Hyper-CVAD and rituximab therapy in HIV-Negative Burkitt (BL) or Burkitt-like (BLL) leukemia/lymphoma and mature B-cell acute lymphocytic leukemia (B-ALL)

PURPOSE: To evaluate the efficacy and toxicity of Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone), a dose-intensive regimen, in adult acute lymphocytic leukemia (ALL). PATIENTS AND METHODS: Adults with newly diagnosed ALL referred since 1992 were entered onto the study; treatment was initiated in 204 patients between 1992 and January 1998. No exclusions were made because of older age, poor performance status, organ dysfunction, or active infection. Median age was 39.5 years; 37% were at least 50 years old. Mature B-cell disease (Burkitt type) was present in 9%, T-cell disease in 17%. Leukocytosis of more than 30 × 109/L was found in 26%, Philadelphia chromosome–positive disease in 16% (20% of patients with assessable metaphases), CNS leukemia at the time of diagnosis in 7%, and a mediastinal mass in 7%. Treatment consisted of four cycles of Hyper-CVAD alternating with four cycles of high-dose methotrexate (MTX) and cytarabine therapy, together with intrathecal CNS prophylaxis and supportive care with antibiotic prophylaxis and granulocyte colony-stimulating factor therapy. Maintenance in patients with nonmature B-cell ALL included 2 years of treatment with mercaptopurine, MTX, vincristine, and prednisone (POMP). RESULTS: Overall, 185 patients (91%) achieved complete remission (CR) and 12 (6%) died during induction therapy. Estimated 5-year survival and 5-year CR rates were 39% and 38%, respectively. The incidence of CNS relapse was low (4%). Compared with 222 patients treated with vincristine, doxorubicin, and dexamethasone (VAD) regimens, our patients had a better CR rate (91% v 75%, P < .01) and CR rate after one course (74% v 55%, P < .01) and better survival (P < .01), and a smaller percentage had more than 5% day 14 blasts (34% v 48%, P = .01). Previous prognostic models remained predictive for outcome with Hyper-CVAD therapy. CONCLUSION: Hyper-CVAD therapy is superior to our previous regimens and should be compared with established regimens in adult ALL.

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B cell acute lymphocytic leukemia in adults. Clinical, morphologic, and immunologic findings.

Journal of Clinical Oncology ◽

10.1200/jco.1986.4.5.737 ◽

1986 ◽

Vol 4 (5) ◽

pp. 737-743 ◽

Cited By ~ 31

Author(s):

P S Gill ◽

P R Meyer ◽

Z Pavlova ◽

A M Levine

Keyword(s):

B Cell ◽

Acute Lymphocytic Leukemia ◽

Disease Free Survival ◽

Lymphocytic Leukemia ◽

Cell Phenotype ◽

History Of ◽

Acquired Immunodeficiency ◽

Immunologic Marker ◽

Immunodeficiency Syndrome

Acute lymphocytic leukemia (ALL) is a heterogeneous group of disorders, clinically, immunologically, and pathologically. ALL of a B cell phenotype (B-ALL) is the least common. We have studied ten adult patients with B-ALL, none of whom had a tumor mass. The median age was 56 years (range, 30 to 90). A history of an altered immune state was noted in four cases: a distant history of Hashimoto's thyroiditis in one, pregnancy in one, and acquired immunodeficiency syndrome in two. Two patients presented with CNS involvement, and in two additional patients CNS leukemia developed during the course of disease. By the French-American-British (FAB) classification system, L3 leukemic morphology was present in nine, whereas L2 was present in one. Circulating leukemic blasts varied from less than 500/dL to greater than 15,000/dL. Eight patients were thrombocytopenic, and eight were anemic at presentation. Immunologic marker studies on leukemic blasts revealed monoclonal kappa light chain marking in nine and monoclonal lambda in one. Following chemotherapy, complete remission was achieved in three patients, two of whom experienced relapse within 9 months. The median survival for the group was 3 months, and only one patient experienced long-term, disease-free survival. We conclude that B-ALL in the adult presents with the classic L3 morphologic picture in the majority and is associated with extremely short survival.

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Comparative Analysis of Systemic and Tumor Microenvironment Proteomes From Children With B-Cell Acute Lymphocytic Leukemia at Diagnosis and After Induction Treatment

Frontiers in Oncology ◽

10.3389/fonc.2020.550213 ◽

2020 ◽

Vol 10 ◽

Author(s):

Geise Ellen Broto ◽

Stephany Corrêa ◽

Fausto Celso Trigo ◽

Everton Cruz dos Santos ◽

Fernanda Tomiotto-Pelissier ◽

...

Keyword(s):

Transcription Factor ◽

B Cell ◽

Acute Lymphocytic Leukemia ◽

Lymphocytic Leukemia ◽

Induction Treatment ◽

Induction Phase ◽

Label Free ◽

Childhood Diseases ◽

Coagulation Proteins ◽

Ifn Γ

Among the childhood diseases, B-cell acute lymphocytic leukemia (B-ALL) is the most frequent type of cancer. Despite recent advances concerning disease treatment, cytotoxic chemotherapy remains the first line of treatment in several countries, and the modifications induced by such drugs in the organism are still poorly understood. In this context, the present study provided a comparative high-throughput proteomic analysis of the cumulative changes induced by chemotherapeutic drugs used in the induction phase of B-ALL treatment in both peripheral blood (PB) and bone marrow compartment (BM) samples. To reach this goal, PB and BM plasma samples were comparatively analyzed by using label-free proteomics at two endpoints: at diagnosis (D0) and the end of the cumulative induction phase treatment (D28). Proteomic data was available via ProteomeXchange with identifier PXD021584. The resulting differentially expressed proteins were explored by bioinformatics approaches aiming to identify the main gene ontology processes, pathways, and transcription factors altered by chemotherapy, as well as to understand B-ALL biology in each compartment at D0. At D0, PB was characterized as a pro-inflammatory environment, with the involvement of several downregulated coagulation proteins as KNG, plasmin, and plasminogen. D28 was characterized predominantly by immune response-related processes and the super expression of the transcription factor IRF3 and transthyretin. RUNX1 was pointed out as a common transcription factor found in both D0 and D28. We chose to validate the proteins transthyretin and interferon-gamma (IFN-γ) by commercial kits and expressed the results as PB/BM ratios. Transthyretin ratio was augmented after induction chemotherapy, while IFN-γ was reduced at the end of the treatment. Considering that most of these proteins were not yet described in B-ALL literature, these findings added to understanding disease biology at diagnosis and highlighted a possible role for transthyretin and IFN-γ as mechanisms related to disease resolution.

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Abstract 3262: Targeting PI3K-coupled MEK/ERK pathway for therapy in pediatric B-cell acute lymphocytic leukemia.

10.1158/1538-7445.am2013-3262 ◽

2013 ◽

Author(s):

Xiang Wang ◽

Ben-shang Li ◽

Li-xia Ding ◽

Chris Liang ◽

Jian Ding ◽

...

Keyword(s):

B Cell ◽

Acute Lymphocytic Leukemia ◽

Lymphocytic Leukemia ◽

Erk Pathway

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Case of the disappearing subdural hygromas in a pediatric patient with acute lymphocytic leukemia

Journal of Neurosurgery Pediatrics ◽

10.3171/2012.7.peds12105 ◽

2012 ◽

Vol 10 (5) ◽

pp. 457-458

Author(s):

Paul E. Kaloostian ◽

Han Chen ◽

Frederick Rupp ◽

Erich Marchand

Keyword(s):

B Cell ◽

Pediatric Patient ◽

Complete Resolution ◽

Acute Lymphocytic Leukemia ◽

Lymphocytic Leukemia ◽

Initial Presentation ◽

Mri Studies ◽

Fluid Collections ◽

The Brain

The authors report the case of a 16-year-old boy with pre-B cell acute lymphocytic leukemia diagnosed 2 weeks earlier. On workup for diffuse headaches he was found to have 10-mm bilateral subdural hygromas with compression of the underlying gyri. He was followed clinically, and 4 days after his initial presentation he underwent MRI studies of the brain, which showed complete resolution of the subdural fluid collections. No change in management was noted during these 4 days. This case is the first known instance of rapid, spontaneously disappearing bilateral subdural hygromas in a pediatric patient.

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Hyper-CVAD + epratuzumab as a salvage regimen for younger patients with relapsed/refractory CD22-positive precursor B-cell acute lymphocytic leukemia

Haematologica ◽

10.3324/haematol.2016.159905 ◽

2017 ◽

Vol 102 (5) ◽

pp. e184-e186 ◽

Cited By ~ 3

Author(s):

Patrice Chevallier ◽

Sylvain Chantepie ◽

Francoise Huguet ◽

Emmanuel Raffoux ◽

Xavier Thomas ◽

...

Keyword(s):

B Cell ◽

Acute Lymphocytic Leukemia ◽

Lymphocytic Leukemia ◽

Salvage Regimen ◽

Younger Patients

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Poor prognosis of children with acute lymphocytic leukemia and increased B cell markers

The Journal of Pediatrics ◽

10.1016/s0022-3476(76)80607-5 ◽

1976 ◽

Vol 89 (6) ◽

pp. 956-958 ◽

Cited By ~ 27

Author(s):

Lawrence J. Wolff ◽

Susan T. Richardson ◽

James B. Neiburger ◽

Rochelle G. Neiburger ◽

Deborah S. Irwin ◽

...

Keyword(s):

B Cell ◽

Poor Prognosis ◽

Acute Lymphocytic Leukemia ◽

Lymphocytic Leukemia ◽

Cell Markers

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PIM Inhibitor SMI-4a Induces Cell Apoptosis and Cell Cycle Arrest in B-Cell Acute Lymphocytic Leukemia Cells Via the JAK2/STAT3 Pathway

Blood ◽

10.1182/blood-2018-99-117804 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4083-4083 ◽

Cited By ~ 1

Author(s):

Xingyi Kuang ◽

Jie Xiong ◽

Weili Wang ◽

Xinyao Li ◽

Tingting Lu ◽

...

Keyword(s):

Cell Cycle ◽

B Cell ◽

Cell Cycle Arrest ◽

Cell Apoptosis ◽

Acute Lymphocytic Leukemia ◽

Lymphocytic Leukemia ◽

Stat3 Pathway ◽

Cycle Arrest ◽

Molecule Inhibitor

Abstract The serine/threonine PIM protein kinases are critical regulators of turmorigenesis in mutiple hematologic malignancies and solid cancers. We used real-time PCR to detect the expression of PIM in B-cell acute lymphocytic leukemia (B-ALL) patients, and found the expression of PIM in B-ALL patients was significantly higher than that in normal controls. SMI-4a is a pan-PIM small molecule inhibitor, and this agent exhibits demonstrable preclinical antitumour activity in a wide range of hematologic malignant cell lines. To further explore the effect of SMI-4a on B-ALL cells, B-ALL cell lines CCRF-SB and Sup-B15 were treated with this small molecule inhibitor, and the results showed that SMI-4a inhibited B-ALL cell proliferation in a dose- and time-dependent manner. Moreover, SMI-4a significantly promoted B-ALL cell apoptosis and caused cell cycle arrest in the G0/G1 phase. The results of Western blot showed that SMI-4a increased the expression of Caspase-3, Caspase-9, Bax and P21, and decreased the expression of Bcl-2 and CDK4. Furthermore, we found that SMI-4a significantly inhibits the activation of the JAK2/STAT3 pathway and HO-1 interferes with the JAK2/STAT3 pathway to inhibit SMI-4a-induced ALL cell apoptosis. Finally, xenograft experiments in NOD/SCID mice were operated to investigate the potential role of SMI-4a in B-ALL tumorigenesis in vivo. To observe the effect of SMI-4a on tumor growth in vivo, NOD/SCID mice were transplanted with B-ALL devied cells, and the tumor-bearing mice were intraperitoneally injected with saline and SMI-4a, respectively. As a result, tretment with SMI-4a resulted in a significant inhibition on tumor growth. In addition, PIM inhibtor obviously reduced the volume and weight of B-ALL cell-derived tumors. TUNEL assay revealed the proportion of apoptotic cells was higher in the SMI-4a-treated group than in the control group. Taken together, our data showed PIM inhibitor (SMI-4a) significantly inhibits the growth of B-ALL cells in vitro and in vivo and promotes apoptosis and cell cycle arrest. This suppressive effect is mediated partly through inhibiting the JAK2/STAT3 pathway activation. Disclosures No relevant conflicts of interest to declare.

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