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Haematological Disease
Published in John S. Axford, Chris A. O'Callaghan, Medicine for Finals and Beyond, 2023
Aims of therapy: Prevention of death from bone marrow failure by supportive therapy is the primary aim.Aim for induction of complete remission, defined as non-detectability of leukaemic blasts plus return of normal cell counts. Increasingly, clinicians are able to detect minimal residual disease (MRD) by molecular or immunological methods. Patients who are MRD-negative after induction chemotherapy have a much better prognosis than those who are MRD-positive.Consolidation of cytotoxic therapy, which may include further cycles of chemotherapy or, in high-risk patients, allogeneic stem cell transplantation, offers the best chance of cure.
Practical Approach to Molecular Biology in Hematopathology
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
Anwar Mikhael, Harold R. Schumacher
In addition to B-ALL, PCR allows the detection of minimal residual disease (MRD) in T-cell ALL. The use of primers specific for TCR-γ and -δ junctions can detect clonal specific PCR products (27). This strategy uncovers the presence of MRD in cases with TCR γ-δ recombinations (27). Since the TAL-1 gene is the most frequently deleted in T-lineage leukemias, detection of TAL-1 gene abnormality strongly indicates the presence of MRD in this subset of T-cell leukemias (28-30).
Minimal Residual Disease
Published in Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey, Innovative Leukemia and Lymphoma Therapy, 2019
Jacques J. M. van Dongen, Tomasz Szczepański, Vincent H. J. van der Velden
Current cytotoxic treatment protocols induce complete remission (CR) in most acute leukemia patients [both acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML)], in some patients with chronic lymphocytic leukemia (CLL), and in most non-Hodgkin’s lymphoma (NHL) and chronic myeloid leukemia (CML) patients. Introduction of allogeneic and autologous hematopoietic stem cell transplantation (HSCT) in treatment protocols has further increased the remission rates in ALL, AML, CML, and NHL. Nevertheless, many of these patients ultimately relapse. Apparently, the treatment protocols are not capable of killing all clonogenic malignant cells in these patients, even though they reached CR according to cytomorphological criteria. The detection limit of cytomorphological techniques is not lower than 1% to 5% of malignant cells, implying that these techniques can provide only superficial information about the effectiveness of the treatment. More sensitive techniques are required for the detection of low frequencies of malignant cells during and after treatment, i.e., detection of minimal residual disease (MRD). MRD techniques should reach sensitivities of at least 10−3 (one malignant cell within thousand normal cells), but sensitivities of 10−4 to 10−6 are preferred. Such sensitivities allow “true” MRD detection and thereby evaluation of the effectiveness of the total treatment and assessment of the contribution of each treatment phase.
HLA-mismatched micro-transplantation as post-remission treatment compared to autologous hematopoietic stem cell transplantation or consolidation with single agent cytarabine for favorable-or intermediate-risk acute myeloid leukemia
Published in Hematology, 2023
Shandong Tao, Dan Zhou, Lixiao Song, Yuan Deng, Yue Chen, Banghe Ding, Zhengmei He, Chunling Wang, Liang Yu
Responses were evaluated according to standard criteria defined by the NCCN Guidelines for AML (www.nccn.org). CR was defined as the disappearance of clinical symptoms and recovery of normal hematopoiesis, with absolute neutrophil counts ≥1.0 × 109/L, platelets ≥100 × 109/L, bone marrow blasts ≤5%, and no evidence of extramedullary leukemia. Relapse was defined as the recurrence of leukemic blasts in the peripheral blood, ≥ 5% blasts in the bone marrow after CR excluding bone marrow regeneration after consolidation chemotherapy or other causes, or evidence of extramedullary leukemia. Flow cytometry and polymerase chain reaction were used to detect minimal residual disease (MRD). Relapse-free survival (RFS) was defined as the time from CR to relapse or death from any cause. Overall survival (OS) was measured as the time from initial diagnosis to death for any reason.
The expression of PHOX2B in bone marrow and peripheral blood predicts adverse clinical outcome in non-high-risk neuroblastoma
Published in Pediatric Hematology and Oncology, 2022
Hongjun Fan, Tianyu Xing, Huimin Hong, Chao Duan, Wen Zhao, Qian Zhao, Xisi Wang, Cheng Huang, Shuai Zhu, Mei Jin, Yan Su, Chao Gao, Xiaoli Ma
Liquid biopsy markers are widely used for the detection of minimal residual disease (MRD) and to predict prognosis in various types of cancer.7,8 In neuroblastoma, the detection of circulating tumor cells using flow cytometry has been explored as a new method of monitoring disease recurrence.9,10 Exosomal microRNAs in the blood have also been proven very useful for predicting the response to induction chemotherapy in patients with high-risk neuroblastoma.11 In our previous studies, cell-free DNA (cfDNA) was shown to be associated with tumor burden, chemotherapy response and disease recurrence in pediatric patients with neuroblastoma.12–14 The plasma MYCN/NAGK ratio was also shown to be a powerful marker for the detection of MYCN amplification in patients with high-risk neuroblastoma.15
Outcomes of pediatric mixed phenotype acute leukemia treated with lymphoid directed therapy: Analysis of an institutional series from India
Published in Pediatric Hematology and Oncology, 2021
Shwetha Seetharam, Priyakumari Thankamony, Kaduveettil Gopinathan Gopakumar, Rekha Appukuttan Nair, Priya Mary Jacob, K. M. Jagathnath Krishna, Binitha Rajeswari, Manjusha Nair, C. S. Guruprasad, V. R. Prasanth
MRD has an important role in the identification of early treatment failure in MPAL.21–25 In the iBFM- AMBI2012 retrospective study, EOI MRD ≥5% was also associated with a 5-year EFS rate of >50%.18 The COG task force only recommend continuing ALL chemotherapy in patients with EOI MRD <5% and end-of-consolidation MRD <0.01%.19 Although the use of minimal residual disease (MRD) measurement in risk stratification is now the standard of care in many countries,21–25 it remains unavailable in resource –limited settings including many centers in India. Despite the lack of facilities for MRD measurement at our center, we observed that the absolute blast percentage on day 8 of steroids and morphological marrow remission at the EOI has prognostic value as patients with GPR and EOI CR had a 4 year EFS for patients of 80% as compared to 16.7% in patients with PPR or induction failure (P value = 0.009). The prednisolone response and morphological remission of EOI marrow may be helpful in deciding the need for further aggressive management including HSCT in patients with MPAL in the resource-limited setting. However, our study is limited by the small numbers and the retrospective nature of the data. Prospective trials are required to validate the role of risk stratification and HSCT in MPAL.