Abstract 2902: Obinutuzumab (GA101) significantly increases overall survival against CD20+ rituximab-sensitive and -resistant Burkitt (BL) and acute lymphoblastic leukemia (B-ALL): potential targeted therapy in patients with high risk BL and pre-B-ALL

2014 ◽  
Author(s):  
Aradhana A. Tiwari ◽  
Janet Ayello ◽  
Carmella van de Ven ◽  
Matthew J. Barth ◽  
Mitchell S. Cairo
Keyword(s):  
Overall Survival ◽  
Targeted Therapy ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Lymphoblastic Leukemia

scholarly journals BCR/ABL1-Like Acute Lymphoblastic Leukemia: From Diagnostic Approaches to Molecularly Targeted Therapy

2021 ◽  
pp. 1-9
Author(s):  
Anna Płotka ◽  
Krzysztof Lewandowski
Keyword(s):  
Flow Cytometry ◽  
Targeted Therapy ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Genetic Alterations ◽  
Diagnostic Analysis ◽  
Cell Precursor ◽  
Molecularly Targeted Therapy ◽  
Diagnostic Approaches

<b><i>Background:</i></b> <i>BCR/ABL1</i>-like acute lymphoblastic leukemia is a newly recognized high-risk subtype of ALL, characterized by the presence of genetic alterations activating kinase and cytokine receptor signaling. This subtype is associated with inferior outcomes, compared to other B-cell precursor ALL. <b><i>Summary:</i></b> The recognition of <i>BCR/ABL1</i>-like ALL is challenging due to the complexity of underlying genetic alterations. Rearrangements of <i>CRLF2</i> are the most frequent alteration in <i>BCR/ABL1</i>-like ALL and can be identified by flow cytometry. The identification of <i>BCR/ABL1</i>-like ALL can be achieved with stepwise algorithms or broad-based testing. The main goal of the diagnostic analysis is to detect the underlying genetic alterations, which are critical for the diagnosis and targeted therapy. <b><i>Key Messages:</i></b> The aim of the manuscript is to review the available data on <i>BCR/ABL1</i>-like ALL characteristics, diagnostic algorithms, and novel, molecularly targeted therapeutic options.

scholarly journals Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia

Blood ◽  
2015 ◽  
Vol 125 (16) ◽  
pp. 2486-2496 ◽  
Author(s):  
Nathalie Dhédin ◽  
Anne Huynh ◽  
Sébastien Maury ◽  
Reza Tabrizi ◽  
Kheira Beldjord ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Complete Remission ◽  
Lymphoblastic Leukemia ◽  
Adult Patients ◽  
Key Points ◽  
First Complete Remission

Key Points SCT in first complete remission is associated with 69.5% 3-year overall survival in high-risk ALL adult patients treated with intensified pediatric-like protocol. Poor early MRD response is a powerful tool to select patients who may benefit from SCT in first complete remission.

Prognostic Impact of Different High Risk Features in Allogeneic Stem Cell Transplantation for Acute Lymphoblastic Leukemia in First Complete Remission.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2303-2303
Author(s):  
Theis Terwey ◽  
Philipp Hemmati ◽  
Gero Massenkeil ◽  
Bernd Dörken ◽  
Renate Arnold
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Complete Remission ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
Prognostic Impact ◽  
Very High ◽  
First Complete Remission

Abstract Abstract 2303 Poster Board II-280 Introduction: In acute lymphoblastic leukemia (ALL) specific clinical and biological features confer high relapse risk and inferior overall survival (OS) after treatment with conventional chemotherapy alone. The differential prognostic impact of these high risk features after treatment with allogeneic hematopoietic stem cell transplantation (HCT) has not been well studied. Patients and Methods: 79 adult ALL patients in first complete remission (CR) received allogeneic HCT at our center between 1995 and 2008. All patients were high or very high risk according to German Multicenter Study Group for Adult ALL (GMALL) criteria. Median age was 36 years (range: 17-68). Patients received high-dose conditioning consisting of 12 Gy total body irradiation ± etoposide ± cyclophosphamide (n=69, 87%) or reduced intensity conditioning (RIC) consisting of fludarabine/busulfan/ATG (n=10, 13%) and HSCT from related (n=34, 43%) or unrelated (n=45, 57%) donors. Bone marrow (n=17, 22%) or peripheral blood stem cells (n=62, 78%) were given. Graft-versus-host-disease prophylaxis was CSA/MTX for high-dose conditioning or CSA/MMF for RIC. Results: Patients were classified as high risk or very high risk due to Philadelphia chromosome-positive disease (Ph+) (n=30, 38%), leukocytosis>30/nl at diagnosis in B-ALL (n=25, 23%), late response to induction therapy in B-ALL (>week 4) (n=13, 16%), early or mature T-ALL (n=13, 16%), pro-B-ALL/t(4;11) (n=8, 10%), persistence of minimal residual disease (MRD) (>week 16) (n=8, 10%) or complex aberrant karyotype (n=6, 8%). 57 patients (72%) presented with one high risk feature, whereas 20 patients (25%) and 2 patients (3%) presented with two or three features, respectively. Currently, after a median follow-up of 56 months (7-169) 49 patients (62%) remain alive. Projected OS of the whole cohort at 1, 2 and 5 years was 78%, 70% and 55% and leukemia-free survival was 77%, 66% and 55%. Cumulative incidence of non-relapse mortality (NRM) and relapse mortality (RM) at 5 years was 23% and 18%, respectively. In multivariate Cox regression analysis, a non-significant trend for inferior OS was seen for patients with early or mature T-ALL (hazard ratio (HR): 2.03 (95%CI: 0.92-4.52), p=0.082), whereas no differential effect on OS, NRM or RM was seen for any other high risk feature (Table 1). In additional analyses, inferior OS (HR 1.81 (95%CI: 1.02-3.29), p=0.043) and increased RM (HR 2.17 (95%CI 1.16-4.05), p=0.015) was observed for patients with more than one high risk feature. Conclusions: In summary, this single center study on allogeneic HCT in high risk ALL found a negative prognostic trend for early or mature T cell immunophenotype. No differential prognostic impact on OS, NRM and RM was seen for other high risk features as defined by GMALL criteria, however this conclusion is limited by the low patient number in some of the subgroups. Overall survival for the whole cohort was 55% at 5 years, with inferior OS and higher RM being observed in patients with more than one high risk feature. Disclosures: No relevant conflicts of interest to declare.

Fludarabine and Targeted Busulfan Is Safe and Effective Conditioning Before Hematopoietic Stem Cell Transplantation in Adult Patients with Acute Lymphoblastic Leukemia in First Remission

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 891-891
Author(s):  
Ghada M Kunter ◽  
Janelle Perkins ◽  
Lia Perez ◽  
Joseph Pidala ◽  
Teresa Field ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Older Patients ◽  
Lymphoblastic Leukemia ◽  
Adult Patients ◽  
Unrelated Donor ◽  
Risk Of Relapse

Abstract Abstract 891 Background: Chemotherapy for adult patients with acute lymphoblastic leukemia (ALL) is associated with high risk of relapse and an overall 2-year survival of 40 to 50%. Allogenic hematopoietic cell transplantation (HCT) in first complete remission (CR1) decreases the risk of relapse and improves outcome over chemotherapy for adult ALL pts, but non-relapse mortality (NRM) is a drawback especially in older patients. In the MRC UKALL XII/ECOG E2993 trial, the 2 year NRM of patient with an allogenic donor was 19% in standard risk patients and 36% in patients over 35 years or those with high risk leukemia. We tested safety and efficacy of a non-irradiation regimen consisting of fludarabine (FLU) and pharmacokinetically-targeted busulfan (BU) for adults with ALL in CR1. Methods: We report the outcomes of 42 consecutive patients with ALL in CR1, 21 positive for the Philadelphia chromosome (Ph+). All patients were in complete morphologic remission before HCT. The median age was 33 (range: 19–62) years, 19 were females and 23 males. Median time from diagnosis to HCT was 6 (range: 3–45) months. Thirty patients were treated to achieve an average daily BU area under the curve (AUC) of 5300 microM-min for 4 days, and 12 patients were treated on a clinical trial to achieve an average daily BU AUC of 6000 to 7500 microM-min for 4 days. Graft-versus-host disease (GVHD) prophylaxis was tacrolimus in all patients, in combination with either methotrexate (88%) or sirolimus (12%). Twenty (48%) patients received grafts from matched related donor, 16 (38%) from matched unrelated donor and 6 (14%) from a mismatched unrelated donor. The median follow-up of surviving patients is 2 (median 1.2–4.3) years. Results: Overall survival at 2 years was 66% (95% CI 52%–81%) for all patients, 70% (95% CI 51%–88%) for Ph- and 63% (95% CI 41%–85%) for Ph+ patients (p=0.59). Overall survival did not differ by age, above or below 35 years (p=0.39). Disease-free survival at 2 years was 59% (95% CI 44%–74%) for all patients, 65% (95% CI 45%–84%) for Ph- and 52% (95% CI 28%–74%) for Ph+ pts (p=0.49). The cumulative incidence of relapse at 2-year was 27% (95% CI 16%–45%). The cumulative incidence of acute GVHD grades II–IV was 64% (95% CI 51%–81%) and grades III–IV GVHD was 25% (95% CI 13%–47%). The cumulative incidence of non-relapse mortality (NRM) was 5% (95% CI 1%–18%) at 100 days and 14% (95% CI 7%–30%) at 2 years. Conclusions: These data show that FLU with myeloablative doses of PK targeted BU is an effective alternative to total body irradiation and etoposide or cyclophosphamide for conditioning patients with ALL without an increased risk of relapse after HCT. The low NRM allows to safely delivering myeloablative chemotherapy and allogenic HCT to older patients. This HCT regimen should be prospectively compared to chemotherapy for adult patients with ALL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Early T-Cell Precursor Acute Lymphoblastic Leukemia (ETP-ALL) Is a High-Risk Subtype in Adults

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1418-1418
Author(s):  
Nitin Jain ◽  
Audrey Lamb ◽  
Susan M. O'Brien ◽  
Farhad Ravandi ◽  
Marina Konopleva ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
High Risk ◽  
Research Funding ◽  
Who Classification ◽  
Lymphoblastic Leukemia ◽  
Cell Precursor

Abstract Background: Early T-cell precursor (ETP) acute lymphoblastic leukemia/lymphoma (ALL) is a recently recognized high-risk T-ALL subgroup. The optimal therapeutic approaches to adult patients with ETP-ALL are poorly characterized. In this study, we compared the outcomes of adults with ETP-ALL who received treatment on frontline regimens to those of patients with other T-ALL immunophenotypic subtypes. Methods: Patients with newly-diagnosed T-ALL who received frontline chemotherapy between the years 2000 and 2014 at The University of Texas MD Anderson Cancer Center (MDACC) were identified and immunophenotypically categorized into early, thymic, and mature per the European Group for the Immunologic Classification of Leukemia (EGIL)/WHO classification. Patients with ETP-ALL were identified on the basis of the following immunophenotype: CD1a(-), CD8(-), CD5(-/dim), and positivity for one or more stem cell or myeloid antigens. Patients received frontline treatment with the following chemotherapy regimens: hyper-CVAD alone (n=43), hyper-CVAD + nelarabine (n=44) or augmented BFM regimen (n=24). Results: A total of 111 patients with T-ALL with adequate immunophenotype data were identified. There was no difference in the outcomes of patients based on the EGIL/WHO subtypes (Fig 1). A total of 19 patients (17%) had ETP-ALL. The complete remission rate (CR)/CR with incomplete platelet recovery (CRp) rate in patients with ETP-ALL was significantly lower than that of non-ETP-ALL patients (73% vs. 91%; p=0.03). The median overall survival for patients with ETP-ALL was 20 months vs. not reached for the non-ETP-ALL patients (p = 0.008) (Fig 2). ETP-ALL remained a high-risk subgroup within the WHO 'Early' group (Fig 3). A subset of patients with early T-ALL had an immunophenotype that resembled that of ETP-ALL except for having ≥75% CD5 expression (ETP+CD5). The OS of patients with ETP+CD5 (n=19) was similar to that of non-ETP-ALL patients and differed from that of ETP-ALL patients (p=0.059). By univariate analysis, the following variables were significant for survival: age, WBC count (<50 vs. ≥50 x109 /L), platelet count (<100 vs. ≥100 x109 /L), LDH (<600 vs. ≥600 IU/L) and ETP-ALL (Table 1). By multivariate analysis, only age (HR: 2.862; 95%CI: 1.140-7.183; p=0.025) and ETP-ALL (HR: 2.275; 95%CI: 1.117-4.631; p=0.023) were significant. Conclusions: ETP-ALL represents a high-risk disease subtype of adult ALL. Allogeneic stem cell transplant in CR1 should be considered. Novel treatment strategies are needed to improve treatment outcomes in this T-ALL subset. Table 1. Univariate and multivariate analysis for survival Parameter Survival UVA MVA P P HR 95%CI Age ≥60 0.013 0.025 2.862 1.140-7.183 Gender 0.24 - - - Diagnosis (ALL vs. LBL) 0.13 - - - WBC < 50.0 (x 109 /L) 0.009 - - - Hemoglobin <10 (g/dL) 0.36 - - - Platelet <100 (x 109 /L) 0.036 - - - LDH <600 (IU/L) 0.045 - - - CNS involvement at Dx 0.18 - - - WHO classification (early, thymic, mature) 0.101 - - - ETP-ALL 0.008 0.023 2.275 1.117-4.631 Treatment received 0.43 - - - Figure 1. Overall survival of patients with T-ALL (N=111) categorized as Early, Thymic and Mature per EGIL/WHO Classification Figure 1. Overall survival of patients with T-ALL (N=111) categorized as Early, Thymic and Mature per EGIL/WHO Classification Figure 2. Overall survival of patients with ETP-ALL (N=19) compared to non-ETP ALL (N=92) Figure 2. Overall survival of patients with ETP-ALL (N=19) compared to non-ETP ALL (N=92) Figure 3. Overall survival of patients with WHO 'early' subcategorized as ETP vs. non-ETP, WHO 'thymic', and WHO 'mature' (N=111) Figure 3. Overall survival of patients with WHO 'early' subcategorized as ETP vs. non-ETP, WHO 'thymic', and WHO 'mature' (N=111) Disclosures Konopleva: Novartis: Research Funding; AbbVie: Research Funding; Stemline: Research Funding; Calithera: Research Funding; Threshold: Research Funding. Cortes:Astellas: Consultancy, Research Funding; BerGenBio AS: Research Funding; Novartis: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Teva: Research Funding; Ambit: Consultancy, Research Funding; Arog: Research Funding; Celator: Research Funding; Jenssen: Consultancy.

scholarly journals Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group

Blood ◽  
2011 ◽  
Vol 118 (2) ◽  
pp. 243-251 ◽  
Author(s):  
Yousif Matloub ◽  
Bruce C. Bostrom ◽  
Stephen P. Hunger ◽  
Linda C. Stork ◽  
Anne Angiolillo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Oncology Group ◽  
Event Free Survival ◽  
Free Survival ◽  
Cancer Group ◽  
Leucovorin Rescue ◽  
Standard Risk

Abstract Children's Cancer Group-1991 selected 2 components from the Children's Cancer Group studies shown to be effective in high-risk acute lymphoblastic leukemia and examined them in children with National Cancer Institute standard-risk acute B-precursor lymphoblastic leukemia. These were (1) vincristine and escalating IV methotrexate (MTX) without leucovorin rescue during the interim maintenance (IM) phases and (2) addition of a second delayed intensification (DI) phase. Eligible patients (n = 2078) were randomly assigned to regimens containing either oral (PO) MTX, PO mercaptopurine, dexamethasone, and vincristine or IV MTX during IM phases, and regimens with either single DI or double DI. Five-year event-free survival (EFS) and overall survival for patients on the PO MTX arms were 88.7% ± 1.4% and 96% ± 0.9% versus 92.6% ± 1.2% and 96.5% ± 0.8% for those on the IV MTX arms (P = .009, P = .66). Five-year EFS and overall survival for patients who received single DI were 90.9% ± 1.3% and 97.1% ± 0.8% versus 90.5% ± 1.3% and 95.4% ± 3.8% for those who received double DI (P = .71, P = .12). No advantage was found for a second DI; however, replacement of PO MTX, PO mercaptopurine, vincristine, and dexamethasone during IM with vincristine and escalating IV MTX improved EFS.

Outcome and Toxicities of Modified Augmented Berlin-Frankfurt-Muenster (ABFM) Therapy Used in the Treatment of Acute Lymphoblastic Leukemia in Adolescent and Young Adult Patients, Single Center Experience From Saudi Arabia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3569-3569
Author(s):  
Suhaib Radi ◽  
Anas Merdad ◽  
Mona Al-Dabbagh ◽  
Ahmed Almohanad Absi ◽  
Ahmad Alsaeed ◽  
...  
Keyword(s):  
Overall Survival ◽  
Saudi Arabia ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
High Risk ◽  
Complete Remission ◽  
Fungal Infections ◽  
Lymphoblastic Leukemia ◽  
Inclusion Criteria

Abstract Abstract 3569 Introduction: Acute lymphoblastic leukemia (ALL) is a neoplasm of precursor lymphoid cells known as lymphoblasts. ALL is the most common cancer in children. The prognosis among Adolescents and young adults (AYA) is intermediate between children, who have a very good prognosis with a 5-year survival rate of 80%, and adults, who have a worse prognosis with an overall survival of about 30–50%. We found no studies in Saudi Arabia which assessed the use of a Berlin-Frankfurt-Muenster (BFM) to treat patients in the AYA group. The purpose of this study is to measure the outcome and toxicities of the BFM protocol used in treatment of ALL patients in the AYA population seeking treatment at Princess Noorah Oncology Center (PNOC), at the National Guard Hospital, Jeddah, Saudi Arabia. PNOC is a tertiary referral center for the Western region of the Kingdom of Saudi Arabia. Patients referred between the ages of 14 to 25 were treated according to an augmented modified version of the Berlin-Frankfurt-Muenster (BFM) protocol. Patients' treatments were based on risk factor stratification. High risk category was identified based on the presence of one of following factors: phenotype of the leukemia (i.e. T-cell ALL is considered high risk), lack of response to therapy on day 29 of induction, cytogenetics, presence of extramedullary disease e.g. testicular or CNS disease and whether they have received steroid treatment prior to the first diagnostic marrow. High risk group was treated with doubled blocks of interim maintenance, delayed intensification the first of delayed intensification blocks included a high dose methotrexate at the dose of 5g/m2 which was first started at our center in 2008. Methodology: This study is a retrospective chart review. Patients who met the inclusion criteria within the last five years were included. The inclusion criteria were those with confirmed ALL (excluding mature B cell phenotype) aged between 14 to 25 years, and were treated with the Modified Augmented Berlin-Frankfurt-Muenster (ABFM) therapy protocol. 45 patients were indentified who fulfilled the above criteria 4 were excluded due to the lack of data and loss to follow up. Data were analyzed using SPSS version 19. Results: The mean age of 41 patients treated was 16.4 years (range; 14 – 25 years). Of 41 patients treated, 23 (56%) were males. Only one patient (2%) had CNS involvement at presentation. B cell ALL compromised 61% of the patients while 39% were T cell ALL. All 41 (100%) patients achieved complete remission after induction therapy however two patients (5%) required extended induction to achieve a complete remission status. Five (12.2%) patients relapsed at a median follow up of 30 months. Two (4.9%) patients died while in complete remission from treatment related causes. The probability of Overall Survival (OS) is 95.1% and 87.8% at 2 and 3 years, respectively. The probability of Event-free Survival (EFS) of our 41 patients is 90.2% and 82.9% at 2 and 3 years respectively. Thirty three (81%) patients developed febrile neutropenia with a total of 50 documented episodes. Thirty two (64%) of the febrile neutropenia episodes occurred during induction and re-intensification phases those two blocks were associated with a statistically significant increased risk of neutropenia (P < 0.001)compared to other blocks. Five (12%) of patients developed fungal infections there is one patient who developed two separate episodes of fungal infection. Four fungal infection episodes occurred during induction and re-intensification phases which constituted the highest risk phases for the development of fungal infections. In 38% of febrile neutropenic episodes an infectious agent was identified in 8% of episodes the isolate was a fungus. Eight patients (20%) developed Venous Thromboembolism (VTE) with a total of 9 episodes. Discussion & Conclusion: In our study population the OS & EFS were comparable to other reported groups despite the relatively increased numbers of T cell ALL (39%) patients compared to the reported average of 15–25%. The reported incidence of VTE is similar to the incidence reported by other groups while the incidence of fungal infections is relatively more than we would have expected. Complete remissions, survival, relapse and death rates are comparable to international studies. However new measures are required to lower the increased rates of fungal infections & VTE for future patients. Disclosures: No relevant conflicts of interest to declare.

Six Months of Maintenance Chemotherapy After Intensified Treatment for Acute Lymphoblastic Leukemia of Childhood

2000 ◽  
Vol 18 (7) ◽  
pp. 1508-1516 ◽  
Author(s):  
Yasunori Toyoda ◽  
Atsushi Manabe ◽  
Masahiro Tsuchida ◽  
Ryohji Hanada ◽  
Koichiro Ikuta ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Remission Induction ◽  
Maintenance Chemotherapy ◽  
Risk Patients ◽  
Standard Risk ◽  
Overall Survival Rates

PURPOSE: We postulated that intensification of chemotherapy immediately after remission induction might reduce the leukemic cell burden sufficiently to allow an abbreviated period of antimetabolite therapy. PATIENTS AND METHODS: Three hundred forty-seven children (ages 1 to 15 years) with previously untreated acute lymphoblastic leukemia (ALL) were enrolled onto the Tokyo L92–13 study, which excluded patients with mature B-cell ALL and patients less than 1 year old. One hundred twenty-four patients were classified as standard risk, 122 as high risk, and 101 as extremely high risk, according to age, peripheral-blood leukocyte count, selected genetic abnormalities, and immunophenotype. All subjects received four drugs for remission induction, followed by a risk-directed multidrug intensification phase and therapy for presymptomatic leukemia in the CNS. Maintenance chemotherapy with oral mercaptopurine and methotrexate was administered for 6 months, with all treatment stopped by 1 year after diagnosis. RESULTS: The mean (± SD) event-free survival (EFS) and overall survival rates for all patients were 59.5% ± 3.4% and 81.5% ± 2.2%, respectively, at 5.5 years after diagnosis. EFS rates by risk category were similar (60.2% ± 6.0% for standard risk, 57.7% ± 5.6% for high risk, and 62.5% ± 5.7% for extremely high risk), whereas overall survival rates differed significantly (91.2% ± 2.7%, 80.0% ± 4.1%, and 72.1% ± 4.5%, respectively, P < .0001 by the log-rank test). There were 107 relapses. Eighty-five (79.4%) of these 107 patients achieved second complete remissions, with subsequent EFS rates of 61.5% ± 7.9% (standard risk), 42.6% ± 8.1% (high risk), and 9.6% ± 6.4% (extremely high risk). Of the five risk factors analyzed, only the response to prednisolone monotherapy among extremely high-risk patients proved important. CONCLUSION: Early treatment intensification did not compensate for a truncated phase of maintenance chemotherapy in children with standard- or high-risk ALL. However, 6 months of antimetabolite treatment seemed adequate for extremely high-risk patients who were good responders to prednisolone and received intensified chemotherapy that included high-dose cytarabine early in the clinical course.

scholarly journals Precision medicine in acute lymphoblastic leukemia

2020 ◽  
Vol 14 (6) ◽  
pp. 689-700 ◽  
Author(s):  
Ching-Hon Pui
Keyword(s):  
Targeted Therapy ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
High Risk ◽  
Cellular Therapy ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Dose Intensity ◽  
Remission Induction ◽  
T Cell Therapy

AbstractThe cure rate of childhood acute lymphoblastic leukemia (ALL) has exceeded 90% in some contemporary clinical trials. However, the dose intensity of conventional chemotherapy has been pushed to its limit. Further improvement in outcome will need to rely more heavily on molecular therapeutic as well as immuno-and cellular-therapy approaches together with precise risk stratification. Children with ETV6-RUNX1 or hyperdiploid > 50 ALL who achieve negative minimal residual disease during early remission induction are suitable candidates for reduction in treatment. Patients with Philadelphia chromosome (Ph)-positive or Ph-like ALL with ABL-class fusion should be treated with dasatinib. BH3 profiling and other preclinical methods have identified several high-risk subtypes, such as hypodiplod, early T-cell precursor, immature T-cell, KMT2A-rearranged, Ph-positive and TCF-HLF-positive ALL, that may respond to BCL-2 inhibitor venetoclax. There are other fusions or mutations that may serve as putative targets, but effective targeted therapy has yet to be established. For other high-risk patients or poor early treatment responders who do not have targetable genetic lesions, current approaches that offer hope include blinatumomab, inotuzumab and CAR-T cell therapy for B-ALL, and daratumumab and nelarabine for T-ALL. With the expanding therapeutic armamentarium, we should start focus on rational combinations of targeted therapy with non-overlapping toxicities.

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