Growth disturbances and metabolic disorders in childhood cancer survivors

2016 ◽  
Vol 62 (5) ◽  
pp. 62-63
Author(s):  
Tatyana Y. Tselovalnikova ◽  
Alla E. Yudina ◽  
Maria G. Pavlova ◽  
Alexey V. Zilov ◽  
Nadezhda A. Mazerkina ◽  
...  
Keyword(s):  
Childhood Cancer ◽  
Metabolic Disorders ◽  
Lymphoblastic Leukemia ◽  
Tolerance Test ◽  
Hormone Deficiency ◽  
Healthy Controls ◽  
Target Height ◽  
Growth Disturbances ◽  
Group 2 ◽  
Group 1

Background. Endocrine consequences such as growth hormone deficiency (GHD), growth disturbances and metabolic disorders are common in childhood cancer survivors.Aim: to evaluate and compare the prevalence of growth disturbances and metabolic disorders in childhood posterior cranial fossa tumors (cPCFT) and acute lymphoblastic leukemia (cALL) survivors.Materials and methods. 40 subjects (21 men, 19 women) who had undergone treatment for cPCFT (group 1) and 25 subjects (9 men, 16 women) after treatment for cALL (group 2) were assessed. Group 1 underwent surgery, chemotherapy (CT) and craniospinal irradiation in a dose of 34.9 ± 1.6 Gy with a boost to the PCF 51.3 ± 9.2 Gy. Group 2 underwent CT (23 subjects were treated with ALL-BFM-90 protocol; 2 subjects were treated with ALL-MB-2002 protocol). All subjects of the group 2 received cranial irradiation in a dose 12,7±2 Gy. Age at the time of the survey in a group 1 and 2 – 19.8 ± 3.05 and 21.2±3.9 years; age at the time of treatment – 10.9 ± 3.4 and 6.9±3.4 years; follow-up – 7.2 ± 4.2 and 13.8±4.9 years, respectively. 16 age and sex matched healthy controls were included. Patient’s anthropometric and laboratory parameters were measured, GHD was diagnosed in group 1 by 2 tests – insulin tolerance test (ITT) and glucagon stimulation test (GST). In group 2 these tests didn't perform. At the time of the survey no one in both groups received GH replacement therapy. Only 5 subjects (3 boys and 2 girls) in group 1 were treated with recombinant human GH during childhood.Results.Final height SDS in the group 1 was significantly less than in the group 2 (p=0.001) and in healthy controls (p<0.001). In the group 1 and 2 there were significantly less patients reached target height compared to healthy controls (p<0.001). Subjects of group 1 rarely reached their target height in comparison to the group 2 (p=0.006). IGF-1 SDS was significantly less in the group 1 (-1.37±1.24) than in the group 2 (0.5±1.24, p<0.001). In group 1 GHD according to GST was diagnosed in 60% of subjects, according to ITT in 82.1% of subjects. Waist circumference was significantly bigger in group 2 compared to the group 1 (p=0.046) and to healthy controls (p=0.001). Overweight was registered in 10% of patients in group 1 and in 16% - in group 2. Dyslipidemia was diagnosed in 50% in group 1, in 19% in group 2 (p=0.226). In group 1 16.7% and in group 2 66.7% of subjects were insulin resistant.Conclusions. After treatment for cPCFT growth disturbances occurred more often than after cALL therapy. Metabolic disorders were diagnosed with different frequency in both cPCFT and cALL survivors. These patients need endocrinologist’ observation.

scholarly journals Surgically treated acromegaly patients have a similar quality of life whether controlled by surgery or requiring additional medical therapy (QuaLAT Study)

Pituitary ◽  
2021 ◽  
Author(s):  
Muhammad Fahad Arshad ◽  
Oluwafunto Ogunleye ◽  
Richard Ross ◽  
Miguel Debono
Keyword(s):  
Quality Of Life ◽  
Medical Treatment ◽  
Physical Component Score ◽  
Healthy Controls ◽  
Component Score ◽  
Post Surgery ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Purpose There is no consensus on quality of life (QOL) in patients with acromegaly requiring medical treatment after surgery compared with those achieving remission by surgery alone. Methods QuaLAT is a cross-sectional study comparing QOL in surgery-only treated acromegaly patients versus those requiring medical treatment post-surgery. Patients attending clinics were identified and divided into—Group 1: patients who had surgery only and were in biochemical remission, Group 2: all patients on medical treatment post-surgery, Group 3: patients from Group 2 with biochemical control. Participants were asked to fill three questionnaires; Acromegaly Quality of Life Questionnaire (ACROQOL), 36-Item Short Form Survey (SF36), and Fatigue Severity Scale (FSS). Results There were 32 patients in Group 1 and 25 in Group 2. There was no difference in QOL scores between groups 1 and 2, as measured by ACROQOL (mean difference [MD] = − 2.5, 95% CI − 16.6 to 11.6; p = 0.72), SF36v2 [Physical component score (PCS) MD = − 4.9, 95% CI − 10.9 to 1.2; p = 0.12; mental component score MD = − 3.0, 95% CI − 10.5 to 4.4; p = 0.44], or FSS (MD = − 0.004, 95% CI − 1.14 to 1.33; p = 0.1). Comparison between groups 1 and 3 however showed that PCS (and 3 subdomains) was significantly better in group 3 (MD = − 8.3, 95% CI − 14.8 to -1.8; p = 0.01). All three QOL scores were lower when compared with healthy controls. Conclusions Medical treatment not only achieves a QOL comparable to surgery, it may also be associated with better QOL in physical subdomains. When compared with healthy controls, QOL remains worse in treated acromegaly patients compared to controls.

GROWTH AND GROWTH HORMONE. IV. LIMITATIONS OF THE GROWTH HORMONE RESPONSE TO INSULIN AND ARGININE AND OF THE IMMUNOREACTIVE INSULIN RESPONSE TO ARGININE IN THE ASSESSMENT OF GROWTH HORMONE DEFICIENCY IN CHILDREN

PEDIATRICS ◽  
1969 ◽  
Vol 43 (6) ◽  
pp. 989-1004
Author(s):  
R. Youlton ◽  
S. L. Kaplan ◽  
M. M. Grumbach
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Gh Deficiency ◽  
Hormone Deficiency ◽  
Insulin Administration ◽  
Arginine Infusion ◽  
Group 3 ◽  
Group 2 ◽  
Serum Gh ◽  
Group 1

The growth hormone (GH) response to insulin-induced hypoglycemia and to arginine infusion has been evaluated in 60 children with growth retardation. These children have been classified into three groups: Group 1-9 children had peak serum growth hormone values of 7 mµg/ml or greater to both stimuli, a normal growth hormone response. Group 2-18 children had peak GH values of ≤ 3 mµg/ml to both stimuli, an abnormal response indicating growth hormone deficiency. Group 3-6 children had a blunted GH response (&gt; 3 &lt; 7 mµg/ml) to both stimuli; 8 showed a normal rise in serum GH following arginine infusion (&gt; 7 mµg/ml) but exhibited no rise, or a minimal one, following insulin administration; 9 children had minimal increase in serum GH concentration following arginine infusion but showed a normal GH response to insulin administration (&gt; 7mµg/ml). Children included in Group 3 represent a heterogenous population. In some patients with a blunted response to both stimuli, evidence of partial or less severe form of GH deficiency was found, whereas in 17 of 18 children exhibiting a disparate response the impaired growth was not attributable to growth hormone deficiency. The blood glucose at all sampling periods was significantly lower following insulin administration in patients in Group 2 than that observed for children in Group 1 and 3. The blood glucose was significantly lower at 90 and 120 minutes following arginine infusion in Group 2 compared to values for patients in Group 1 and 3. Changes in serum insulin in response to the infusion of arginine did not provide a useful index of discrimination among these groups. Administration of diethylstilbestrol, 10 mg/day times 2 days, prior to testing can modify the GH response to both hypoglycemia and arginine; it is a useful ancillary procedure in children with blunted or disparate responses. These studies suggest that two types of stimulation tests are necessary to establish the diagnosis of isolated GH deficiency with a high degree of probability.

scholarly journals Effect of the first and second postpartum partial milking on blood serum calcium concentration in dairy cows

2014 ◽  
Vol 59 (No. 3) ◽  
pp. 128-133
Author(s):  
E.G. Salgado-Hernández ◽  
A. Aparicio-Cecilio ◽  
F.H. Velásquez-Forero ◽  
D.A. Castillo-Mata
Keyword(s):  
Blood Serum ◽  
Dairy Cows ◽  
Serum Calcium ◽  
Metabolic Disorders ◽  
Calcium Concentration ◽  
Atomic Absorption Spectrophotometry ◽  
Serum Calcium Concentration ◽  
Group 2 ◽  
Group 1

Parturient paresis and subclinical hypocalcemia are frequent metabolic disorders in dairy cows postpartum. The aim of this study was to determine the effect of postpartum partial milking in the first two milkings on blood serum calcium concentration in dairy cows. Twenty multiparous Holstein dairy cows were randomized into two groups. Cows of group 1 (n = 10) were partially milked at the first and second milking postpartum. Cows of group 2 (n = 10) were completely milked. Blood samples were collected from all animals 5&ndash;7 days before calving, within 30 min after calving, and 4, 8, 12, 16, 20, 24, 28, and 32 h after calving for determination of serum calcium (Ca), phosphorus (P), and magnesium (Mg) concentrations. Colostrum production was registered and sampled in the first and second milking. Concentration of Ca in colostrum was determined by atomic absorption spectrophotometry. Serum Ca and P concentrations decreased in both groups after parturition (P &lt; 0.05) and remained low during 32 h postpartum with no difference observed between groups (P &gt; 0.05). Serum concentrations of Mg were stable in all samples and no statistical difference was observed between groups (P &gt; 0.05). Colostrum production was higher in completely milked cows only in the first postpartum milking (P &lt; 0.05), but there was no difference between groups at the second milking. Total Ca secretion in colostrum was higher in the complete milking group at the first and second postpartum milking. Colostrum Ca secretion increased at the second milking with respect to the first one in both groups (P &lt; 0.05). There was no correlation between serum Ca and colostrum Ca (P &gt; 0.05). In this study, the partial milking of colostrum in the first and second milking postpartum did not prevent subclinical hypocalcemia in dairy cows. &nbsp;

P5273Trabecular complexity as a subclinical structural alteration in Fabry cardiomyopathy: a cardiac magnetic resonance study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
D Lazzeroni ◽  
A Camporeale ◽  
F Moroni ◽  
S Garibaldi ◽  
S Pica ◽  
...  
Keyword(s):  
Fractal Dimension ◽  
Cardiac Magnetic Resonance ◽  
T1 Mapping ◽  
Cardiac Involvement ◽  
Fractal Dimensions ◽  
Healthy Controls ◽  
Lv Mass ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Background Heart involvement represents the main cause of death in Fabry Disease (FD), thus its early detection is important to define the optimal therapeutic strategy. Recently, a disproportionate increase in myocardial trabeculation has been described in FD by cardiac magnetic resonance (CMR), even in early (prehypertrophic) stage of the disease. In addition, CMR with T1 mapping can identity the presence of myocardial sphingolipid storage (causing lowering of native T1 values) in more than 50% of FD patients with no LVH. However, it is not clear whether a relationship exists between trabecular complexity and sphingolipid storage in FD. Aim To explore the association between myocardial trabecular complexity, quantified by endocardial border fractal analysis, and sphingolipid storage, described by CMR T1 mapping, in different stages of Fabry cardiomyopathy. Methods Study population included 60 subjects: 15 FD patients with no detectable signs of cardiac involvement (no LVH, normal T1; 2 M, age 30.6±14; Group 1); 15 FD patients with early sphingolipid storage (no LVH, low T1; 9 M, age 33±9.6; Group 2); 15 FD patients with LVH (11 M, age 53.5±9.6; Group 3); 15 healthy controls (9 M, age 34±10). Patients and controls underwent CMR with T1 mapping; disease severity was quantified using Mainz Severity Score Index (MSSI). Myocardial trabecular fractal dimension was evaluated, blinded to patients'characteristics, on short axis cine images using the Image J dedicated plug-in FracLac, deriving the following parameters: total, basal, mid-ventricular and apical fractal dimensions. Results Total fractal dimension was higher in all Fabry groups compared to controls. Indeed, a gradient of total fractal dimension was observed, with this parameter gradually increasing from healthy controls to Groups 3 (1.27±0.02 in controls vs 1.29±0.02 in Group 1 vs 1.30±0.02 in Group 2 vs 1.34±0.02 in Group 3; p<0.001) (Figure 1A). Interestingly, both total and basal fractal dimensions were significantly higher in Group 1 compared to controls (1.27±0.02 vs 1.29±0.02, p=0.044 and 1.26±0.04 vs 1.30±0.03; p=0.007, respectively). Moreover, considering the total population, fractal dimension showed significant correlations with: i) T1 values (r=−0.567; p<0.001 - Figure 1B); ii) LV mass (r=0.674, p<0.001); iii) trabecular mass expressed as percentage of global LV mass (r=0.611; p<0.001); iv) MSSI (r=0.535; p<0.001). Conclusion Cardiac involvement in FD is characterized by a progressive increase in fractal dimension of endocardial trabeculae (Figure 1C). Both total and basal myocardial trabeculation are increased in Fabry patients even before the presence of detectable sphingolipid storage, thus representing a very early sign of cardiac involvement.

scholarly journals 2699. Pneumococcal Vaccination During Chemotherapy in Children Treated for Acute Lymphoblastic Leukemia

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S949-S949
Author(s):  
Sarah Dorval ◽  
Léna Coïc ◽  
Denis Blais ◽  
Jean-Marie Leclerc ◽  
Caroline Laverdière ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Pneumococcal Infection ◽  
Pneumococcal Vaccination ◽  
Booster Vaccination ◽  
Maintenance Phase ◽  
Vaccination Schedule ◽  
Serum Samples ◽  
Group 2 ◽  
Group 1

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.

Treatment of Adult T-ALL with a Pediatric Asparaginase-Intensive Protocol Results in Survival Benefit When Compared to Other Adult Based Protocols

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3956-3956
Author(s):  
Murtadha K. Al-Khabori ◽  
Mark Minden ◽  
Vikas Gupta ◽  
Aaron D. Schimmer ◽  
Andre C. Schuh ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Treatment Regimen ◽  
Lymphoblastic Leukemia ◽  
Remission Induction ◽  
Entire Group ◽  
Induction Phase ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
Group 2 ◽  
Group 1

Abstract T cell acute lymphoblastic leukemia (T-ALL) accounts for 14–22% of adult ALL. No prospective comparisons between different chemotherapy protocols have been done. Since 2000 a modified DFCI protocol (Silverman et al, Blood2001;97:121–1218) has been used as standard treatment for all newly diagnosed patients with T-ALL at Princess Margaret Hospital (PMH). This protocol includes a remission induction phase, a CNS prophylaxis phase with intrathecal chemotherapy and 12 Gy cranial irradiation, a 30-week intensification phase including weekly asparaginase, and a 72-week maintenance phase. We compared outcomes using this regimen to previous results for all newly diagnosed T-ALL from 1990 – 2000 at PMH using the standard institutional protocol in use at the time. Between 1990–2000, 44 patients (Group 1) were treated with a variety of protocols, including 9203ALL PMH protocol (11 patients), L10 (2 pts), Protocol C (7 pts), HyperCVAD (15 pts) and ECOG E2993 (9 pts). From 2000–2007, 33 T-ALL patients were treated with modified DFCI protocol (Group 2). The median age for all patients was 31 years (range 14–69 years). There was no significant difference between the two groups with respect to age at diagnosis, presenting WBC (median or percent &gt; 100 ×109/L), CSF positivity, or cytogenetics. More patients from Group 1 underwent allogeneic stem cell transplantation (BMT) in CR-1 (54%) as compared to those in Group 2 (54% vs. 14%, P = 0.001), primarily due to a change in BMT policy in 2002. The median follow up was 23 months (range 1–161 months) for the entire group and 53 months (range 14–161 months) for the surviving patients. Sixty-nine patients (90%) achieved complete remission, and 37 patients have relapsed. The CR rates were not significantly different between the two groups. The 3-year failure-free survival (FFS) was significantly higher in Group 2 (DFCI protocol) as compared with Group 1 (other protocols) (89% vs. 27%, P = 0.0001). Multivariate analysis using Cox proportional hazard model showed only the treatment regimen received (DFCI vs. others) to have a statistically significant impact on FFS (P = 0.0001). The 3-year overall survival (OS) was significantly higher in the DFCI group compared to the group receiving the other protocols (81% vs. 45%, P = 0.0006). On multivariate analysis, only the treatment regimen received (P=0.001) and the CSF status (P=0.014) had a significant impact on OS; BMT did not have a significant impact on OS. When patients were censored at the time of transplant, the FFS and OS analyses still showed statistically significant benefit for patients treated on DFCI protocol (P = 0.0001 and 0.03, respectively). In summary, treatment outcomes have markedly improved from 2000 onward as compared to the previous decade. Although improvements in supportive care and reduced use of allogeneic BMT may have been factors, it is likely that the institution of the DFCI pediatric protocol was the primary factor in the improved outcome. These results support the use of such pediatric asparaginase-intensive pediatric protocols for adult T-ALL.

Flow Cytometric Minimal Residual Disease Levels After First Inducton Can Define T-Acute Lymphoblastic Leukemia Patients with High Risk of Relapse

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4817-4817 ◽  
Author(s):  
Veselka Nikolova ◽  
Velizar Shivarov ◽  
Ricardo Morilla
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Treatment Options ◽  
Phenotypic Expression ◽  
Time Points ◽  
Group 2 ◽  
Time Point ◽  
Group 1

Abstract Abstract 4817 T-cell acute lymphoblastic leukemia (T-ALL) patients have increased risk for treatment resistance and early relapse. The precise bone marrow evaluation for the presence of minimal residual disease (MRD) is essential for guiding treatment options. This requires techniques more sensitive than the level of sensitivity of light microscopic technique such as multicolour flow cytometry (FCM). Immunophenotypic alterations called leukemia associated immunophenotypic patterns (LAIP) (i.e.aberrant myeloid markers) and ectopic phenotypic expression (i.e. appearance of immature phenotypes such as TdT, CD1a and CD3 outside their normal site in the thymus) are of benefit to track the residual leukemic cells in T-ALL. A retrospective data analysis of MRD was done comprising T-ALL patients diagnosed and followed-up at the Institute of Cancer Research/Royal Marsden Hospital by means of 3-colour flow cytometry (3C FCM).The aim was to answer a question whether the 3C FCM can reliably split patients into two groups (positive, MRD+ and negative, MRD-) and predict a subsequent relapse and to define a right time point for performing MRD tests. Eight patients were enrolled in the study following the inclusion criteria: (i) complete remission after 1st induction phase of chemotherapy, (ii) presence of LAIP or an ectopic phenotypic expression, and (iii) monitored at defined time points after initial treatment. MRD was measured during the first year of treatment as follows: at the end of phase 1 induction (day 29–35, MRD1), before the start of consolidation (3 months, MRD2), after consolidation (MRD3), during the maintenance therapy (12 months, MRD4). Immunophenotyping was performed on lysed-washed bone marrow samples using CD45 gating strategy and originally defined blast gates at diagnosis. The phenotypes to be followed-up included: TdT+/CytCD3+, CD34+/CYTCD3+, TdT+/CD2+, CD8+/CD10+, CD2+/CD10+, CD7+/CD10+, CD7+/CD33+, CD7+CD34+. Patients were divided into 2 groups in relation to subsequent relapse. Group 1 included 6 patients without relapse. Patient characteristics of the group were: male:female 5:1, mean age 17.7 years, overall survival (OS) 59 months, relapse free survival (RFS) 85 months. Group 2, relapsed patients, included 2 men, mean age 56 years, OS 13 months, RFS 8.5 months. According to the EGIL classification system the 2 men in Group 2 were with an early T-precursor phenotype, whilst Group 1 was heterogenous but cortical-T-ALL predominated. Cytogenetics/FISH and RQ-PCR studies were performed at diagnosis and showed normal karyotype in only one of the Group 2 patients. MRD results showed a difference between the two groups as regards MRD1 and MRD2 time points. Group 1 patients had negative or low MRD levels (below 0.18%) in their MRD1 bone marrow - MRD-, n=4 and MRD+,n=2 (0.18% and 0.12% respectively, sensitivity 0.04%). Those of them who were tested at MRD2 and MRD3 were negative. Both patients in Group 2 showed higher levels of MRD positivity at MRD1 (1% of total bone marrow cells), the first one of them also being positive at MRD2 and the second one becoming MRD+ at MRD4 time point. Although turning to MRD- at MRD3 time point both Group 2 patients relapsed 2.5 and 4.5 months, respectively, after the end of consolidation treatment. Additionally, Group 1 patients had a significantly longer RFS than Group 2 (median 58 months RFS vs. 8.5 months; P <0.001). Conclusions: Reliable detection of MRD in T-ALL is possible by 3C FCM using a combination of TdT and a T cell marker (cytCD3 or mCD3) as such a combination is normally found exclusively in the thymus. The higher MRD-positive levels in Group 2 reflect the more resistant disease in this group and higher probability of early relapse and shortened overall survival. Early T-cell precursor phenotype in these patients appeared to be a subtype at very high risk for treatment failure irrespective of the lack or the presence of genetic lesions. Based on MRD positivity above 0.18% at time points MRD1 or both MRD1 and MRD2 these patients need reassessment of treatment options and more intensive therapy has to be considered for relapse prevention. Finally, the results of our retrospective study suggest the usefulness of implementation of MRD testing by FCM for taking clinical decisions in the prospective clinical trials for novel therapies for T-ALL. Acknowledgments: The study was supported by the Union for International Cancer Control, Geneva, Switzerland (Grant ICRETT-080–2011) Disclosures: No relevant conflicts of interest to declare.

Therapy Related Acute Lymphoblastic Leukemia: Pethema Experience

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4994-4994
Author(s):  
Nicholas John Kelleher ◽  
David Gallardo ◽  
Salut Brunet ◽  
Pau Montesinos ◽  
Josep-Maria Ribera ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Cytotoxic Therapy ◽  
Survival Group ◽  
Significant Difference ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

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.

Predictive Value of Minimal Residual Disease: Analysis By Flow-Cytometry in Children with Relapsed Acute Lymphoblastic Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2494-2494
Author(s):  
Myriam Ruth Guitter ◽  
Jorge Gabriel Rossi ◽  
Elisa Sajaroff ◽  
Carolina Carrara ◽  
Pizzi Silvia ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
P Value ◽  
Time Points ◽  
Group 3 ◽  
Group 2 ◽  
To Receive ◽  
Group 1

Abstract Introduction: Despite the advances observed in the outcome of pediatric acute lymphoblastic leukemia (ALL) treatment during the last 20 years, relapse remains the most common cause of treatment failure in childhood ALL. Several factors have been associated to the prognosis of these patients; however, minimal residual disease (MRD) emerges as a relevant predictor of outcome. Objectives: The aims of this study were to assess MRD by flow-cytometry in relapsed ALL and to evaluate its prognostic impact as a predictor factor of outcome at the end of the induction therapy and prior to hematopoietic stem cell transplantation (HSCT). Patients and Methods: From Aug'10 to Jun'15, 123 ALL patients were treated at our center. MRD determination at least at two time-points during relapse treatment was a requirement for considering a patient eligible for the present study. Sixty-six cases were excluded due to the following causes: 10 patients died during induction, 2 died early in complete remission (CR), 29 did not respond to chemotherapy, in 13 patients MRD determination was not performed: 4 did not have clinical data available, 4 patients were Down Syndrome and 4 children received treatment for relapse in other centers. Thus, fifty-seven patients achieved CR and were evaluated for MRD at two time points. Of them, 56 patients belonged to S4 and S3 and 1 patient to S1 group as defined by the Berlin-Frankfurt-Münster stratification for relapsed ALL. MRD was analyzed by multiparametric flow-cytometry following ALL-IC 2009 guidelines. Negative MRD was defined as disclosing less than 0.1% of blasts. For this analysis, patients were stratified based on MRD levels at two different time points: after end of induction, before HSCT or at any other time point during the follow-up for patients who did not undergo HSCT. Three groups were defined: Group-1: negative at both time points (n= 23), Group-2: positive at 1 time point (n= 13) and Group-3: positive at both time points (n= 21). Patients who relapsed before receiving HSCT were considered Group-3. Twenty-five patients underwent HSCT: 13 of them from Group-1, 9 from Group-2 (2 had positive MRD previous to receive HSCT) and 3 patients from Group-3. HSCT was performed with matched familiar donor in 16 cases and matched unrelated donor in 9 cases. Results: The distribution of events according to receiving or not HSCT was: 5 died due to transplant related mortality (TRM), 9 relapsed after receiving HSCT and 16 during treatment with chemotherapy. With a median follow-up of 16 (range: 6-67) months, overall 3-year EFS probability (EFSp) (SE) was 32 (8)%. The 3-year EFSp was 75 (11)% for Group-1, 24 (14)% for Group-2 and 0% for Group-3 (p-value <0.00001). Comparing patients who did not receive HSCT vs. patients who did, EFSp (SE) was 32 (12)% and 29 (11)% respectively (p-value: non-significant). The EFSp (SE) according to MRD groups in patients who underwent HSCT was: Group-1: 53 (19)%, Group-2: 14 (13)% and 0% for Group-3 (p-value: 0.06). Conclusions: MRD quantification by flow-cytometry demonstrated to be a significant prognostic factor for relapsed ALL. Both, TRM and death in CR rates, were high and should be decreased by improving supportive measures. MRD determination by flow-cytometry in patients who underwent HSCT showed a trend to achieve a better EFSp, thus representing a relevant tool for stratifying relapsed ALL patients in order to achieve a better selection of patients to receive HSCT. Disclosures No relevant conflicts of interest to declare.

Survival Trends in Adult T-Acute Lymphoblastic Leukemia / Lymphoma (ALL), a Comparative Analysis of 92 Patients By Year of Diagnosis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2490-2490
Author(s):  
Hassan B Alkhateeb ◽  
Tasha Lin ◽  
Moussab Damlaj ◽  
Aref Al-Kali ◽  
Naseema Gangat ◽  
...  
Keyword(s):  
Overall Survival ◽  
Comparative Analysis ◽  
Acute Lymphoblastic Leukemia ◽  
Research Funding ◽  
Lymphoblastic Leukemia ◽  
Autologous Transplantation ◽  
Cell Transplant ◽  
Patient Groups ◽  
Group 2 ◽  
Group 1

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.

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