Immunophenotypic Pattern and Treatment Outcome after Completion of Induction Remission in Children with Acute Lymphoblastic Leukemia

2021 ◽  
Vol 8 (1) ◽  
pp. 59-64
Author(s):  
Farah Diba ◽  
Md. Anwarul Karim ◽  
Shahinoor Akter Soma ◽  
Indira Chowdhury ◽  
Showkat Mamun ◽  
...  

Background: Acute lymphoblastic leukemia (ALL) is presented with different immunophenotypic pattern. Objective: The purpose of the study was to evaluate the immunophenotypic pattern of ALL and also, to recognize the frequency of different ALL subtypes and treatment outcome after induction remission therapy. Methodology: This prospective study was conducted in the Department of Paediatric Hematology and Oncology at Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh from June 2017 to July 2018 for a period of one year. Newly diagnosed admitted cases of ALL aged 1 to 17.9 years were included. Immunophenotyping from aspirate marrow samples were done in a special hematology laboratory. Patients were monitored during induction remission period with physical examination and required investigations. Result: Among 87 analyzed patients, 81 patients (93.1%) were B-cell ALL and 6 patients (6.9%) were T-cell ALL. After completion of induction remission therapy 61 patients had undergone complete remission and among them B cell ALL were 56(69.1%) and T cell were 5(83.3%) (P=0.464). None of the patient had partial response or induction failure. Complication were developed in 53(60.91%) patients during induction therapy. Most common cause of death was septicemia (22/26). Death was more in patients who had total WBC count >50X109/L (p=0.017) and received regimen B (p=0.031). Conclusion: B cell ALL was more common and most of the patients had undergone complete remission after induction remission therapy. Journal of Current and Advance Medical Research, January 2021;8(1):59-64

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4550-4550 ◽  
Author(s):  
Yu Zhu ◽  
Guangsheng He ◽  
Kourong Miao ◽  
Huayuan Zhu ◽  
Weyi Shen ◽  
...  

Abstract The refractory/relapsed acute Lymphoblastic Leukemia (ALL) is featured by high therapy difficulty and poor prognosis. The CAG regiment used for 6 refractory/relapsed T-cell ALL patients achieved very high complete remission (CR) rate[1]. So how about CAG regiment for B-cell ALL? What is the situation after the expansion of the case number? Whether the reponse rate, adverse reactions would be improved, if use other anthracyclines, such as idarubicin, pirarubicin, instead of aclacinomycin for the refractory/relapsed ALL? So combining cytarabine and granulocyte-colony stimulating factor (G-CSF), based on idarubicin, aclacinomycin or pirarubicin respectively, the IAG, CAG or PAG were used for refractory/relapsed acute lymphoblasticleukemia, and the response rate and adverse reactions were elevated. It was to use the priming re-induction regiment for 43 cases of refractory/relapsed acute lymphoblastic leukemia (ALL) patients (Table 1). The clinical effects and adverse reactions were evaluated by non-random use of the IAG regiment (13 cases), CAG regiment (18 cases) and TAG regiment (12 cases). 20 cases of the priming regiments are the total complete remission (CR) ones (46.5%), 7 cases are the partial remission (PR) ones (9.6%), and 16 cases are the non-remission (NR) ones (37.2%), i.e., the overall response rate (ORR) is 62.8%. Among the patients in the IAG group, 7 cases are the complete remission (CR) ones (53.8%), 2 cases are the partial remission (PR) ones (15.4%), and the overall response rate (ORR) is 69.2%. In the CAG group, there are 8 CR cases (44.4%), 3 PR cases (16.6%) with an ORR of 61%. And in the TAG group, there are 5 CR cases (41.7%), 2 PR cases (16.6%) with an ORR of 58.3%. No statistical difference is found by the comparison of ORRs among the three groups (P=0.837). There were no marked statistical difference found between the elderly group or not (60.0% vs 54.3%; P=0.272), hyperleukocytic group or not (50% vs 64.9%; P=0.808), the T cell ALL and B cell ALL (68.4% vs 54.1%; P=0.542). Current adverse reactions (Table 2), including bone marrow suppression, infection, gastrointestinal reaction and liver function impairment are tolerable after anti-infection, blood cell increase and transfusion therapy. No statistical difference is found when compared in pairs or simultaneously for the three groups. Preliminary results show that the priming chemotherapy regimens based on small doses of anthracyclines are characterized by high remission rate, good tolerance, minor non-hematological toxic and side-effects, and definitive curative effect in the treatment of refractory/relapsed ALL patients. No statistical difference exists for the curative effects, adverse reactions, and prognosis of different anthracyclines. Table 1. Clinical Data of Patients Clinical index CAG (n=18) IAG (n=13) TAG (n=12) P Median age (year, range) 26 (18-58) 24 (14-78) 56 (20-85) 0.008* Median number of leukocyte before the treatment (range) 3.7 (0.61-44) 6.1 (0.34-65.7) 2.18 (0.66-10.5) 0.243* Gender (case) 0.525** Male (n=31) 12 11 8 Female (n=12) 6 2 4 Immunophenotype 0.591** T cell (n=20) 7 6 7 B cell (n=23) 11 7 5 Note: *the kruskal-wallis test is adopted. Table 2. Adverse Reactions for the Three Regiments Adverse Reaction CAG (n=18) IAG (n=13) TAG (n=12) P Hematological toxicity 1.000 Neutropenia of Level IIII-IV 18 13 12 Anemia of Level IIII-IV 18 13 12 Thrombocytopenia of Level IIII-IV 18 13 12 Gastrointestinal reaction 0.486 Level I-II 3 2 0 Level III-IV 0 0 0 Liver function impairment 0.222 Level I-II 5 1 2 Level III-IV 1 0 0 Renal function impairment Level I-II 0 0 0 Level III-IV 0 0 0 Infection 0.861 Level I-II 9 6 5 Level III-IV 0 1 0 Disclosures No relevant conflicts of interest to declare.


2021 ◽  
pp. 106002802098841
Author(s):  
Zachery Halford ◽  
Carli Coalter ◽  
Vanessa Gresham ◽  
Tabitha Brown

Objective: To assess the current literature for blinatumomab in the treatment of adult and pediatric B-cell acute lymphoblastic leukemia (ALL). Data Sources: We conducted a PubMed (inception to December 11, 2020) and ClinicalTrials.gov systematic literature search using the following terms: blinatumomab, Blincyto, lymphoblastic leukemia, and bispecific T-cell engager. Study Selection and Data Extraction: All relevant published articles, package inserts, and meeting abstracts evaluating the use of blinatumomab in ALL were considered for inclusion. Data Synthesis: Blinatumomab, a first-in-class bispecific T-cell engager monoclonal antibody, facilitates cytotoxic T-cell activation and subsequent eradication of CD19-positive B cells. The confirmatory phase III TOWER trial demonstrated superior overall survival (OS) with blinatumomab compared with standard chemotherapy (7.7 months vs 4.0 months) in relapsed and refractory (R/R) B-cell ALL. In the phase II BLAST trial, blinatumomab achieved a complete measurable residual disease (MRD) response in 78% of evaluable patients, with a median OS of 36.5 months. Potentially life-threatening cytokine release syndrome and neurotoxicity occurred in approximately 15% and 65% of patients, respectively. Relevance to Patient Care and Clinical Practice: Following initial Food and Drug Administration approval in 2014, blinatumomab gained expanded approval in pediatric patients and in Philadelphia chromosome-positive R/R ALL. In 2018, blinatumomab became the first and only drug approved for the treatment of persistent MRD in any hematologic malignancy. Emerging data demonstrate promising efficacy with blinatumomab in specific ALL settings, including frontline therapy, as a bridge to transplantation, and in “chemotherapy-free” combination regimens. Conclusions: Blinatumomab provides a paradigm-shifting treatment option; however, many questions surrounding optimal patient selection, sequencing, and cost-effectiveness remain.


2020 ◽  
Author(s):  
HUI ZHANG ◽  
Chuang Jiang ◽  
Haiyan Liu ◽  
Wenge Hao ◽  
Pengfei Wang ◽  
...  

Abstract Background Refractory/relapsed acute lymphoblastic leukemia (RR-ALL) remains to be a leading cause of treatment failure and subsequent death. Forkhead box O1 (FOXO1) belongs to the forkhead family of transcription factors, its specific role in RR-ALL has not yet been determined in B-cell ALL (B-ALL). The purpose of this study was to investigate the expression and prognostic value in ALL. Methods RNA sequencing was applied to an ALL case with induction failure to identify the causal events. The transcription activity was examined with luciferase reporter assay. FOXO1 mRNA expression level was examined using real-time quantitative PCR. Association analysis was performed to correlate FOXO1 transcription with childhood B-ALL prognosis and relapse. Results In this ALL case with induction failure, we successfully identified a novel MEIS1-FOXO1 fusion gene. The transcription activity of MEIS1-FOXO1 was significantly abolished as compared to wild-type FOXO1. Low FOXO1 expression level was strongly associate with unfavorable subtype, MRD positivity and relapse. Conclusions FOXO1 loss of function associates with ALL high-risk stratification and relapse, which might be due to drug resistance.


1988 ◽  
Vol 6 (1) ◽  
pp. 56-61 ◽  
Author(s):  
C H Pui ◽  
D L Williams ◽  
P K Roberson ◽  
S C Raimondi ◽  
F G Behm ◽  
...  

To correlate leukemic cell karyotype with immunophenotype, we studied 364 children with acute lymphoblastic leukemia (ALL). A prognostically favorable cytogenetic feature, hyperdiploidy greater than 50 chromosomes, was found in 33% of cases classified as common ALL antigen positive (CALLA+) early pre-B (common) ALL, in contrast to 18% of pre-B cases (P = .012), 5% of T cell cases (P less than .001), and none of the B cell cases (P less than .001) or cases of CALLA negative (CALLA-) early pre-B ALL (P = .002). The frequency of translocations, an adverse cytogenetic feature, was significantly lower in CALLA+ early pre-B ALL cases (35%) than in B cell (100%; P less than .0001), pre-B (59%; P less than .001), or CALLA- early pre-B (62%; P = .016) cases. Thus, patterns of chromosomal change differ widely among the major immunophenotypic groups of ALL and may account for reported differences in responsiveness to treatment.


2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Le Li ◽  
Ying Wang

AbstractAcute lymphoblastic leukemia (ALL) is a hematologic malignancy arising from precursors of the lymphoid lineage. Conventional cytotoxic chemotherapies have resulted in high cure rates of up to 90% in pediatric ALL, but the outcomes for adult patients remain suboptimal with 5-year survival rates of only 30%-40%. Current immunotherapies exploit the performance of antibodies through several different mechanisms, including naked antibodies, antibodies linked to cytotoxic agents, and T-cell re-directing antibodies. Compared with chemotherapy, the application of an antibody–drug conjugates (ADC) called inotuzumab ozogamicin in relapsed or refractory (R/R) CD22+. ALL resulted in a complete remission (CR) rate of 81% and an overall median survival of 7.7 months with reduced toxicity. Similarly, blinatumomab, the first FDA-approved bispecific antibody (BsAb), produced a 44% complete response rate and an overall median survival of 7.7 months in a widely treated ALL population. In addition, approximately 80% of patients getting complete remission with evidence of minimal residual disease (MRD) achieved a complete MRD response with the use of blinatumomab. These results highlight the great promise of antibody-based therapy for ALL. How to reasonably determine the place of antibody drugs in the treatment of ALL remains a major problem to be solved for ongoing and future researches. Meanwhile the combination of antibody-based therapy with traditional standard of care (SOC) chemotherapy, chimeric antigen receptor (CAR) T-cell therapy and HSCT is also a challenge. Here, we will review some important milestones of antibody-based therapies, including combinational strategies, and antibodies under clinical development for ALL.


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