scholarly journals Novel therapies vs hematopoietic cell transplantation in myelofibrosis: who, when, how?

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 453-462
Author(s):  
James England ◽  
Vikas Gupta
Keyword(s):  
Cell Transplantation ◽  
Medical Therapy ◽  
Hematopoietic Cell Transplantation ◽  
Myeloproliferative Neoplasms ◽  
Philadelphia Chromosome ◽  
Optimal Timing ◽  
Jak2 Mutation ◽  
Hematopoietic Stem ◽  
Curative Therapy ◽  
Duration Of Disease

Abstract Myelofibrosis is one of the classical Philadelphia chromosome–negative myeloproliferative neoplasms characterized by progressive marrow failure and chronic inflammation. Discovery of the JAK2 mutation paved the way for development of small molecular inhibitors and further facilitated the research in understanding of molecular biology of the disease. Development of novel medications and synergistic combinations with standard JAK inhibitor (JAKi) therapy may have the potential to improve depth and duration of disease control and symptomatic benefit, whereas advancements in allogeneic hematopoietic stem cell transplantation (HCT) have improved tolerability and donor availability, allowing for more patients to pursue this potentially curative therapy. The increase in options for medical therapy and changing risk profile of HCT is leading to increased complexity in counseling patients on choice of management strategy. In this case-based review, we summarize our approach to symptom-directed medical therapy, including the use of novel drugs and combination therapies currently under study in advanced clinical trials. We outline our recommendations for optimal timing of HCT, including risk-adapted selection for early HCT as opposed to delayed HCT after upfront JAKi therapy, as well as the use of pretransplant JAKi and alternative donor sources.

scholarly journals A Systematic Review of Machine Learning Techniques in Hematopoietic Stem Cell Transplantation (HSCT)

Sensors ◽  
2020 ◽  
Vol 20 (21) ◽  
pp. 6100
Author(s):  
Vibhuti Gupta ◽  
Thomas M. Braun ◽  
Mosharaf Chowdhury ◽  
Muneesh Tewari ◽  
Sung Won Choi
Keyword(s):  
Machine Learning ◽  
Systematic Review ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Machine Learning Techniques ◽  
Support Vector ◽  
Hematopoietic Stem ◽  
Curative Therapy ◽  
Learning Techniques

Machine learning techniques are widely used nowadays in the healthcare domain for the diagnosis, prognosis, and treatment of diseases. These techniques have applications in the field of hematopoietic cell transplantation (HCT), which is a potentially curative therapy for hematological malignancies. Herein, a systematic review of the application of machine learning (ML) techniques in the HCT setting was conducted. We examined the type of data streams included, specific ML techniques used, and type of clinical outcomes measured. A systematic review of English articles using PubMed, Scopus, Web of Science, and IEEE Xplore databases was performed. Search terms included “hematopoietic cell transplantation (HCT),” “autologous HCT,” “allogeneic HCT,” “machine learning,” and “artificial intelligence.” Only full-text studies reported between January 2015 and July 2020 were included. Data were extracted by two authors using predefined data fields. Following PRISMA guidelines, a total of 242 studies were identified, of which 27 studies met the inclusion criteria. These studies were sub-categorized into three broad topics and the type of ML techniques used included ensemble learning (63%), regression (44%), Bayesian learning (30%), and support vector machine (30%). The majority of studies examined models to predict HCT outcomes (e.g., survival, relapse, graft-versus-host disease). Clinical and genetic data were the most commonly used predictors in the modeling process. Overall, this review provided a systematic review of ML techniques applied in the context of HCT. The evidence is not sufficiently robust to determine the optimal ML technique to use in the HCT setting and/or what minimal data variables are required.

scholarly journals Novel strategies for the treatment of myelofibrosis driven by recent advances in understanding the role of the microenvironment in its etiology

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1662 ◽  
Author(s):  
Zimran Eran ◽  
Maria Zingariello ◽  
Maria Teresa Bochicchio ◽  
Claudio Bardelli ◽  
Anna Rita Migliaccio
Keyword(s):  
Stem Cell ◽  
Cell Clone ◽  
Myeloproliferative Neoplasms ◽  
Philadelphia Chromosome ◽  
Extramedullary Hematopoiesis ◽  
The Novel ◽  
Hematopoietic Stem ◽  
Biochemical Alterations ◽  
Curative Therapy ◽  
History Of

Myelofibrosis is the advanced stage of the Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), characterized by systemic inflammation, hematopoietic failure in the bone marrow, and development of extramedullary hematopoiesis, mainly in the spleen. The only potentially curative therapy for this disease is hematopoietic stem cell transplantation, an option that may be offered only to those patients with a compatible donor and with an age and functional status that may face its toxicity. By contrast, with the Philadelphia-positive MPNs that can be dramatically modified by inhibitors of the novel BCR-ABL fusion-protein generated by its genetic lesion, the identification of the molecular lesions that lead to the development of myelofibrosis has not yet translated into a treatment that can modify the natural history of the disease. Therefore, the cure of myelofibrosis remains an unmet clinical need. However, the excitement raised by the discovery of the genetic lesions has inspired additional studies aimed at elucidating the mechanisms driving these neoplasms towards their final stage. These studies have generated the feeling that the cure of myelofibrosis will require targeting both the malignant stem cell clone and its supportive microenvironment. We will summarize here some of the biochemical alterations recently identified in MPNs and the novel therapeutic approaches currently under investigation inspired by these discoveries.

scholarly journals APPENDICEAL DISEASE IN HEMATOPOIETIC CELL TRANSPLANTATION

2021 ◽  
Author(s):  
Zachary Wright ◽  
Francis Essien ◽  
John Renshaw ◽  
Michael Wiggins ◽  
Alexander Brown ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Medical Therapy ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Transplant Patients

Appendiceal diseases are relatively rare reported complications during hematopoietic stem cell transplantation with no guidance on management. Pre- and post-transplant patients should receive a trial of medical therapy with appendectomy after recovery but prior to transplant in the former and plan for appendectomy after completion of immunosuppression in the latter.

scholarly journals Allogeneic hematopoietic stem-cell transplantation for myelofibrosis

2020 ◽  
Vol 11 ◽  
pp. 204062072090600
Author(s):  
Lining Zhang ◽  
Fan Yang ◽  
Sizhou Feng
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Myeloproliferative Neoplasms ◽  
Conditioning Regimen ◽  
Philadelphia Chromosome ◽  
Janus Kinase ◽  
Hematopoietic Stem

Myelofibrosis is one of the Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms with heterogeneous clinical course. Though many treatment options, including Janus kinase (JAK) inhibitors, have provided clinical benefits and improved survival, allogeneic hematopoietic stem-cell transplantation (AHSCT) remains the only potentially curative therapy. Considering the significant transplant-related morbidity and mortality, it is crucial to decide who to proceed to AHSCT, and when. In this review, we discuss recent updates in patient selection, prior splenectomy, conditioning regimen, donor type, molecular mutation, and other factors affecting AHSCT outcomes. Relapse is a major cause of treatment failure; we also describe recent data on minimal residual disease monitoring and management of relapse. In addition, emerging studies have reported pretransplant therapy with ruxolitinib for myelofibrosis showing favorable results, and further research is needed to explore its use in the post-transplant setting.

scholarly journals Oral mucositis in patients with acute myeloid leukemia treated with allogeneic hematopoietic stem cell transplantation in relation to the conditioning used prior to transplantation

2021 ◽  
Author(s):  
Aleksandra Wysocka-Słowik ◽  
Lidia Gil ◽  
Zuzanna Ślebioda ◽  
Agnieszka Kręgielczak ◽  
Barbara Dorocka-Bobkowska
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cell Transplantation ◽  
Oral Mucositis ◽  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Conditioning Regimen ◽  
World Health ◽  
Post Transplantation ◽  
Hematopoietic Stem ◽  
Acute Myeloid

AbstractThis study was designed to investigate the frequency and severity of oral mucositis in patients with acute myeloid leukemia after allogeneic hematopoietic cell transplantation, in relation to the type of conditioning used. Eighty patients diagnosed with acute myeloid leukemia were assigned to two groups based on the conditioning regimen used before transplantation. The intensity of oral inflammatory lesions induced by chemotherapy (oral mucositis) was evaluated according to a 5-point scale recommended by World Health Organization. Oral mucosa was investigated in all patients before the transplantation and during two subsequent stages of the post-transplantation procedure in relation to the conditioning regimen used. Mucositis in the oral cavity was observed in the majority of patients (66%) in the first week after transplantation, whereas the largest percentage of patients suffering oral lesions (74%) occurred in the second week after transplantation. A significantly higher percentage of patients with mucositis was observed in the group which underwent myeloablation therapy (74% of MAC and 50% of RIC patients in the first week; 83% of MAC and 53% of RIC patients in the second examination).The severity of mucositis after transplantation was higher in the MAC patients compared to the RIC patients. The highest mean value of the mucositis index was recorded in the second week in the MAC group (1.59). In AML sufferers receiving allo-HSCT, oral mucositis is a significant complication of the transplantation. This condition is more frequent and more severe in patients after treatment with myeloablation therapy.

scholarly journals Total Body Irradiation for Hematopoietic Stem Cell Transplantation: What Can We Agree on?

2021 ◽  
Vol 28 (1) ◽  
pp. 903-917
Author(s):  
Mitchell Sabloff ◽  
Steven Tisseverasinghe ◽  
Mustafa Ege Babadagli ◽  
Rajiv Samant
Keyword(s):  
Cell Transplantation ◽  
Total Body Irradiation ◽  
Hematopoietic Cell Transplantation ◽  
Conditioning Regimen ◽  
Late Toxicity ◽  
Hepatic Function ◽  
Vascular Supply ◽  
Entire Body ◽  
Hematopoietic Stem ◽  
Total Body

Total body irradiation (TBI), used as part of the conditioning regimen prior to allogeneic and autologous hematopoietic cell transplantation, is the delivery of a relatively homogeneous dose of radiation to the entire body. TBI has a dual role, being cytotoxic and immunosuppressive. This allows it to eliminate disease and create “space” in the marrow while also impairing the immune system from rejecting the foreign donor cells being transplanted. Advantages that TBI may have over chemotherapy alone are that it may achieve greater tumour cytotoxicity and better tissue penetration than chemotherapy as its delivery is independent of vascular supply and physiologic barriers such as renal and hepatic function. Therefore, the so-called “sanctuary” sites such as the central nervous system (CNS), testes, and orbits or other sites with limited blood supply are not off-limits to radiation. Nevertheless, TBI is hampered by challenging logistics of administration, coordination between hematology and radiation oncology departments, increased rates of acute treatment-related morbidity and mortality along with late toxicity to other tissues. Newer technologies and a better understanding of the biology and physics of TBI has allowed the field to develop novel delivery systems which may help to deliver radiation more safely while maintaining its efficacy. However, continued research and collaboration are needed to determine the best approaches for the use of TBI in the future.

Outcome of Allogeneic Hematopoietic Stem-Cell Transplantation in Adult Patients With Acute Lymphoblastic Leukemia: No Difference in Related Compared With Unrelated Transplant in First Complete Remission

2004 ◽  
Vol 22 (14) ◽  
pp. 2816-2825 ◽  
Author(s):  
Michael G. Kiehl ◽  
Ludwig Kraut ◽  
Rainer Schwerdtfeger ◽  
Bernd Hertenstein ◽  
Mats Remberger ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Hematopoietic Stem ◽  
First Complete Remission

Purpose The role of unrelated allogeneic stem-cell transplantation in acute lymphoblastic leukemia (ALL) patients is still not clear, and only limited data are available from the literature. We analyzed factors affecting clinical outcome of ALL patients receiving a related or unrelated stem-cell graft from matched donors. Patients and Methods The total study population was 264 adult patients receiving a myeloablative allogeneic stem-cell transplant for ALL at nine bone marrow transplantation centers between 1990 and 2002. Of these, 221 patients receiving a matched related or unrelated graft were analyzed. One hundred forty-eight patients received transplantation in complete remission; 62 patients were in relapse; and 11 patients were refractory to chemotherapy before transplant. Fifty percent of patients received bone marrow, and 50% received peripheral blood stem cell from a human leukocyte antigen–identical related (n = 103), or matched unrelated (n = 118) donor. Results Disease-free survival (DFS) at 5 years was 28%, with 76 patients (34%) still alive (2.2 to 103 months post-transplantation), and 145 deceased (65 relapses, transplant-related mortality, 45%). We observed an advantage regarding DFS in favor of patients receiving transplantation during their first complete remission (CR) in comparison with patients receiving transplantation in or after second CR (P = .014) or who relapsed (P < .001). We observed a clear trend toward improved survival in favor of B-lineage ALL patients compared with T-lineage ALL patients (P = .052), and Philadelphia chromosome–positive patients had no poorer outcome than Philadelphia chromosome–negative patients. Total-body irradiation–based conditioning improved DFS in comparison with busulfan (P = .041). Conclusion Myeloablative matched related or matched unrelated allogeneic hematopoietic stem-cell transplantation in ALL patients should be performed in first CR.

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