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1.
Christianne Bourlon Dennis Lacayo-Leñero Sergio I. Inclán-Alarcón Roberta Demichelis-Gómez 《Current oncology reports》2018,20(4):36
Purpose of Review
The purpose of this review is to discuss the potential role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for Philadelphia-negative (Ph?) adult acute lymphoblastic leukemia (ALL) in first complete remission (CR1) in the era of minimal residual disease (MRD).Recent Findings
Allo-HSCT continues to have a role in the therapy of a selected group of high-risk adult patients with ALL in CR1. Although the clinical significance of MRD has been studied less extensively in adults with ALL than in children, recent studies support its role as the strongest prognostic factor that can identify patients that are unlikely to be cured by standard chemotherapy and benefit from undergoing allo-HSCT. In addition, MRD status both pre- and post-HSCT has been found to correlate directly with the risk of relapse.Summary
Currently, the clinical challenge consists on applying MRD and molecular failure to integrate novel agents and immunotherapy to lower MRD before allo-HSCT and to modulate the graft versus leukemia (GVL) effect after transplant.2.
Purpose of review
This study aims to provide an overview of the classification, incidence, genomic alterations, and clinical implications of Philadelphia-like Acute Lymphoblastic Leukemia (Ph-like ALL) in adults.Recent findings
Ph-like ALL is a high-risk subtype of B cell precursor ALL with characteristic genomic alterations in children and adults. A standard approach for diagnosis is missing and currently mainly based on gene expression analysis. The incidence is age depended and highest in adolescents and younger adults (age 16–39) where 19–28% of patients belong to this subtype. Ph-like ALL is associated with persistence of minimal residual disease (MRD) and inferior prognosis. Some genomic alterations respond to specific treatment approaches and provide hope for tailored therapies.Summary
Ph-like ALL in adults is an aggressive and high-risk subtype of B cell precursor ALL. Without consensus definition, diagnosis is difficult and current publications highlight the importance of stringent MRD monitoring to guide risk-adapted treatment strategies.3.
Victor M. Orellana-Noia Michael G. Douvas 《Current hematologic malignancy reports》2018,13(2):100-108
Purpose of review
Adolescent and Young Adult (AYA) Oncology is a relatively new field encompassing research in the unique pathophysiology, clinical care, and psychosocial issues facing patients between the ages of 15 and 40 with cancer. About 100,000 of the approximately 1.5 million people diagnosed annually with cancer in the USA are in this age range. This chapter will review notable new developments in the care of adolescents and young adults with acute lymphoblastic leukemia (ALL) within the last 3 years.Recent findings
The preponderance of data favors the treatment of AYA ALL patients with pediatric-inspired treatment regimens due to better relapse-free and overall survival. Minimal residual disease (MRD) measurement is emerging as an important prognostic factor and can serve as a new measure of efficacy of the addition of novel therapies to the treatment of patients with new diagnoses. There have been several treatment advances ranging from new cytotoxic agents for ALL to new antibody-based therapy to novel immune therapies such as CAR-T cells.Summary
The care of AYA ALL patients is improving as the unique issues for this patient population are addressed.4.
Nicholas J. Short Hagop Kantarjian Elias Jabbour Farhad Ravandi 《Current hematologic malignancy reports》2018,13(2):91-99
Purpose of Review
Older adults with acute lymphoblastic leukemia (ALL) have worse survival compared to their younger counterparts. Here, we review the reasons for the poorer outcomes of older patients with ALL and also summarize the current and future therapeutic approaches to ALL in the elderly population.Recent Findings
The poor outcomes of older adults with ALL are driven largely by lack of tolerance to standard-dose chemotherapy, which leads to unacceptably high rates of myelosuppression-related deaths. Recent studies have shown promising results with the use of low-intensity or chemotherapy-free regimens in older patients with ALL, which are able to retain efficacy without excess toxicity.Summary
Novel antibody constructs such as inotuzumab ozogamicin and blinatumomab as well as potent later-generation tyrosine kinase inhibitors such as ponatinib hold significant promise in the management of ALL in the older adult. Innovative combination strategies may further improve the outcomes of these patients.5.
Purpose of Review
This review aimed to provide updated guidelines for the management of children with acquired aplastic anemia (AA), particularly focusing on hematopoietic stem cell transplantation (HSCT).Recent Findings
Failure-free survival for children with aplastic anemia has been shown to be better after bone marrow transplantation (BMT) from matched or one-locus mismatched related donors (MRD/1MMRD) than after immunosuppressive therapy (IST). A combination of the absence of minor paroxysmal nocturnal hemoglobinuria clones and short telomere length was identified as a strong predictor of a poor response to IST. Upfront HSCT from matched unrelated donors (MUD) and MRD was recently demonstrated to have comparable outcomes. Moreover, unrelated cord blood transplantation (UCBT) and haploidentical HSCT have shown promising outcomes, and the fludarabine/melphalan-based regimen has resulted in excellent survival without poor graft function.Summary
BMT from MRD/1MMRD is the treatment of choice. When a MRD/1MMRD is not available, upfront BMT from a MUD should be considered for patients with only a slim chance of responding to IST. UCBT and haploidentical HSCT are promising options. This updated treatment algorithm should improve overall outcomes for children with AA.6.
Purpose of Review
Allogeneic hematopoetic stem cell transplantation (HSCT) is a curative option for children and adolescents with high-risk leukemia. Although acute complications were reduced during the last decade, considerable late effects are still limiting the overall success rate. This article emphasizes the specific pediatric aspects of long-term aftercare following myeloablative HSCT and provides an organ-based overview that covers main clinical patterns, incidence, and risk factors enhanced by current references and screening guidelines.Recent Findings
In the last years, several attempts were made to separate pediatric outcome data from findings in adults. It turned out that not only the indication for but also the time and the procedures of HSCT substantially differ. Nearly any organ might be affected after the complex transplantation process and includes endocrinopathies, musculoskeletal disorders, cardiopulmonary complications, and secondary malignancies.Summary
Patients after HSCT in childhood have a high risk for developing a wide range of late sequelae and may benefit from regular screening and early intervention. The occurrence and patterns of late effects depend on the intensity and severity of conditioning and are strongly associated with patient’s age at transplant and beginning of complications.7.
Joseph Bubalo 《Current hematologic malignancy reports》2018,13(2):109-113
Purpose of Review
To highlight the breadth and types of mental distress experienced by hematopoietic stem cell transplant (HSCT) patients and highlight the need for better prevention and management of delirium.Recent Findings
Recent publications highlight additional risks factors which predict for mental distress during the HSCT process. Despite new medications and additional psychological reports, there is little progress in non-pharmacologic or medication therapy in the prevention and treatment of delirium.Summary
Mental distress, especially delirium, is common during the HSCT process. The morbidity associated with delirium and other mental distress can still be significant at 6–12 months after the completion of the procedure affecting patient functioning and quality of life (QOL). Medication interventions may be helpful but should be used sparingly for targeted patients during HSCT. Additional interventions are needed to prevent and treat delirium in HSCT patients.8.
Background
Allogeneic hematopoietic stem cell transplantation (HSCT) is nowadays implemented as a standard treatment in hematological oncology. In a few years there are expected to be 500,000 long-term survivors of HSCT worldwide and the numbers will show a clear increase. Little is known about suicidal ideation and suicide in the context of HSCT.Objective
The current state of knowledge on suicide after HSCT was systematically reviewed. Specific and as yet unresolved issues are presented.Material and methods
A systematic literature search on the topics of HSCT and suicide was carried out in the Medline and Embase databases. The results are discussed in detail.Results
Only seven articles were found that address the topic of suicide and suicidal ideations after HSCT. In two publications the topic is only mentioned without any further analysis. In one case report important indications of specific risk factors within the HSCT setting are presented.Conclusion
There is an alarming paucity of investigations on suicide after HSCT. The existing publications indicate a twofold increase of the risk of suicide for patients who had to undergo a HSCT. Younger men with somatic and/or psychological stress are particularly at risk The suicide risk is elevated for many years after therapy; therefore, an ongoing screening of long-term survivors is recommended. There is a substantial lack of specialized knowledge on suicide after HSCT. Furthermore, case reports suggest a deleterious impairment of communication in the context of HSCT. Practical advice as part of a proactive suicide prevention is discussed in this article.9.
T. de Rojas S. Martínez-Álvarez S. Lerma-Lara M. Á. Díaz L. Madero M. Ramírez 《Clinical & translational oncology》2018,20(5):584-590
Purpose
Corticoid-induced osteonecrosis (ON) of femoral head can lead to severe hip joint impairment and hip replacement, with negative impact in young survivors of acute lymphoblastic leukaemia (ALL) with long life expectancy. We aim to improve quality of life in these patients with a novel approach.Methods/patients
Based on the regenerative capacities of mesenchymal stem cells (MSCs), we performed locally implanted autologous cell therapy in two adolescents suffering of bilateral femoral ON. This required a simple, minimally invasive surgical procedure.Results
Both patients experienced significant pain relief and restoration of gait kinematic values. Radiographic evaluation showed cessation of hip collapse. No toxicities/complications were observed after a 4-year follow-up.Conclusions
Our preliminary results suggest that autologous MSCs can be considered as a novel treatment for children and young adults with ON after overcoming ALL. It may avoid hip replacement and improve quality of life of leukaemia survivors.10.
Arend v. Stackelberg Martin Schrappe Dirk Reinhardt Meinolf Suttorp 《Der Onkologe》2016,22(12):923-932
Background
Leukemia is the most frequent malignant disease in childhood. Acute and chronic diseases of lymphatic or myeloid origin can be distinguished.Results
Acute lymphoblastic leukemia (ALL) is the most frequent type of leukemia with more than 80?% of all leukemias, acute myeloid leukemia accounts for 15?% and chronic myeloid leukemia (CML) 2–3?%. Chronic lymphatic leukemias do not occur in childhood. Whereas various primary and secondary tumor genetic lesions could be determined as the basis of the disease in ALL and AML, CML has a monogenetic origin caused by the BCR-ABL1 fusion gene. With the contemporary multimodal chemotherapy strategies the prognosis of leukemia is excellent. In selected patients with an unfavorable prognosis allogeneic hematopoietic stem cell transplantation (HSCT) is indicated and CML can be specifically treated with tyrosine kinase inhibitors.Perspectives
Many new therapeutic agents with targeted mechanisms of action are being investigated in clinical trials with respect to efficacy and safety in pediatric leukemia. In the future, it is hoped that unspecific chemotherapy can partly be replaced by targeted therapies with reduced side effects, with the aim of reducing the acute side effects and the substantial delayed toxicity.11.
Purpose of Review
To review recent studies that address important questions regarding the treatment of Philadelphia chromosome-positive ALL.Recent Findings
Less intensive non-myelosuppressive induction approaches can produce comparable anti-leukemic responses with less toxicity. Second-generation tyrosine kinase inhibitors (TKIs) are not clearly associated with superior outcomes compared to imatinib. Ponatinib is associated with lower early relapse rates, but has additional vascular risks. Patients achieving complete molecular response (CMR) appear to have comparable survivals with chemotherapy?+?TKI alone as compared with allogeneic stem cell transplant (alloSCT). In contrast, those not achieving CMR have superior outcomes with alloSCT. There is no clear evidence of benefit for post-transplant TKI therapy. Patients resistant to chemotherapy?+?TKIs may respond to blinatumomab or inotuzumab; these agents may also convert some patients to CMR.Summary
Future studies should further explore the potential of ponatinib and antibody-based therapies to more precisely define optimal molecular responses.12.
Purpose of Review
Cellular therapy using T cells modified to express chimeric antigen receptors (CAR-T cells) has had striking success in patients that have failed previous treatment for CD19+ B cell non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), or acute lymphoblastic leukemia (ALL). Curative therapy for this group of diseases has previously been limited to allogeneic hematopoietic cell transplantation HCT (alloHCT). The recent results of CAR-T cell therapy raise the question of how best to integrate CAR-T cell therapy and alloHCT in the care of these patients.Recent Findings
Within the past 2 years, results from larger trials and increased follow-up of patients treated with CD19 CAR-T cell therapy suggest that some may achieve durable remission without transplant.Summary
The balance of efficacy and toxicity for CAR-T cell therapy and alloHCT vary by disease type, disease status at the time of treatment, patient characteristics, and the specific therapy employed. There are early signals that subsequent transplantation of patients who have achieved remission with CAR-T may be a potentially viable (though expensive) strategy.13.
Background
The prognosis of adult patients with acute leukemia has continuously improved over the years due to the introduction of new diagnostic and therapeutic procedures and progress in the field of supportive therapy.Methods
This article gives an overview of the currently available options and the clinical approach to the diagnostics and therapy of acute leukemia.Results
The standardization as well as improvements in diagnostic procedures, in particular by immunocytological and genetic procedures, allow a more rapid determination of the exact diagnosis. In addition to age and performance status of patients, an established panel of cytogenetic and molecular markers allows an individual risk stratification for selecting the most appropriate therapeutic procedure for each patient. In acute myeloid leukemia (AML) younger patients with genetically determined intermediate and poor risk status benefit from allogeneic stem cell transplantation whereas patients in the low risk group are still primarily treated with conventional induction chemotherapy with anthracycline and cytarabine. The poor prognosis of elderly patients with AML has been improved by the development of stem cell transplantation procedures with reduced intensity conditioning and for patients not suitable for stem cell transplantation, the introduction of less toxic demethylating substances allows a substantial improvement in outcome and quality of life compared to cytoreductive therapy alone. The additional role of targeted therapies in AML is still under investigation. In adult patients with acute lymphoblastic leukemia (ALL), the standard systemic therapy still consists of complex cytotoxic regimens which have been modified from pediatric protocols. Biologically and genetically determined subgroups of ALL patients as well as poor responders, who can be identified by the detection of significant molecular determined residual disease (MRD) after standard therapy, benefit from allogeneic transplantation in first remission. In patients with bcr-abl positive ALL, the implementation of first and second generation tyrosine kinase inhibitors has led to rapidly rising response rates and less toxicity. Patients with relapsed ALL may benefit from new molecular options, e.g. bispecific antibodies. Additionally, improved standardization and supportive care, particularly due to the introduction of modern antimycotic agents, increase the treatment options and improve the prognosis of patients with acute leukemia.Conclusion
The improved diagnostic and therapeutic options for patients with acute leukemia require a complex management. Currently only subgroups of patients benefit from molecular targeted therapeutic strategies. Due to this increasing complexity in the management, patients with acute leukemia should be treated in academic centers and within clinical trials.14.
Purpose of Review
Minimal or measurable residual disease (MRD) detected by multiparameter flow cytometry (MFC) is an independent prognostic indicator in acute leukemia. However, the predictive value of MFC MRD is affected by technical challenges, interpretive complexities, and inadequate standardization, particularly in acute myeloid leukemia (AML). Here, we critically review the methodological principles of the MFC MRD assay and discuss clinical implications of MRD.Recent Findings
Key components of MFC MRD assays to be discussed include the principles of MFC, panel selection, analysis approaches, level of quantifiable MRD and calculation, reporting, and areas of improvements. Key components of clinical implications include context-dependent detection threshold and the integral role of MRD assessment by MFC in the era of ever-expanding molecular testing.Summary
With advancements in technology and standardization, MFC along with molecular assays will continue to play an important role in MRD assessment to evaluate treatment response and risk stratification.15.
Purpose of Review
Acute graft versus host disease (aGVHD) is a frequent cause of treatment-related mortality after allogeneic hematopoietic stem cell transplantation (alloHCT), with few effective treatment options beyond systemic steroids. Discovery of biomarkers for aGVHD may provide insight into the pathophysiology of aGVHD and suggest novel mechanisms for treatment.Recent Findings
We highlight biomarkers within innate immune activation, T-cell-mediated tissue damage, endothelial damage, dysbiosis, and poor wound healing that can be obtained prior to transplant, in the early transplant period, or at the onset of aGVHD.Summary
aGVHD biomarkers have predictive and prognostic utility but also suggest novel mechanisms of recipient tissue damage and impaired regenerative capacity. These mechanisms should be further studied and tested in therapeutic clinical trials to improve outcomes post-alloHCT.16.
Katherine C. Pehlivan Brynn B. Duncan Daniel W. Lee 《Current hematologic malignancy reports》2018,13(5):396-406
Purpose of Review
Genetically engineered T cells expressing a chimeric antigen receptor (CAR-T) targeting specific antigens present on acute lymphoblastic leukemia (ALL) blasts have generated promising results in children and adults with relapsed and refractory disease. We review the current evidence for CAR-T cell therapy in ALL, associated toxicities, and efforts to improve durable response to therapy.Recent Findings
CD19-directed CAR-T cells have recently been approved by the FDA for use in children and young adults with ALL and in adults with diffuse large B cell lymphoma (DLBCL) in the relapsed/refractory setting. CD22-directed CAR-T cells have shown efficacy against leukemia as well in a recent clinical trial, representing the first alternative CAR target to approach comparable efficacy to CD19 CAR-T cells. Standardization of toxicity grading and management, strategies to combat significant relapse rates after CAR-T therapy, and applicability of CAR-T cells to treat central nervous system (CNS) disease remain challenges in the field and represent priorities for continued research.Summary
CAR-T cells are a feasible, effective, and rapidly evolving therapy for patients with relapsed and refractory B cell malignancies.17.
18.
Terrence J. Bradley Justin M. Watts Ronan T. Swords 《Current hematologic malignancy reports》2018,13(6):507-515
Purpose of Review
Myelodysplastic syndrome (MDS) is a clinically and molecularly heterogeneous disease, which primarily occurs in older adults. Although hypomethylating agents have survival benefit and are the current standard of care, many MDS patients will not garner a response from therapy. For those who do respond, most responses are not durable, and the only hope for a cure is allogeneic stem cell transplant. New therapies to improve outcomes are urgently needed.Recent Findings
Clinical trials combining standard hypomethylating agents with novel experimental agents are underway in an effort to improve clinical outcomes in MDS patients. Several of these small molecules have demonstrated the ability to augment the response rates of hypomethylating agents alone, including complete remission rates, in both the front line and refractory settings.Summary
Combination approaches utilizing hypomethylating agents and novel-targeted therapies have demonstrated the ability to improve response rates in MDS patients in both the front line and salvage settings, and thus may change the standard of care.19.
Viktor Grünwald Florian Länger H. J. Raatschen Andreas Beilken 《Clinical sarcoma research》2016,6(1):5
Background
Desmoid-type fibromatosis (DF) is a rare disease, which often occurs in young adults. Medical treatment is an important option in the treatment algorithm of DF. Different chemotherapeutic regimens showed clinical activity in DF, but overall treatment tolerability remains poor for this patient cohort. Novel approaches investigated tyrosine kinase inhibitors in DF, but tolerability remained an issue.Case presentation
We treated a patient with progressive DF after failure of chemotherapy for 1 year with singe agent bevacizumab. He achieved a symptomatic and radiologic response while attainning excellent tolerability.Conclusions
This is the first report on single agent bevacizumab in DF, which showed both, good tolerability and efficacy in our patient, thereby warranting future trials in DF.20.