patients. The optimal treatments for HR myeloma have not been fully worked out; therefore, these patients should be considered for clinical trials...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913519/transplantation-for-myelodysplastic-syndromes-who-when-and-which-conditioning-regimens
#2
Wael Saber, Mary M Horowitz
Allogeneic hematopoietic stem cell transplantation (HCT) is the only curative therapy for myelodysplastic syndrome (MDS). Broad application is hindered by high risks of transplant-related morbidity and mortality, especially in the older age range represented by the MDS population. However, recent advances in strategies to minimize regimen-related toxicity make HCT a viable option for many more patients. Appropriate selection of patients involves consideration of patient factors, including use of geriatric assessment tools and comorbidity scales, that predict risks of regimen-related toxicity as well as disease factors, including genetic markers, which predict survival with both non-HCT and HCT therapy...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913510/frontline-therapy-and-role-of-high-dose-consolidation-in-mantle-cell-lymphoma
#3
Simon Rule
Mantle cell lymphoma (MCL) is a rare and aggressive form of non-Hodgkin lymphoma. It is predominantly a disease of older individuals, with a median age at presentation of ∼70 years. For the majority of patients, the management revolves around immuno-chemotherapy often followed by maintenance rituximab, and at relapse, a range of options are available. For the younger patient, it is possible to be more intensive with therapy, consolidate responses with high-dose procedures, and in a few there might be the prospect of a cure...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913499/novel-agents-and-strategies-in-transplant-eligible-patients-with-relapsed-and-refractory-hodgkin-lymphoma
#4
Craig Moskowitz
The majority of patients with Hodgkin lymphoma are cured with frontline therapy; however, 10% to 15% with early-stage disease and 20% to 30% with advanced stage require second-line therapy that includes a potentially curative transplant, of which an additional 50% to 55% are cured. Those with multiply relapsed disease traditionally would receive novel agents on a clinical trial or combination chemotherapy as a potential bridge to an allogeneic stem cell transplant. This treatment paradigm has changed with the availability of brentuximab vedotin, an antibody drug conjugate used pre- and post-ASCT, as well as for palliation...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913469/can-we-make-a-better-match-or-mismatch-with-kir-genotyping
#5
Rohtesh S Mehta, Katayoun Rezvani
Natural killer (NK) cell function is regulated by a fine balance between numerous activating and inhibitory receptors, of which killer-cell immunoglobulin-like receptors (KIRs) are among the most polymorphic and comprehensively studied. KIRs allow NK cells to recognize downregulation or the absence of HLA class I molecules on target cells (known as missing-self), a phenomenon that is commonly observed in virally infected cells or cancer cells. Because KIR and HLA genes are located on different chromosomes, in an allogeneic environment such as after hematopoietic stem cell transplantation, donor NK cells that express an inhibitory KIR for an HLA class I molecule that is absent on recipient targets (KIR/KIR-ligand mismatch), can recognize and react to this missing self and mediate cytotoxicity...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913467/transplantation-for-bone-marrow-failure-current-issues
#6
Régis Peffault de Latour
The preferred treatment of idiopathic aplastic anemia (AA) is allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen (HLA)-identical sibling donor. Transplantation from a well-matched unrelated donor (MUD) may be considered for patients without a sibling donor after failure of immunosuppressive therapy, as may alternative transplantation (mismatched, cord blood or haplo-identical HSCT) for patients without a MUD. HSCT may also be contemplated for congenital disorders in cases of pancytopenia or severe isolated cytopenia...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913459/children-with-rare-diseases-of-neutrophil-granulocytes-from-therapeutic-orphans-to-pioneers-of-individualized-medicine
#7
Christoph Klein
Neutrophil granulocytes are the most abundant immune cells in the blood yet the pathways orchestrating their differentiation and biological function remain incompletely understood. Studying (ultra-) rare patients with monogenetic defects of neutrophil granulocytes may open new horizons to understand basic principles of hematopoiesis and innate immunity. Here, recent insights into genetic factors controlling myelopoiesis and their more general role in biology will be presented in a clinical perspective. Advances in supportive care, first and foremost the use of recombinant human granulocyte-colony stimulating factor, has made a substantial difference for the quality of life and life expectancy of patients with congenital neutropenia (CN)...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913458/therapy-related-myeloid-neoplasms-does-knowing-the-origin-help-to-guide-treatment
#8
Michael Heuser
Therapy-related myeloid neoplasms (t-MN) combine t-MDS and therapy related acute myeloid leukemia (t-AML) patients in one entity because of their similar pathogenesis, rapid progression from t-MDS to t-AML, and their equally poor prognosis. Treatment with epipodophyllotoxins like etoposide has been associated with a short interval between treatment and development of t-AML, with fusion oncogenes like KMT2A/MLL-MLLT3 and a better prognosis. In contrast, treatment with alkylating agents has been associated with a longer latency, an initial MDS phase, adverse cytogenetics, and a poor prognosis...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27912993/rehabilitation-in-chronic-graft-versus-host-disease
#9
REVIEW
Sean Robinson Smith, Arash Asher
Chronic graft-versus-host disease is a potentially debilitating complication of allogeneic hematopoietic stem cell transplantation. Due to the direct inflammatory effects of the disease on tissue, and the impact on muscle and bone of the high-dose glucocorticoid immunosuppression used to treat the disease, patients are at risk of developing multifactorial functional impairment. This review outlines the clinical assessment and rehabilitation interventions to manage aspects of the disease that cause the most impairment: involvement of the skin/fascial and cardiopulmonary organ systems, as well as steroid-induced myopathy and bone and joint destruction...
February 2017: Physical Medicine and Rehabilitation Clinics of North America
https://www.readbyqxmd.com/read/27912759/intestinal-dysbiosis-and-allogeneic-hematopoietic-progenitor-cell-transplantation
#10
REVIEW
Vikram M Raghunathan, Iris Sheng, Seah H Lim
The intestinal microbiota is a diverse and dynamic ecosystem that is increasingly understood to play a vital role in human health. Hematopoietic stem cell transplant recipients undergo prolonged exposure to antimicrobials, chemotherapeutic agents, and immunosuppressants, resulting in profound shifts in the gut microbiome. A growing body of research has revealed the ways in which these microbiologic shifts shape immune modulation, affecting susceptibility to infections and graft-versus-host disease, the two major post-transplant complications in this population...
December 3, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27910184/clinical-significance-of-pre-transplant-circulating-cd3-cd4-cd161-cell-frequency-on-the-occurrence-of-neutropenic-infections-after-allogeneic-stem-cell-transplantation
#11
Tae Woo Kim, Sung-Eun Lee, Ji-Young Lim, Da-Bin Ryu, Young-Woo Jeon, Jae-Ho Yoon, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Hee-Je Kim, Seok Lee, Seok-Goo Cho, Dong-Wook Kim, Jong Wook Lee, Woo-Sung Min, Chang-Ki Min
BACKGROUND: Few studies have been performed to identify factors that are associated with an increased risk of infections during the neutropenic period in patients undergoing allogeneic stem cell transplantation (allo-SCT). The aim of this study was to identify the host immune cells responsible for infections before engraftment. METHODS: A total of 282 patients who underwent allo-SCT were enrolled. Peripheral blood samples were collected before conditioning therapy...
December 2, 2016: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/27909887/similar-outcome-after-allogeneic-stem-cell-transplantation-with-a-modified-flamsa-conditioning-protocol-substituting-4%C3%A2-gy-tbi-with-treosulfan-in-an-elderly-population-with-high-risk-aml
#12
Udo Holtick, Marco Herling, Natali Pflug, Geothy Chakupurakal, Silke Leitzke, Dominik Wolf, Michael Hallek, Christof Scheid, Jens M Chemnitz
The fludarabine, amsacrine, and cytarabine (FLAMSA)-reduced-intensity conditioning (RIC) protocol has been described to be effective in patients with high-risk and refractory acute myeloic leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (aSCT). To increase safety and tolerability of the conditioning, we previously reported the feasibility to substitute the TBI component by treosulfan in elderly AML patients. We now present long-term follow-up data on patients treated with FLAMSA/treosulfan compared to the original FLAMSA/4Gy TBI protocol...
December 1, 2016: Annals of Hematology
https://www.readbyqxmd.com/read/27909435/immune-reconstitution-after-allogeneic-hematopoietic-stem-cell-transplantation
#13
REVIEW
Justyna Ogonek, Mateja Kralj Juric, Sakhila Ghimire, Pavankumar Reddy Varanasi, Ernst Holler, Hildegard Greinix, Eva Weissinger
The timely reconstitution and regain of function of a donor-derived immune system is of utmost importance for the recovery and long-term survival of patients after allogeneic hematopoietic stem cell transplantation (HSCT). Of note, new developments such as umbilical cord blood or haploidentical grafts were associated with prolonged immunodeficiency due to delayed immune reconstitution, raising the need for better understanding and enhancing the process of immune reconstitution and finding strategies to further optimize these transplant procedures...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27909215/cure-for-thalassemia-major-from-allogeneic-hematopoietic-stem-cell-transplantation-to-gene-therapy
#14
Alok Srivastava, Ramachandran V Shaji
Allogeneic hematopoietic stem cell transplantation has been established for several decades as a gene replacement therapy for patients with thalassemia major and now offers very high rates of cure to those who are able to access this therapy. Outcomes have improved tremendously over the last decade even in high-risk patients. The limited data available suggests that the long-term outcome is also excellent with >90% survival but for best results, hematopoietic stem cell transplantation should be offered early before any end organ damage occurs...
December 1, 2016: Haematologica
https://www.readbyqxmd.com/read/27907031/in-vitro-pre-clinical-validation-of-suicide-gene-modified-anti-cd33-redirected-chimeric-antigen-receptor-t-cells-for-acute-myeloid-leukemia
#15
Kentaro Minagawa, Muhammad O Jamil, Mustafa Al-Obaidi, Larisa Pereboeva, Donna Salzman, Harry P Erba, Lawrence S Lamb, Ravi Bhatia, Shin Mineishi, Antonio Di Stasi
BACKGROUND: Approximately fifty percent of patients with acute myeloid leukemia can be cured with current therapeutic strategies which include, standard dose chemotherapy for patients at standard risk of relapse as assessed by cytogenetic and molecular analysis, or high-dose chemotherapy with allogeneic hematopoietic stem cell transplant for high-risk patients. Despite allogeneic hematopoietic stem cell transplant about 25% of patients still succumb to disease relapse, therefore, novel strategies are needed to improve the outcome of patients with acute myeloid leukemia...
2016: PloS One
https://www.readbyqxmd.com/read/27906171/combined-nifuroxazide-and-sat05f-therapy-reduces-graft-versus-host-disease-after-experimental-allogeneic-bone-marrow-transplantation
#16
Huijie Jia, Tiesuo Zhao, Yinghua Ji, Xiaolong Jia, Wenjing Ren, Chen Li, Minming Li, Yali Xiao, Hui Wang, Kailin Xu
Acute graft-versus-host disease (aGvHD) is the major barrier to the broader use of allogenetic hematopoietic stem cells. However, currently these are no highly specific and efficient drugs. Monotherapy is not sufficient and more efficient and safe therapeutic regimen are urgent need. Studies demonstrated TLR9 and Stat3 signal pathways are critical for antigen-presenting cell maturation and T-cell activation, which are important mediators in aGvHD. Specific block these two critical signal pathways using their inhibitors SAT05f and nifuroxazide may be the novel strategies for aGvHD therapy...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906067/aspartylglycosaminuria-a-review
#17
REVIEW
Maria Arvio, Ilkka Mononen
Aspartylglucosaminuria (AGU), a recessively inherited lysosomal storage disease, is the most common disorder of glycoprotein degradation with a high prevalence in the Finnish population. It is a lifelong condition affecting on the patient's appearance, cognition, adaptive skills, physical growth, personality, body structure, and health. An infantile growth spurt and development of macrocephalia associated to hernias and respiratory infections are the key signs to an early identification of AGU. Progressive intellectual and physical disability is the main symptom leading to death usually before the age of 50 years...
December 1, 2016: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/27905258/hla-mismatched-haploidentical-transplantation-using-low-dose-anti-thymocyte-globulin-atg-thymoglobulin
#18
Shinichi Kako, Yu Akahoshi, Naonori Harada, Hirofumi Nakano, Kazuaki Kameda, Tomotaka Ugai, Ryoko Yamasaki, Hidenori Wada, Yuko Ishihara, Koji Kawamura, Kana Sakamoto, Miki Sato, Masahiro Ashizawa, Kiriko Terasako-Saito, Shun-Ichi Kimura, Misato Kikuchi, Hideki Nakasone, Rie Yamazaki, Junya Kanda, Yoshinobu Kanda
Objectives To clarify optimal strategies for human leukocyte antigen (HLA)-mismatched haploidentical hematopoietic stem cell transplantation (HSCT). Methods Twelve patients who underwent HSCT from a haploidentical related donor using low-dose thymoglobulin were analyzed retrospectively. Thymoglobulin was added to conditioning regimens at 2.5 mg/kg/day for 2 days (days -4 and -3). Prophylaxis against graft-versus-host disease (GVHD) was performed with cyclosporine and methotrexate. Results The median age of the patients was 33 years...
December 1, 2016: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/27905193/high-pretransplant-hepcidin-levels-are-associated-with-poor-overall-survival-and-delayed-platelet-engraftment-after-allogeneic-hematopoietic-stem-cell-transplantation
#19
Soichiro Sakamoto, Hiroshi Kawabata, Junya Kanda, Tatsuki Uchiyama, Chisaki Mizumoto, Toshiyuki Kitano, Tadakazu Kondo, Masakatsu Hishizawa, Naohisa Tomosugi, Akifumi Takaori-Kondo
Iron overload is considered a risk factor for mortality in patients with hematopoietic malignancies. Hepcidin is a key regulator of systemic iron balance. We previously reported dynamic changes of serum hepcidin-25 levels in patients with hematologic malignancies after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study, we retrospectively analyzed the association of pretransplant hepcidin-25 levels with overall survival (OS), engraftment, and other clinical outcomes of allo-HSCT in patients with hematologic malignancies...
December 1, 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27904816/an-unusual-presentation-of-nocardiosis-in-an-allogeneic-transplant-recipient
#20
Uroosa Ibrahim, Amina Saqib, Farhan Mohammad, Terenig Terjanian
Nocardiosis is a rare cause of opportunistic infection post hematopoietic stem cell transplant (HSCT) occurring in about 0.3% of patients. The risk factors include delayed immune reconstitution, prolonged neutropenia, and graft-versus-host disease. The most common site of infection is the lung, followed by the brain and the skin. Concomitant pulmonary and central nervous system (CNS) nocardiosis is an extremely rare entity as presented in our case. We present the case of a 72-year-old male at 137 days post transplant presenting with complaints of headache and slurred speech...
October 17, 2016: Curēus
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