scholarly journals INCIDENCE, RISKS AND OUTCOME OF EXTRA MEDULLARY RELAPSE IN ACUTE LYMPHOBLASTIC LEUKEMIA IN CHILDREN AND ADULTS: A RETROSPECTIVE COHORT STUDY

2021 ◽  
Vol 10 (4) ◽  
pp. 3238-3245
Author(s):  
Sawhney Jyothi

Extra medullary relapse (EMR) is the major concern of treatment failure in acute lymphoblastic leukemia (ALL). Hence, their early detection may improve prognosis. Aim of the study is to identify risk factors and outcome of EMR patients with and without concurrent medullary relapse. We retrospectively analyzed 113 patients of ALL who presented with EMR in a tertiary cancer care hospital. Patients were divided into two groups; Group 1, combined EMR (with medullary relapse) and Group 2, isolated EMR (without medullary relapse). Clinical characteristics including total leukocyte count (TLC) & peripheral blood blast percentage during presentation, phenotype, initial central nervous system (CNS) involvement and BCR-ABL translocation were analyzed to identify risk factors for EMR. Incidence of EMR in our study was 15.7% (113/720 patients). Two year incidence of combined EMR and isolated EMR was 10.1% and 5.5% respectively. CNS, followed by testis was common sites of EMR. TLC >50x109/L and peripheral blood blast percentage >50% at presentation was common in Group 1. BCR-ABL translocation was frequent in Group 2 and in adults compared to children (p=0.027). While Group 1 patients presented with leukocytosis (TLC >10X109/L), Group 2 patients presented with leukopenia (TLC <4X109 p=0.001). p=0.001).>50X109/L and BCR-ABL translocation were identified as risk factors for combined EMR (p=0.004) and for in adults with isolated EMR (p=0.001) respectively.

2021 ◽  
pp. 72-74
Author(s):  
Sarat Das ◽  
Prasanta Kr. Baruah ◽  
Sandeep Khakhlari ◽  
Gautam Boro

Introduction: Leukemias are neoplastic proliferations of haematopoietic stem cells and form a major proportion of haematopoietic neoplasms that are diagnosed worldwide. Typing of leukemia is essential for effective therapy because prognosis and survival rate are different for each type and sub-type Aims: this study was carried out to determine the frequency of acute and chronic leukemias and to evaluate their clinicopathological features. Methods: It was a hospital based cross sectional study of 60 patients carried out in the department of Pathology, JMCH, Assam over a period of one year between February 2018 and January 2019. Diagnosis was based on peripheral blood count, peripheral blood smear and bone marrow examination (as on when available marrow sample) for morphology along with cytochemical study whenever possible. Results: In the present study, commonest leukemia was Acute myeloid leukemia (AML, 50%) followed by Acute lymphoblastic leukemia (ALL 26.6%), chronic myeloid leukemia (CML, 16.7%) and chronic lymphocytic leukemia (CLL, 6.7%). Out of total 60 cases, 36 were male and 24 were female with Male:Female ratio of 1.5:1. Acute lymphoblastic leukemia was the most common type of leukemia in the children and adolescents. Acute Myeloid leukemia was more prevalent in adults. Peripheral blood smear and bone Conclusion: marrow aspiration study still remains the important tool along with cytochemistry, immunophenotyping and cytogenetic study in the diagnosis and management of leukemia.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S949-S949
Author(s):  
Sarah Dorval ◽  
Léna Coïc ◽  
Denis Blais ◽  
Jean-Marie Leclerc ◽  
Caroline Laverdière ◽  
...  

Abstract Background Children undergoing therapy for acute lymphoblastic leukemia (ALL) are at high risk of invasive pneumococcal disease (IPD). Immunization with conjugated vaccines following chemotherapy is recommended for pediatric patients. In an attempt to provide an earlier protection against invasive pneumococcal infection, we aimed to assess immunity to S. pneumoniae among children vaccinated during chemotherapy for ALL. Methods We retrospectively analyzed the rate of seroprotection among ALL children treated in our institution in accordance with the DFCI ALL Consortium protocol between 2007 and 2014. A pneumococcal conjugate vaccine (PCV) booster was given to all subjects after the end of chemotherapy (groups 1 and 2). In group 2, a PCV dose was also administered during the maintenance phase. Clinical characteristics as well as individual immunization records were collected from our local immunization database. All children were up to date with their vaccination schedule at diagnosis. Serum samples were obtained on a routine follow-up visit, after the end of chemotherapy and after the PCV vaccine booster to measure serotype-specific IgG pneumococcal antibodies. Antibody level ≥0.35µg/mL was considered protective. Patients with seroprotective antibodies level for ≥ 50% of serotypes contained in vaccines were defined as seroprotected. Results 62 children [34 girls (54.8%)] were included in the analysis. Median age at diagnosis was 45 months (range:12–160). At the end of chemotherapy, 34.2% of children in group 1 (13/38) and 79.2% in group 2 (19/24) were seroprotected (P < 0.01). Median interval of time between the end of chemotherapy and the PCV booster vaccination was 6 months (range: 2–64 months). After PCV-13 booster, the rate of seroprotection raised to 100% (38/38) in group 1 and 91.7% in group 2 (22/24). Conclusion Rates of pneumococcal seroprotected children treated for ALL are low at the end of chemotherapy. However, PCV booster during chemotherapy could be useful to increase the level of seroprotection and shorten the period of susceptibility to IPD. After chemotherapy for ALL, children benefit from a PCV booster to enhance seroprotection. Disclosures All authors: No reported disclosures.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4994-4994
Author(s):  
Nicholas John Kelleher ◽  
David Gallardo ◽  
Salut Brunet ◽  
Pau Montesinos ◽  
Josep-Maria Ribera ◽  
...  

Abstract Background Therapy related acute lymphoblastic leukemia, a subset of secondary acute lymphoblastic leukemia has been estimated as accounting for between 1.2 and 6.9% of all adult acute lymphoblastic leukemia cases. It has been associated with an increased frequency of high risk cytogenetic alterations and with worse clinical outcomes. It has been suggested these patients should be included in high risk treatment protocols. Method In order to evaluate these characteristics in a group of similar patients we contacted centres working within the PETHEMA group to request data on patients diagnosed with ALL asking for clinical information including the presence or absence of previous neoplasia and of previous cytotoxic therapy along with treatment responses and survival data. Results We received information on 429 patients of whom 22 had received cytotoxic therapy for a prior neoplasm.Patients were divided into group 1 with prior cytotoxic therapy, group 2 with prior neoplasia without cytotoxic therapy and group 3 de novo ALL. We found patients in group 3 to be younger than the other two groups Group 1( 55 years) Group 2 (65 years) Group 3 (34 years) (p=0.001). No statistically significant difference was shown for white cell count, cytopenias, CNS involvement, LDH or for B versus T immunophenotype. Nor did our series show a significant difference in the frequencies of high risk cytogenetics between the groups. Figures for complete remission [Group 1- 13 (93%); Group 2- 6 (75%); Group 3-346 (85%) p=0.477] were higher in group 1 therapy related ALL compared with de novo patients without reaching clinical significance. Nor was a statistically significant difference shown for 3 year overall survival [Group 1 (80%); Group 2 (38%); Group 3 (47%) p=0.151] , 3 year event free survival [Group 1 (67%); Group 2 (38%); Group 3 (42%) p=0.24] or for complete remission duration [Group 1 (75%);Group 2 (50%); Group 3 (60%) p=0.462] Conclusion Apart from age, our series did not show an increase in poor risk clinical or cytogenetic features in therapy related ALL patients compared with de novo disease cases and nor was clinical outcome demonstrated to be worse. This would suggest that risk stratification should be carried out using currently recognized parameters without specifically taking into account the status of therapy related disease. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2490-2490
Author(s):  
Hassan B Alkhateeb ◽  
Tasha Lin ◽  
Moussab Damlaj ◽  
Aref Al-Kali ◽  
Naseema Gangat ◽  
...  

Abstract Background: Adult T-cell acute lymphoblastic leukemia / lymphoma (T-ALL) is an rare and aggressive hematological malignancy with overall survival (OS) according to the UKALL XII/E2993 of 48% at 5 years (Marks et al, Blood 2009). Over the last decade, the incorporation of L-asparaginase, dose intensification (similar to pediatric protocols), availability of newer agents such as clofarabine (Dec 2004) and nelarabine (Oct 2005) have been shown to improve outcomes. We carried out this study to see if the above mentioned changes in treatment have translated to an OS benefit. Methods: After due IRB approval, adults diagnosed with T-ALL from 1990-2014 at Mayo Clinic were identified. All clinical and pathologic data was retrospectively reviewed Comparative analysis was performed based on year of diagnosis before and after 2005 (Group 1, diagnosis prior to 2005, and Group 2, diagnosis post 2005). Survival was estimated using the Kaplan-Meier Method and log-rank test. Chi-square test was used to compare variables. Results: A. Patient Characteristics: Between 1990 and 2014, a total of 92 consecutive patients (pts) with T-ALL were identified. Median age at diagnosis was 33 years (range; 18-88 years) with 72% males. Distribution of pts by year of diagnosis was as follows: Group 1(n= 47) (51%), and Group 2 (n=45) (49%). Median overall survival was 97.2 months. Median follow up for Group 1 was 50 months, during which time 23 (39%) deaths were documented, and 22.8 months (0.9 - 115.4) for Group 2 at which time19 deaths (42%) were documented (p= 0.04). Pts in Group 2 were older than Group1 (median age 41 vs 27 years (p= 0.004). Apart from age, the two groups were similar in other characteristics (Table 1). B. Therapy received by patient groups: We observed a high use of L-asparaginase containing regimens in Group 1 vs Group 2 [35(74%) pts vs 19 (42%), p=0.0013]. In contrast there was an increase in use of Hyper-CVAD in Group 2; 23(51%) vs. 3 (6%) (p<0.0001). There was no difference in the use of intensive pediatric protocols (p=0.11). There was a trend of increased use of nelarabine in Group 2, however clofarabine usage was not different (p=0.09, and p=0.6 respectively) (Table1). Allogenic stem cell transplant was offered more in Group 2 compared to Group 1, 16 (36%) patients vs. 10 (21%) patients (p=0.0009). In contrast, 7 (19%) patients underwent autologous transplantation in group 1 vs. none in group 2 (p=0.0009). C. Overall outcome by patient groups: We did not observe any difference in CR, or relapse rates among the two groups. The median OS and time to relapse were also not statistically different among Group 1 and 2 [102.6 vs 61.8 months Figure A, and 7.1 vs 14.1 months respectively]. Furthermore, age adjusted survival analysis was also not statistically significant. Conclusion: In this large cohort of adult T-ALL patients, in spite of significant advances in treatment strategies over the last two decades, we observed no difference in overall and relapse free survival prior to and after 2005. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Al-Kali: Celgene: Research Funding. Thompson:Kite Pharma: Research Funding. Witzig:Spectrum: Research Funding; Novartis: Research Funding; Celgene: Research Funding; Amgen: Honoraria; Valeant Pharma: Equity Ownership.


2010 ◽  
Vol 28 (11) ◽  
pp. 1911-1918 ◽  
Author(s):  
Silvia R. Brandalise ◽  
Vitória R. Pinheiro ◽  
Simone S. Aguiar ◽  
Eduardo I. Matsuda ◽  
Rosemary Otubo ◽  
...  

PurposeTo describe event-free survival (EFS) and toxicities in children with low-risk acute lymphoblastic leukemia (ALL) assigned to receive either continuous 6-mercaptopurine (6-MP) and weekly methotrexate (MTX) or intermittent 6-MP with intermediate-dose MTX, as maintenance treatment.Patients and MethodsBetween October 1, 2000, and December 31, 2007, 635 patients with low-risk ALL were enrolled onto Brazilian Childhood Cooperative Group for ALL Treatment (GBTLI) ALL-99 protocol. Eligible children (n = 544) were randomly allocated to receive either continuous 6-MP/MTX (group 1, n = 272) or intermittent 6-MP (100 mg/m2/d for 10 days, with 11 days resting) and MTX (200 mg/m2every 3 weeks; group 2, n = 272).ResultsThe 5-year overall survival (OS) and EFS were 92.5% ± 1.5% SE and 83.6% ± 2.1% SE, respectively. According to maintenance regimen, the OS was 91.4% ± 2.2% SE (group 1) and 93.6% ± 2.1% SE (group 2; P = .28) and EFS 80.9% ± 3.2% SE (group 1) and 86.5% ± 2.8% SE (group 2; P = .089). Remarkably, the intermittent regimen led to significantly higher EFS among boys (85.7% v 74.9% SE; P = .027), while no difference was seen for girls (87.0% v 88.8% SE; P = .78). Toxic episodes were recorded in 226 and 237 children, respectively. Grade 3 to 4 toxic events for groups 1 and 2 were, respectively, 273 and 166 for hepatic dysfunction (P = .002), and 772 and 636 for hematologic episodes (P = .005). Deaths on maintenance were: seven (group 1) and one (group 2).ConclusionThe intermittent use of 6-MP and MTX in maintenance is a less toxic regimen, with a trend toward better long-term EFS. Boys treated with the intermittent schedule had significantly better EFS.


2020 ◽  
Vol 21 (6) ◽  
pp. 403-410
Author(s):  
Apichaya Puangpetch ◽  
Rawiporn Tiyasirichokchai ◽  
Samart Pakakasama ◽  
Supaporn Wiwattanakul ◽  
Usanarat Anurathapan ◽  
...  

Aim: 6-Mercaptopurine (6MP) is key to the treatment of acute lymphoblastic leukemia (ALL) as part of maintenance therapy. NUDT15 was identified as a novel thiopurine regulator conferring 6MP sensitivity. The aim of this study was to evaluate the influence of NUDT15 variants on 6MP-induced neutropenia in Thai children with ALL. Materials & methodology: Genotyping of NUDT15 (c.415C>T; rs116855232) and c.36_37insGGAGTC; rs554405994) was performed by Sanger sequencing in 100 patients with ALL. Patients were classified into wild-type (group 1), heterozygous variant (group 2) and homozygous variant (group 3). Clinical and laboratory features during the first 6 months of maintenance therapy were investigated. Therapy-induced neutropenia was observed in 31 patients during the weeks 1–8 (early myelotoxicity), while therapy-induced neutropenia was observed in 47 patients during the weeks 9–24 (late myelotoxicity). Results: There were 85 wild-type patients, 14 heterozygous variant patients and one homozygous variant patient. NUDT15 variants were associated with neutropenia as compared with wild-type (odds ratio: 17.862; 95% CI: 4.198–75.992, padj = 9.5 × 10-5). Multivariate analysis showed that the low-risk group was associated with neutropenia (p = 0.014) in the first 8 weeks of 6MP therapy. Group 2 and group 3 patients had significantly lower absolute neutrophil counts compared with group 1. The adjusted dose during the first 6 months of maintenance therapy with NUDT15 genotype group 1, 2 and 3 were 50, 36.6 and 12.5 mg/m2/day, respectively. Conclusion: Taken together, our results indicate NUDT15 variants may cause neutropenia, and the 6MP dosage should be considered in patients according to the NUDT15 variants to inform personalized 6MP therapy.


2019 ◽  
Vol 71 (5) ◽  
pp. 1271-1280 ◽  
Author(s):  
Jessica Bate ◽  
Ray Borrow ◽  
Julia Chisholm ◽  
Stuart C Clarke ◽  
Elizabeth Dixon ◽  
...  

Abstract Background Children with acute lymphoblastic leukemia (ALL) are at increased risk of developing invasive pneumococcal disease. This study describes the immunogenicity of 13-valent pneumococcal conjugate vaccine (PCV13) during and after chemotherapy. Methods Children with ALL were allocated to study groups and received a single dose of PCV13: group 1, maintenance chemotherapy; group 2, end of chemotherapy; group 3, 6 months after chemotherapy. A protective vaccine response was defined as at least 10 of 12 serotypes (or &gt;83% of serotypes with data) achieving postvaccination serotype-specific immunoglobulin G ≥0.35 µg/mL and ≥4-fold rise, compared to prevaccination at 1 and 12 months. Results One hundred eighteen children were recruited. Only 12.8% (5/39; 95% confidence interval [CI], 4.3%–27.4%) of patients vaccinated during maintenance (group 1) achieved a protective response at 1 month postvaccination and none had a protective response at 12 months. For group 2 patients, 59.5% (22/37; 95% CI, 42.1%–75.3%) achieved a response at 1 month and 37.9% (11/29; 95% CI, 20.7%–57.7%) maintained immunity at 12 months. For group 3 patients, 56.8% (21/37; 95% CI, 39.5%–72.9%) achieved a protective response at 1 month and 43.3% (13/30; 95% CI, 25.5%–62.6%) maintained immunity at 12 months. Conclusions This study demonstrated that the earliest time point at which protective immunity can be achieved in children with ALL is on completion of chemotherapy. This is earlier than current recommendations and may improve protection during a period when children are most susceptible to infection. Clinical Trials Registration EudraCT 2009-011587-11.


2016 ◽  
Vol 1 (1) ◽  
pp. 172-178
Author(s):  
G. A. Aleskerova

The article tells about the main stages of improving treatment regimens for acute lymphoblastic leukemia (ALL) in children, from monotherapy with prednisolone and 6-mercaptopurine to novel multicomponent risk-adapted chemotherapy protocols. The focus is on evaluating risk factors which varied with the expansion of knowledge about the molecular biological profile of ALL. Only the detailed analysis of the clinical and immunobiological characteristics of ALL allowed to develop novel, highly effective treatment schemes leading to recovery in over 80% of patients.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3940-3940
Author(s):  
Andrew S. Freiberg ◽  
Deborah Kees-Folts ◽  
Anne-Marie Dyer ◽  
Megan Taylor

Abstract Background: The most common form of cancer in children is acute leukemia, with acute lymphoblastic leukemia (ALL) comprising approximately seventy-five percent of these. The initial month of therapy (induction) for all children with ALL includes high dose steroids. One of the side effects of these steroids is hypertension. Objective: To determine the incidence and risk factors of hypertension during induction chemotherapy for acute lymphoblastic leukemia in children. Methods: Retrospective analysis was performed of data collected from all children diagnosed with acute lymphoblastic leukemia (ALL) at Hershey Medical Center (HMC) in 2004 and 2005 (n = 37). Each blood pressure from presentation through the four weeks of induction was recorded. To minimize the effect of a single high blood pressure measurement, median systolic and diastolic pressures were determined for each of the four weeks of induction therapy. These pressures were compared to published age matched norms. For each patient and each week of therapy, the percentile (&lt;50, 50–90, 90–95, &gt;99) was determined. Results: Thirty-seven children (21 male, 16 female) met study criteria, with a median age of five. Thirteen of these patients received prednisone and twenty-four received dexamethasone. Overall, 95% of children had mean systolic or diastolic pressures &gt;90th percentile, 81 had pressures &gt;95th percentile, and 51% were above the 99th percentile for at least one week of induction. By contrast, only 32%, 19%, and 11% had pressures at these levels at initial presentation. The incidence of significant hypertension increased significantly during the four weeks of induction. Only three children (10%) with pressures above the 95th percentile were clearly noted in the medical record to be hypertensive, and only two children (6.7%) with pressures this high were treated. Conclusions: Hypertension is common and underrecognized during induction chemotherapy for childhood ALL. The incidence of hypertension increases weekly during induction chemotherapy.


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