Results of the AIEOP-BFM ALL 2000 Study for Childhood Acute Lymphoblastic Leukemia IN AIEOP High Risk Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 319-319
Author(s):  
Valentino Conter ◽  
Maria Grazia Valsecchi ◽  
Maurizio Aricò ◽  
Carmelo Rizzari ◽  
Rosanna Parasole ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Poor Response ◽  
Cranial Radiotherapy ◽  
Hematopoietic Stem ◽  
Innovative Therapies ◽  
Risk Patients

Abstract Abstract 319 Aim: The Italian Association of Pediatric Haematology and Oncology (AIEOP) patients, diagnosed in the period September 2000-July 2006, were treated in the context of the AIEOP-BFM ALL 2000 Study. Some differences in high risk (HR) treatment and hematopoietic stem cell transplantation (HSCT) indications justify separate reporting of results obtained by AIEOP and BFM respectively. We report here the AIEOP experience. Patients and methods: Overall, 1999 AIEOP Ph negative Acute Lymphoblastic Leukemia (ALL) patients were eligible to the AIEOP-BFM ALL 2000 Study. High Risk (HR) criteria were: t(4;11) translocation, Prednisone Poor Response (PPR), no complete remission (CR) at day 33, high minimal residual disease (MRD) levels (≥10-3) at day 78 (HR-MRD). Treatment consisted of protocol I (patients were randomised to receive either dexametasone or prednisone in induction), 3 HR polychemotherapy blocks, a randomized comparison between delayed intensification based on protocol II repeated twice or protocol III repeated thrice, cranial radiotherapy (CRT), maintenance therapy for a total of 2 years of treatment. Results: 311 patients were classified as being at HR (15.6% of the total ALL population) and had an overall event-free survival (EFS) and Survival of 58.7%(standard error 2.9) and 70.1%(2.7), respectively. For the 204 patients randomized to different steroids in protocol I, we observed a 5-year EFS of 62.7%(5.0) and 62.3%(4.8) and a 5-year Survival of 72.7%(4.7) and 72.8%(4.3) for dexamethasone and prednisone arm, respectively. The 5-year EFS was 44.4%(4.5) in 132 patients at HR for MRD, 36.4%(14.5) for the 11 patients at HR for t(4;11), 41.2%(11.9) for the 17 patients at HR for no CR at day 33, 74.6%(3.7) for the 151 patients at HR only for PPR. Patients at HR with <10-3 (44/258) or negative (82/258) MRD levels at day 78 had a 5-year EFS of 63.4%(7.3) and 79.4%(4.9), respectively. Among 80 patients who underwent allogeneic HSCT at a median time of 6 months from diagnosis, 68 had HR-MRD or t(4;11) or no CR at day 33. After adjusting for waiting time to transplantation, their 5-year EFS was 51.7%(6.6) compared with a 5-year EFS of 44.6%(5.8) in patients with the same features and treated given chemotherapy only (p=0.72). Conclusions: These data show that AIEOP-BFM ALL 2000 HR therapy is very effective for patients defined at HR for PPR. These patients could thus be considered for some treatment reduction, i.e. sparing most toxic therapeutic elements such as CRT. MRD identifies patients at HR (8.7% of the analysed population, 42% of HR patients), who have a poor outcome despite receiving intensive BFM treatment, including HSCT, and who may thus be eligible for innovative therapies. Disclosures: No relevant conflicts of interest to declare.

The Outcome of Childhood High-Risk Acute Lymphoblastic Leukemia: 10 Years of Experience with the ALL-BFM 95 Protocol in Chinese Single Centre

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5241-5241
Author(s):  
Yongsheng Ruan ◽  
Xuedong Wu ◽  
Chunfu Li ◽  
Xiaoqin Feng
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Poor Response ◽  
Rank Test ◽  
Event Free Survival ◽  
Single Centre ◽  
Hematopoietic Stem ◽  
Free Survival

Abstract Objectives: To evaluate the effectiveness and the practicability of Acute Lymphoblastic Leukemia Berlin-Frankfurt-Münster 95 (ALL-BFM 95) protocol in treating childhood high-risk (HR) acute lymphoblastic leukemia (ALL) in Chinese single centre. Methods: A retrospective analysis of 47 children with novo high risk ALL from July 2003 and August 2013 was performed. These children treated by the ALL-BFM 95 protocol. Median follow-up time was 39 months (16~127months). Survival was evaluated by Kaplan Meier analysis and Log-Rank test. Results:Relapse-related death occurred in 12 of 47 patients (25.5%), and 5 of 47 patients (10.6%) were treatment-related mortality. Five-year probability of event-free-survival (pEFS) were found to be 62.4%. High risk ALL children only with prednisone poor response(PPR) has good outcome who’s Five-year probability of event-free-survival (pEFS) could reach to 80%. Children with hematopoietic stem cell transplantation (HSCT) after chemotherapy achieved significantly better pEFS than only chemotherapy (77.3% vs 51.6%，p=0.035). pEFS for B-cell precursor and T-cell ALL was 64.5% and 57.1%, respectively（P=0.633）. Conclusions: ALL-BFM 95 protocol can also improve the outcome of childhood high risk ALL in China. The leading causes of death were relapse. HSCT treatment had better outcome than only chemotherapy in high risk ALL children in CR1 phase. Disclosures No relevant conflicts of interest to declare.

scholarly journals Personalized therapy in pediatric high-risk B-cell acute lymphoblastic leukemia

2020 ◽  
Vol 11 ◽  
pp. 204062072092757 ◽  
Author(s):  
Seth E. Karol ◽  
Ching-Hon Pui
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Risk Patients ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Disease Stratification ◽  
Cure Rates ◽  
Minimal Residual

Although cure rates for pediatric acute lymphoblastic leukemia (ALL) have now risen to more than 90%, subsets of patients with high-risk features continue to experience high rates of treatment failure and relapse. Recent work in minimal residual disease stratification and leukemia genomics have increased the ability to identify and classify these high-risk patients. In this review, we discuss this work to identify and classify patients with high-risk ALL. Novel therapeutics, which may have the potential to improve outcomes for these patients, are also discussed.

Minimal Residual Disease At 3 Months, Combined to the Presence of IKZF1 Deletion in B-Lineage or Absence of NOTCH1 pathway Mutation in T-Lineage, Recapitulates the Disease Risk Assessment in Adults with Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia - A GRAALL Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 572-572 ◽  
Author(s):  
Kheira Beldjord ◽  
Elizabeth Macintyre ◽  
Véronique Lhéritier ◽  
Marie-Laure Boulland ◽  
Thibaut Leguay ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Minimal Residual Disease ◽  
Disease Risk ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Cns Involvement ◽  
Risk Patients ◽  
Minimal Residual

Abstract Abstract 572 Aim. In recent series of adults with acute lymphoblastic leukemia (ALL), the GRAALL (ASH 2009, abstract 577) and other cooperative groups have confirmed the strong prognostic value of Ig/TCR minimal residual disease (MRD) on patient outcome. Despite this, age, WBC, CNS involvement, recurrent chromosomal translocations, and early response to steroids and chemotherapy remain frequently used to tailor post-remission therapy and envision allogeneic stem cell transplantation (SCT) in most adult ALL trials. We updated our MRD study, now with 262 patients who all achieved complete remission (CR) after the first induction and were assessed for MRD after induction (MRD1, at 6 weeks) and consolidation (MRD2, at 12 weeks). One hundred and fifty-eight patients had Philadelphia chromosome (Ph)-negative B-cell precursor ALL (BCP-ALL), while 104 had T-cell ALL (T-ALL). Since 107 of the BCP-ALL (68%) were studied for IKZF1 deletion and 90 of the T-ALL patients (87%) for NOTCH1/FBXW7 mutations, we were able to reassess the MRD significance according to these newly described oncogenic markers. These two covariates (i.e. MRD and IKZF1/NOTCH1/FBXW7 genetics) allowed us to redefine a much simpler yet more powerful stratification of disease risk in both BCP- ALL and T-ALL subsets. Methods. All 262 patients studied (median age, 31.5 years) were treated in the GRAALL-2003 and GRAALL-2005 trials. Although they were younger and had more frequently circulating blasts, other characteristics and outcome did not differ from patients treated in the same trials but not assessed for MRD. Ig/TCR MRD levels were determined according to Euro-MRD guidelines (Leukemia 2007;21:604). IKZF1 deletions were assessed by multiplex multi-fluorescent PCR. NOTCH1/FBXW7 mutations were assessed as previously described (Blood 2009;113:3918). Multivariate backward stepwise selection Cox models were used for the cumulative incidence of relapse (CIR), disease-free (DFS) and overall survival (OS) endpoints, after censoring transplanted patients at SCT. Models were always adjusted on age (35-year cutoff), WBC (30 and 100 G/L cutoff for BCP- and T-ALL, respectively), CNS involvement, and trial. Additional BCP-specific covariates included CD20 expression, t(4;11) and t(1;19) translocations, and IKZF1 deletion. Additional T-specific covariates included cortical immunophenotype according to the EGIL classification, TLX1 overexpression, and NOTCH1/FBXW7 mutation. Finally, allogeneic SCT was re-evaluated in the newly defined risk subsets, as a time-dependent covariate. Results. An initial multivariate analysis revealed that among blood response after 1 week of steroid, bone marrow response after 2 weeks of therapy, and molecular response at both MRD1 and MRD2 time-points, the MRD2 level was the main and sole independent predictor of relapse (P=0.003). In BCP-ALL patients, persistent MRD2 and IKZF1 deletion were the only two independent factors identified, the presence of at least one factor defining 51% high-risk patients with 52% versus 15% CIR (HR, 3.8; P= 0.008), 41% versus 81% DFS (HR, 3.6; P= 0.005), and 54% versus 80% OS (HR, 3.9; P= 0.015) at 4 years. Allogeneic SCT in first CR significantly decreased relapse incidence and prolonged DFS in these new high-risk BCP-ALL patients (HR, 0.23 and 0.40; P= 0.016 and 0.05, respectively). In T-ALL patients, persistent MRD2 and lack of NOTCH1/FBXW7 mutation were the only two independent factors identified, the presence of at least one factor defining 49% high-risk patients with 64% versus 12% CIR (HR, 6.4; P= 0.002), 36% versus 88% DFS (HR, 6.4; P= 0.002), and 41% versus 95% OS (HR, 7.3; P= 0.015) at 4 years. SCT had no significant effect on relapse incidence and DFS in these new high-risk T-ALL patients. Conclusion. In adult patients with Ph-negative ALL treated with the pediatric-inspired GRAALL regimen, IKZF1 deletion in BCP-ALL, NOTCH1/FBXW7 mutation in T-ALL, and MRD at 3 months in both subsets replace all classical risk factors, leading to a new simplified prognostic scoring system based only on IKZF1 and NOTCH1/FBXW7 genetics and MRD clearance. This new risk score identifies approximately half of the patients as good-risk, with a relapse incidence as low as 10–15%. It will be validated and used prospectively in the next generation of GRAALL trials, to stratify both new drug evaluation and SCT in first CR. Disclosures: No relevant conflicts of interest to declare.

scholarly journals IKZF1deletions Coupled with CD20 Expression Represents a Novel High-Risk Subtype in Adult B-Cell Progenitor Acute Lymphoblastic Leukemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4474-4474
Author(s):  
Bingqing Tang ◽  
Zhixiang Wang ◽  
Dainan Lin ◽  
Xianjun He ◽  
Zihong Cai ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
B Cell ◽  
Validation Cohort ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem ◽  
Poor Outcome ◽  
Cd20 Expression ◽  
Cell Acute Lymphoblastic Leukemia

Abstract Genetic deletions of IKZF1 are associated with poor prognosis in B-cell acute lymphoblastic leukemia (B-ALL). Here we investigated the effect of IKZF1 deletions (IKZF1 del) plus with immunotype in adult B-ALL in PDT-ALL-2016 cohort. This cohort study involved 161 patients with B-ALL from 2016 to 2019, with detailed information about IKZF1 del and CD20 expression. Validation cohort consists N= patients from TARGET cohort. IKZF1 del was detected in 36.0% of patients with 3-year event-free survival (EFS) of 37.2±6.7% and overall survival (OS) of 51.1±7.3%, compared to IKZF1 wild-type (IKZF1 wt) with EFS 55.4±5.1% (P&lt;0.01) and OS 74.6±4.5% (P&lt;0.05), respectively. CD20 expression was also associated with inferior EFS than CD20-negative group (P&lt;0.05). Furthermore, IKZF1 del coupled with CD20 expression, termed as IKZF1 del/CD20+, comprised 12.4% of patients with 3-year EFS of 25.0±9.7% compared with IKZF1 wt (P&lt;0.05 ) and IKZF1 del/CD20- (P&lt;0.05 ) groups, respectively. Multivariable analyses demonstrated independence of IKZF1 del/CD20+ with highest hazard ratio for EFS and OS. Furthermore, the prognostic strength of IKZF1 del/CD20+ was confirmed in TARGET validation cohort. Eighty-one patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT). Notably, neither IKZF1 del(P=0.6288), CD20 (P=0.0705) or IKZF1 del/CD20 (P=0.3410) groups were identified as poor outcome in allo-HSCT cohort. Collectively, our data demonstrate that IKZF1 del/CD20+ represents a very high-risk subtype in adult B-ALL; and particularly, allo-HSCT could overcome the poor outcome of IKZF1 del and IKZF1 del/CD20+. Disclosures No relevant conflicts of interest to declare.

Outcome of Early T-Cell Precursor Acute Lymphoblastic Leukemia in AIEOP Patients Treated with the AIEOP-BFM ALL 2000 Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3780-3780 ◽  
Author(s):  
Valentino Conter ◽  
Maria Grazia Valsecchi ◽  
Barbara Buldini ◽  
Rosanna Parasole ◽  
Franco Locatelli ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
High Risk ◽  
Induction Therapy ◽  
Lymphoblastic Leukemia ◽  
Cell Precursor ◽  
Hematopoietic Stem ◽  
Phase Ib ◽  
High Risk Patients ◽  
Risk Patients

Abstract Aim: To evaluate the outcome of the Italian Association of Pediatric Hematology and Oncology (AIEOP) patients diagnosed with Early T-cell Precursor (ETP) Acute Lymphoblastic Leukemia (ALL) in the period September 2000-December 2011 and treated in the context of the AIEOP-BFM ALL 2000 Study and the subsequent - very similar – AIEOP ALL R2006 Study. Patients and methods: ETP-ALL was defined by staining negative for CD1a and CD8, mildly positive or negative for CD5 and positive for at least one of CD34, CD117, HLADR, CD13, CD33, CD11b, or CD65 antigens. Treatment consisted of BFM protocol I either with dexamethasone or prednisone in phase IA, 4 HDMTX courses (5 g/sqm over 24 hrs) in non-high risk patients or 3 poly-chemotherapy blocks in high risk patients, delayed intensification based on protocol(s) II or III, protracted intrathecal therapy or cranial radiotherapy, maintenance therapy for a total of 2 years of treatment. Hematopoietic stem cell transplantation (HSCT) was indicated for patients with poor treatment response assessed either morphologically at day +8 (Prednisone Poor Response, PPR) or day +33 (no Complete Remission, CR) or by PCR at day +78 (high-level Minimal Residual Disease, HR-MRD; ≥10-3). Results: Of the 439 T-ALL eligible patients, 34 had ETP ALL. The incidence (7.7%) may be underestimated since the full set of the data needed was not available for all patients. Out of the 34 patients with ETP ALL 14 were at high risk due to PPR; of them, 3 were HR-MRD and 5 did not achieve CR after Phase IA of induction therapy (including one with HR-MRD). Of the remaining 20 patients (all prednisone good responders), 3 patients were at high risk due to resistance to Phase IA and HR-MRD (n=1) or HR-MRD only (n=2). 17/30 patients could not be monitored by MRD due to death in Induction (n=1), or absent (n=10) or inadequate PCR markers (n=6). Of the17 patients monitored by MRD, 13 had HR-MRD at day 33 and 6 of them also at day +78. One patient died during induction therapy. The remaining 33 achieved morphological CR: 27 after phase IA and 6 (those resistant to phase IA) after phase IB of protocol I. Of 12 patients who underwent HSCT, 3 died of HSCT-related complications and 3 relapsed. With a median follow-up of 6.6 years, the 5-year event-free survival (EFS) and Survival in the 34 ETP ALL patients were of 60.9%(SE 8.5) and 66.6%(8.3), versus 71.2%(2.3) and 77.1%(2.1) respectively in the non-ETP patients. The overall cumulative incidence of relapse was 27.3%(7.8) and 22.2%(2.1) in ETP and non-ETP T-ALL patients, respectively (p=0.52). EFS in ETP vs non-ETP patients was respectively 81.9%(9.5) vs 83.8%(2.4) in non high risk patients (p=0.87) and 41.2%(11.9) vs 53.2%(4.0) in high risk patients (p=0.24). Conclusions: The outcome of T-ALL patients treated with BFM-type therapy is comparable in ETP and non-ETP for those with good response to initial chemotherapy; it was slightly, but not significantly, inferior in ETP-ALL patients with poor initial response. Phase IB treatment element is very effective in ETP-ALL, suggesting that intensification with antimetabolite and alkylating agents may be beneficial, while the benefit of HSCT in first CR needs to be further investigated. Disclosures No relevant conflicts of interest to declare.

Minimal Residual Disease–Guided Treatment Deintensification for Children With Acute Lymphoblastic Leukemia: Results From the Malaysia-Singapore Acute Lymphoblastic Leukemia 2003 Study

2012 ◽  
Vol 30 (19) ◽  
pp. 2384-2392 ◽  
Author(s):  
Allen Eng Juh Yeoh ◽  
Hany Ariffin ◽  
Elaine Li Leng Chai ◽  
Cecilia Sze Nga Kwok ◽  
Yiong Huak Chan ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Remission Induction ◽  
Intermediate Risk ◽  
Risk Patients ◽  
Standard Risk ◽  
Minimal Residual

Purpose To improve treatment outcome for childhood acute lymphoblastic leukemia (ALL), we designed the Malaysia-Singapore ALL 2003 study with treatment stratification based on presenting clinical and genetic features and minimal residual disease (MRD) levels measured by polymerase chain reaction targeting a single antigen-receptor gene rearrangement. Patients and Methods Five hundred fifty-six patients received risk-adapted therapy with a modified Berlin-Frankfurt-Münster–ALL treatment. High-risk ALL was defined by MRD ≥ 1 × 10−3 at week 12 and/or poor prednisolone response, BCR-ABL1, MLL gene rearrangements, hypodiploid less than 45 chromosomes, or induction failure; standard-risk ALL was defined by MRD ≤ 1 × 10−4 at weeks 5 and 12 and no extramedullary involvement or high-risk features. Intermediate-risk ALL included all remaining patients. Results Patients who lacked high-risk presenting features (85.7%) received remission induction therapy with dexamethasone, vincristine, and asparaginase, without anthracyclines. Six-year event-free survival (EFS) was 80.6% ± 3.5%; overall survival was 88.4% ± 3.1%. Standard-risk patients (n = 172; 31%) received significantly deintensified subsequent therapy without compromising EFS (93.2% ± 4.1%). High-risk patients (n = 101; 18%) had the worst EFS (51.8% ± 10%); EFS was 83.6% ± 4.9% in intermediate-risk patients (n = 283; 51%). Conclusion Our results demonstrate significant progress over previous trials in the region. Three-drug remission-induction therapy combined with MRD-based risk stratification to identify poor responders is an effective strategy for childhood ALL.

scholarly journals DAC-Based Conditioning Regimen Versus Standard Conditioning Regimen for Myelodysplastic Syndrome

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 31-32
Author(s):  
Yintian Zhang ◽  
Min Dai ◽  
Ya Gao ◽  
Ying Xu ◽  
Weiru Li ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Protective Factor ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Poor Response ◽  
Multivariable Logistic Regression Analysis ◽  
Hematopoietic Stem ◽  
Poor Risk ◽  
Risk Patients

B ackground : Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curable way for Myelodysplastic syndromes (MDS). There are still some patients have a poor prognosis after transplantation, including high frequency of relapse, poor response to salvage therapy and short overall survival. This study aimed to investigate whether DAC-based conditioning regimen improves survival compared with standard conditioning regimen for MDS patients. Methods : One hundred and forty-seven patients with MDS were enrolled in this prospective multicenter study. Eligible patients were randomly assigned to DAC-based conditioning regimen or standard conditioning regimen before allo-HSCT in a 1:1 ratio. Patients in standard conditioning regimen group received busulfan (3.2 mg/kg/day on days -7 to -4) and cyclophosphamide (60 mg/kg/day on days -3 and -2) for allo-HSCT. DAC-based conditioning regimen comprising decitabine (20 mg/m2/day on days -14 to -10), busulfan (3.2 mg/kg/day on days -7 to -4), and cyclophosphamide (60 mg/kg/day on days -3 and -2). The primary endpoint was overall survival after randomization. This trial was registered at ClinicalTrials.gov (NCT 02744742). Results: The median time to neutrophil reconstitution was 12 (8-35) days and 12 (9-34) days in the DAC-based conditioning regimen and standard conditioning regimen groups, respectively (P=0.577). The median platelet reconstitution time was 14 (9-68) days and 14 (10-90) days in the DAC-based conditioning regimen and standard conditioning regimen groups, respectively (P=0.017). Median follow-up was 419 (range, 1-1697) days. Overall survival was longer for DAC-based conditioning regimen than for standard conditioning regimen (P=0.034). 3-year OS was 62% (95%CI 46-98%) in the DAC-based conditioning regimen group and 43% (95%CI 29-64%) in the standard conditioning regimen group. 3-year GRFS was 50% (95%CI 34-74%) and 39% (95%CI 26-58%) in the DAC-based conditioning regimen and standard conditioning regimen groups, respectively (P=0.183). 3-year relapse incidence was 12% (95%CI 3-11%) and 25% (95%CI 11-29%) in the DAC-based conditioning regimen and standard conditioning regimen groups, respectively (P=0.209). There were no significant differences in the incidence of graft-versus-host disease, the incidence of infections, and other adverse events between two groups. The treatment-related mortality rate at 3 years was 30% (95% CI 13-34%) and 45% (95% CI 30-67%) in DAC conditioning and standard conditioning group, respectively(P=0.061). Stratified and multivariable logistic regression analysis showed that DAC-based conditioning regimen is an independent favorable factor for OS for very poor risk patients (HR 0.42, 95% CI, 0.19-0.93, P= 0.03) and a protective factor for CIR for patients with high-risk karyotype(HR 0.56, 95% CI, 0.18-1.36, P=0.04). Conclusions: Our study demonstrates that DAC-based conditioning regimen had a survival benefit versus standard conditioning regimen in MDS patients, especially for very poor risk cases according to IPSS-R. DAC conditioning also has lower relapse for patients with high-risk karyotypes, shorter platelet reconstitution and tolerable toxicity. These results may contribute to improving the management of MDS patients for better survival. Disclosures No relevant conflicts of interest to declare.

Successful allografting for relapsing pediatric ALL: The results of two decades.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e22000-e22000
Author(s):  
O. Bulent Zulfikar ◽  
Basak Koc
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Treatment Options ◽  
Poor Response ◽  
Response To Treatment ◽  
Laboratory Findings ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct

e22000 Background: The prognosis of children and adolescents with acute lymphoblastic leukemia (ALL) has dramatically improved. This success is associated with both by multiagent chemotherapy regimens and by definition of clinical, biological and treatment response that allow the administration of risk-adapted therapy, including allogeneic hematopoietic stem cell transplantation (HSCT). In treatment of relapsed and resistance ALL, allogeneic HSCT continues to play a major curative role. In the present study, we desciribed the patients who underwent HSCT in our clinic in the last 21 years. Methods: From 1999 to 2020, 147 patients who diagnosed with ALL and treated with the COG protocols at the Istanbul University Oncology Institute were retrospectively reviewed and 17 of them relapsed. HSCT was applied 7 of the relapsed cases and also 3 resistant cases who had suitable matched donors. The demographic features, laboratory findings and treatment responses of 10 patients were recorded from the patients’ medical records. Results: All 10 patients were B-ALL with median diagnosis age of 79.5 months (range: 32-195) and 5 were male. Characteristics of patients given in Table 1. HSCT was performed due to late relaps in 7 patients. Three of the 7 relaps were only bone marrow and other 4 had combined. Patient #2 had both breast, conjunctiva and bone marrow for the 1st relaps and only conjunctiva for the 2nd one and this patient had also t(9;22) in the 1st relaps. Patient #3 had bone marrow+central nervous system relaps and patient #7 had bone marrow for the 1st relaps and testis and bone marrow for the 2nd one. Other 3 had poor response to treatment and Minimal Residual Disease (MRD) was high in End of Introduction (EoI) and End of Consolidation (EoC)). All patients had allogeneic HSCT and 8 are alive. Conclusions: HSCT remains the standard-of-care treatment for ALL patients who carry high-risk features predicting leukemia recurrence and for those experiencing high-risk first relapse or multiple relapses. Additionally, defining the indications of HSCT are dynamic and it could change according to treatment options as well as new molecular and biological findings. It is important to identify the patients who have high relapse risk and HSCT should have priority in patients whom MRD is high in EoI and EoC.[Table: see text]

scholarly journals Recent advances in the management of pediatric acute lymphoblastic leukemia

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2635 ◽  
Author(s):  
Jan Starý ◽  
Ondřej Hrušák
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Organ Damage ◽  
Hematopoietic Stem ◽  
The Past ◽  
Group Assignment ◽  
Disease Biology ◽  
Early Treatment Response ◽  
Risk Patients

Acute lymphoblastic leukemia (ALL) is the most common malignancy in childhood. Despite enormous improvement of prognosis during the last half century, ALL remains a major cause of childhood cancer-related mortality. During the past decade, whole genomic methods have enhanced our knowledge of disease biology. Stratification of therapy according to early treatment response measured by minimal residual disease allows risk group assignment into different treatment arms, ranging from reduction to intensification of treatment. Progress has been achieved in academic clinical trials by optimization of combined chemotherapy, which continues to be the mainstay of contemporary treatment. The availability of suitable volunteer main histocompatibility antigen-matched unrelated donors has increased the rates of hematopoietic stem cell transplantation (HSCT) over the past two decades. Allogeneic HSCT has become an alternative treatment for selected, very-high-risk patients. However, intensive treatment burdens children with severe acute toxic effects that can cause permanent organ damage and even toxic death. Immunotherapeutic approaches have recently come to the forefront in ALL therapy. Monoclonal antibodies blinatumomab and inotuzumab ozogamicin as well as gene-modified T cells directed to specific target antigens have shown efficacy against resistant/relapsed leukemia in phase I/II studies. Integration of these newer modalities into combined regimens with chemotherapy may rescue a subset of children not curable by contemporary therapy. Another major challenge will be to incorporate less toxic regimens into the therapy of patients with low-risk disease who have a nearly 100% chance of being cured, and the ultimate goal is to improve their quality of life while maintaining a high cure rate.

Superior Survival Associated with Early Lymphocyte Regeneration after Cytoreductive Chemotherapy in Childhood Acute Lymphoblastic Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4494-4494
Author(s):  
Satya Prakash Yadav ◽  
Luciano Dalla-Pozza ◽  
Peter J. Shaw
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Time Points ◽  
Risk Patients ◽  
Standard Risk ◽  
Disease Free

Abstract Post autologous stem cell transplantation (ASCT) studies have demonstrated that early absolute lymphocyte count (ALC) recovery is associated with prolonged survival. A potential explanation for the survival advantage associated with ALC recovery after ASCT is the possibility that early immune reconstitution may have a protective effect against residual disease progression. This is analogous to the graft -versus-tumor effect in allogeneic bone marrow transplantation recipients whereby the donor immune system is responsible for the eradication of residual disease in the host. If true then ALC following cytoreductive chemotherapy without transplantation could help predict patients at increased risk of relapse. The relationship of ALC with clinical outcomes following cytoreductive chemotherapy for childhood acute lymphoblastic leukemia (ALL) is unknown. We evaluated all 91 children treated according to BFM 95 protocol at a single center with ALL from 1997 to 2002.We studied if the recovering ALC post induction (Day33) in all patients, post consolidation (Day79) in standard risk patients and day +28 from commencement of 1st high risk block of chemotherapy for high risk patients can predict clinical outcome. These time points correlate with minimal residual disease as per recent studies. Of the 91 patients 77 were standard risk, 7 were high risk and remaining 7 had very high risk disease as per BFM 95 criteria. Patients were analyzed according to overall and disease free survival. Mean lymphocyte counts were calculated and survival curves drawn based on a median count for all patients. The study shows that post chemotherapy recovery of ALC correlates with overall survival at all time points studied. Post induction (Day 33) mean ALC in disease free survivors v patients who had relapsed was 1.89 v 1.10 x 109/L.Similarly for these groups the recovering ALC was higher on post consolidation (Day 79) 1.28 v 0.97 x 109/L. Post 1st high risk block also showed a significant difference between survivors and relapsing high risk patients 1.47 v 0.96 x 109/L. Post Day 33 patients were split into those with ALC greater or less than 1.0 x 109/L. Overall survival was 94 % for patients with ALC greater than 1.0x 109/L on day 33 and 52 % for patients with ALC less than 1.0x 109/L on day 33 at median follow up of 3 years (median survival not reached v 20 months). If lymphocyte numbers are influencing outcome by an autologous immune anti-tumor effect, this knowledge could be used to influence and benefit future therapies to treat ALL in children. In conclusion, we confirm the association between early ALC recovery and superior survival after cytoreductive chemotherapy in children with ALL. Since the limitations of a retrospective analysis, our results should be viewed with caution and prospective studies that attempt to link specific lymphocytes subsets and outcome after cytoreductive chemotherapy in ALL are needed before any firm conclusions are drawn.

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