Pediatric B‐Cell Lymphoma With Lymphoblastic Morphology,TdT Expression,MYC Rearrangement,and Features Overlapping With Burkitt Lymphoma

Burkitt lymphoma (BL) and B‐lymphoblastic lymphoma are subtypes of pediatric non‐Hodgkin lymphoma with different presenting features, treatment, and outcomes. This case report documents a 5‐year‐old female who presented with B‐cell lymphoma with lymphoblastic morphology, terminal deoxynucleotidyl transferase expression, MYC rearrangement, and features overlapping with BL. Genomic microarray analysis identified a gain on the long arm of chromosome 1 without other definitive changes. She was treated according to a BL protocol and remains in remission 16‐months after initial diagnosis.     

Blinatumomab activity in a patient with Down syndrome B‐precursor acute lymphoblastic leukemia

Persistent minimal residual disease (MRD) after consolidation may indicate chemotherapy insensitivity in B‐precursor acute lymphoblastic leukemia (BP‐ALL). Given the strong association of MRD and outcome in non‐Down syndrome (non‐DS) BP‐ALL, it is likely that MRD levels are also of prognostic significance in DS BP‐ALL. We report here the successful use of blinatumomab, a bispecific T‐cell engager antibody construct, in a patient with DS BP‐ALL and persistent MRD at the end of consolidation. Blinatumomab has been shown to have excellent results in patients with relapsed/refractory BP‐ALL. This patient had no significant toxicity and achieved MRD negativity after only one cycle of blinatumomab.     

Characterization of the anti‐CD22 targeted therapy,moxetumomab pasudotox,for B‐cell precursor acute lymphoblastic leukemia

Moxetumomab pasudotox is a second‐generation recombinant immunotoxin against CD22 on B‐cell lineages. Antileukemic activity has been demonstrated in children with chemotherapy‐refractory B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL), with variable responses. Here, we report in vitro and in vivo evaluation of moxetumomab pasudotox treatment of human cell lines and patient‐derived cells as a preliminary study to understand characteristics of sensitivity to treatment. Binding, internalization, and apoptosis were evaluated using fluorescently tagged moxetumomab pasudotox. Studies in NOD‐scid IL2Rg^null mice showed a modest survival benefit in mice engrafted with 697 cells but not in NALM6 or the two patient‐derived xenograft models.     

Translocation t(8;14)(q24;q11) with concurrent PTEN alterations and deletions of STIL/TAL1 and CDKN2A/B in a pediatric case of acute T‐lymphoblastic leukemia: A genetic profile associated with adverse prognosis

We report a pediatric case of acute T‐lymphoblastic leukemia (T‐ALL) with NOTCH1^wt, FBXW7^wt, STIL/TAL1, and PTEN (exons 2, 3, 4, 5) monoallelic deletions, biallelic CDKN2A/B deletion, and a minor t(8;14)(q24;q11)‐positive subclone. Undetectable by a flow cytometric minimal residual disease assay, the t(8;14)(q24;q11) subclone expanded as detected by fluorescence in situ hybridization from 5% at diagnosis to 26% before consolidation and 100% at relapse bearing a monoallelic deletion (exons 2, 3) with a new frameshift mutation of PTEN and the same set of remaining molecular alterations. This case documents an unfavorable prognostic potential of a co‐occurrence of this set of molecular genetic events and addresses risk stratification in T‐ALL.     

Development of diffuse large B cell lymphoma during the maintenance therapy for B-lineage acute lymphoblastic leukemia

Non-Hodgkin lymphoma (NHL) is a very rare complication of acute lymphoblastic leukemia (ALL). A Japanese boy presented with B-lineage ALL at the age of 2.5. He was treated with chemotherapy for standard-risk ALL. While he was receiving maintenance treatment 2 years and 9 months after the diagnosis of ALL, diffuse large B cell lymphoma (DLBL) was diagnosed from a biopsy of an abdominal mass. DLBL was treated by surgical resection followed by chemotherapy for 6 months. The patient has been free from the recurrence of ALL or DLBL for 16 months after the development of DLBL.     

Hyper‐eosinophilia in granular acute B‐cell lymphoblastic leukemia with myeloid antigen expression

Acute lymphoblastic leukemia with eosinophilia (ALLEo) is a rare but a distinctive clinical entity. Clinical features of idiopathic hyper‐eosinophilic syndrome (HES) can be seen in patients with ALLEo. We report a 10‐year‐old girl, in whom HES was initially suspected but further investigation confirmed the diagnosis of acute B‐cell lymphoblastic leukemia with myeloid antigen expression. Clinical response to chemotherapy was excellent with achievement of complete remission for 4 years. Serum interleukin‐3 and ‐5 were elevated at presentation and normalized with disappearance of eosinophilia after induction therapy, supporting the reactive nature of eosinophilia in ALLEo. Hematologic malignancy should be considered in patients with hyper‐eosinophilia, before attributing it to HES.     

Ig/TCR基因重排在儿童急性T淋巴细胞白血病中的表达模式特点

目的 探讨免疫球蛋白(Ig)/ T细胞受体(TCR)基因重排在儿童急性T淋巴细胞白血病(T-ALL)中的表达模式特点及其与临床生物学特征的相关性。方法 回顾性纳入首都医科大学附属北京儿童医院(我院)2005年1月1日至2008年12月31日收治的初治T-ALL患儿,分析其初诊时骨髓单个核细胞的Ig/TCR基因重排情况,根据重排情况分为阳性组和阴性组,比较不同组别的临床生物学特征。结果 ①52例儿童T-ALL中男37例(71.2%),入院时中位年龄8.0(1.8~16.0)岁,初诊时WBC中位数为140.5(2.7~667.1)×10⁹·L^-1,中危38例(73.1%)、高危14例(26.9%)。中位随访时间136.3(1.2~171.7)个月,长期完全缓解38例(73.1%)、复发10例(19.2%),其他原因死亡4例(7.7%)。②TCRB、TCRG、TCRD和IgH克隆性基因重排的发生率分别为85%、85%、38%和21%,94%的患儿检出至少1种基因重排,88%的患儿检出至少2种基因重排。TCRB、TCRD、TCRG和IgH重排分别以完全性V_β-(D_β)-J_β、V_δ-J_δ、V_γⅠ-J_γ1.3/2.3和D_H-J_H不完全重排为主。各种重排的胚系片段使用和连接区序列极具多样性。③ 10例复发患儿中有6例检测了复发时的Ig/TCR基因重排模式,4例与初诊时完全一致,2例发生改变。④SIL-TAL1融合基因阳性率在11例IgH重排阳性患儿中0%(0/14),在41例IgH重排阴性患儿中为34.1%(14/41),P=0.025。⑤TCRB基因重排阳性组高危比例(20.5%,9/44)低于阴性组(62.5%,5/8),P=0.025。TCRB或TCRG基因重排阳性组第33 d缓解率(89.4%,42/44)高于阴性组(10.6%,5/8),P=0.022,第78 d MRD水平≥10^-3的比例(10.8%,4/37)低于阴性组(50.0%,3/6),P=0.045。结论 儿童T-ALL初诊时Ig/TCR克隆性基因重排的胚系片段使用和连接区序列极具多样性,有助于进一步性MRD 检测标志的筛选。     

Outpatient low toxic regimen with bortezomib in relapsed/refractory acute lymphoblastic leukemia in pediatrics and AYA patients: Single‐center Mexican experience

Relapsed or refractory acute lymphoblastic leukemia represents a major challenge in low‐ and middle‐income countries where new therapies are not easily accessible. Combinations of cost‐effective drugs should be considered as a bridge for hematopoietic stem cell transplantation. We retrospectively analyzed pediatric and adolescent and young adult patients who received reinduction with a protocol based on l ‐asparaginase, doxorubicin, vincristine, dexamethasone, and bortezomib (BZ). Fifteen patients were included. Total complete response (CR) was achieved by nine of 15 patients (60%); five patients achieved CR with negative minimal residual disease, two achieved complete morphological response (CR), and two complete morphological response without platelet recovery. Eleven patients (73%) were not hospitalized and 10 (66%) did not require any blood component transfusions. There were no cases of serious toxicity or mortality. Nine patients (60%) underwent transplant. Five‐year overall survival was 40%. This BZ‐based protocol is effective and safe when administered as an outpatient regimen and feasible in a low resource setting.     

Blinatumomab as a bridge to further therapy in cases of overwhelming toxicity in pediatric B‐cell precursor acute lymphoblastic leukemia: Report from the Israeli Study Group of Childhood Leukemia

Tremendous progress in the therapy of pediatric acute lymphoblastic leukemia (ALL) has been achieved through combination cytotoxic chemotherapy, leading to high cure rates, at the cost of significant life‐threatening toxicity. The bispecific T‐cell engager blinatumomab, recently approved for relapsed/refractory ALL, has a unique nonmyelotoxic toxicity profile. As blinatumomab causes B‐cell depletion, the safety of its use during severe chemotherapy‐induced toxicity is unclear. We report 11 pediatric patients with ALL, treated with blinatumomab following overwhelming chemotherapy‐associated toxicity, with recovery of all patients and successful bridging to further antileukemia therapy. Blinatumomab can be considered for rare patients who cannot tolerate cytotoxic therapy.     

A medication diary‐book for pediatric patients with acute lymphoblastic leukemia in Indonesia

Background

Event‐free survival of pediatric patients with acute lymphoblastic leukemia (ALL) in Yogyakarta, Indonesia was low (20%). The aim of the study was to evaluate the effectiveness of using a medication diary‐book on the treatment outcome of childhood ALL.

Procedure

A randomized study was conducted with 109 pediatric patients with ALL in a pediatric oncology center in Yogyakarta, Indonesia. Both intervention and control groups received a structured parental education program and donated chemotherapy. The intervention group received a medication diary‐book to remind parents and families to take oral chemotherapy and present for scheduled appointments or admissions. Event‐free survival estimate (EFS) at 3 years was assessed.

Results

Among pediatric patients with ALL with highly educated mothers (senior high school or higher), the EFS‐estimate at 3 years of the intervention group was significantly higher than the EFS‐estimate at 3 years of the control group (62% vs. 29%, P = 0.04). Among pediatric patients with ALL with low‐educated mothers, no significant difference was found in the EFS‐estimates at 3 years between the intervention and control group (26% vs. 18%, P = 0.86).

Conclusions

We conclude that a medication diary‐book might be useful to improve the survival of pediatric patients with ALL in resource‐limited settings, particularly in patients with highly educated mothers. Pediatr Blood Cancer 2013;60:1593–1597. © 2013 Wiley Periodicals, Inc.