scholarly journals Polymorphism of Biotransformation Genes and Risk of Relapse in Childhood Acute Leukemia

2009 ◽  
Vol 12 (1) ◽  
pp. 21-35 ◽  
Author(s):  
O Gra ◽  
Zh Kozhekbaeva ◽  
O Makarova ◽  
E Samochatova ◽  
T Nasedkina
Keyword(s):  
Bone Marrow ◽  
Acute Leukemia ◽  
Childhood Leukemia ◽  
Hematological Malignancy ◽  
Lymphoblastic Leukemia ◽  
Leukemia Relapse ◽  
Polymorphic Variants ◽  
Childhood Acute Leukemia ◽  
Primary Leukemia ◽  
Risk Of Relapse

Polymorphism of Biotransformation Genes and Risk of Relapse in Childhood Acute LeukemiaLeukemia is a hematological malignancy that involves bone marrow. Polymorphism of biotransformation genes plays an important role in primary childhood leukemia and affects the incidence and character of acute leukemia relapse. A biochip designed to assess some polymorphisms of biotransformation genes was used to determine the frequency of the polymorphic variants ofCYP1A1, CYP2D6, GSTT1, GSTM1, MTHFR, MTRR, NQO1, CYP2C9, CYP2C19andNAT2in 332 children with acute lymphoblastic leukemia (ALL) and 71 children with acute myeloblastic leukemia (AML). TheCYP1A1 *1/*2A, GSTT1non null andGSTM1non null genotypes were more frequent in patients with primary leukemia than in relapse. Analysis of theNAT2genotype frequency revealed a characteristic genotype for each type of leukemia, which prevailed in patients with relapse: the genotype341C/-, 481T/-, 590G/G, 857G/Gprevailed in ALL patients with relapse, and the genotype341T/T, 481C/C, 590A/- in AML patients with relapse when compared with patients having primary ALL or AML, respectively. Thus, the polymorphisms ofCYP1A1, GSTT1, GSTM1andNAT2genes can be considered as markers for risk of relapse in childhood acute leukemia and can be used for the prognosis and individualization of standard therapy.

scholarly journals Ocular manifestations of childhood acute leukemia in a tertiiary level eye centre of Kathmandu, Nepal

2014 ◽  
Vol 6 (2) ◽  
pp. 197-204 ◽  
Author(s):  
Deepak Khadka ◽  
Ananda Sharma ◽  
Jeevan K Shrestha ◽  
Gauri S Shrestha ◽  
Pun N Shrestha ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Leukemia ◽  
Childhood Leukemia ◽  
Lymphoblastic Leukemia ◽  
University Teaching ◽  
Ocular Involvement ◽  
Cross Sectional ◽  
Ocular Manifestations ◽  
Blast Cells ◽  
Childhood Acute Leukemia

Introduction: In some instances, the understanding of the ocular manifestations in childhood leukemia is not only important to establish the diagnosis but also reflects the disease state and prognosis. Objective: To study the ocular manifestations of childhood acute leukemia among the children attending a tertiary-level hospital in Nepal. Materials and methods: A cross-sectional, descriptive study was undertaken at the B.P. Koirala Lions Centre for Ophthalmic Studies (BPKLCOS) and Kanti Children Hospital (KCH), Kathmandu, over a period of one-and-a-half years. Children diagnosed with acute childhood leukemia referred to the BPKLCOS from the Oncology Unit of the KCH and the Emergency Department of the Tribhuvan University Teaching Hospital (TUTH) were included in the study, using a non-probability sampling method. Results:Of the 71 cases with childhood acute leukemia, 55 (77.5%; 95% CI = 66% - 85%) had acute lymphoblastic leukemia(ALL)whereas the other 16 (23%) had acute myeloblastic leukemia (AML). Ocular involvement were seen in 33 cases (46%) and were more frequent in cases of AML as compared to those with ALL (p=0.001, OR 5.0, 95% CI= 1.4 – 17.5). Direct ocular involvement and secondary ocular involvement were observed in 12 (16.9%) and 29 (40.8%) subjects, respectively. Ocular symptoms were present in only 11 cases (15.49%). Cerebro-spinal fluid (CSF) and bone marrow examination in cases with direct ocular involvement showed 10 cases (83.3%) positive for blast cells in the CSF and 6 cases (50%) positive for blast cells in bone marrow. The most common secondary manifestation was retinal haemorrhage, seen in 23 cases (32.4%). Conclusion: In view of the high asymptomatic ocular involvement and the significant visual morbidity, a routine ophthalmic examination is recommended as an integral part of the medical examination in all cases of childhood acute leukemia.DOI: http://dx.doi.org/10.3126/nepjoph.v6i2.11678Nepal J Ophthalmol 2014; 6(12):  pp. 197-204

scholarly journals Acute leukemia of childhood: A single institution's experience

2005 ◽  
Vol 57 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Bojana Slavkovic ◽  
Marija Guc-Scekic ◽  
Gordana Bunjevacki ◽  
S. Djuricic ◽  
Aleksandra Krstic ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Acute Leukemia ◽  
Childhood Leukemia ◽  
Lymphoblastic Leukemia ◽  
Chromosomal Rearrangements ◽  
Age Distribution ◽  
Normal Karyotype ◽  
Mediterranean Countries ◽  
B Lineage ◽  
Childhood Acute Leukemia

The aim of this study was to investigate distribution of immunophenotypic and cytogenetic features of childhood acute leukemia (AL) in the cohort of 239 newly diagnosed patients registered at the leading pediatric oncohematology center in the country during a six-year period (1996-2002). With approximately 60-70% of all childhood AL cases in Serbia and Montenegro being diagnosed and treated in this institution the used data represent a valid research sample to draw conclusions for entire country. On the basis of five phenotypic markers, the distribution of immunological subtypes was as follows: 169 (70.7%) expressed B-cell marker CD19 (137 were CD10 positive and 32 CD10 negative), 37 (15.5%) belonged to T-lineage acute lymphoblastic leukemia (T-ALL) (cyCD3 positive), and 33 (13.8%) were acute myeloblastic leukemia (AML) (CD13 positive and/or CD33 positive in the absence of lymphoid-associated antigens). The ratio of males and females was 1.5:1. Most of the cases were between the ages of 2 and 4, and were predominantly B-lineage acute lymphoblastic leukemia (B-ALL) cases. Another peak of age distribution was observed at the age of 7. The frequency of T-ALL (18% of ALL) was similar to that reported for Mediterranean countries: France (19.4%), Greece (28.1%), Southern Italy (28.3%), and Bulgaria (28.0%). Cytogenetic analyses were performed in 193 patients: 164 ALL and 29 AML. Normal karyotype was found in 57% of ALL and in 55% of AML patients, while cytogenetic abnormalities including structural, numerical, and complex chromosomal rearrangements were found in 43% of ALL and in 45% of AML patients. Our results represent a contribution to epidemiological aspects of childhood leukemia studies.

scholarly journals Lineage switch in acute leukemia

Blood ◽  
1984 ◽  
Vol 64 (3) ◽  
pp. 701-706 ◽  
Author(s):  
S Stass ◽  
J Mirro ◽  
S Melvin ◽  
CH Pui ◽  
SB Murphy ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Leukemia ◽  
Childhood Leukemia ◽  
Clonal Selection ◽  
Lymphoblastic Leukemia ◽  
Cell Lineage ◽  
Leukemic Cell ◽  
High Dose ◽  
Drug Induced ◽  
Lineage Switch

Abstract Conversions of leukemic cell lineage (lymphoid or myeloid) have been reported only rarely. Our review of the cytochemical and immunophenotypic features of 89 cases of childhood leukemia in marrow relapse indicated lineage switch (lymphoid to myeloid or the reverse) in six patients (6.7%). Five patients with acute lymphoblastic leukemia (ALL) at diagnosis had converted to acute nonlymphoblastic leukemia (ANLL), and one had converted from ANLL to ALL. Each child received lineage-specific multiagent chemotherapy when initially diagnosed, and all achieved a complete remission. After conversion, four patients readily achieved second remissions with treatment for the phenotype evident at lineage switch. Two patients with ANLL at conversion failed ALL-directed reinduction, while one of the two responded to high-dose cytarabine but died during bone marrow hypoplasia, emphasizing the importance of prompt recognition of lineage switch and selection of an appropriate plan of retreatment. Cytogenetic studies disclosed evidence of clonal selection in one patient and clonal stability in two. These findings indicate an unexpectedly high frequency of lineage switch in patients who relapse in the bone marrow after intensive chemotherapy. Although specific causative factors could not be identified, our observations suggest at least two general mechanisms for lineage switch in acute leukemia. In one, chemotherapy appears to eradicate the dominant clone present at diagnosis, permitting expansion of a secondary clone with a different phenotype. In the second, drug-induced changes in the original clone may either amplify or suppress differentiation programs so that phenotypic shift is possible.

scholarly journals Maternal Residential Proximity to Major Roadways and the Risk of Childhood Acute Leukemia: A Population-Based Case-Control Study in Texas, 1995–2011

2019 ◽  
Vol 16 (11) ◽  
pp. 2029 ◽  
Author(s):  
Erin C. Peckham-Gregory ◽  
Minh Ton ◽  
Karen R. Rabin ◽  
Heather E. Danysh ◽  
Michael E. Scheurer ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Early Life ◽  
Childhood Leukemia ◽  
Lymphoblastic Leukemia ◽  
Birth Certificate ◽  
Population Based ◽  
Residential Proximity ◽  
Early Life Exposure ◽  
Proximity Measures ◽  
Childhood Acute Leukemia

Acute leukemia is the most common pediatric malignancy. Some studies suggest early-life exposures to air pollution increase risk of childhood leukemia. Therefore, we explored the association between maternal residential proximity to major roadways and risk of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Information on cases with acute leukemia (n = 2030) was obtained for the period 1995–2011 from the Texas Cancer Registry. Birth certificate controls were frequency matched (10:1) on birth year (n = 20,300). Three residential proximity measures were assessed: (1) distance to nearest major roadway, (2) residence within 500 meters of a major roadway, and (3) roadway density. Multivariate logistic regression was used to generate adjusted odds ratios (aOR) and 95% confidence intervals (CI). Mothers who lived ≤500 meters to a major roadway were not more likely to have a child who developed ALL (OR = 1.03; 95% CI: 0.91–1.16) or AML (OR = 0.84; 95% CI: 0.64–1.11). Mothers who lived in areas characterized by high roadway density were not more likely to have children who developed ALL (OR = 1.06, 95% CI: 0.93–1.20) or AML (OR = 0.83, 95% CI: 0.61–1.13). Our results do not support the hypothesis that maternal proximity to major roadways is strongly associated with childhood acute leukemia. Future assessments evaluating the role of early-life exposure to environmental factors on acute leukemia risk should explore novel methods for directly measuring exposures during relevant periods of development.

Nd: Yag laser treatment for sub-hyaloid hemorrhage in childhood acute leukemia

1970 ◽  
Vol 4 (1) ◽  
pp. 102-107 ◽  
Author(s):  
D Khadka ◽  
AK Sharma ◽  
JK Shrestha ◽  
B Pant ◽  
S Pant ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Myeloid Leukemia ◽  
Childhood Leukemia ◽  
Randomized Clinical Trials ◽  
Lymphoblastic Leukemia ◽  
Visual Disability ◽  
Tractional Retinal Detachment ◽  
Yag Laser ◽  
Retinal Breaks ◽  
Childhood Acute Leukemia

Introduction: Sub-hyaloid haemorrhage is common in acute leukemia. Objective: To investigate the effects of Nd: YAG Laser hyaloidotomy in 11 eyes of 8 patients with pre-macular haemorrhage in acute childhood leukemia. Materials and methods: Premacular sub-hyaloid haemorrhage is one of the leading causes of visual disability in children with acute leukemia. Eleven eyes of 8 patients attending Kanti Children Hospital and BP Koirala Lions Centre for Ophthalmic Studies from January 2006 to July 2007 with premacular subhyaloid haemorrhage were included in the study and treated with Nd: YAG Laser. The haemorrhage originated from acute myeloid leukemia (AML) in 4 cases (6 eyes) and acute lymphoblastic leukemia (ALL) in 4 cases (5 eyes). Results: Drainage of premacular sub-hyaloid haemorrhage into the vitreous cavity within 3 months succeeded in 9 eyes out of 11 eyes treated. One eye had a dense clotted haemorrhage and the other had a re-bleed. Overall visual improvement was equal in both AML and ALL cases. No obvious epiretinal membrane, retinal breaks and tractional retinal detachment occurred in any eye. Conclusion: Nd: Yag laser hyaloidotomy is a relatively safe, simple and alternative treatment for eyes with a dense premacular sub-hyaloid haemorrhage in acute childhood leukemia. The risks and benefits have to be weighed in randomized clinical trials to establish Nd: YAG hyaloidotomy treatment as a routine procedure in leukemic children. DOI: http://dx.doi.org/10.3126/nepjoph.v4i1.5860 NEPJOPH 2012; 4(1): 102-107

scholarly journals Lineage switch in acute leukemia

Blood ◽  
1984 ◽  
Vol 64 (3) ◽  
pp. 701-706 ◽  
Author(s):  
S Stass ◽  
J Mirro ◽  
S Melvin ◽  
CH Pui ◽  
SB Murphy ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Leukemia ◽  
Childhood Leukemia ◽  
Clonal Selection ◽  
Lymphoblastic Leukemia ◽  
Cell Lineage ◽  
Leukemic Cell ◽  
High Dose ◽  
Drug Induced ◽  
Lineage Switch

Conversions of leukemic cell lineage (lymphoid or myeloid) have been reported only rarely. Our review of the cytochemical and immunophenotypic features of 89 cases of childhood leukemia in marrow relapse indicated lineage switch (lymphoid to myeloid or the reverse) in six patients (6.7%). Five patients with acute lymphoblastic leukemia (ALL) at diagnosis had converted to acute nonlymphoblastic leukemia (ANLL), and one had converted from ANLL to ALL. Each child received lineage-specific multiagent chemotherapy when initially diagnosed, and all achieved a complete remission. After conversion, four patients readily achieved second remissions with treatment for the phenotype evident at lineage switch. Two patients with ANLL at conversion failed ALL-directed reinduction, while one of the two responded to high-dose cytarabine but died during bone marrow hypoplasia, emphasizing the importance of prompt recognition of lineage switch and selection of an appropriate plan of retreatment. Cytogenetic studies disclosed evidence of clonal selection in one patient and clonal stability in two. These findings indicate an unexpectedly high frequency of lineage switch in patients who relapse in the bone marrow after intensive chemotherapy. Although specific causative factors could not be identified, our observations suggest at least two general mechanisms for lineage switch in acute leukemia. In one, chemotherapy appears to eradicate the dominant clone present at diagnosis, permitting expansion of a secondary clone with a different phenotype. In the second, drug-induced changes in the original clone may either amplify or suppress differentiation programs so that phenotypic shift is possible.

Philadelphia chromosome and terminal transferase-positive acute leukemia: similarity of terminal phase of chronic myelogenous leukemia and de novo acute presentation.

1983 ◽  
Vol 1 (11) ◽  
pp. 669-676 ◽  
Author(s):  
K Jain ◽  
Z Arlin ◽  
R Mertelsmann ◽  
T Gee ◽  
S Kempin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Leukemia ◽  
Chronic Myelogenous Leukemia ◽  
Lymphoblastic Leukemia ◽  
Allogeneic Bone Marrow Transplantation ◽  
Philadelphia Chromosome ◽  
Myelogenous Leukemia ◽  
Allogeneic Bone ◽  
Leukocyte Antigen ◽  
Terminal Transferase

Twenty-eight patients with Philadelphia chromosome (Ph1)--positive and terminal transferase (TdT)--positive acute leukemia (AL) were treated with intensive chemotherapy used for adult acute lymphoblastic leukemia (L-10 and L-10M protocols). Fifteen patients had a documented chronic phase of Ph1-positive chronic myelogenous leukemia preceding the acute transformation (TdT + BLCML) while the remaining 13 patients did not (TdT + Ph1 + AL). An overall complete remission (CR) rate of 71% was obtained with a median survival of 13 months in the responders. Clinical presentation, laboratory data, cytogenetics, response to treatment, and survivals of the two groups of patients are compared. These results appear to be similar, suggesting a common or closely related origin. Since the overall survival of those receiving chemotherapy maintenance is poor, three patients underwent allogeneic bone marrow transplantation (BMT) from histocompatibility leukocyte antigen--matched siblings after they achieved CR. One of them is a long-term survivor (35 + months) with a Ph1-negative bone marrow. New techniques such as BMT should be considered in young patients with a histocompatibility leukocyte antigen--compatible sibling once a CR has been achieved.

FLAG/FLAG-IDA regimen for children with relapsed/refractory acute leukemia in the era of targeted novel therapies

2018 ◽  
Vol 25 (8) ◽  
pp. 1831-1838 ◽  
Author(s):  
Omima Mustafa ◽  
Khalid Abdalla ◽  
Aeshah A AlAzmi ◽  
Naglla Elimam ◽  
Mohammed Burhan Abrar ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Bone Marrow Transplantation ◽  
Complete Remission ◽  
Acute Leukemia ◽  
Salvage Therapy ◽  
Marrow Transplantation ◽  
Lymphoblastic Leukemia ◽  
Hematologic Toxicity ◽  
Novel Therapies

Background Outcomes of relapsed/refractory childhood acute leukemia remain poor. We analyzed the safety/efficacy of fludarabine, cytarabine, and granulocyte colony stimulating factor, with/without idarubicin (FLAG ± IDA) as salvage therapy compared with recent published results of novel therapies. Methods This retrospective study included children aged 1 to 15 years with relapsed/refractory acute leukemia who received FLAG ± IDA salvage therapy from January 2000 to December 2014. Patients with infant leukemia, mixed lineage leukemia, Philadelphia-positive acute leukemia, or secondary leukemia were excluded. Result Fifty patients were identified: 25 with acute lymphoblastic leukemia and 25 with acute myeloid leukemia. The median age at initiation of FLAG ± IDA was seven years. Site of relapse was the bone marrow in 29, isolated central nervous system in 11, and combined in 10 patients. FLAG ± IDA was used after first relapse in 68% and after multiple relapses in 32%. Complete remission was achieved in 34 (68%) patients. No variables predictive of complete remission were identified. Grade 3 or greater toxicity was observed in 96% and 6% died from toxicity. Toxicities included hematologic toxicity (96%), infection (52%), and enterocolitis (28%). Twenty-four of 50 (48%) patients achieved a sustained complete remission and survived to bone marrow transplantation. The five-year overall survival was 23.9% ± 6.9%. Patients achieving second complete remission and patients proceeding to bone marrow transplantation following second complete remission demonstrated significantly improved overall survival (p = 0.001). Conclusion Despite a 68% complete remission rate using FLAG ± IDA, only 48% of patients survived to bone marrow transplantation. The regimen was associated with 96% toxicity and only one in four patients was alive at five years. This underscores the need to find more effective lower toxicity salvage regimens.

scholarly journals Expression of the three myeloid cell-associated immunoglobulin G Fc receptors defined by murine monoclonal antibodies on normal bone marrow and acute leukemia cells

Blood ◽  
1989 ◽  
Vol 73 (7) ◽  
pp. 1951-1956
Author(s):  
ED Ball ◽  
J McDermott ◽  
JD Griffin ◽  
FR Davey ◽  
R Davis ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Monoclonal Antibodies ◽  
Acute Leukemia ◽  
Cell Sorting ◽  
Lymphoblastic Leukemia ◽  
Mononuclear Phagocytes ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Normal Bone Marrow ◽  
Normal Bone

Monoclonal antibodies (MoAbs) have been prepared recently that recognize the three cell-surface receptors for the Fc portion of immunoglobulin (Ig), termed Fc gamma RI (MoAb 32.2), Fc gamma R II (MoAb IV-3), and Fc gamma R III (MoAb 3G8) that are expressed on selected subsets of non-T lymphocyte peripheral blood leukocytes. In the blood, Fc gamma R I is expressed exclusively on monocytes and macrophages, Fc gamma R II on granulocytes, mononuclear phagocytes, platelets, and B cells, and Fc gamma R III on granulocytes and natural killer (NK) cells. We have examined the expression of these molecules on normal bone marrow (BM) cells and on leukemia cells from the blood and/or BM in order to determine their normal ontogeny as well as their distribution on leukemic cells. BM was obtained from six normal volunteers and from 170 patients with newly diagnosed acute leukemia. Normal BM cells were found to express Fc gamma R I, II, and III with the following percentages: 40%, 58%, and 56%, respectively. Cell sorting revealed that both Fc gamma R I and Fc gamma R II were detectable on all subclasses of myeloid precursors as early as myeloblasts. Cell sorting experiments revealed that 66% of the granulocyte-monocyte colony-forming cells (CFU-GM) and 50% of erythroid burst-forming units (BFU-E) were Fc gamma R II positive with only 20% and 28%, respectively, of CFU-GM and BFU-E were Fc gamma R I positive. Acute myeloid leukemia (AML) cells expressed the three receptors with the following frequency (n = 146): Fc gamma R I, 58%; Fc gamma R II, 67%; and Fc gamma R III, 26% of patients. Despite the fact that Fc gamma R I is only expressed on monocytes among blood cells, AML cells without monocytoid differentiation (French-American-British [FAB]M1, M2, M3, M6) were sometimes positive for this receptor. However, Fc gamma R I was highly correlated with FAB M4 and M5 morphology (P less than .001). Fc gamma R II was also correlated with FAB M4 and M5 morphology (P = .003). Cells from 11 patients with acute lymphoblastic leukemia were negative for Fc gamma R I, but six cases were positive for Fc gamma R II and III (not the same patients). These studies demonstrate that Ig Fc gamma R are acquired during normal differentiation in the BM at or before the level of colony-forming units. In addition, we show that acute leukemia cells commonly express Fc gamma R.

scholarly journals Combinations of Drugs in the Treatment of Acute Leukæmias

1965 ◽  
Vol 58 (11P2) ◽  
pp. 988-990 ◽  
Author(s):  
C Gordon Zubrod
Keyword(s):  
Acute Leukemia ◽  
Childhood Leukemia ◽  
Task Force ◽  
Leukemic Cell ◽  
The United States ◽  
Leukemic Cells ◽  
Clinical Relapse ◽  
Acute Leukemias ◽  
Human Leukemic Cells ◽  
Childhood Acute Leukemia

In the United States, the Acute Leukemia Task Force has been studying ways to achieve chemical control over the acute leukemias. It was found that L1210 mouse leukemia is an excellent predictive model for childhood acute leukemia. Examination of the kinetics of cell generation led to the conclusions that a single cell could multiply to a lethal number of cells in a relatively short time, and that therapy must destroy every cell. Extension of these hypotheses to childhood leukemia has permitted estimates of generation time of human leukemic cells; the size of the leukemic cell population at clinical relapse and the fractional destruction of cells by individual drugs. By the use of combinations of antileukemic drugs complete cell destruction has been approached in a few patients with early leukemia.

Sign in / Sign up

Export Citation Format

Share Document