scholarly journals Osteopathic Treatment and Evaluation in the Clinical Setting of Childhood Hematological Malignancies

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6321
Author(s):  
Monica Barbieri ◽  
William Zardo ◽  
Chiara Frittoli ◽  
Clara Rivolta ◽  
Valeria Valdata ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Sports Medicine ◽  
Goal Attainment ◽  
Hematological Malignancies ◽  
Immunosuppressive Treatment ◽  
Spinal Column ◽  
Exercise Program ◽  
Clinical History ◽  
Hematopoietic Stem ◽  
Osteopathic Treatment

Children: adolescents, and young who are adults affected with hematological malignancies (CAYA-H) and who are undergoing intensive phases of cancer treatment, including hematopoietic stem cell transplantation (HSCT), experience diminished functional ability. This study was aimed at assessing the feasibility, efficacy, safety, and satisfaction of an osteopathic intervention in CAYA-H attending an 11-week precision-based exercise program (PEx). All of the participants were given 4–10 treatments according to the prescription ordered by the sports medicine doctor in charge of the PEx, and the following outcomes were assessed: (1) spinal column range of motion (ROM) by palpation; (2) lower and upper limb joints ROM by a goniometer; (3) orthostatic posture by plumb line assessment; (4) chest and abdomen mobility by inspection and palpation; (5) cranial-sacral rhythmic impulse (CRI) by palpation; and (6) adverse effects. Goal attainment scaling (GAS) was used to identify the accomplishment of a desired clinical result. Moreover, HSCT patients who were affected with graft-versus-host disease and/or osteonecrosis had their joints assessed in terms of ROM as tools to monitor the effectiveness of immunosuppressive treatment. A total of 231 CAYA-H were identified, and 104 participated in the study (age 10.66 ± 4.51 yrs; 43% F). PEx plus osteopathy reached positive GAS scores by improving the ROMs of the spinal column and/or limbs (81% and 78%, respectively), chest and abdomen mobility (82%), and CRI (76%). Only minor reversible adverse effects were noticed during the study. Together, our data seem to initiate a new course where osteopathy could be useful in evaluating structural edges due to the clinical history of each CAYA-H. Given the contributions that were obtained by the GAS scores, osteopathic treatment seems to reveal interesting potential that can be targeted in the future.

scholarly journals Should the BCRA1/2-mutations healthy carriers be valid candidates for hematopoietic stem cell donation?

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Alberto Fresa ◽  
Simona Sica
Keyword(s):  
Hematological Malignancies ◽  
Conditioning Regimen ◽  
Stress Factors ◽  
Brca Mutations ◽  
Hematopoietic Stem ◽  
Mutational Status ◽  
Stem Cell Donation ◽  
Radiation Treatments ◽  
Healthy Carriers

AbstractIt’s still not clear whether the mutational status of BRCA-mutated healthy hematopoietic stem cells (HSCs) donors could have an impact on the engraftment. Comparing the studies present in literature, we focused on the correlation between BRCA mutations and the development of hematological malignancies and Fanconi anemia (FA); then, we explored HSCs types, frequencies, and functions in the presence of BRCA mutations, as well as the reconstitution of hematopoiesis after chemotherapy and radiation treatments. The role of BRCA mutations in the FA showed a possible involvement in the onset of the disease; the mutation carriers, indeed, did not show any sign of the typical phenotype of the FA. BRCA mutational status can be considered as a risk factor for hematological malignancies, but only for secondary malignancies and/or in the presence of bone marrow stress factors. Currently we don’t know if a conditioning regimen could be compensated by BRCA mutated HSCs, even if murine models tried to show the possible differences between fully mutated, haploinsufficient and normal HSCs. Thus, given the downregulating effect of the mutations on hematopoiesis, it could be questionable to use the HSCs of a BRCA-mutated donor in the presence of another available donor with the same compatibility.

scholarly journals Gene Transcription as a Therapeutic Target in Leukemia

2021 ◽  
Vol 22 (14) ◽  
pp. 7340
Author(s):  
Alvina I. Khamidullina ◽  
Ekaterina A. Varlamova ◽  
Nour Alhuda Hammoud ◽  
Margarita A. Yastrebova ◽  
Alexandra V. Bruter
Keyword(s):  
Gene Transcription ◽  
Molecular Mechanisms ◽  
Hematological Malignancies ◽  
Mechanisms Of Action ◽  
Special Program ◽  
Cell Plasticity ◽  
Hematopoietic Stem ◽  
Promising Strategy ◽  
Tumor Cell Plasticity ◽  
Transcriptional Landscape

Blood malignancies often arise from undifferentiated hematopoietic stem cells or partially differentiated stem-like cells. A tight balance of multipotency and differentiation, cell division, and quiescence underlying normal hematopoiesis requires a special program governed by the transcriptional machinery. Acquisition of drug resistance by tumor cells also involves reprogramming of their transcriptional landscape. Limiting tumor cell plasticity by disabling reprogramming of the gene transcription is a promising strategy for improvement of treatment outcomes. Herein, we review the molecular mechanisms of action of transcription-targeted drugs in hematological malignancies (largely in leukemia) with particular respect to the results of clinical trials.

scholarly journals Cysteine Cathepsins and Their Prognostic and Therapeutic Relevance in Leukemia

2021 ◽  
Author(s):  
Mohit Arora ◽  
Garima Pandey ◽  
Shyam S. Chauhan
Keyword(s):  
Antigen Processing ◽  
Hematological Malignancies ◽  
Expression Patterns ◽  
Aberrant Expression ◽  
Hematopoietic Stem ◽  
Cysteine Cathepsins ◽  
Expression Activity ◽  
Available Information ◽  
Antigen Processing And Presentation ◽  
Selection Of

AbstractCysteine cathepsins are lysosomal proteases that require Cys-His ion pair in their catalytic site for enzymatic activity. While their aberrant expression and oncogenic functions have been widely reported in solid tumors, recent findings suggest that these proteases also play an important role in the pathogenesis of hematological malignancies. In this review, we summarize the potential clinical implications of cysteine cathepsins as diagnostic and prognostic markers in leukemia, and present evidences which supports the utility of these proteases as potential therapeutic targets in hematological malignancies. We also highlight the available information on the expression patterns, regulation, and potential functions of cysteine cathepsins in normal hematopoiesis and hematological malignancies. In hematopoiesis, cysteine cathepsins play a variety of physiological roles including regulation of hematopoietic stem cell adhesion in the bone marrow, trafficking, and maturation. They are also involved in several functions of immune cells which include the selection of lymphocytes in the thymus, antigen processing, and presentation. However, the expression of cysteine cathepsins is dysregulated in hematological malignancies where they have been shown to play diverse functions. Interestingly, several pieces of evidence over the past few years have demonstrated overexpression of cathepsins in leukemia and their association with worst survival outcomes in patients. Strategies aimed at altering the expression, activity, and subcellular localization of these cathepsins are emerging as potential therapeutic modalaties in the management of hematological malignancies. Recent findings also suggest the involvement of these proteases in modulating the immune response in leukemia and lymphomas.

scholarly journals BK virus-associated hemorrhagıc cystitis in patients wıth allogeneıc hematopoıetıc cell transplantation: report of three cases

2017 ◽  
Vol 9 (2) ◽  
Author(s):  
Duygu Mert ◽  
Hikmetullah Batgi ◽  
Alparslan Merdin ◽  
Sabahat Çeken ◽  
Mehmet Sinan Dal ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Hemorrhagic Cystitis ◽  
Immunosuppressive Treatment ◽  
Active Agent ◽  
Bk Virus ◽  
Cell Transplant ◽  
Hematopoietic Stem

BK virus is a human polyoma virus. It is acquired in early childhood and remains life-long latent in the genitourinary system. BK virus replication is more common in receiving immunosuppressive therapy receiving patients and transplant patients. BK virus could cause hemorrhagic cystitis in patients with allogeneic stem cell transplantation. Hemorrhagic cystitis is a serious complication of hematopoietic stem cell transplantation. Hemorrhagic cystitis could cause morbidity and long stay in the hospital. Diagnosis is more frequently determined by the presence of BK virus DNA detected with quantitative or real-time PCR testing in serum or plasma and less often in urine. The reduction of immunosuppression is effective in the treatment of BK virus infection. There are also several agents with anti-BK virus activity. Cidofovir is an active agent against a variety of DNA viruses including poliomyoma viruses and it is a cytosine nucleotide analogue. Intravenous immunoglobulin IgG (IVIG) also includes antibodies against BK and JC (John Cunningham) viruses. Hereby, we report three cases of hemorrhagic cystitis. Hemorrhagic cystitis developed in all these three cases of allogeneic stem cell transplantation due to acute myeloid leukemia (AML). BK virus were detected as the cause of hemorrhagic cystitis in these patients. Irrigation of the bladder was performed. Then levofloxacin 1×750 mg intravenous and IVIG 0.5 gr/kg were started. But the hematuria did not decreased. In the first case, treatment with leflunomide was started, but patient died due to refractory AML and severe graft-versus-host disease after 4th day of leflunamide and levofloxacin treatments. Cidofovir treatment and the reduction of immunosuppressive treatment decreased the BK virus load and resulted symptomatic improvement in the second case. Initiation of cidofovir was planned in the third case. Administration of cidofovir together with the reduction of immunosuppression in the treatment of hemorrhagic cystitis associated with BK virus in allogeneic stem cell transplant recipients could be a good option.

scholarly journals Identification and Age-dependent Increase of Platelet Biased Human Hematopoietic Stem Cells

2022 ◽  
Author(s):  
Merve Aksoz ◽  
Grigore-Aristide Gafencu ◽  
Bilyana Stoilova Stoilova ◽  
Mario Buono ◽  
Yiran Meng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Hematological Malignancies ◽  
Hematopoietic Stem ◽  
Cell Lineages ◽  
Cells Of Origin ◽  
Human Individual ◽  
Age Dependent ◽  
Human Hscs

Hematopoietic stem cells (HSC) reconstitute multi-lineage human hematopoiesis after clinical bone marrow transplantation and are the cells-of-origin of hematological malignancies. Though HSC provide multi-lineage engraftment, individual murine HSCs are lineage-biased and contribute unequally to blood cell lineages. Now, by combining xenografting of molecularly barcoded adult human bone marrow (BM) HSCs and high-throughput single cell RNA sequencing we demonstrate that human individual BM HSCs are also functionally and transcriptionally lineage biased. Specifically, we identify platelet-biased and multi-lineage human HSCs. Quantitative comparison of transcriptomes from single HSCs from young, and aged, BM show that both the proportion of platelet-biased HSCs, and their level of transcriptional platelet priming, increases with age. Therefore, platelet-biased HSCs, as well as their increased prevalence and elevated transcriptional platelet priming during ageing, are conserved between human and murine hematopoiesis.

scholarly journals The Role of Bruton’s Kinase Inhibitors in Chronic Lymphocytic Leukemia: Current Status and Future Directions

2021 ◽  
Author(s):  
Tadeusz Robak ◽  
Magda Witkowska ◽  
Piotr Smolewski
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Adverse Effects ◽  
Kinase Inhibitors ◽  
Clinical History ◽  
Lymphocytic Leukemia ◽  
Current Status ◽  
Covalent Inhibitors ◽  
History Of ◽  
Reduced Toxicity ◽  
Btk Inhibitors

The use of the Bruton’s tyrosine kinase (BTK) inhibitors has changed the management and clinical history of patients with chronic lymphocytic leukemia (CLL). BTK is a critical molecule that interconnects B-cell antigen receptor (BCR) signaling. BTKIs are classified into two categories: irreversible (covalent) inhibitors and reversible (non-covalent) inhibitors. Ibrutinib is the first irreversible BTK inhibitor approved by the U.S. Food and Drug Administration in 2013 as a breakthrough therapy in CLL patients. Subsequently, several studies evaluated the efficacy and safety of new agents with reduced toxicity when compared with ibrutinib. Two other irreversible, second-generation BTK inhibitors, acalabrutinib and zanubrutinib, were developed to reduce ibrutinib-mediated adverse effects. Additionally, new reversible BTK inhibitors are currently under development in an early phase studies to improve their activity and to diminish adverse effects. This review summarizes the pharmacology, clinical efficacy, safety, dosing, drug-drug interactions associated with the treatment of CLL with BTK inhibitors, and examines its further implications.

scholarly journals SECOND ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES

2019 ◽  
Vol 64 (1) ◽  
pp. 35-48
Author(s):  
L. A. Kuzmina ◽  
Z. V. Konova ◽  
E. N. Parovichnikova ◽  
M. Y. Drokov ◽  
V. A. Vasilyeva ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Disease Progression ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Graft Failure ◽  
Hematological Malignancies ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem

Background.Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a standard treatment for many patients with hematological malignancies. Complications of allo-HSCT are frequently associated either with a relapse of the underlying disease or a graft failure. Second transplantation can be offered to selected patients and is seen as the only curative option. In this paper, we report the experience of managing 24 such patients, all of whom underwent a second allo-HSCT.Patients and methods.The research involved 24 patients (12 males/12 females) suffering from acute myeloid leukemia (AML, n = 14), acute lymphoblastic leukemia (ALL, n = 4), myeloproliferative disease (MPD, n = 3) and myelodysplastic syndrome (MDS, n = 3). The patients’ age ranged from 18 to 56 years, with the median age being 32 years. All the patients underwent a second allo-HSCT due to the disease relapse (n = 11) or graft failure (n = 13). 12 patients underwent a second allo-HSCT within the period of less than 6 months after the first allo-HSCT.Results.Following the second allo-HSCT, engraftment occurred in 18/24 (75 %) patients, while 3 patients demonstrated graft failure and 3 — disease progression. Out of 18 patients having engrafted, 9 (50%) died during the first 100 days after allo-HSCT as a result of severe infections or visceral toxicity. 3 more lethal outcomes were recorded in later periods due to the disease progression. The overall mortality rate after the second allo-HSCT equalled 61.5 %. The median overall survival (OS) and disease-free survival (DFS) rates were 13.5 months and 10.59 months, respectively. Three-year OS and DFS were 38.5 % and 27.6 % respectively. Significant differences in terms of OS were detected for patients with a longer interval (>6 months) between the first and second allo-HSCT. The change of a donor was not associated with a better clinical outcome.

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