scholarly journals How I treat acute lymphoblastic leukemia in older adolescents and young adults

Blood ◽  
2015 ◽  
Vol 125 (24) ◽  
pp. 3702-3710 ◽  
Author(s):  
Emily Curran ◽  
Wendy Stock
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Kinase Inhibitors ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Intensive Therapy ◽  
Survival Rates ◽  
Age Groups ◽  
Disease Free Survival ◽  
Current Approach ◽  
Adolescent And Young Adult

Abstract At the intersection between children and older adults, the care of adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) poses unique challenges and issues beyond those faced by other age groups. Although the survival of AYA patients is inferior to younger children, growing evidence suggests that AYA patients have improved outcomes, with disease-free survival rates of 60% to 70%, when treated with pediatric-based approaches. A holistic approach, incorporating a multidisciplinary team, is a key component of successful treatment of these AYA patients. With the appropriate support and management of toxicities during and following treatment, these regimens are well tolerated in the AYA population. Even with the significant progress that has been made during the last decade, patients with persistence of minimal residual disease (MRD) during intensive therapy still have a poor prognosis. With new insights into disease pathogenesis in AYA ALL and the availability of disease-specific kinase inhibitors and novel targeted antibodies, future studies will focus on individualized therapy to eradicate MRD and result in further improvements in survival. This case-based review will discuss the biology, pharmacology, and psychosocial aspects of AYA patients with ALL, highlighting our current approach to the management of these unique patients.

scholarly journals Practical guidance for the management of acute lymphoblastic leukemia in the adolescent and young adult population

2020 ◽  
Vol 11 ◽  
pp. 204062072090353 ◽  
Author(s):  
Francesca Carobolante ◽  
Sabina Chiaretti ◽  
Cristina Skert ◽  
Renato Bassan
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Older Patients ◽  
Kinase Inhibitors ◽  
Lymphoblastic Leukemia ◽  
Adult Population ◽  
Survival Rates ◽  
Age Groups ◽  
Treatment Compliance ◽  
Adolescent And Young Adult ◽  
Similar Treatment

The outstanding therapeutic progress achieved with modern pediatric regimens in childhood acute lymphoblastic leukemia (ALL) led efforts to explore whether a similar treatment approach could be equally effective and safe in older patients, starting initially with older adolescents and young adults (AYA), variably defined in different studies by an age between 15–18 and 25–39 years. Several comparative and noncomparative trials of this type have been carried out during the last two decades, enrolling thousands of patients. Almost without exception, the new strategy improved patients’ outcomes compared with traditional adult treatments in B-lineage and T-lineage Philadelphia (Ph) chromosome-negative B-ALL, while the use of tyrosine kinase inhibitors (TKI) led to comparative progress in Ph+ ALL, a former high-risk subset more typically observed in older age groups. At present, highly effective pediatric-based regimens warrant 5-year survival rates of 60–70% in AYA patients. In view of these data, the same approach was progressively extended to older patients, improving the results up to 55 years of age. Issues of treatment compliance and drug-related toxicity have thus far prevented a comparable therapeutic advancement in patients aged >55 years. This critical review updates and summarizes with pertinent examples this global, positive therapeutic change, and examines how to promote further progress with new targeted therapies that include novel immuno-therapeutics and other agents developed against the many molecular dysfunctions detectable in various ALL subsets. Substantial progress is expected to occur soon, bringing AYA survival figures very close to that of children, and also to improve the outcome of ALL at all ages.

scholarly journals Acute lymphoblastic leukemia in adolescent and young adults: treat as adults or as children?

Blood ◽  
2018 ◽  
Vol 132 (4) ◽  
pp. 351-361 ◽  
Author(s):  
Nicolas Boissel ◽  
André Baruchel
Keyword(s):  
Young Adults ◽  
Acute Lymphoblastic Leukemia ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Age Distribution ◽  
Adolescent And Young Adult ◽  
Contributing Factors ◽  
Term Survival ◽  
Hematopoietic Stem

Abstract Adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) are recognized as a unique population with specific characteristics and needs. In adolescents age 15 to 20 years, the use of fully pediatric protocols is supported by many comparative studies of pediatric and adult cooperative groups. In young adults, growing evidence suggests that pediatric-inspired or even fully pediatric approaches may also dramatically improve outcomes, leading to long-term survival rates of almost 70%, despite diminishing indications of hematopoietic stem-cell transplantation. In the last decade, better knowledge of the ALL oncogenic landscape according to age distribution and minimal residual disease assessments has improved risk stratification. New targets have emerged, mostly in the heterogeneous B-other group, particularly in the Philadelphia-like ALL subgroup, which requires both in-depth molecular investigations and specific evaluations of targeted treatments. The remaining gap in the excellent results reported in children has many other contributing factors that should not be underestimated, including late or difficult access to care and/or trials, increased acute toxicities, and poor adherence to treatment. Specific programs should be designed to take into account those factors and finally ameliorate survival and quality of life for AYAs with ALL.

scholarly journals Management of adult Ph-positive acute lymphoblastic leukemia

Hematology ◽  
2015 ◽  
Vol 2015 (1) ◽  
pp. 406-413 ◽  
Author(s):  
Sabina Chiaretti ◽  
Robin Foà
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Kinase Inhibitors ◽  
Stem Cell Transplant ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
The Elderly ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant

Abstract Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) has been regarded for decades as the ALL subgroup with the worse outcome. It represents the most frequent genetic subtype of adult ALL, and increases progressively with age. The introduction of tyrosine kinase inhibitors (TKIs) has enabled to obtain complete hematologic remissions (CHRs) in virtually all patients, including the elderly, to improve disease-free survival and overall survival, as well as to increase the percentage of patients who can undergo an allogeneic stem cell transplant (allo-SCT). The current management of adult Ph+ ALL patients relies on the use of a TKI with or without chemotherapy followed by an allo-SCT, which still remains the only curative option. Minimal residual disease screening is permitting not only a better stratification of patients, but has also allowed to reconsider the role of autologous stem cell transplant for a set of patients who do not have a donor or are not eligible for an allo-SCT. At present, clinical challenges are represented by the emergence of resistant mutations, particularly the gatekeeper T315I, for which alternative approaches, comprising novel TKIs or therapies based on the combination of TKI with immunotherapeutic strategies, are being considered in order to overcome resistance.

scholarly journals Advances in the Diagnosis and Treatment of Pediatric Acute Lymphoblastic Leukemia

2021 ◽  
Vol 10 (9) ◽  
pp. 1926
Author(s):  
Hiroto Inaba ◽  
Ching-Hon Pui
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Detailed Analysis ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Treatment Strategies ◽  
Chemotherapeutic Agents ◽  
Response To Treatment ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Therapeutic Implications

The outcomes of pediatric acute lymphoblastic leukemia (ALL) have improved remarkably during the last five decades. Such improvements were made possible by the incorporation of new diagnostic technologies, the effective administration of conventional chemotherapeutic agents, and the provision of better supportive care. With the 5-year survival rates now exceeding 90% in high-income countries, the goal for the next decade is to improve survival further toward 100% and to minimize treatment-related adverse effects. Based on genome-wide analyses, especially RNA-sequencing analyses, ALL can be classified into more than 20 B-lineage subtypes and more than 10 T-lineage subtypes with prognostic and therapeutic implications. Response to treatment is another critical prognostic factor, and detailed analysis of minimal residual disease can detect levels as low as one ALL cell among 1 million total cells. Such detailed analysis can facilitate the rational use of molecular targeted therapy and immunotherapy, which have emerged as new treatment strategies that can replace or reduce the use of conventional chemotherapy.

scholarly journals Approach to the Adult Acute Lymphoblastic Leukemia Patient

2019 ◽  
Vol 8 (8) ◽  
pp. 1175 ◽  
Author(s):  
Valentina Sas ◽  
Vlad Moisoiu ◽  
Patric Teodorescu ◽  
Sebastian Tranca ◽  
Laura Pop ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Kinase Inhibitors ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
High Risk Patient ◽  
Late Relapse ◽  
Published Data ◽  
Hematopoietic Stem

During recent decades, understanding of the molecular mechanisms of acute lymphoblastic leukemia (ALL) has improved considerably, resulting in better risk stratification of patients and increased survival rates. Age, white blood cell count (WBC), and specific genetic abnormalities are the most important factors that define risk groups for ALL. State-of-the-art diagnosis of ALL requires cytological and cytogenetical analyses, as well as flow cytometry and high-throughput sequencing assays. An important aspect in the diagnostic characterization of patients with ALL is the identification of the Philadelphia (Ph) chromosome, which warrants the addition of tyrosine kinase inhibitors (TKI) to the chemotherapy backbone. Data that support the benefit of hematopoietic stem cell transplantation (HSCT) in high risk patient subsets or in late relapse patients are still questioned and have yet to be determined conclusive. This article presents the newly published data in ALL workup and treatment, putting it into perspective for the attending physician in hematology and oncology.

scholarly journals Outcomes after late bone marrow and very early central nervous system relapse of childhood B-acute lymphoblastic leukemia: a report from the Children's Oncology Group phase III study AALL0433

Haematologica ◽  
2020 ◽  
Vol 106 (1) ◽  
pp. 46-55 ◽  
Author(s):  
Glen Lew ◽  
Yichen Chen ◽  
Xiaomin Lu ◽  
Susan R. Rheingold ◽  
James A. Whitlock ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Bone Marrow ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Central Nervous System Relapse ◽  
Oncology Group

Outcomes after relapse of childhood B-acute lymphoblastic leukemia (B-ALL) are poor, and optimal therapy is unclear. Children’s Oncology Group study AALL0433 evaluated a new platform for relapsed ALL. Between March 2007 and October 2013 AALL0433 enrolled 275 participants with late bone marrow or very early isolated central nervous system (iCNS) relapse of childhood B-ALL. Patients were randomized to receive standard versus intensive vincristine dosing; this randomization closed due to excess peripheral neuropathy in 2010. Patients with matched sibling donors received allogeneic hematopoietic cell transplantation (HCT) after the first three blocks of therapy. The prognostic value of minimal residual disease (MRD) was also evaluated in this study. The 3-year event free and overall survival (EFS/OS) for the 271 eligible patients were 63.6% +/- 3.0% and 72.3% +/- 2.8% respectively. MRD at the end of Induction-1 was highly predictive of outcome, with 3-year EFS/OS of 84.9 +/- 4.0% and 93.8 +/- 2.7% for patients with MRD <0.1%, vs. 53.7 +/- 7.8% and 60.6 +/- 7.8% for patients with MRD ≥0.1% (p<0.0001). Patients who received HCT vs. chemotherapy alone had an improved 3-year disease-free survival (77.5 +/- 6.2% vs. 66.9 +/- 4.5%, p=0.03) but not OS (81.5 +/- 5.8% for HCT vs. 85.8 +/- 3.4% for chemotherapy, p=0.46). Patients with early iCNS relapse fared poorly, with a 3-year EFS/OS of 41.4% +/- 9.2% and 51.7% +/- 9.3%, respectively. Infectious toxicities of the chemotherapy platform were significant. The AALL0433 chemotherapy platform is efficacious for late bone marrow relapse of B-ALL, but with significant toxicities. The MRD threshold of 0.1% at the end of Induction-1 was highly predictive of outcome. The optimal role for HCT for this patient population remains uncertain. This trial is registered at clinicaltrials.gov (NCT# 00381680).

scholarly journals Outcome of Children With Hypodiploid Acute Lymphoblastic Leukemia: A Retrospective Multinational Study

2019 ◽  
Vol 37 (10) ◽  
pp. 770-779 ◽  
Author(s):  
Ching-Hon Pui ◽  
Paola Rebora ◽  
Martin Schrappe ◽  
Andishe Attarbaschi ◽  
Andre Baruchel ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Survival Rate ◽  
Hematopoietic Cell Transplantation ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Allogeneic Transplantation ◽  
Remission Induction ◽  
Event Free Survival ◽  
Free Survival

PURPOSE We determined the prognostic factors and utility of allogeneic hematopoietic cell transplantation among children with newly diagnosed hypodiploid acute lymphoblastic leukemia (ALL) treated in contemporary clinical trials. PATIENTS AND METHODS This retrospective study collected data on 306 patients with hypodiploid ALL who were enrolled in the protocols of 16 cooperative study groups or institutions between 1997 and 2013. The clinical and biologic characteristics, early therapeutic responses as determined by minimal residual disease (MRD) assessment, treatment with or without MRD-stratified protocols, and allogeneic transplantation were analyzed for their impact on outcome. RESULTS With a median follow-up of 6.6 years, the 5-year event-free survival rate was 55.1% (95% CI, 49.3% to 61.5%), and the 5-year overall survival rate was 61.2% (95% CI, 55.5% to 67.4%) for the 272 evaluable patients. Negative MRD at the end of remission induction, high hypodiploidy with 44 chromosomes, and treatment in MRD-stratified protocols were associated with a favorable prognosis, with a 5-year event-free survival rate of 75% (95% CI, 66.0% to 85.0%), 74% (95% CI, 61.0% to 89.0%), and 62% (95% CI, 55.0% to 69.0%), respectively. After exclusion of patients with high hypodiploidy with 44 chromosomes and adjustment for waiting time to transplantation and for covariables in a Poisson model, disease-free survival did not differ significantly ( P = .16) between the 42 patients who underwent transplantation and the 186 patients who received chemotherapy only, with an estimated 5-year survival rate of 59% (95% CI, 46.5% to 75.0%) versus 51.5% (95% CI, 44.7% to 59.4%), respectively. Transplantation produced no significant impact on outcome compared with chemotherapy alone, especially among the subgroup of patients who achieved a negative MRD status upon completion of remission induction. CONCLUSION MRD-stratified treatments improved the outcome for children with hypodiploid ALL. Allogeneic transplantation did not significantly improve outcome overall and, in particular, for patients who achieved MRD-negative status after induction.

CpG Oligonucleotides Induce Anti-Leukemia Activity in a Syngeneic Murine Model of Acute Lymphoblastic Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2830-2830
Author(s):  
Alix E. Seif ◽  
Marlo D. Bruno ◽  
Junior Hall ◽  
Valerie I. Brown ◽  
Stephan A. Grupp ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Nk Cells ◽  
Bone Marrow Cells ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Intensive Therapy ◽  
Significant Proportion ◽  
Cpg Odn

Abstract Acute lymphoblastic leukemia (ALL) accounts for 80% of all pediatric leukemias and is the most common form of childhood cancer. While most children with ALL are cured by current therapies, refractory and relapsed ALL comprise a significant proportion of all pediatric cancers. Furthermore, nearly half of all ALL diagnoses occur in adults, who carry a much poorer prognosis, with the majority dying of relapsed disease. Relapsed ALL generally requires intensive therapy with significant associated morbidity and mortality. Development of novel therapies is essential to improving outcomes. DNA oligodeoxynucleotides containing CpG motifs (CpG ODN) stimulate anti-tumor immune activity via Toll-like receptor 9 (TLR9) activation and are currently in clinical trials for a variety of solid tumors. We have previously reported that CpG ODN stimulation alters antigen presentation by human ALL cells, enhancing allogeneic Th1 responses. In addition, we have shown that CpG ODN administration in vivo reduces the leukemic burden of primary human ALL xenografts in Nod-SCID mice, and that this activity is mediated in part by NK cells. To further the development of CpG ODN as a novel therapeutic agent for ALL, we have investigated the induction of anti-ALL activity by CpG ODN in a syngeneic ALL setting. CpG ODN did not exhibit direct toxicity against cell lines derived from leukemic Eμ-ret transgenic mice in vitro, nor did it alter CD40 or CD86 expression or cytokine production. However, using a flow cytometry-based in vitro killing assay we observed CpG ODN-induced elimination of leukemia cells when cultured with splenocytes or bone marrow cells from Eμ-ret transgene-negative mice (P=0.0388). The difference between CpG ODN-treated and untreated controls became more pronounced with increasing effector:target ratios (P<0.0001). Preliminary data show that depletion of NK cells markedly decreases the magnitude of the observed effect, supporting the hypothesis that this cell type is involved in targeted control of ALL in this model. The ability of CpG ODN to exert anti-leukemia activity in a syngeneic setting suggests that it may have utility as an adjuvant therapy. To test this hypothesis we administered CpG ODN (or PBS) to syngeneic leukemia-bearing mice 2 days after completion of a chemotherapy regimen used to reduce leukemia burden. When mice were sacrificed 3 weeks after treatment, we found significantly reduced leukemia burden in bone marrow (P=0.0019), spleen (P<0.00001) and blood (P=0.00028) of CpG ODN-treated mice. Cell-depletion and cytokine-neutralization assays are currently ongoing to define the mechanism of action of CpG ODN in these settings. To our knowledge, this is the first demonstration of CpG ODN-induced anti-ALL activity in a post-chemotherapy syngeneic model, suggesting that this agent has the potential to treat minimal residual disease and to reduce the incidence of relapse.

scholarly journals T-cell acute lymphoblastic leukemia

Hematology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 580-588 ◽  
Author(s):  
Elizabeth A. Raetz ◽  
David T. Teachey
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
De Novo ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Disease Response ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Relapsed Disease ◽  
Modern Genomic

Abstract T-cell acute lymphoblastic leukemia (T-ALL) is biologically distinct from its B lymphoblastic (B-ALL) counterpart and shows different kinetic patterns of disease response. Although very similar regimens are used to treat T-ALL and B-ALL, distinctions in response to different elements of therapy have been observed. Similar to B-ALL, the key prognostic determinant in T-ALL is minimal residual disease (MRD) response. Unlike B-ALL, other factors including age, white blood cell count at diagnosis, and genetics of the ALL blasts are not independently prognostic when MRD response is included. Recent insights into T-ALL biology, using modern genomic techniques, have identified a number of recurrent lesions that can be grouped into several targetable pathways, including Notch, Jak/Stat, PI3K/Akt/mTOR, and MAPK. With contemporary chemotherapy, outcomes for de novo T-ALL have steadily improved and now approach those observed in B-ALL, with approximately 85% 5-year event-free survival. Unfortunately, salvage has remained poor, with less than 25% event-free and overall survival rates for relapsed disease. Thus, current efforts are focused on preventing relapse by augmenting therapy for high-risk patients, sparing toxicity in favorable subsets and developing new approaches for the treatment of recurrent disease.

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