scholarly journals Early T Acute Lymphoblastic Leukemia in Childhood: Prevalence and Clinical Characteristics

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3656-3656
Author(s):  
Jorge Gabriel Rossi ◽  
Carolina Carrara ◽  
Patricia L. Rubio ◽  
Cristina N. Alonso ◽  
Andrea Bernasconi ◽  
...  
Keyword(s):  
Chromosomal Abnormalities ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Poor Response ◽  
Early Response ◽  
Response To Treatment ◽  
Differentiation Potential ◽  
Lineage Switch ◽  
Conventional Cytogenetics

Abstract Background: Early T precursor ALL has been defined as a poor prognosis subtype, characterized phenotypically by absence of CD1a and CD8, CD5 weak expression and presence of at least one myeloid and progenitor cell marker. Objectives: Our aims were to identify Early T-ALL among our T ALL cases, based on the characteristic phenotype and thus evaluate the prevalence, biological characteristics and outcome of this particular subset of T-ALL Methods: From April ’94 to December ’13, 197 T-ALL cases were diagnosed and 20 of them showed the typical Early T marker profile by flow cytometry (FC). Conventional cytogenetics, FISH and RT-PCR studies were performed according to standard techniques. Clonality assessment for TRG, TRB, TRD, IGH and IGK was performed by PCR (Biomed-2), heteroduplex and sequencing. Results: Sex distribution was: 16 males and 4 females; median of age: 7.9 (range: 0.3-16.6) years; median WBC: 14.9 (range: 0.6-254.0) x109/L. All but one case expressed CD34, 70% HLA-DR, 61% CD117 and 50% TdT. The most frequently expressed myeloid markers were: CD33 (85%) and CD13 (55%). Three cases expressed g/d TCR. Chromosomal abnormalities were detected in 14 of 16 evaluated cases, in 5 of them compromising 12p13 region. TCR/IgH rearrangements were detected in 63% (10/16). FLT3-ITD mutations were found in 14 % (2/14). Patients were treated with BFM-based ALL schedules and were stratified as Intermediate Risk ALL (n: 7) and High Risk ALL (n: 13) according to protocol criteria. Early response to treatment was poor in 16 cases: 6 presented poor response to prednisone (day 8), 3 MRD >10%, 5 presented bone marrow M2-M3 and 2 non response. Seventeen cases (85%) achieved CR on day 33 and 2 achieved CR later. Five patients underwent HSCT in first CR. Three patients relapsed at 5, 6 and 65 months from diagnosis and one showed lineage switch to M5-AML at 12 months from CR. Three pts died in CR (2 after HSCT and 1 patient with primary immunodeficiency due to pneumonia) and one is in palliative care. Twelve patients remain in CR with a median follow-up of 54 (r: 8-144) months. Conclusions: The prevalence of Early T precursor phenotype within T ALL was 10.5% in our setting. The most frequent progenitor marker was CD34 and CD33 among myeloid markers. Of note, translocations involving 12p13 region were found in 5 patients. Sixty percent of patients remain disease free, although longer follow-up is needed in order to define prognosis of this group in our cohort of patients. The lineage switch case supports the notion of the myeloid differentiation potential of these blasts. Disclosures No relevant conflicts of interest to declare.

ETV6/RUNX1-Postitive Childhood Acute Lymphoblastic Leukemia (ALL): Do Additional Aberrations Influence Treatment Response and Outcome?

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2403-2403
Author(s):  
Maria Ampatzidou ◽  
Stephanos I. Papadhimitriou ◽  
George Paterakis ◽  
Loizos Petrikkos ◽  
Dimitrios Pavlidis ◽  
...  
Keyword(s):  
Prognostic Markers ◽  
Conflicts Of Interest ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia ◽  
Clonal Diversity ◽  
Early Response ◽  
Response To Treatment ◽  
Childhood All ◽  
Biological Features

Abstract ETV6/RUNX1 rearrangement, being the most common genetic abnormality in childhood ALL, is combined with controversial prognostic behavior and frequent late relapses, indicating the need for identification of additional prognostic markers. In our study, we examined the relation between ETV6/RUNX1 and presenting clinical/biological features, co-existing subclones/secondary aberrations, early response to treatment (MRD) and their impact on outcome in a pediatric cohort of 133 ALL pts , treated in one Center over a 12-year period. Data from 133 newly diagnosed ALL pts(83 males) with a median age of 5.1 yrs(range 1.2-16.7), have been retrospectively recorded and analyzed. Pts were consecutively diagnosed and homogeneously treated on BFM based protocols during the years 2000-2011. FISH evaluation using commercial probe sets was performed for the detection of ETV6-RUNX1, E2A-PBX1, BCR-ABL fusion genes, MLL gene rearrangements as well as ETV6, RUNX1, CDKN2A/2B and other gene duplications, deletions or amplifications. Twenty seven pts (27/133, 20.3%) were tested positive for the t(12;21)(p13;q22) translocation(16 males), with a median age of 3.9 yrs(range 2.0-16.7). Immunophenotype revealed 22/27 common (81.5%) and 5/32 pre-B cases (18.5%). All pts were characterized as GPR and treated in the IR Arm. 8/27 (29.6%) were positive for the ETV6/RUNX1 fusion gene only with no secondary aberrations. 19/27 ETV6/RUNX1-positive pts (70.4%) harbored additional structural or numerical genetic abnormalities while 8 of those pts showed presence of subclones with multiple patterns of additional ETV6 and RUNX1 aberrations. The most common abnormalities were del12p13(37%), 3-6x21q22(22.2%), del9p21(18.5%), +21(14.8%), and 2-3xETV6/RUNX1(18.5%). On day 15, 13/27 ETV6/RUNX1+ pts (48.1%) presented with FCM-MRD(d15) values≥10-3 while the corresponding percent among IR ETV6/RUNX1- pts was 46.9%. Out the 8 pts with sole t(12;21)(p13;q22) translocation, only 25%(2/8 pts) presented with MRD(d15)>10-3 while among the 19 pts with additional aberrations, the corresponding percent was 52.6% (10/19). Interestingly, referring only to ETV6/RUXN1+ pts with subclones, the percent reflecting MRD(d15)>0.1% rises to 87.5% (7/8 pts). Among the 14 pts with no MRD(d15) detection only 1/14 appeared with clonal heterogeneity. 3/27 pts (11.1%) relapsed, in a median time of 30.3 months (median follow-up time 64 months). Common features of all relapses were sub-clonal diversity at diagnosis, del(9p21) and MRD(d15) positivity. 5-year RFS for the ETV6/RUNX1+ subgroup was 86.4%±7.4 vs 87.7%±3.5 for ETV6/RUNX1- pts. The presence of the ETV6/RUNX1 fusion gene as a favorable genetic marker did not seem to have a statistically significant impact on the probability of relapse (p=0.906). The 5-year RFS for those with MRD≥0.1% was limited to 67.3% ±16.0, while the corresponding rate for MRD- pts reached 100%. ETV6/RUNX1+ childhood ALL is characterized by extreme heterogeneity and the prognostic value of the fusion itself varies, depending on coexisting clinical and biological features. In our series, the presence of additional genetic aberrations/subclones (such as del9p21 or ETV6/RUNX1 duplication) and impaired FCM-MRD clearance, influences patient outcome. Longer follow-up is needed in order to further validate these initial results. FISH and FCM data may help establish new prognostic markers to predict relapse and refine risk stratification. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Clinical Utility of Morphological Evaluation of Day 14 Bone Marrow Biopsies in Acute Myeloid Leukemia Patients Undergoing Standard Induction Chemotherapy: Time to Change Practice?

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1004-1004 ◽  
Author(s):  
Yehuda E. Deutsch ◽  
German Campuzano-Zuluaga ◽  
Matthew P Salzberg ◽  
Alexandra Gomez Arteaga ◽  
Justin M. Watts ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Predictive Value ◽  
Chromosomal Abnormalities ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Response To Treatment ◽  
Bone Marrow Biopsies ◽  
Count Recovery

Abstract Introduction Early bone marrow (BM) evaluation (during aplasia or at “day 14” (D14)) in patients with AML undergoing conventional induction therapy has been adopted from clinical practice in pediatric acute lymphoblastic leukemia (ALL). While it has been shown that early persistence of AML correlates with decreased complete remission (CR) rates and overall survival (OS), unlike in ALL, there are no data to indicate that early initiation of re-induction therapy based on these findings will positively influence outcome. In fact, early re-induction, especially in older patients, may increase morbidity and mortality from prolonged cytopenias, infectious complications, and longer hospital stays. Moreover, it can be challenging to determine the nature of scattered blasts identified in a hypocellular BM at D14, as they may represent normal recovering marrow elements or malignant blasts. Even if malignant, the chemosensitivityof these cells will only be fully determined by later assessment of the BM at the time of expected count recovery (“day 28”). For these reasons, early re-induction therapy may not be advisable. In this retrospective study, we sought to evaluate the validity of D14 BM assessments as post-therapy prognostication to guide treatment decisions in AML. Methods We conducted a retrospective institutional study (2006-2014) of AML patients undergoing routine induction chemotherapy where diagnostic, interim (around D14) and recovery (D21-42) BM evaluations were available for review. Clinical information and pathology data were retrieved from our institutional database. Responses at D14 were categorized morphologically into three categories: optimal response (OR, blasts ≤5%), indeterminate response (IR, blasts 6-19%), and residual leukemia (RL, blasts ≥20% or a relative decrease in blast count from baseline of <20%). Published response criteria were used to define responses at marrow recovery. Suboptimal response (SOR) at D14 was defined as either IR or RL during the assessment period. Mann-Whitney's U test was used to compare non-normally distributed variables. The Fisher's exact test was employed to assess for associations between response to treatment at D14 and likelihood of recovering in CR. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of a D14 BM to predict CR were calculated for patients that were observed without re-induction. Results Evaluable patients (n=98) had a mean age of 51 years (20-73), and 45% were male. The median BM blast percentages at diagnosis, D14 and recovery were respectively 54.5%, 0% and 2.5% (Figure 1). There was a significantly greater absolute decrease in blast percentage from diagnosis to D14 in patients who recovered in CR compared to those who did not achieve CR (median: 53.5% vs 23.0%, P = 0.001). In patients that got early re-induction therapy for SOR at D14, the relative differential in baseline and D14 BM blasts was significantly lower compared to patients with D14 SOR who did not get re-induction therapy (median: 21.8% vs 77.8%, P=0.004) Ninety patients did not receive early re-induction therapy. Of these, 86 (95.6%) achieved CR and 4 patients (4.4%) recovered counts with residual leukemia. Fourteen (14.3%) patients were classified as SOR at D14. Of these, 6 (6.7%) did not receive re-induction therapy and 4 of these 6 patients (67%) achieved a CR. Eight patients received early re-induction therapy based on SOR at D14 (IR = 2, RL = 6); of these, 4 patients (50%) achieved CR at count recovery. Achieving an OR at D14 was predictive of achieving CR at recovery (sensitivity = 95.3%, PPV = 97.6%). However, not achieving an OR at D14 had low specificity (50%) and NPV (33.3%) for achieving CR (P = 0.021). Conclusions Our results indicate that a SOR at the D14 BM evaluation does not uniformly identify patients with primary induction failure (low NPV) and should not be used to dictate the timing of re-induction therapy. We confirmed the PPV of achieving an OR at D14 as previously reported, but we argue that no additional prognostic data is provided by an OR at D14, beyond what can already be predicted by pre-treatment variables (e.g., age and chromosomal abnormalities). We suggest that the D14 BM should be omitted from the routine evaluation of AML patients during induction therapy outside the context of a clinical trial. Figure 1 Figure 1. Progression and percentage of blasts at diagnosis, day 14 and recovery assessments (n = 98). Disclosures No relevant conflicts of interest to declare.

Conventional and Molecular Cytogenetic Responses in Patients with Myelodysplastic Syndrome (MDS) with Deletion 5q Treated with Lenalidomide.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1746-1746
Author(s):  
Rita Coutinho ◽  
Dolors Costa ◽  
Ana Carrió ◽  
Ana Vidal ◽  
Mohammed Belkaid ◽  
...  
Keyword(s):  
Chromosomal Abnormalities ◽  
Conflicts Of Interest ◽  
Significant Proportion ◽  
Response To Treatment ◽  
Fish Analysis ◽  
Additional Information ◽  
Erythroid Response ◽  
Hematologic Response ◽  
Cytogenetic Remission

Abstract Abstract 1746 Poster Board I-772 Background and objectives Interstitial deletions of the long arm of chromosome 5 - del (5q) - are the most common chromosomal abnormalities in MDS. Del (5q) is detected in 14 % of the patients. Lenalidomide induces complete cytogenetic remissions and abolishes transfusion dependence in a significant proportion of these patients, apparently correlated with the malignant clone suppression. The objectives of this study were to assess clinical and cytogenetic responses to Lenalidomide and to establish the relationship between the number of 5q deleted cells detected by conventional cytogenetics (CG) and by fluorescence in situ hybridization (FISH) previously and after treatment. Due to its larger sensitivity, the FISH technique might be able to predict an eventual loss of response to treatment. Patients and methods Bone marrow samples were collected at diagnosis and every 6 months from the beginning of treatment with lenalidomide. CG and FISH (with LSI EGR1 (5q31)SO/D5S23, D5S721 (5p15.2) probe, from Vysis) studies were performed in all samples, even in the cases that a complete cytogenetic remission was confirmed by karyotype during the treatment follow-up. Results We have treated 9 transfusion dependent MDS patients with lenalidomide, with a median age of 76 years (45-92). Four of the patients had one additional cytogenetic anomaly besides 5q deletion. Due to high clinical and cytological suspicion, one of the patients had a trisomy 9 by karyotype (2/20 metaphase) and was diagnosed of del (5q) by FISH, with a low clonal load (9,4% of deleted nuclei). Six patients were low IPSS risk, while 2 were Int-1 and one was Int-2 risk IPSS. All patients achieved complete erythroid response and transfusion independence (in a median of 8 weeks of treatment) and are still in response. Treatment was stopped in two patients after achieving complete hematologic response, maintaining normal hemoglobine levels for > 24 months. Five patients achieved cytogenetic remission, but 2 of them relapsed in a latter phase of the treatment (25 and 30 months). FISH analysis could not predict cytogenetic relapse in these two cases. Conclusions Our results support the established high efficacy of lenalidomide in MDS with del (5q). In our experience a single additional cytogenetic anomaly did not compromise hematologic response. Moreover, in our study FISH analysis did not bring additional information to CG analysis in prediction of response and follow-up in the majority of the cases. Disclosures No relevant conflicts of interest to declare.

Amplification of AML1 Does Not Impact Early Outcome of Children with Acute Lymphoblastic Leukemia (ALL) Treated with Risk-Directed Chemotherapy: A Report From the Children's Oncology Group (COG).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2598-2598
Author(s):  
Nyla A. Heerema ◽  
Andrew J. Carroll ◽  
Michael J. Borowitz ◽  
Meenakshi Devidas ◽  
Eric C. Larson ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
Early Response ◽  
Response To Therapy ◽  
Chromosome 21 ◽  
Single Chromosome ◽  
Early Outcome ◽  
Early Results

Abstract Abstract 2598 Poster Board II-574 Amplification of a region of chromosome 21 (which includes the AML1 (RUNX1) locus (amp(AML1)) has been reported as a recurring abnormality in pediatric ALL that is associated with increased age (median 9 years), a low white blood cell (WBC) count, and a poor outcome. (Moorman et al Blood 109:2327, 2007; Attarbaschi et al JCO 26:3046, 2008). Early results in these studies indicated approximately a 75% event-free survival (EFS) at 2 years. Amp(AML1) can be reliably detected only by fluorescence in situ hybridization (FISH), and can be recognized when blasts are tested by FISH for the presence of the TEL(ETV6)/RUNX1 translocation. We reviewed the clinical features and outcome of children with ALL and amp(AML1) treated on current generation COG trials from 2003–2009 (median follow up 1.2 years, range: 0.03–3.83 yrs). Diagnosis of amp(AML1) required at least 5 copies of AML1, with 4 copies on a single chromosome. Children with B-precursor ALL received a 3- or 4-drug induction based on NCI risk group, with post-induction therapy based on further risk stratification variables measured during the first month of induction. Patients with a poor early response to therapy (day 15 bone marrow (BM) with >5% blasts or day 29 BM minimal residual disease (MRD) >0.1%) were non-randomly assigned to receive augmented chemotherapy. Treatment was not altered for patients with amp(AML1). Since June 1, 2007, ETV6/RUNX1 FISH was required on all children enrolled on this study. From Dec 29, 2003 to June 1, 2007, FISH was not required on all patients so ascertainment of amp(AML1) may not be complete. There were 89/5470 (1.6%) children with B-precursor ALL in whom amp(AML1) was detected. Similar to previous reports (see Table), their median age was 9.1 years, median WBC was 4.5×109/l; and 55.1% were female, a higher proportion than previously reported (43%–48%). While the distribution of day 29 MRD by flow cytometry was different, NCI risk group distribution, 2-year EFS and overall survival (OS) were similar between patients with and without amp(AML1). Of the 10 events that occurred in patients with amp(AML1), there were 3 induction failures, 3 induction deaths, and 4 relapses. Thus, early response to risk-adapted therapy is similar in children with and without amp(AML1). We conclude that, using risk-adapted therapy, children with ALL and amp(AML1) have an early outcome similar to those lacking this feature; however, longer follow up is needed to determine the full impact of amp(AML1) on eventual outcome. Disclosures: No relevant conflicts of interest to declare.

scholarly journals MON-073 Hyperinsulinemic Hypoglycemia Responsive to Diazoxide Due to a Previously Unknown ABCC8 Dominant Mutation

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Veronica M Figueredo ◽  
Alejandro Diaz ◽  
Pedro Pagan Banchs
Keyword(s):  
Brain Mri ◽  
Poor Response ◽  
White Matter Injury ◽  
Response To Treatment ◽  
Hyperinsulinemic Hypoglycemia ◽  
Dominant Mutation ◽  
Suspected Sepsis ◽  
Intravenous Glucose ◽  
History Of

Abstract Background: Hyperinsulinism is the most common cause of persistent hypoglycemia. It results from different genetic defects, the most common being recessive and dominant mutations in the ABCC8/KCNJ11 genes. The majority of recessive mutations have a poor response to Diazoxide, while dominant mutations are highly variable in both clinical presentation and response to treatment. Prompt recognition and management is critical to avoid irreversible brain damage. Clinical case: A 38-week gestation male, born via emergent c-section due to decreased fetal movement, presented with neonatal hypoglycemia. Pregnancy was uncomplicated and mother had a normal OGTT. Patient had a history of suspected sepsis, seizures, pulmonary hypertension and respiratory distress requiring intubation. Blood glucose was undetectable at birth and required multiple dextrose 10% boluses. A critical sample with a glucose of 47 mg/dL showed an elevated insulin at 30.3 m IU/mL with undetectable ketone levels. Lactic acid, ammonia, cortisol, GH, plasma amino acids, acylcarnitine profile and uric organic acids where all normal for a hypoglycemic state. He required intravenous glucose infusion with GIR up to 17 mg/kg/min to maintain normoglycemia. A brain MRI at 11 days of life showed findings of white matter injury. Subsequent genetic testing identified a heterozygous c.4051G&gt;A (p.Val1351Met) variant in ABCC8, classified as “of uncertain significance”. However, an entry in the ClinVar database (RCV000714711.1) exists from a research lab and was classified as likely pathogenic. Analysis of parental samples showed that the mother was heterozygous for the same genetic variant. She did not have a history of hypoglycemia. Patient was started on diazoxide (8 mg/kg/day) and chlorothiazide with resolution of hypoglycemia. At a follow up visit at 5 months of age, there was no history of hypoglycemia, and no need for adjustments of the diazoxide dose by weight (dose at that time of 7.4 mg/kg/day). Conclusion: The ABCC8 reported here is a dominant mutation causing hyperinsulinemic hypoglycemia responsive to diazoxide with a milder phenotype later in infancy. Longitudinal follow up of the case is warranted to understand the long term progress in patients with this particular mutation. Reference: Adam MP, Ardinger HH, Pagon RA, Wallace SE, et al. None. 1993. Familial hyperinsulinism.

Biallelic loss ofCDKN2Ais associated with poor response to treatment in pediatric acute lymphoblastic leukemia

2016 ◽  
Vol 58 (5) ◽  
pp. 1162-1171 ◽  
Author(s):  
Marcin Braun ◽  
Agata Pastorczak ◽  
Wojciech Fendler ◽  
Joanna Madzio ◽  
Bartlomiej Tomasik ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Poor Response ◽  
Response To Treatment ◽  
Pediatric Acute Lymphoblastic Leukemia

Co-Existence of Various Sub-Clones in TEL-AML1 Positive Acute Lymphoblastic Leukemia in Association with Sub-Microscopic Deletion of AML1.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1096-1096
Author(s):  
Amos Toren ◽  
Rachel Rothman ◽  
Bella Bielorai ◽  
Malka Reichart ◽  
Ninette Amariglio ◽  
...  
Keyword(s):  
Minimal Residual Disease ◽  
Gene Rearrangement ◽  
Chromosomal Abnormalities ◽  
Residual Disease ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Submicroscopic Deletion ◽  
Minimal Residual

Abstract The TEL/AML1 fusion gene is the most common gene rearrangement in pediatric acute lymphoblastic leukemia (ALL). Although considered to be a low risk leukemia it has a 20% risk of late relapse. The coexistence of different sub clones at diagnosis, based on polymerase chain reaction (PCR) studies of Ig/TCR gene rearrangement, was recently reported in this subtype of ALL. Their different response to chemotherapy may explain the emergence of certain sub clones at relapse, and may serve as a marker for minimal residual disease follow-up. Several chromosomal rearrangements such as t(9;22), t(8;21), inv(16) and rearrangements of the MLL gene are frequently associated with submicroscopic deletions and some of them have prognostic significance. Such deletions were not reported in t(12;21) positive ALL. Bone marrow cells from 76 pediatric patients with ALL at diagnosis were analyzed for the presence of the TEL/AML1 fusion gene by interphase fluorescence in situ hybridization (FISH). We used a new system of combined analysis enabling a very large-scale study of the cells of interest with regard to morphology, FISH and immunophenotyping. Fourteen patients were positive for the translocation. Four of them had several sub clones associated with various combinations of additional chromosomal abnormalities. The most striking was an atypical and unexpected hybridization pattern consistent with a submicroscopic deletion of the 5′ region of the AML1 breakpoint (intron2) not previously reported. We describe the use of a larger probe for AML1 (AML1/ETO) to exclude the possibility of insertion of TEL into the AML1 region without breakage and to reduce the false positivity due to optical fusion. This may enable a better monitoring of minimal residual disease in cases with submicroscopic deletion. All patients had some sub-clones with TEL deletion. Other abnormalities included trisomy and tetrasomy 21 as well as double TEL-AML1 fusion. The analysis of numerous sub-clones at presentation in these patients suggests clonal evolution at an early stage of the disease. These sub-clones may have different sensitivities to chemotherapy, and some of them may reappear at relapse. The frequency of AML1 deletion in t(12;21) in addition to other chromosomal abnormalities, is unknown. The involvement of these findings in the generation of leukemic sub clones, their prognostic significance and role in minimal residual disease follow-up deserves further studies in a large number of patients and a longer follow-up.

Combined Analysis of Treatments for Pediatric T-ALL in KYCCSG Protocols, ALL-96 and ALL-02.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4102-4102
Author(s):  
Yasuhiro Okamoto ◽  
Yoshihisa Nagatoshi ◽  
Akinobu Matsuzaki ◽  
Aiko Suminoe ◽  
Hideki Nakayama ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Chromosomal Abnormalities ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Cranial Irradiation ◽  
High Dose ◽  
Costal Margin ◽  
Hematopoietic Stem ◽  
Combined Analysis

Abstract Abstract 4102 Background Previously we reported the result of Kyushu-Yamaguchi Children's Cancer Study Group (KYCCSG) protocol, ALL-96, for pediatric acute lymphoblastic leukemia (ALL) (ASH meeting in 2005). The 7-year event-free survival (EFS) and overall survival (OS) rates were 72% (95% CI; 68 - 76 %) and 85 % (95% CI; 80 - 90 %), respectively. Following protocol, ALL-02, was aimed to assess the usefulness of polymerase chain reaction (PCR)-based minimal residual disease (MRD) in the same context as ALL-96 protocol. Purpose In this combined analysis, we analyzed the outcome and risk factors for relapse/survival in children with T-ALL who were treated with the ALL-96/ALL-02 protocols. Study Design and Treatment A total of 42 patients (22 of 218 in ALL-96 and 20 of 165 in ALL-02, 26 males and 16 females) with median age of 8 years (range 1 - 14) were treated. Patients were classified into 2 groups, standard risk (SR) and high risk (HR). HR patients had one of the followings: high white blood cell (WBC) counts more than 50,000/μl, T-cell immunophenotype, central nervous system (CNS) disease at diagnosis, organomegaly (hepatomegaly or splenomegaly more than 5 cm below costal margin), M2/3 marrow at day 15 of induction therapy. Both protocols consisted of induction, early intensification, consolidation, late intensification and maintenance therapy. Predonisolone (PSL), weekly vincristine (VCR), 4 doses of daunorubicin (DNR), 8 doses of L-asparaginase (L-asp) and 2 or 4 doses of intrathecal (IT) methotrexate (MTX) depending on the CNS status, were given during induction. In early intensification, DNR, cytarabine (CA), etoposide and 6-mercaptopurine (6-MP) were given. Consolidation consisted of intermediate dose of MTX, combination of cyclophosphamide(CPM), CA and 6-MP, and high dose CA. Late intensification similar to induction included 2 weeks of dexamethasone (DEX), weekly VCR, 2 doses of pirarubicin, single dose of CPM, 5 doses of L-asp and IT-MTX followed by combination of CA, 6-MP, IT-MTX along with 18 Gy cranial irradiation in 12 fractions. In ALL-96 protocol, patients were randomized to receive maintenance therapy of either combination of 6-MP/MTX and DEX/ VCR pulse (A-arm) or LSA2L2-type therapy (B-arm). In ALL-02 protocol, A-arm was chosen as a maintenance therapy based on result of ALL-96. No patient underwent hematopoietic stem cell transplantation (SCT) in 1st complete remission (CR). Results Median follow-up periods were 96 and 38 months in ALL-96 and ALL-02, respectively. Two patients were off-protocol before achieving CR because of toxicity and chromosome abnormality with t(4;11). Induction rate in 40 patients was 95%. All 14 events were relapses and TRM rate was 0%. Last event occurred at 40 months. The sites of relapse were isolated BM in 9, isolated testis in 2, isolated CNS in 1 and combined sites in 2. Nine died from disease progression and 2 died from toxicity after SCT in 2nd CR. The 4-year EFS and OS rates in all patients were 55 % (95 % CI; 39 – 71 %) and 71 % (95 % CI; 56 -86 %), respectively. EFS of ALL-96 and ALL-02 were 50 %[95 % CI; 29 -71 %]) and 65 % [95 % CI; 45 - 85 %]), respectively. OS of ALL-96 and ALL-02 were 59 % [95 % CI; 39 – 80 %]) and 90 % [95 % CI; 77 - 103 %]), respectively (p = 0.063). EFS of patients treated in A and B arm were 60 % [95 % CI; 41 -71 %]) and 55 % [95 % CI; 25 - 84 %]), respectively. None of age, sex, organomagaly, WBC, chromosomal abnormalities, CNS status, protocol, and maintenance arm was identified as a risk factor for relapse or survival. Two of 10 (ALL-96) and 3 of 4 (ALL-02) relapsed patients have survived with allogeneic SCT. Conclusion Although T-ALL patients received an intensified treatment including cranial radiation, the outcome was unsatisfactory. One possible explanation for better OS in ALL-02 protocol is that the majority of relapsed patients in ALL-02 were salvaged by SCT in 2nd CR. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document