Analysis of outcomes and prognostic factors of acute lymphoblastic leukemia patients treated by MCP841 protocol: A regional cancer center experience

Kapoor, Akhil; Kalwar, Ashok; Kumar, Narender; Singhal, Mukesh Kumar; Beniwal, Surender; Kumar, Harvindra Singh

doi:10.4103/1735-1995.178754

Cited by 7 publications

(9 citation statements)

References 32 publications

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“…Moreover, deaths due to treatment-related toxicity (TRT) in Indian ALL patients ranges between 2%–24% [ 5 ], which is ten times higher than in high-income countries [ 6 ]. Multicentre protocol (MCP 841) for pediatric population and German multicenter ALL (GMALL) protocol for adults were developed as effective tools to treat ALL patients in the absence of risk stratification criteria, and for a cost-effective strategy in limited-resource settings [ 7 ]. These two protocols, include the administration of drugs that require minimal supportive care therapy, thus reducing the costs of treatment.…”

Section: Introductionmentioning

confidence: 99%

Association of NUDT15 c.415C>T and FPGS 2572C>T Variants with the Risk of Early Hematologic Toxicity During 6-MP and Low-Dose Methotrexate-Based Maintenance Therapy in Indian Patients with Acute Lymphoblastic Leukemia

Kumar

Dorababu

Thakkar

et al. 2020

Genes

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Genetic variants influencing the pharmacokinetics and/or pharmacodynamics of the chemotherapeutic drugs used in Acute Lymphoblastic Leukemia (ALL) therapy often contribute to the occurrence of treatment related toxicity (TRT). In this study, we explored the association of candidate genetic variants with early hematological TRT (grade 3–4) occurring within the first 100 days of low-dose methotrexate and 6-mercaptopurine based maintenance therapy (n = 73). Fourteen variants in the following candidate genes were genotyped using allele discrimination assay by real-time PCR: ABCB1, DHFR, GGH, FPGS, MTHFR, RFC1, SLCO1B1, TPMT, and NUDT15. Methotrexate polyglutamate (MTXPG3-5) levels in red blood cells were measured by LC-MS/MS. Early hematological TRT (grade 3–4) was seen in 54.9% of patients. The NUDT15c.415T allele was associated with early TRT occurrence [HR: 3.04 (95% CI: 1.5–6.1); p = 0.007]. Sensitivity of early TRT prediction improved (from 30.7% to 89.7%) by considering FPGS variant (rs1544105’T’) carrier status along with NUDT15c.415T allele [HR = 2.7 (1.5–4.7, p = 0.008)]. None of the considered genetic variants were associated with MTXPG3-5 levels, which in turn were not associated with early TRT. NUDT15c.415T allele carrier status could be used as a stratifying marker for Indian ALL patients to distinguish patients at high or low risk of developing early hematological TRT.

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Section: Introductionmentioning

confidence: 99%

Association of NUDT15 c.415C>T and FPGS 2572C>T Variants with the Risk of Early Hematologic Toxicity During 6-MP and Low-Dose Methotrexate-Based Maintenance Therapy in Indian Patients with Acute Lymphoblastic Leukemia

Kumar

Dorababu

Thakkar

et al. 2020

Genes

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“…80% of infants with ALL have an MLL rearrangement which confers a very dismal prognosis regardless of age and is treated according to a specific chemotherapeutic regimen such as Interfant-06 protocol in infantile age. 19,20 Most pediatric ALL regimens are based on the pillars developed by the Berlin-Frankfurt-Münster (BFM) group in the 1970s. 12 In the total XV protocol, the combination of vincristine, L-asparaginase and a glucocorticoid boomingly induces marrow, CNS and testicular remission in 95% of ALL patients which is the goal of induction therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Some Indian oncologists advocate the use of high dose cytarabine instead of whole cranial radiation. 19 As for maintenance therapy, it generally lasts for 2-3 years more in boys than in girls, since it is acknowledged that males relapse more frequently than females. Bone marrow transplant remains the sanctuary in cases where induction fails, patients relapse on treatment or within the first year following conclusion of chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Acute lymphoid leukemia in Lebanese children: A retrospective study

Khalifé

Khazen

Khalife

et al. 2022

Clinical Epidemiology and Global Health

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Acute lymphoid leukemia (ALL) is the most common malignant disease affecting children, accounting for approximately 25% of all childhood cancers. Hence, the majority of these children are in developing countries. ALL is one of the major public health problems affecting the Lebanese children. Our objective was to investigate the epidemiology, laboratory findings and treatment efficacy in ALL children and extrapolate these results to the guidelines used internationally. This retrospective observational cohort study was performed using routine clinical data of 75 ALL children, with age ranging from 0 to 18 years old, attending three major hospitals in Beirut (Lebanon) over a period of thirteen years. Our results showed that males constituted 54.6% of all ALL patients and that ALL is predominant between ages 3-6 years, and that 85.3% of children were pre B-cell ALL. Furthermore, the results showed that there was an association between ALL type and age. Male patients had the highest numbers of high and low risk patients. Moreover, 48% of ALL patients had a WBC count less than 10,000/ μL. An association was found between risk group and initial WBC. Cytogenetic abnormalities were detected in 17% of all patients. 73% of the patients cleared their lymphoblasts by day 15 of induction. Moreover, 63% of patients were free of disease for more than 5 years and 27% had complete remission, while 8% of patients died; of whom one had Down syndrome.This study highlights the situation of ALL in children in Lebanon. It provides a realistic overview that may help establish national guidelines for the investigation and management of childhood ALL.

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“…This suggests higher proportion of T-cell ALL in Kerala, like in other parts of the country. [4,8,20,21] Three treatment regimens were simultaneously used during the 5 years studied. None superior in terms of response to treatment or event-free 5-year survival.…”

Section: Discussionmentioning

confidence: 99%

“…[1,2] In India, survival rates vary from 36% to 53%, reflecting limitations in health care, differences in general health, and probably the biology of ALL. [3][4][5] Treatment of leukemia had been marked by risk factors whose prognostic utility has decreased with development of specific diagnostic modalities. Unfortunately, many cases do not possess features known to warrant such specific therapy.…”

Section: Introductionmentioning

confidence: 99%

Five-Year Survival Rate and the Factors for Risk-Directed Therapy in Acute Lymphoblastic Leukemia

Varghese

Joobomary

Savida

2018

Indian Journal of Medical and Paediatric Oncology

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Background: Acute lymphoblastic leukemia (ALL) has 5-year survival of more than 90% in many advanced cancer research institutes. However, advanced cancer care is not available to majority of poor in developing countries. The experience of treating such patients in a resource-scarce setting is described herewith. Of the 75 individuals studied, 11% of the children were stunted, >21% were underweight, and 16% of the under-five children had acute malnutrition. Massive hepatosplenomegaly and lymphadenopathy were present in 75% and 77% children, respectively. About 71% patients achieved complete remission (CR). A total of 30 (40%) children lived for >5 years after diagnosis and 21 (28%) of them had event-free 5 years. Weight for height for under-five children ( P = 0.029) and total count ( P = 0.019) were found to be significantly associated with deaths during induction. Weight for age ( P = 0.024), weight for height of under-five children ( P = 0.009), and lymphadenopathy ( P = 0.049) had a strong association with 5-year event-free survival. Using multivariate model, only weight for height among under five remained significantly associated with induction deaths ( P = 0.021) and absence of lymphadenopathy with event-free 5-year survival ( P = 0.042). Context: ALL has 5-year survival of >90% in many advanced cancer research institutes. However, advanced care is not available to majority of poor in the periphery of developing countries. Data available on the survival and the factors affecting the outcome among patients treated in poor resource settings are limited. Aims: This study aims to find the 5-year survival rate and the factors for risk-directed therapy in the region. Settings and Design: Cross-sectional analytical study at a tertiary center of public health in central Kerala. Subjects and Methods: Retrospective analysis of case sheets of 75 children who were treated at the institute from March 2006 to March 2011. Statistical Analysis Used: Univariate and Multivariate analysis using IBM SPSS Statistics for Windows, Version 20.0. Results: : Of the 75 individuals studied, 11% of the children were stunted, >21% were underweight, and 16% of the under-five children had acute malnutrition. Massive hepatosplenomegaly and lymphadenopathy were present in 75% and 77% children, respectively. About 71% patients achieved CR. A total of 30 (40%) children lived for >5 years after diagnosis and 21 (28%) of them had event-free 5 years. Weight for height for under-five children ( P = 0.029) and total count ( P = 0.019) were found to be significantly associated with deaths during induction. Weight for age ( P = 0.024), weight for height of under-five children ( P = 0.009), and ly...

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Analysis of outcomes and prognostic factors of acute lymphoblastic leukemia patients treated by MCP841 protocol: A regional cancer center experience

Cited by 7 publications

References 32 publications

Association of NUDT15 c.415C>T and FPGS 2572C>T Variants with the Risk of Early Hematologic Toxicity During 6-MP and Low-Dose Methotrexate-Based Maintenance Therapy in Indian Patients with Acute Lymphoblastic Leukemia

Association of NUDT15 c.415C>T and FPGS 2572C>T Variants with the Risk of Early Hematologic Toxicity During 6-MP and Low-Dose Methotrexate-Based Maintenance Therapy in Indian Patients with Acute Lymphoblastic Leukemia

Acute lymphoid leukemia in Lebanese children: A retrospective study

Five-Year Survival Rate and the Factors for Risk-Directed Therapy in Acute Lymphoblastic Leukemia

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