Background Infant acute lymphoblastic leukemia (ALL) is an infrequent disease characterized by clinical and biological features related to poor prognosis. Adapted therapies were designed without a clear consensus regarding the best treatment options. We aimed to compare the outcome between infant ALL cases receiving Interfant versus BFM‐based protocols. Procedure This is a retrospective observational study. From April 1990 to June 2018, infant ALL cases were enrolled in one of the five consecutive treatment protocols. Clinical, demographic, and biological features and outcome were evaluated. A comparative analysis was performed between Interfant protocols and BFM‐based protocols. Results During the studied period, 1913 ALL patients were admitted and 116 (6%) were infants. Treatment administered was: ALL‐BFM’90 (n = 16), 1‐ALL96‐BFM/HPG (n = 7), Interfant‐99 (n = 39), Interfant‐06 (n = 35), and ALLIC‐BFM’2009 (n = 19). The 5‐year event‐free survival probability (EFSp) was 31.9(standard error [SE] 4.6)% for the entire population, with a significant difference among risk groups according to Interfant‐06 criteria (P = .0029). KMT2A‐rearrangement status was the strongest prognostic factor (P = .048), independently of the protocol strategy. The median time for relapse was 24.1 months for patients with minimal residual disease (MRD)‐negative versus 11.5 months for those with MRD‐positive (P = .0386). EFSp and cumulative relapse risk probability (CRRp) were similar. Interfant protocols showed comparable induction (8.1% vs 7.1%, P = .852) and complete remission mortality (21.6% vs 28.6%, P = .438), failing to reduce the relapse rate (48.5% vs 30.7%, P = .149). Conclusions Interfant protocols and BFM‐based protocols presented comparable results. The risk group stratification proposed by Interfant‐06 was validated by our results, and MRD seems useful to identify patients with an increased risk of early relapse.

An association of deletions in the IKZF1 gene (IKZF1del) with poor prognosis in acute lymphoblastic leukemia (ALL) has been demonstrated. Additional deletions in other genes (IKZF1plus) define different IKZF1del subsets. We analyzed the influence of IKZF1del and/or IKZF1plus in the survival of children with ALL. From October 2009 to July 2021, 1055 bone marrow samples from patients with ALL were processed by Multiplex ligation-dependent probe amplification (MLPA). Of them, 28 patients died during induction and 4 were lost-in-follow-up, resulting in an eligible 1023 cases. All patients were treated according to ALLIC-BFM-2009-protocol. Patients were classified into three subsets: IKZF1not-deleted (IKZFF1not-del), IKZF1deleted (IKZF1del) and IKZF1del plus deletion of PAX5, CDKN2A, CDKN2B and/or alterations in CRLF2 with ERG-not-deleted (IKZF1plus). The LFSp and SE were calculated with the Kaplan–Meier calculation and compared with a log-rank test. From the 1023 eligible patients, 835 (81.6%) were defined as IKZF1not-del, 94 (9.2%) as IKZF1del and 94 (9.2%) as IKZF1plus. Of them, 100 (9.8%) corresponded to Standard-Risk (SRG), 629 (61.5%) to Intermediate-Risk (IRG) and 294 (28.7%) to High-Risk (HRG) groups. LFSp(SE) was 7 5(2)% for IKZF1not-del, 51 (6)% for IKZF1del and 48 (6)% for IKZF1plus (p-value < 0.00001). LFSp(SE) according to the risk groups was: in SRG, 91 (4)% for IKZF1not-del, 50 (35)% IKZF1del and 100% IKZF1plus (p-value = ns); in IRG, 77 (2)% IKZF1not-del, 61 (10)% IKZF1del and 54 (7)% IKZF1plus (p-value = 0.0005) and in HRG, 61 (4)% IKZF1not-del, 38 (8)% IKZF1del and 35 (9)% IKZF1plus (p-value = 0.0102). The IKZF1 status defines a population of patients with a poor outcome, mainly in IRG. No differences were observed between IKZF1del versus IKZF1plus. MLPA studies should be incorporated into the risk-group stratification of pediatric ALL.

Children with Down syndrome (DS) are at an increased risk of developing clonal myeloproliferative disorders. The balance between treatment intensity and treatment-related toxicity has not yet been defined. We analyzed this population to identify risk factors and optimal treatment. This single-center retrospective study included 78 DS patients <16 years-old with Transient Abnormal Myelopoiesis (TAM, n = 25), Acute Myeloblastic Leukemia (DS-AML, n = 41) of which 35 had classical Myeloid Leukemia associated with DS (ML-DS) with megakaryoblastic immunophenotype (AMKL) and 6 sporadic DS-AML (non-AMKL). Patients with DS-AML were treated according to four BFM-based protocols. Classical ML-DS vs. non-DS-AMKL were compared and the outcome of ML-DS was analyzed according to treatment intensity. Only four patients with TAM required cytoreduction with a 5-year Event-Free Survival probability (EFSp) of 74.4 (±9.1)%. DS-AML treatment-related deaths were due to infections, with a 5-year EFSp of 60.6 (±8.2)%. Megakaryoblastic immunophenotype was the strongest good-prognostic factor in univariate and multivariate analysis (p = 0.000). When compared ML-DS with non-DS-AMKL, a better outcome was associated with a lower relapse rate (p = 0.0002). Analysis of administered treatment was done on 32/33 ML-DS patients who achieved CR according to receiving or not high-dose ARA-C block (HDARA-C), and no difference in 5-year EFSp was observed (p = 0.172). TAM rarely required treatment and when severe manifestations occurred, early intervention was effective. DS-AML good outcome was associated with AMKL with a low relapse-rate. Even if treatment-related mortality is still high, our data do not support the omission of HDARA-C in ML-DS since we observed a trend to detect a higher relapse rate in the arm without HDARA-C.

Spinal cord compression (SCC) is an unusual manifestation of leukemias and lymphomas in children and defines an oncological emergency frequently unsuspected, being a cause of severe sequelae. Our aim was to analyze the characteristics of patients who presented signs or symptoms of spinal cord compression in early phases of malignant hematopoietic diseases. From November-1988 to July-2022, 3878 patients with leukemia and lymphoma were diagnosed. Of them, 36 children (0.92%) presented spinal cord compression signs/symptoms in early phases of their diagnosis: Acute Lymphoblastic Leukemia (n=18), Acute Myeloblastic Leukemia and Myeloid Sarcoma (n=7), Non-Hodgkin Lymphomas (n=9) and Hodgkin Lymphoma (n=2). Clinical characteristics, images and hematological findings, treatment strategies, results and sequelae were analyzed. Sex distribution was 3.5/1 (M/F) and the media age at diagnosis was 10 (range: 4.9-16.9) years. The most common symptoms were back pain (34/36), functional impotence (27/36) and sphincter compromise (10/36). The media time from symptom onset to diagnosis was 47,5 (range: 0-300) days. Magnetic resonance imaging was performed on 33 (92%) patients and showed epidural mass (n=16) or vertebral collapse (n=17) in all of them. Two patients received initial radiotherapy and 11 decompressive surgeries for the management of the urgency spinal cord compression. Bone marrow aspiration was the diagnostic procedure in 69% of cases. All patients received chemotherapy and 94% achieved complete remission. Severe sequelae were observed in 10 patients (paraplegia with neurogenic bladder and kyphoscoliosis). Leukemia and lymphoma should be considered as a differential diagnosis when spinal cord compression is suspected, and magnetic resonance imaging is the mandatory study to confirm this diagnosis as a matter of urgency. Bone marrow involvement was evident due to hematological alterations in 95% of cases allowing to guide the diagnosis and initiate treatment early to reduce sequelae.