GMP CAR-T cell production
This article reviews the issues that must be addressed in order to achieve this goal. It includes the manufacturing infrastructure, the regulatory environment, practical aspects of production, and the costs involved. (Source: Best Practice and Research Clinical Haematology)
Source: Best Practice and Research Clinical Haematology - April 2, 2018 Category: Hematology Source Type: research

Indolent lymphomas
Publication date: March 2018 Source:Best Practice & Research Clinical Haematology, Volume 31, Issue 1 Author(s): Brad Kahl (Source: Best Practice and Research Clinical Haematology)
Source: Best Practice and Research Clinical Haematology - April 2, 2018 Category: Hematology Source Type: research

CARs and other T cell therapies for MM: The clinical experience
Publication date: Available online 27 March 2018 Source:Best Practice & Research Clinical Haematology Author(s): Sophia Danhof, Michael Hudecek, Eric L. Smith Harnessing the endogenous immune system to eliminate malignant cells has long been an intriguing approach. After considerable success in the treatment of B-cell acute lymphoblastic leukemia, chimeric antigen receptor (CAR)-modified T cells have entered early clinical evaluation in the field of multiple myeloma (MM). The choice of suitable non-CD19 target antigens is challenging and a variety of myeloma-associated surface molecules have been under preclinical...
Source: Best Practice and Research Clinical Haematology - April 2, 2018 Category: Hematology Source Type: research

Advances in the use of Natural Receptor- or Ligand-Based Chimeric Antigen Receptors (CARs) in haematologic malignancies
Publication date: Available online 27 March 2018 Source:Best Practice & Research Clinical Haematology Author(s): Joana M. Murad, David Graber, Charles L. Sentman Chimeric antigen receptors (CAR)-T cell therapy has recently made promising advances towards treatment of B-cell malignancies. This approach makes use of an antibody-derived single chain variable fragment (scFv)-based CAR to target the CD19 antigen. Currently scFvs are the most common strategy for creation of CARs, but tumor cells can also be targeted using non-antibody based approaches with designs focused on the interaction between natural receptors and...
Source: Best Practice and Research Clinical Haematology - April 2, 2018 Category: Hematology Source Type: research

Off the shelf T cell therapies for hematologic malignancies
Publication date: Available online 28 March 2018 Source:Best Practice & Research Clinical Haematology Author(s): Bruce J. McCreedy, Vladimir V. Senyukov, Kim T. Nguyen Adoptive transfer of autologous CAR-T cells can induce durable remissions in patients with relapsed/refractory hematologic malignancies. However, multiple challenges exist for manufacturing CAR-T cells from patients with advanced disease including inability to manufacture a product, disease progression or death while waiting for the CAR-T product to be available, and heterogeneity among autologous CAR-T products that contributes to unpredictable and...
Source: Best Practice and Research Clinical Haematology - April 2, 2018 Category: Hematology Source Type: research

Toxicities associated with immunotherapies for hematologic malignancies
Publication date: Available online 28 March 2018 Source:Best Practice & Research Clinical Haematology Author(s): Mark B. Leick, Marcela V. Maus Immunotherapy has generated tremendous hope for patients with cancer that is refractory to standard approaches. Hematologic malignancies have taken the lead in harnessing the most recent advances in cell-based immunotherapies, such as CAR T cells, and some patients have achieved durable remissions. However, these T-cell-engaging therapies are associated with a new set of toxicities which need to be managed by caretakers, oncologists, nurses, and healthcare staff. In this r...
Source: Best Practice and Research Clinical Haematology - April 2, 2018 Category: Hematology Source Type: research

Novel therapies for relapsed/refractory mantle cell lymphoma
Publication date: Available online 2 November 2017 Source:Best Practice & Research Clinical Haematology Author(s): Puja C. Arora, Craig A. Portell Mantle cell lymphoma is an aggressive Non-Hodgkin's lymphoma that is considered incurable with standard therapies. Most patients treated with frontline immunochemotherapy relapse within a few years and do not usually respond to salvage chemotherapy. Persistent activation of the B-cell receptor pathway is critical to the pathogenesis of mantle cell lymphoma. Inhibition of Bruton's tyrosine kinase, an essential B-cell receptor pathway component with ibrutinib has shown cl...
Source: Best Practice and Research Clinical Haematology - December 16, 2017 Category: Hematology Source Type: research

Optimal management of the young patient CLL patient
Publication date: Available online 2 November 2017 Source:Best Practice & Research Clinical Haematology Author(s): John N. Allan, Richard R. Furman The emergence of targeted therapy for patients with chronic lymphocytic leukemia (CLL) has permanently altered the therapeutic landscape. In both upfront and relapsed settings, safe and effective oral kinase inhibitors are available which rival the responses and durability seen with standard chemo immunotherapy regimens. In 2016, ibrutinib was granted Federal Drug Administration approval for first-line therapy in patients with CLL. While its role as initial therapy for...
Source: Best Practice and Research Clinical Haematology - December 16, 2017 Category: Hematology Source Type: research

Risk stratification in follicular lymphoma
Publication date: Available online 15 November 2017 Source:Best Practice & Research Clinical Haematology Author(s): Carla Casulo Advances in the understanding of FL biology, molecular characteristics and clinical risk factors are further highlighting the heterogeneity of this disease. Historically used prognostic factors were broadly based on clinical and laboratory features at the time of diagnosis. However novel prognostic factors are emerging that can be studied at the time of diagnosis, and relapse, and use a variety of tools including gene alterations and diagnostic imaging. These novel discoveries are being ...
Source: Best Practice and Research Clinical Haematology - December 16, 2017 Category: Hematology Source Type: research

Novel agents for relapsed and refractory follicular lymphoma
Publication date: Available online 16 November 2017 Source:Best Practice & Research Clinical Haematology Author(s): Chan Yoon Cheah, Nathan H. Fowler Follicular lymphoma is one of the most common non-Hodgkin's lymphomas. Although current frontline regimens are associated with high response rates, most patients still relapse. When progression is discovered, re-establishing the diagnosis and ruling out transformation in paramount. The outcomes following relapse have been improving due to the activity and increasing availability of novel agents with various mechanisms of action. Despite these advances, single agent a...
Source: Best Practice and Research Clinical Haematology - December 16, 2017 Category: Hematology Source Type: research

Overview on the management of non-gastric MALT lymphomas
Publication date: Available online 14 November 2017 Source:Best Practice & Research Clinical Haematology Author(s): Irene Defrancesco, Luca Arcaini Extranodal marginal zone B-cell lymphomas (EMZLs) of the mucosa-associated lymphoid tissue (MALT) are indolent lymphomas which can present at any extranodal site. The most frequent localizations (other than stomach) are ocular adnexa, salivary gland, skin, lung and thyroid. Chronic inflammation and antigenic stimulation are a potential risk for the development of MALT lymphomas. While Helicobacter Pylori is known to be associated with gastric MALT lymphoma and antibiot...
Source: Best Practice and Research Clinical Haematology - November 15, 2017 Category: Hematology Source Type: research

The role of stem cell transplantation in follicular lymphoma
Publication date: Available online 3 November 2017 Source:Best Practice & Research Clinical Haematology Author(s): Georg Hess With the introduction of novel treatments paradigms to if or when to use transplantation strategies for patients with follicular lymphoma have changed substantially. Autologous transplantation has been intensively evaluated as consolidation after first induction treatment with positive effects, however the introduction of Rituximab led to comparable improvements and HDT has been moved to relapse treatment. In this indication HDT was frequently use already at first relapse, but now is domina...
Source: Best Practice and Research Clinical Haematology - November 10, 2017 Category: Hematology Source Type: research

Should rituximab replace splenectomy in the management of splenic marginal zone lymphoma?
Publication date: Available online 7 November 2017 Source:Best Practice & Research Clinical Haematology Author(s): Christina Kalpadakis, Gerassimos A. Pangalis, Maria K. Angelopoulou, Sotirios Sachanas, Theodoros P. Vassilakopoulos Background SMZL is a relatively rare low grade B-cell lymphoma, characterized usually by an indolent clinical behavior. Since there is no prospective randomized trials to establish the best treatment approach, decision on therapeutic management should be based on the available retrospective series. Based on these data, rituximab and splenectomy appear to be the most effective. Splenecto...
Source: Best Practice and Research Clinical Haematology - November 8, 2017 Category: Hematology Source Type: research

What is the optimal initial management of the younger mantle cell lymphoma patient?
Publication date: Available online 1 November 2017 Source:Best Practice & Research Clinical Haematology Author(s): Rory McCulloch, Simon Rule The last 20 years has seen considerable advances made in the management of younger patients with mantle cell lymphoma. The use of high dose cytarabine and rituximab in induction therapy, usually followed by autologous stem cell transplant consolidation, has become established practice and the median overall survival now exceeds 10 years. However, this high intensity upfront approach is not necessarily appropriate for all newly diagnosed patients. A minority exhibit disease t...
Source: Best Practice and Research Clinical Haematology - November 1, 2017 Category: Hematology Source Type: research

Management of untreated advanced stage follicular lymphoma: Role of patient discernment
Publication date: Available online 1 November 2017 Source:Best Practice & Research Clinical Haematology Author(s): Jayadev Manikkam Umakanthan, Mathew A. Lunning Follicular lymphoma is the most common indolent non-Hodgkin lymphoma. Advanced stage disease is common at diagnosis. The timing of treatment for follicular lymphoma is best approached by considering the combination of presence or absence of symptoms along with estimation of tumor burden. Upfront treatment strategies should take into initial presentation variables, pace of disease progression and goals of care after discussion with the patient. Treatment a...
Source: Best Practice and Research Clinical Haematology - November 1, 2017 Category: Hematology Source Type: research

What is the optimal management of older CLL patients?
Publication date: Available online 1 November 2017 Source:Best Practice & Research Clinical Haematology Author(s): Jennifer A. Woyach CLL is the most common leukemia in older adults with a median age at diagnosis of 71. Therefore, management of patients with this disease must take into account the older age of most patients and consequences of this in terms of functional status and organ function. This review will discuss the management of CLL with regards to observation prior to the initiation of therapy, functional status, and initial treatment. We will discuss criteria for the initiation of therapy, and how ini...
Source: Best Practice and Research Clinical Haematology - November 1, 2017 Category: Hematology Source Type: research

Pathogenesis of follicular lymphoma
Publication date: Available online 1 November 2017 Source:Best Practice & Research Clinical Haematology Author(s): Tracy Lackraj, Rashmi Goswami, Robert Kridel Follicular lymphoma (FL) is presented as a germinal centre B-cell lymphoma that is characterized by an indolent clinical course, but remains – paradoxically – largely incurable to date. The last years have seen significant progress in our understanding of FL lymphomagenesis, which is a multi-step process beginning in the bone marrow with the hallmark t(14; 18)(q32; q21) translocation. The pathobiology of FL is complex and combines broad somatic ...
Source: Best Practice and Research Clinical Haematology - November 1, 2017 Category: Hematology Source Type: research

Transformation of follicular lymphoma – Why does it happen and can it be prevented?
Publication date: Available online 1 November 2017 Source:Best Practice & Research Clinical Haematology Author(s): Brian K. Link Follicular lymphoma is a clinical disease with a multitude of presentations and behaviors. Although infrequent, transformation of follicular lymphoma to a more aggressive behaving subtype – prototypically diffuse large B-cell lymphoma – confers a substantially adverse prognosis. There is no consensus for optimal management after transformation is recognized. Historically considered a distinct clinical event, this review highlights the multiple subclinical transformational eve...
Source: Best Practice and Research Clinical Haematology - November 1, 2017 Category: Hematology Source Type: research

Mutational complexity in myelodysplasia
Publication date: Available online 25 October 2017 Source:Best Practice & Research Clinical Haematology Author(s): R. Coleman Lindsley Myelodysplastic syndromes are characterized by genetic and clinical heterogeneity. Some mutations are able to drive clonal hematopoiesis without causing clinical consequences, while other mutations may have significant impact, including the transformation to leukemia. This review aims to describe the pathogenesis of myelodysplastic syndromes (MDS) by focusing on 3 aspects: combinatorial genetic events, environmental factors, and inherited genetic conditions. (Source: Best Practice ...
Source: Best Practice and Research Clinical Haematology - October 26, 2017 Category: Hematology Source Type: research

Do cytogenetics affect the post-remission strategy for older patients with AML in CR1?
Publication date: Available online 7 October 2017 Source:Best Practice & Research Clinical Haematology Author(s): James Foran Data have shown that intensified cytarabine in consolidation for treatment of acute myeloid leukemia (AML) does not equally benefit patients older than 60 years, and older patients experience significantly more neurotoxicity than younger patients. In addition, older patients are more likely to have abnormal or unfavorable cytogenetics, which also tend to confer limited efficacy with intensified cytarabine. This poses a treatment dilemma as to the best post remission therapy to treat older p...
Source: Best Practice and Research Clinical Haematology - October 8, 2017 Category: Hematology Source Type: research

Familial myelodysplastic syndrome/acute myeloid leukemia
Publication date: Available online 4 October 2017 Source:Best Practice & Research Clinical Haematology Author(s): Jane E. Churpek A growing number of inherited genetic loci that contribute to myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) development in both children as well as adults are rapidly being identified. In recognition of the clinical impact of this emerging field, the World Health Organization, National Comprehensive Cancer Network, and European LeukemiaNet have all added consideration of inherited predisposition to MDS/AML classification and management. Study of these disorders is providing ...
Source: Best Practice and Research Clinical Haematology - October 5, 2017 Category: Hematology Source Type: research

How can one optimize induction therapy in AML?
Publication date: Available online 4 October 2017 Source:Best Practice & Research Clinical Haematology Author(s): Selina M. Luger Induction therapy for acute myeloid leukemia has not changed much since 1973, when the 7 + 3 regimen of cytarabine and daunorubicin was born. Since then, various strategies have been evaluated to improve patient response, including dose intensification, the incorporation of additional agents into the regimen, the development of novel agents, and modified approaches for older patients. Recently, two novel agents, CPX-351 and gemtuzumab ozogamicin, have been approved by the US F...
Source: Best Practice and Research Clinical Haematology - October 5, 2017 Category: Hematology Source Type: research

Autologous hematopoietic cell transplantation for adult acute myeloid leukemia: An obsolete or resurfacing concept?
Publication date: Available online 22 September 2017 Source:Best Practice & Research Clinical Haematology Author(s): Hillard M. Lazarus, Najla El Jurdi Improving long-term outcomes of adult acute myeloid leukemia (AML) patients remains a challenge. Major scientific and clinical advances have led to a better understanding of the disease biology, and the majority of patients achieve a complete remission (CR) after induction therapy. Relapse risk, however, remains considerable and is the leading cause of death in this patient population. Significant efforts to improve outcomes emphasize use of post-remission therapie...
Source: Best Practice and Research Clinical Haematology - September 23, 2017 Category: Hematology Source Type: research

Relapsed acute lymphoblastic leukemia: Is it crucial to achieve molecular remission prior to transplant?
Publication date: Available online 22 September 2017 Source:Best Practice & Research Clinical Haematology Author(s): Mary Eapen In patients with acute lymphoblastic leukemia (ALL) the risk of recurrent leukemia influences the choice of treatment between chemotherapy and allogeneic hematopoietic cell transplantation. The evaluation of minimal residual disease (MRD) is now considered to be the greatest progress in risk stratification in regard to leukemia recurrence. Achieving molecular remission at the end of induction therapy after diagnosis or after relapse has influenced treatment choice. Failure to achieve mole...
Source: Best Practice and Research Clinical Haematology - September 23, 2017 Category: Hematology Source Type: research

Intracellular protein degradation: From a vague idea thru the lysosome and the ubiquitin-proteasome system and onto human diseases and drug targeting
Publication date: Available online 22 September 2017 Source:Best Practice & Research Clinical Haematology Author(s): Aaron Ciechanover Between the 1950s and 1980s, scientists were focusing mostly on how the genetic code is transcribed to RNA and translated to proteins, but how proteins are degraded has remained a neglected research area. With the discovery of the lysosome by Christian de Duve it was assumed that cellular proteins are degraded within this organelle. Yet, several independent lines of experimental evidence strongly suggested that intracellular proteolysis is largely non-lysosomal, but the mechanisms ...
Source: Best Practice and Research Clinical Haematology - September 23, 2017 Category: Hematology Source Type: research

The evolving role of genomic testing in assessing prognosis of patients with myelodysplastic syndromes
Publication date: Available online 22 September 2017 Source:Best Practice & Research Clinical Haematology Author(s): David P. Steensma The introduction into routine hematology-oncology clinical practice of molecular genetic testing assays based on next-generation sequencing platforms is prompting reassessment of the importance of molecular assay results in comparison to existing disease-specific risk stratification tools based on clinical assessment and light microscopy. For patients with myelodysplastic syndromes (MDS), the most commonly used tools for prognostication currently include the International Prognosti...
Source: Best Practice and Research Clinical Haematology - September 23, 2017 Category: Hematology Source Type: research

Impact of allogeneic hematopoietic cell transplantation on the outcome of older patients with acute myeloid leukemia
Publication date: Available online 22 September 2017 Source:Best Practice & Research Clinical Haematology Author(s): Frederick R. Appelbaum For younger patients with intermediate- or high-risk acute myeloid leukemia (AML) in first remission, allogeneic hematopoietic cell transplantation (HCT) offers the best chance of cure and therefore is the treatment of choice. The role of allogeneic HCT in the treatment of older patients is less well defined. In this review, four issues concerning the role of HCT in the treatment of older AML patients will be addressed: the frequency of allogeneic HCT in the older AML populati...
Source: Best Practice and Research Clinical Haematology - September 23, 2017 Category: Hematology Source Type: research

Cytokine release syndrome: Who is at risk and how to treat
Publication date: Available online 22 September 2017 Source:Best Practice & Research Clinical Haematology Author(s): Noelle Frey T-cell engaging therapies such as blinatumomab and anti-CD19 chimeric antigen receptor (CAR) T cells have revolutionized our approach to patients with relapsed and refractory acute lymphoblastic leukemia (ALL). However, the immune activation responsible for high remission rates is also responsible for the unique treatment-related toxicity of cytokine release syndrome (CRS). The clinical signs of CRS include fever, hemodynamic instability, and capillary leak, which correlate with T-cell a...
Source: Best Practice and Research Clinical Haematology - September 23, 2017 Category: Hematology Source Type: research

AML in 2017: Advances in clinical practice
Publication date: Available online 22 September 2017 Source:Best Practice & Research Clinical Haematology Author(s): Jacob M. Rowe Numerous advances have been made in the biology and treatment of acute myeloid leukemia (AML) in 2017. These include the integration of the assessment of minimal residual disease (MRD) into clinical practice, the approval and near approval of new agents, improvement in therapy for older patients, and the development of a number of promising new agents, including IDH inhibitors, a Hedgehog signaling pathway inhibitor, and a histone deacetylase inhibitor. In addition, the concept of chem...
Source: Best Practice and Research Clinical Haematology - September 23, 2017 Category: Hematology Source Type: research

Which factors influence the development of GVHD in HLA-matched or mismatched transplants?
Publication date: Available online 22 September 2017 Source:Best Practice & Research Clinical Haematology Author(s): Effie W. Petersdorf The sheer diversity of HLA alleles makes the probability of finding matched unrelated donors for patients requiring hematopoietic cell transplantation (HCT) a complex situation. New evidence suggests that mismatching at certain HLA loci may provide a greater benefit in terms of graft-versus-leukemia effect than other mismatches when HLA-matched donors are not available. This review summarizes the current understanding of HLA matching requirements for unrelated donor HCT. (Source:...
Source: Best Practice and Research Clinical Haematology - September 23, 2017 Category: Hematology Source Type: research

Which new agents will be incorporated into frontline therapy in acute myeloid leukemia?
Publication date: Available online 22 September 2017 Source:Best Practice & Research Clinical Haematology Author(s): Richard M. Stone For 4 decades, new agents had not been approved for use in treating acute myeloid leukemia (AML). The long dry spell was broken in 2017, however, with the approval or recommendation for approval of several agents: midostaurin for addition to chemotherapy in mutant FLT3 patients undergoing intensive chemotherapy, enasidenib in advanced mutant IDH2 patients, CPX-351 in secondary AML patients, and gemtuzumab ozogamicin in conjunction with standard chemotherapy in AML. This review surve...
Source: Best Practice and Research Clinical Haematology - September 23, 2017 Category: Hematology Source Type: research

Philadelphia chromosome negative B-cell acute lymphoblastic leukemia in older adults: Current treatment and novel therapies
Publication date: Available online 3 August 2017 Source:Best Practice & Research Clinical Haematology Author(s): Kristen M. O'Dwyer, Jane L. Liesveld The management of older adult patients with Philadelphia chromosome negative (Ph-) B-acute lymphoblastic leukemia (ALL) remains a challenge. Older adults with Ph- B-ALL have the highest rates of treatment failure and treatment complications, and thus there is no standard treatment approach in this clinical setting. Approximately 16% of patients with newly diagnosed Philadelphia chromosome negative (Ph-) acute lymphoblastic leukemia (ALL) are aged 60 years or older [2...
Source: Best Practice and Research Clinical Haematology - August 3, 2017 Category: Hematology Source Type: research

The what, when and how of CAR T cell therapy for ALL
Publication date: Available online 3 August 2017 Source:Best Practice & Research Clinical Haematology Author(s): Noelle Frey Chimeric Antigen Receptor (CAR) T cells that have been engineered to target CD19 have shown great promise in patients with relapsed and refractory B cell acute lymphocytic leukemia with remission rates of 70–90%. Some remissions have successfully bridged patients to a curable allogeneic stem cell transplant, some responses have been durable without further treatment, and some patients have achieved durable remissions for relapsed ALL after allogeneic stem cell transplant. Cytokine rele...
Source: Best Practice and Research Clinical Haematology - August 3, 2017 Category: Hematology Source Type: research

How should we treat a patient with relapsed Ph-negative B-ALL and what novel approaches are being investigated?
Publication date: Available online 3 August 2017 Source:Best Practice & Research Clinical Haematology Author(s): Nicola Goekbuget Despite significant improvements in outcome of newly diagnosed B-precursor ALL, the results in relapsed or refractory adult ALL are overall poor. Large retrospective studies revealed significant differences in terms of outcome, with particularly poor response rates in early or refractory relapses, whereas late relapses usually respond very well to repeated standard induction. Particularly new immunotherapy compounds like the CD19 bispecific antibody Blinatumomab and the conjugated CD22 ...
Source: Best Practice and Research Clinical Haematology - August 3, 2017 Category: Hematology Source Type: research

How should we treat the AYA patient with newly diagnosed ALL?
Publication date: Available online 3 August 2017 Source:Best Practice & Research Clinical Haematology Author(s): Nicolas Boissel Adolescent and young adult (AYA) patients with acute lymphoblastic leukaemia (ALL) are recognized as a unique population with specific characteristics and needs. In adolescents aged 15–20 years old, the use of full paediatric protocols is supported by many comparative studies of paediatric and adult cooperative groups. In young adults, growing evidence suggests that paediatric-inspired approaches may also improve outcomes and lead to long-term survival rates of almost 70%. In the l...
Source: Best Practice and Research Clinical Haematology - August 3, 2017 Category: Hematology Source Type: research

Pharmacogenomics in acute lymphoblastic leukemia
Publication date: Available online 27 July 2017 Source:Best Practice & Research Clinical Haematology Author(s): Shawn H.R. Lee, Jun J. Yang Pharmacogenomics is a fast-growing field of personalized medicine using a patient's genomic profile to determine drug disposition or response to drug therapy, in order to develop safer and more effective pharmacotherapy. Childhood acute lymphoblastic leukemia (ALL), being the most common malignancy in childhood, which is treated with uniform and standardized clinical trials, is remarkably poised for pharmacogenomic studies. In the last decade, unbiased genome-wide association ...
Source: Best Practice and Research Clinical Haematology - July 27, 2017 Category: Hematology Source Type: research

What is the optimal initial management of the older MCL patient?
Publication date: Available online 19 July 2017 Source:Best Practice & Research Clinical Haematology Author(s): Johanna C. Kluin-Nelemans, Jeanette K. Doorduijn The current first line treatment of a patient with mantle cell lymphoma (MCL) is often considered as too toxic for elderly patients. The elderly, however, comprise the majority of the patients with MCL. The results of several recent studies have shown that the outcome of this patient group is not as dismal as in the past. Indeed, if patients are not considered frail, and can tolerate rituximab and moderate intensive chemotherapy such as R-CHOP followed by ...
Source: Best Practice and Research Clinical Haematology - July 20, 2017 Category: Hematology Source Type: research

Which patients should I transplant with acute lymphoblastic leukemia?
Publication date: Available online 13 July 2017 Source:Best Practice & Research Clinical Haematology Author(s): Tsofia Inbar, Jacob M. Rowe, Netanel A. Horowitz Allogeneic hematopoietic cell transplantation for acute lymphoblastic leukemia (ALL) offers curative therapy for patients who are in complete remission. Historically, there was great hesitation to offer this modality to patients with ALL due to the high attendant morbidity and mortality. Furthermore, the outstanding results in childhood ALL led many to believe that significant long-term survival could be achieved using chemotherapy-based regimens alone. Th...
Source: Best Practice and Research Clinical Haematology - July 13, 2017 Category: Hematology Source Type: research

Acute lymphoblastic leukemia (ALL)
Publication date: Available online 11 July 2017 Source:Best Practice & Research Clinical Haematology Author(s): Anjali Advani (Source: Best Practice and Research Clinical Haematology)
Source: Best Practice and Research Clinical Haematology - July 11, 2017 Category: Hematology Source Type: research

How should we treat older adults with Ph+ adult ALL and what novel approaches are being investigated?
Publication date: Available online 5 July 2017 Source:Best Practice & Research Clinical Haematology Author(s): Matthew Wieduwilt Treatment of older patients with Philadelphia-chromosome-positive (Ph+) acute lymphoblastic leukemia presents unique challenges. Advanced age, comorbidities, high treatment-related death rates with traditional chemotherapy, and relapse combine to yield poor survival. Reduced-intensity induction with BCR-ABL1 targeted tyrosine kinase inhibitors (TKIs) and corticosteroids yields CR rates 96–100% with no induction mortality but relapse is nearly certain without effective consolidation...
Source: Best Practice and Research Clinical Haematology - July 6, 2017 Category: Hematology Source Type: research

How do we measure MRD in ALL and how should measurements affect decisions. Re: Treatment and prognosis?
Publication date: Available online 6 July 2017 Source:Best Practice & Research Clinical Haematology Author(s): Xueyan Chen, Brent L. Wood Minimal residual disease (MRD) is the most significant independent prognostic factor in acute lymphocytic leukemia (ALL). Monitoring MRD using sensitive techniques, including multiparametric flow cytometry (MFC) and quantitative polymerase chain reaction (qPCR)-based methods, has improved the assessment of treatment response and risk stratification for clinical management. New molecular methods, such as high-throughput next-generation sequencing (NGS), have evolved into routine ...
Source: Best Practice and Research Clinical Haematology - July 6, 2017 Category: Hematology Source Type: research

The biology of Philadelphia chromosome-like ALL
Publication date: Available online 6 July 2017 Source:Best Practice & Research Clinical Haematology Author(s): Kathryn G. Roberts Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a recently described subtype of B-cell precursor ALL with a gene expression profile similar to Ph-positive ALL and a high frequency of IKZF1 alterations. The prevalence of Ph-like ALL increases with age, ranging from 10-15% of children to over 25% of young adults with ALL. It occurs more frequently in males and is associated with adverse clinical features including elevated minimal residual disease levels and poo...
Source: Best Practice and Research Clinical Haematology - July 6, 2017 Category: Hematology Source Type: research

How is the Ph-like signature being incorporated into ALL therapy?
Publication date: Available online 15 June 2017 Source:Best Practice & Research Clinical Haematology Author(s): Luke Maese, Sarah K. Tasian, Elizabeth A. Raetz Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a recently identified high risk disease subtype characterized by a gene expression profile similar to that observed in Philadelphia chromosome-positive (Ph-positive) ALL, but without an underlying BCR-ABL1 translocation. Adults and children with Ph-like ALL harbor a diversity of alterations that all lead to activated kinase signaling. Outcomes for patients with Ph-like ALL are poor, ...
Source: Best Practice and Research Clinical Haematology - June 23, 2017 Category: Hematology Source Type: research

Which tyrosine kinase inhibitor should we use to treat Philadelphia chromosome-positive acute lymphoblastic leukemia?
Publication date: Available online 15 June 2017 Source:Best Practice & Research Clinical Haematology Author(s): Nicholas J. Short, Hagop Kantarjian, Elias Jabbour, Farhad Ravandi The incorporation of tyrosine kinase inhibitors (TKIs) into chemotherapy regimens has significantly improved the long-term survival of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Successive generations of TKIs with increased potency against BCR-ABL and broader spectrum of activity against ABL kinase domain mutations have led to incremental improvements in the outcomes of patients with this d...
Source: Best Practice and Research Clinical Haematology - June 16, 2017 Category: Hematology Source Type: research

How is the Ph-like signature being incorporated into therapy?
Publication date: Available online 15 June 2017 Source:Best Practice & Research Clinical Haematology Author(s): Luke Maese, Sarah K. Tasian, Elizabeth A. Raetz Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a recently identified high risk disease subtype characterized by a gene expression profile similar to that observed in Philadelphia chromosome-positive (Ph-positive) ALL, but without an underlying BCR-ABL1 translocation. Adults and children with Ph-like ALL harbor a diversity of alterations that all lead to activated kinase signaling. Outcomes for patients with Ph-like ALL are poor, ...
Source: Best Practice and Research Clinical Haematology - June 16, 2017 Category: Hematology Source Type: research

Hepatitis C virus – Associated marginal zone lymphoma
Publication date: Available online 11 February 2017 Source:Best Practice & Research Clinical Haematology Author(s): Marine Armand, Caroline Besson, Olivier Hermine, Frédéric Davi The link between hepatitis C virus (HCV) infection and the development of B-cell non-Hodgkin lymphoma is now well established and based on a number of epidemiological studies. It is further supported by the observation of lymphoma regression after HCV eradication by antiviral treatment. The far most frequent entities are marginal zone lymphoma (MZL) and diffuse large B-cell lymphoma (DLBCL). MZL usually emerge on a backgroun...
Source: Best Practice and Research Clinical Haematology - February 27, 2017 Category: Hematology Source Type: research

Hepatitis C virus - associated marginal zone lymphoma
Publication date: Available online 11 February 2017 Source:Best Practice & Research Clinical Haematology Author(s): Marine Armand, Caroline Besson, Olivier Hermine, Frédéric Davi The link between hepatitis C virus (HCV) infection and the development of B-cell non-Hodgkin lymphoma is now well established and based on a number of epidemiological studies. It is further supported by the observation of lymphoma regression after HCV eradication by antiviral treatment. The far most frequent entities are marginal zone lymphoma (MZL) and diffuse large B-cell lymphoma (DLBCL). MZL usually emerge on a backgroun...
Source: Best Practice and Research Clinical Haematology - February 10, 2017 Category: Hematology Source Type: research

Clinical aspects and therapy of gastrointestinal MALT lymphoma
Publication date: Available online 30 January 2017 Source:Best Practice & Research Clinical Haematology Author(s): Catherine Thieblemont, Emanuele Zucca Extranodal marginal zone B-cell lymphomas of the mucosa associated lymphoid tissue (MALT) arise from lymphoid populations that are induced by chronic inflammation in extranodal sites. Among the MALT lymphomas, gastrointestinal (GIT) MALT lymphoma is the most frequent compared to non-GIT MALT lymphoma arising from other sites. Gastric MALT lymphoma has been the first to be described with the evidence of an etiopathogenetic link provided by the association between H...
Source: Best Practice and Research Clinical Haematology - January 30, 2017 Category: Hematology Source Type: research

Bacteria Associated with Marginal Zone Lymphomas
Publication date: Available online 28 January 2017 Source:Best Practice & Research Clinical Haematology Author(s): Maurilio Ponzoni, Andrés JM. Ferreri In the last decades some bacteria have been associated with a various extent with marginal zone (extra nodal, nodal and splenic types) lymphomas are frequently associated with chronic infections, with important clinical, molecular, biological, and therapeutic implications. The well-known correlation between Helicobacter pylori and gastric MALT-lymphoma, the recently reported links between Chlamydia psittaci and ocular adnexal MALT-lymphoma and Borrelia burgd...
Source: Best Practice and Research Clinical Haematology - January 27, 2017 Category: Hematology Source Type: research

Pathology of nodal marginal zone lymphomas
Publication date: Available online 5 December 2016 Source:Best Practice & Research Clinical Haematology Author(s): Stefano Pileri, Maurilio Ponzoni Nodal marginal zone B cell lymphomas (NMZLs) are a rare group of lymphoid disorders part of the spectrum of marginal zone B-cell lymphomas, which encompass splenic marginal one B-cell lymphoma (SMZL) and extra nodal marginal zone of B-cell lymphoma (EMZL), often of MALT-type. Two clinicopathological forms of NMZL are recognized: adult-type and pediatric-type, respectively. NMZLs show overlapping features with other types of MZ, but distinctive features as well. In this...
Source: Best Practice and Research Clinical Haematology - December 28, 2016 Category: Hematology Source Type: research