scholarly journals Acute Lymphoblastic Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

2021 ◽  
Vol 19 (9) ◽  
pp. 1079-1109
Author(s):  
Patrick A. Brown ◽  
Bijal Shah ◽  
Anjali Advani ◽  
Patricia Aoun ◽  
Michael W. Boyer ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Supportive Care ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Treatment Strategies ◽  
Adolescent And Young Adult ◽  
Cancer Center ◽  
Nccn Guidelines ◽  
Treatment Regimens

The NCCN Guidelines for Acute Lymphoblastic Leukemia (ALL) focus on the classification of ALL subtypes based on immunophenotype and cytogenetic/molecular markers; risk assessment and stratification for risk-adapted therapy; treatment strategies for Philadelphia chromosome (Ph)-positive and Ph-negative ALL for both adolescent and young adult and adult patients; and supportive care considerations. Given the complexity of ALL treatment regimens and the required supportive care measures, the NCCN ALL Panel recommends that patients be treated at a specialized cancer center with expertise in the management of ALL This portion of the Guidelines focuses on the management of Ph-positive and Ph-negative ALL in adolescents and young adults, and management in relapsed settings.

scholarly journals How I Treat Adult Acute Lymphoblastic Leukemia in India

2021 ◽  
Author(s):  
Prasanth Ganesan ◽  
Smita Kayal
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Adult Population ◽  
Current Approach ◽  
Adolescent And Young Adult ◽  
Infection Rates ◽  
Treatment Regimens ◽  
High Infection ◽  
Adult Acute Lymphoblastic Leukemia ◽  
Young Adult Population

AbstractSurvival of children with acute lymphoblastic leukemia (ALL) has improved from 10% to 90% over the last six decades. Survival gains in adult ALL have been more modest and confined to the adolescent and young adult population. Age is an important factor in determining outcomes in ALL. Additional factors like adverse biology, less intense treatment regimens, and poorer tolerance to therapy contribute to inferior survival among adults. Indian physicians face unique challenges while managing these patients. These are high infection rates, limited access to high-end investigations, and newer drugs. In this context, the management decisions in an individual patient are highly nuanced. Through a case-based review, we discuss representative scenarios in adult ALL where we detail our current approach to treatment in the context of available evidence.

scholarly journals Prognostic significance of CD20 expression in adults with de novo precursor B-lineage acute lymphoblastic leukemia

Blood ◽  
2009 ◽  
Vol 113 (25) ◽  
pp. 6330-6337 ◽  
Author(s):  
Deborah A. Thomas ◽  
Susan O'Brien ◽  
Jeffrey L. Jorgensen ◽  
Jorge Cortes ◽  
Stefan Faderl ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Philadelphia Chromosome ◽  
Younger Age ◽  
Cd20 Expression ◽  
Prognostic Implications ◽  
B Lineage

Abstract Immunophenotypic classification of acute lymphoblastic leukemia (ALL) has well-recognized prognostic implications. The significance of CD20 expression has been evaluated in childhood precursor B-lineage ALL with conflicting results. We retrospectively analyzed the influence of CD20 expression on outcome in 253 adults with de novo precursor B-lineage ALL treated with either conventional (VAD/CVAD) or intensive (hyper-CVAD) frontline chemotherapy regimens in the pre-rituximab era. Overall, CD20 positivity of at least 20% was associated with lower 3-year rates of complete remission duration (CRD; 20% vs 55%, P < .001) and overall survival (OS; 27% vs 40%, p = .03). In the CD20 negative subset, the 3-year rates for CRD (58% vs 42%, p = .04) and OS (60% vs 28%, P < .001) were superior for hyper-CVAD compared with VAD/CVAD; rates were particularly favorable for the CD20 negative younger age group (68% and 85%, respectively). In contrast, 3-year CRD and OS rates were uniformly poor for the CD20-positive group regardless of therapy (27% or less). Multivariate analysis for event-free survival identified older age, leukocyte count higher than 30 × 109/L, presence of Philadelphia chromosome, high systemic risk classification, and CD20 positivity as independent predictors of worse outcome. In conclusion, CD20 expression in de novo adult precursor B-lineage ALL appears to be associated with a poor prognosis. Incorporation of monoclonal antibodies directed against CD20 into frontline chemotherapy regimens warrants investigation.

Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Showing Complete Molecular Response Following Imatinib (Glivec®) - combined chemotherapy

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3971-3971
Author(s):  
Inas Ahmed Asfour ◽  
Shereen Ahmed El Shazly
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Molecular Level ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Treatment Strategies ◽  
Normal Karyotype ◽  
Molecular Response ◽  
Molecular Remission ◽  
Complete Molecular Response

Abstract The Philadelphia (Ph) chromosome is the result of a reciprocal translocation between chromosomes 9 and 22 [t (9; 22)] and is characterized at the molecular level by expression of the BCR-ABL fusion gene. It is the most frequent genetic aberration in adult acute lymphoblastic leukemia (ALL), being detectable in 30–40%of patients with B-precursor ALL. In our initial work we report two cases of grossly negative (Ph) ALL, that showed a complete molecular response after an imatinib based chemotherapy. In the first case we report a 17-year-old male who was admitted because of bony aches and fever. A diagnosis of acute lymphoblastic leukemia was made on the basis of a 95% infiltration of leukemic cells in his bone marrow. Standard G-banding chromosome analysis of bone marrow cells revealed a normal karyotype. And subsequent fluorescent in situ hybridization (FISH) examination showed a 20% positivity for the Philadelphia chromosome. As for the second case we report a 19 years old male patient who was presented with complaints of recurrent epistaxis and bony aches. He was also found to have acute lymphoblastic leukemia due to bone marrow infiltration with 55% blasts that showed a normal karyotype using the G- banding, and a positive Philadelphia chromosome-using FISH method - in 31 % of the examined cells. Both patients received combination chemotherapy incorporating imatinib mesylate; Glivec® in a dose of 400 mg/day continuously all through the induction, consolidation and subsequent re-enforcement courses. They both achieved complete hematological, cytogenetic as well as molecular remission that was maintained-thus far- for a total period of 20 and 11 months respectively. We postulated that there might have been two clones, both a Ph-positive clone and Ph-negative clone, with subsequent sensitivity of this Ph positive clone to the incorporated targeted treatment, as was evidenced by disappearance of the Ph-positive cells in subsequent FISH analysis and the negativity of the real time quantitative polymerase chain reaction (RT-QPCR) for BCR/ABL gene. Several investigators have studied the role of Hematopoeitic stem cell transplantation (HSCT) in the context of Ph+ ALL patients, which showed superior results when compared to conventional chemotherapy in means of remission induction as well as relapse rates, Dombret et al.2002. The highly successful introduction of the first ABL-kinase inhibitor imatinib into the treatment of Philadelphia chromosome positive chronic myeloid leukemia (CML) has led to clinical testing of imatinib in Ph+ALL. It has recently been approved for Ph+ALL in Europe and Japan. Given the much more aggressive nature of Ph+ALL when compared with chronic or even accelerated phase CML, a variety of imatinib-based treatment strategies have been explored in ALL(Ottman et al.,2007). Yet thus far the exploration of these treatment modalities in the very rare entity of gross normal karyotype and molecular level cytogenetic aberrations remains to be elucidated. Conclusion: Molecular remission on tyrosine kinase inhibitors in patient with ALL Ph +ve may open the door to revising the treatment strategies offered thus far for that subset of patients, as a new stratifying factor. Our work offers a unique protocol for utilizing imatinib as an integral part of the chemotherapy protocols normally offered for these patients, but yet at a lower dose, and raises the question of whether they should be transplanted in accordance with the current guidelines and if so when? More patients experience and controlled randomized trials are needed and eagerly awaited.

Adolescent and Young Adult Patients with Acute Lymphoblastic Leukemia (ALL) Treated with Modified Augmented Berlin-Frankfurt-Muenster (ABFM) Therapy

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1527-1527
Author(s):  
Michael E. Rytting ◽  
Deborah A. Thomas ◽  
Elias Jabbour ◽  
Anna R.K. Franklin ◽  
Gautam Borthakur ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Young Adults ◽  
Acute Lymphoblastic Leukemia ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Disease Free Survival ◽  
Adolescent And Young Adult ◽  
Days Of Therapy ◽  
Grade Iii

Abstract Abstract 1527 Several pediatric-based protocols for treatment of acute lymphoblastic leukemia (ALL) in adolescents and young adults have been completed or are ongoing. Some studies have enrolled patients (pts) up to age 55 years, and, so far, results have been satisfactory. Augmented Berlin-Frankfurt-Muenster (ABFM) has been shown to be an effective and tolerable treatment for ALL in adolescents. To evaluate the efficacy and toxicity of this therapy in young adults, we designed a protocol of modified ABFM therapy for pts with ALL from age 12 to 40 years old. 83 pts have been enrolled on protocol and are evaluable for toxicity. 68 pts with de novo Philadelphia chromosome negative ALL have completed at least 29 days of therapy (induction) on protocol. They have the following characteristics: 56 (82%) pts have pre-B ALL and 12 (18%) have T-ALL. The median age is 21 (mean=23; range=13–39). The median presenting WBC=5.3 (mean=32; range= 0.4–494). 65/68 (96%) pts have achieved a remission. One patient died during induction. 50 (74%) pts have attained remission by 15 days of induction, while 15 (22%) have been slow responders. 5/68 (7%) pts have required an extension of induction by 2 weeks. At day 29 of therapy, 38 (56%) pts had negative minimal residual disease (MRD) by flow cytometry, 20 (29%) patients were positive for MRD, 10 were suspicious or not available. By day 84 of therapy, 49 (72%) pts were negative for MRD and 9 (13%) were positive. Currently, there have been 17 relapses and 10 deaths. Toxicities in the entire group include severe asparaginase allergy in 15 (18%) pts, thrombus formation in 16 (19%) pts, hyperbilirubinemia grade III-IV in 19 (23%) pts, ALT/AST grade III-IV in 23 (28%) pts, CNS stroke-like symptoms in 6 (7%) pts, hypofibrinogen grade III-IV in 26 (31%), pancreatitis in 6 (7%), and avascular necrosis in 6 (7%) pts. Hepatic toxicity has resolved completely within two weeks in almost all pts as has the CNS toxicity. In summary, induction success, by morphology and flow cytometry, has been satisfactory with this regimen. CRD and OS have not been significantly better than with HyperCVAD therapy for this age group. Expected toxicities have been prominent, but mostly transient. Hypofibrinogenemia is frequent, but bleeding is rare. Thrombosis and severe allergic reactions are more frequent than in pediatric trials. For pts 25 years of age and younger, the overall survival (OS) and disease free survival (DFS) at 2 years are 88% and 84% respectively. For pts > 25 years of age, the OS and DFS at two years are 65% and 50% respectively. This difference in OS between the groups is statistically significant. Continued enrollment is anticipated to further evaluate the survival differences between these two patient groups. Disclosures: No relevant conflicts of interest to declare.

Development and Refinement of Augmented Treatment Regimens for Pediatric High-Risk Acute Lymphoblastic Leukemia

2012 ◽  
pp. 611-615
Author(s):  
Stephen P. Hunger
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Children And Adolescents ◽  
Western Europe ◽  
Randomized Clinical Trials ◽  
Kinase Inhibitor ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Cooperative Groups ◽  
Treatment Regimens

Overview: The 5-year survival rate for children and adolescents with acute lymphoblastic leukemia (ALL) is now at least 90%. However, clinical features (age and initial white blood cell count [WBC]), early treatment response, and the presence/absence of specific sentinel genomic lesions can identify subsets of high-risk (HR) ALL patients with a much higher risk of treatment failure. Chemotherapy regimens used to treat HR ALL have been refined over the past 3 decades through randomized clinical trials conducted by the Children's Oncology Group (COG) in North America and the Berlin-Frankfurt-Muenster (BFM) group in Western Europe. Contemporary COG HR ALL treatment regimens were developed from the BFM-76 regimen, with subsequent changes that led to development and refinement of a so-called augmented BFM (ABFM) regimen used today. Although contemporary COG and BFM treatment regimens are not identical, there are many more similarities than differences. With improvements in survival, it has become clear that although the outcome of some patients with HR ALL can be improved by optimizing use of standard cytotoxic chemotherapy agents, this approach has had only limited success for other patient subsets. In contrast, introduction of the tyrosine kinase inhibitor imatinib has led to dramatic outcome improvements for children and adolescents with Philadelphia chromosome–positive ALL. Genomic studies are identifying new sentinel genomic lesions that can serve as potential therapeutic targets, which will likely lead to the testing of novel and/or targeted therapies in more children with HR ALL. Such studies will require increased collaboration between Western European and North American cooperative groups.

scholarly journals Novel monoclonal antibody-based treatment strategies in adults with acute lymphoblastic leukemia

2019 ◽  
Vol 10 ◽  
pp. 204062071984949 ◽  
Author(s):  
Veronica A. Guerra ◽  
Elias J. Jabbour ◽  
Farhad Ravandi ◽  
Hagop Kantarjian ◽  
Nicholas J. Short
Keyword(s):  
Monoclonal Antibodies ◽  
Acute Lymphoblastic Leukemia ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Treatment Strategies ◽  
Poor Overall Survival ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Treatment Regimens ◽  
Treatment Paradigm

Adult acute lymphoblastic leukemia (ALL) has a poor overall survival compared with pediatric ALL where cure rates are observed in more than 90% of patients. The recent development of novel monoclonal antibodies targeting CD20, CD19, and CD22 has changed the long-term outcome of this disease, both in the frontline setting (e.g. rituximab) and for patients with relapsed/refractory disease (e.g. inotuzumab ozogamicin and blinatumomab). The CD3-CD19 bispecific T-cell-engaging antibody blinatumomab is also the first drug approved in ALL for patients with persistent or recurrent measurable residual disease, providing a new treatment paradigm for these patients. Several new agents are also in development that use novel constructs or target alternative surface epitopes such as CD123, CD25, and CD38. Herein, we review the role of monoclonal antibodies in adult ALL and summarize the current and future approaches in ALL, including novel combination therapies and the possibility of early incorporation of these agents into treatment regimens.

scholarly journals Pediatric Acute Lymphoblastic Leukemia, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology

2020 ◽  
Vol 18 (1) ◽  
pp. 81-112 ◽  
Author(s):  
Patrick Brown ◽  
Hiroto Inaba ◽  
Colleen Annesley ◽  
Jill Beck ◽  
Susan Colace ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Acute Lymphoblastic Leukemia ◽  
Supportive Care ◽  
Clinical Practice Guidelines ◽  
Practice Guidelines ◽  
Disease Risk ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem ◽  
Nccn Guidelines ◽  
Pediatric All

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Advancements in technology that enhance our understanding of the biology of the disease, risk-adapted therapy, and enhanced supportive care have contributed to improved survival rates. However, additional clinical management is needed to improve outcomes for patients classified as high risk at presentation (eg, T-ALL, infant ALL) and who experience relapse. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for pediatric ALL provide recommendations on the workup, diagnostic evaluation, and treatment of the disease, including guidance on supportive care, hematopoietic stem cell transplantation, and pharmacogenomics. This portion of the NCCN Guidelines focuses on the frontline and relapsed/refractory management of pediatric ALL.

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