scholarly journals Successful Outpatient Administration of Blinatumomab Infusion in Pediatric Patients with Acute Lymphoblastic Leukemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4028-4028
Author(s):  
Lora Bojilova-Dor ◽  
Kerice Pinkney ◽  
Brian Cauff ◽  
Deborah Kramer ◽  
Anne M Schaefer ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Multidisciplinary Team ◽  
Pediatric Patients ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Toxicity Profile ◽  
Home Setting ◽  
Home Based ◽  
Effective Manner

Abstract Introduction: Acute lymphoblastic leukemia (ALL) is the most common type of pediatric cancer. Unfortunately, approximately 15% of children with high-risk B-cell ALL (B-ALL) relapse after frontline chemotherapy. Treatment of relapsed/refractory B-ALL is still challenging, and more effective novel therapies are urgently warranted. Blinatumomab, a first in class bispecific antibody therapeutic, has demonstrated superiority compared to standard chemotherapy in patients with B-ALL and has a manageable toxicity profile. Blinatumomab functions by binding to CD19 expressed on B-cells and CD3 expressed on T-cells, resulting in T-cell-mediated killing of CD19-positive cells common in B-cell malignancies. Despite remarkable efficacy and a manageable toxicity profile compared to standard-of-care chemotherapy, blinatumomab poses unique healthcare system challenges related to preparation, administration, toxicity monitoring, and medication error prevention. The drug's success in helping patients achieve complete remission relies on its continuous and uninterrupted administration. In order to ensure that it is delivered in the safest and most effective manner, education on its unique logistical and administration challenges is imperative. Objectives: The primary objective of this study is to describe and share the 6 years of institutional experience on the outpatient delivery of blinatumomab for the management of pediatric patients with B-ALL as per Children's Oncology Group protocols, as well as to retrospectively analyze the safety of this novel 28-day home-based therapy. Methods: A multidisciplinary team composed of physicians, nurses, and pharmacists was created to address administration challenges associated with blinatumomab infusions. Although blinatumomab requires a 28-day continuous infusion, it is not necessary for patients to remain hospitalized for the entire cycle. To ensure tolerability prior to discharge, patients are monitored closely during the first 3 days of Cycle 1 and 2 days of Cycle 2 for signs of cytokine release syndrome and neurological toxicities. Once discharged, they are seen every 96/72 hours for bag changes in either an outpatient hematology/oncology unit or by home health for those off study. Results: A total of 16 patients were treated with blinatumomab between May 2015 and June 2021; 10 were newly diagnosed and 6 were in first relapse. Of the 26 total infusions, 24 were successfully completed without significant adverse reactions. Two patients treated for relapsed disease had to discontinue therapy; one experienced neurotoxicity within 72 hours of blinatumomab infusion initiation and the other developed refractory disease and was switched to another protocol. No adverse events were observed in the home setting. Discussion: The team was successfully able to transform the original inpatient-only blinatumomab protocol to the outpatient setting. Retrospective analysis over 6 years demonstrates a clinically significant reduced rate of complications of blinatumomab administration in comparison to previous reports (Amicucci et al. 2021), which can be attributed to careful multidisciplinary team planning and delivery. This study confirms the feasibility of a home-based continuous blinatumomab infusion without adverse effects on safety. Additionally, this outpatient protocol leads to cost savings associated with reduced length of stay and an overall improved quality of life for pediatric patients able to receive therapy at home with their caregivers. Disclosures No relevant conflicts of interest to declare.

Crebbp HAT Domain Mutations Are Frequently Detected in Adult Acute Lymphoblastic Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1419-1419
Author(s):  
Kenji Tokunaga ◽  
Shunichiro Yamaguchi ◽  
Eisaku Iwanaga ◽  
Tomoko Nanri ◽  
Taizo Shimomura ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
B Cell ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Genetic Alterations ◽  
Adult Patients ◽  
Prognostic Impact ◽  
Pediatric All ◽  
Crebbp Gene

Abstract Abstract 1419 Aims: Molecular pathogenesis of acute lymphoblastic leukemia (ALL) has largely been verified in pediatric patients and the identification of genetic alterations have contributed to stratifying therapeutic applications. In adult patients with ALL, cytogenetic and genetic abnormalities have not sufficiently been elucidated and therapeutic improvement has been hindered. CREB binding protein (CREBBP) is a transcriptional coactivator that interacts with a diverse range of transcription factors and regulates transcription by histone acetylation in hematopoiesis. Mutations of the CREBBP gene are recently found in approximately 2–4% of pediatric patients with ALL. Especially in relapsed cases, the mutations prevail (18–63%) and are possible markers for prediction of relapse in pediatric ALL. In adult patients with ALL, the clinical significance of CREBBP mutations remains to be determined. Here we examined adult ALL patients in an attempt to determine the incidence, clinical characteristics and prognostic impact of the CREBBP mutations. Methods: We investigated 71 adult patients with newly diagnosed ALL treated with JALSG protocols between 1986 and 2010. Age ranged from 15 to 86 years, with a median of 54 years. CREBBP mutations are dominantly identified in histone acetyltransferase (HAT) domain. HAT domain in the CREBBP gene was amplified with RT-PCR using RNA isolated from the peripheral blood or bone marrow mononuclear cells at diagnosis and was subjected to direct sequencing. We compared clinical profiles between patients with and without CREBBPHAT domain mutations. This study was approved by the Institutional Review Boards and informed consent was obtained from each patient according to guidelines based on the revised Declaration of Helsinki. Results: CREBBP HAT domain mutations were detected in 8 of 71 (11.3%) patients: one nonsense mutation, five insertion mutations with frameshifts, and five missense mutations. Two patients harbored biallelic mutations. The mutations at diagnosis in adult patients were seen more frequently than those in pediatric patients ever reported. Such mutations were not completely identical to those detected in pediatric ALL, but were seen in the region within the HAT domain, indicating that such mutations are loss-of-function mutations. The mutations were found in both B-cell (6/53: 11.3%) and T-cell (1/9: 11.1%) ALL, and distributed in patients harboring IKZF1 alterations (3/31: 9.7%) or the BCR-ABL fusion gene (2/19: 10.5%). There were no statistical difference in age, sex, leukocyte, platelet counts and complete remission rate between patients with and without the CREBBP HAT domain mutations. Patients with the mutations had a trend with worse cumulative incidence of relapse (P=0.4637), relapse-free survival (P=0.4195) and OS (P=0.2349) compared to patients lacking the mutations, but statistical significance was not detected in this small cohort. Conclusions: CREBBP HAT domain mutations at diagnosis in adult ALL are found more frequently than in pediatric ALL. This may be one of the mechanisms that adult ALL has been associated with poor OS compared with pediatric ALL. In this study, CREBBP HAT domain mutations were observed in various subtypes of ALL: both B-cell and T-cell ALL, and both Philadelphia chromosome positive and negative ALL. In pediatric ALL, CREBBP mutations were frequently seen in relapsed patients but not in previously untreated patients. These observations suggest that CREBBP mutations play an important role in an additional late event(s) leading to the development and progression of ALL. Our study implies the possibility that mutations of the CREBBP gene are associated with the pathogenesis and prognostic marker of adult ALL and represent specific epigenetic modifiers in adult ALL, serving as potential therapeutic targets. Disclosures: No relevant conflicts of interest to declare.

ERG Intragenic Deletion Characterizes a Distinct Oncogenic Subtype of B-Cell Precursor Acute Lymphoblastic Leukemia with a Favourable Outcome Despite Frequent IKZF1 Deletions

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 121-121
Author(s):  
Emmanuelle Clappier ◽  
André Baruchel ◽  
Jérôme Rapion ◽  
Aurélie Caye ◽  
Ahlème Khemiri ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Favourable Outcome ◽  
Fish Analysis ◽  
Cell Precursor ◽  
Pcr Assay ◽  
Genetic Lesion ◽  
Intragenic Deletion

Abstract Abstract 121 The genetic landscape of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in children above 10 years and adolescents remains poorly defined. Specifically, more than half of these patients have none of the cytogenetic abnormalities that define oncogenic subtypes and underlie risk stratification. To uncover new genetic abnormalities in these unassigned cases, we studied 85 BCP-ALL from patients aged 10 to 17 diagnosed at St-Louis hospital (Paris, France), for which the main classifying genetic lesions were assessed (i.e. high hyperdiploidy, t(12;21)/ETV6-RUNX1, t(1;19)/TCF3-PBX1, t(9;22)/BCR-ABL1, iAMP21, MLL translocations, low hypodiploidy, and near haploidy). Fifty of these BCP-ALL presented no classifying genetic lesions. Paired leukemic and remission samples could be analysed by high density array-CGH (Agilent 1M arrays) in 17 of these unassigned cases. We focused on acquired, focal, and recurrent copy-number abnormalities. A mono-allelic intragenic deletion of the ETS-related Gene (ERG) was found in 3 cases. ERG belongs to the ETS family of transcription factors and is implicated in chromosomal translocations associated with several cancer types including acute myeloid leukemia. The possibility of a cryptic unbalanced translocation was ruled out in the 3 cases by FISH analysis. The deletions encompassed exons 3 to 7, or 3 to 9, and the breakpoints were tightly clustered. Based on the breakpoint sequences we designed a PCR assay that allowed us to screen ERG intragenic deletions in the whole cohort. ERG deletion was identified in 9 additional cases, none of them having any of the known classifying genetic lesions, bringing up to 25% (12 out of 50) the frequency of ERG deletion in unassigned BCP-ALL of children older than 10. These results suggested that ERG deletion characterized a novel oncogenic subtype of BCP-ALL. Of note, these results were consistent with independent data of Harvey et al. (2010) that reported ERG deletions in a distinct gene-expression cluster. To confirm and extend these findings in the whole population of paediatric BCP-ALL, we used our breakpoint-specific PCR assay to screen ERG deletions in an independent cohort of 822 unselected patients aged 1 to 17, enrolled in the EORTC 58951 trial. ERG deletion was identified in 31/822 (3.7%) patients. Again, none of them had another known classifying genetic lesion, confirming that ERG deletion characterizes a distinct oncogenic subtype. Patients with ERG deletion were significantly older compared to other patients (median 7.0 vs 4.0, p=0.002), but they had similar white blood counts at diagnosis. They had a favourable outcome, with a 8-year event free survival (EFS) of 82.4% and overall survival (OS) of 96.0%, which is similar to EFS of 83.4% and OS of 91.6% obtained for patients having no very high risk initial features (i.e. no t(9;22)/BCR-ABL1, MLL rearrangement or haploidy/low hypodiploidy). IKZF1 deletion is a cooperative genetic lesion that has been recently shown to be associated with a poor outcome in BCP-ALL. Remarkably, the incidence of IKZF1 deletions in patients with ERG deletion was significantly higher than in other BCR-ABL1-negative patients, especially when considering the IKZF1 intragenic deletion Δ4-7 (10/31, 32.3% vs 34/744, 4.6%, P<0.001), and this regardless of age. Surprisingly, IKZF1 deletion had no impact on the prognosis of ERG deleted patients. Indeed, patients combining ERG and IKZF1 Δ4-7 deletions had a better outcome than other BCR-ABL1-negative patients with IKZF1 deletions (8-year EFS 83.3% vs 53.0%, hazard ratio (HR) 0.19, 95% CI 0.02–1.41; p=0.069). Altogether, we have identified a novel oncogenic subtype of BCP-ALL characterized by ERG deletion. This subtype is frequently associated with IKZF1 deletions, suggesting a preferred oncogenic cooperation. Importantly, despite having older age and frequent IKZF1 deletions, which are factors usually predictive of a poor prognosis, patients with ERG deletion have a favourable outcome. Therefore, this genetic abnormality may be systematically assessed as part of the diagnostic work-up of BCP-ALL and taken into account when considering treatment stratification. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Novel MEIS1-FOXO1 Fusion Gene in a Case of Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5283-5283
Author(s):  
Chuang Jiang ◽  
Jiabi Qian ◽  
Wenge Hao ◽  
Wei LIU ◽  
Shuhong Shen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia ◽  
Functional Study ◽  
Cell Precursor ◽  
Foxo1 Gene

Abstract Background: Thanks to the total therapy and systemic basic-translation research, the overall survival rate in children with acute lymphoblastic leukemia (ALL) has dramatically improved to almost 90% over these past few decades. FOXO1 gene belongs to the forkhead family of transcription factors, which play roles in myogenic growth and differentiation. Translocation of FOXO1 with PAX3 has been reported in pediatric alveolar rhabdomyosarcoma. In B-cell precursor ALL, two cases with FOXO1 fusions have been identified already, while its function on ALL remains unknown. Here, we report a novel MEIS1-FOXO1 fusion gene in a case with B-ALL. Methods: Flowcytometery, karyotype, RT-PCR and fluorescence in were employed, MEIS1-FOXO1 was identified as novel fusion gene in a case of pediatric BCP-ALL. Using IL-3 dependent BaF3 cells as study model to test the leukemia transformation potential of MEIS1-FOXO1. Results: A novel MEIS1-FOXO1 fusion was identified in one cease of pediatric B-ALL. Panel next generation sequencing (NGS) showed that the leukemia clone had concurrent NRASG12D, TP53R273H, WHSC1E1099K, ABCC1R1166X, PHGR1H37P, HOXA3P219L and DSTP4606L somatic mutation. This patient was enrolled in CCCG-ALL2015 clinical trial (ChiCTR-IPR-14005706) and achieved completed remission and low minimal residual disease (MRD) level (MRD<0.01%) at day 19 from induction therapy. Functional study showed that MEIS1-FOXO1 fusion gene can potentiate BaF3 cells growth independent of IL3 supplement, as compared to those without MEIS1-FOXO1 fusion transduction. In the meanwhile, we have found that MEIS1-FOXO1 fusion gene can drive cells into S-phase with concurrent decreased G0/G1 phase, which might be its oncogenic role in leukemogenesis. Using qPCR methods, we have found that MEIS1-FOXO1 fusion gene altered the cell cycle related genes expression. Conclusions: Integrating the FOXO1-fusion reports, our data have added more evidence to underline the role of FOXO1 deregulation in the pathogenesis of acute lymphoblastic leukemia. Novel fusion of MEIS1-FOXO1 can potentiate B-ALL via cell cycle entry. Detailed mechanisms involved into the MEIS1-FOXO1 should be further investigated. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

scholarly journals Two Cases of Pediatric Acute Lymphoblastic Leukemia with t(5;14): a Challenging and Unique Entity

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4870-4870
Author(s):  
Renee-Pier Fortin-Boudreault ◽  
Elaine W. Leung ◽  
Mylene Bassal
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Pediatric Patients ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Behavior Changes ◽  
Low Grade ◽  
Cell Transplant ◽  
St Depression ◽  
Pediatric All

Background: Pre-B acute lymphoblastic leukemia (B-ALL) with the t(5;14) translocation occurs in less than 1% of B-ALL diagnoses. This translocation links the IGH on chromosome 14 with IL-3, which results in hypereosinophilia. Interestingly, circulating blasts or cytopenias usually don't accompany the eosinophilia. Patients often present with symptoms related to the eosinophilia, which can be quite morbid, and can delay the diagnosis of ALL. Few pediatric patients with this association have been described in the literature. The presentation and outcome can be quite variable, although it is thought that the prognosis in those patients is worse than standard ALL. Objectives: To review the laboratory and clinical features of pediatric ALL with t(5;14). Methods: Cases of pediatric patients with ALL and t(5;14) diagnosed at the Children's Hospital of Eastern Ontario between 1995 and 2003 were reviewed. Results: We present two 11 year old children, a female and a male, who were diagnosed with B-ALL with t(5;14). The first one presented with a persisting low-grade fever and weight loss as well as asymptomatic lung infiltrates on the chest xray. The second patient presented with chest pain, fever, abdominal pain, as well as a petechial rash and splinter hemorrhages. His EKG showed ST depression, his troponins were elevated and an echocardiogram showed heart dysfunction. He went on and developed behavior changes and cerebral microinfarcts. Common to their presentation was the presence of hyperoesinophilia and absence of circulating blasts. Both had aggressive disease with persistent positive minimal residual disease (MRD) after consolidation and reinduction, which sent them to stem cell transplant. Conclusion: ALL with t(5;14) is a rare entity that usually presents with hypereosinophilia. While eosinophilia can be asymptomatic, it can also be the cause of important morbidity. Diagnosis can be delayed because of the absence of blasts in the peripheral blood and lack of severe cytopenia. Finally, due to its rarity, there is very little information available on how this cytogenic abnormality impacts prognosis, which seems to be worse than ALL without this translocation. Disclosures No relevant conflicts of interest to declare.

scholarly journals JAK2 Aberrations in Childhood B-Cell Precursor Acute Lymphoblastic Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 583-583
Author(s):  
Elisabeth M.P. Steeghs ◽  
Isabel S. Jerchel ◽  
Willemieke de Goffau-Nobel ◽  
Alex Q. Hoogkamer ◽  
Judith M. Boer ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Induced Resistance ◽  
Conflicts Of Interest ◽  
Ex Vivo ◽  
Lymphoblastic Leukemia ◽  
Annexin V ◽  
Leukemic Cell ◽  
Leukemic Cells ◽  
Cell Precursor

Abstract Background In high risk pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients, gain of function mutations and translocations affecting JAK2 have been described. These mutations and translocations result in aberrant kinase signaling and may therefore serve as an ideal target for precision medicines. Aim Evaluate the frequency and prognosis of JAK2 lesions among different subtypes of childhood BCP-ALL, and study the efficacy of the JAK1/2 inhibitors momelotinib and ruxolitinib. Methods This study comprised 77 BCR-ABL1-like cases and 76 B-other cases which were screened for JAK2 translocations using RT-PCR. Furthermore a representative pediatric cohort of 461 newly diagnosed BCP-ALL cases was screened for JAK2 mutations using targeted next-generation sequencing. Clinical analyses were performed in 341 BCP-ALL patients. Patient-derived-xenograft (PDX) cells were isolated from NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice, which were injected with primary leukemic cells. Purity of PDX cells was enriched to over 90% and presence or absence of JAK2 lesions was validated. PDX and primary leukemic cells were exposed to a dilution series of momelotinib or ruxolitinib for four days. Where indicated, cells were pre-incubated with 25 ng/ml TSLP for 1 hour. In mono-culture assays, cytotoxicity was quantified using MTT and in co-culture assays flow cytometry was used. Leukemic cells were discriminated from mesenchymal stromal cells (MSCs) using CD19 and viability was assessed by Annexin V and Propidium Iodide. Western blotting was used to study protein expression levels. Results JAK2 translocations were detected in 6.5% of BCR-ABL1-like cases (3 PAX5-JAK2 cases, 1 TERF2-JAK2 case and 1 BCR-JAK2 case), but not in B-other cases. JAK2 mutations were identified in 3.5% of all BCP-ALL cases, which included JAK2 mutations in BCR-ABL1-like (7.6%), B-other (11.9%), and high hyperdiploid cases (1.6%), but not in MLL rearranged, BCR-ABL1-positive, ETV6-RUNX1-positive or TCF3-PBX1-positive cases. Cumulative incidence of relapse in patients harboring JAK2 lesions was as poor as in JAK2 wildtype BCR-ABL1-like and B-other patients. Efficacy of the JAK1/2 inhibitors momelotinib and ruxolitinib was examined in JAK2 lesion positive (primary and PDX) leukemic cells. Inhibitors were cytotoxic in both translocated and mutated cells, although efficacy in JAK2 mutated cells highly depended on CRLF2 activation by TSLP. CRLF2 activation resulted in downstream STAT5 activation and sensitization towards ruxolitinib compared to unstimulated cells (p < 0.05). Cells harboring JAK2 translocations signaled independently of CRLF2. Although momelotinib and ruxolitinib exposure blocked downstream STAT1/5 phosphorylation, both inhibitors also induced accumulation of phosphorylated JAK2Y1007. Consequently, release of the inhibitors resulted in a profound re-activation of JAK2 signaling, observed by upregulation of downstream STAT1/5 signaling. Furthermore, we observed microenvironment-induced resistance. Culturing leukemic cells in the presence of primary bone marrow MSCs induced resistance to ruxolitinib, compared to leukemic cells in single cultures (p < 0.05). A similar trend was observed for momelotinib. In addition, patients harboring JAK2 mutations displayed a heterogeneous leukemic cell population. Mouse xenograft models revealed different outgrowth patterns of leukemic cells, in which the JAK2 mutated clone persisted, decreased or even disappeared, resulting in outgrowth of JAK2 wildtype leukemic cells. Moreover, JAK2 mutations were not mutually exclusive for other pathway mutations (e.g. KRAS). Conclusion JAK2 translocations and mutations were detected in poor prognostic BCP-ALL cases. In ex vivo assays, the JAK1/2 inhibitors momelotinib and ruxolitinib were cytotoxic in JAK2 aberrant cells. Despite these promising findings, we identified certain limitations of these inhibitors. Inhibitors induced accumulation of phosphorylated JAK2Y1007, which resulted in a profound re-activation of JAK2 signaling upon their release. Furthermore, our data suggest that the effect of JAK inhibition may be compromised by mutations in alternative survival pathways and by microenvironment-induced resistance. Taken together, our data yield important directives for the clinical use of JAK inhibitors in pediatric BCP-ALL. 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.

Concurrent Subcutaneous Panniculitis-like T-Cell Lymphoma and B-Cell Acute Lymphoblastic Leukemia in 2 Pediatric Patients

2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Geoffrey A. Smith ◽  
Anya L. Levinson ◽  
Robert T. Galvin ◽  
Leah E. Lalor ◽  
Timothy McCalmont ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
B Cell ◽  
Pediatric Patients ◽  
Cell Lymphoma ◽  
Lymphoblastic Leukemia ◽  
T Cell Lymphoma ◽  
Cell Acute Lymphoblastic Leukemia
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